silicon and Disease-Models--Animal

Approximately three million workers in the United States are estimated to be exposed to silica, man-made mineral fibers, and asbestos. The lung is the primary target organ of concern. Each of these substances is composed predominantly of silicon and oxygen; asbestos and silica are crystalline, and asbestos and man-made mineral fibers are fibers. Man-made mineral fibers and asbestos are used as insulating agents, with the former having generally replaced the latter in recent years. Silica is used in foundries, pottery, and brick making, and is encountered by miners. A meta-analysis of 16 of the largest studies with well-documented silica exposure and low probability of confounding by other occupational exposures, indicates a relative risk (RR) of 1.3 (95 percent confidence interval [CI] = 1.2-1.4). Lung cancer risks are highest and most consistent for silicotics, who have received the highest doses (RR = 2.3, CI = 2.2-2.4, across 19 studies). The data for mineral fibers continue to support the International Association for Research on Cancer's 1988 judgment that mineral fibers are a possible human carcinogen (Group 2B). Recent epidemiologic studies provide little evidence for lung carcinogenicity for either glass wool or rock/slag wool. Ceramic fibers, a much less common exposure than glass wool and rock/slag wool, are of concern because of positive animal studies, but there are insufficient human data. Regarding asbestos, its carcinogenicity for the lung and mesothelium is well established. With regard to the controversy over chrysotile and mesothelioma, the data suggest chrysotile does cause mesothelioma, although it may be less potent than amphibole asbestos.

Topics: Animals; Asbestos; Asbestos, Serpentine; Carcinogens; Ceramics; Confidence Intervals; Confounding Factors, Epidemiologic; Construction Materials; Crystallization; Disease Models, Animal; Glass; Humans; Lung Neoplasms; Mesothelioma; Meta-Analysis as Topic; Mineral Fibers; Mining; Occupational Diseases; Occupational Exposure; Oxygen; Probability; Risk Factors; Silicon; Silicon Dioxide; Silicosis; United States

Ulcerative colitis (UC) is a non-specific inflammatory bowel disease that causes ulcers and erosions in the colonic mucosa and becomes chronic with cycles of amelioration and exacerbation. Because its exact etiology remains largely unclear, and the primary therapy is limited to symptomatic treatment, the development of new therapeutic agent for UC is highly desired. Because one of the disease pathogenesis is involvement of oxidative stress, it is likely that an appropriate antioxidant will be an effective therapeutic agent for UC. Our silicon (Si)-based agent, when ingested, allowed for stable and persistent generation of massive amounts of hydrogen in the gastrointestinal tract. We demonstrated the Si-based agent alleviated the mental symptom as well as the gastrointestinal symptoms, inflammation, and oxidation associated with dextran sodium sulfate-induced UC model through Hydrogen and antioxidant sulfur compounds. As the Si-based agent was effective in treating UC in the brain and large intestine of mice, it was considered to be capable of suppressing exacerbations and sustaining remission of UC.

Topics: Animals; Antioxidants; Brain; Colitis, Ulcerative; Colon; Dextran Sulfate; Disease Models, Animal; Hydrogen; Mice; Silicon

Noise-induced hearing loss (NIHL) is one of the leading causes of sensorineural hearing loss with global importance. The current treatment of choice for patients with hearing problems is a hearing aid or a cochlear implant. However, there is currently no treatment to restore physiological hearing. The development of preventive drugs is currently the focus of hearing research. In order to test the efficacy of a drug, the active ingredient has to be applied at reliable concentrations over a period of time. Osmotic minipumps can provide local drug delivery into the perilymph. Combined with a cochlear implant or a tube, the implantation of the pumps may lead to increased hearing thresholds. Such surgery-related threshold shifts complicate the examination of other factors, such as noise. The aim of the present study was to develop an animal model for the examination of substances that potentially prevent NIHL. For this purpose, six male guinea pigs were unilaterally implanted with a silicon catheter with a hook-shaped microcannula at its tip, attached to an artificial perilymph containing osmotic minipump. One week after surgery, the animals were exposed to four hours of a musical piece, presented at 120 dB SPL, to induce a threshold shift. The implantation of the hook-delivery device caused a moderate threshold shift that allows to detect an additional noise-induced temporary threshold shift. This method enables to investigate drug effects delivered prior to the noise insult in order to establish a preventive strategy against noise-induced temporary threshold shifts. The established drug delivery approach allows the release of drugs into the inner ear in a known concentration and for a known duration. This provides a scientific tool for basic research on drug effects in normal hearing animals.

Topics: Animals; Cochlea; Disease Models, Animal; Ear, Inner; Guinea Pigs; Hearing; Hearing Loss, Noise-Induced; Male; Silicon

Cannabinoids are widely studied as therapeutic agents for the treatment of various diseases. Among them, THC and CBD are two important phytocannabinoids which have served as structural templates for the design of synthetic analogs. In this study, we designed and synthesized a variety of novel cannabinoids based on the structural backbones of THC and CBD using the carbon-silicon switch strategy. A dimethyl silyl group was introduced as the tail group and two series of novel compounds were designed and synthesized, which showed a wide range of binding affinity for CB1 and CB2 receptors. Among them, compound 15b was identified as a non-selective CB1 and CB2 agonist and 38b as a selective agonist for the CB2 receptor. Preliminary screening showed that both compounds have improved metabolic stability than their carbon analogs and good in vivo pharmacokinetic profiles. Furthermore, both 15b and 38b significantly alleviated the phenotype of experimental autoimmune encephalomyelitis (EAE) in mice.

Topics: Animals; Cannabinoids; Carbon; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Discovery; Encephalomyelitis, Autoimmune, Experimental; Male; Mice; Mice, Inbred C57BL; Molecular Structure; Multiple Sclerosis; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Silicon; Structure-Activity Relationship

Tumor angiogenesis is a complex process that is unamenable to intravital whole-process monitoring, especially on microscopic assessment of tumor microvessel and quantifying microvascular hemodynamics before and after the nanotherapeutics, which hinder the understanding of nanotheranostics outcomes in tumor treatment. Herein, a new photoacoustic (PA) imaging-optical coherence tomography angiography (OCTA)-laser speckle (LS) multimodal imaging strategy is first proposed, which is not only able to precisely macro guide the thermo-chemotherapy of tumor by monitoring blood oxygen saturation (SaO

Topics: Animals; Antimetabolites, Antineoplastic; Brain Neoplasms; Disease Models, Animal; Fluorouracil; Glioma; Humans; Male; Mice; Mice, Inbred BALB C; Multimodal Imaging; Nanostructures; Oxygen Saturation; Photoacoustic Techniques; Silicon; Tomography, Optical Coherence

Removal of chondroitin sulfate proteoglycans (CSPGs) with chondroitinase ABC I (ChABC) facilitates axonal plasticity, axonal regeneration and remyelination, following injury to the central nervous system (CNS). However, the ChABC rapidly undergoes thermal inactivity and needs to be injected repeatedly. Here this limitation was overcame by immobilizing the ChABC on porous silicon (PSi) nanoparticles (ChABC@PSi). The efficacy of immobilized ChABC on CSPGs level and the demyelination insult was assessed in mice corpora callosa demyelinated by 6 weeks cuprizone (CPZ) feeding. ChABC@PSi was able to reduce the amount of CSPGs two weeks after animals treatment. CSPGs digestion by ChABC@PSi reduced the extent of demyelinated area as well as the astrogliosis. Furthermore, ChABC@PSi treatment increased the number of newly generated oligodendrocyte lineage cells which imply for enhanced myelin repair. Our results showed that effective CSPGs digestion by ChABC@PSi enhanced remyelination in CPZ model. Accordingly, ChABC@PSi may have a great potential to be used for treatment of diseases like multiple sclerosis and spinal cord injury by promoting the regeneration of damaged nerves.

