Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

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Ethics in clinical research focuses largely on identifying and implementing the acceptable conditions for exposure of some individuals to risks and burdens for the benefit of society at large. Ethical guidelines for clinical research were formulated only after discovery of inhumane behaviour with participants during research experiments. The Nuremberg Code was the first international code laying ethical principles for clinical research. With increasing research all over, World Health Organization formulated guidelines in the form of Declaration of Helsinki in 1964. The US laid down its guidelines for ethical principles in the Belmont Report after discovery of the Tuskegee's Syphilis study. The Indian Council of Medical Research has laid down the 'Ethical Guidelines for Biomedical Research on Human Subjects' in the year 2000 which were revised in 2006. It gives twelve general principles to be followed by all biomedical researchers working in the country. The Ethics Committee stands as the bridge between the researcher and the ethical guidelines of the country. The basic responsibility of the Ethics Committee is to ensure an independent, competent and timely review of all ethical aspects of the project proposals received in order to safeguard the dignity, rights, safety and well-being of all actual or potential research participants. A well-documented informed consent process is the hallmark of any ethical research work. Informed consent respects individual's autonomy, to participate or not to participate in research. Concepts of vulnerable populations, therapeutic misconception and post trial access hold special importance in ethical conduct of research, especially in developing countries like India, where most of the research participants are uneducated and economically backward.

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Conventional furosemide tablets are practically insoluble in water, have slow onset of action (45-60 min) and poor bioavailability (39-53%), and therefore cannot be given in emergency clinical situations like hypertension or pulmonary edema. So purpose of research was to provide a fast dissolving oral dosage form of furosemide, which can provide quick onset of action by using concept of mixed hydrotropy. Initially solubility of furosemide was determined individually in 4 hydrotropic agents namely urea, sodium acetate, sodium benzoate, sodium citrate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as solvent. Highest solubility was obtained in 40% sodium benzoate solution. Then different combinations of 2, 3 and 4 hydrotropic agents in different ratios were used to determine solubility, so that total concentration of hydrotropic agents was always 40%. Highest solubility was obtained in solution of urea+sodium benzoate+sodium citrate at optimum ratio of 15:20:5. This optimized combination was utilized in preparing solid dispersions by common solvent technique using distilled water as solvent. Solid dispersions were evaluated for flow properties, XRD, DSC, SEM and were also compressed to form tablets. Dissolution studies of conventional and prepared tablets were done using USP Type II apparatus. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing bioavailability of poorly water-soluble drugs by dissolving drug in nonionized form. The magical enhancement in solubility of furosemide is clear indication of its potential to be used in future for other poorly water-soluble drugs in which low bioavailability is major concern.

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Granulocyte macrophage colony stimulating factor, a potent hematopoietic cytokine, has been shown to stimulate production of white blood cells following chemotherapy. Therefore, the granulocyte macrophage colony stimulating factor gene is a potential candidate for the treatment of different pathological conditions. The purpose of this study is to investigate the suitability of chitosan as carrier for pORF-hGMCSF plasmid encoding granulocyte macrophage colony stimulating factor gene and also to study the effect of complexes on protein production and cell proliferation. Chitosan/pGM-CSF complexes were prepared using different (+/-) ratios (from 0.01/1 to 5/1). Complex formation was checked with agarose gel electrophoresis. The size and zeta potential values were measured. Enzyme and serum stability of complexes were studied. In vitro transfection properties of complexes were studied in HeLa cells. According to agarose gel electrophoresis, full complexation was obtained at 0.1/1 and higher chitosan/pGM-CSF ratios. Complexes having about 132 nm size and +13.7 mV zeta potential value were obtained. Chitosan complexes protected plasmid against enzymatic and serum effects. The gene expression-dependent cell proliferation after transfection of chitosan/pGM-CSF complexes at 72 h was markedly increased in comparision with the level of control group. These results indicate that the effect of chitosan/pGM-CSF complexes on cell proliferation was changed with N/P ratio and time-dependently. For GM-CSF therapy, chitosan/pGM-CSF complexes may be used as alternative to conventional protein treatments. Chitosan may be a good carrier for pORF-hGMCSF. Further, in vivo study is ongoing.

