orabase and Inflammation

Postoperative tissue adhesion is a complex inflammatory disorder in which tissues that normally remain separated in the body grow into each other. Seroma is a common postoperative complication that arises when serous fluid collects in the space generated following surgeries that require extensive dissection and that create large empty spaces. Postsurgical tissue adhesion and seroma formation are two serious surgical complications that have received more attention recently from the biomaterials community. This paper provides a review of the pathogenesis and treatment of these surgical complications, with a thorough overview of biomaterial-based treatment and prevention methods.

Topics: Animals; Biocompatible Materials; Carboxymethylcellulose Sodium; Cellulose, Oxidized; Dextrans; Humans; Hyaluronic Acid; Inflammation; Models, Animal; Phospholipids; Polyethylene Glycols; Postoperative Complications; Seroma; Surgical Procedures, Operative; Tissue Adhesions

Full healing was achieved within eight weeks in a malignant fungating wound using the principles of the TIME paradigm. This concept appears to provide a structured and systematic approach for managing such non-healing wounds.

Topics: Adult; Bandages, Hydrocolloid; Breast Neoplasms; Carboxymethylcellulose Sodium; Clinical Protocols; Drug Combinations; Exudates and Transudates; Female; Gelatin; Humans; Humidity; Infection Control; Inflammation; Metronidazole; Nursing Assessment; Odorants; Palliative Care; Patient Selection; Pectins; Polyenes; Referral and Consultation; Skin Care; Skin Neoplasms; Wound Healing; Wound Infection

This report describes a paradoxical inflammatory reaction to Seprafilm caused by extensive adhesion formation early in the postoperative period. A female patient had development of small bowel obstruction immediately after an uneventful low anterior resection for rectal carcinoma with placement of Seprafilm. The obstruction did not improve with nonoperative therapy. At laparotomy, extensive adhesions necessitating bowel resection and ileostomy were noted. Pathology results showed a giant cell foreign body reaction to Seprafilm. A literature search yielded only two other instances of adverse reactions to Seprafilm. The information provided by this and other atypical reports suggests that further studies aimed at identifying the incidence and pathophysiological mechanisms for such paradoxical reactions are needed.

Topics: Aged; Biocompatible Materials; Carboxymethylcellulose Sodium; Female; Gastric Outlet Obstruction; Humans; Hyaluronic Acid; Ileostomy; Inflammation; Laparotomy; Omentum; Postoperative Complications

Osteoarthritis (OA) is a prevalent degenerative joint condition with no effective disease modifying treatments. In this study, we aimed to address multiple OA hallmarks using a combination of pro-chondrogenic sulfated carboxymethylcellulose (sCMC) and anti-catabolic tissue inhibitor of metalloproteases 3 (Timp3) in relevant disease systems. Firstly, we chemically sulfated carboxymethylcellulose to impart a negative charge and improve the stability of cationic Timp3. The modified sCMC exhibited a molecular weight of 10 kDa and a degree of sulfation of ∼10 %. We further demonstrated that sulfation of CMC confers pro-chondrogenic characteristics. Subsequently, we demonstrated that the combination of sCMC and Timp3 effectively reduced key OA hallmarks, such as matrix degradation, inflammation, and protease expression, in a goat ex vivo OA model compared to individual treatments. We further demonstrated that the anti-OA effect of sCMC and Timp3 is mediated through the suppression of NFκB and JNK activation. To validate the clinical potential and mechanism of action, we conducted experiments on human OA explants. The combination treatment synergistically reduced the expression of MMP13 and NFκB in human OA explants. Overall, sCMC-mediated enhancement of Timp3 efficacy synergistically reduced OA-like traits and demonstrates the potential for OA amelioration.

Topics: Carboxymethylcellulose Sodium; Cartilage, Articular; Chondrocytes; Humans; Inflammation; NF-kappa B; Osteoarthritis; Sulfates

