EVALUATION OF IN VIVO ANTI-DIABETIC ACTIVITY OF ROOT OF CRATAEVA MAGNA LOUR., ON STREPTOZOTOCIN-INDUCED DIABETIC RATS

Objective: The purpose of the study is to evaluate the anti-diabetic effect of the ethanolic extract of root of Crataeva magna Lour., on streptozotocin-induced diabetic rats. Methods: Streptozotocin (45 mg/kg) was used to induce the diabetes mellitus in rats. Afterward, the diabetic rats will be divided into four groups Group I rats served as diabetic control rats, Group II rats were induced diabetes and treated with standard drug through oral intragastric tube, Group III and Group IV were treated with ethanolic extract (200 and 400 mg/kg). Glibenclamide as reference was to evaluate the effect of the extract. Results: The administration of extract decreased the fasting blood glucose and body weight as well as increased level of total cholesterol and triglycerides which and decreased and HDL level. SGPT and SGOT level were significantly reduced in treatment group. Blood urea and creatinine were a significant difference in blood urea and creatinine. Conclusion: The extract of C.magna Lour. exhibited significant anti-diabetic activity evident from blood glucose level, body weight, serum cholesterol profile, SGOT, SGPT, serum creatinine, and serum urea level

Development and Characterization of Irbesartan Nanoparticles

INTRODUCTION:Nanoparticles are defined as particulate dispersions or solid particles with a size in the range of 10-1000nm. The drug is dissolved, entrapped, encapsulated or attached to a nanoparticle matrix. Depending upon the method of preparation, nanoparticles, nanospheres or nanocapsules can be obtained. Nanocapsules are systems in which the drug is confined to a cavity surrounded by a unique polymer membrane, while nanospheres are matrix systems in which the drug is physically and uniformly dispersed. In recent years, biodegradable polymeric nanoparticles, particularly those coated with hydrophilic polymer such as poly(ethylene glycol) (PEG) known as long-circulating particles, have been used as potential drug delivery devices because of their ability to circulate for a prolonged period time target a particular organ, as carriers of DNA in gene therapy, and their ability to deliver proteins, peptides and genesAIM OF WORK:Development of nanoparticles are one of the emerging fields of nanotechnology with several potential application in drug delivery, clinical medicine and research as well as in other discipline. The use of nanoparticles as drug carrier system is a very attractive controlled drug release. Irbesartan is an angiotensin receptor blockers used mainly for the treatment of hypertension. It belongs to class Π drug according to biopharmaceutical classification system. The bioavailability of the valsartan after oral administration is low (60%) with higher variability. The present study was aimed at developing nanoparticle of irbesartan in order to improve the bioavailability and efficacy in treatment of hypertension. Irbesartan is a poorly water soluble drug. To increase solubility of the drug and reduce the dose frequency and improve the bioavailability the study was aimed at nanoparticle of Irbesartan. Thus the present work is to Develop and characterize a nanoparticulate drug delivery system of antihypertensive drug (Irbesartan) and also 1. To increase the solubility 2. To overcome variable systemic availability. 3. To overcome side effect. 4. To overcome the drug resistance on long term. 5. Specific site drug delivery at controlled rate. 6. Prolonged systemic circulation.PLAN AND SCOPE OF WORK:1. Preformulation studies involve observation of physical and chemical data available. The identification of raw materials and compatibility studies between drug and polymer is to be done by using Infrared spectrophotometry. 2. Preparation of Irbesatran Nanoparticles prepared by Precipitation Method. 3. Formulation of Irbesartan Nanoparticles in various ratios of drug and polymer. 4. The best formulation will be selected based on the results of following parameters. The prepared nanoparticles is to be evaluated by following chemical characteristics Drug entrapment efficiency, In vitro drug release of formulated nanoparticles. 5. Surface morphology of formulation (SEM) of the optimized formulation. 6. Zeta potential analysis of the optimized formulation. 7. Stability studies for the best formulation at different temperature. 8. Drug release kinetics.SUMMARY AND CONCLUSION:The present study was aimed to develop a nanoparticulate drug delivery system of antihypertensive drug irbesartan using polymer ( poly vinyl alcohol).The polymer enhances the binding of irbesartan nanoparticles in specific or targeted site with sustained release of drug increasing therapeutic efficacy. These nanoparticles may also reduce the dose frequency with desired therapeutic response. All batches of nanoparticles (F1-F10) were prepared by nano precipitation method. The entrapment efficiency of the optimized formulation F7 (drug 50mg, polyvinyl alcohol 75mg, β –cyclodextin 10 mg) was 99.38 ±0.08 and invitro drug release was 98.46% after 24 hours. It also obey the zero order, follows diffusion and erosion mechanism of release. Surface morphology of optimized formulation (F7) indicated that lrbesartan nanoparticles were found to be in average nanometer range(358.4nm) and showed ideal surface morphology. The stability test performed revealed that the formulation (F7) showed no change in its characters. The optimized formulation (F7) was also examined for zeta potential determinations. The formulation(F7) showed maximum deviation of 9.16 mV which demonstrated that the particles are separate and highly repelling property found to be more useful in decreasing opsonization and favors target specificity. The developed irbesartan nanoparticle formulation increases water solubility, reduces the dose frequency and improves the bioavailability of drug