Topics: Animals; Chondroitin ABC Lyase; Disease Models, Animal; Enzymes, Immobilized; Humans; Male; Mice; Multiple Sclerosis; Myelin Sheath; Nanoparticles; Silicon

Accumulating evidence indicates much higher failure rates for biomedical titanium implants in diabetic patients. This phenomenon is attributed to impaired osteoblastic function, suppressed angiogenesis capacity, and abnormal osteoclast activation in diabetic patients. Our previous study demonstrated that titanium implants coated with highly crystalline nanostructured hydroxyapatite (nHA) promoted the osteogenic differentiation of bone marrow stromal cells (BMSCs) and bone-implant osseointegration under healthy conditions. Furthermore, recent studies showed that silicon-substituted biomaterials exhibited excellent osteogenesis and angiogenesis performance while repressing osteoclastogenesis. Hence, we proposed that a combination of nanostructural modification and Si substitution might produce synergetic effects to mitigate the impaired osseointegration of bone implants under diabetes mellitus (DM) conditions. To confirm this hypothesis, titanium implants coated with highly crystalline Si-substituted nHA (Si-nHA) were successfully fabricated via atmospheric plasma spraying combined with hydrothermal treatment. An in vitro study demonstrated that compared to the original HA coating, the nHA coating improved osteogenic and angiogenic differentiation and altered the OPG/RANKL ratio of DM-BMSCs. In addition, the Si-nHA coating further enhanced cell proliferation, improved osteogenic and angiogenic differentiation, and repressed osteoclastogenesis in DM-BMSCs. An in vivo study confirmed that the titanium implants coated with nHA or Si-nHA effectively promoted bone formation and bone-implant osseointegration in a diabetic rabbit model, with the Si-nHA coating exhibiting the best stimulatory effect. Collectively, the results suggest that the nanostructured topography and Si substitution act synergistically to ameliorate the poor bone regeneration and osseointegration associated with DM. Thus, the results provide a promising coating method for dental and orthopedic applications under diabetic conditions.

Topics: Alloxan; Animals; Coated Materials, Biocompatible; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Disease Models, Animal; Durapatite; Hypoglycemic Agents; Male; Nanostructures; Osseointegration; Particle Size; Rabbits; Silicon; Surface Properties

We have developed Si-based agent which can generate a large amount of hydrogen. Si-based agent continues generating hydrogen for more than 24 h by the reaction with water under conditions similar to those in bowels, i.e., pH8.3 and 36 °C, and generates ~400 mL hydrogen. To investigate beneficial effects for diseases associated with oxidative stress, Si-based agent is administered to remnant kidney rats and Parkinson's disease mice. Rats are fed with control or Si-based agent-containing diet for 8 weeks. Si-based agent is found to greatly suppress the development of renal failure and the parameters of oxidative stress. Treatment with Si-based agent in a mouse model of hemi-Parkinson's disease induced by 6-hydroxydopamine attenuated degeneration of dopaminergic neurons and prevented impairment of motor balance and coordination. These findings indicate that the Si-based agent shows renoprotective and neuroprotective effects presumably via suppression of oxidative stress by generation of hydrogen.

Topics: Animals; Disease Models, Animal; Hydrogen; Kidney; Male; Mice; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Renal Insufficiency, Chronic; Rotarod Performance Test; Silicon; Tyrosine 3-Monooxygenase

Humans are exposed to charged particles in different scenarios. The use of protons and high-linear energy transfer (LET) in cancer treatment is steadily growing. In outer space, astronauts will be exposed to a mixed radiation field composed of both protons and heavy ions, in particularly the long-term space missions outside of earth's magnetosphere. Thus, understanding the radiobiology and transforming potential of these types of ionizing radiation are of paramount importance.. We examined the effect of 10 or 100 cGy of whole-body doses of protons or. We found that Mlh1 deficient animals are highly prone to develop lymphomas when exposed to either low doses of protons or. Although the incidence of malignancy is related to radiation quality, and increased due to loss of Mlh1, the phenotype of the tumors is independent of LET.

Topics: Aging; Animals; Disease Models, Animal; DNA Mismatch Repair; Female; Gene Expression Profiling; Hematopoietic System; Humans; Linear Energy Transfer; Lymphoma; Male; Mice; MutL Protein Homolog 1; Neoplasms, Radiation-Induced; Penetrance; Protons; Radiation Exposure; Sequence Analysis, RNA; Silicon; Space Flight; Whole-Body Irradiation

In this study, we examined the effect of differing gap lengths on regeneration of transected recurrent laryngeal nerves using silicon tubes containing type I collagen gel and the ability of this regeneration to result in restoration of vocal fold movements in rats. We simulated nerve gaps in Sprague-Dawley rats by transecting the left recurrent laryngeal nerves and bridged the nerve stumps using silicon tubes containing type 1 collagen gel. Three experimental groups, in which the gap lengths between the stumps were 1, 3, or 5 mm, were compared with a control group in which the nerve was transected but was not bridged. After surgery, we observed vocal fold movements over time with a laryngoscope. At week 15, we assessed the extent of nerve regeneration in the tube, histologically and electrophysiologically. We also assessed the degree of atrophy of the thyroarytenoid muscle (T/U ratio). Restoration of vocal fold movements was observed in 9 rats in the 1-mm group, in 6 rats in the 3-mm group, and in 3 rats in the 5-mm group. However, in most rats, restoration was temporary, with only one rat demonstrating continued vocal fold movements at week 15. In electromyograph, evoked potentials were observed in rats in the 1-mm and 3-mm groups. Regenerated tissue in the tube was thickest in the 1-mm group, followed by the 3-mm and 5-mm groups. The regenerated tissue showed the presence of myelinated and unmyelinated nerve fibers. In assessment of thyroarytenoid muscle atrophy, the T/U ratio was highest in the 1-mm group, followed by the 3-mm and 5-mm groups. We successfully regenerated the nerves and produced a rat model of recurrent laryngeal nerve regeneration that demonstrated temporary recovery of vocal fold movements. This rat model could be useful for assessing novel treatments developing in the future.