Fluorouracil (5-FU) is a widely used chemotherapeutic agent in various malignant tumors. However, intestinal toxicity is considered the irritant unavoidable adverse effect during the course therapy. The aim of the current study was to screen the effect of a new selective histamine receptor 1 blocker and platelet-activating factor (PAF) blocker on 5-FU induced intestinal toxicity. Five groups (6 rats each) of adult male rats (Wistar) were arranged as follows: (1) control group that was treated with carboxymethylcellulose, (2) a group that received rupatadine (higher dose) only, (3) a group that received 5-FU and (4) and (5) groups that received 5-FU plus lower or higher dose rupatadine, respectively. At end of the experiment, we determined intestinal malondialdehyde (MDA), glutathione reduced (GSH), nitric oxide (NO), tumor necrosis factor (TNF-α), interleukin 1β, 6, 10 (IL-1β, IL-6, IL-10), PAF, histamine, myeloperoxidase, cysteine-aspartic acid protease-3 (caspase-3), and nuclear factor kappa B (NF-κB) as well as the histological analysis. 5-FU injection caused marked elevation of MDA, NO, TNF-α, IL-1β, IL-6, PAF, histamine, myeloperoxidase, caspase-3, and NF-κB expressions. The intoxicated animals showed deficient GSH and IL-10 along with significant loss of villi, disorganized crypts, and inflammatory cell infiltration. Rupatadine pretreatment reduced the previously mentioned parameters, preserved a nearly normal intestinal mucosa picture with replenished GSH and elevated IL-10. In conclusion, rupatadine is a dual histamine receptor 1, and a PAF blocker could reduce 5-FU-induced oxidative damage, inflammation, apoptosis, and ulceration of the intestinal epithelium. Rupatadine may be a valuable modality to decrease 5-FU induced intestinal mucositis.

Topics: Animals; Apoptosis; Aspartic Acid Proteases; Carboxymethylcellulose Sodium; Caspase 3; Cysteine; Fluorouracil; Glutathione; Histamine; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; Intestinal Mucosa; Irritants; Male; Malondialdehyde; NF-kappa B; Nitric Oxide; Permeability; Peroxidase; Rats; Rats, Wistar; Tumor Necrosis Factor-alpha

Commonly used synthetic dietary emulsifiers, including carboxymethylcellulose (CMC) and polysorbate-80 (P80), promote intestinal inflammation. We compared abilities of CMC vs. P80 to potentiate colitis and impact human microbiota in an inflammatory environment using a novel colitis model of ex-germ-free (GF) IL10

Topics: Animals; Biomarkers; Body Weight; Carboxymethylcellulose Sodium; Colitis; Colon; Emulsifying Agents; Feces; Female; Gastrointestinal Microbiome; Gene Expression Regulation; Humans; Inflammation; Inflammatory Bowel Diseases; Male; Metabolic Networks and Pathways; Mice, Inbred C57BL; Polysorbates; RNA, Messenger

Inflammation is a well-characterized critical driver of gastrointestinal cancers. Previous findings have shown that intestinal low-grade inflammation can be promoted by the consumption of select dietary emulsifiers, ubiquitous component of processed foods which alter the composition and function of the gut microbiota. Using a model of colitis-associated cancer, we previously reported that consumption of the dietary emulsifiers carboxymethylcellulose or polysorbate-80 exacerbated colonic tumor development. Here, we investigate the impact of dietary emulsifiers consumption on cancer initiation and progression in a genetical model of intestinal adenomas. In APC

Topics: Adenoma; Animals; Carboxymethylcellulose Sodium; Carcinogenesis; Cell Proliferation; Colorectal Neoplasms; Diet; Emulsifying Agents; Female; Food Additives; Gastrointestinal Microbiome; Gastrointestinal Tract; Inflammation; Intestinal Mucosa; Intestines; Male; Mice; Mice, Inbred C57BL; Polysorbates

Topics: Animals; Antioxidants; beta-Cyclodextrins; Carboxymethylcellulose Sodium; Cyclodextrins; Diabetes Mellitus; Drug Carriers; Drug Liberation; Eugenol; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Hydrogels; Inflammation; Mice, Inbred C57BL; NF-kappa B; Receptors, Lipoprotein; Vascular Endothelial Growth Factor A; Wound Healing

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 immense burden imposed by chronic wounds-those persisting over 6 weeks despite active intervention-on patients and health services is well recognised. There are various reasons for why a wound fails to progress towards closure, and clinicians must investigate the underlying cause of wound chronicity, as this information guides the management of such wounds. The TIME framework (T=tissue; I=infection/inflammation; M=moisture balance; E=wound edges) is a useful tool for practitioners to systematically undertake wound assessment and product selection. This article discusses chronic wound management based on the TIME framework, examining the aspects to be considered when managing chronic wounds. It also describes the process of dressing selection for overcoming the various barriers to wound healing, specifically discussing the AQUACEL family of dressings.

