orabase and Disease-Models--Animal

Although the safety of vaccine approaches for central nervous system (CNS) malignancies has been established in early phase clinical trials, the success of a vaccine strategy will depend critically on the ability of effector T cells to home in to CNS tumors and durably exert antitumor effects. Based on our recent studies, efficient CNS tumor homing is a characteristic of cytotoxic T lymphocytes (CTLs) with a type 1 phenotype (Tc1), and this appears to be related to the Tc1 response to the type 1 CXC chemokine ligand (CXCL) 10 [also known as interferon (IFN)-inducible protein (IP)-10] and expression of an integrin receptor very late antigen (VLA)-4 on Tc1. In addition, we have previously shown that direct intratumoral delivery of dendritic cells (DCs) ex vivo engineered to secrete IFN-alpha further enhances Tc1 homing via upregulation of CXCL10/IP-10 in the tumor microenvironment. As a means to induce IFN-alpha and CXCL10/IP-10 in the CNS tumor microenvironment in a clinically feasible manner, we used administration of polyinosinic-polycytidylic acid stabilized by lysine and carboxymethylcellulose (poly-ICLC), a ligand for toll-like receptor 3 and melanoma differentiation-associated gene 5 (MDA5) in combination with vaccinations targeting CTL epitopes derived from glioma-associated antigens (GAAs). The combination of subcutaneous vaccination and i.m. poly-ICLC administration remarkably promoted systemic induction of antigen GAA-specific Tc1s expressing VLA-4 in the CNS tumors and improved the survival of tumor-bearing mice in the absence of detectable autoimmunity. Based on these data, we have implemented a phase I/II vaccination study using type 1 polarizing DCs loaded with GAA peptides in combination with poly-ICLC in patients with recurrent malignant glioma.

Topics: Animals; Brain Neoplasms; Cancer Vaccines; Carboxymethylcellulose Sodium; Disease Models, Animal; Glioma; Humans; Immunotherapy; Mice; Poly I-C; Polylysine; RNA, Double-Stranded; RNA, Viral; T-Lymphocytes; T-Lymphocytes, Cytotoxic; Toll-Like Receptor 3

To evaluate the efficacy of hyaluronate/carboxymethylcellulose (HA/CMC) membrane and melatonin separately and in combination in reducing adhesion reformation following adhesiolysis of surgically induced adhesions in a rat uterine horn adhesion model.. A randomized, prospective study was carried out in a university animal laboratory. Ninety-eight female Sprague-Dawley albino rats were operated on. Following infliction of standard lesions, all the animals underwent second operations after one week. In all the animals, there were dense and vascular adhesions only between the uterine horns. These adhesions were lysed. Following the completion of adhesiolysis, the animals were randomized before closure of the abdomen to one of four groups (melatonin, HA/CMC membrane, combination of melatonin and HA/CMC membrane, control group). Seven days after the second surgery, the third operations were carried out and adhesions were scored. The main outcome measures were type, tenacity, and extent of adhesions. Total adhesion scores were determined.. Adhesion scores in the melatonin and HA/CMC membrane groups were similar, and significantly lower than those in the control group (P < 0.001). Adhesion scores in the combination group were lower than those in the other three groups (P < 0.001).. Melatonin and HA/CMC membrane are both effective separately in preventing adhesion reformation following adhesiolysis, but in combination they are significantly more beneficial.

Topics: Administration, Topical; Animals; Carboxymethylcellulose Sodium; Combined Modality Therapy; Disease Models, Animal; Female; Free Radical Scavengers; Hyaluronic Acid; Melatonin; Membranes, Artificial; Peritoneal Diseases; Postoperative Complications; Prospective Studies; Random Allocation; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Treatment Outcome; Uterine Diseases; Uterus

Stomahesive skin-protection powder has been reported to be useful as a skin-care and skin-barrier product for the management of stomas. This study aimed to evaluate its efficacy, in terms of wound healing, moisture retention and pain management, as an alternative to conventional dressing materials. Both clinical and animal studies were undertaken.. The efficacy of the Stomahesive powder was tested by measuring the thickness of granulation tissue formed in a total skin defect in a db/db mouse model. We then compared the healing process using either the skin-protection powder or a conventional film dressing material. In the clinical study 17 patients with various intractable ulcers were treated with Stomahesive powder, and healing was evaluated.. In the mouse model, granulation tissue in the wounds treated with the powder was 2.86 times thicker than that of the wounds treated with the film dressing. In the clinical study, 16 out of 17 wounds healed completely.. The Stomahesive powder could be an effective treatment modality for contact ulceration, superficial ulcers with complex contours and morphology, and superficial ulcers contaminated by liquid faeces or vaginal discharge that have not responded to conventional dressings.. None.

Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Drug Combinations; Drug Evaluation; Female; Gelatin; Granulation Tissue; Humans; Male; Mice; Mice, Inbred Strains; Middle Aged; Occlusive Dressings; Pectins; Polyenes; Powders; Skin Care; Skin Ulcer; Statistics, Nonparametric; Wound Healing

To investigate the effect of sodium carboxymethylcellulose (SCMC) and the combination of low molecular weight heparin (LMWH) with SCMC in the prevention of intraperitoneal adhesion.. Thirty-eight rats underwent bilateral surgical injury to the uterine horn and the parietal peritoneum. In 13 rats, a solution of SCMC was instilled at laparotomy. In 11 rats, LMWH was delivered on to serosal and peritoneal defects, and SCMC was instilled. As a control group 14 rats were included in the study.. Surgical Research Laboratory, Erciyes University.. Female Wistar-Albino rats, weighing 200 to 250 g each.. Adhesions between the uterine horn and the abdominal sidewall were scored for extent and severity two weeks after the initial surgery.. Although the mean adhesion score both in the SCMC group (2.8, s.d. 1.15) and in the SCMC with LMWH group (1.6, s.d 1.18) was found to be significantly lower than in the control group (3.4, s.d. 0.89) (p < 0.05 and p < 0.001, respectively), more favorable adhesion prophylaxis was achieved in the SCMC with LMWH group in comparison with the SCMC treatment group without any hemorrhagic complications (p < 0.001).. We conclude that SCMC with LMWH are highly effective in reducing postoperative adhesions in this animal model. SCMC with LMWH appears promising in adhesion prophylaxis.

Topics: Animals; Carboxymethylcellulose Sodium; Data Interpretation, Statistical; Disease Models, Animal; Female; Heparin, Low-Molecular-Weight; Rats; Rats, Wistar; Tissue Adhesions; Uterine Diseases; Uterus

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Down-Regulation; Estradiol; Estrous Cycle; Female; Follicle Stimulating Hormone; Hypoglycemic Agents; Interleukin-18; Letrozole; Luteinizing Hormone; Metformin; Ovulation; Polycystic Ovary Syndrome; Rats; Testosterone; Tumor Necrosis Factor-alpha

In 80% to 90% of the patients intra-abdominal adhesions occur after abdominal surgery, which can cause small-bowel obstruction, chronic abdominal pain, female infertility and difficulty during reoperation. A novel crosslinked hyaluronic acid gel is evaluated regarding its anti-adhesive capacities in an ischemic button model in rats.. 51 adult, male Wistar rats from a registered breeder, received eight ischemic buttons each and were treated with hyaluronic acid gel (HA, HyaRegen. Macroscopic evaluation of adhesion formation did not differ between the groups. The number of organs involved in adhesions in the HA gel group was significantly lower compared to HA-CMC (p = .041) and the control group (p = .012). A significantly, 1.36-fold higher. HA gel application reduces the number of organs involved in adhesions in an ischemic button model, but no overall reduction in adhesion formation was encountered. Macrophage subtype 2 polarization and high

Topics: Animals; Carboxymethylcellulose Sodium; Cross-Linking Reagents; Disease Models, Animal; Gels; Hyaluronic Acid; Ischemia; Macrophages; Male; Matrix Metalloproteinase 1; Membranes, Artificial; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions

Carboxymethyl cellulose granules (CMC-G) and kappa-carrageenan/polyethylene oxide/polyethylene glycol dressing (KPP-D) hemostatic agents, developed through radiation-induced crosslinking and sterilization, were tested in Sprague-Dawley rats using three bleeding models: (a) deep wound with the puncture of femoral artery; (b) aortic puncture; and (c) partial nephrectomy. Dressing and granules were applied in the animals without sustained compression and monitored for a period of 7 or 14 days. Comparisons were made against the commercial chitosan-based agent, Celox (CLX). Primary outcomes observed were bleeding time, the incidence of re-bleeding, animal survival, as well as gross and microscopic changes. The KPP-D group showed the shortest bleeding time for all bleeding models (a. 2.75 ± 0.64, b. 1.63 ± 0.54, c. 2.05 ± 0.62), significantly faster than all the other treatment groups. KPP-D also registered the highest survival rate of 100% with no display of gross abnormalities. CMC-G showed comparable bleeding time with CLX products but had a better survival rate at 98% compared to 96%. The incidence of re-bleeding was greater in CLX treated groups as well as more occurrence of granular adhesions that impacted mortality outcomes. Findings indicate the efficacy of KPP-D in the treatment of severe hemorrhage due to traumatic injury and intraoperative cases, while CMC-G was more suited for external trauma. Complications arising from inflammation, granules deposition, and adhesions emphasize stringent handling and removal of granular hemostat as a critical consideration in hemostat development and testing.

Topics: Animals; Aorta; Bandages; Bleeding Time; Carboxymethylcellulose Sodium; Carrageenan; Disease Models, Animal; Femoral Artery; Gamma Rays; Hemorrhage; Hemostatics; Male; Polyethylene Glycols; Rats, Sprague-Dawley

This study aimed to evaluate the efficacy and safety of transplantation with human corneal limbal epithelial (HCLE) cell sheets cultured on carboxymethyl cellulose (CMC)-dopamine (DA)-coated substrates and harvested via enzymatic digestion of CMC with cellulase in a rabbit animal model of limbal stem cell deficiency (LSCD). Synthesized CMC-DA was pretreated onto the surface of culture plates. Then, HCLE cells were cultured on precoated CMC-DA and HCLE cell sheets were harvested using cellulase-containing cell culture medium. HCLE cell sheets were evaluated using a live/dead assay, histological examination, and immunofluorescence staining. For in vivo assessment, HCLE cell sheets were transplanted in a rabbit model of LSCD for 2 weeks to determine the effectiveness of the repair. Primary culture of HCLE cells stained positively for p63, cytokeratin (CK)15, and CK12. HCLE cell sheets were generated with a well-preserved morphology and transparency ranging in size from 15 to 19 mm after cellulase-assisted cell sheet generation. HCLE cell sheets uniformly stained positively for human mitochondria, p63, CK15, CK12, CK3/2p, and zonula occludens (ZO)-1. HCLE cell sheet transplantation in a rabbit model of LSCD improved the corneal opacity and neovascularization scores. Transplanted HCLE cell sheets stained positively for p63 and CK12. Transplantation of HCLE cell sheets harvested on CMC-DA coating combined with cellulase is a safe and efficient procedure for corneal epithelial regeneration in a rabbit model of LSCD. This system could enable a promising strategy to regenerate corneal epithelium by transplantation in ocular surface disorders.

Topics: Animals; Carboxymethylcellulose Sodium; Cornea; Corneal Diseases; Disease Models, Animal; Dopamine; Epithelial Cells; Epithelium, Corneal; Heterografts; Humans; Limbus Corneae; Rabbits; Stem Cells

An important mechanism involved in dry eye (DE) is the association between tear hyperosmolarity and inflammation severity. Inflammation in DE might be mediated by the NLRP3 inflammasome, which activated by exposure to reactive oxygen species (ROS). A combination of carboxymethylcellulose (CMC) and α-melanocyte stimulating hormone (α-MSH) may influence DE through this mechanism, thus avoiding defects of signal drug. In this study, we assessed whether treatment comprising CMC combined with α-MSH could ameliorate ocular surface function; we found that it promoted tear secretion, reduced the density of fluorescein sodium staining, enhanced the number of conjunctival goblet cells, and reduced the number of corneal apoptotic cells. Investigation of the underlying mechanism suggested that the synergistic effect of combined treatment alleviated DE inflammation through reduction of ROS level and inhibition of the NLRP3 inflammasome in human corneal epithelial cells. These findings indicate that combined CMC + α-MSH treatment could ameliorate lesions and restore ocular surface function in patients with DE through reduction of ROS level and inhibition of NLRP3 signalling.

Topics: alpha-MSH; Animals; Apoptosis; Carboxymethylcellulose Sodium; Cell Line; Conjunctiva; Cornea; Disease Models, Animal; Dry Eye Syndromes; Epithelial Cells; Female; Goblet Cells; Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Wistar; Reactive Oxygen Species; Scopolamine; Signal Transduction; Tears

The present study was conducted to investigate the therapeutic effects of a potent polyphenol, fisetin, on the letrozole-induced rat model of polycystic ovary syndrome (PCOS).. Twenty-four female Wistar rats (42 days old) were divided into four groups: control group (received carboxy methylcellulose (CMC 0.5 %)), PCOS group treated with letrozole (1 mg/kg), fisetin group received same dose of letrozole + fisetin (10 mg/kg), and metformin group received same dose of letrozole + metformin (300 mg/kg). At the end of the experiment, biochemical (glucose, lipid profile) and hormonal (insulin, testosterone, estradiol, and progesterone) parameters were analyzed. Histological examinations of ovaries were also conducted by hematoxylin and eosin (H&E) staining. Real-time polymerase chain reaction (PCR) and western blotting were carried out for cytochrome P450 17A1 (CYP17A1), sirtuin-1 (SIRT1), and 5' AMP-activated protein kinase (AMPK) gene expression in the ovaries. Furthermore, enzymatic activities of antioxidants including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the ovaries were analyzed by colorimetric method.. Letrozole administration resulted in a remarkable abnormality in biochemical and hormonal parameters. Fisetin normalized levels of glucose, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), testosterone, estradiol, and progesterone. Moreover, fisetin increased expression levels of SIRT1 and AMPK, and decreased expression level of CYP17A1 in the ovaries. Additionally, fisetin showed protective effect by enhancing antioxidant activities of CAT, SOD, and GPx depleted secondary to induction of PCOS. Fisetin effects were comparable to metformin, as the standard drug used for treatment of PCOS.. Our results showed that, fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations in the key genes involved in energy homeostasis and antioxidant enzymes, suggesting that it may have a key role in combating with PCOS.

Topics: AMP-Activated Protein Kinases; Animals; Antineoplastic Agents, Phytogenic; Blood Glucose; Carboxymethylcellulose Sodium; Catalase; Disease Models, Animal; Estradiol; Female; Flavonols; Gene Expression; Glutathione Peroxidase; Humans; Insulin; Letrozole; Metformin; Ovary; Polycystic Ovary Syndrome; Progesterone; Rats; Rats, Wistar; Sirtuin 1; Steroid 17-alpha-Hydroxylase; Superoxide Dismutase; Testosterone

Topics: Administration, Oral; Animals; Biomarkers; Carboxymethylcellulose Sodium; Chromatography, Liquid; Diazepam; Disease Models, Animal; Drug Overdose; GABA Modulators; Male; Neurotransmitter Agents; Phenobarbital; Rats, Wistar; Tandem Mass Spectrometry

In hernia surgery, soaking of meshes in antibiotics before implantation is a prophylactic strategy for minimizing the risk of infection while providing minimal, local, drug doses. This study describes the development and application of an antibacterial mesh coating comprising a carboxymethylcellulose gel loaded with rifampicin in a preclinical model of Staphylococcus aureus and S. epidermidis infection in rabbits.. In vitro, rifampicin-carboxymethylcellulose gel demonstrated great activity against Staphylococcus aureus/S. epidermidis, while being innocuous for fibroblasts. In vivo, rifampicin-carboxymethylcellulose gel-coated implants displayed full bacterial clearance and optimal tissue integration, irrespective of the strain of Staphylococcus. In contrast, uncoated and carboxymethylcellulose gel-coated implants exhibited macro/microscopic signs of infection and impaired tissue integration. Macrophage responses were less in rifampicin-carboxymethylcellulose gel implants than in uncoated mesh (Staphylococcus aureus/S. epidermidis; P < .01) and carboxymethylcellulose gel (S. epidermidis; P < .05) implants. Bloodstream levels of rifampicin were undetectable.. Soaking meshes in rifampicin-carboxymethylcellulose gel inhibited effectively the bacterial adhesion to the mesh without compromising the tissue repair. This antibiotic gel constitutes an easy-to-use and effective prophylactic strategy that potentially reduce the prevalence of postoperative mesh infection.

Topics: Animals; Anti-Bacterial Agents; Antibiotic Prophylaxis; Carboxymethylcellulose Sodium; Disease Models, Animal; Hernia, Abdominal; Herniorrhaphy; Humans; Male; Microbial Sensitivity Tests; Rabbits; Rifampin; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Surgical Mesh; Surgical Wound Infection

Nanosized dioscin-loaded zein-CMC (DZC) complex comprising dioscin (glycoside saponin), zein (corn protein), and carboxymethyl cellulose (CMC) is fabricated through anti-solvent coprecipitation. The optimized ratio of zein to CMC for the homogenous complexation is 5:1, and DZC maintains its stability in a wide range of pH (3.0-8.0) and ionic strength (0-50 mm NaCl). No biological toxicity of DZC is found in Caenorhabditis elegans with a normal lifespan and body size. Parkinson's disease (PD) is characterized by the loss of dopamine (DA) and dopaminergic neurons. In cat-2 mutant with defective biosynthesis of DA, DZC-fed animals show intact DA behaviors including basal slowing response (≈60%) and alcohol avoidance (≈80%). Such DA promotional effects are a result of the enhanced expression/activation of DA transporter, DAT-1 in DA neurons. Taken together, DZC has a potential for preventing PD as an oral-administered drugs and supplements.