Synthesis, Characterization & Biological Evaluation of Some Novel 1, 3, 4-Oxadiazole Derivatives

Substituted oxadiazole, 5-(2-hydroxyphenyl)-1, 3, 4-oxadiazole-2(3H)-thione was synthesized from salicylic acid. The titled oxadiazole derivatives were synthesized by making substitution at free N-(3H) position of 5-(2-hydroxyphenyl)-1, 3, 4-oxadiazole-2(3H)-thione through mannich condensation. Substituted oxadiazole, 5-(4-hydroxyphenyl)-1, 3, 4-oxadiazole-2(3H)-thione was synthesized from p-hydroxy benzoic acid. The titled oxadiazole derivatives were synthesized by making substitution at free N-(3H) position of 5-(4-hydroxyphenyl)-1, 3, 4-oxadiazole-2(3H)-thione through mannich condensation. The synthesized compounds were characterized by melting point and solubility and subjected to various analytical techniques like Thin Layer Chromatography, IR and NMR spectral studies. Synthesized compounds ODAZ 06, PDAZ 06, ODAZ 05, PDAZ 05, ODAZ 03, and PDAZ 03 compounds posses highly significant anti-convulsant activity. The synthesized compounds ODAZ 03, PDAZ 03, ODAZ 01, PDAZ 01 ODAZ 06, and PDAZ 06 possess significant anti-inflammatory activity at 90 mins. The synthesized compound ODAZ 03 possesses highly significant antinociceptive activity. The synthesized compounds Compound, ODAZ 04, PDAZ 04, ODAZ 03, PDAZ 03, ODAZ 02, PDAZ 02 posses significant anti-bacterial activity against both G(+ve) and G(-ve) organisms. The synthesized compounds Compound, ODAZ 03, PDAZ 03, ODAZ 04, PDAZ 04, ODAZ 05, PDAZ 05 posses significant anti-fungal activity against Candida albicans, Aspargillus nigar The synthesized compounds Compound, ODAZ,ODAZ 05, PDAZ 05, ODAZ 04, PDAZ 04, ODAZ 03, PDAZ 03 posses significant anthelmintic activity against pheritima posthum

FORMULATION AND EVALUATION OF INDOMETHACIN EXTENDED RELEASE PELLETS

Objective: The present investigation was to design pellets loaded with Indomethacin for extended release. Indomethacin is a non steroidal anti inflammatory drug (NSAID) commonly used for reduction of pain and inflammation. To improve the bioavailability indomethacin was prepared by fluidised bed coating tablet technology. Methods: Indomethacin pellets were prepared using hydroxy propyl methyl cellulose and ethyl cellulose as a polymer in different concentration. Pellets were evaluated for physico - chemical properties such as hardness, friability, thickness, weight variation, drug content uniformity and capsule lock length. In vitro drug release studies were carried out USP rotating basket type I method and the samples were analyzed at 319nm by UV spectrophotometer. Results: FT-IR studies revealed that there was no interaction betweeen drug and polymers used in the study. The drug release from F5 formulation was found to zero order kinetic model. It was also found linear in higuchi plot which confirms that diffusion is one of the mechanism of drug release. Conclusion: Among these formulations, Formulation (F5) containing Ethyl cellulose (4cps) 5mg & HPC 20 mg and extended release coating upto 7% showed optimized release pattern.The optimized formulation (F5) releases the drug upto 24hrs and fulfilled the requirements such as cost effective and high patient compliance

Systemically administered central nervous system drugs induced ocular side effects: a review

