Enhanced antihyperlipidemic potential of gemfibrozil under co-administration with piperine.

Gemfibrozil is a well-known potent antihyperlipidemic drug with the capacity to lower triglyceride and cholesterol levels, which are responsible for most cardiovascular and cerebrovascular diseases. In addition, gemfibrozil has a potent activity at elevating the high density lipoprotein levels. However, this drug has a very short half-life of about 2 â€‹h and toxicity is observed in the liver as the dose increases. The drug piperine has the capacity to enhance the bioavailability of other drugs without altering their basic properties as well as improving their activity. In this study, we aimed to enhance the bioavailability of gemfibrozil as well as making it more potent and less toxic by applying piperine as a bio-enhancer. Thus, piperine was co-administered to rats with gemfibrozil and the antihyperlipidemic activity was tested when fed on a high fat diet. The results showed that co-administration of gemfibrozil with piperine decreased the elevated triglyceride and cholesterol levels to normal, and they performed significantly better than the individual drugs. Weight gain was controlled effectively by drug administration together with piperine compared with other groups. Hepatic function analyses demonstrated that the potentiation of gemfibrozil did not alter the hepatic function but instead it improved significantly by normalizing the elevated serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase levels. The plasma drug concentration of gemfibrozil was studied over time, where the enhanced activity of the drug reached its Cmax within 1 â€‹h of administration and the activated drug level was observed in the blood for 4 â€‹h.

Effect of minerals and heavy metals in sand samples of Ponnai river, Tamil Nadu, India.

River sand samples have been collected from Ponnai river, Tamil Nadu, India for characterization of minerals and heavy metals by different spectroscopic techniques. Initially, the samples were subjected by Fourier Transform-Infra Red (FT-IR) spectroscopic technique and infra-red absorption bands values are observed in the range of 515-520, 695-700, 775-780 cm-1 which shows the presence of quartz in all the samples. Similarly, infra-red peaks were absorbed for feldspar, kaolinite, calcite, gibbsite and organic carbon and confirmed by X-Ray diffraction (XRD) technique. Additionally, zircon, aragonite, magnetite and kyanite minerals were identified in the samples using only the XRD method. The concentration of heavy metals such as Pb, Cr, Zn, Ni, Hg, As, Mn, Cu has been determined by flame atomic absorption spectrometry (FAAS). An average metal concentration measured in mg kg-1 were: Pb 0.12, As 0.15, Hg 0.13, Cu 2.80, Zn 10.15 Cr 12.70, Ni 2.86 and Mn 104.94 and hence found in the order of Mn > Cr > Zn > Ni > Cu > As > Hg > Pb. These average values do not exceed the world average value and hence potentially do not affect the quality of sand in the river. In addition to that, presences of heavy metals are confirmed by scanning electron microscope equipped with energy dispersive X-ray spectrometry (SEM/EDS) analysis. In order to understand the possible natural and anthropogenic sources of heavy metals, multivariate statistical techniques such as Pearson correlation, principal component and cluster analysis were performed. Results obtained from the statistical techniques were good agreement with each other.

Promising upshot of silver nanoparticles primed from Gracilaria crassa against bacterial pathogens.

BACKGROUND: The study on newer antimicrobial agent from metal based nano materials has augmented in recent years for the management of multidrug resistance microorganisms. In our present investigation, we synthesized silver nanoparticles (AgNP's) from red algae, Gracilaria crassa as beginning material which effectively condensed the silver ions to silver nanoparticles with less price tag and no risk. METHODS: Silver nanoparticles were prepared by simple reaction of 1 mM AgNO3 with G. crassa extracts at room temperature. The fabricated AgNP's were subjected for characterization and screened against various microorganisms for antibacterial activity. RESULTS: UV-Vis spectroscopy (200-800 nm), XRD, FESEM and EDAX, were performed for AgNP's. UV-Vis spectroscopy demonstrated the absorption edge at 443 nm and EDAX pattern is purely due to the particle size and face centered cubic (fcc) symmetry of nanoparticles. Average size lays at 122.7 nm and zeta potential was found to be -34.9 mV. The antibacterial outcome of synthesized AgNP's (at the dose of 20 and 40 µg/ml) was evaluated against Escherichia coli, Proteus mirabilis, Bacillus subtilis and Pseudomonas aeruginosa. The mechanism of synthesized AgNP's bactericidal bustle is discussed in terms of interaction with the cell membrane of bacteria. The activity was found to be sky-scraping in a dose dependent manner. CONCLUSION: Thus, environmental friendly, cost effective, non hazardous stable nanoparticles were prepared by green synthesis using red algae, G. crassa. Synthesized G. crassa AgNP's were in acceptable size and shape. Further, it elicits better bactericidal activity against microorganism. This will assure the out put of superior antibacterial formulation for near future.