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Out of the 30 actinobacterial cultures screened for antimicrobial activity, 28 cultures were found to produce active products against various pathogenic microorganisms such as Gram-negative, Gram-positive bacteria and yeast, using a modified cross streak method. The modified method helped in easy quantification of results and also in ruling out probable mutual antibiosis. The actinobacterial strains that showed the ability to produce antimicrobial compounds belonged to Streptomyces (53%), Micromonospora (13%) and Actinomadura (10%) genera. Streptomyces sp. strain MMA-5 showed the highest multispecific antibiosis efficiency score value. Broad antibiotic spectrum activity was exhibited by Streptomyces sp. strain MMA-2 and Micromonospora sp. strain MMA-8. The multidrug resistant human pathogenic yeast strain Candida albicans was inhibited by 18 actinobacterial strains.

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The present study was undertaken to investigate the antihyperglycemic and antihyperlipidemic effects of ethanol extract of Plectranthus amboinicus in normal and alloxan-induced diabetic rats. Diabetes was induced in Wistar rats by single intraperitoneal administration of alloxan monohydrate (150 mg/kg). Normal as well as diabetic rats were divided into groups (n=6) receiving different treatments. Graded doses (200 mg/kg and 400 mg/kg) of ethanol extract of Plectranthus amboinicus were studied in both normal and alloxan-induced diabetic rats for a period of 15 days. Glibenclamide (600 μg/kg) was used as a reference drug. Oral administration with graded doses of ethanol extract of Plectranthus amboinicus exhibited hypoglycemic effect in normal rats and significantly reduced the peak glucose levels after 120 min of glucose loading. In alloxan-induced diabetic rats, the daily oral treatment with ethanol extract of Plectranthus amboinicus showed a significant reduction in blood glucose. Besides, administration of ethanol extract of Plectranthus amboinicus for 15 days significantly decreased serum contents of total cholesterol, triglycerides whereas HDL-cholesterol, total proteins and calcium were effectively increased. Furthermore, effect of ethanol extract of Plectranthus amboinicus showed profound elevation of serum amylase and reduction of serum lipase. Histology examination showed ethanol extract of Plectranthus amboinicus exhibited almost normalization of damaged pancreatic architecture in rats with diabetes mellitus. Studies clearly demonstrated that ethanol extract of Plectranthus amboinicus leaves possesses hypoglycemic and antihyperlipidemic effects mediated through the restoration of the functions of pancreatic tissues and insulinotropic effect.

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The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron.

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The powder samples and methanol extract of 11 medicinal plants were subjected to analysis of proximate composition and measurement of antioxidant activity. Different parameters studied include phenolic contents, moisture, ash, crude fiber, fats and waxes. The assays employed were ferric reducing antioxidant power, trolox equivalent antioxidant capacity and scavenging effect on the 1,1-diphenyl-2-picrylhydrazyl free radical. Results obtained indicate that the antioxidant potential varied significantly from plant to plant. The total phenolic contents were determined spectrophotometrically using Folin-Ciocalteu reagent. Significant correlation is observed between ferric reducing antioxidant power and phenolic contents (R² = 0.96). These findings show that the polyphenolic constituents in the extracts are responsible for free radical scavenging capacity.

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Solid dispersions of mefanamic acid with a water-soluble polymer polyvinyl pyrrolidine and a super disintegrant, primojel were prepared by common solvent and solvent evaporation methods employing methanol as the solvent. The dissolution rate and dissolution efficiency of the prepared solid dispersions were evaluated in comparison to the corresponding pure drug. Solid dispersions of mefenamic acid showed a marked enhancement in dissolution rate and dissolution efficiency. At 1:4 ratio of mefenamic acid-primojel a 2.61 fold increase in the dissolution rate of mefenamic acid was observed with solid dispersion. The solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrants alone. Mefanamic acid-primojel-polyvinyl pyrrolidine (1:3.2:0.8) solid dispersion gave a 4.11 fold increase in the dissolution rate of mefenamic acid. Super disintegrants alone or in combination with polyvinyl pyrrolidine could be used to enhance the dissolution rate of mefenamic acid.

