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A bioartificial pancreas, a medical device entrapping islets of Langerhans (islets) in an immunoisolative membrane, has been regarded as one of the most promising approaches to treat insulin-dependent diabetic patients. In this study, various modifications of alginate-chitosan microcapsules were made such as the inclusion of polyethylene glycol (PEG) and the use of crosslinkers such as carbodiimide (EDC) and glutaraldehyde (GA) in the core and onto the microcapsule membrane surface. A characterization of the modified microcapsules in terms of mechanical stability and albumin diffusion as well as their surface properties using SEM was performed. A mild GA treatment greatly enhanced the mechanical stability of the microcapsules, and this treatment did not affect the coating process of chitosan or PEG. The biological response to such microcapsules was evaluated by microencapsulation of red blood cells (RBC) and subsequent observation of their hemoglobin release. The encapsulated RBC in the PEG-GA coated microcapsules were found to be less hemolytic and had improved stability and biocompatibility. The results suggest the possibility of developing biological assist organs by microencapsulation of mammalian cells such as islets or liver cells in immunoisolative microcapsules in the near future.

ABSTRACT:A mild chitosan/calcium alginate microencapsulation process, as applied to encapsulation of biological macromolecules such as albumin and hirudin, was investigated. The polysaccharide chitosan was reacted with sodium alginate in the presence of calcium chloride to form microcapsules with a polyelectrolyte complex membrane. Hirudin-entrapped alginate beads were further surface coated with polyethylene glycol (PEG) via glutaraldehyde functionalities. It was observed that approximately 70% of the content is being released into Tris-HCl buffer, pH 7.4 within the initial 6 h and about 35% release of hirudin was also observed during treatment with 0.1 M HCl, pH 1.2 for 4 h. But acid-treated capsules had released almost all the entrapped hirudin into Tris-HCl, pH 7.4 media within 6 h. From scanning electron microscopic and swelling studies, it appears that the chitosan and PEG have modified the alginate microcapsules and subsequently the protein release. The microcapsules were also prepared by adding dropwise albumin-containing sodium alginate mixture into a PEG-CaCl 2 system. Increasing the PEG concentration resulted in a decrease rate of albumin release. The results indicate the possibility of modifying the formulation to obtain the desired controlled release of bioactive peptides (hirudin), for a convenient gastrointestinal tract delivery system.

The Chennai Urban Population Study investigates a South Indian population with a high prevalence of cardiovascular disease associated with the metabolic syndrome (MS). The Ala54Thr polymorphism in the fatty acid-binding protein 2 (FABP2) gene as well as the T-455C and C-482T polymorphisms in the apolipoprotein C-III (APOC3) gene promoter have been associated with features of the MS in specific populations. This study evaluates in Asian-Indians the association between these polymorphisms with MS and dyslipidemia, defined according to National Cholesterol Education Program Adult Treatment Panel III. Allelic frequencies in 70 controls and 110 patients with diabetes from the Chennai Urban Population Study were 52.9% for FABP2 Thr54, 73.0% for APOC3 -482T, and 80.2% for APOC3 -455C. The polymorphisms were in agreement with Hardy-Weinberg equilibrium. Controls carrying FABP2 Thr54 were more likely to have MS than noncarriers (Fisher's exact test P = 0.031; odds ratio = 6.9 with a 95% confidence interval of 1.1, 43.9). Those carrying at least one polymorphic allele in both genes had a higher likelihood of having MS than wild type (Fisher's exact test P = 0.003; odds ratio = 12.1 with a 95% confidence interval of 1.88, 77.6). Dyslipidemia was associated with the polymorphism as well. The polymorphisms were not associated with MS in patients with diabetes. The association of the polymorphisms with MS and dyslipidemia could contribute to the high cardiovascular disease prevalence in this population.