Topics: Animals; Caenorhabditis elegans; Carboxymethylcellulose Sodium; Diosgenin; Disease Models, Animal; Parkinson Disease; Zein

There is an association between food additive emulsifiers and the prevalence of Crohn's disease. This study aimed to investigate: (i) the effect of different classes of emulsifiers on markers of intestinal inflammation in mice and (ii) the feasibility, nutritional adequacy and symptom impact of restricting all emulsifier classes in Crohn's disease. Mice were exposed to different classes of emulsifiers (carboxymethycellose, polysorbate-80, soy lecithin, gum arabic) in drinking water for 12-weeks, after which markers of inflammation and metabolism were measured. A low emulsifier diet was developed to restrict all classes of emulsifiers and its feasibility measured over 14-days in 20 participants with stable Crohn's disease. Crohn's disease-related symptoms, disease control, body weight and composition, nutrient intake and food-related quality of life (QoL) were measured. All emulsifiers resulted in lower murine colonic length compared with control (mean 9.5 cm (SEM 0.20)), but this only reached significance for polysorbate-80 (8.2 cm (0.34),

Topics: Adult; Animals; Biomarkers; Body Weights and Measures; Carboxymethylcellulose Sodium; Colon; Crohn Disease; Diet; Disease Models, Animal; Emulsifying Agents; Feasibility Studies; Female; Food Additives; Gum Arabic; Humans; Inflammation; Lecithins; Male; Mice; Mice, Inbred C57BL; Middle Aged; Polysorbates; Young Adult

The toxicity of sodium carboxymethyl cellulose (CMC), which has GRAS status and has been determined as "ADI non specified", was re-evaluated with a new modelling and molecular-based data. For this purpose, CMC, a food additive, was injected to the yolk sac (food) of the zebrafish embryo by the microinjection method at the 4th hour of fertilization at different concentrations. As a result, it was found that CMC showed no toxic effects within the framework of the parameters studied. But, we determined increasing lipid accumulation in zebrafish embryos exposed to CMC in a dose-dependent manner. To elucidate the mechanism underlying this lipid accumulation, the expression levels of genes related to obesity-linked lipid metabolism were examined. Our findings show that while CMC does not cause a toxic effect in zebrafish embryos, it can lead important effects on lipid metabolism by causing changes in the expression of some genes associated with obesity.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Embryo, Nonmammalian; Food; Food Additives; Humans; Lipid Metabolism; Obesity; Sodium; Zebrafish

Few burn dressings can self-regulate the optimal humidity levels that are required for wound healing, while also providing good anti-adhesive properties to prevent damage that can occur when wound dressings are changed. Consequently, a water-soluble carboxymethylcellulose sodium/sodium alginate/chitosan (CMC-Na/SA/CS) composite hydrogel has been developed as a potential burn wound dressing, with orthogonal testing revealing an optimal ratio of CMC-Na, SA, and CS as 2, 3, and 1 wt % for hydrogel preparation, respectively. The resultant hydrogel has been formulated into composite wound dressings that were then used for the treatment of deep second degree burn wounds in Sprague-Dawley (SD) rats. Analysis of the physical properties of this dressing revealed that it exhibits good water vapor permeability properties that promote the healing of deep second-degree burn wounds. The pro-healing mechanism of the dressing has been investigated Vascular endothelial growth factor (VEGF) expression was upregulated and basic fibroblast growth factor (bFGF) expression was downregulated in the early periods of wound healing, with upregulation of bFGF then occurring at a later stage of wound healing. At the same time, the wound dressing decreased the levels of tumor necrosis factor-α and interleukin-6, thus validating its beneficial effect on the wound healing process at a biomolecular level. In conclusion, this new hydrogel dressing was shown to exhibit excellent self-regulatory and anti-adhesive properties that synergistically promote the healing of burn wounds in rats, thus providing promising results that may have clinical applications. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1471-1482, 2019.

Topics: Alginates; Animals; Burns; Carboxymethylcellulose Sodium; Chitosan; Disease Models, Animal; Hydrogels; Male; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Wound Healing; Wounds and Injuries

Adhesion formation that occurred after alkali-induced injury of the cecum was used as a novel adhesion model in rats, and it was compared with that of a common adhesion model after abrading the cecum. Using the novel adhesion model, inhibition of adhesion formation by a chymase inhibitor, Suc-Val-Pro-PheP(OPh)2, and by sodium hyaluronate/carboxymethylcellulose (Seprafilm) was evaluated, and their mechanisms were assessed. The degree of adhesion formation was more severe and more stable in the alkali-induced injury model than in the abrasion-induced injury model. Both the chymase inhibitor and Seprafilm showed significant attenuation of the degree of adhesion 14 days after alkali-induced injury. Chymase activity in the cecum was significantly increased after alkali-induced injury, but it was significantly attenuated by the chymase inhibitor and Seprafilm. Myeloperoxidase and transforming-growth factor (TGF)-β levels were significantly increased after alkali-induced injury, but they were attenuated by both the chymase inhibitor and Seprafilm. At the level of the adhesions, the numbers of both chymase-positive cells and TGF-β-positive cells were significantly increased, but their numbers were reduced by the chymase inhibitor and Seprafilm. In conclusion, a chymase inhibitor attenuated the degree of adhesions to the same degree as Seprafilm in a novel peritoneal adhesion model that was more severe and more stable than the common adhesion model, and not only the chymase inhibitor, but also Seprafilm reduced the chymase increase at the adhesions.

Topics: Animals; Carboxymethylcellulose Sodium; Cecum; Chymases; Disease Models, Animal; Gene Expression; Hyaluronic Acid; Male; Peritoneal Diseases; Peroxidase; Protease Inhibitors; Rats; Rats, Sprague-Dawley; Tissue Adhesives; Transforming Growth Factor beta

Microglia play crucial roles in the maintenance of brain homeostasis. Activated microglia show a biphasic influence, promoting beneficial repair and causing harmful damage via M2 and M1 microglia, respectively. It is well-known that microglia are initially activated to the M2 state and subsequently switch to the M1 state, called M2-to-M1 class switching in acute ischemic models. However, the activation process of microglia in chronic and sporadic hypertension remains poorly understood. We aimed to clarify the process using a chronic hypertension model, the deoxycorticosterone acetate (DOCA)-salt-treated Wistar rats.. After unilateral nephrectomy, the rats were randomly divided into DOCA-salt, placebo, and control groups. DOCA-salt rats received a weekly subcutaneous injection of DOCA (40 mg/kg) and were continuously provided with 1% NaCl in drinking water. Placebo rats received a weekly subcutaneous injection of vehicle and were provided with tap water. Control rats received no administration of DOCA or NaCl. To investigate the temporal expression profiles of M1- and M2-specific markers for microglia, the animals were subjected to the immunohistochemical and biochemical studies after 2, 3, or 4 weeks DOCA-salt treatment.. Hypertension occurred after 2 weeks of DOCA and salt administration, when round-shaped microglia with slightly shortened processes were observed juxtaposed to the vessels, although the histopathological findings were normal. After 3 weeks of DOCA and salt administration, M1-state perivascular and parenchyma microglia significantly increased, when local histopathological findings began to be observed but cerebrovascular destruction did not occur. On the other hand, M2-state microglia were never observed around the vessels at this period. Interestingly, prior to M1 activation, about 55% of perivascular microglia transiently expressed Ki-67, one of the cell proliferation markers.. We concluded that the resting perivascular microglia directly switched to the pro-inflammatory M1 state via a transient proliferative state in DOCA-salt rats. Our results suggest that the activation machinery of microglia in chronic hypertension differs from acute ischemic models. Proliferative microglia are possible initial key players in the development of hypertension-induced cerebral vessel damage. Fine-tuning of microglia proliferation and activation could constitute an innovative therapeutic strategy to prevent its development.

Topics: Animals; Antigens, CD; Blood Pressure; Brain; Calcium-Binding Proteins; Carboxymethylcellulose Sodium; Cell Proliferation; Desoxycorticosterone Acetate; Disease Models, Animal; Functional Laterality; Hypertension; Ki-67 Antigen; Magnetic Resonance Imaging; Male; Microfilament Proteins; Microglia; Mineralocorticoids; Nephrectomy; Rats; Rats, Wistar; Sodium Chloride; Time Factors

Back pain commonly arises from intervertebral disc (IVD) damage including annulus fibrosus (AF) defects and nucleus pulposus (NP) loss. Poor IVD healing motivates developing tissue engineering repair strategies. This study evaluated a composite injectable IVD biomaterial repair strategy using carboxymethylcellulose-methylcellulose (CMC-MC) and genipin-crosslinked fibrin (FibGen) that mimic NP and AF properties, respectively. Bovine ex vivo caudal IVDs were evaluated in cyclic compression-tension, torsion, and compression-to-failure tests to determine IVD biomechanical properties, height loss, and herniation risk following experimentally-induced severe herniation injury and discectomy (4 mm biopsy defect with 20% NP removed). FibGen with and without CMC-MC had failure strength similar to discectomy injury suggesting no increased risk compared to surgical procedures, yet no biomaterials improved axial or torsional biomechanical properties suggesting they were incapable of adequately restoring AF tension. FibGen had the largest failure strength and was further evaluated in additional discectomy injury models with varying AF defect types (2 mm biopsy, 4 mm cruciate, 4 mm biopsy) and NP removal volume (0%, 20%). All simulated discectomy defects significantly compromised failure strength and biomechanical properties. The 0% NP removal group had mean values of axial biomechanical properties closer to intact levels than defects with 20% NP removed but they were not statistically different and 0% NP removal also decreased failure strength. FibGen with and without CMC-MC failed at super-physiological stress levels above simulated discectomy suggesting repair with these tissue engineered biomaterials may perform better than discectomy alone, although restored biomechanical function may require additional healing with the potential application of these biomaterials as sealants and cell/drug delivery carriers.

Topics: Animals; Annulus Fibrosus; Biocompatible Materials; Biomechanical Phenomena; Carboxymethylcellulose Sodium; Cattle; Cross-Linking Reagents; Disease Models, Animal; Diskectomy; Fibrin; Hydrogels; In Vitro Techniques; Injections, Spinal; Intervertebral Disc Displacement; Iridoids; Materials Testing; Methylcellulose; Nucleus Pulposus

Systems consisting of a polyelectrolyte solution in contact with a cross-linked polyelectrolyte network are ubiquitous (e.g., biofilms, drug-delivering hydrogels, and mammalian extracellular matrices), yet the underlying physics governing these interactions is not well understood. Here, we find that carboxymethyl cellulose, a polyelectrolyte commonly found in processed foods and associated with inflammation and obesity, compresses the colonic mucus hydrogel (a key regulator of host-microbe interactions and a protective barrier) in mice. The extent of this polyelectrolyte-induced compression is enhanced by the degree of polymer negative charge. Through animal experiments and numerical calculations, we find that this phenomenon can be described by a Donnan mechanism. Further, the observed behavior can be quantitatively described by a simple, one-parameter model. This work suggests that polymer charge should be considered when developing food products because of its potential role in modulating the protective properties of colonic mucus.

Topics: Animals; Bacterial Infections; Biofilms; Carboxymethylcellulose Sodium; Colon; Disease Models, Animal; Glycoproteins; Host-Pathogen Interactions; Humans; Hydrogels; Inflammation; Mice; Mucus; Obesity; Polyelectrolytes; Polymers

This study aimed to investigate the chemical characteristics and the effects of an orabase gel with Cashew Gum Polysaccharide (CG-P) from Anacardium occidentale L. on alveolar bone loss and relative mRNA expression of TNF-α, IL-1β, RANK, RANKL, and OPG in the periodontal tissue of Wistar rats (Rattus norvegicus) subjected to ligature-induced periodontitis. Crude cashew gum was collected and purified by chemical processes; then, the CG-P was mixed with orabase gel. Female rats were randomly divided into four groups of six animals each: saline 0.9% (Sal Group); orabase gel (Gel Group); 50mg CG-P/1g orabase gel (CG-P50 Group) and 150mg CG-P/1g orabase gel (CG-P150 Group). Periodontitis was induced in the animals; they were treated for 20days with one daily topical application. The purification process of CG-P presented high yield and resulted in a protein-free product. The treatment with CG-P150 (150mg CG-P/1g orabase gel) significantly reduced alveolar bone loss, decreased the relative mRNA expression of TNF-α, IL-1β, RANKL and the RANKL/OPG ratio, and caused a significant decrease in myeloperoxidase activity of the gingival tissue. Thus, the CG-P in orabase represents a potential adjuvant drug for the treatment of periodontitis and possible source of new biotechnological discoveries.

Topics: Alveolar Bone Loss; Anacardium; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Inflammation; Interleukin-1beta; Oxidative Stress; Periodontitis; Peroxidase; Polysaccharides; RANK Ligand; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

The purpose of this study was to compare the effects of the oral administration of natural curcumin and a chemically modified curcumin (CMC2.24) on osteoclast-mediated bone resorption, apoptosis, and inflammation in a murine model of experimental periodontal disease.. Fifty male rats were distributed among the following treatment groups: (i) 2% carboxymethylcellulose, (ii) CMC2.24 30 mg/kg body weight, (iii) Curcumin 100 mg/kg body weight and (iv) no treatment. Compounds were administered daily by oral intubation over a 15-day period of time. Periodontal disease was induced by injections of LPS (lipopolysaccharide) into the gingival tissues three times per week. Contralateral sides were injected with the same volume of PBS (phosphate buffered saline) vehicle. After 15 days, hemimaxillae and gingival tissues were harvested. Bone resorption was assessed by μCT (microcomputer tomography). Formalin-fixed, paraffin embedded histological sections were stained with haematoxylin/eosin (H/E) for the assessment of cellular infiltrate or subjected to immunohistochemistry for detecting TRAP (tartrate-resistant acid phosphatase)-positive cells and caspase-3. Apoptosis was assessed in the gingival tissues by DNA fragmentation.. CMC2.24 and curcumin caused a significant reduction of the inflammatory cell infiltrate, however μCT analysis showed that only CMC2.24 reduced bone resorption and the number of TRAP-positive multinucleated cells (osteoclasts). Curcumin, but not CMC2.24, significantly reduced the number of apoptotic cells in the gingival tissues and of osteocytes in the alveolar bone crest.. The results suggest that CMC2.24 and curcumin inhibit inflammation by different mechanisms, but only CMC2.24 was capable of reducing alveolar bone resorption in the LPS-induced model of periodontitis.

Topics: Administration, Oral; Alveolar Bone Loss; Animals; Apoptosis; Body Weight; Bone and Bones; Carboxymethylcellulose Sodium; Caspase 3; Curcumin; Disease Models, Animal; Gingiva; Immunohistochemistry; Inflammation; Lipopolysaccharides; Male; Osteoclasts; Periodontitis; Rats; Tartrate-Resistant Acid Phosphatase; Time Factors; Tomography

Animal models of sciatic nerve injury are commonly used to study neuropathic pain as well as axon regeneration. Inflammation/immune response at the site of nerve lesion is known to be an essential trigger of the pathological changes that have a critical impact on nerve repair and regeneration; moreover, the damage to peripheral nerve can cause a loss of sensory function and produces a persistent neuropathic pain. N-Acylethanolamines (NAEs) involve a family of lipid molecules existent in animal and plant, of which is N-palmitoylethanolamide (PEA) that arouses great attention owing to its anti-inflammatory, analgesic, and neuroprotective activities. The modulation of specific amidases for NAEs (and in particular NAE-hydrolyzing acid amidase NAAA, which is more selective for PEA) could be a condition to preserve its levels. Here, we investigated, in a mice model of sciatic nerve crush, the effect of 2-pentadecyl-2-oxazoline (PEA-OXA) the oxazoline of PEA that reportedly modulates activity of NAAA.. In this experimental model, the mice, following the sciatic nerve crush, were treated daily with PEA-OXA at a dose of 10 mg\\kg for 14 days. Therefore, we evaluated the effects of PEA-OXA on the degree of injury, on the inhibition of neuropathic pain, and on the inflammatory process, as in the improvement of reparative processes and therefore in the restoration of locomotor function.. Our results showed that PEA-OXA (10 mg/kg) treatment, daily, for 14 days after sciatic nerve crush, have an anti-inflammatory and neuroprotective effect and moreover have an analgesic protective effect on hypersensitivity, and improve the functional recovery after nerve crush.. Therefore, treatment with PEA-OXA as a whole has shown a protective effect, which makes it a powerful candidate for the treatment of peripheral nerve injury and neuropathic pain.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Carboxymethylcellulose Sodium; Cytokines; Disease Models, Animal; Gene Expression Regulation; Hyperalgesia; I-kappa B Proteins; Male; Mast Cells; Mice; Nerve Growth Factor; Neuralgia; Neuroglia; Oxazoles; Pain Threshold; Psychomotor Performance; Recovery of Function; Sciatic Neuropathy; Tubulin

To create more useful, effective and safer anti-adhesion materials, we developed a thermally cross-linked gelatin film. In this study, we examined the physical properties of the film such as the physical strength and the adhesiveness to reveal the handling properties and biological properties, such as the anti-adhesion effect, the influence on cell proliferation, and the cytotoxicity to reveal the anti-adhesion mechanism, especially in comparison with the conventional hyaluronic acid and carboxymethylcellulose film (the conventional film). A tensile test under dry and wet conditions and shearing stress test showed that the gelatin film has significant higher maximum tensile stress and fracture strain than the conventional film. In the study using a rat model of cecum adhesion, the anti-adhesion effect of the gelatin film was significantly superior to that of the conventional film. In the cell proliferation test, the number of fibroblast cells on the gelatin film increased at each time point, while no cell proliferation was observed on the conventional film. Furthermore, in the cytotoxicity test using a colony assay and Live/Dead assay, the extract of the gelatin film had no cytotoxicity, while the extract of the conventional film had cytotoxicity considerably. These results suggest that the gelatin film provides better handling than the conventional film, due to better physical strength and ductility of the film. In addition, the gelatin film has a significantly greater anti-adhesion effect than the conventional film without any cytotoxicity. Therefore, the gelatin film is quite favorable as an anti-adhesion material. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 689-696, 2018.

Topics: Adhesiveness; Animals; Carboxymethylcellulose Sodium; Cecum; Cell Proliferation; Cross-Linking Reagents; Disease Models, Animal; Dogs; Female; Fibroblasts; Gelatin; Humans; Hyaluronic Acid; Polymers; Rats; Tensile Strength; Tissue Adhesions

Perineural adherences represent a problem after surgery involving peripheral neural system. Fat-grafting with adipose derived stem cells (ASCs) with their pro-regenerative characteristics can be important to prevent the neural damage or to facilitate the neural regeneration. Our idea was to use the fat-grafting as an anti-adherence device and test its efficacy on a postsurgical scar animal model and comparing to an antiadhesive gel. 32 athymic mice were operated under magnification, we exposed both sciatic nerves. We randomly divided all sciatic nerves into four experimental groups: burning (1), burning + carboxy-methylcellulose and poly- ethylene oxide (CMC-PEO) (2) + human adipose fat tissue (3), control group (4). Bio-mechanical evaluation was performed to measure the peak force required to pull out the nerve from the muscular bed.. in the CMC-PEO group the peak pull out force was 0.37 Newton. In the fat grafted group we registered a peak pull out force of 0.35 N (t Student 0.913). In burning group the force necessary to tear the nerve apart was markedly superior (0.46 N). In control group, we reported the minimal strength (0.31 N) to slide the nerve from the tissue. Histologically, in the group treated with fat-grating, a thinner scar layer was highlighted. Considering the results of this study we can support the efficacy in animal experimental model of fat graft as an anti-adherence device in peripheral nerve surgery.