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The present study was designed to compare the curative role of proton pump inhibitors, omeprazole, rabeprazole and lansoprazole against dexamethasone-induced ulcer model. Dexamethasone (5 mg/kg/day) was used as an ulcerogen. Dexamethasone suspended in 1% CMC in water was given orally to all rats. Omeprazole (20 mg/kg), rabeprazole (20 mg/kg), and lansoprazole (20 mg/kg) were administered by oral route 30 minutes prior to dexamethasone for ulcer protective studies, gastric secretion and mucosal studies. Effects of proton pump inhibitors were determined by the evaluation of various biochemical parameters such as estimation of myeloperoxidase, cortisol, alkaline phosphatase, malondialdehyde, endogenous anti-oxidants like superoxide dismutase, catalase and reduced glutathione. In dexamethasone induced ulcer model, omeprazole showed significant decrease in malondialdehyde, myeloperoxidase, alkaline phosphatase level and increase in superoxide dismutase, catalase and reduced glutathione level as compared to rabeprazole and lansoprazole. Omeprazole showed significant reduction in cortisol content where as rabeprazole and lansoprazole did not show significant changes as compared to control. The result indicates that omeprazole is the most effective and selective proton pump inhibitor in dexamethasone induced ulcer model as compared to rabeprazole and lansoprazole.

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Genistein, an isoflavone, has been demonstrated to promote the health of human beings by reducing the incidence of specific chronic diseases, namely, cancer and atherosclerosis. The present investigation explores a novel method of extraction of genistein from soy source which consists of a bioconversion reaction using fermentation by microorganism namely Streptomyces roseolus NRRL B-5424. In situ bioconversion of genistein glycoside to aglycone was carried out by the microbe. Such methodology has not been reported hitherto. Optimization of upstream and downstream parameters was done for maximum extraction of genistein. Genistein was isolated in a powder form by column chromatography and preparative thin layer chromatography and was characterized using massspectrometry, nuclear magnetic resonance and infrared spectroscopy and its purity determined using high performance liquid chromatography. Genistein was extracted with 91.04% purity and extraction efficiency was 67.01%.

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Embelin (2,5-dihydroxy-3-undecyl-2,5-cyclohexadiene-1,4-benzoquinone) is a phenolic compound found in the fruits of Embelia tsjeriam-cottam and is responsible for the medicinal properties of the plant Thus the fruits are harvested at a large scale before maturity leading to depletion of population. Since the chemical constituents of medicinal plants are directly associated with the harvesting time, a study was conducted in different forest areas of Chhattisgarh, India, to standardize the harvesting time of Baividang fruits on the basis of their embelin content during 2005-08. The embelin content was determined by RP-HPLC and varied from 1.09 to 5.21% (w/w). The immature fruits collected in October contain an average of 1.67% embelin whereas mature fruits collected in December on an average contain 4.64% embelin. On the basis of our findings it can be concluded that fruits should be harvested after attaining maturity to get better quality produce and also to maintain the sustainability of plant.

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The present study deals with the estimation by RP-HPLC of two different drug components hydrochlorothiazide and metoprolol tartrate present in a tablet formulation. It is a simple, fast, precise and accurate high performance liquid chromatographic method. It is performed using phosphate buffer along with methanol as mobile phase, in the proportion of 60:40. The separation is done on a C ₁₈ column and it is estimated at a λ_max of 226 nm with a flow of 1 ml/min. The detection limits range from a 0.013 to 0.075 mg/ml for hydrochlorothiazide and 0.10 to 0.60 mg/ml for metoprolol tartrate, respectively. The specificity for interference of any peak with main peak of interest is checked. A scan of the individual drug was taken for assuring the λ_max . The system suitability by precision is also checked to ensure the analytical method. The method was found to be accurate and precise for estimation of the two drugs simultaneously.