Previous investigations have shown that ibuprofen inhibits the second wave of platelet aggregation and blocks the conversion of 14 C-arachidonic acid to thromboxane. However, the influence of the drug on platelet function and cyclooxygenase is transitory, lasting only 24 hours. The present study has taken advantage of the shortlived influence of ibuprofen to study its interaction with the long-term effects of aspirin. As expected, both aspirin and ibuprofen supressed platelet cyclooxygenase activity and function, but addition of aspirin to ibuprofen-treated platelets did not increase the degree of inhibition in vitro. Platelet function and prostaglandin synthesis recovered completely 26 hours following ingestion of ibuprofen, but remained compromised 26 hours after taking aspirin. When 650 mg of aspirin was administered after ibuprofen, platelet function and cyclooxygenase activity recovered as completely at 26 hours as did platelets which had been exposed to ibuprofen alone. Thus, prior exposure to ibuprofen in vivo completely protected cyclooxygenase from the irreversible effects of aspirin. Our findings indicate that ibuprofen-like indomethacin and other nonsteroidal antiinf lammatory drugs react with the heme group of cyclooxygenase to prevent arachidonic acid conversion. Since ibuprofen completely blocks the effects of aspirin in platelets in vitro and in vivo, aspirin's primary influence on inhibition of cyclooxygenase must also be through action on the heme portion of the enzyme, rather than acetylation of the protein. 12 Investigations into its mechanism of action several years ago 3 " 5 suggested that it suppressed conversion of arachidonic acid by acetylating the enzyme cyclooxygenase. Other potent inhibitors of prostaglandin formation, however, are incapable of acetylating proteins and must block cyclooxygenase in some other manner.6 " 14 Studies in our laboratory using a cell-free system demonstrated that inhibitors of prostaglandin synthesis (including aspirin, indomethacin, tolmetin, and ibuprofen) prevented arachidonic acid oxidation by interfering with the action of ferrous iron or

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Ischemic stroke represents one of the leading causes of death and disability in both the United States and abroad, particularly for patients with prior ischemic stroke or transient ischemic attack (TIA). A quintessential aspect of secondary stroke prevention is the use of different pharmacological agents, mainly antiplatelets and anticoagulants. Antiplatelets and anticoagulants exhibit their effect by blocking the activation pathways of platelets and the coagulation cascade, respectively. Clinical trials have demonstrated the safety and efficacy of antiplatelets for noncardioembolic stroke prevention, while anticoagulants are more often used for cardioembolic stroke prevention. Commonly used antiplatelets include aspirin, clopidogrel, and aggrenox (aspirin plus extended-release dipyridamole). Furthermore, commonly used anticoagulants include warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban. Each of these drugs has a unique mechanism of action, and they share some common adverse events such as gastrointestinal bleeding and intracranial hemorrhage in more serious cases. Consequently, physicians should carefully assess the benefits and risks of using different antiplatelet or anticoagulant therapies when managing patients with previous ischemic stroke or TIA. This review discuses the published literature on major clinical trials assessing the efficacy of different antiplatelet and anticoagulant drugs under varying circumstances and the subsequent guidelines that have been developed by the American Heart Association/American Stroke Association. Additionally, the role of imaging in stroke prevention is discussed.

Based on the premise of achieving blood compatibility through mimicking the chemical constitutents of the biologically insert surface of the unactivated platelet membrane, a process was developed that entails the covalent grafting of modified phosphatidylcholine molecules to materials including silica, polypropylene, and polytetrafluoroethylene (PTFE) polymer films. These materials were characterized using x-ray photoelectron spectroscopy (XPS) and contactangle measurements. The phosphatidylcholine-containing materials (PC materials) were used as substrates in the plateletadhesion assays and were subjected to enzymatic degradation evaluation. Phosphatidylcholine-grafted silica materials do not support platelet adhesion. In addition the number of adherent platelets correlate with the amount of grafted phospholipid present, as indicated by the phosphorus/ carbon ratio obtained by XPS analysis. Platelet adhesion to phosphatidylcholine-grafted polypropylene and PTFE was inhibited 80% and 90%, respectively, when compared with platelet adhesion to unmodified polypropylene and PTFE.