Several systemic drugs have reported ocular and visual side effects that affect patient management. It is imperative to be familiar with the associated side effects which can be mild or transient and may seriously threaten vision. This article deals briefly with the mechanisms and reasons that account for the impact that systemically administered central nervous system (CNS) drugs can exert on the visual or ocular system. The eye care practitioner can be instrumental in detecting and reporting ocular side effects, advising patients and collaborating with other members of the patient’s healthcare team. One of the difficulties include becoming familiar with the countless systemic medications prescribed to patients. Another is being able to correlate a particular side effect with a suspected drug. Several of the ocular adverse effects such as glaucoma, cataract, blurred vision, color vision, optic neuritis, maculopathy, dry eye, etc., are vision threatening and often patients fail to recognize or describe the symptoms appropriately. Therefore, physicians and paramedical members like staff nurses, clinical pharmacists and other members must make adequate observations while recommending these drugs to patients

Iron-sparing Response of Mycobacterium avium subsp. paratuberculosis is strain dependent

<p>Abstract</p> <p>Background</p> <p>Two genotypically and microbiologically distinct strains of <it>Mycobacterium avium </it>subsp. <it>paratuberculosis </it>(MAP) exist - S and C MAP strains that primarily infect sheep and cattle, respectively. Concentration of iron in the cultivation medium has been suggested as one contributing factor for the observed microbiologic differences. We recently demonstrated that S strains have defective iron storage systems, leading us to propose that these strains might experience iron toxicity when excess iron is provided in the medium. To test this hypothesis, we carried out transcriptional and proteomic profiling of these MAP strains under iron-replete or -deplete conditions.</p> <p>Results</p> <p>We first complemented <it>M. smegmatis</it>Δ<it>ideR </it>with IdeR of C MAP or that derived from S MAP and compared their transcription profiles using <it>M. smegmatis mc</it>^<it>2</it><it>155 </it>microarrays. In the presence of iron, sIdeR repressed expression of <it>bfrA </it>and MAP2073c, a ferritin domain containing protein suggesting that transcriptional control of iron storage may be defective in S strain. We next performed transcriptional and proteomic profiling of the two strain types of MAP under iron-deplete and -replete conditions. Under iron-replete conditions, C strain upregulated iron storage (BfrA), virulence associated (Esx-5 and antigen85 complex), and ribosomal proteins. In striking contrast, S strain downregulated these proteins under iron-replete conditions. iTRAQ (isobaric tag for relative and absolute quantitation) based protein quantitation resulted in the identification of four unannotated proteins. Two of these were upregulated by a C MAP strain in response to iron supplementation. The iron-sparing response to iron limitation was unique to the C strain as evidenced by repression of non-essential iron utilization enzymes (aconitase and succinate dehydrogenase) and upregulation of proteins of essential function (iron transport, [Fe-S] cluster biogenesis and cell division).</p> <p>Conclusions</p> <p>Taken together, our study revealed that C and S strains of MAP utilize divergent metabolic pathways to accommodate in vitro iron stress. The knowledge of the metabolic pathways these divergent responses play a role in are important to 1) advance our ability to culture the two different strains of MAP efficiently, 2) aid in diagnosis and control of Johne's disease, and 3) advance our understanding of MAP virulence.</p

A Genome-Wide Association Study Provides New Evidence That CACNA1C Gene is Associated With Diabetic Cataract

PURPOSE: Diabetic cataract is one of the major eye complications of diabetes. It was reported that cataract occurs two to five times more frequently in patients with diabetes compared with those with no diabetes. The purpose of this study was to identify genetic contributors of diabetic cataract based on a genome-wide association approach using a well-defined Scottish diabetic cohort. METHODS: We adapted linked e-health records to define diabetic cataract. A diabetic cataract case in this study was defined as a type 2 diabetic patient who has ever been recorded in the linked e-health records to have cataracts in both eyes or who had previous cataract extraction surgeries in at least one eye. A control in this study was defined as a type 2 diabetic individual who has never been diagnosed as cataract in the linked e-health records and had no history of cataract surgeries. A standard genome-wide association approach was applied. RESULTS: Overall, we have 2341 diabetic cataract cases and 2878 controls in the genetics of diabetes audit and research in Tayside Scotland (GoDARTS) dataset. We found that the P value of rs2283290 in the CACNA1C gene was 8.81 × 10(−10), which has reached genome-wide significance. We also identified that the blood calcium level was statistically different between diabetic cataract cases and controls. CONCLUSIONS: We identified supporting evidence that CACNA1C gene is associated with diabetic cataract. The role of calcium in the cataractogenesis needs to be reevaluated in future studies