Topics: Animals; Biocompatible Materials; Collagen; Disease Models, Animal; Gels; Male; Nerve Regeneration; Rats; Rats, Sprague-Dawley; Recurrent Laryngeal Nerve; Recurrent Laryngeal Nerve Injuries; Silicon

Chronic renal failure is exacerbated by oxidative stress, and this condition is difficult to treat in advanced stages. Because of the lack of effective treatments, the disease is a global public health concern. We developed a Si-based agent that continuously generates hydrogen for more than 24 h by reacting with water under conditions similar to those in the gastrointestinal tract. Given the efficacy of hydrogen in the treatment of conditions associated with oxidative stress, we examined whether the Si-based agent had beneficial effects on the development of renal failure. The Si-based agent was orally administered to rats that were developing renal failure. Rats underwent 5/6 nephrectomy to establish a remnant kidney model. Specifically, on day -7, rats underwent right 2/3 nephrectomy, followed by light nephrectomy on day 0. Starting on day -3, the rats were administered a control or Si-based agent-containing diet for 8 weeks. Compared with the findings in control rats, the Si-based agent greatly suppressed the increases of both serum creatinine and urinary protein levels. All analyzed parameters of oxidative stress were significantly suppressed in the Si-based agent groups. Histopathological examination illustrated that glomerular hypertrophy was suppressed by the treatment. Quantitative real-time reverse transcription-polymerase chain reaction revealed that sirtuin 1 and heme oxygenase-1 expression was increased in the Si-based agent groups, suggesting improved antioxidant activity and reduced hypoxia. In addition, caspase-3 and interleukin-6 expression was suppressed in the Si-based agent groups, indicating the alleviation of apoptosis and inflammation. In conclusion, oral administration of a Si-based agent resulted in renoprotective effects, presumably by suppressing oxidative stress via hydrogen generation.

Topics: Administration, Oral; Animals; Antioxidants; Caspase 3; Cell Hypoxia; Creatinine; Disease Models, Animal; Down-Regulation; Heme Oxygenase-1; Hydrogen; Interleukin-6; Kidney; Kidney Failure, Chronic; Male; Nephrectomy; Oxidative Stress; Rats; Rats, Sprague-Dawley; Silicon; Sirtuin 1; Up-Regulation

Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.

Topics: Animals; Cell Line, Tumor; Disease Models, Animal; Doxorubicin; Drug Carriers; Drug Compounding; Exocytosis; Exosomes; Female; Humans; Male; Mice; Nanoparticles; Neoplasms; Neoplastic Stem Cells; Porosity; Proof of Concept Study; Silicon; Spheroids, Cellular; Xenograft Model Antitumor Assays

Elevated intraocular pressure (IOP) is a well-documented risk factor for glaucoma. Here we describe a novel, effective method for consistently inducing stable IOP elevation in mice that mimics the post-operative complication of using silicone oil (SO) as a tamponade agent in human vitreoretinal surgery. In this protocol, SO is injected into the anterior chamber of the mouse eye to block the pupil and prevent inflow of aqueous humor. The posterior chamber accumulates aqueous humor and this in turn increases the IOP of the posterior segment. A single SO injection produces reliable, sufficient, and stable IOP elevation, which induces significant glaucomatous neurodegeneration. This model is a true replicate of secondary glaucoma in the eye clinic. To further mimic the clinical setting, SO can be removed from the anterior chamber to reopen the drainage pathway and allow inflow of aqueous humor, which is drained through the trabecular meshwork (TM) at the angle of the anterior chamber. Because IOP quickly returns to normal, the model can be used to test the effect of lowering IOP on glaucomatous retinal ganglion cells. This method is straightforward, does not require special equipment or repeat procedures, closely simulates clinical situations, and may be applicable to diverse animal species. However, minor modifications may be required.

Topics: Animals; Aqueous Humor; Disease Models, Animal; Injections, Intraocular; Intraocular Pressure; Male; Mice; Mice, Inbred C57BL; Ocular Hypertension; Oils; Retinal Ganglion Cells; Silicon

The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr

Topics: Animals; Arthroplasty, Replacement; Bone Regeneration; Cartilage; Cell Differentiation; Cell Proliferation; Cells, Cultured; Ceramics; Chondrocytes; Disease Models, Animal; Drug Carriers; Guided Tissue Regeneration; Histocytochemistry; Osteochondritis; Printing, Three-Dimensional; Rabbits; Signal Transduction; Silicon; Strontium; Tissue Scaffolds; Treatment Outcome; X-Ray Microtomography

Up to 15% of combat trauma cases are accompanied by neuroinjuries with nerve gap formation that need to be bridged using various techniques and materials. Both with this prevalence of limb loss, especially traumatic amputations, tends to grow. Loosed limbs must be prosthetized by modern functional mind-controlled prosthesis based on nerve- or brain-computer interfaces. This study aimed at morphological evaluation of interaction between nerve fibers and silicon wires with different surface properties using peripheral nerve injury and grafting model. Experiment was performed on 50 male Wistar rats, weighing 180-250 g. Rats from experimental groups underwent sciatic nerve injury Sunderland 5 degree with a 10 mm gap formation that was subsequently filled with conduit consisting of decellularized aorta, carboxymethylcellulose gel and a set of longitudinally oriented p-type silicon wires 2-20 µm in diameter. We used silicon wires with native oxide in group Ia, with hydrogen-cleaned surface in group Ib and thermally grown oxide in group Ic. The gap in control groups was filled with decellularized aorta with gel alone (group II) or by autoneurograft (group III). 6 weeks postoperatively the conduit site was harvested and light microscopy performed. Implantation of conduit with native oxide on silicon wires surface resulted in more complete and equal neurotization of the conduit site with close adherence between the newly-formed nerve fibers and silicon wires, in comparison with groups where wires with other surface properties have been used. P-type silicon wires with native oxide are seems to be more suitable than other types of wires for further electrode preparation as a part of regenerative implants.

Topics: Animals; Disease Models, Animal; Male; Nerve Fibers; Nerve Regeneration; Peripheral Nerve Injuries; Prostheses and Implants; Rats, Wistar; Sciatic Nerve; Silicon; Surface Properties

The development of nanoscaled theranostic agents for cancer combination therapies has received intensive attention in recent years. In this report, a degradable hollow mesoporous PEG-Si/C-DOX NP is designed and fabricated for pH-responsive, photoacoustic imaging-guided highly effective chemo-thermal combination therapy. The intrinsic hollow mesoporous structure endows the as-synthesized nanoparticles (NPs) with a high drug loading capacity (31.1%). Under NIR (808 nm) irradiation, the photothermal conversion efficiency of the Si/C NPs is as high as 40.7%. Preferential accumulation of the PEG-Si/C-DOX NPs around tumor tissue was demonstrated with photoacoustic images. Cellular internalization of the NPs and release of the DOX in nuclei are shown with fluorescent images. With efficient NIR photothermal conversion and high DOX loading capacity, the PEG-Si/C-DOX NPs are demonstrated to have remarkable cancer-cell-killing ability and to achieve complete in vivo tumor elimination via combinational chemo-thermal therapy. Last but not least, the NPs show good biodegradability and biosafety, making them a promising candidate for multifunctional drug delivery and cancer theranostic.

Topics: Animals; Antineoplastic Agents; Carbon; Carcinoma; Cell Line, Tumor; Disease Models, Animal; Doxorubicin; Drug Therapy; Heterografts; Histocytochemistry; Humans; Hyperthermia, Induced; Mice, Nude; Nanoparticles; Neoplasm Transplantation; Photoacoustic Techniques; Silicon; Treatment Outcome

Ongoing inflammation and endothelial dysfunction occurs within the local microenvironment of heart failure, creating an appropriate scenario for successful use and delivery of nanovectors. This study sought to investigate whether cardiovascular cells associate, internalize, and traffic a nanoplatform called mesoporous silicon vector (MSV), and determine its intravenous accumulation in cardiac tissue in a murine model of heart failure.. In vitro cellular uptake and intracellular trafficking of MSVs was examined by scanning electron microscopy, confocal microscopy, time-lapse microscopy, and flow cytometry in cardiac myocytes, fibroblasts, smooth muscle cells, and endothelial cells. The MSVs were internalized within the first hours, and trafficked to perinuclear regions in all the cell lines. Cytotoxicity was investigated by annexin V and cell cycle assays. No significant evidence of toxicity was found. In vivo intravenous cardiac accumulation of MSVs was examined by high content fluorescence and confocal microscopy, with results showing increased accumulation of particles in failing hearts compared with normal hearts. Similar to observations in vitro, MSVs were able to associate, internalize, and traffic to the perinuclear region of cardiomyocytes in vivo.. Results show that MSVs associate, internalize, and traffic in cardiovascular cells without any significant toxicity. Furthermore, MSVs accumulate in failing myocardium after intravenous administration, reaching intracellular regions of the cardiomyocytes. These findings represent a novel avenue to develop nanotechnology-based therapeutics and diagnostics in heart failure.