Formulation and comparative evaluation of poly herbal anti-acne face wash gels.

CONTEXT: Rauvolfia serpentina (L). Benth. ex Kurz. (Apocynaceae) possessing antibacterial properties are widely used in modern herbal medicines. Curcuma longa L. (Zingiberaceae), a readily available antiseptic, possess antioxidant, antibacterial, blood purifying and antiinflammatory properties and used in various skin creams. Azadirachta indica A. Juss. (Meliaceae) possess astringent, antiviral, discutient, stimulant and antibacterial properties and works excellently well against acne and keeps the skin healthy. OBJECTIVE: Acne is the common skin problem that 85% of the teenagers face today. In this study, poly herbal anti-acne face wash gels were prepared using two polymers Carbopol and hydroxy propyl methyl cellulose (HPMC) along with the extracts of plants Rawvolfia serpentina, Curcuma longa, and Azadiracta indica. MATERIALS AND METHODS: The gel formulations were prepared in four different concentrations of 50, 100, 200 mg/ml as Gel-CRB 100, Gel-HPMC 50, Gel-HPMC 100, Gel-HPMC 200, respectively. The formulations were tested for the anti-acne activity by turbidimetric method. RESULTS: RESULTS showed that the gels were non-irritant, stable and posses anti-acne activity. The efficacy when tested with a standard was almost same to that of Clindamycin gel. DISCUSSION AND CONCLUSION: From this study, Gel-HPMC 100 was proved to be stable and considered as an effective herbal formulation for acne treatment.

Synthesis, hydrolysis studies and phamacodynamic profiles of amide prodrugs of dexibuprofen with amino acids.

The present investigation deals with the synthesis of novel prodrugs of dexibuprofen with amino acids with an aim to achieve potent anti-inflammatory activity and less gastrointestinal toxicity. Structures of synthesized compounds were confirmed by spectral and elemental analyses. In vitro hydrolytic studies in simulated intestinal fluid, 80% plasma and rat faecal matter showed satisfactory release of dexibuprofen due to enzymatic cleavage. The synthesized prodrugs were evaluated for anti-inflammatory activity, analgesia, ulcerogenicity and histopathology. The anti-inflammatory activity of dexibuprofen was 43.3% whereas an improved value of 73.4, 77.3, 72.8 and 64.5% was observed for the synthesized prodrugs. The percentage analgesia of the prodrugs increased, whereas a decrease in the mean ulcer index values than dexibuprofen was observed. The histopathological studies revealed less ulceration in the gastric region when treated with prodrugs. Thus, the prodrugs were proved to be better in action as compared with the parent drug.

Tyrosine and glycine derivatives as potential prodrugs: design, synthesis, and pharmacological evaluation of amide derivatives of mefenamic acid.

This study deals with the synthesis, pharmacological activity, and kinetic studies of mefenamic acid (MA) prodrugs of tyrosine and glycine. The synthesis involved a series of protection and deprotection reactions. The hydrolysis of these prodrugs in the intestine was confirmed by hydrolysis kinetics studies in simulated gastric fluid, simulated intestinal fluid, and 80% plasma. The prodrugs were also evaluated for analgesic, anti-inflammatory, and ulcerogenic activities. The glycine prodrug showed maximum analgesic activity of 86%, and both tyrosine and glycine prodrugs showed better anti-inflammatory activity of 74% and 81%, respectively, when compared to the 40% of MA. Further, the prodrugs showed fewer gastric ulcers compared to MA; tyrosine and glycine prodrugs had an average ulcer index of 9.1 and 4.5, respectively, while an average ulcer index of 24.2 was observed with MA. These findings suggest that both prodrugs are better in action as compared to MA, and are advantageous in having fewer gastrointestinal side effects.

Design, synthesis, hydrolysis kinetics and phamacodynamic profiles of histidine and alanine conjugates of aceclofenac.