Topics: Bandages; Carboxymethylcellulose Sodium; Chronic Disease; Humans; Inflammation; Tissue Survival; Wound Healing; Wound Infection; Wounds and Injuries

Dietary emulsifiers carboxylmethylcellulose (CMC) and polysorbate 80 (P80) alter the composition of the intestinal microbiota and induce chronic low-grade inflammation, ultimately leading to metabolic dysregulations in mice. As both gut microbiota and intestinal health can influence social and anxiety-like behaviors, we investigated whether emulsifier consumption would detrimentally influence behavior. We confirmed that emulsifier exposure induced chronic intestinal inflammation, increased adiposity, and altered gut microbiota composition in both male and female mice, although the specific microboal taxa altered following emulsifier consumption occurred in a sex-dependent manner. Importantly, emulsifier treatment altered anxiety-like behaviors in males and reduced social behavior in females. It also changed expression of neuropeptides implicated in the modulation of feeding as well as social and anxiety-related behaviors. Multivariate analyses revealed that CMC and P80 produced distinct clustering of physiological, neural, and behavioral effects in male and female mice, suggesting that emulsifier treatment leads to a syndrome of sex-dependent changes in microbiota, physiology, and behavior. This study reveals that these commonly used food additives may potentially negatively impact anxiety-related and social behaviors and may do so via different mechanisms in males and females.

Topics: Adiposity; Animals; Anxiety; Behavior, Animal; Carboxymethylcellulose Sodium; Emulsifying Agents; Female; Gastrointestinal Microbiome; Inflammation; Male; Mice; Mice, Inbred C57BL; Polysorbates; Social Behavior

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

Topics: ADAMTS Proteins; Carboxymethylcellulose Sodium; Complement Activation; Cytokines; HEK293 Cells; Humans; Inflammation; Macrophages; Nanotubes, Carbon; Properdin; Protein Binding; THP-1 Cells

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

Topics: Animals; Antioxidants; Apoptosis; Carboxymethylcellulose Sodium; Catalase; Collagen; Drug Carriers; Drug Delivery Systems; Endothelial Cells; Humans; Hydrogen Peroxide; Inflammation; Interleukin-10; Oxidative Stress; Peptides; Rats; Reactive Oxygen Species; Reperfusion Injury; Retina

The natural biopolymers usually need to be chemically modified by crosslinking reagents to improve their mechanical properties. In the present research, the feasibility of using the dialdehyde carboxymethyl cellulose (DCMC) as a crosslinking reagent was systematically studied. DCMC was prepared by oxidizing carboxymethyl cellulose using sodium periodate. The formation of dialdehyde groups was confirmed by FTIR and the degree of oxidation was determined. The biocompatibility of DCMC was investigated by evaluating its cytotoxicity to L929 fibroblasts and histocompatibility in rat model via intramuscular and subcutaneous injection. DCMC-crosslinked carboxymethyl chitosan (DCMC-CMCTS) was prepared and characterized using the glutaraldehyde-crosslinked CMCTS (GA-CMCTS) as control. The result demonstrated that DCMC was non-cytotoxic, biodegradable and biocompatible. The DCMC-CMCTS displayed significantly better thermostability, swelling capacity and cyto-compatibility compared with GA-CMCTS. Our data provided experimental basis for the future application of DCMC as a novel crosslinking reagent.

Topics: Animals; Carbohydrate Sequence; Carboxymethylcellulose Sodium; Cellulose; Cross-Linking Reagents; Cytotoxins; Feasibility Studies; Fibroblasts; Inflammation; Male; Microscopy, Electron, Scanning; Molecular Sequence Data; Rats; Rats, Sprague-Dawley

Iron oxide nanoparticles (NPs) have been proposed for many biomedical applications as in vivo imaging and drug delivery in cancer treatment, but their toxicity is an ongoing concern. When NPs are intravenously administered, the endothelium represents the first barrier to tissue diffusion/penetration. However, there is little information about the biological effects of NPs on endothelial cells. In this work we showed that cobalt-ferrite (CoFe2O4) NPs affect endothelial cell integrity by increasing permeability, oxidative stress, inflammatory profile and by inducing cytoskeletal modifications. To overcome these problems, NPs have be loaded into biocompatible gels to form nanocomposite hybrid material (polysaccharide hydrogels containing magnetic NPs) that can be further conjugated with anticancer drugs to allow their release close to the target. The organic part of hybrid biomaterials is a carboxymethylcellulose (CMC) polymer, while the inorganic part consists of CoFe2O4 NPs coated with (3-aminopropyl)trimethoxysilane. The biological activity of these hybrid hydrogels was evaluated in vitro and in vivo. Our findings showed that hybrid hydrogels, instead of NPs alone, were not toxic on endothelial, stromal and epithelial cells, safe and biodegradable in vivo. In conclusion, biohydrogels with paramagnetic NPs as cross-linkers can be further exploited for antitumor drug loading and delivery systems.