Topics: Adhesiveness; Adipose Tissue; Animals; Burns; Carboxymethylcellulose Sodium; Cicatrix; Disease Models, Animal; Humans; Mice; Mice, Nude; Nerve Regeneration; Polyethylene Glycols; Sciatic Nerve

Alginate is a natural rich anionic polysaccharide (APS), commonly available as calcium alginate (CAPS). It can maintain a physiologically moist microenvironment, which minimises bacterial infection and facilitates wound healing at a wound site. Patients with burn injuries suffer from pain and an inflammatory response. In this study, we evaluated the CAPS dressing and traditional dressing containing carboxymethyl cellulose (CMC) for wound healing and scar tissue formation in a burn model of rat and swine. In our pilot study of a burn rat model to evaluate inflammatory response and wound healing, we found that the monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-β were up-regulated in the CAPS treatment group. Next, the burn swine models tested positive for MCP-1 in a Gram-positive bacterial infection, and there was overproduction of TGF-β during the burn wound healing process. Rats were monitored daily for 1 week for cytokine assay and sacrificed on day 28 post-burn injury. The swine were monitored over 6 weeks. We further examined the pain and related factors and inflammatory cytokine expression in a rodent burns model monitored everyday for 7 days post-burn. Our results revealed that the efficacy of the dressing containing CAPS for wound repair post-burn was better than the CMC dressing with respect to natural wound healing and scar formation. The polysaccharide-enriched dressing exerted an antimicrobial effect on burn wounds, regulated the inflammatory response and stimulated anti-inflammatory cytokine release. However, one pain assessment method showed no significant difference in the reduction in levels of adenosine triphosphate in serum of rats after wound dressing in either the CAPS or CMC group. In conclusion, a polysaccharide-enriched dressing outperformed a traditional dressing in reducing wound size, minimising hypertrophic scar formation, regulating cytokines and maximising antimicrobial effects.

Topics: Alginates; Animals; Bandages, Hydrocolloid; Burns; Carboxymethylcellulose Sodium; Disease Models, Animal; Glucuronic Acid; Hexuronic Acids; Pilot Projects; Rats; Swine; Wound Healing

Monitoring patients with burn wounds for infection is standard practice because failure to rapidly and specifically identify a pathogen can result in poor clinical outcomes, including death. Therefore, a method that facilitates detection and identification of pathogens in situ within minutes of biopsy would be a significant benefit to clinicians. Mass spectrometry is rapidly becoming a standard tool in clinical settings, capable of identifying specific pathogens from complex samples. Imaging mass spectrometry (IMS) expands the information content by enabling spatial resolution of biomarkers in tissue samples as in histology, without the need for specific stains/antibodies. Herein, a murine model of thermal injury was used to study infection of burn tissue by Pseudomonas aeruginosa. This is the first use of IMS to detect P. aeruginosa infection in situ from thermally injured tissue. Multiple molecular features could be spatially resolved to infected or uninfected tissue. This demonstrates the potential use of IMS in a clinical setting to aid doctors in identifying both presence and species of pathogens in tissue.

Topics: Animals; Biomarkers; Burns; Carboxymethylcellulose Sodium; Disease Models, Animal; Gelatin; Mice; Optical Imaging; Pseudomonas aeruginosa; Pseudomonas Infections; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The increased risks conferred by inflammatory bowel disease (IBD) to the development of colorectal cancer gave rise to the term "colitis-associated cancer" and the concept that inflammation promotes colon tumorigenesis. A condition more common than IBD is low-grade inflammation, which correlates with altered gut microbiota composition and metabolic syndrome, both present in many cases of colorectal cancer. Recent findings suggest that low-grade inflammation in the intestine is promoted by consumption of dietary emulsifiers, a ubiquitous component of processed foods, which alter the composition of gut microbiota. Here, we demonstrate in a preclinical model of colitis-induced colorectal cancer that regular consumption of dietary emulsifiers, carboxymethylcellulose or polysorbate-80, exacerbated tumor development. Enhanced tumor development was associated with an altered microbiota metagenome characterized by elevated levels of lipopolysaccharide and flagellin. We found that emulsifier-induced alterations in the microbiome were necessary and sufficient to drive alterations in major proliferation and apoptosis signaling pathways thought to govern tumor development. Overall, our findings support the concept that perturbations in host-microbiota interactions that cause low-grade gut inflammation can promote colon carcinogenesis. Cancer Res; 77(1); 27-40. ©2016 AACR.

Topics: Animals; Carboxymethylcellulose Sodium; Cell Transformation, Neoplastic; Colitis; Colonic Neoplasms; Disease Models, Animal; Emulsifying Agents; Food Additives; Gastrointestinal Microbiome; Male; Mice; Mice, Inbred C57BL; Polysorbates

Topics: Animals; Carboxymethylcellulose Sodium; Cornea; Disease Models, Animal; Dry Eye Syndromes; Glycerol; Hyaluronic Acid; Lubricant Eye Drops; Preservatives, Pharmaceutical; Rabbits; Wound Healing

Perineural scar formation is responsible for pain and loss of function after surgical procedures. Neurolysis and application of anti-adhesion gels are required to restore a gliding surface. We tested a carboxymethylcellulose (CMC) and polyethylene oxide (PEO) gel on mouse sciatic nerve to describe its safety and efficacy.. Adult mice underwent a surgical procedure in which we burned the muscular bed of the sciatic nerve bilaterally (Burned group) and applied anti-adhesion gel to 1 of the nerves (Burned+gel group). After 3 weeks, we studied scar tissue by biomechanical and histological evaluation.. Both histological and biomechanical analysis showed that the gel reduced perineural scarring. The difference between the Burned and Burned+gel groups was statistically significant.. CMC-PEO gel can reduce perineural scar tissue. In histological section, scar tissue was present in both groups, but in the Burned+gel group a gliding surface was identified between scar and nerve.

Topics: Animals; Biomechanical Phenomena; Burns; Carboxymethylcellulose Sodium; Disease Models, Animal; Mice; Mice, Inbred ICR; Peripheral Nervous System Diseases; Polyethylene Glycols; Surface-Active Agents

To investigate the therapeutic effectiveness of ion-activated mucoadhesive hydrogel system in the treatment of experimental bacterial keratitis.. Mucoadhesive systems were prepared using gellan or sodium alginate alone and combined with sodium carboxymethylcellulose (NaCMC) to enhance the gel bioadhesion properties. The in vivo antimicrobial efficacy of selected mucoadhesive systems was studied in an experiment on bacterial keratitis in rabbit's eyes and compared with that of the marketed conventional eyedrops.. Ocular tolerance was studied in the eye of albino rabbits and tested formulations were non-irritant with no sign of inflammation. Better improvement in experimental bacterial keratitis in rabbit eyes was observed in animals treated with mucoadhesive hydrogel formulation (GG5 and GS5) compared with marketed drug solution.. The developed system is a viable alternative to conventional eyedrops of GTN due to its ability to enhance bioavailability through its longer precorneal residence time.

Topics: Alginates; Animals; Anti-Bacterial Agents; Biological Availability; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Corneal Ulcer; Disease Models, Animal; Drug Carriers; Eye Infections, Bacterial; Fluoroquinolones; Gatifloxacin; Glucuronic Acid; Hexuronic Acids; Hydrogels; Polysaccharides, Bacterial; Rabbits; Staphylococcal Infections; Staphylococcus aureus; Treatment Outcome

To evaluate macro and microscopically the adhesions developed after using the anti-adherence compound sodium hyaluronate and carboxymethylcellulose (SH-CBMC) gel and to determine the volume of the adhesions using a stereological estimation.. The study was experimental, random, comparative, and prospective. The subjects of the study were male Wistar rats divided in three groups (n = 10). Group I (control) included rats with no peritoneal injury. Group II rats had a 2 cm diameter injury created bilaterally in the parietal peritoneum at 3 cm from the abdominal midline with electrocautery coated with physiological solution. Group III rats were given the same injuries and coated with SH-CBMC gel. All groups were followed up postoperatively for 30 days, after which a laparotomy was performed to macroscopically determine the presence and type of adhesions. Experimental models were euthanized with anesthetic overdose and biopsies were taken for histopathological examination and stereological estimate of the volume of adhesions.. Macroscopic adhesions were 20% less prevalent in Group III compared to Group II, which presented 40% more multiple and firm adhesions, unlike in Group III, in which they were unique and lax. There was a statistically significant decrease in the presence and number of adhesions in rats treated with SH-CBMC gel. Inflammatory infiltrate was significantly lower in rats treated with SH-CBMC gel, but there were no differences in connective tissue, fibrosis, and angiogenesis among groups. There was no statistical difference in the overall volume of adhesions among the treatment groups.. SH-CBMC gel reduces macroscopic presence and number of adhesions and the severity of the inflammatory infiltrate.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Gels; Hyaluronic Acid; Laparotomy; Male; Peritoneal Diseases; Peritoneum; Prospective Studies; Random Allocation; Rats; Rats, Wistar; Tissue Adhesions

Background Postoperative adhesions are the result of aberrant peritoneal healing. As they are the leading cause of postoperative bowel obstruction, anti-adherence barriers are advocated for their prevention. This study looks into the effect of these biomaterials on the healing of intestinal anastomoses. Materials and Methods Thirty-three New Zealand White rabbits underwent laparotomy, transection of the terminal ileum, and creation of an end-to-end anastomosis. Animals were randomized into 3 groups: the Control group (n = 11); the Icodextrin group, receiving icodextrin 4% intraperitonealy (n = 11); and the HA/CMC group, having the anastomosis wrapped with a hyaluronic acid/carboxymethylcellulose film (n = 11). All animals were sacrificed on the seventh postoperative day. Macroscopic adhesions were graded and anastomotic strength was tested by the burst pressure. Histological healing was assessed in a semiquantitative way for the presence of ulceration, reepithelization, granulation tissue, inflammation, eosinophilic infiltration, serosal inflammation, and microscopic adhesions. Univariate and multivariate analysis was used. Results are given as medians with interquartile range. Results The median adhesion scores were the following: Control 1 (0-3), Icodextrin 0 (0-1), HA/CMC 0 (0-0), P = .017. The burst pressure did not differ between the groups; however, all except one bowel segments tested burst away from the anastomosis. The macroscopic and histological anastomotic healing was comparable in all 3 groups. A poor histological anastomotic healing score was associated with a higher adhesion grade (odds ratio = 1.92; 95% confidence interval = 1.06-3.47; P = .032). Conclusion Adhesion formation was inhibited by the materials tested without direct detrimental effects on anastomotic healing. Poor anastomotic healing provokes adhesions even in the presence of anti-adhesion barriers.

Topics: Anastomosis, Surgical; Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Disease Models, Animal; Glucans; Glucose; Hyaluronic Acid; Icodextrin; Ileum; Injections, Intralesional; Injections, Intraperitoneal; Laparotomy; Rabbits; Random Allocation; Reference Values; Tissue Adhesions; Treatment Outcome; Wound Healing

The aim of this study was to determine the effects of two anti-inflammatory agents on the abnormalities in colonic endocrine cells in dextran sodium sulfate (DSS)-induced colitis. Colitis was induced in male Wistar rats (n=45) using DSS; a further 15 rats without colitis were included in a healthy control group. The animals with DSS-induced colitis were randomly divided into 3 treatment groups as follows: i) DSS group, rats were treated with 0.5 ml of 0.5% carboxymethyl cellulose (CMC); ii) DSS‑G group, rats were treated with 3-[(dodecylthiocarbonyl)‑methyl]‑glutarimide (DTCM‑G), a novel activator protein 1 (AP-1) inhibitor, 20 mg/kg in CMC; and iii) DSS‑Q group, rats were treated with dehydroxymethylepoxyquinomicin, a nuclear factor κB (NF-κB) inhibitor, 15 mg/kg in CMC. The treatments were administered intraperitoneally, twice daily for 5 days, after which the animals were sacrificed and tissue samples from the colon were immunostained for chromogranin A (CgA), serotonin, peptide YY (PYY), enteroglucagon, pancreatic polypeptide (PP), somatostatin, leukocytes, B/T lymphocytes, B lymphocytes, T lymphocytes, macrophages/monocytes and mast cells. The densities of these endocrine and immune cells were quantified by computer‑aided image analysis. The densities of CgA-, serotonin-, PYY- and enteroglucagon-producing cells were significantly higher, and those of PP- and somatostatin-producing cells were significantly lower in the DSS‑G, DSS‑Q and control groups than in the DSS group. The densities of all the immune cells were lower in the DSS‑G, DSS‑Q and control groups than in the DSS group. The densities of all endocrine cell types and immune cells in both the DSS groups treated with anti‑inflammatory agents were restored to control levels. In conclusion, our data demonstrate that there is an interaction between endocrine and immune cells during inflammation. This interaction with subsequent changes in endocrine cells is responsible for the clinical manifestation of colitis symptoms.

Topics: Animals; Anti-Inflammatory Agents; Benzamides; Carboxymethylcellulose Sodium; Colitis; Colon; Cyclohexanones; Dextran Sulfate; Disease Models, Animal; Endocrine Cells; Male; NF-kappa B; Piperidones; Rats; Rats, Wistar; Transcription Factor AP-1

This study presents the first investigation of the antiviral effects of the liposome-encapsulated PolyICLC (LE-PolyICLC) on Dengue virus (DENV) in a mouse model. In vivo efficacy studies showed that LE-PolyICLC acted to increase antiviral mechanisms mainly through promoting cytokine expression associated with innate immunity, such as IFN-γ. In addition, the pro-inflammatory cytokine TNF-α was also increased, while IL-6 level was decreased in serum. The titers of total antibodies against DENV2 in mice were also elevated. Administration of LE-PolyICLC not only alleviated the loss of body weight, degree of morbidity, and pathological damage in brains, but also reduced the viral titers and expression of viral E protein in the brain. Notably, the effectiveness of LE-PolyICLC was better than PolyICLC on the basis of the data presented in this study. These results, therefore, set a foundation for further development of LE-PolyICLC as an attractive candidate of antiviral agents to be used in both prophylactic and therapeutic settings in DENV diseases.

Topics: Animals; Antibody Formation; Antigens, Viral; Antiviral Agents; Brain; Carboxymethylcellulose Sodium; Cytokines; Dengue; Dengue Virus; Disease Models, Animal; Liposomes; Mice; Mice, Inbred BALB C; Poly I-C; Polylysine; RNA, Viral; Virus Replication

We developed a novel hydrogel derived from sodium carboxymethylcellulose (CMC) in which phosphatidylethanolamine (PE) was introduced into the carboxyl groups of CMC to prevent perineural adhesions. This hydrogel has previously shown excellent anti-adhesive effects even after aggressive internal neurolysis in a rat model. Here, we confirmed the effects of the hydrogel on morphological and physiological recovery after nerve decompression. We prepared a rat model of chronic sciatic nerve compression using silicone tubing. Morphological and physiological recovery was confirmed at one, two, and three months after nerve decompression by assessing motor conduction velocity (MCV), the wet weight of the tibialis anterior muscle and morphometric evaluations of nerves. Electrophysiology showed significantly quicker recovery in the CMC-PE group than in the control group (24.0 ± 3.1 vs. 21.0± 2.1 m/s (p < 0.05) at one months and MCV continued to be significantly faster thereafter. Wet muscle weight at one month significantly differed between the CMC-PE (BW) and control groups (0.148 ± 0.020 vs. 0.108 ± 0.019%BW). The mean wet muscle weight was constantly higher in the CMC-PE group than in the control group throughout the experimental period. The axon area at one month was twice as large in the CMC-PE group compared with the control group (24.1 ± 17.3 vs. 12.3 ± 9 μm2) due to the higher ratio of axons with a larger diameter. Although the trend continued throughout the experimental period, the difference decreased after two months and was not statistically significant at three months. Although anti-adhesives can reduce adhesion after nerve injury, their effects on morphological and physiological recovery after surgical decompression of chronic entrapment neuropathy have not been investigated in detail. The present study showed that the new anti-adhesive CMC-PE gel can accelerate morphological and physiological recovery of nerves after decompression surgery.

Topics: Animals; Axons; Biomechanical Phenomena; Carboxymethylcellulose Sodium; Decompression, Surgical; Disease Models, Animal; Electrophysiological Phenomena; Hydrogel, Polyethylene Glycol Dimethacrylate; Male; Muscle, Skeletal; Nerve Compression Syndromes; Phosphatidylethanolamines; Rats; Rats, Inbred Lew; Tissue Adhesions

The development of an effective rat model of incisional surgical site infection (SSI) has so far proven difficult. In this study, we created a novel incisional SSI model and validated it in terms of both macroscopic and microscopic aspects including its response to treatment using antimicrobial wound-dressing, Aquacel Ag(®). Wounds were created on the dorsum of rats. 3-0 Vicryl(®) threads inoculated with Escherichia coli were inserted in the wound beds in the infection group (n = 6). The wounds were closed for two days to induce infection and then opened and covered with polypropylene sheets during the study. Aquacel Ag was placed under the polypropylene sheet in the infected wounds of the Aquacel Ag group rats (n = 6). The wounds in the control group (n = 6) contained sterile Vicryl thread that had not been inoculated with E. coli. The macroscopic appearance, wound area, bacterial counts, and histology of each group were evaluated. The infection group demonstrated significantly lower wound healing (p < 0.001), greater bacterial counts (median [interquartile range] ratings, 2.15 × 10(7) [0.51 × 10(7)-53.40 × 10(7)] vs 2.07 × 10(4) [0.60 × 10(4)-4.45 × 10(4)] CFU/g, respectively; p < 0.01), and severer histological inflammation (p < 0.001) than the control group. The Aquacel Ag group was only able to show significantly better wound healing than the infection group (p < 0.001). The new incisional SSI model exhibited all clinical manifestations of incisional SSI. It could be utilized to assess the effectiveness of newly developed treatments for incisional SSI.

Topics: Animals; Bandages; Carboxymethylcellulose Sodium; Disease Models, Animal; Escherichia coli; Escherichia coli Infections; Male; Rats; Rats, Sprague-Dawley; Silver; Surgical Wound Infection; Wound Healing

We aimed to evaluate the effects of the barrier agent sodium carboxymethyl cellulose (SCMC) with and without dexamethasone for the prevention of postoperative adhesion formation in a rat model of postoperative peritoneal adhesion. A total of 160 three-month old male and female Wistar rats underwent a laparotomy, and adhesions were induced by ileocecal abrasion. Rats were randomly assigned to 4 groups (n=40 each): group A, untreated; group B, treated with SCMC only; group C1, treated with SCMC + 3 mg dexamethasone, and group C2, treated with SCMC + 8 mg dexamethasone. After 12 days, adhesion formation and histopathological changes were compared. In groups A, B, C1, and C2, the mortality rates were 10, 5, 5, and 5%, respectively. In groups C1 and C2, the adhesions were filmy and easy to dissect and were milder compared with those in groups A and B. The total adhesion score in group C1 (3.38±0.49) was significantly lower than that of group B (6.01±0.57; P<0.01) or group A (8.01±0.67; P<0.05). There was no significant difference in adhesion formation between groups C1 and C2. Compared with groups A and B, groups C1 and C2 exhibited milder histopathological changes. SCMC in combination with dexamethasone can prevent adhesion formation and is a better barrier agent than SCMC alone. The safety and feasibility of SCMC in combination with dexamethasone to prevent adhesion formation after abdominal surgery warrants further clinical study.