The gastrointestinal toxicity associated with aceclofenac can be reduced by condensing its carboxylic acid group with methyl esters of amino acids like histidine and alanine to give amide linkage by the Schotten-Baumann method. Physicochemical characterization of the conjugates was carried out by various analytical and spectral methods. The synthesized conjugates were also subjected to in vitro hydrolysis in simulated gastric fluid (SGF) at pH 1.2, simulated intestinal fluid (SIF) at pH 7.4 and SIF+ 80% human plasma at pH 7.4. The release of free aceclofenac from histidine and alanine conjugated aceclofenac showed negligible hydrolysis in SGF compared to SIF. This indicated that the conjugates do not break in stomach, but release aceclofenac in SIF. Both synthesized conjugates showed excellent pharmacological response and encouraging hydrolysis rate in SIF and SIF + 80% human plasma. Marked reduction of the ulcer index and comparable increase in analgesic and anti-inflammatory activities were obtained in both cases compared to aceclofenac alone. These findings suggest that the conjugates are better in action compared to the parent drug and have fewer gastrointestinal side-effects.

Pioglitazone does not enhance the effectiveness of lifestyle modification in preventing conversion of impaired glucose tolerance to diabetes in Asian Indians: results of the Indian Diabetes Prevention Programme-2 (IDPP-2).

AIMS/HYPOTHESIS: The objective of this prevention programme was to study whether combining pioglitazone with lifestyle modification would enhance the efficacy of lifestyle modification in preventing type 2 diabetes in Asian Indians with impaired glucose tolerance. METHODS: In a community-based, placebo-controlled 3 year prospective study, 407 participants with impaired glucose tolerance (mean age 45.3 +/- 6.2 years, mean BMI 25.9 +/- 3.3 kg/m(2)) were sequentially grouped to receive either: lifestyle modification plus pioglitazone, 30 mg (n = 204) or lifestyle modification plus placebo (n = 203). The participants and investigators were blinded to the assignment. The primary outcome was development of diabetes. RESULTS: At baseline, both groups had similar demographic, anthropometric and biochemical characteristics. At year 3, the response rate was 90.2%. The cumulative incidence of diabetes was 29.8% with pioglitazone and 31.6% with placebo (unadjusted HR 1.084 [95% CI 0.753-1.560], p = 0.665). Normoglycaemia was achieved in 40.9% and 32.3% of participants receiving pioglitazone and placebo, respectively (p = 0.109). In pioglitazone group, two deaths and two non-fatal hospitalisations occurred due to cardiac problems; in the placebo group there were two occurrences of cardiac disease. CONCLUSIONS/INTERPRETATION: Despite good adherence to lifestyle modification and drug therapy, no additional effect of pioglitazone was seen above that achieved with placebo. The effectiveness of the intervention in both groups was comparable with that of lifestyle modification alone, as reported from the Indian Diabetes Prevention Programme-1. The results are at variance with studies that showed significant relative risk reduction in conversion to diabetes with pioglitazone in Americans with IGT. An ethnicity-related difference in the action of pioglitazone in non-diabetic participants may be one explanation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00276497 FUNDING: This study was funded by the India Diabetes Research Foundation.

Antimicrobial, wound healing and antioxidant activities of Anthocephalus cadamba.

Anthocephalus cadamba (Roxb.) Miq. Syn A. chinensis (Lamk) A. Rich (Rubiaceae) is ethnomedicinally widely used in the form of paste by tribe in western Ghats for treating skin diseases. In this context, antimicrobial potential of A. cadamba against a wide range of microorganisms was studied. To validate the ethnotherapeutic claims of the plant in skin diseases, wound healing activity was studied, besides antioxidant activity to understand the mechanism of wound healing. The alchoholic and aqueous extract of this plant showed significant antibacterial and antifungal activity against almost all the organisms: Micrococcus luteus, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and four fungi Candida albicans, Trichophyton rubrum--dermatophyte fungi, Aspergillus niger, Aspergillus flavus and Aspergillus nidulans--systemic fungi, with especially good activity against the dermatophyte (Trichophyton rubrum) and some infectious bacteria (Escherichia coli, Proteus mirabilis and Staphylococcus aureus) with an MIC of 2.5 microg/disc. The results show that A. cadamba extract has potent wound healing capacity as shown from the wound contraction and increased tensile strength. The results also indicated that A. cadamba extract possesses potent antioxidant activity by inhibiting lipid peroxidation and increase in the superoxide dismutase (SOD) and catalase activity.

Persistent impaired glucose tolerance has similar rate of risk factors as for diabetes--results of Indian diabetes prevention programme (IDPP).