Topics: Antineoplastic Agents; Biocompatible Materials; Carboxymethylcellulose Sodium; Cell Line; Cobalt; Drug Delivery Systems; Endothelial Cells; Ferric Compounds; Human Umbilical Vein Endothelial Cells; Humans; Hydrogels; Inflammation; Nanoparticles; Oxidative Stress; Permeability

The aim of this study is to investigate the expected adhesion-modifying effect of clinoquinol which has metal-chelating feature that limits the inflammation and fibroblastic activity.. A total of 40 Wistar Albino rats were included, which were divided into 5 groups. Group-1 constituted the sham group. Other groups, adhesions were induced by performing cecal abrasion on the rats. For treatment, saline solution was added to Group-2, carboxymethylcellulose was added to Group-3, methylene blue was added to Group-4, and clioquinol was added to Group-5. Blood samples were obtained from the heart to measure IL-10 and TNF α-levels. Adhesions were evaluated both macroscopically and histopathologically.. Clioquinol reduced adhesions at significant level via decreasing the inflammation and fibroblastic activity in the adhesion-induced rats. At macroscopic level, carboxymethylcellulose and clioquinol were the most potent agents in reducing adhesions. Nonetheless, significant foreign body-reaction was observed in the carboxymethylcellulose-treated group.. Clioquinol could reduce the formation of intra-abdominal adhesions. It exerts this activity by limiting the inflammation and fibroblastic activity between the intestines and serous surfaces. Furthermore, it does not induce a foreign body reaction. Due to these properties, we conclude that clioquinol can be used as an alternative agent to prevent adhesions.

Topics: Animals; Carboxymethylcellulose Sodium; Cecum; Clioquinol; Inflammation; Interleukin-10; Male; Postoperative Complications; Rats; Rats, Wistar; Tissue Adhesions; Tumor Necrosis Factor-alpha

The intestinal tract is inhabited by a large and diverse community of microbes collectively referred to as the gut microbiota. While the gut microbiota provides important benefits to its host, especially in metabolism and immune development, disturbance of the microbiota-host relationship is associated with numerous chronic inflammatory diseases, including inflammatory bowel disease and the group of obesity-associated diseases collectively referred to as metabolic syndrome. A primary means by which the intestine is protected from its microbiota is via multi-layered mucus structures that cover the intestinal surface, thereby allowing the vast majority of gut bacteria to be kept at a safe distance from epithelial cells that line the intestine. Thus, agents that disrupt mucus-bacterial interactions might have the potential to promote diseases associated with gut inflammation. Consequently, it has been hypothesized that emulsifiers, detergent-like molecules that are a ubiquitous component of processed foods and that can increase bacterial translocation across epithelia in vitro, might be promoting the increase in inflammatory bowel disease observed since the mid-twentieth century. Here we report that, in mice, relatively low concentrations of two commonly used emulsifiers, namely carboxymethylcellulose and polysorbate-80, induced low-grade inflammation and obesity/metabolic syndrome in wild-type hosts and promoted robust colitis in mice predisposed to this disorder. Emulsifier-induced metabolic syndrome was associated with microbiota encroachment, altered species composition and increased pro-inflammatory potential. Use of germ-free mice and faecal transplants indicated that such changes in microbiota were necessary and sufficient for both low-grade inflammation and metabolic syndrome. These results support the emerging concept that perturbed host-microbiota interactions resulting in low-grade inflammation can promote adiposity and its associated metabolic effects. Moreover, they suggest that the broad use of emulsifying agents might be contributing to an increased societal incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.