Topics: Animals; Carboxymethylcellulose Sodium; Dexamethasone; Disease Models, Animal; Drug Therapy, Combination; Female; Laparotomy; Male; Peritoneal Diseases; Peritoneum; Postoperative Complications; Random Allocation; Rats, Wistar; Tissue Adhesions

Cerebrospinal fluid shunt operations have reduced the morbidity and mortality of hydrocephalus, but have potential complications. Ventriculoperitoneal (vp) shunt obstruction is one of the common complications of shunt surgery. The obstruction is caused by fibrosis and is usually located on the tip of the ventricular and/or peritoneal catheter.. In our study, we aimed to demonstrate the known antifibrotic effects of heparin, hyaluronate/carboxymethylcellulose, and icodextrin on peritoneal catheter obstruction in a vp shunt model in rats.. Thirty-two male Sprague-Dawley rats were used in this study. A shunt catheter was placed in the abdominal cavity. In the control group, isotonic solution, in the study groups, heparin, sodium hyaluronate/carboxymethylcellulose (HA/CMC), and icodextrin were intraperitoneally applied. The severity of adhesions and inflammation around the peritoneal catheter was evaluated after the rats were killed on day 30.. One animal in the heparin group died due to intra-abdominal hemorrhage. We found the most adhesions in the control group. All three drugs (heparin, HA/CMC, icodextrin) were effective for adhesion prevention. HA/CMC was more effective than heparin, and icodextrin was most effective. There was a statistically significant difference between the icodextrin and the control group (p = 0.007).. The intra-abdominal instillation of icodextrin, HA/CMC, and heparin, especially icodextrin, can decrease the rate of vp shunt dysfunction by preventing formation of intraperitoneal fibrosis.

Topics: Animals; Carboxymethylcellulose Sodium; Dialysis Solutions; Disease Models, Animal; Fibrinolytic Agents; Glucans; Glucose; Heparin; Hyaluronic Acid; Icodextrin; Laxatives; Male; Peritoneal Fibrosis; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Ventriculoperitoneal Shunt; Viscosupplements

Cryptococcus neoformans is the most common cause of fungal meningoencephalitis in AIDS patients. Depletion of CD4 cells, such as occurs during advanced AIDS, is known to be a critical risk factor for developing cryptococcosis. However, the role of HIV-induced innate inflammation in susceptibility to cryptococcosis has not been evaluated. Thus, we sought to determine the role of Type I IFN induction in host defense against cryptococci by treatment of C. neoformans (H99) infected mice with poly-ICLC (pICLC), a dsRNA virus mimic. Unexpectedly, pICLC treatment greatly extended survival of infected mice and reduced fungal burdens in the brain. Protection from cryptococcosis by pICLC-induced Type I IFN was mediated by MDA5 rather than TLR3. PICLC treatment induced a large, rapid and sustained influx of neutrophils and Ly6Chigh monocytes into the lung while suppressing the development of eosinophilia. The pICLC-mediated protection against H99 was CD4 T cell dependent and analysis of CD4 T cell polyfunctionality showed a reduction in IL-5 producing CD4 T cells, marginal increases in Th1 cells and dramatic increases in RORγt+ Th17 cells in pICLC treated mice. Moreover, the protective effect of pICLC against H99 was diminished in IFNγ KO mice and by IL-17A neutralization with blocking mAbs. Furthermore, pICLC treatment also significantly extended survival of C. gattii infected mice with reduced fungal loads in the lungs. These data demonstrate that induction of type I IFN dramatically improves host resistance against the etiologic agents of cryptococcosis by beneficial alterations in both innate and adaptive immune responses.

Topics: Animals; Carboxymethylcellulose Sodium; CD4-Positive T-Lymphocytes; Cryptococcus neoformans; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Interferon Inducers; Interferon Type I; Meningitis, Cryptococcal; Mice; Mice, Inbred C57BL; Mice, Knockout; Poly I-C; Polylysine

To evaluate effects of a novel multi-ingredient artificial tear formulation containing carboxymethylcellulose (CMC) and hyaluronic acid (HA) in a murine dry eye model.. Dry eye was induced in mice (C57BL/6) using an intelligently controlled environmental system (ICES). CMC+HA (Optive Fusion™), CMC-only (Refresh Tears(®)), and HA-only (Hycosan(®)) artificial tears and control phosphate-buffered saline (PBS) were administered 4 times daily and compared with no treatment (n = 64 eyes per group). During regimen 1 (prevention regimen), mice were administered artificial tears or PBS for 14 days (starting day 0) while they were exposed to ICES, and assessed on days 0 and 14. During regimen 2 (treatment regimen), mice exposed to ICES for 14 days with no intervention were administered artificial tears or PBS for 14 days (starting day 14) while continuing exposure to ICES, and assessed on days 0, 14, and 28. Corneal fluorescein staining and conjunctival goblet cell density were measured.. Artificial tear-treated mice had significantly better outcomes than control groups on corneal staining and goblet cell density (P < 0.01). Mice administered CMC+HA also showed significantly lower corneal fluorescein staining and higher goblet cell density, compared with CMC (P < 0.01) and HA (P < 0.05) in both regimens 1 and 2.. The artificial tear formulation containing CMC and HA was effective in preventing and treating environmentally induced dry eye. Improvements observed for corneal fluorescein staining and conjunctival goblet cell retention suggest that this combination may be a viable treatment option for dry eye disease.

Topics: Animals; Carboxymethylcellulose Sodium; Conjunctiva; Cornea; Disease Models, Animal; Dry Eye Syndromes; Female; Fluorescein; Fluorescent Dyes; Goblet Cells; Hyaluronic Acid; Lubricant Eye Drops; Mice; Mice, Inbred C57BL; Treatment Outcome

Staphylococci account for a large proportion of hospital-acquired infections, especially among patients with indwelling devices. These infections are often caused by biofilm-producing strains, which are difficult to eradicate and may eventually cause bacteremia and metastatic infections. Recent evidence suggests that mesenchymal stem cells can enhance bacterial clearance in vivo.. In this study, a rat model with carboxymethyl cellulose pouch infection was used to analyze the efficacy of bone marrow-derived mesenchymal stromal cells (BMSCs) against the methicillin-resistant Staphylococcus aureus.. The results showed that the administration of BMSCs effectively reduced the number of bacterial colonies and the expression of many cytokines and chemokines (such as interleukin [IL]-6, IL-1β, IL-10 and CCL5). Unlike the fibroblast control groups, the pouch tissues from the BMSC-treated rats showed the formation of granulations, suggesting that the healing of the wound was in progress.. The results indicate that the treatment of BMSCs can reduce methicillin-resistant S aureus infection in vivo, thereby reducing the inflammatory response.

Topics: Animals; Bone Marrow Cells; Carboxymethylcellulose Sodium; Cell- and Tissue-Based Therapy; Disease Models, Animal; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Methicillin-Resistant Staphylococcus aureus; Rats; Staphylococcal Infections

Maternal infection during pregnancy is associated with an increased risk of schizophrenia and autism in the offspring. Supporting this correlation, experimentally activating the maternal immune system during pregnancy in rodents produces offspring with abnormal brain and behavioral development. We have developed a nonhuman primate model to bridge the gap between clinical populations and rodent models of maternal immune activation (MIA).. A modified form of the viral mimic, synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-L-lysine) was delivered to two separate groups of pregnant rhesus monkeys to induce MIA: 1) late first trimester MIA (n = 6), and 2) late second trimester MIA (n = 7). Control animals (n = 11) received saline injections at the same first or second trimester time points or were untreated. Sickness behavior, temperature, and cytokine profiles of the pregnant monkeys confirmed a strong inflammatory response to MIA.. Behavioral development of the offspring was studied for 24 months. Following weaning at 6 months of age, MIA offspring exhibited abnormal responses to separation from their mothers. As the animals matured, MIA offspring displayed increased repetitive behaviors and decreased affiliative vocalizations. When evaluated with unfamiliar conspecifics, first trimester MIA offspring deviated from species-typical macaque social behavior by inappropriately approaching and remaining in immediate proximity of an unfamiliar animal.. In this rhesus monkey model, MIA yields offspring with abnormal repetitive behaviors, communication, and social interactions. These results extended the findings in rodent MIA models to more human-like behaviors resembling those in both autism and schizophrenia.

Topics: Animals; Behavior, Animal; Brain; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Macaca mulatta; Maternal Deprivation; Maternal Exposure; Mental Disorders; Poly I-C; Polylysine; Pregnancy; Pregnancy Complications, Infectious; Prenatal Exposure Delayed Effects; Social Behavior; Stereotyped Behavior; Vocalization, Animal

Intra-abdominal adhesions following surgery are a major source of morbidity and mortality including abdominal pain and small bowel obstruction. This study evaluated the safety of PVA gel (polyvinyl alcohol and carboxymethylated cellulose gel) on intestinal anastomoses and its potential effectiveness in preventing adhesions in a clinically relevant large animal model.. Experiments were performed in a pig model with median laparotomy and intestinal anastomosis following small bowel resection. The primary endpoint was the safety of PVA on small intestinal anastomoses. We also measured the incidence of postoperative adhesions in PVA vs. control groups: group A (eight pigs): stapled anastomosis with PVA gel compared to group B (eight pigs), which had no PVA gel; group C (eight pigs): hand-sewn anastomosis with PVA gel compared to group B (eight pigs), which had no anti-adhesive barrier. Animals were sacrificed 14 days after surgery and analyzed.. All anastomoses had a patent lumen without any stenosis. No anastomoses leaked at an intraluminal pressure of 40 cmH2O. Thus, anastomoses healed very well in both groups, regardless of whether PVA was administered. PVA-treated animals, however, had significantly fewer adhesions in the area of stapled anastomoses. The hand-sewn PVA group also had weaker adhesions and trended towards fewer adhesions to adjacent organs.. These results suggest that PVA gel does not jeopardize the integrity of intestinal anastomoses. However, larger trials are needed to investigate the potential of PVA gel to prevent adhesions in gastrointestinal surgery.

Topics: Anastomosis, Surgical; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Gels; Intestine, Small; Laparotomy; Polyvinyl Alcohol; Suture Techniques; Swine; Tissue Adhesions; Wound Healing

To compare the efficacy of three types of ocular lubricants in protecting corneal epithelial cells in dry eye animal models.. Ocular lubricants containing 0.1% or 0.3% sodium hyaluronate (SH), carboxymethylcellulose (CMC), or hydroxypropyl methylcellulose (HPMC) were tested. First, ocular lubricant containing 0.002% fluorescein was dropped onto the rabbit corneas. The fluorescein intensity as an index of retention was measured. Second, a rabbit dry eye model was made by holding the eye open with a speculum, and 50 μL of each ocular lubricant was dropped onto the cornea. After 3 hours, the corneas were stained with 1% methylene blue (MB), and the absorbance of MB was measured. Third, a rat dry eye model was treated with the ocular lubricants for 4 weeks, and the corneal fluorescein staining was scored. Eyes treated with physiological saline were used as controls. Finally, immunohistochemistry was used to analyze occludin, an epithelial barrier protein, in cultured human corneal epithelial cells pretreated with ocular lubricants and desiccated for 20 or 60 minutes.. Our results showed that 0.3% SH had a significantly longer retention time than the other lubricants (all P < 0.01). The absorbance of MB was significantly lower in the 0.3% SH group. The corneas of rats exposed to 0.3% SH had significantly lower fluorescein staining scores. A significantly higher number of occludin-positive cells were found after exposure to 0.3% SH than other lubricants.. Ocular lubricant containing 0.3% SH would be preferable to treat patients with dry eye syndrome.

Topics: Animals; Carboxymethylcellulose Sodium; Cornea; Disease Models, Animal; Dry Eye Syndromes; Hyaluronic Acid; Hypromellose Derivatives; Male; Methylcellulose; Ophthalmic Solutions; Rabbits; Rats; Treatment Outcome; Viscosupplements

Lesions with great loss of skin and extensive burns are usually treated with heterologous skin grafts, which may lead rejection. Cell therapy with mesenchymal stem cells is arising as a new proposal to accelerate the healing process. We tested a new therapy consisting of sodium carboxymethylcellulose (CMC) as a biomaterial, in combination with adipose-derived stem cells (ADSCs), to treat skin lesions in an in vivo rat model. This biomaterial did not affect membrane viability and induced a small and transient genotoxicity, only at the highest concentration tested (40 mg/mL). In a rat wound model, CMC at 10 mg/mL associated with ADSCs increased the rate of cell proliferation of the granulation tissue and epithelium thickness when compared to untreated lesions (Sham), but did not increase collagen fibers nor alter the overall speed of wound closure. Taken together, the results show that the CMC is capable to allow the growth of ADSCs and is safe for this biological application up to the concentration of 20 mg/mL. These findings suggest that CMC is a promising biomaterial to be used in cell therapy.

Topics: Adipose Tissue; Animals; Carboxymethylcellulose Sodium; Cell Proliferation; Cell Survival; Cell- and Tissue-Based Therapy; Cells, Cultured; Collagen; Disease Models, Animal; Immunohistochemistry; Keratins; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Rats, Wistar; Skin; Tissue Engineering; Tissue Scaffolds; Wound Healing; Wounds and Injuries

The objective of this study was to assess whether carboxymethyl cellulose- (CMC-) based hydrogel containing BioC (biphasic calcium phosphate (BCP); tricalcium phosphate (TCP) : hydroxyapatite (Hap) = 70 : 30) and bone morphogenic protein-2 (BMP-2) led to greater bone formation than CMC-based hydrogel containing BioC without BMP-2. In order to demonstrate bone formation at 4 and 8 weeks, plain radiographs, microcomputed tomography (micro-CT) evaluation, and histological studies were performed after implantation of all hybrid materials on an 8 mm defect of the right tibia in rats. The plain radiographs and micro-CT analyses revealed that CMC/BioC/BMP-2 (0.5 mg) led to much greater mineralization at 4 and 8 weeks than did CMC/BioC or CMC/Bio/BMP-2 (0.1 mg). Likewise, bone formation and bone remodeling studies revealed that CMC/BioC/BMP-2 (0.5 mg) led to a significantly greater amount of bone formation and bone remodeling at 4 and 8 weeks than did CMC/BioC or CMC/BioC/BMP-2 (0.1 mg). Histological studies revealed that mineralized bone tissue was present around the whole circumference of the defect site with CMC/BioC/BMP-2 (0.5 mg) but not with CMC/BioC or CMC/BioC/BMP-2 (0.1 mg) at 4 and 8 weeks. These results suggest that CMC/BioC/BMP-2 hybrid materials induced greater bone formation than CMC/BioC hybrid materials. Thus, CMC/BioC/BMP-2 hybrid materials may be used as an injectable substrate to regenerate bone defects.

Topics: Animals; Bone Morphogenetic Protein 2; Bone Regeneration; Bone Substitutes; Calcium Phosphates; Carboxymethylcellulose Sodium; Disease Models, Animal; Osteogenesis; Rats; Rats, Sprague-Dawley; Tibia; X-Ray Microtomography

The aim was to investigate the effect of the arborvitae seed on cognitive function and α7-nicotinic acetylcholine receptor (α7nAChR) protein expression of the hippocampus in model rats with Alzheimer's disease (AD). Thirty-six adult Wistar rats were randomly divided into the control, test, and drug groups. A dose of Aβ1-40 was injected into the rats' hippocampus in the test and drug groups and the control rats were injected with the same amount of normal saline. After the model was successful, the rats in the control and test groups were gavaged with sodium carboxymethyl cellulose (500 mg/kg) and the rats in the drug group were gavaged with arborvitae seed powder (500 mg/kg) for 15 days. The Morris water maze test was used for cognitive function. The effect of arborvitae seed on α7nAChR protein immunoreactivity on the hippocampus neurons was studied by the immunohistochemistry method. Behavioral tests showed that the mean escape latencies and search time of the test group were obviously longer than the control and drug groups. The percentage of the search distance of the test group was shorter than that of the control and drug groups. The immunohistochemistry results are as follows: α7nAChR-positive cells and optical density in the hippocampus of the rats in the test group are less than that of the rats in the control and drug groups (all P < 0.01). Arborvitae seed can treat AD by increased expression of α7nAChR.

Topics: alpha7 Nicotinic Acetylcholine Receptor; Alzheimer Disease; Amyloid beta-Peptides; Animals; Behavior, Animal; Carboxymethylcellulose Sodium; Cognition; Disease Models, Animal; Hippocampus; Immunohistochemistry; Peptide Fragments; Plant Extracts; Rats; Rats, Wistar; Seeds; Thuja

Demineralized bone matrix (DBM) is a bone substitute biomaterial used as an excellent grafting material. Some factors such as carrier type might affect the healing potential of this material. The background data discuss the present status of the field: Albumin as a main protein in blood and carboxymethyl cellulose (CMC) were applied frequently in the DBM gels. We investigated the bone-repairing properties of 2 DBMs with different carriers. Bone regeneration in 3 groups of rat calvaria treated with DBM from the Iranian Tissue Bank Research and Preparation Center, DBM from Hans Biomed Corporation, and an empty cavity was studied. Albumin and CMC as carriers were used. The results of bone regeneration in the samples after 1, 4, and 8 weeks of implantation were compared. The block of the histologic samples was stained with hematoxylin and eosin, and the percentage area of bone formation was calculated using the histomorphometry method. The results of in vivo tests showed a significantly stronger new regenerated bone occupation in the DBM with albumin carrier compared with the one with CMC 8 weeks after the implantation. The 2 types of DBM had a significant difference in bone regeneration. This difference is attributed to the type of carriers. Albumin could improve mineralization and bioactivity compared with CMC.

Topics: Albumins; Animals; Bone Matrix; Bone Regeneration; Bone Substitutes; Carboxymethylcellulose Sodium; Disease Models, Animal; Male; Rats; Rats, Wistar; Skull; Wound Healing

Capsular contracture is the most troublesome complication after aesthetic breast surgery. Capsule formation can be seen as a normal foreign body reaction caused by implant insertion into the body. Pathological capsular contracture can lead to severe symptoms including pain, tenderness, and breast distortion. Hypertrophic scar hypothesis, one of the prevailing theories, implicates hematoma, granuloma, or other factors in capsular contractures. There are also animal studies that measure adhesion-induced capsule using fibrin glue. The authors performed the experiment to evaluate reductions in capsule formation using antiadhesion agent (AAA).. Twelve smooth-surfaced cohesive-gel implants were implanted in 12 New Zealand white rabbits weighing 1.8 to 2.6 kg. These 5 × 5 × 1 cm sized miniature implants were designed in accordance with products currently used for breast augmentation. After skin incision, the exposed latissimus dorsi muscle was elevated, and a submuscular pocket was made. The rabbits were divided into 2 groups. In the experimental group (n = 6), the implant and 2 mL of AAA (Guardix) were inserted into the pocket under the muscle. In the control group (n = 6), implants and 2 mL of saline were inserted into the pocket. During the 2-month follow-up period, the rabbits were imaged monthly by 3-dimensional computed tomography to study capsule formation changes. After 2 months, the animals were euthanized, and implants with peri-implant capsule were excised. We evaluated capsule thickness, collagen pattern, and myofibroblast ratio on ventral, lateral, and dorsal aspects in a blinded fashion.. No significant differences in capsule thickness or capsular contractures were observed on gross examination or 3-dimensional computed tomography. On histological evaluation, capsule was thinner on all aspects (ventral, P = 0.027; lateral, P = 0.027; dorsal, P = 0.028; all P < 0.05), the pattern of collagen had more parallel alignment at low density, and the myofibroblast ratio was lower (ventral, P = 0.009; lateral, P = 0.002; dorsal, P = 0.004; all P < 0.05) in the experimental group than in control group.. We suggest that AAA can be helpful in reducing capsule formation. Later, clinical trials are needed to evaluate this finding.