OBJECTIVE: To determine the occurrence of persistent impaired glucose tolerance (IGT) (two times OGTT positive) and to compare the physical and clinical characteristics with subjects having transient IGT or diabetes. RESEARCH DESIGN AND METHODS: Nondiabetic subjects aged 35-55 years were screened (n=10,839, M:W 8667:2172) using 2h capillary blood glucose. IGT was diagnosed in 1332 (12.3%). Among them, 1025 (77%) responded for a second OGTT and 531 subjects (51.8%) had persistent IGT. Biochemical, demographic and anthropometric characteristics were compared among the normal (NGT, 30.1%), IGT and diabetic subjects (DM, 18%) at second GTT. RESULTS: All had similar age. BMI, waist circumference and body fat percentage were lower in NGT than in IGT and diabetes. IGT and diabetes had similar characteristics. Family history of diabetes was the highest in persistent IGT. CONCLUSION: Among the screened subjects, 1 in 20 had persistent IGT. Subject with persistent IGT had higher rates of risk factors for diabetes, such as high BMI, waist circumference and body fat percentage.

Temporal changes in prevalence of diabetes and impaired glucose tolerance associated with lifestyle transition occurring in the rural population in India.

AIMS/HYPOTHESIS: The rural Indian population is undergoing lifestyle transition due to socio-economic growth. This study was done to determine the temporal changes in prevalence of diabetes and IGT that could have occurred in a rural population in India as a result of the lifestyle transition. METHODS: A cross-sectional study of 1213 Asian-Indian subjects aged 20 years or over was done to look for the prevalence of diabetes and IGT using the 1999 WHO criteria. The temporal changes were assessed in comparison with a similar study conducted 14 years previously. The factors associated with the temporal changes were also analysed. RESULTS: Nearly a three-fold increase in age- and sex-adjusted prevalence of diabetes (from 2.20% to 6.36%) was seen in 2003 when compared with a similar study done 14 years before. Prevalence of IGT did not change significantly (7.44% in 1989 vs 7.18% in 2003). Improvement in living conditions had occurred during the period, occupational changes were seen, the number of manual labourers had decreased and economic conditions had improved. BMI and waist circumference had increased. After correcting for age, sex and differences in time periods, waist circumference and physical inactivity showed significant associations with the increased prevalence of diabetes. CONCLUSIONS/INTERPRETATION: Demographic transition due to improved living conditions in rural India was associated with a three-fold increase in the prevalence of diabetes. Increased upper body adiposity and physical inactivity showed significant association with this phenomenon.

Evaluation of anti-inflammatory potential of Pavetta indica Linn. leaf extract (family: Rubiaceae) in rats.

The anti-inflammatory potential of methanol extract of Pavetta indica Linn. leaves (Family: Rubiaceae) was evaluated against several models of inflammation such as carragenin, histamine and dextran induced pedal inflammation in rats. The extract showed 48.41%, 41.10% and 24.22% inhibition respectively; when compared to that of control animals. The effect was comparable with that of the standard drug indomethacin, a standard non-steroidal anti-inflammatory drug. Simultaneous subplantar administration of the extract and carrageenin in a mixture helps in differentiating true anti-inflammatory action from an apparent anti-inflammatory effect due to counter-irritant activity. The methanol extract also effectively and significantly reduced cotton pellet induced granuloma. The percentage of inhibition was 62.78 at the dose 500 mg/kg, thereby suggesting its activity in the proliferative phase of the inflammatory process.

Studies on anti-diarrhoeal activity of Ficus hispida. Leaf extract in rats.

Methanol extract of Ficus hispida L. showed significant inhibitory activity against castor oil-induced diarrhoea and PGE(2)-induced enteropooling in rats. It also showed a significant reduction in gastro-intestinal motility on charcoal meal test in rats. The results obtained establish the F. hispida leaf extract as an anti-diarrhoeal agent.

Studies on the antiinflammatory activity of Betula alnoides bark.

The antiinflammatory activity of Betula alnoides extract was evaluated in acute and subacute inflammation models. The extract was also evaluated for antiinflammatory activity in sheep RBC induced sensitivity and in membrane stabilization models. Except for the sheep RBC induced sensitivity model, the extract showed significant antiinflammatory activity.

Prevalence of overweight in urban Indian adolescent school children.

The prevalence of diabetes mellitus (DM) and cardiovascular disease (CVD) is increasing in urban India. Overweight in adolescence is a marker of overweight in adult age, and it shows an association with the above diseases. There have been meagre data from India on the prevalence of childhood obesity. The objective of the study was to quantify the prevalence of overweight and its risk factors in adolescent children in urban India. School students in the age group of 13-18 years (n = 4700, M:F 2382:2318) were studied. Body mass index (BMI) was measured. Data on physical activity, food habits, occupation of parents and their economic status, birth weight of the children and age at menarche in girls were obtained by questionnaire. Age-adjusted prevalence of overweight was 17.8% for boys and 15.8% for girls. It increased with age and was higher in lower tertiles of physical activity and in higher socio-economic group. Birth weight and current BMI were positively associated. The study highlighted the high prevalence of overweight in adolescent children in urban India. Life style factors influenced BMI in adolescent age.