Topics: Adiposity; Animals; Carboxymethylcellulose Sodium; Colitis; Diet; Emulsifying Agents; Feces; Female; Gastrointestinal Tract; Germ-Free Life; Inflammation; Intestinal Mucosa; Male; Metabolic Syndrome; Mice; Microbiota; Obesity; Polysorbates

Hernias can be repaired by reinforcement of damaged fascia using biomaterials to provide stabilisation. Repair materials are usually porous, through which cells infiltrate, proliferate and secrete ECM. Their efficacy relies on good tissue integration and resolution of host defence mechanisms. Therefore, understanding the dynamics by which biomaterials interact with tissue will provide knowledge to advance prosthesis design. Furthermore, determining host response in real time would provide significant advantage both clinically and scientifically over the current terminal process of histology.. 3 materials comprising synthetic and composite (synthetic materials hybridised with a resorbable biologic component) meshes were implanted into a rat full-thickness abdominal wall excision model. Their efficacy was evaluated using histopathology whilst also monitoring systemic concentrations of cytokines associated with inflammation and wound healing to predict material outcome over 12 weeks.. The noncomposite material (polyester) and Material B (polypropylene mesh with oligocaprone film and polydioxanone glue) stimulated the largest degree of adhesion from the 3 materials tested, although after 28 days adhesions were stronger to Material B. Histologically, all 3 materials integrated well with abdominal musculature and infiltrated completely with cells.. Analysis of systemic inflammation biomarkers confirmed inflammation elicited by surgeries and meshes irrespective of their composition. However, at an early postoperative endpoint (i.e., 1 week), some biomarkers, namely, IL-18 and RANTES, appeared to discriminate the noncomposite mesh from the composite materials, although in this study all materials successfully repaired the defects without recurrence or external indicators of postoperative chronic pain.

Topics: Abdominal Wall; Absorbable Implants; Animals; Biomarkers; Carboxymethylcellulose Sodium; Cytokines; Foreign-Body Reaction; Herniorrhaphy; Hyaluronic Acid; Inflammation; Inflammation Mediators; Male; Models, Animal; Polydioxanone; Polyesters; Polypropylenes; Prosthesis Design; Rats, Wistar; Surgical Mesh; Time Factors; Tissue Adhesives; Wound Healing

This study aimed to investigate the protective effect of emodin on endoplasmic reticulum (ER) stress in rats with severe acute pancreatitis (SAP) and the underlying molecular mechanism. Sprague-Dawley male rats were randomly divided into sham operation group, SAP model group, and emodin treatment group. SAP was constructed through injecting sodium taurocholate into pancreatic and biliary duct in rats. Half an hour before establishing the animal model, emodin or sodium carboxymethylcellulose was intragastrically administrated to the rats in respective group. Rats were killed at 3, 6, and 12 h postdisease induction. The amylase, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels in serum, pancreatic histopathology, acinar ER ultrastructure, protein expression of Bip, IRE1α,TRAF2, ASK1, p-JNK, and p-p38 MAPK in pancreas were examined. Sodium taurocholate induced pancreatic injury and ER lumen dilated in exocrine pancreas in rats at 3-, 6-, and 12-h time points. ER stress transducers Bip, IRE1α, and their downstream molecules TRAF2, ASK1 in pancreatitis were upregulated. Furthermore, phosphorylation of JNK and p38MAPK in pancreas was increased, which induced high expression level of inflammatory cytokines such as TNF-α and IL-6. Treatment with emodin obviously ameliorated pancreatic injury and decreased the release of amylase and inflammatory cytokines. Further studies showed that emodin significantly decreased the expression of Bip, IRE1α, TRAF2, and ASK1, inhibited phosphorylation of JNK and p38 MAPK in pancreas in rats at all time points. Emodin could reduce pancreatic injury and restrain inflammatory reaction in SAP rats partly via inhibiting ER stress transducers IRE1α and its downstream molecules.

Topics: Amylases; Animals; Carboxymethylcellulose Sodium; Emodin; Endoplasmic Reticulum Stress; Endoribonucleases; Heat-Shock Proteins; Inflammation; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Male; MAP Kinase Kinase Kinase 5; Multienzyme Complexes; p38 Mitogen-Activated Protein Kinases; Pancreas; Pancreatitis, Acute Necrotizing; Phosphorylation; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Rats; Rats, Sprague-Dawley; Taurocholic Acid; TNF Receptor-Associated Factor 2; Tumor Necrosis Factor-alpha; Up-Regulation