Topics: Animals; Breast Implantation; Breast Implants; Carboxymethylcellulose Sodium; Disease Models, Animal; Drug Combinations; Follow-Up Studies; Hyaluronic Acid; Implant Capsular Contracture; Prosthesis Design; Rabbits; Tissue Adhesions; Wound Healing

We have developed a polymer conjugate (Cellax) composed of acetylated carboxymethylcellulose (CMC), docetaxel (DTX), and PEG, designed to enhance the pharmacokinetics (PK) and antitumor efficacy of DTX. Our design placed an emphasis on nanoparticle self-assembly to protect DTX during blood transport, stability of the nanoparticle, and PEGylation to enhance PK. Compared to Taxotere, Cellax exhibited a 38.6 times greater area under the curve (AUC), and significantly lower clearance (2.5%) in PK. Less than 10% of DTX was released from Cellax in the blood circulation, indicating that Cellax were stable during blood transport. Cellax reduced non-specific distribution of DTX to the heart, lung and kidney by 48, 90, and 90%, respectively, at 3 h, compared to Taxotere. The uptake of Cellax at 3 h in the liver and spleen was high (15-45 μg DTX/g) but declined rapidly to <10 μg DTX/g in 24 h, and induced no measurable toxicity at 170 mg DTX/kg. Taxotere, on the other hand, displayed non-specific uptake in all the examined normal tissues and induced significant apoptosis in the lung and kidney at 40 mg DTX/kg. The tumor uptake of Cellax was 5.5-fold more than that by Taxotere and the uptake occurred within 3 h after injection and persisted for 10 days. The conjugate exhibited enhanced efficacy in a panel of primary and metastatic mouse tumor models. These results clearly demonstrated that Cellax improved the pharmacokinetics, biodistribution and efficacy of DTX compared to Taxotere with reduced toxicity.

Topics: Animals; Antineoplastic Agents; Carboxymethylcellulose Sodium; Disease Models, Animal; Docetaxel; Drug Screening Assays, Antitumor; Intracellular Space; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasm Metastasis; Neoplasms; Polyethylene Glycols; Polymers; Taxoids; Tissue Distribution; Treatment Outcome

Injectable scaffolds present compelling opportunities for wound repair and regeneration because of their ability to fill irregularly shaped defects and deliver biologics such as growth factors. In this study, we investigated the properties of injectable polyurethane (PUR) biocomposite scaffolds and their application in cutaneous wound repair using a rat excisional model. The scaffolds have a minimal reaction exotherm and clinically relevant working and setting times. Moreover, the biocomposites have mechanical and thermal properties consistent with rubbery elastomers. In the rat excisional wound model, injection of settable biocomposite scaffolds stented the wounds at early time points, resulting in a regenerative rather than a scarring phenotype at later time points. Measurements of wound length and thickness revealed that the treated wounds were less contracted at day 7 compared to blank wounds. Analysis of cell proliferation and apoptosis showed that the scaffolds were biocompatible and supported tissue ingrowth. Myofibroblast formation and collagen fiber organization provided evidence that the scaffolds have a positive effect on extracellular matrix remodeling by disrupting the formation of an aligned matrix under elevated tension. In summary, we have developed an injectable biodegradable PUR biocomposite scaffold that enhances cutaneous wound healing in a rat model.

Topics: Animals; Apoptosis; Carboxymethylcellulose Sodium; Cell Proliferation; Collagen; Disease Models, Animal; Hyaluronic Acid; Immunohistochemistry; Injections; Isocyanates; Ki-67 Antigen; Lysine; Male; Polyethylene Glycols; Polyurethanes; Rats, Sprague-Dawley; Rheology; Tissue Scaffolds; Wound Healing; Wounds and Injuries

A carboxymethylcellulose-based polymer conjugate with nanoparticle forming properties (Cellax) has been shown to enhance the pharmacokinetics, specificity of biodistribution, anti-tumor efficacy and safety of docetaxel (DTX) in comparison to the Taxotere™ formulation. We examined Cellax and Taxotere efficacy in four tumor models (EMT-6, B16F10, PC3, and MDA-MB-231), and observed variances in efficacy. To explore whether differences in tumor uptake of Cellax were responsible for these effects, we incorporated superparamagnetic iron oxide nanoparticles (SPIONs) into Cellax particles to enable magnetic resonance (MR) imaging (Cellax-MR). In the EMT-6 tumor model, Cellax-MR nanoparticles exhibited peak tumor accumulation 3-24 h post intravenous injection, and 3 days post-treatment, significant MR contrast was still detected. The amount of Cellax-MR deposited in the EMT-6 tumors was quantifiable as a hypointense volume fraction, a value positively correlated with drug content as determined by LC/MS analysis (R(2) = 0.97). In the four tumor models, Cellax-MR uptake was linearly associated with anti-tumor efficacy (R(2) > 0.9), and was correlated with blood vessel density (R(2) > 0.9). We have affirmed that nanoparticle uptake is variable in tumor physiology, and that this efficacy-predictive parameter can be non-invasively estimated in real-time using a theranostic variant of Cellax.

Topics: Animals; Carboxymethylcellulose Sodium; Cell Line, Tumor; Contrast Media; Disease Models, Animal; Docetaxel; Dose-Response Relationship, Drug; Drug Delivery Systems; Female; Humans; Magnetic Resonance Imaging; Male; Mice; Nanoparticles; Neoplasms; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1; Staining and Labeling; Subcutaneous Tissue; Taxoids; Tissue Distribution; Treatment Outcome

Adhesion formation after surgery for peritonitis-related conditions, with such associated complications as intestinal obstruction, pain, and infertility, remains an important problem. Applying a liquid barrier intra-peritoneally might reduce initial adhesion formation.. A combination of the cecal ligation and puncture model of peritonitis with the side-wall defect (SWD) model of adhesion formation was performed. Forty rats were assigned randomly to receive no barrier or 1 mL or 2 mL of the cross-linked polyvinyl alcohol and carboxymethylcellulose (PVA/CMC) hydrogel A-Part(®) Gel (B. Braun Aesculap AG, Tuttlingen, Germany). After 14 days, the animals were sacrificed, and adhesion formation and abscess formation were scored.. Thirty animals survived, distributed equally among the groups. There were significantly fewer adhesions to the SWD in the PVA/CMC groups (median 0) than in the control group (median 26%-50%) (p<0.05). The median tenacity of the adhesions was significantly higher in the control group (Zühlke score 2) than in the PVA/CMC groups (Zühlke score 0) (p<0.05). The amount and size of intra-abdominal abscesses were not significantly different in the three groups.. In this experiment, PVA/CMC hydrogel reduced the amount of adhesions to the SWD and between viscera significantly with equal risk of abscess formation.

Topics: Abdominal Abscess; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Male; Peritonitis; Polyvinyl Alcohol; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions

Benzalkonium chloride (BAC) is known to cause corneal epithelial damage. In this study we investigated the effect of a BAC solution containing a thickening agent, which enhanced residence time in the eyes, on corneal wound healing using in vivo rat model debrided corneal epithelium. 0.5% or 1.0% methylcellulose (MC), carboxymethylcellulose (CMC) and hydroxypropyl-methylcellulose (HPMC) were used as the thickening agent. The levels of corneal wound healing of rat eyes injected with saline were alone approximately 45.0% at 12 h and 93.6% at 24 h after corneal epithelial abrasion, and healing was almost complete at 36 h. The healing rate in the rat eye treated just with MC, CMC and HPMC was higher than that in those injected with saline. In contrast to the treatment result using only this thickening agent, the healing rate in the eye treated with BAC was lower than that in those injected with saline: the corneal wounds in the BAC-treated eye showed approximately 20% healing at 12 h after abrasion. The injection of 0.02% BAC solution containing MC, CMC and HPMC more significantly delayed the healing than did the injection of 0.02% BAC alone. The results show that the in vivo evaluation method for corneal damage using rat debrided corneal epithelium reflects a toxic change depending upon residence time. These findings provide valuable safety and efficacy information for use in the design of eye drops.

Topics: Adjuvants, Pharmaceutic; Animals; Benzalkonium Compounds; Carboxymethylcellulose Sodium; Cells, Cultured; Disease Models, Animal; Drug Design; Epithelium, Corneal; Humans; Hypromellose Derivatives; Methylcellulose; Ophthalmic Solutions; Preservatives, Pharmaceutical; Rats; Rats, Wistar; Solutions; Time Factors; Wound Healing

The objective of the study was to study the relationship between autoimmune pancreatitis (AIP) and colitis in C57BL/6 interleukin 10-deficient (IL-10KO) mice and to compare the extrapancreatic involvement of AIP between IL-10KO and MRL/Mp mice that developed pancreatitis.. Six-week-old female IL-10KO and MRL/Mp mice were injected intraperitoneally with polyinosinic polycytidylic acid (poly I:C) twice weekly for 8 or 12 weeks, respectively. The mice were killed, and the severity of inflammation in the pancreas, colon, liver, bile duct, and salivary gland was assessed using histological scoring systems. T-cell subsets derived from IL-10KO mice with pancreatitis were adoptively transferred into recombination activating gene 2-deficient mice.. Administration of poly I:C induced pancreatitis and accelerated the development of colitis in IL-10KO mice. Pancreatitis was characterized by specific destruction of exocrine glands and the production of various autoantibodies. Involvement of the liver and bile duct was observed in both IL-10KO and MRL/Mp mice, but sialadenitis was present only in MRL/Mp mice. Adoptive transfer of CD4(+) T cells from AIP mice induced pancreatitis in recipient mice.. Pancreatitis in IL-10KO mice resembles human type 1 AIP and is not associated with colitis. Genetic background may affect susceptibility to extrapancreatic involvement in type 1 AIP.

Topics: Adoptive Transfer; Animals; Autoantibodies; Autoimmune Diseases; Carboxymethylcellulose Sodium; CD4-Positive T-Lymphocytes; Cholangitis; Colitis; Disease Models, Animal; Exocrine Glands; Female; Hepatitis; Humans; Interferon Inducers; Interleukin-10; Mice; Mice, Inbred MRL lpr; Mice, Knockout; Pancreatitis; Poly I-C; Polylysine; Severity of Illness Index; Sialadenitis

Intraperitoneal adhesion is a serious surgical postoperative complication. Using a rat model, we compared the effectiveness of intraperitoneally administered zinc-modified sodium carboxymethyl cellulose (Zn(2+)-SCMC) and hyaluronic acid (HA) in preventing postoperative intraperitoneal adhesions.. Peritoneal adhesions were induced in 120 Wistar rats by scraping the cecal mucosa. The rats were randomized into a no treatment group (n = 40) or into a treatment group in which 3 ml of HA (n = 40) or Zn(2+)-SCMC (n = 40) was administered intraperitoneally before the abdominal wall was closed. Following sacrifice two weeks later, the intraperitoneal adhesions were scored and tissues were examined histologically using HE staining.. Eight animals died, five in the untreated group (mortality rate, 12.5%), two in the HA group (mortality rate, 5.0%) and one in the Zn(2+)-SCMC group (mortality rate, 2.5%). Relative to the untreated group, the incidence of intraperitoneal adhesions was 77.5% in the HA and 48.7% in the Zn(2+)-SCMC group, with the incidence significantly lower in the Zn(2+)-SCMC group (P < 0.001). Both agents prevented intraperitoneal adhesions by promoting the repair of the abdominal serosa.. Administration of Zn(2+)-SCMC was more effective in preventing intraperitoneal adhesions than HA.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Hyaluronic Acid; Male; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions

Preconditioning with a low dose of harmful stimulus prior to injury induces tolerance to a subsequent ischemic challenge resulting in neuroprotection against stroke. Experimental models of preconditioning primarily focus on neurons as the cellular target of cerebral protection, while less attention has been paid to the cerebrovascular compartment, whose role in the pathogenesis of ischemic brain injury is crucial. We have shown that preconditioning with polyinosinic polycytidylic acid (poly-ICLC) protects against cerebral ischemic damage. To delineate the mechanism of poly-ICLC protection, we investigated whether poly-ICLC preconditioning preserves the function of the blood-brain barrier (BBB) in response to ischemic injury. Using an in vitro BBB model, we found that poly-ICLC treatment prior to exposure to oxygen-glucose deprivation maintained the paracellular and transcellular transport across the endothelium and attenuated the drop in transendothelial electric resistance. We found that poly-ICLC treatment induced interferon (IFN) β mRNA expression in astrocytes and microglia and that type I IFN signaling in brain microvascular endothelial cells was required for protection. Importantly, this implicates a potential mechanism underlying neuroprotection in our in vivo experimental stroke model, where type I IFN signaling is required for poly-ICLC-induced neuroprotection against ischemic injury. In conclusion, we are the first to show that preconditioning with poly-ICLC attenuates ischemia-induced BBB dysfunction. This mechanism is likely an important feature of poly-ICLC-mediated neuroprotection and highlights the therapeutic potential of targeting BBB signaling pathways to protect the brain against stroke.

Topics: Analysis of Variance; Animals; Animals, Newborn; Blood-Brain Barrier; Brain Infarction; Carboxymethylcellulose Sodium; Cells, Cultured; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Gene Expression Regulation; Glucose; Hypoxia; Infarction, Middle Cerebral Artery; Interferon Regulatory Factor-1; Interferon-beta; Ischemic Preconditioning; Mice; Mice, Inbred C57BL; Mice, Knockout; Neuroglia; Neuroprotective Agents; Poly I-C; Polylysine; RNA, Messenger; Signal Transduction; Tight Junctions; Time Factors

Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic compound. The parent FLBZ is metabolized to its reduced (R-FLBZ) and hydrolyzed (H-FLBZ) metabolites. There are no data on the potential nematodicidal activity of R-FLBZ, the main plasma metabolite found in sheep and mice. The goal of the current work was to assess the efficacy of FLBZ and R-FLBZ against Trichinella spiralis in a mouse model.. Both compounds were administered to Balb/c mice infected with T. spiralis as either a cyclodextrin aqueous solution or as a carboxymethylcellulose suspension. Treatments were performed orally (5 mg/kg) at 1 day after infection with T. spiralis. The efficacy of the treatments was assessed at day 6 after infection.. While the efficacy obtained for FLBZ and R-FLBZ administered as a solution was 94 and 98%, respectively, the efficacies obtained after the treatment with FLBZ suspensions were 38% (FLBZ) and 64% (R-FLBZ).. Under the current experimental conditions, a high nematodicidal efficacy of both FLBZ and R-FLBZ administered as solution preparations was observed.

Topics: Administration, Oral; Animals; Anthelmintics; Carboxymethylcellulose Sodium; Cyclodextrins; Disease Models, Animal; Mebendazole; Mice; Mice, Inbred BALB C; Oxidation-Reduction; Trichinella spiralis; Trichinellosis

This study investigated critical physicochemical attributes of low (LV), medium (MV) and high molecular weight (HV) sodium carboxymethylcellulose (SCMC) scaffolds in partial thickness wound healing. SCMC scaffolds were prepared by solvent-evaporation technique. Their in vitro erosion, moisture affinity, morphology, tensile strength, polymer molecular weight and carboxymethyl substitution, and in vivo wound healing profiles were determined. Inferring from rat wound size, re-epithelialization and histological profiles, wound healing progressed with HV scaffold>LV-MV scaffold>control with no scaffold. The transepidermal water loss (TEWL) from wound of rats treated by control>HV scaffold>LV-MV scaffold. HV scaffold had the highest tensile strength of all matrices and was resistant to erosion in simulated wound fluid. In spite of constituting small nanopores, it afforded a substantial TEWL than MV and LV scaffolds from wound across an intact matrix through its low moisture affinity characteristics. The HV scaffold can protect moisture loss without its excessive accumulation at wound bed which hindered re-epithelialization process. Regulation of transepidermal water movement and wound healing by scaffolds was governed by SCMC molecular weight instead of its carboxymethyl substitution degree or matrix pore size distribution, with large molecular weight HV preferred over lower molecular weight samples.

Topics: Animals; Bandages, Hydrocolloid; Burns; Carboxymethylcellulose Sodium; Chemical Phenomena; Disease Models, Animal; Male; Materials Testing; Rats; Rats, Sprague-Dawley; Skin; Spectroscopy, Fourier Transform Infrared; Tensile Strength; Wound Healing

Postoperative peritoneal adhesions following gynaecological surgery remain a clinically relevant problem. One approach to prevent adhesion formation is to apply physical barriers such as hydrogels.. A physically crosslinked polyvinyl alcohol and carboxymethylcellulose (PVA/CMC) hydrogel (A-Part) was characterized in vitro. Three different traumatization methods were evaluated in a rabbit uterine study. To determine its anti-adhesion efficacy, the hydrogel was first tested in an in vivo pilot study and then in a larger trial to compare it with icodextrin 4% solution (Adept) and controls.. Rheological measurements showed an increased elasticity of the hydrogel after freezing. In vivo experiments revealed a clear reduction in incidence, extent and severity of adhesions compared to the icodextrin 4% solution and the untreated control group.. These results warrant further investigation of the PVA/CMC A-Part hydrogel in clinical trials focused on gynaecological procedures.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Gynecologic Surgical Procedures; Hydrogels; Pilot Projects; Polyvinyl Alcohol; Rabbits; Rheology; Tissue Adhesions

Dexamethasone (DXN) is an effective anti-inflammatory drug in the treatment of acute and chronic eye disease such as uveitis. It is relatively lipophilic and permeates biological membranes quite easily. However, its low aqueous solubility limits its clinical usefulness. To circumvent this problem Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as solubilizer and penetration enhancer for DXN. The purpose of this study was to develop HP-β-CD based pH-induced mucoadhesive hydrogel for ophthalmic delivery of DXN to treat uveitis.. The formation of inclusion complex of DXN with HP-β-CD was characterized in solution and solid states by phase solubility, X-ray diffractometry and IR spectrum analyses. To improve ocular retention and sustained action Carbopol 980 NF and sodium carboxymethylcellulose (NaCMC) were added to the formulations as phase transition and mucoadhesive agents, respectively.. The HP-β-CD-based hydrogel system enhanced the solubility of DXN and the apparent stability constant (k') of the DXN-HP-β-CD inclusion complex was found to be 258.62 M(-1). The optimum concentrations of Carbopol 980NF and NaCMC for the mucoadhesive hydrogel were 0.2% (w/v) and 0.4% (w/v), respectively. This mucoadhesive hydrogel could flow freely under non-physiological condition and showed the character of pseudoplastic fluid under both physiological and non-physiological conditions. In vitro release of DXN from the HP-β-CD complex in simulated tear fluid (STF, pH- 7.4), was influenced significantly by the properties and concentration of Carbopol and NaCMC. In vivo studies in rabbit eye showed a marked improvement in anti-inflammatory activity of mucoadhesive hydrogel-treated eye compared with a marketed solution formulation in a uveitis-induced rabbit eye model.. The developed HP-β-CD-based mucoadhesive system is a viable alternative to conventional eye drops of DXN due to its ability to enhance bioavailability through its longer precorneal residence time and ability to sustain the release of the drug.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Acrylic Resins; Animals; Anti-Inflammatory Agents; Aqueous Humor; beta-Cyclodextrins; Biological Availability; Carboxymethylcellulose Sodium; Cell Count; Dexamethasone; Disease Models, Animal; Drug Delivery Systems; Excipients; Hydrogels; Hydrogen-Ion Concentration; Ophthalmic Solutions; Rabbits; Spectrophotometry, Infrared; Uveitis, Anterior; Viscosity; X-Ray Diffraction

Curcumin is a tumeric-derived, water-insoluble polyphenol with potential beneficial health effects for humans. It has been shown to have preventive as well as therapeutic effects in chemically induced murine models of colitis. To investigate whether curcumin exerts a similar effect on the spontaneous colitis in interleukin (IL)-10 gene-deficient mice, we gavaged these mice daily for 2 weeks with 200 mg/kg per day curcumin emulsified in carboxymethyl cellulose, a food additive generally used as a viscosity modifier. Mice fed the curcumin/carboxymethyl cellulose mixture and those receiving carboxymethyl cellulose alone demonstrated similar reductions in histological injury score and colon weight/length ratio compared to water-fed controls. However, significant reductions in pro-inflammatory cytokine release in intestinal explant cultures were only seen in mice treated with the curcumin mixture. Our data demonstrate that in IL-10 gene-deficient mice, both oral curcumin and carboxymethyl cellulose, appear to have modifying effects on colitis. However, curcumin has additional anti-inflammatory effects mediated through a reduced production of potent pro-inflammatory mucosal cytokines.