Antitussive effect of Asparagus racemosus root against sulfur dioxide-induced cough in mice.

The methanol extract of Asparagus racemosus root (200 and 400 mg/kg, p.o.) showed significant antitussive activity on sulfur dioxide-induced cough in mice, the cough inhibition (40.0 and 58.5%, respectively) being comparable to that of 10-20 mg/kg of codeine phosphate (36.0 and 55.4%, respectively).

Protective effect of leaf extract of Ficus hispida Linn. against paracetamol-induced hepatotoxicity in rats.

The methanol extract of the leaves of Ficus hispida Linn. (Moraceae) was evaluated for hepatoprotective activity in rats by inducing acute liver damage by paracetamol (750 mg/kg, p.o.). The extract at an oral dose of 400 mg/kg exhibited a significant protective effect by lowering the serum levels of transaminase (SGOT and SGPT), bilirubin and alkaline phosphatase (ALP). These biochemical observations were supplemented by histopathological examination of liver sections. The activity of extract was also comparable to that of Liv-52 a known hepatoprotective formulation.

Antibacterial activity of Litsea glutinosa bark.

The methanol extract of the bark of Litsea glutinosa showed antibacterial activity, comparable to chloramphenicol, against all 16 tested microorganisms.

Molecular mechanism of the intestinal biotin transport process.

Previous studies have characterized different aspects of the cellular/membrane mechanism and regulation of the intestinal uptake process of the water-soluble vitamin biotin. Little, however, is known about the molecular mechanisms of the uptake process. In this study, we have identified a cDNA from rat small intestine that appears to be involved in biotin transport. The open reading frame of this cloned cDNA consisted of 1,905 bases and was identical to that identified for the vitamin transporter in placental tissue. Significant heterogeneity, however, was found in the 5' untranslated region of this clone, with three distinct variants (II, III, IV) being identified in the small intestine; the placental variant (variant I), however, was not present in the small gut. Variant II was found to be the predominant form expressed in the rat small and large intestines. Functional identity of the cloned intestinal cDNA was confirmed by stable expression in COS-7 cells, which showed a four- to fivefold increase in biotin uptake in transfected COS-7 cells compared with controls. The induced biotin uptake in transfected COS-7 cells was found to be 1) Na(+) dependent, 2) saturable as a function of concentration with an apparent K(m) of 8. 77 microM and a V(max) of 779.7 pmol. mg protein(-1). 3 min(-1), and 3) inhibited by unlabeled biotin and pantothenic acid and their structural analogs. The distribution of complementary mRNA transcripts of the cloned cDNA along the vertical and longitudinal axes of the intestinal tract was also determined. Results of this study describe the molecular characteristics of the intestinal biotin absorption process and report the identification of a cDNA that encodes a Na(+)-dependent biotin uptake carrier that appears to exist in the form of multiple variants.

Transport of thiamine in human intestine: mechanism and regulation in intestinal epithelial cell model Caco-2.

The present study examined the intestinal uptake of thiamine (vitamin B(1)) using the human-derived intestinal epithelial cells Caco-2 as an in vitro model system. Thiamine uptake was found to be 1) temperature and energy dependent and occurred with minimal metabolic alteration; 2) pH sensitive; 3) Na(+) independent; 4) saturable as a function of concentration with an apparent Michaelis-Menten constant of 3.18 +/- 0.56 microM and maximal velocity of 13.37 +/- 0.94 pmol. mg protein(-1). 3 min(-1); 5) inhibited by the thiamine structural analogs amprolium and oxythiamine, but not by unrelated organic cations tetraethylammonium, N-methylnicotinamide, and choline; and 6) inhibited in a competitive manner by amiloride with an inhibition constant of 0.2 mM. The role of specific protein kinase-mediated pathways in the regulation of thiamine uptake by Caco-2 cells was also examined using specific modulators of these pathways. The results showed possible involvement of a Ca(2+)/calmodulin (CaM)-mediated pathway in the regulation of thiamine uptake. No role for protein kinase C- and protein tyrosine kinase-mediated pathways in the regulation of thiamine uptake was evident. These results demonstrate the involvement of a carrier-mediated system for thiamine uptake by Caco-2 intestinal epithelial cells. This system is Na(+) independent and is different from the transport systems of organic cations. Furthermore, a CaM-mediated pathway appears to play a role in regulating thiamine uptake in these cells.