We aimed to evaluate whether using sodium hyaluronate carboxymethylcellulose membrane (Seprafilm™) can facilitate assessment of hepatic microcirculation via orthogonal polarization spectroscopy (OPS) by preventing intra-abdominal adhesions and whether Seprafilm™ as a foreign material can evoke local or systemic inflammatory reactions. After the right median hepatic vein was ligated, rats received either placement of Seprafilm™ or untreated with observation of 1 or 4 weeks (n = 6/group). Hepatic microcirculation was visualized. Systemic and local inflammatory reactions were evaluated by blood count, histology and immunohistochemical staining for CD68. Seprafilm™ significantly (P < 0.05) prevented intra-abdominal adhesion formation compared to non-Seprafilm™ groups (adhesion score: 0 vs 1.3 ± 0.5 at POW1 and 0.3 ± 0.5 vs 3.5 ± 1.4 at POW4). Placement of Seprafilm™ provided sufficient liver surface for acquisition of OPS videos during the harvest procedure. Adhesiolysis in non-Seprafilm™ groups prevented visualization of hepatic microcirculation. A severe local foreign body reaction with formation of a "fibrin-like" membrane containing CD68-positive inflammatory histiocytic cells and mesothelial cells was observed in Seprafilm™ groups even at POW4. Use of Seprafilm™ conferred visualization of hepatic microcirculation after long term observation in experimental setting. In clinical situation, we would suggest being very cautious in immuno-compromised patients because of an ongoing local foreign body reaction caused by Seprafilm™.

Topics: Animals; Carboxymethylcellulose Sodium; Hyaluronic Acid; Inflammation; Liver; Male; Membranes, Artificial; Microcirculation; Microscopy, Video; Postoperative Complications; Rats; Rats, Inbred Lew; Tissue Adhesions

Oleanolic acid (OA) is a triterpenoid known for its anti-inflammatory and anti-cancer properties; however, the anti-inflammatory effects of OA on lipopolysaccharide (LPS)-mediated pro-inflammatory responses have not been studied. Here, we first investigated the possible anti-inflammatory effects of OA against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) induced by LPS and the associated signaling pathways. We found that OA inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to HUVECs. OA also suppressed acetic acid-induced hyperpermeability and carboxymethylcellulose-induced leukocyte migration in vivo. Further studies revealed that OA suppressed the production of tumor necrosis factor-α and activation of nuclear factor-κB by LPS. Collectively, these results suggest that OA has anti-inflammatory effects by inhibiting hyperpermeability, the expression of CAMs, and the adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapeutic agent for vascular inflammatory diseases.

Topics: Acetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carboxymethylcellulose Sodium; Cell Adhesion; Cell Line; Cell Movement; Cell Survival; E-Selectin; Endothelium, Vascular; Enzyme Activation; Female; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Intercellular Adhesion Molecule-1; Lipopolysaccharides; Mice; Mice, Inbred ICR; NF-kappa B; Oleanolic Acid; Transendothelial and Transepithelial Migration; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

A major obstacle thwarting preclinical development of microbicides is the lack of a validated biomarker of cervicovaginal inflammation. Therefore, the present study aims to identify novel noninvasive soluble markers in a murine model for assessment of microbicide mucosal safety. By performing cytokine antibody array analysis, we identified two adhesion molecules, L-selectin and P-selectin, which significantly increased when mucosal inflammation was triggered by nonoxynol-9 (N9), an anti-HIV-1 microbicide candidate that failed clinical trials, in a refined murine model of agent-induced cervicovaginal inflammation. We found that patterns of detection of L-selectin and P-selectin were obviously different from those of the two previously defined biomarkers of cervicovaginal inflammation, monocyte chemotactic protein 1 (MCP-1) and interleukin 6 (IL-6). The levels of these two soluble selectins correlated better than those of MCP-1 and IL-6 with the duration and severity of mucosal inflammation triggered by N9 and two approved proinflammatory compounds, benzalkonium chloride (BZK) and sodium dodecyl sulfate (SDS), but not by two nonproinflammatory compounds, carboxymethyl celluose (CMC; microbicide excipients) and tenofovir (TFV; microbicide candidate). These data indicated that L-selectin and P-selectin can serve as additional novel cervicovaginal inflammation biomarkers for preclinical mucosal safety evaluation of candidate microbicides for the prevention of infection with HIV and other sexually transmitted pathogens.