Topics: Animals; Biocompatible Materials; Disease Models, Animal; Heart; Heart Failure; Humans; Injections, Intravenous; Male; Mice; Mice, Inbred C57BL; Myocardium; Myocytes, Cardiac; Nanostructures; Polymers; Silicon

Calcium ions react with silicic acid released from dissolving porous silicon nanoparticles to create an insoluble calcium silicate shell. The calcium silicate shell traps and protects an siRNA payload, which can be delivered to neuronal tissues in vitro or in vivo. Gene delivery is enhanced by the action of targeting and cell-penetrating peptides attached to the calcium silicate shell.

Topics: Animals; Brain; Brain Injuries; Calcium Compounds; Cell Line, Tumor; Disease Models, Animal; Mice; Nanoparticles; Porosity; RNA, Small Interfering; Silicates; Silicon

To understand the relationship between rapamycin loading/release and surface chemistries of porous silicon (pSi) to optimize pSi-based intravitreal delivery system.. Three types of surface chemical modifications were studied: (1) pSi-COOH, containing 10-carbon aliphatic chains with terminal carboxyl groups grafted via hydrosilylation of undecylenic acid; (2) pSi-C12, containing 12-carbon aliphatic chains grafted via hydrosilylation of 1-dodecene; and (3) pSiO2-C8, prepared by mild oxidation of the pSi particles followed by grafting of 8-hydrocarbon chains to the resulting porous silica surface via a silanization.. The efficiency of rapamycin loading follows the order (micrograms of drug/milligrams of carrier): pSiO2-C8 (105 ± 18) > pSi-COOH (68 ± 8) > pSi-C12 (36 ± 6). Powder X-ray diffraction data showed that loaded rapamycin was amorphous and dynamic drug-release study showed that the availability of the free drug was increased by 6-fold (compared with crystalline rapamycin) by using pSiO2-C8 formulation (P = 0.0039). Of the three formulations in this study, pSiO2-C8-RAP showed optimal performance in terms of simultaneous release of the active drug and carrier degradation, and drug-loading capacity. Released rapamycin was confirmed with the fingerprints of the mass spectrometry and biologically functional as the control of commercial crystalline rapamycin. Single intravitreal injections of 2.9 ± 0.37 mg pSiO2-C8-RAP into rabbit eyes resulted in more than 8 weeks of residence in the vitreous while maintaining clear optical media and normal histology of the retina in comparison to the controls.. Porous silicon-based rapamycin delivery system using the pSiO2-C8 formulation demonstrated good ocular compatibility and may provide sustained drug release for retina.

Topics: Animals; Cells, Cultured; Delayed-Action Preparations; Disease Models, Animal; Drug Delivery Systems; Follow-Up Studies; Humans; Immunosuppressive Agents; Intravitreal Injections; Macular Degeneration; Particle Size; Porosity; Rabbits; Silicon; Sirolimus; Surface Properties

Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than previously estimated which could explain why absolute silicon deficiency is difficult to achieve but, when it is achieved in young growing animals, it results in stunted growth and abnormal development of bone and other connective tissues.

Topics: Aging; Animals; Connective Tissue; Disease Models, Animal; Female; Rats; Rats, Sprague-Dawley; Silicon

Proliferative vitreoretinopathy (PVR) is the most common cause of poor visual outcomes in association with retinal detachment surgeries and ocular trauma. Daunorubicin (DNR) has shown the strongest efficacy in proliferation inhibition in vitro. However, clinical studies have shown only mild effect owing to limitations of narrow therapeutic window and short vitreous half-life.. Three milligrams of DNR-loaded particles were intravitreally injected into 18 pigmented rabbits, and vitreous samples were collected up to 84 days for analysis. Thirty-seven rabbits were used for a dose-escalation (1, 3, 6 mg) safety and efficacy study in a rabbit PVR model using a pretreatment design.. Loading efficiency of DNR was 108.55 ± 12 μg per 1 mg particles. Eighty-four days of follow-up did not reveal any adverse reaction. Pharmacokinetic analysis demonstrated a vitreous half-life of 29 days with a maximum DNR concentration of 178 ng/mL and a minimum concentration of 29 ng/mL at day 84. Daunorubicin-loaded porous silicon (pSi) particles were dosed 8 to 9 weeks before PVR induction, and PVR severity score was dose dependent (Spearman ρ = -0.25, P = 0.0005). Proliferative vitreoretinopathy with tractional retinal detachment was 88% in the control group, 63% in the low-dose group, 14% in the medium-dose group, and 0% in the high-dose group (Cochran-Armitage Trend Test, Z = 8.99, ρ = -0.67, P < 0.0001).. Daunorubicin-loaded pSi particles can safely reside in the vitreous for at least 3 months. The pSi-based delivery expanded the therapeutic window of DNR by a factor of 862 and drove down the minimum effective concentration by a factor of 175.

Topics: Animals; Daunorubicin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Delivery Systems; Porosity; Rabbits; Silicon; Topoisomerase II Inhibitors; Vitreoretinopathy, Proliferative; Vitreous Body

Dietary silicon has been positively linked with vascular health and protection against atherosclerotic plaque formation, but the mechanism of action is unclear.. We investigated the effect of dietary silicon on 1) serum and aorta silicon concentrations, 2) the development of aortic lesions and serum lipid concentrations, and 3) the structural and biomechanic properties of the aorta.. Two studies, of the same design, were conducted to address the above objectives. Female mice, lacking the apolipoprotein E (apoE) gene, and therefore susceptible to atherosclerosis, were separated into 3 groups of 10-15 mice, each exposed to a high-fat diet (21% wt milk fat and 1.5% wt cholesterol) but with differing concentrations of dietary silicon, namely: silicon-deprived (-Si; <3-μg silicon/g feed), silicon-replete in feed (+Si-feed; 100-μg silicon/g feed), and silicon-replete in drinking water (+Si-water; 115-μg silicon/mL) for 15-19 wk. Silicon supplementation was in the form of sodium metasilicate (feed) or monomethylsilanetriol (drinking water).. The serum silicon concentration in the -Si group was significantly lower than in the +Si-feed (by up to 78%; P < 0.003) and the +Si-water (by up to 84%; P < 0.006) groups. The aorta silicon concentration was also lower in the -Si group than in the +Si-feed group (by 65%; P = 0.025), but not compared with the +Si-water group. There were no differences in serum and aorta silicon concentrations between the silicon-replete groups. Body weights, tissue wet weights at necropsy, and structural, biomechanic, and morphologic properties of the aorta were not affected by dietary silicon; nor were the development of fatty lesions and serum lipid concentrations.. These findings suggest that dietary silicon has no effect on atherosclerosis development and vascular health in the apoE mouse model of diet-induced atherosclerosis, contrary to the reported findings in the cholesterol-fed rabbit model.