Topics: Administration, Oral; Analysis of Variance; Animals; Carboxymethylcellulose Sodium; Colitis; Curcumin; Disease Models, Animal; Emulsions; Enzyme-Linked Immunosorbent Assay; Interferon-gamma; Interleukin-10; Interleukin-17; Mice; Peroxidase

Interferon (IFN) therapy in humans often causes flu-like symptoms by an unknown mechanism. Poly ICLC is a synthetic dsRNA and a Toll-like receptor 3 (TLR3) agonist with a strong IFN-inducing ability. In this work, we analyzed the effect of poly ICLC on pulmonary responses to influenza and respiratory syncytial virus (RSV) infections in the cotton rat (Sigmodon hispidus) model. Viral replication, pulmonary inflammation, and expression of IFN, TLR, and chemokines were monitored and compared. Antiviral effect of poly ICLC against influenza virus and RSV was best achieved at high poly ICLC concentrations that, in the absence of virus infection, induced a strong IFN response. The antiviral doses of poly ICLC, however, also increased lung inflammation, an unexpected finding because of the reported poly ICLC safety in BALB/c mice. Similarly, in contrast to murine model, pathology of RSV infection was increased in cotton rats treated with poly ICLC. Augmented lung inflammation was accompanied by an earlier induction of IFN and TLR responses and a stronger chemokine expression. Overall, these findings indicate significant association between antiviral IFN action and pulmonary inflammation and highlight important animal model-specific variations in the potential of IFN to cause pathology.

Topics: Animals; Bronchoalveolar Lavage; Carboxymethylcellulose Sodium; Chemokines; Disease Models, Animal; Gene Expression Regulation; Influenza A virus; Interferons; Lung; Mice; Orthomyxoviridae Infections; Pneumonia; Poly I-C; Polylysine; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Sigmodontinae; Toll-Like Receptor 3; Viral Load

Antiadhesive barrier solution (AABS) has been proven to prevent intraabdominal adhesion by reducing inflammation and fibrosis formation. Because this mechanism can also be applied to capsule formation after the breast implant insertion, we hypothesize that AABS can reduce capsular contraction and evaluate the efficacy of AABS on perisilastic implant capsule formation after submuscular insertion. A silicone block was inserted beneath the panniculus carnosus muscle in 10 rats. The experiment group received 0.1 mL of AABS (Guardix, Hanmi Medical Co.) instilled into the pocket, whereas the control group received 0.1 mL saline solution. Periimplant capsules were excised after 4 weeks and were evaluated for inflammatory cell count, capsular thickness, collagen pattern, and amount of myofibroblast. The inflammatory cell count and the capsular thickness were lower in the experiment group than in the control group (P < 0.05). The collagen pattern was loose and parallel in the experiment group, and the amount of myofibroblast was much less compared with the control group. AABS reduced the amount of inflammatory cells, myofibroblast, and capsular thickness. It also made the collagen fibers in the capsule loose and parallel. Therefore, AABS seemed to be effective in reducing the periimplant capsule formation.

Topics: Animals; Breast Implantation; Carboxymethylcellulose Sodium; Cell Count; Contracture; Disease Models, Animal; Drug Combinations; Hyaluronic Acid; Immunohistochemistry; Male; Rats; Rats, Sprague-Dawley; Silicones; Tissue Adhesions

Cystic echinococcosis (CE) is an important public health problem worldwide. Flubendazole, administered in tablets, has shown poor in vivo efficacy against CE in humans. However, flubendazole prepared as a solution caused a marked reduction in hydatid cysts developed in mice. The goal of the current work was to compare the chemoprophylactic effect of flubendazole formulated either as a hydroxypropyl-β-cyclodextrin solution or as a carboxymethylcellulose suspension in secondary CE in mice.. Balb/C mice were infected with Echinococcus granulosus protoscoleces. One day after infection, the animals were allocated into 3 different experimental groups: unmedicated control and treated at the time point of infection with flubendazole either prepared as a solution or suspension given twice a day during 15 days. Six months after infection, the animals were sacrificed to collect and weight parasitic cysts. Cyst samples recovered from infected mice of each experimental group were prepared for both scanning and transmission electron microscopy.. Both flubendazole formulations induced a significant reduction in cyst weight compared to the cysts recovered from the unmedicated control animals. Both formulations showed similar flubendazole-induced ultrastructural morphological changes.. Flubendazole offers a great potential to become a drug of choice in the preventive treatment of cystic echinococcosis.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Antinematodal Agents; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Chemistry, Pharmaceutical; Disease Models, Animal; Echinococcosis; Mebendazole; Mice; Mice, Inbred BALB C; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission

Detergents and emulsifiers added to food may destroy the mucus barrier, which normally isolates bacteria from the intestinal wall, and lead to chronic bowel inflammation in susceptible persons. We investigated the influence of 2% carboxymethylcellulose (CMC) on the biostructure of the intestinal microbiota in IL-10 gene-deficient mice.. Twenty to 27-week-old IL-10 gene-deficient mice received either 2% CMC solution (n = 7) or water (n = 6) orally for 3 weeks. Intestinal bacteria were investigated using fluorescence in situ hybridization in paraffin-fixed sections of the intestine.. CMC-treated IL-10 gene-deficient mice demonstrated a massive bacterial overgrowth, distention of spaces between villi, with bacteria filling these spaces, adherence of bacteria to the mucosa, and migration of bacteria to the bottom of the crypts of Lieberkuehn. Leukocytes migrated into the intestinal lumen in 4 of the 7 CMC mice. The changes were similar to those observed in Crohn's disease in humans and were absent in control animals.. CMC induces bacterial overgrowth and small bowel inflammation in susceptible animals. Because of its ubiquity in products and its unrestricted use in food of the industrial world, CMC is an ideal suspect to account for the rise of IBD in the 20th century.

Topics: Animals; Bacteria; Blind Loop Syndrome; Carboxymethylcellulose Sodium; Disease Models, Animal; Genetic Predisposition to Disease; In Situ Hybridization, Fluorescence; Inflammation; Interleukin-10; Intestinal Mucosa; Intestine, Small; Mice

The aim of this study was to evaluate and compare the in vitro and in vivo transdermal potential of bioadhesive gels of ketoprofen by using gelling polymers like sodium carboxymethylcellulose, xanthan gum, poloxamer 407 and carbopol 934P as bioadhesive polymer with and without penetration enhancer (oleic acid). The effect of oleic acid as a penetration enhancer was examined when it was added to the bioadhesive formulations. Gels were evaluated for bioadhesive force and viscosity. To study the in vitro potential of these formulations, permeation studies were performed with Franz diffusion cell using excised rat abdominal skin. Carrageenan induced rat paw edema model was used to investigate their in vivo performance. The commercial formulation of ketoprofen was used as a reference formulation. The in vitro permeation studies indicate that ketoprofen bioadhesive gel of poloxamer 407 with penetration enhancer was superior to gels of sodium carboxymethylcellulose and xanthan gum with penetration enhancer (oleic acid). The permeation rate of ketoprofen from poloxamer 407 based bioadhesive gel with 15% v/w penetration enhancer was higher (rat abdominal skin flux = 0.421 +/- 0.032 mg/cm(2)/h) than the permeation rate of sodium carboxymethylcellulose and xanthan gum based bioadhesive gel with 15% v/w penetration enhancer. In the paw edema test poloxamer 407 based bioadhesive gel with 15% v/w penetration enhancer showed the best permeation and effectiveness. The in vitro and in vivo studies showed that bioadhesive gels of ketoprofen could be used for effective therapy.

Topics: Acrylates; Adhesiveness; Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carboxymethylcellulose Sodium; Carrageenan; Chemistry, Pharmaceutical; Disease Models, Animal; Dosage Forms; Drug Carriers; Drug Compounding; Edema; Gels; In Vitro Techniques; Ketoprofen; Kinetics; Male; Oleic Acid; Permeability; Poloxamer; Polymers; Polysaccharides, Bacterial; Rats; Rats, Wistar; Skin; Skin Absorption; Viscosity

Previously, we reported carboxymethyl cellulose (CMC) binding to human corneal epithelial cells and promoting corneal epithelial wound closure in vitro. Using an animal model, the efficacy of CMC in promoting corneal wound healing was examined.. Following corneal epithelial wounding of NZ white rabbits, CMC (0.2% or 1.0%) or control vehicle (PBS) was administered topically (4 times daily for 3 days) to wounded and unwounded eyes with or without contact lens wear. Wound healing in response to the treatments was measured as percentage reduction of fluorescein-stained wound area 0 to 72 hr post-wounding. Corneas were examined histologically and expression of zonula occludens-1 (ZO-1) tight-junction was detected by immunohistochemistry.. Percentage wound reduction in CMC-treated groups was significantly greater than controls (p < 0.05) at 24 and 32 hr. Complete wound closure was observed by 48 hr in 100% of CMC-treated eyes compared to 45% of vehicle-treated eyes. CMC also promoted wound closure dose-dependently. Epithelial cells formed an intact layer following CMC-treatment whereas vehicle-treated cells were less ordered. Strong ZO-1 expression in corneal epithelia of CMC-treated eyes was observed at 72 hr. Contact lens wear appeared to delay wound closure compared to without lens wear during CMC-treatment (p = 0.001).. CMC promoted dose-dependent corneal epithelial wound healing. CMC stimulated ZO-1 expression, indicating accelerated corneal epithelial resistance barrier regeneration.

Topics: Administration, Topical; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Dose-Response Relationship, Drug; Epithelium, Corneal; Eye Injuries; Fluorophotometry; Immunoenzyme Techniques; Membrane Proteins; Ophthalmic Solutions; Phosphoproteins; Rabbits; Tight Junctions; Wound Healing; Zonula Occludens-1 Protein

Topics: Alginates; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Exudates and Transudates; Glucuronic Acid; Hexuronic Acids; Materials Testing; Occlusive Dressings; Silver Compounds; Swine; Time Factors; Treatment Outcome; Wound Healing; Wounds and Injuries

This study compared Parietex composite mesh (PCM) with Sepramesh (SM) in terms of strength of tissue incorporation, adhesion formation, and mesh shrinkage, using an animal model.. A two-phase, prospective, randomized study using 44 New Zealand white rabbits. Each animal underwent creation of a standardized ventral hernia defect, followed by repair using either SM or PCM. Half of each group was sacrificed and examined at 1 month, and the remainder at 5 months. Outcomes measurements were strength of incorporation (SOI), type and area of adhesions (AA), and mesh shrinkage.. SOI for PCM was much greater than for SM, both at 1 month (60.8 N versus 42.6 N) and 5 months (70.9 N versus 31.5 N). The incidence of bowel adhesions was lower with PCM than SM, both at 1 month (1 versus 6) and at 5 months (0 versus 4). At 5 months, PCM demonstrated lower AA, both as a percentage of the mesh (5.6% versus 12.8%) and in terms of absolute area involved (321 mm(2) versus 840 mm(2)). PCM underwent considerably more shrinkage than SM, at both 1 month (38.2% versus 18.1%) and 5 months (17.4% versus 6.1%).. PCM demonstrated a substantially stronger SOI, which improved over time, and SOI of SM decreased. PCM was also superior in terms of adhesion prevention, but underwent considerably more shrinkage in this experimental model.

Topics: Abdominal Wall; Animals; Carboxymethylcellulose Sodium; Collagen; Disease Models, Animal; Equipment Design; Hernia, Ventral; Hyaluronic Acid; Hydrogel, Polyethylene Glycol Dimethacrylate; Intestinal Diseases; Omentum; Peritoneal Diseases; Polyesters; Polypropylenes; Prospective Studies; Rabbits; Random Allocation; Surface Properties; Surgical Mesh; Time Factors; Tissue Adhesions

Toll-like receptor (TLR)3 ligands serve as natural inducers of pro-inflammatory cytokines capable of promoting Type-1 adaptive immunity, and TLR3 is abundantly expressed by cells within the central nervous system (CNS). To improve the efficacy of vaccine strategies directed against CNS tumors, we evaluated whether administration of a TLR3 ligand, polyinosinic-polycytidylic (poly-IC) stabilized with poly-lysine and carboxymethylcellulose (poly-ICLC) would enhance the anti-CNS tumor effectiveness of tumor peptide-based vaccinations.. C57BL/6 mice bearing syngeneic CNS GL261 glioma or M05 melanoma received subcutaneous (s.c.) vaccinations with synthetic peptides encoding CTL epitopes--mEphA2 (671-679), hgp100 (25-33) and mTRP-2 (180-188) for GL261, or ovalbumin (OVA: 257-264) for M05. The mice also received intramuscular (i.m.) injections with poly-ICLC.. The combination of subcutaneous (s.c.) peptide-based vaccination and i.m. poly-ICLC administration promoted systemic induction of antigen (Ag)-specific Type-1 CTLs expressing very late activation antigen (VLA)-4, which confers efficient CNS-tumor homing of vaccine-induced CTLs based on experiments with monoclonal antibody (mAb)-mediated blockade of VLA-4. In addition, the combination treatment allowed expression of IFN-gamma by CNS tumor-infiltrating CTLs, and improved the survival of tumor bearing mice in the absence of detectable autoimmunity.. These data suggest that poly-ICLC, which has been previously evaluated in clinical trials, can be effectively combined with tumor Ag-specific vaccine strategies, thereby providing a greater index of therapeutic efficacy.

Topics: Animals; Antigens, Neoplasm; Cancer Vaccines; Carboxymethylcellulose Sodium; Cell Line, Tumor; Combined Modality Therapy; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; Ephrin-A2; Epitopes; Glioma; Humans; Injections, Intramuscular; Integrin alpha4beta1; Ligands; Lymphocytes, Tumor-Infiltrating; Mice; Mice, Inbred C57BL; Ovalbumin; Peptides; Poly I-C; Polylysine; Staining and Labeling; T-Lymphocytes, Cytotoxic; Toll-Like Receptor 3; Treatment Outcome; Up-Regulation; Vaccination

The purpose of this study was to compare the effects of anti-adhesion materials in postoperative adhesions.. Rats were assigned to five groups: Group 1: Control. Group 2: chitin layers were used. Group 3: Na-hyaluronate / carboxymethylcellulose layers were used. Group 4: Na-hyaluronate gel was poured into the abdomen. Group 5: methylprednisolone was injected. The adhesion frequency and grade were scored according to Granat. Blood was taken for Hb, AST, BUN and albumin levels determination.. The adhesion frequencies (right and left) and grades were as follow in Groups; I: 82%, 91%, 2.63 +/- 1.22; II: 8.3%, 25%, 0.58 +/- 0.66; III: 17%, 33%, 1.08 +/- 1.08; IV: 50%, 58%, 1.41 +/- 1.44; V: 50%, 42%, 1.41 +/- 1.50. The adhesion phase in all study groups was found significantly low compared to control group, p < 0.05. No difference was observed among serologic and hematological parameters in all groups.. All the materials used significantly lowered the adhesion frequency and grade.

Topics: Abdominal Cavity; Animals; Anti-Inflammatory Agents; Biocompatible Materials; Carboxymethylcellulose Sodium; Chitin; Disease Models, Animal; Female; Hyaluronic Acid; Membranes, Artificial; Methylprednisolone; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Wistar; Severity of Illness Index; Tissue Adhesions; Wound Healing

To investigate and compare the performance of two widely used silver-containing, fibre-based dressings (Silvercel and Aquacel Ag) in terms of exudate management, wound-site adherence, dressing integrity, retention of dressing debris within wounds, frequency of debris-associated foreign body reactions and the impact of both debris and tissue reactions on wound-tissue integrity.. The dressings were evaluated in a porcine partial-thickness exudating wound model (an in vivo model of moderate to high exudation up to post-wounding day 4, and low exudation from days 4 to 7). Dressing performance was assessed using a panel of semi-quantitative scales.Wound-exudate retention, dressing structure following exposure to exudate, and adherence to wound tissues were compared macroscopically; the extent of trapped dressing debris, any ensuing tissue reactions and the level of resulting tissue disruption were compared histologically.. Silvercel was found to be significantly more effective in terms of wound exudate management than Aquacel Ag. On exposure to high levels of wound exudate, Silvercel retained its shape and mechanical strength, and remained at the site of application. In contrast, Aquacel Ag formed a fluid (semi-fibrous) gel, with minimal mechanical integrity and variable retention at the wound site. Silvercel was significantly more adherent to wound tissues than Aquacel Ag, but the level of trapped dressing debris, the frequency of ensuing foreign body reactions and the level of consequent wound-tissue disruption was lower, although not statistically, in the Silvercel-treated wounds.. These results suggest that the potential adverse clinical consequences of unmanaged wound exudate may be less likely in Silvercel than Aquacel Ag-treated wounds. In addition, the adverse effects of dressing adherence may be less likely in Aquacel Ag-treated wounds, although such benefits may be negated by the potentially deleterious effects of elevated dressing debris deposition. In view of these findings, further development of absorbent fibre-based dressings should be directed at maximising exudate management, minimising dressing adherence and preventing dressing-debris entrapment.