Topics: Adenine; Animals; Anti-Infective Agents; Benzalkonium Compounds; Biomarkers; Carboxymethylcellulose Sodium; Cervix Uteri; Chemokine CCL2; Female; HIV Infections; Inflammation; Interleukin-6; L-Selectin; Mice; Mice, Inbred C57BL; Mucous Membrane; Nonoxynol; Organophosphonates; P-Selectin; Sodium Dodecyl Sulfate; Tenofovir

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

Excess or "uncontrolled" proteinase activity in the wound bed has been implicated as one factor that may delay or compromise wound healing. One proteinase group--matrix metalloproteinases--includes collagenases, elastase, and gelatinases and can be endogenous (cell) or exogenous (bacterial) in origin. A study was conducted to assess the ability of five silver-containing wound care products to reduce a known matrix metalloproteinase supernatant concentration in vitro. Four silver-containing wound dressings (a carboxy-methyl cellulose, a nanocrystalline, a hydro-alginate, and a collagen/oxidized regenerated cellulose composite dressing), along with a 0.5% aqueous silver nitrate [w/v] solution and controls for matrix metalloproteinase-2 and matrix metalloproteinase-9 sourced from ex vivo dermal tissue and blood monocytes, respectively, were used. Extracts were separated and purified using gelatine-Sepharose column chromatography and dialysis and polyacrylamide gel electrophoretic zymography was used to analyze specific matrix metalloproteinase activity. All dressings and the solution were shown to sequester both matrix metalloproteinases. The silver-containing carboxy-methyl cellulose dressing showed significantly greater sequestration for matrix metalloproteinase-2 at 6 and 24 hours (P< 0.001) compared to the other treatments. For matrix metalloproteinase-9, both the carboxy-methyl cellulose dressing and the oxidized regenerated cellulose dressing achieved significant sequestration when compared to the other treatments at 24 hours (P <0.001), which was maintained to 48 hours (P < 0.001). Results from this study show that silver-containing dressings are effective in sequestering matrix metalloproteinase-2 and -9 and that this can be achieved without a sacrificial protein (eg, collagen). Although the varying ability of wound dressings to sequester matrix metalloproteinases has been shown in vitro, further in vivo evidence is required to confirm these findings.

Topics: Alginates; Analysis of Variance; Animals; Anti-Infective Agents, Local; Bandages; Carboxymethylcellulose Sodium; Cell Culture Techniques; Chromatography, Agarose; Debridement; Drug Evaluation, Preclinical; Electrophoresis, Polyacrylamide Gel; Exudates and Transudates; Horses; Inflammation; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Phagocytosis; Polyesters; Polyethylenes; Silver Nitrate; Skin Care; Wound Healing; Wounds and Injuries

Cell-impermeable inhibitors of phospholipase A2 were prepared by linking inhibiting molecules to macromolecular carriers which prevent the inhibitor's internalization. These preparations inhibit the release of oxygen reactive species from neutrophils and cell death induced by inflammatory agents, as well as bleomycin-induced lung injury.

Topics: Animals; Carboxymethylcellulose Sodium; Cell Membrane Permeability; Cells, Cultured; Cricetinae; Humans; Inflammation; Neutrophils; Phosphatidylethanolamines; Phospholipases A; Phospholipases A2; Reactive Oxygen Species

Potent chemotactic activity for neutrophils was detected in rat inflammatory exudate induced by a subcutaneous injection of lipopolysaccharide in a carboxymethyl-cellulose suspension. We purified and characterized chemoattractants from the exudate by the following procedures: carboxymethyl-Sephadex C-25 ion-exchange chromatography; G3000SW gel-filtration chromatography; preparative reverse-phase high-pressure liquid chromatography; rechromatography on reverse-phase HPLC. Two chemotactic factors were purified and their N-terminal amino acid sequences were determined. One factor was a protein in which the first 20 N-terminal amino acids were identical to those of rat cytokine-induced neutrophil chemoattractant (CINC), a counterpart of human gro/melanoma growth-stimulating activity (MGSA). The other factor was highly similar to mouse macrophage inflammatory protein 2 (MIP-2). Mouse MIP-2, a chemotactic factor for neutrophils, is a member of the interleukin-8 family; however the protein we purified had higher similarity to human gro/MGSA than to human interleukin-8. These results indicate that, in rats, chemotactic factors for neutrophils induced by lipopolysaccharide stimulation are not counterparts of interleukin-8, but are gro/CINC-related peptides.