Topics: Animals; Aorta; Apolipoproteins E; Atherosclerosis; Body Weight; Cholesterol, HDL; Cholesterol, LDL; Diet; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Endothelium, Vascular; Female; Mice; Mice, Inbred C57BL; Mice, Knockout; Plaque, Atherosclerotic; Silicon; Triglycerides

Dysfunction of corneal epithelial stem cells can result in painful and blinding disease of the ocular surface. In such cases, treatment may involve transfer of growth factor and normal adult stem cells to the ocular surface. Our purpose was to develop an implantable scaffold for the delivery of drugs and cells to the ocular surface. We examined the potential of novel composite biomaterials fabricated from electrospun polycaprolactone (PCL) fibres into which nanostructured porous silicon (pSi) microparticles of varying sizes (150-250 μm or <40 μm) had been pressed. The PCL fabric provided a flexible support for mammalian cells, whereas the embedded pSi provided a substantial surface area for efficient delivery of adsorbed drugs and growth factors. Measurements of tensile strength of these composites revealed that the pSi did not strongly influence the mechanical properties of the polymer microfiber component for the Si loadings evaluated. Human lens epithelial cells (SRA01/04) attached to the composite materials, and exhibited enhanced attachment and growth when the materials were coated with foetal bovine serum. To examine the ability of the materials to deliver a small-drug payload, pSi microparticles were loaded with fluorescein diacetate prior to cell attachment. After 6 hours (h), cells exhibited intracellular fluorescence, indicative of transfer of the fluorescein diacetate into viable cells and its subsequent enzymatic conversion to fluorescein. To investigate loading of large-molecule biologics, murine BALB/c 3T3 cells, responsive to epidermal growth factor, insulin and transferrin, were seeded on composite materials. The cells showed significantly more proliferation at 48 h when seeded on composites loaded with these biologics, than on unloaded composites. No cell proliferation was observed on PCL alone, indicating the biologics had loaded into the pSi microparticles. Drug release, measured by ELISA for insulin, indicated a burst followed by a slower, continuous release over six days. When implanted under the rat conjunctiva, the most promising composite material did not cause significant neovascularization but did elicit a macrophage and mild foreign body response. These novel pressed pSi-PCL materials have potential for delivery of both small and large drugs that can be released in active form, and can support the growth of mammalian cells.

Topics: Animals; Biocompatible Materials; Cattle; Cell Proliferation; Cells, Cultured; Conjunctiva; Disease Models, Animal; Drug Combinations; Drug Delivery Systems; Eye Diseases; Humans; Materials Testing; Mice; Mice, Inbred BALB C; Polyesters; Porosity; Rats; Rats, Sprague-Dawley; Silicon; Tensile Strength

The use of nanoparticle carriers for the sustained release of cytotoxic drugs in cancer therapy can result in fewer adverse effects and can thus be of great benefit for the patient. Recently, a novel nanocomposite, prepared by the encapsulation of THCPSi nanoparticles within solid lipids (SLN), was developed and characterized as a promising drug delivery carrier in vitro. The present study describes the in vivo evaluation of unmodified THCPSi nanoparticles and THCPSi-solid lipid nanocomposites (THCPSi-SLNCs) as potential drug delivery carriers for cancer therapy by using (18)F radiolabeling for the detection of the particle biodistribution in mice. Passive tumor targeting of (18)F-THCPSis and (18)F-THCPSi-SLNCs by the enhanced permeation and retention effect was investigated in a murine breast cancer model. Encapsulation of THCPSi nanoparticles with solid lipids improved their accumulation in tumors at a 7 week time point (tumor-to-liver ratio 0.10 ± 0.08 and 0.24 ± 0.09% for (18)F-THCPSis and (18)F-THCPSi-SLNCs, respectively).

Topics: Animals; Autoradiography; Cell Line, Tumor; Disease Models, Animal; Drug Carriers; Female; Humans; Infusions, Intravenous; Lipids; Liver; Mammary Neoplasms, Experimental; Mice; Microscopy, Electron, Transmission; Nanocomposites; Nanoparticles; Nanotechnology; Neoplasms; Porosity; Serum Albumin, Bovine; Silicon; Time Factors; Tissue Distribution

The implantable stimulator for epileptic seizure suppression with loading impedance adaptability was proposed in this work. The stimulator consisted of the high voltage generator, output driver, adaptor, and switches, can constantly provide the required 40-μA stimulus currents, as the loading impedance varied within 10 kΩ -300 kΩ. The performances of this design have been successfully verified in silicon chip fabricated by a 0.35- μm 3.3-V/24-V CMOS process. The power consumption of this work was only 1.1 mW-1.4 mW. The animal test results with the fabricated chip of proposed design have successfully verified in the Long-Evans rats with epileptic seizures.

Topics: Animals; Biomedical Engineering; Brain; Deep Brain Stimulation; Disease Models, Animal; Electric Impedance; Electric Power Supplies; Electrodes, Implanted; Electronics, Medical; Epilepsy; Equipment Design; Rats; Rats, Long-Evans; Signal Processing, Computer-Assisted; Silicon

Four cylindrical silicon tissue cages (TC, internal volume: 6.7 ± 0.11 cm(3)) were inserted subcutaneously in 29 young healthy cats. A mild inflammatory reaction was induced by intracaveal injection of 1 mL of a 2%λ-carrageenan solution. TC exudate was subsequently sampled at predetermined times (up to 120 h) to measure exudate leucocyte counts and the concentrations of protein and eicosanoids. TC remained in situ for 9-10 months and were well tolerated. Leucocyte counts peaked at 34 h (50.1 ± 57.6 × 10(3) cells/mm(3) ) and returned towards baseline after 72 h. Protein concentration increased from 26.2 ± 2.7 g/L to a peak of 35.9 ± 6.0 g/L at 12 h before returning to baseline at 48 h. Exudate prostaglandin (PG)E(2) concentration peaked at 24 h (11.7 ± 13.7 ng/mL) and returned to baseline by 120 h. Repeated collection of fluid from noninjected cages did not increase transudate PGE(2). Ketoprofen (2 mg/kg, subcutaneously) suppressed exudate PGE(2) at 24 h. The carrageenan-stimulated TC model is an ethical and novel means of investigating soft tissue inflammation in the cat, in which exudate PGE(2) acts as surrogate marker of cyclooxygenase-2 activity. This model will facilitate the investigation of in vivo pharmacokinetics and pharmacodynamics of anti-inflammatory drugs in this species.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Carrageenan; Cat Diseases; Cats; Diffusion Chambers, Culture; Dinoprostone; Disease Models, Animal; Exudates and Transudates; Inflammation; Injections, Subcutaneous; Leukocyte Count; Silicon

To study the intravitreal application of silicon quantum dots (QDs) and their capabilities to deliver electrical stimulation to the retinal cells and to assess the potential effect on retinal electrophysiology and anatomy.. A Royal College of Surgeon rat model of retinal degeneration was used in this study. A total of 32 eyes were used, divided in four groups of 8 eyes each; the first group received the silicon-based QD, the second group received an inactive gold-based QD, the third group received a sham injection, and the fourth group was used as a control. An electroretinogram (ERG) was done at baseline and thereafter every week for 9 weeks. At the end of the follow-up, eyes were collected for further pathologic analysis and nuclei cell counts.. Eyes within the silicon-based QD group showed a definite but transient increase in the waves of the ERG, especially in the rod response compared with the sham and control groups (P < 0.05). The pathologic examination demonstrated a higher nuclei count in the QD group, consistent with a higher cell survival rate than that in the sham and control groups in which cells degenerated as expected.. Intravitreal injection of silicon-based QD seems to be safe and well tolerated, with no evident toxic reaction and demonstrates a beneficial effect by prolonging cell survival rate and improving ERG patterns in a well-established model of retinal degeneration. (ClinicalTrials.gov numbers NCT00407602, NCT01490827.).