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A series of new dicarboxylic acid derivatives of 1,3,4-thiadiazines, 1,4-benzopiperizines, 1,4-thiazines, 1,3-thiazoles, 1,3-oxazoles and 1,3-imidazoles have been synthesized in 80-87% yield by the environmentally benign microwave induced technique involving the cyclocondensation of 2,3-dibromosuccinic acid with 2-aminothiophenol, o-phenylene diamine, 1,2,4-triazole, amidinothiocarbamide, amidinocarbamide and guanidine hydrochloride. The structures of all newly synthesized compounds have been established on the basis of analytical and spectral data. Evaluation of antibacterial and antifungal activity showed that almost all compounds exhibited better results than reference drugs thus they could be promising candidates for novel drugs.

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The objective of this work was to develop and validate a simple, rapid, precise, and accurate high performance thin layer chromatography method for simultaneous determination of withanolide A and bacoside A in combined dosage form. The stationary phase used was silica gel G60F ₂₅₄ . The mobile phase used was mixture of ethyl acetate: methanol: toluene: water (4:1:1:0.5 v/v/v/v). The detection of spots was carried out at 320 nm using absorbance reflectance mode. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found to be linear between 200 to 800 ng/spot for withanolide A and 50 to 350 ng/spot for bacoside A. The limit of detection and limit of quantification for the withanolide A were found to be 3.05 and 10.06 ng/spot, respectively and for bacoside A 8.3 and 27.39 ng/spot, respectively. The proposed method can be successfully used to determine the drug content of marketed formulation.

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In this paper we report the synthesis of a new family of 4-alkyl isocoumarin derivatives having bromo carbonyl and amino carbonyl group at 3^rd position of the heterocyclic ring. Synthesis, spectral analysis and bioactivity of new isocoumarin derivatives are discussed in this paper. Some of the synthesized compounds displayed comparable antibacterial activity and some of the new compounds showed an interesting inhibitory effect on the growth of four pathogen fungi involved in plant diseases. A fair number of compounds were found to have good analgesic property on comparing with standard drug analgin.

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The present study was undertaken to establish the diuretic activity of ethanol and aqueous extract of dried leaves of Garcinia cambogia in rats. Aqueous and ethanol extracts of leaves were administered to experimental rats orally at doses of 100 and 200 mg/kg and compared with furosemide (20 mg/kg, intraperitoneally) as the standard. The parameters measured for diuretic activity were total urine volume, urine concentration electrolytes such as sodium, potassium and chloride have been evaluated . The rats treated with ethanol extract of Garcinia cambogia and aqueous extract of Garcinia cambogia in a dose of 100 and 200 mg/kg showed higher urine output when compared to the respective control. Both ethanol and aqueous extracts have showed a significant dose-dependent increase in the excretion of electrolytes when compared to the control group.

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Two triterpenoids, taraxerone and tricadenic acid A were isolated from the methanol extract of the outer bark of Schleichera oleosa available in Darjeeling foothills. A preliminary study on their antimicrobial activities was also performed against some fungal and bacterial species. The structure of these compounds was determined by means of chemical characterisation and IR, NMR spectral data.

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The c-Jan N-terminal kinases are members of the mitogen activated protein kinase family of signaling proteins. Amino pyridine based compounds, 4-anilino pyrimidine derivatives, and 2-pyridine carboxamide derivatives have been identified as potent JNK inhibitors with good cellular activity. In this study we calculated molecular topological and quantum chemical descriptors of 15 training compounds and three quantitative structure activity relationships models have been constructed. The significance of three models is judged on the basis of correlation, Fischer F test and quality factor (Q). This study is helpful for screening potent inhibitors of protein kinases.

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Thymus serpyllum L. grown in Kumaon region of Western Himalaya was investigated for essential oil content and composition in different seasons. The oils of fresh samples were obtained by hydrodistillation. The yield of essential oil (% v/w) during different seasons varied from 0.07 to 0.28% with the highest in summer season, at vegetative stage. The oils were analyzed by GC and GC-MS. Major components of all the samples were thymol (19.4-60.1%), λ-terpinene (0.3-13.8%) and p-cymene (3.5-10.4%). The results clearly indicated that season has significant effect on quality and quantity of thyme oil.