Topics: Amino Acid Sequence; Animals; Carboxymethylcellulose Sodium; Chemokine CXCL1; Chemokine CXCL2; Chemokines, CXC; Chemotactic Factors; Chemotaxis, Leukocyte; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Growth Substances; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-8; Lipopolysaccharides; Male; Molecular Sequence Data; Neutrophils; Rats; Rats, Sprague-Dawley; Rats, Wistar

Inflammatory reactions were compared in the air pouch and the CMC pouch. Inflammation was induced by injection of CMC as a non-specific irritant, lipopolysaccharide (LPS) as an activator of macrophages, and methylated bovine serum albumin (m-BSA) as an inducer of delayed type hypersensitivity. There was no prominent difference in the inflammatory reactions following injection of 2% CMC solution into a 4-day-old air pouch and a 3-day-old CMC pouch. On the other hand, injection of 4 ml of 100 ng/ml LPS into each of the pouches enhanced the inflammatory reactions in the CMC pouch several-fold compared with those in the air pouch. A similar tendency was found in the case of an injection of 1 ml of 1 mg/ml m-BSA in rats sensitized with 1 mg of m-BSA. The enhanced inflammatory reactions induced by the injection of LPS or m-BSA were inhibited by dexamethasone, but not by indomethacin. These results indicate that the enhanced inflammatory reactions induced by CMC are related to lining tissue formation, which was a common characteristic in both pouches. Enhanced inflammatory reactions following injection of LPS and m-BSA were related to the activation of macrophages and newly formed blood vessels, which were not characteristic features in the air pouch, but were in the CMC pouch, in addition to the lining tissue. Cyclo-oxygenase products were not associated with the reactions.

Topics: Air Sacs; Animals; Carboxymethylcellulose Sodium; Dexamethasone; Hypersensitivity, Delayed; Indomethacin; Inflammation; Lipopolysaccharides; Macrophage Activation; Male; Rats; Rats, Inbred Strains; Serum Albumin, Bovine; Time Factors

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

CBS-1108, 2- acetylthiophene 2- thiazolyhydrazone , inhibits 5-lipoxygenase activity in polymorphonuclear leukocytes (PMNs) (IC50 = 2 X 10(-6) M), 12-lipoxygenase (IC50 = 9 X 10(-6) M) and cyclooxygenase (IC50 = 2 X 10(-6) M) in platelets. Inhibition of the two pathways of arachidonic acid cascade could lead to additional beneficial anti-inflammatory activity by comparison with classical aspirin-like drugs. In fact, only inhibitors of both cyclooxygenase and lipoxygenase such as NDGA and CBS-1108 inhibit leukocyte migration in an animal model of acute inflammatory response.

Topics: Animals; Arachidonate Lipoxygenases; Aspirin; Blood Platelets; Carboxymethylcellulose Sodium; Chemotaxis, Leukocyte; Cyclooxygenase Inhibitors; Humans; Inflammation; Lipoxygenase Inhibitors; Male; Neutrophils; Rabbits; Rats; Rats, Inbred Strains; Thiazoles

Induction of an experimental inflammation of the air-pouch type with the aid of zymosan (known to activate the alternative pathway of the complement system) was carried out in an attempt to induce a reproducible inflammatory model suitable for quantitative studies. Rats were injected subcutaneously with 8 ml of air on the dorsal surface to make an air-pouch, followed 24h later by 4 ml of 1.6% (w/v) zymosan suspension. This induced inflammatory responses. Treatment with zymosan suspension provoked exudation of fluid, accumulation of polymorphnuclear leukocytes (PMN) in the pouch and the development of granulation tissue as a wall of the pouch. Approximately half of the PMN in the pouch formed a characteristic layer of aggregated cells sticking onto the inner surface of the pouch wall. They were counted after being completely disaggregated by means of incubation with trypsin. In preliminary experiments with potential anti-inflammatory drugs, local application of a novel anti-complementary agent, K-76COONa, inhibited leukocyte accumulation in the pouch, whereas the potent anti-inflammatory agent, dexamethasone, was ineffective. By contrast, exudation of the pouch fluid was effectively inhibited by dexamethasone but not by K-76COONa.

Topics: Animals; Anti-Inflammatory Agents; Carboxymethylcellulose Sodium; Complement Inactivator Proteins; Dexamethasone; Granulation Tissue; Inflammation; Male; Rats; Rats, Inbred Strains; Sesquiterpenes; Zymosan