Topics: Adaptation, Ocular; Animals; Cell Count; Cell Survival; Dark Adaptation; Disease Models, Animal; Electric Stimulation Therapy; Electrodes, Implanted; Electroretinography; Female; Gold; Intravitreal Injections; Male; Quantum Dots; Rats; Rats, Mutant Strains; Retina; Retinal Degeneration; Retinal Ganglion Cells; Silicon

Zinc eluted from siliconized latex (SL) increases resistance of Pseudomonas aeruginosa to imipenem in vitro. A foreign body peritonitis model was used to evaluate the activity of imipenem using SL or silicone (S) implants. No differences were observed in mortality, positive blood cultures and tissue bacterial counts between SL and S implants. Implant-associated counts, however, were significantly higher in the SL group. It is concluded that SL decreases the activity of imipenem against P. aeruginosa.

Topics: Animals; Anti-Bacterial Agents; Bacterial Load; Catheters; Disease Models, Animal; Drug Antagonism; Female; Foreign Bodies; Imipenem; Latex; Liver; Mice; Mice, Inbred C57BL; Peritonitis; Pseudomonas aeruginosa; Pseudomonas Infections; Silicon; Spleen; Treatment Outcome; Zinc

Stroke is among the most frequent causes of death and adult disability, especially in highly developed countries. However, treatment options to date are very limited. To meet the need for novel therapeutic approaches, experimental stroke research frequently employs rodent models of focal cerebral ischaemia. Most researchers use permanent or transient occlusion of the middle cerebral artery (MCA) in mice or rats. Proximal occlusion of the middle cerebral artery (MCA) via the intraluminal suture technique (so called filament or suture model) is probably the most frequently used model in experimental stroke research. The intraluminal MCAO model offers the advantage of inducing reproducible transient or permanent ischaemia of the MCA territory in a relatively non-invasive manner. Intraluminal approaches interrupt the blood flow of the entire territory of this artery. Filament occlusion thus arrests flow proximal to the lenticulo-striate arteries, which supply the basal ganglia. Filament occlusion of the MCA results in reproducible lesions in the cortex and striatum and can be either permanent or transient. In contrast, models inducing distal (to the branching of the lenticulo-striate arteries) MCA occlusion typically spare the striatum and primarily involve the neocortex. In addition these models do require craniectomy. In the model demonstrated in this article, a silicon coated filament is introduced into the common carotid artery and advanced along the internal carotid artery into the Circle of Willis, where it blocks the origin of the middle cerebral artery. In patients, occlusions of the middle cerebral artery are among the most common causes of ischaemic stroke. Since varying ischemic intervals can be chosen freely in this model depending on the time point of reperfusion, ischaemic lesions with varying degrees of severity can be produced. Reperfusion by removal of the occluding filament at least partially models the restoration of blood flow after spontaneous or therapeutic (tPA) lysis of a thromboembolic clot in humans. In this video we will present the basic technique as well as the major pitfalls and confounders which may limit the predictive value of this model.

Topics: Animals; Brain Ischemia; Disease Models, Animal; Infarction, Middle Cerebral Artery; Mice; Middle Cerebral Artery; Silicon

Accumulation of PrP(Sc), an abnormal form of cellular prion protein (PrP), in the brain of animals and humans leads to fatal neurodegenerative disorders known as prion diseases. Limited protease digestion of PrP(Sc) produces a truncated form called PrP(27-30) that retains prion infectivity and is the main marker of disease targeted in most diagnostic tests. In the search for new anti-prion molecules, drug-screening assays on prion-infected murine cells have been oriented toward decreasing levels of PrP(27-30). In contrast, we screened for drugs promoting multimers of PrP(27-30), illustrating a possible stabilization of mouse PrP(Sc) species, because recent studies aiming to characterize the conformational stability of various prion strains showed that stable recombinant amyloids produced more stable prion strain, leading to longest incubation time. We identified a family of thienyl pyrimidine derivatives that induce SDS-resistant dimers and trimers of PrP(27-30). Bioassays performed on mice brain homogenates treated with these compounds showed that these thienyl pyrimidine derivatives diminished prion infectivity in vivo. Oligomeric-induced activity by thienyl pyrimidine compounds is a promising approach not only to understanding the pathogenesis of prions but also for prion diagnostics. This approach could be extended to other neurodegenerative "prionopathies," such as Alzheimer's, Huntington, or Parkinson's diseases.

Topics: Anilides; Animals; Brain; Cell Line, Tumor; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Endopeptidase K; Glial Fibrillary Acidic Protein; Humans; Mice; Models, Molecular; Neuroblastoma; Peptide Fragments; Peptide Hydrolases; Prion Diseases; Protein Conformation; PrPC Proteins; Pyrimidines; Silicon; Statistics, Nonparametric; Time Factors; Transfection

Capsular fibrosis is one of the most severe complications that can occur in connection with silicone breast implants. Should this case arise, a periprosthetic deposition of fibroid tissue may evolve. Transforming growth factor (TGF)-beta is one of the most important mediators in relation to such processes.. The chinazolinone derivative halofuginone is a type I collagen synthesis inhibitor that interferes with the TGF-beta signaling pathway. The work at hand examines the local antifibrotic effectiveness of halofuginone lactate, which has been biotechnologically bound to the silicone implant's surface. The experiments in relation to this were conducted in vivo on two groups of seven Sprague-Dawley rats. Group I received untreated silicone implants, and group II received halofuginone-coated silicone implants.. Submusculary embedded halofuginone-coated silicone implants have shown no systemic side effects. The histologic and immunohistologic examinations of the periprostatic capsules revealed a significant decrease of CD68 histiocytes, TGF-beta, fibroblasts, collagen type I and type III, and capsular thickness after a 3-month period.. The results confirmed a decrease in foreign body responses to halofuginone surface-modified silicone implants and mark their potential for obtaining a lessened capsular fibrosis by way of a local antifibrotic effect.

Topics: Animals; Breast Implants; Coated Materials, Biocompatible; Collagen Type I; Disease Models, Animal; Female; Fibrosis; Foreign-Body Reaction; Mammary Glands, Animal; Piperidines; Protein Synthesis Inhibitors; Quinazolinones; Rats; Rats, Sprague-Dawley; Silicon; Treatment Outcome

Adipose tissue-derived stromal cells (ATSCs) have recently gained widespread attention as a potential alternate source to bone marrow-derived mesenchymal stem cells with a proliferative capacity and a similar ability to undergo multilineage differentiation. In this study, we evaluated the effectiveness of freshly isolated autologous ATSCs-containing atelocollagen matrix with silicon membrane (ACMS) on wound healing of diabetic (db/db) mice. Cultured ATSCs from (db/db) mice secreted significant amounts of growth factors and cytokines, which are suitable for wound repair. Two full thickness round skin defects were made on the backs of healing-impaired db/db mice. Freshly isolated autologous ATSCs-containing ACMS or ACMS alone were applied to the wounds. Twelve mice were treated and then killed at 1 or 2 weeks (n = 6 each). Histologic sections of the wounds were prepared at each time period after treatment. Histologic examination demonstrated significantly advanced granulation tissue formation, capillary formation, and epithelialization in diabetic healing-impaired wounds treated with autologous ATSCs-containing ACMS, compared with mice treated with ACMS alone. These results suggested that transplantation of autologous ATSCs-containing ACMS significantly accelerated wound healing in diabetic healing-impaired db/db mice.