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This study was undertaken to investigate the possible effect of hydroalcoholic root extract of Rubia cordifolia against indomethacin-induced enterocolitis in rats. Male Wistar rats received vehicle or hydroalcoholic root extract of Rubia cordifolia (300 and 600 mg/kg) for 11 consecutive days. Enterocolitis was induced by subcutaneous administration of indomethacin (7.5 mg/kg) on 8 ^th and 9 ^th day. The colonic mucosal injury was assessed by macroscopic scoring and histopathological examination. Furthermore, the serum lactate dehydrogenase activity was estimated. Indomethacin treatment to rats produced acute intestinal inflammation, manifested by a thickening of the bowel wall, mesenteric haemorrhage, mesentery adhesion and multiple mucosal ulcers of small intestine and colon. Treatment with hydroalcoholic root extract of Rubia cordifolia revealed less damage to intestinal tissue and decreased serum lactate dehydrogenase activity which was elevated by induction of colitis. The present data suggests protective effect of Rubia cordifolia in indomethacin-induced enterocolitis and may be beneficial in patients with inflammatory bowel diseases.

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The purpose of the present study is to undertake a docking study of some benzoxazinone derivatives on human peroxisome proliferator activated receptor co-crystallized with an alpha-aryloxyphenylacetic acid agonist using Glide 4.5. The QikProp program was used to obtain the absorption, distribution, metabolism and excretion properties of the analogues. The intermolecular hydrogen bonding interaction of the best-fit ligands were found to be associated with Tyr473, Ser289, Hie 449, Hip 323, Ser 342 and Gly 284 amino acid residue at the receptor active site. Among all the observed interaction with similar binding pattern, the presence of methyl carboxypentyl side chain (Lig. No. 21) showed additional interaction with Ser 342 and the affinity was increased by carboxyl oxygen (as hydrogen bond acceptor) with a best Glide score of -14.54 as compared to the co-crystallized aryloxyphenyl acetic acid which achieved a glide score of -12.50.

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The aim of the current research was to evaluate the immunomodulatory potential of methanol extract of Aegle marmelos in an experimental animal model of cellular and humoral immunity. Administration of methanol extract of Aegle marmelos (500 and 1000 mg/kg, p.o.) and Ocimum sanctum (100 mg/kg, p.o.), produced significant increase in adhesion of neutrophils and an increase in phagocytic index in carbon clearance assay. Both doses of Aegle marmelos prevented the mortality induced by bovine Pasteurella multocida in mice. Moreover, all treated groups demonstrated significant elevation in circulating antibody titre in the indirect haemagglunation test. From the above results, it can be concluded that methanol extract of Aegle marmelos possess immunomodulatory potential by stimulating cellular and humoral immune mechanisms. However, low dose of methanol extract of Aegle marmelos was more effective for augmenting cellular immunity, whereas, high dose was more inclined towards humoral immunity.

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Antifungal activity of Embelia ribes was evaluated on eight different fungal species by employing various concentrations of seed extract (0.5-2.0 mg). All the concentrations of seed extract inhibited the fungal growth, whereas maximum activity was observed at 2.0 mg concentration of seed extract. Among different doses, the diameter of inhibition zones ranged from 9 to 18 mm in various fungal species and increased with the increase in the concentration of test solution. Among all the fungi, high inhibition zones were observed in Colletotricum crassipes (18 mm). This was followed by Cladosporium (17.5 mm), Armillaria mellea (17 mm), Colletotricum capsici (17 mm), Aspergillus niger (16.5 mm), Rhizopus oryzae (16.5 mm), respectively. Aspergillus terreus and Candida albicans showed less inhibition zones (15.5 and 16.0 mm) compared to other organisms. The present study clearly demonstrated the antifungal properties of Embelia ribes.

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