Topics: Alginates; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Exudates and Transudates; Glucuronic Acid; Hexuronic Acids; Materials Testing; Occlusive Dressings; Silver Compounds; Statistics, Nonparametric; Swine; Time Factors; Treatment Outcome; Wound Healing; Wounds and Injuries

Critical size defects in ovine tibiae, stabilised with intramedullary interlocking nails, were used to assess whether the addition of carboxymethylcellulose to the standard osteogenic protein-1 (OP-1/BMP-7) implant would affect the implant's efficacy for bone regeneration. The biomaterial carriers were a 'putty' carrier of carboxymethylcellulose and bovine-derived type-I collagen (OPP) or the standard with collagen alone (OPC). These two treatments were also compared to "ungrafted" negative controls. Efficacy of regeneration was determined using radiological, biomechanical and histological evaluations after four months of healing. The defects, filled with OPP and OPC, demonstrated radiodense material spanning the defect after one month of healing, with radiographic evidence of recorticalisation and remodelling by two months. The OPP and OPC treatment groups had equivalent structural and material properties that were significantly greater than those in the ungrafted controls. The structural properties of the OPP- and OPC-treated limbs were equivalent to those of the contralateral untreated limb (p > 0.05), yet material properties were inferior (p < 0.05). Histopathology revealed no residual inflammatory response to the biomaterial carriers or OP-1. The OPP- and OPC-treated animals had 60% to 85% lamellar bone within the defect, and less than 25% of the regenerate was composed of fibrous tissue. The defects in the untreated control animals contained less than 40% lamellar bone and more than 60% was fibrous tissue, creating full cortical thickness defects. In our studies carboxymethylcellulose did not adversely affect the capacity of the standard OP-1 implant for regenerating bone.

Topics: Animals; Biocompatible Materials; Biomechanical Phenomena; Bone Diseases; Bone Morphogenetic Protein 7; Bone Morphogenetic Proteins; Bone Regeneration; Carboxymethylcellulose Sodium; Collagen Type I; Disease Models, Animal; Drug Carriers; Drug Implants; Female; Radiography; Recombinant Proteins; Sheep; Tibia; Transforming Growth Factor beta

The purpose of this study was to compare the intra-abdominal adhesion formation following ventral hernia repair by using oxidized regenerated cellulose (ORC) as a barrier underneath polypropylene mesh (PPM), and sodium hyaluronate/carboxymethylcellulose (HA/CMC)-coated PPM.. A ventral abdominal defect was created in each of 30 male rats which were divided into three groups. In group 1 (control) the defect was repaired with PPM; in group 2 ORC was laid over the viscera and the defect was repaired with PPM, and in group 3 HA/CMC-coated PPM was used for the repairing procedure. On the 28th postoperative day all the rats were sacrificed and adhesions were evaluated by laparoscopic exploration followed by histopathological examination.. Animals treated with ORC and PPM, and HA/CMC-coated PPM showed significantly less adhesions than the control group (p = 0.026) and the intra-abdominal adhesions of the rats in these two groups were significantly easier to release than in the control group (p = 0.001). There was no significant difference between the ORC and HA/CMC groups.. ORC used together with PPM is as effective as HA/CMC-coated PPM and ORC can be used as an adhesion barrier in intra-abdominal hernia repair.

Topics: Adjuvants, Immunologic; Animals; Carboxymethylcellulose Sodium; Cellulose, Oxidized; Disease Models, Animal; Hemostatics; Hernia, Ventral; Hyaluronic Acid; Laparoscopy; Male; Rats; Rats, Sprague-Dawley; Surgical Mesh; Tissue Adhesions

To investigate the effectiveness of melatonin in preventing post-operative adhesion formation and to compare it with the efficacy of hyaluronate/carboxymethylcellulose membrane in a rat model.. Following pilot studies, 35 rats were operated on in the full study. In 15 animals (group one), 10 standard lesions were inflicted in each uterine horn (total 30 horns) and melatonin was applied before closure of the abdomen. In the second group, 20 animals were operated on and one of the uterine horns (total 20 horns) with standard lesions was treated with hyaluronate/carboxymethylcellulose membrane and the other uterine horn served as a control. Second-look operations were performed 1 week later and adhesion scores were compared.. The adhesion scores of uterine horns treated with melatonin and of uterine horns treated with hyaluronate/carboxymethylcellulose membrane were significantly lower than the scores of the controls (P < 0.001). There was no statistically significant difference between the adhesion scores of uterine horns treated with melatonin and of uterine horns treated with hyaluronate/carboxymethylcellulose membrane (P > 0.05).. Both melatonin and hyaluronate/carboxymethylcellulose membrane were effective in prevention of adhesion formation in a rat uterine horn model.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Free Radical Scavengers; Hyaluronic Acid; Melatonin; Membranes, Artificial; Peritoneal Diseases; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions

Peritendinous adhesions are the most important complication of flexor tendon injury. In this study, Seprafilm was used for the prevention of peritendinous adhesions following flexor tendon repair. Seprafilm Bioresorbable Membrane (Genzyme Corporation, Cambridge, MA) contains sodium hyaluronate and carboxymethyl cellulose. Thirty New Zealand white male rabbits were divided equally into 3 groups. In all groups, the deep flexor tendon of the third finger of the left back foot was cut and repaired by Kessler-Tajima suture technique. In the first study group following tendon repair, Seprafilm was wrapped around the repaired tendon. In the second study group, sodium hyaluronate gel was injected to the operation field after tendon repair. In the control group, no external material was applied to the field. The study groups had better range of motion. Histopathologically, study groups had less adhesions compared with the control groups. As a result, it was concluded that in rabbit the peritendinous adhesions following flexor tendon repairs could be lowered with Seprafilm and hyaluronic acid.

Topics: Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Disease Models, Animal; Hyaluronic Acid; Male; Membranes, Artificial; Rabbits; Tendon Injuries; Tendons; Time Factors; Tissue Adhesions; Wound Healing

Adhesions between viscera and mesh may result in intestinal obstruction and fistulae formation. Fewer adhesions with sodium carboxymethylcellulose (SCMC)-coated polypropylene mesh (PM) has been reported, but impaired wound healing was the major concern. We investigated the adhesion-prevention effect of SCMC in different concentrations, as coating only on visceral face of PM and its effects on wound healing. A full-thickness abdominal wall defect was created in 28 rats, which were then divided into three groups. In Group I (control), the defect was repaired with PM only; in Group II and Group III, the defects were repaired with 1% and 1.6% SCMC-coated-PM, respectively. All animals were sacrificed at day 30, and histological evaluation and adhesion scoring were done. Animals in the group in which 1.6% SCMC-coated PM was used developed significantly fewer adhesions compared with other animals (P=0.04). Histological evaluation using a semiquantitative scoring system showed no difference between the groups in fibrosis and inflammation scores (P=0.9 and P=0.3, respectively), and thickness of fibrosis on mesh was also similar (P=0.5). SCMC in 1.6% concentration as coating only on the visceral face of PM reduced the incidence and severity of adhesions without impairing wound healing.

Topics: Animals; Carboxymethylcellulose Sodium; Coated Materials, Biocompatible; Disease Models, Animal; Female; Hernia, Ventral; Laparotomy; Male; Polypropylenes; Postoperative Complications; Probability; Rats; Rats, Sprague-Dawley; Reference Values; Sensitivity and Specificity; Surgical Mesh; Tissue Adhesions; Wound Healing

Sodium hyaluronate-carboxymethylcellulose (HA/CMC) formulations are gels that effectively reduce postoperative adhesions in both animals and humans, when placed in the peritoneal or pelvic cavities concomitant with surgical manipulation. However, it has been suggested that the use of these products may increase the risk of peritoneal infection after contamination with intestinal contents during surgery. Using the rat intra-abdominal sepsis model, we found that administration of HA/CMC gels before bacterial challenge did not increase mortality but did significantly protect rats against lethal infection. This effect was dose and time dependent. Protection was conferred not by the HA/CMC gels themselves but by 1-(3-dimethylaminopropyl)-3-ethylurea (EDU), a small molecule released from the gel complex under physiologic conditions. Our results suggest that the protective effect exhibited by EDU is related to down-regulation of T cell-dependent responses and suppression of the proinflammatory-cytokine cascade associated with mortality during the early phase of disease.

Topics: Abdominal Abscess; Adjuvants, Immunologic; Animals; Carboxymethylcellulose Sodium; Cytokines; Disease Models, Animal; Dose-Response Relationship, Drug; Escherichia coli Infections; Gels; Hyaluronic Acid; Male; Rats; Rats, Wistar; Sepsis; Spleen; T-Lymphocytes; Time Factors; Urea

To evaluate the effects of two barriers, one solution, and two pharmacologic agents, in single or in combined use, for preventing postsurgical adhesion formation in the rat model.. A randomized, prospective study to evaluate the ability of leuprolide acetate, oxidized regenerated cellulose, medroxyprogesterone acetate, sodium hyaluronate, sodium hyaluronate/carboxymethyl cellulose, in single or in combined use, for preventing adhesion formation in a rat model.. Wistar female rats.. University animal laboratory.. Intramuscular injection of pharmacologic agents before surgery and intraperitoneal application of barriers and solution at the end of surgery.. Two weeks after surgery, a second laparotomy was performed and the extent of adhesion formation was determined.. All the treatment groups had fewer, less severe adhesions when compared with controls. The combination of medroxyprogesterone acetate and oxidized regenerated cellulose did enhance the adhesion-reducing capacity of oxidized regenerated cellulose. The performance of sodium hyaluronate solution for adhesion prevention was statistically significant, when compared with oxidized regenerated cellulose alone, or sodium hyaluronate used with carboxymethyl cellulose film.. Pharmacologic agents, barriers, or solutions result in significant reduction of postsurgical adhesions. The sodium hyaluronate solution alone and medroxyprogesterone acetate treatment alone had the least adhesion prevention scores. However, neither monotherapy nor combined therapy proved to be significantly more beneficial.

Topics: Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Cellulose, Oxidized; Disease Models, Animal; Double-Blind Method; Drug Therapy, Combination; Female; Fertility Agents, Female; Hyaluronic Acid; Leuprolide; Medroxyprogesterone Acetate; Membranes, Artificial; Postoperative Complications; Progesterone Congeners; Rats; Rats, Wistar; Tissue Adhesions

Hyaluronate sodium in the form of a bioresorbant membrane reduces the development of intra-abdominal adhesions frequently found after implantation of synthetic mesh in the context of surgical hernia repair.. The effect of hyaluronate on the formation of adhesions was evaluated when applied laparoscopically as a bioresorbant membrane to protect the peritoneal surface of a synthetic mesh.. Experimental animal model.. A peritoneal defect 5 cm in diameter was bilaterally created in the abdominal wall of each of 9 pigs by laparoscopy. A polypropylene mesh was fixed with clips onto these defects on both sides. In each of the animals, only on one side, the synthetic mesh was also covered by a hyaluronate membrane.. The incidence and severity of adhesions (grade 0-4, where 0 indicates no adhesion; 1, filmy avascular adhesions; 2, vascular adhesions; 3, cordlike fibrous adhesions; and 4, plain fibrous adhesions) were determined after 45 days, comparing treated and untreated sides by autopsy results and histological features.. Adhesions, mainly grades 3 and 4, occurred in 7 of the 9 animals in those meshes not covered by hyaluronate; 2 untreated animals did not develop adhesions. On the other hand, only 1 of the 9 animals developed adhesions (grade 2) at the mesh concealed by the hyaluronate membrane.. The bioresorbant hyaluronate membrane significantly reduced the formation of peritoneal adhesions (1-sided sign test, P<.05) induced by the insertion of a polypropylene mesh, when compared with the contralateral implants not protected by hyaluronate. Thus, hyaluronate membranes are efficient for reducing the incidence of peritoneal adhesions.

Topics: Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Disease Models, Animal; Hernia, Ventral; Hyaluronic Acid; Incidence; Laparoscopy; Membranes, Artificial; Polypropylenes; Postoperative Complications; Severity of Illness Index; Surgical Mesh; Swine; Tissue Adhesions

Intra-abdominal infection is complicated by adhesion and abscess formation. We have assessed the adhesion- and abscess-reducing capacity of various solution volumes and concentrations of two polyanionic polysaccharides, hyaluronan (HA) and carboxymethylcellulose (CMC), in a rat peritonitis model.. In 192 male Wistar rats a bacterial peritonitis was induced using cecal ligation and puncture. After 24 h the abdomen was reopened and the ligated cecum resected. Animals were randomized into three control groups, nine groups treated with various solution volumes (1 to 8 ml) containing different HA concentrations, and four groups treated with 1.7% CMC solution. Rats were killed at day 7, postoperatively, and adhesions were scored at five abdominal sites on a scale from 0 to 4. The presence and size of intra-abdominal abscesses were noted.. Fifty-four rats (28%) prematurely died. There was no significant difference in mortality between treatment groups and controls. Treatment with CMC (P < 0.001) and low (0.2 and 0.4%) concentrations of HA (P < 0.005) significantly reduced intra-abdominal adhesion formation. High volumes of 0.2 and 0.4% HA were most effective (P = 0.01). The effect of CMC was volume independent. The incidence of abdominal abscesses was also significantly reduced by treatment with either CMC (P < 0.001) or low concentrations of HA (P < 0.001). With regard to abscess formation the effect was independent of the volume administered for HA, while low volumes of CMC were most effective (P < 0.005).. Intraperitoneal treatment with either CMC or low-viscosity HA solution reduced intra-abdominal adhesion and abscess formation in a rat peritonitis model. The volume-induced reduction in adhesion formation suggests a hydroflotation effect of HA solution.

Topics: Abscess; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Hyaluronic Acid; Male; Peritonitis; Rats; Rats, Wistar; Tissue Adhesions

Patients in whom enterolysis is performed are at high risk for recurrence of adhesions and for injury during adhesiolysis. Therefore, the aim of this study was to assess the safety of sodium hyaluronate-based bioresorbable membrane (Seprafilm) after myotomy and enterotomy.. A total of 60 rabbits underwent laparotomy with equal distribution to one of three groups: creation of either three repaired, or three unrepaired myotomies, or three repaired enterotomies. Thus, a total of 180 defects were created in the same anatomic positions. One-half of the animals in each group had the surface of the myotomies or enterotomies covered by Seprafilm. Fourteen days later, after complete absorption of Seprafilm, the presence of intra-abdominal abscess, adhesions, and the integrity of the suture line were evaluated by a surgeon blinded to the use of Seprafilm and by a standard radiographic isobaric contrast study. Statistical analysis was done by use of Fisher's exact test; significance was set at P < 0.05.. The incidence of adhesions in the repaired myotomy group were 2 (6.6 percent) and 9 (30 percent) in the Seprafilm and control (nonSeprafilm) groups, respectively (P < 0.05); in the unrepaired myotomy group, 2 (6.6 percent) and 10 (33 percent) in the Seprafilm and control groups, respectively (P < 0.05); and in the enterotomy group, 28 (94 percent) and 29 (97 percent) in the Seprafilm and control groups, respectively (P = not significant). A single phlegmon occurred in the myotomy group at a Seprafilm site (1.6 (1/60) vs. 0 percent, P = not significant). There were no leaks in this group. In the enterotomy group, the incidence of phlegmons was 33 percent (10/30) in the Seprafilm group, whereas it was 27 percent (8/30) in the nonSeprafilm group (P = not significant). The incidence of leaks was 6.6 (2/30) and 10 percent (3/30) in the Seprafilm and nonSeprafilm group, respectively (P = not significant).. The use of Seprafilm at the sites of myotomies significantly reduced the incidence of adhesions. Effectiveness at the enterotomy site may have been attenuated by a greater inflammatory response. Importantly, Seprafilm did not increase septic mortality in any group.

Topics: Absorbable Implants; Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Disease Models, Animal; Hyaluronic Acid; Ileum; Intestinal Obstruction; Laparotomy; Membranes, Artificial; Rabbits; Wound Healing

To assess the efficacy of Oxiplex (FzioMed, Inc., San Luis Obispo, CA) barriers.. Film of polyethylene oxide and carboxymethylcellulose (Oxiplex) were tested for strength and tissue adherence. Films were selected for evaluation in models for biocompatability and adherence. Three films were selected for evaluation in efficacy studies, and one was evaluated for effects on bacterial peritonitis. Handling characteristics of Oxiplex film were evaluated via laparoscopy.. University laboratory.. Rabbits, rats, pigs.. Placement of Oxiplex prototypes at the site of injury.. Mechanical properties, biocompatibility, tissue adherence, adhesion development, infection potentiation, and device handling.. Mechanical tests indicated that tensile strength and elongation were inversely correlated. All films tested had excellent tissue adherence properties. Selected films, based on residence time and biocompatibility, prevented adhesion formation in all animals and were highly efficacious in preventing adhesion reformation. The optimal Oxiplex prototype prevented adhesion reformation in 91% of the animals. This Oxiplex film, dyed to allow visualization, prevented adhesion reformation and did not affect bacterial peritonitis. In a laparoscopic model, the Oxiplex film, delivered in FilmSert forceps, via a 5.0-mm trocar, rapidly unfurled and could be easily applied to tissue with strong adherence.. These data show development of an adhesion prevention material that is tissue adherent, can be placed via laparoscopy, and does not affect host resistance.

Topics: Absorbable Implants; Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Cellulose; Disease Models, Animal; Female; Laparoscopy; Materials Testing; Peritonitis; Polyethylene Glycols; Rabbits; Rats; Rats, Sprague-Dawley; Stress, Mechanical; Surgical Wound Infection; Swine; Tissue Adhesions

In cases such as incisional hernia repair, polypropylene mesh (PPM) can be exposed to the underlying viscera and cause adhesions to the mesh. In this study, a composite prosthesis that was designed to be less susceptible to adhesion formation than PPM was evaluated in a rabbit incisional hernia repair model.. A 5 x 7-cm full-thickness defect was created in the abdominal wall of 30 female New Zealand White rabbits. Ten animals each were repaired with PPM, Bard Composix (PP/ePTFE), or Sepramesh biosurgical composite-a polypropylene mesh coated on one side with chemically modified sodium hyaluronate and carboxymethylcellulose (HA/CMC). The animals were sacrificed after 28 days and the overall performance, including adhesion formation and tissue integration by histology and mechanical testing, was evaluated.. In the Sepramesh group, there was a significant reduction in the percentage of surface area covered by adhesions and a significant increase in the percentage of animals with no adhesions compared to standard materials. The tissue integration strength and overall cellular response were similar in all groups. A partially remesothelialized peritoneal surface was often apparent overlying the Sepramesh implant.. Sepramesh biosurgical composite effectively repaired abdominal wall defects in rabbits and reduced adhesion development to the mesh compared to the use of a PPM and a PP/ePTFE composite.

Topics: Absorbable Implants; Animals; Carboxymethylcellulose Sodium; Cecal Diseases; Coated Materials, Biocompatible; Disease Models, Animal; Female; Hernia, Inguinal; Hyaluronic Acid; Polypropylenes; Postoperative Complications; Rabbits; Tissue Adhesions

Intraperitoneal adhesions are a significant problem (increased morbidity, mortality, and cost) for patients undergoing abdominal procedures. Although a variety of approaches (e.g., fibrinolytic agents, anti-inflammatory drugs, or barrier/separation methods) have been used with some success in preventing adhesions, a comparison of these different modalities has yet to be performed in a model that objectively measures intraperitoneal adhesion formation. Our objectives were to establish an objective, reproducible model of intraperitoneal adhesion formation and to establish efficacy of different treatment modalities in decreasing the strength and extent of intraperitoneal adhesions. In this two-part study, a rat model establishing an objective measure of both the strength and extent of intraperitoneal adhesions was used to compare different treatment modalities. Fibrinolytic agents [recombinant tissue plasminogen activator (rtPA), streptokinase, and urokinase], anti-inflammatory drugs (dexamethasone and tolmetin sodium), and barrier methods [sodium carboxymethylcellulose (CMC), and sodium hyaluronate] and a control group were compared in the first phase. In the second phase, the two most successful agents (rtPA, CMC) were compared both alone and in combination against a commercially available barrier agent (Seprafilm) and a control group. In the first phase of the study, rtPA was the only agent that had a statistically significant effect in decreasing the strength of adhesions. CMC was the only agent that demonstrated a decrease in the extent of adhesions, and the difference tended toward significance. In the second phase, the combination of rtPA and CMC showed a significant decrease in both the strength and extent of adhesions when compared with those of the control group. This decrease was also observed in the group treated with Seprafilm, which showed no difference from the rtPA + CMC group. We conclude that, in this reproducible adhesion model, only the combination of rtPA + CMC and Seprafilm significantly reduced both the strength and the extent of intraperitoneal adhesions.