Topics: Adipose Tissue; Animals; Biocompatible Materials; Collagen; Disease Models, Animal; Male; Mice; Silicon; Skin, Artificial; Stromal Cells; Transplantation, Autologous; Wound Healing

Silicon is important for the proper growth and development of bone and connective tissues. This study was designed to investigate if water-soluble silicon could be used for the treatment of postmenopausal osteoporosis. Silicon (Si 20 mg/kg body weight/day) was administrated orally to 17-week-old ovariectomized (OVX) rats for 4 weeks. Silicon did not alter weight gain in OVX rats. Silicon supplementation significantly increased the bone mineral density of the femur (p < 0.05, vs. OVX control group) and tibia in OVX rats (p < 0.05, vs. OVX control group). Serum alkaline phosphatase and osteocalcin, two bone formation biomarkers tested, were not significantly altered, but urinary calcium and phosphorous excretion tended to decrease with silicon supplementation. OVX rats with silicon supplementation showed a relatively higher serum CTx compared to the nonsupplemented OVX group (p < 0.01, vs. OVX control group). According to these results, short-term soluble silicon supplementation improved bone mineral density in OVX-induced osteoporosis.

Topics: Alkaline Phosphatase; Animals; Biomarkers; Bone Density; Calcium; Dietary Supplements; Disease Models, Animal; Femur; Humans; Male; Osteocalcin; Osteoporosis, Postmenopausal; Ovariectomy; Rats; Rats, Sprague-Dawley; Silicon; Solubility; Tibia

Differences among models in the temporal evolution of ischemia after middle cerebral artery occlusion (MCAO) in rats may considerably influence the results of experimental treatment studies. Using diffusion and perfusion imaging, we compared the spatiotemporal evolution of ischemia in Sprague-Dawley rats after permanent MCAO (pMCAO) with different types of sutures. Male Sprague-Dawley rats were randomly assigned to pMCAO produced with either 4-0 silicone coated (n=8), or 3-0 uncoated monofilaments (n=8). Serial determination of quantitative cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) maps were performed up to 3 h after pMCAO. Lesion volumes were calculated by using previously validated thresholds and correlated with infarct volume corrected for edema defined by 2,3,5-triphenyltetrazolium chloride (TTC) staining at 24 h after MCAO. The ADC/CBF-defined mismatch volume in the 4-0 coated suture model was present significantly longer (up to 120 min) compared to the uncoated 3-0 suture model (30 min). The TTC-derived infarct volume was significantly larger in the coated model (290.3+/-32.8 mm(3)) relative to the uncoated model (252.3+/-34.6 mm(3)). This study demonstrates that the type of suture may significantly influence the spatiotemporal evolution of the ADC/CBF-mismatch as well as the final infarct volume. These inter-model variations must be taken into account when assessing new therapeutic approaches on ischemic lesion evolution in the rat MCAO model.

Topics: Animals; Cerebrovascular Circulation; Diffusion; Diffusion Magnetic Resonance Imaging; Disease Models, Animal; Functional Laterality; Infarction, Middle Cerebral Artery; Male; Perfusion; Rats; Rats, Sprague-Dawley; Silicon; Surface Properties; Sutures; Tetrazolium Salts; Time Factors

Nontypeable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract infections, including otitis media and bronchitis. The persistence of NTHi in vivo is thought to involve bacterial persistence in a biofilm community. Therefore, there is a need for further definition of bacterial factors contributing to biofilm formation by NTHi. Like other bacteria inhabiting host mucosal surfaces, NTHi has on its surface a diverse array of lipooligosaccharides (LOS) that influence host-bacterial interactions. In this study, we show that LOS containing sialic (N-acetyl-neuraminic) acid promotes biofilm formation by NTHi in vitro and bacterial persistence within the middle ear or lung in vivo. LOS from NTHi in biofilms was sialylated, as determined by comparison of electrophoretic mobilities and immunochemical reactivities before and after neuraminidase treatment. Biofilm formation was significantly reduced in media lacking sialic acid, and a siaB (CMP-sialic acid synthetase) mutant was deficient in biofilm formation in three different in vitro model systems. The persistence of an asialylated siaB mutant was attenuated in a gerbil middle ear infection model system, as well as in a rat pulmonary challenge model system. These data show that sialylated LOS glycoforms promote biofilm formation by NTHi and persistence in vivo.

Topics: Acute Disease; Animals; Biofilms; Disease Models, Animal; Ear, Middle; Gerbillinae; Haemophilus Infections; Haemophilus influenzae; Lipopolysaccharides; Lung; Otitis Media; Rats; Rats, Sprague-Dawley; Respiratory Tract Infections; Sialic Acids; Silicon

There are currently no therapies to restore vision to patients blinded by photoreceptor degeneration. This project concerns an experimental approach toward a semiconductor-based subretinal prosthetic designed to electrically stimulate the retina. The present study describes surgical techniques for implanting a silicon microphotodiode array in the cat subretinal space and subsequent studies of implant biocompatibility and durability. Using a single-port vitreoretinal approach, implants were placed into the subretinal space of the right eye of normal cats. Implanted retinas were evaluated post-operatively over a 10 to 27 month period using indirect ophthalmoscopy, fundus photography, electroretinography, and histology. Infrared stimulation was used to isolate the electrical response of the implant from that of the normal retina. Although implants continued to generate electrical current in response to light, the amplitude of the implant response decreased gradually due to dissolution of the implant's gold electrode. Electroretinograms recorded from implanted eyes had normal waveforms but were typically 10-15% smaller in amplitude than those in unimplanted left eyes. The nonpermeable silicon disks blocked choroidal nourishment to the retina, producing degeneration of the photoreceptors. The laminar structure of the inner retinal layers was preserved. Retinal areas located away from the implantation site appeared normal in all respects. These results demonstrate that silicon-chip microphotodiode-based implants can be successfully placed into the subretinal space. Gold electrode-based subretinal implants, however, appear to be unsuitable for long-term use due to electrode dissolution and subsequent decreased electrical activity.

Topics: Animals; Blindness; Cats; Disease Models, Animal; Electric Stimulation; Electrodes, Implanted; Electrophysiology; Electroretinography; Ophthalmoscopy; Photoreceptor Cells, Vertebrate; Prosthesis Design; Prosthesis Implantation; Retina; Retinal Diseases; Silicon

One of the challenging issues in modern biomedical science is the increasing number of osteoporosis patients due to the expansion of elderly populations. Among aging-related pathogenic changes, alterations in bone function and skeletal pathogenesis is a particularly important issue of concern. Osteoporosis is one of the most serious bone-related pathogenic states, as it causes serious loss of quality of life. Alterations in estrogen levels in accordance with aging are one of the key risk factors for osteoporosis. Complexed estrogen actions on bones can be traced by analyzing bone mineral components, as those elements accumulate as mineral complexes, reflecting the context of multiple cellular reactions such as bone resorption/osteogenesis. We have analyzed bone trace element composition in ovariectomized (OVX-treated) Cynomolgus monkey models in this study. In order to gain insights into the effects of such defects on bone trace element composition, inductively coupled plasma atomic emissions spectrometry (ICP-AES) analysis was performed. Marked changes in bone trace element levels were found in vertebral bones of OVX-treated Cynomolgus monkeys. An assessment of these trace element spectra in OVX model animals is discussed. These results could provide useful markers for understanding the physiological states of bones in postmenopausal women.

Topics: Animals; Body Weight; Bone Density; Calcium; Disease Models, Animal; Estradiol; Female; Macaca fascicularis; Magnesium; Osteoporosis; Ovariectomy; Ovary; Phosphorus; Silicon; Sodium; Spectrophotometry; Spine; Sulfur; Trace Elements; Zinc

To clarify the time course of toxicological effects of tetraethoxysaline [Si(OC2H5)4, TEOS] on the kidney and the relationship between blood silicon levels (Si-B) and the effects, 250 mg/kg or 500 mg/kg TEOS was intraperitoneally administered to ten 5-week-old male ICR mice (SPF grade) in each group, and morphological and functional changes of the kidney were assessed at 12 h, 24 h, 3 days and 2 weeks after administration of TEOS. Injury to tubular epithelial cells was observed in mice killed 12 and 24 h after administration, and its severity increased with increasing dosage. The mean values of blood urea nitrogen exhibited dose-related increase in mice sacrificed 24 h after the administration. The concentrations of Si-B increased in order of the administered doses of TEOS, and then decreased steadily. The results of Si-B were consistent with the concept that renal toxicity of TEOS is mediated by siliceous compounds. The kidney was recovering from injury 3 days after administration, and had developed tubulointerstitial nephritis, which could be regarded as repaired lesion of acute injury, by 2 weeks after administration.

Topics: Animals; Blood Urea Nitrogen; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Kidney; Kidney Function Tests; Kidney Tubules; Male; Mice; Mice, Inbred ICR; Microscopy, Electron; Nephritis, Interstitial; Silanes; Silicon; Specific Pathogen-Free Organisms

Two 8-wk experiments were conducted with Sprague-Dawley weanling rats to determine whether interactions occurring between Zn and Si, or a nutritional deficiency of either Cu or Zn, affect silica urolith formation. In Exp. 1, concentrations of 0, 540, and 2,700 mg of Si/kg of diet from tetraethylorthosilicate were used with dietary Zn concentrations of 4, 12, and 500 mg/kg of diet in a 3 x 3 factorial arrangement. In Exp. 2, copper at 1 or 5 mg/kg of diet and Zn at 4, 12, and 500 mg/kg of diet were used in a 2 x 3 factorial arrangement. All diets in Exp. 2 contained 2,700 mg of Si/kg. Silica uroliths occurred in all treatments providing, 2,700 mg of Si/kg of diet. There was a trend (P = .17) toward a reduction of silica urolith incidence with increasing concentrations of dietary Zn in Exp. 1. In Exp. 2, a deficiency of Zn, and a Cu deficiency exacerbated by 500 mg of Zn/kg of diet, increased (P < .05) silica urolith formation. An antagonism between Si and Zn, as demonstrated previously in the rat, may not be of a sufficient magnitude to be applicable to the prevention of silica urolithiasis. The data further demonstrate that Zn deficiency and, to a lesser extent, Cu deficiency contributed to silica urolith formation in rats fed diets having a high content of absorbable Si. However, 540 mg of Si/kg of diet may potentiate the metabolic activity of Zn, as indicated by a 23% Si-mediated weight gain response in Zn-deficient rats.

Topics: Alkaline Phosphatase; Animals; Body Weight; Calcium; Copper; Disease Models, Animal; Magnesium; Male; Phosphorus; Rats; Rats, Sprague-Dawley; Silicon; Silicon Dioxide; Urinary Calculi; Zinc

In the fetus with congenital hydrocephalus, obstruction to the flow of cerebrospinal fluid (CSF) results in ventricular dilation and neurologic impairment. Decompression of the obstructed ventricles before birth may ameliorate the damage and allow normal development to proceed. Although appealing, this pathophysiologic rationale has not been adequately tested because a satisfactory fetal model has not been available. We have developed a model of obstructive hydrocephalus in the fetal lamb and rhesus monkey by injecting kaolin into the cisterna magna through the posterior atlanto-occipital membrane early in the last trimester. Preliminary studies injecting silicone oil were unsuccessful. The development of fetal ventriculomegaly was followed using prenatal ultrasonography. Massive hydrocephalus developed in six sheep, three liveborn at term and three stillborn after premature vaginal delivery, and in 2 fetal rhesus monkeys. All treated animals had external signs of hydrocephalus with marked cranial enlargement. Neuropathologic examinations demonstrated fibrosis of the leptomeninges and subarachnoid spaces around the fourth ventricle. Dilation of the lateral and third ventricles resulted, with attenuation of the cerebral white matter. On histologic examination, the grey matter was relatively well preserved, while the white matter was severely attenuated. This model mimics the clinical and pathologic picture seen in human infants and should allow us to study the pathophysiology of congenital obstructive hydrocephalus and the efficacy and feasibility of its correction in utero.

Topics: Animals; Disease Models, Animal; Female; Hydrocephalus; Kaolin; Macaca mulatta; Pregnancy; Sheep; Silicon

The article deals with results of morphological and electron-microscopy studies of the lungs in experimental pulmonary alveolar proteinosis in rats. The disease was reproduced in experiments on 500 animals by means of chronic inhalation of electro-welding copper-containing aerosols, condensations (smokes) which may develop under similar concentrations during electric welding. The lungs were investigated at intervals ranging from several days to two years from the beginning of the experiment, the duration of which was 9 months, the dayly exposure of the animals in inhalation cameras being three hours. The intra-alveolar content was composed of products of accelerated life activity of the cells of the alveolar epithelium as well as of perished phagocytes (proteins, lipids). The degree of manifestation of the process depended upon concentration of aerosol and duration of the experiment. In the zones of pulmonary alveolar proteinosis there were observed thickenings of the basal membranes, sclerosis of interalveolar partitions, slow replacement of perished macrophages by new ones, which were the causes of prolonged resolution of the alveols content. Pulmonary alveolar proteinosis (lipoproteinosis) should not be considered as a variety of pneumonia or edema of alveols.

Topics: Air Pollutants; Animals; Copper; Disease Models, Animal; Histocytochemistry; Iron; Lipid Metabolism; Lipoproteins; Macrophages; Metals; Microscopy, Electron; Nitrous Oxide; Occupational Diseases; Oxides; Ozone; Proteins; Pulmonary Alveolar Proteinosis; Pulmonary Alveoli; Rats; Silicon; Welding

Topics: Aluminum; Animals; Calcium; Disease Models, Animal; Dust; Iron; Male; Occupational Medicine; Pneumoconiosis; Rats; Silicon

Topics: Animals; Disease Models, Animal; Ear, Middle; Eustachian Tube; Haplorhini; Injections; Otitis Media; Rubber; Silicon; Tympanic Membrane