Topics: Animals; Anti-Inflammatory Agents; Biocompatible Materials; Carboxymethylcellulose Sodium; Disease Models, Animal; Fibrinolytic Agents; Hyaluronic Acid; Male; Membranes, Artificial; Peritoneal Diseases; Rats; Rats, Sprague-Dawley; Tissue Adhesions

Postoperative intra-abdominal adhesions are a major source of postsurgical morbidity. Pelvic irradiation increases the likelihood of adhesion development. The purpose of this study was to evaluate the effects of hyaluronic acid-carboxymethylcellulose film, which was designed as a barrier to prevent adhesions, on the healing of ileal anastomoses performed on irradiated rat bowel.. Sixty-eight female Sprague-Dawley rats underwent whole pelvic irradiation with a single fraction of 1700 cGy. Twenty weeks later the rats underwent exploratory laparotomy with segmental ileal resection and reanastomosis. Eighteen of the anastomoses were wrapped in hyaluronic acid-carboxymethylcellulose film. Fifty anastomoses were not treated with any adhesion-inhibiting barrier. On the fifth postoperative day the animals underwent another laparotomy for evaluation of the anastomotic sites.. At the second laparotomy 93% of the rats treated with hyaluronic acid-carboxymethylcellulose film were found to have perianastomotic abscesses. In the non-hyaluronic acid-carboxymethylcellulose film group the perianastomotic abscess rate was 24% (P <.0001).. Among previously irradiated rats undergoing small-bowel resection and anastomosis, hyaluronic acid-carboxymethylcellulose film was associated with a markedly increased rate of abscess formation at the operative site.

Topics: Abscess; Anastomosis, Surgical; Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Hyaluronic Acid; Ileum; Membranes, Artificial; Radiation Injuries, Experimental; Rats; Rats, Sprague-Dawley; Tissue Adhesions; Wound Healing

Repeat cardiac surgical procedures are associated with increased technical difficulty and risk because of the previous formation of dense adhesions between the heart and the surrounding tissues. Dilute solutions of sodium hyaluronic acid (NaHA) and carboxymethyl cellulose (CMC) have been shown to prevent postoperative abdominal and pelvic adhesions and could therefore potentially inhibit adhesion formation following cardiac surgery. Adhesion prevention using 0.1% NaHA, 0.4% NaHA, or 0.1% CMC solutions was examined in a canine abrasion/desiccation pericardial adhesion model (5 animals/group) and compared to 10 animals treated with Ringer's lactate (RL) solution alone. The pericardium and heart were coated with 25 ml of test or control solution prior to and after pericardiotomy, after controlled gauze abrasion, after 30 min of desiccation, and prior to closure. At 6 weeks, animals were reexplored and adhesions were scored in a blinded manner by three to four surgeons using a 0-4 scale. Scores of 2 or greater were considered clinically significant. Mean adhesion scores from the left epicardium were 0.0 in animals treated with 0.1% NaHA, 0.6 in animals treated with 0.4% NaHA or 1% CMC, and 2.3 in animals treated with RL (P < 0.05 Duncan's ANOVA). In addition, none of the animals treated with 0.1% NaHA, 20% of the animals treated with 0.4% NaHA, and 20% of the animals treated with 1% CMC had clinically significant adhesions, whereas 80% of animals treated with RL had such adhesions. Sodium hyaluronic acid and CMC solutions, used as tissue coatings during cardiac surgery, inhibit the formation of undesired postoperative adhesions. Application of these biocompatible polymer solutions during surgery could reduce the technical difficulty and risk of repeat cardiac surgical procedures.

Topics: Animals; Carboxymethylcellulose Sodium; Cardiac Surgical Procedures; Disease Models, Animal; Dogs; Heart Diseases; Hyaluronic Acid; Pericardium; Postoperative Complications; Postoperative Period; Tissue Adhesions

Adhesion formation between viscera and mesh is almost inevitable following incisional hernia repair with prosthetic mesh. Such adhesions may lead to intestinal obstruction and enterocutaneous fistulae formation and make further laparotomies extremely difficult. Sodium carboxymethylcellulose (SCMC) and Interceed TC7 (oxidized regenerated cellulose) as physical barriers have been shown to be effective in reducing postoperative adhesions.. To evaluate the effects of SCMC and Interceed TC7, we used an incisional hernia model in rats. A ventral abdominal defect (15 x 25 mm) was created in each of 36 male rats which were then divided into three equal groups. In Group I (control) the defect was repaired with polypropylene mesh (PPM) only; in Group II the defect was repaired after a layer of Interceed TC7 was laid over the viscera with Interceed TC7-covered PPM; in Group III the defect was repaired after a layer of SCMC was laid over the viscera with SCMC-coated PPM. Six of the animals from each group were sacrificed at Postoperative Day 7 and the adhesions were scored. The remaining 6 were sacrificed at Day 30 and histological evaluation was made in addition to the adhesion score.. Animals in the SCMC-treated group developed significantly less adhesions (P = 0.0002) compared with control and Interceed TC7-treated groups. However, histological analysis revealed poor fibroblast proliferation with impaired wound healing in the SCMC group.. SCMC prevented adhesion formation but seriously impaired wound healing, and Interceed TC7 was ineffective in preventing adhesion in this model.

Topics: Animals; Carboxymethylcellulose Sodium; Cellulose, Oxidized; Disease Models, Animal; Hernia; Herniorrhaphy; Male; Polypropylenes; Prostheses and Implants; Rats; Rats, Sprague-Dawley; Tissue Adhesions

A rabbit serosal scarification model was utilized to compare the ability of four drugs, previously administered peri-operatively to horses undergoing exploratory celiotomy, to prevent the development of postoperative intestinal adhesions. The substances compared were 32% Dextran 70 (7 mL/kg), 1% sodium carboxymethylcellulose (7 mL/kg), trimethoprim-sulfadiazine (30 mg/kg), and flunixin meglumine (1 mg/kg). The first two were administered intra-abdominally following surgery, while the latter two were administered systemically in the peri-operative period. Fibrous adhesions were evident in all animals in the untreated serosal scarification group. No significant difference in the number of animals with adhesions was found between the untreated control group and any treatment group, nor among the treatment groups. Microscopic examination of adhesions collected at postmortem examination revealed fibers consistent with cotton, surrounded by a giant-cell reaction and ongoing acute inflammation. The source of the fibers was likely the cotton laparotomy sponges used to scarify the intestinal surface, since the pattern in the granuloma and sponge fibers appeared similar under polarized light. Though consistent intestinal adhesion formation was produced in the rabbit, the presence of foreign body granulomas may prevent consideration of this model for future research. The drugs tested were ineffective in preventing the formation of postoperative small intestinal adhesions in this model.

Topics: Animals; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Carboxymethylcellulose Sodium; Cicatrix; Clonixin; Dextrans; Disease Models, Animal; Jejunal Diseases; Jejunum; Postoperative Complications; Rabbits; Random Allocation; Sulfadiazine; Tissue Adhesions; Trimethoprim

Finding an effective treatment for viral infections that cause encephalitis remains an important problem. A model of human alphavirus infections, Semliki Forest virus, causes lethal encephalitis in weanling mice. Mice are viremic within 24 hr of an intraperitoneal challenge with the equivalent of three 75% lethal doses of Semliki Forest virus. Virus reaches the brain by 48 hr, and mortality results in all mice in 5-7 days. Introduction of virus intracranially accelerates the course of the infection. Neither anti-Semliki Forest virus hyperimmune serum nor the potent interferon inducer poly I:CLC given intraperitoneally are protective when used therapeutically after an intracranial virus infection, but a combination of 1,000 U hyperimmune serum and 80 micrograms/mouse of poly I:CLC results in a 50% survival rate. This combination treatment of intracranial Semliki Forest virus infection eliminates detectable viremia and reduces virus load in the brain over the course of the infection. These data show that when combined, specific antibody and an interferon inducer can interact synergistically to protect mice from alphavirus infections of the central nervous system even when given after the virus is replicating in the target organ.

Topics: Alphavirus Infections; Animals; Brain; Carboxymethylcellulose Sodium; Disease Models, Animal; Drug Administration Schedule; Encephalitis, Viral; Female; Immunization, Passive; Injections, Intraperitoneal; Injections, Intraventricular; Interferon Inducers; Interferons; Mice; Poly I-C; Polylysine; Semliki forest virus; Viremia

Peritoneal adhesions continue to be a significant cause of postoperative complications. Elucidating the origin of these adhesions has been hampered by the lack of a reproducible animal model. The purpose of this study was to create a standardized model in which a single, specific adhesion could be objectively measured. With this model the kinetics of adhesion formation were then evaluated. A variety of potential antiadhesive agents were then tested and compared.. In this study a reproducible, quantitative rat model was developed that used uniform defects on the peritoneal wall and cecal surface. The resulting adhesions were subsequently scored, and their strength was measured with a tensiometer. An evaluation of the kinetics of peritoneal adhesion formation was obtained by using a timed removal of silicone elastomer sheeting held between the two injured surfaces. The following antiadhesive agents were evaluated: Ringer's lactate solution; dextran 70 (32%); modified carboxymethylcellulose (1.0% and 2.0%); an absorbable barrier of specially knitted material composed of oxidized regenerated cellulose; fibrin sealant; silicone elastomer film; and expanded polytetrafluoroethylene membrane.. Evaluation of the kinetics of peritoneal adhesion formation indicated that the susceptibility for adhesion formation was significantly decreased or eliminated after the first 36 hours. Evaluation of antiadhesion agents indicated that the magnitude of adhesion prevention was directly proportional to the agent's ability to remain at the site of injury during the critical period of adhesion formation. Permanent barriers (silicone elastomer film, expanded polytetrafluoroethylene membrane) provided the greatest antiadhesion effect but were not believed to be ideal agents because they remained at the site of injury well after the critical period of adhesion formation. The incidence of adhesion formation for the other agents was as follows: control (34 of 34), Ringer's lactate (12 of 12), absorbable barrier of knitted cellulose (10 of 10), 32% dextran 70 (8 of 12), 1% carboxymethylcellulose (6 of 12), fibrin sealant (4 of 9), and 2% carboxymethylcellulose (4 of 12).. The efficacy of antiadhesion agents appears to be related to the agent's viscosity, ability to coat the wound surface, and residence time at the site of injury. In this rat model an agent that remained on the injured surfaces for at least 36 hours after injury appeared to be more effective in reducing adhesion formation than an agent with a shorter residence time.

Topics: Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Cecal Diseases; Cellulose; Dextrans; Disease Models, Animal; Disease Susceptibility; Female; Fibrin Tissue Adhesive; Isotonic Solutions; Kinetics; Membranes, Artificial; Peritoneal Diseases; Polytetrafluoroethylene; Postoperative Complications; Rats; Rats, Sprague-Dawley; Ringer's Lactate; Silicone Elastomers; Stress, Mechanical; Time Factors; Tissue Adhesions

The antifibrotic effects of an interferon inducer, polyinosinic-polycytidylic acid complexed with poly-L-lysine (poly ICLC), was evaluated in a bleomycin-hamster model of pulmonary fibrosis. Hamsters received three consecutive intratracheal doses of bleomycin (2.5, 2.0, and 1.5 U/kg/5 ml) or saline at weekly intervals. Poly ICLC at three doses (0.5, 1.0, and 1.5 mg/kg body weight) or saline was injected intraperitoneally by daily and semiweekly regimens for four weeks, and animals were sacrificed at five weeks. In both the daily and semiweekly poly ICLC regimens, hamsters receiving bleomycin plus poly ICLC demonstrated increased mortality and decreased weight gain compared to the vehicle and bleomycin control groups. The groups receiving bleomycin plus daily poly ICLC demonstrated poly ICLC-dose related effects for weight changes, lung hydroxyproline and lung prolyl hydroxylase activity. Depending on the poly ICLC dose, bleomycin plus daily poly ICLC produced significantly decreased hydroxyproline or significantly increased hydroxyproline and prolyl hydroxylase activity compared to the bleomycin control group. In contrast, the groups receiving bleomycin plus semiweekly poly ICLC did not demonstrate poly ICLC-dose related effects or significant differences from the bleomycin control group for any of the biochemical assays performed. The results of this study indicate that, depending on dose and regimen, poly ICLC can reduce collagen accumulation or produce a synergistic toxicity when administered with multiple doses of bleomycin. The toxic effects may restrict the therapeutic potential of poly ICLC in combination with bleomycin for anticancer therapy.

Topics: Animals; Bleomycin; Carboxymethylcellulose Sodium; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Hydroxyproline; Injections, Intraperitoneal; Interferon Inducers; Lipid Peroxidation; Lung; Male; Mesocricetus; Poly I-C; Polylysine; Procollagen-Proline Dioxygenase; Pulmonary Fibrosis; Superoxide Dismutase; Weight Gain

Various regimens to reduce postoperative intraperitoneal adhesion formation have been tested; however, none has been consistently successful. The purpose of this study was to compare the efficacy of three compounds instilled into the peritoneal cavity--32% dextran 70, 0.9% normal saline and sodium carboxymethylcellulose--to no therapy on their ability to prevent postoperative adhesion formation in the New Zealand white rabbit. Bilateral posterior uterine horn incisions and cecal and transverse colon abrasions were performed during a two-phased study on each of 25 rabbits that were randomly assigned in a blind fashion into one of four study groups. Two weeks postoperatively, each rabbit underwent an autopsy to assess the magnitude of intraperitoneal adhesion formation. Adhesion scores were determined by counting the number of adhesions and assigning one or two points for each thin, filmy or dense, broad adhesion. As compared to no therapy, all three substances tested significantly reduced adhesion formation. Although 32% dextran 70 and 0.9% normal saline showed similar results, the degree of adhesion formation was reduced most significantly with sodium carboxymethylcellulose (P < .002) Sodium carboxymethylcellulose is effective in preventing postoperative adhesion formation in the New Zealand white rabbit.

Topics: Animals; Carboxymethylcellulose Sodium; Dextrans; Disease Models, Animal; Drug Evaluation, Preclinical; Female; Genital Diseases, Female; Instillation, Drug; Peritoneal Diseases; Postoperative Complications; Rabbits; Random Allocation; Severity of Illness Index; Single-Blind Method; Sodium Chloride; Tissue Adhesions

Viscosity-enhancing agents such as carboxymethylcellulose (CMC) can alter absorption of solutes and fluid exchange in the small intestine. We investigated whether the standard World Health Organization oral rehydration solution (WHO-ORS) with the addition of CMC would improve net water and sodium absorption in rats using an in vivo intestinal perfusion technique. Four WHO-ORS, containing either 0, 2.5, 5.0, or 10.0 g/L of CMC, were perfused in rats with a well-tested model of cathartic-induced chronic osmotic diarrhea (D) and in normal controls (C). In D rats, the ORSs with CMC improved sodium absorption at the three concentrations used (p < 0.01). The same effect was shown in C rats. Net water absorption was also enhanced in D rats given ORSs with CMC, although the changes in C animals were less marked. The improvement in sodium and water absorption in both C and D rats positively correlated with the log of relative ORS viscosity. Ultrastructural examination of tissues perfused with 10 g/L of CMC showed an extended brush border glycocalyx. This study indicates that CMC added to WHO-ORS in the perfused rat jejunum improves the effectiveness of the solution by increasing sodium and water absorption.

Topics: Animals; Carboxymethylcellulose Sodium; Chronic Disease; Diarrhea; Disease Models, Animal; Fluid Therapy; Intestinal Absorption; Male; Microscopy, Electron; Rats; Rats, Sprague-Dawley; Rehydration Solutions; Sodium; Viscosity; Water

Efficacy of a 1% solution of sodium carboxymethylcellulose (CMC) infused into the peritoneal cavity of ewes was evaluated for prevention of intraperitoneal adhesions resulting from surgery of the reproductive tract. Six ewes were assigned to each of 4 groups. Group-1 ewes were controls that underwent ventral midline celiotomy and exploration of the abdominal viscera. Group-2 ewes were treated similarly to group-1 ewes, except that a 1% solution of CMC (14 ml/kg of body weight) was infused into the peritoneal cavity. This group was studied to determine whether CMC would cause changes in the peritoneal cavity. Group-3 comprised ewes representing a uterine trauma model. Ewes underwent abdominal exploration, but in addition had a standard embryo collection technique performed on 1 uterine horn and hysterotomy performed on the opposite uterine horn. Group-4 ewes were treated like group-3 ewes, except that, similar to treatment of group-2 ewes, CMC was infused into the peritoneal cavity. All ewes were euthanatized and necropsied 12 to 14 days after surgery. Abdominal adhesions were evaluated, and an adhesion severity score was assigned to each ewe on the basis of number and severity of the adhesions. Ewes of all groups had abdominal adhesions. Significantly (P less than 0.05) lower adhesion score was observed in ewes given CMC (groups 2 and 4) than in the adhesion model (group 3). Significant difference was not observed in adhesion score when groups 1, 2, or 4 were compared. Though not statistically significant, fewer adhesions were observed in ewes of groups 2 and 4 than in group-1 ewes.

Topics: Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Female; Infusions, Parenteral; Omentum; Peritoneal Diseases; Sheep; Sheep Diseases; Tissue Adhesions; Uterus

In a carboxymethyl cellulose (CMC) air pouch inflammation model, accumulation of exudate decreased at a relatively rapid rate and almost disappeared 3 days after a 2% CMC injection into the preformed air pouch. After a second injection of 2% CMC solution into the 1-day-old CMC pouch on the day following the first CMC injection, the decrease in rate of exudate was similar to the change seen after the first CMC injection. In another group of rats, 3 days after the first CMC injection when inflammation had subsided, a second injection of 2% CMC solution into the 3-day-old CMC pouch resulted in a marked increase of exudate accumulation, inflammatory cell infiltration and vascular permeability. Histologically, large numbers of macrophages accumulated in the 3-day-old CMC pouch and fibroblast proliferation and newly formed blood vessels were also visible. The enhanced exudative reaction was significantly inhibited by dexamethasone but not by indomethacin. These results indicate that the enhanced inflammatory reactions appear to be closely correlated with the increase of reactivity at the site of inflammation and the exudative reaction was not mediated by cyclo-oxygenase products.

Topics: Acute Disease; Air; Animals; Carboxymethylcellulose Sodium; Disease Models, Animal; Drug Administration Schedule; Exudates and Transudates; Inflammation; Male; Microscopy, Electron; Rats; Rats, Inbred Strains