Serotonergic mechanisms in the 6-Hz psychomotor seizures in mice.

Serotonin (5-hydroxytrytamine (5-HT)) plays an important role in experimental seizures. Recently, we reported the depletion of 5-HT by parachlorophynylalanine (PCPA) in whole brain to enhance 6-Hz psychomotor seizures in mice. In the present work, we investigated the effect of 5-HT depletion in cortex and hippocampus, brain regions relevant for epilepsy, on behavioral and ultra-structural changes following 6-Hz psychomotor seizures in mice. In addition, we studied the effect of sodium valproate (SVP) on behavioral, biochemical, and ultra-structural effects induced by 6 Hz. Behavioral changes induced by 6 Hz stimulation were characterized as the increased duration of Straub's tail, stun position, twitching of vibrissae, forelimb clonus, and increased rearing and grooming. PCPA administration further enhanced while SVP reduced these behaviors in mice. The 6-Hz psychomotor seizure induced ultra-structural changes in both cortex and hippocampus in mice treated with PCPA. Furthermore, PCPA administrations followed by 6Hz-induced seizures were accompanied by reduced hippocampal and cortical 5-HT. SVP attenuated the PCPA-induced ultra-structural changes and alterations of 5-HT content in the mouse brain. The study suggests the involvement of 5-HT in the 6 Hz psychomotor seizures and in the mechanisms of action of SVP against such seizures in mice.

Effect of piperine on pharmacokinetics of sodium valproate in plasma samples of rats using gas chromatography-mass spectrometry method.

UNLABELLED: Piperine (PIP) is used as anticonvulsant in traditional Chinese medicine. Co-administration of low-dose sodium valproate with PIP has been regarded to have potential anticonvulsant activity. AIM: This study was intended to investigate the effect of PIP on the pharmacokinetics of sodium valproate (SVP) in the plasma samples of rats using gas chromatography-mass spectrometry (GC-MS) method. MATERIALS AND METHODS: The plasma samples obtained after oral administration of SVP, 150 mg/kg and SVP, 150 mg/kg + PIP, and 5 mg/kg to male Wistar rats were used to quantify the concentrations in plasma using GC-MS method. RESULTS: A simple and accurate method developed in-house was applied for the analysis of plasma samples of Wistar rats after oral administration of SVP and PIP + sodium valproate, respectively. The pharmacokinetic parameters reported 14.8-fold increase in plasma concentration (maximum observed concentration in the concentration-time profile), 4.6-fold increase in area under the curve and slightly prolonged time to reach that concentration (1 h) of SVP in presence of PIP. CONCLUSION: The study reaffirms the bioenhancing effect of PIP suggesting possibility of dose reduction of SVP while co-adminstering with PIP.

The Effect of Subchronic Dosing of Ciproxifan and Clobenpropit on Dopamine and Histamine Levels in Rats.

The present study was designed to investigate the effect of once daily for 7-day (subchronic treatment) dosing of histamine H3 receptor antagonists, ciproxifan (CPX) (3 mg/kg, i.p.), and clobenpropit (CBP) (15 mg/kg, i.p), including clozapine (CLZ) (3.0 mg/kg, i.p.) and chlorpromazine (CPZ) (3.0 mg/kg, i.p.), the atypical and typical antipsychotic, respectively, on MK-801(0.2 mg/kg, i.p.)-induced locomotor activity, and dopamine and histamine levels in rats. Dopamine and histamine levels were measured in striatum and hypothalamus, respectively, of rat brain. Atypical and typical antipsychotics were used to serve as clinically relevant reference agents to compare the effects of the H3 receptor antagonists. MK-801-induced increase of horizontal activity was reduced with CPX and CBP. The attenuation of MK-801-induced locomotor hyperactivity produced by CPX and CBP was comparable to CLZ and CPZ. MK-801 raised dopamine levels in the striatum, which was reduced in rats pretreated with CPX and CBP. CPZ also lowered striatal dopamine levels, though the decrease was less robust compared to CLZ, CPX and CBP. MK-801 increased histamine content although to a lesser degree. Subchronic treatment with CPX and CBP exhibited further increase in histamine levels in the hypothalamus compared to the MK-801 treatment alone. Histamine H3 receptor agonist, R-α methylhistamine (10 mg/kg, i.p.) counteracted the effects of CPX and CBP. In conclusion, the subchronic dosing of CPX/CBP suggests some antipsychotic-like activities as CPX/CBP counteracts the modulatory effects of MK-801 on dopamine and histamine levels and prevents MK-801-induced hyperlocomotor behaviors.

Inhibitory effect of Careya arborea on inflammatory biomarkers in carrageenan-induced inflammation.

CONTEXT: Careya arborea Roxb. (Lecythidaceae) has multiple applications in traditional medicine; it exhibits analgesic, antibacterial, anti-inflammatory, antiulcer, and protective effects. However, the effect of C. arborea on biochemical and immmunological inflammatory mediators has not been explored. OBJECTIVE: The present study investigates the anti-inflammatory potential of the methanol extract of C. arborea stem bark and further assesses its possible mechanism on the modulation of inflammatory biomarkers. MATERIALS AND METHODS: Anti-inflammatory activity of C. arborea methanol extract (CAME) was evaluated (100 and 200 mg/kg, p.o) using indomethacin (10 mg/kg, p.o) as the standard drug in Wistar albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. The anti-inflammatory mechanism was studied by measuring malondialdehyde (MDA), C-reactive protein (CRP), nitric oxide (NO), myeloperoxidase (MPO), TNF-α, and IL-1ß levels in both control and treated groups. A protocol has also been established to quantify quercetin and betulinic acid content in CAME using HPTLC fingerprint. RESULTS: Careya arborea significantly (p < 0.001) decreased carrageenan-induced paw edema, showed a reduction of 48.87 and 65.53% at doses of 100 and 200 mg/kg, respectively. Moreover, CAME significantly decreased the MDA, CRP, NO, and MPO levels, elevated by carrageenan induced inflammation. CAME also markedly down-regulated serum TNF-α and IL-1ß levels. These findings were further supported by the histological study. The content of quercetin and betulinic acid in CAME was found to be 0.177 and 3.14%, respectively. CONCLUSION: Several mechanisms, including the inhibition of pro-inflammatory cytokines, enzymes and mediators release, appear to account for the anti-inflammatory potential of C. arborea.

Design, synthesis, in silico molecular docking and biological evaluation of novel oxadiazole based thiazolidine-2,4-diones bis-heterocycles as PPAR-γ agonists.

A library of novel 1,3,4-oxadiazole and 2-4-thiazolidinedione based bis-heterocycles 7 (a-r) has been synthesized which exhibited significant PPAR-γ transactivation and blood glucose lowering effect comparable with the standard drugs Pioglitazone and Rosiglitazone. Compounds 7m and 7r did not cause body weight gain and were found to be free from hepatotoxic and cardiotoxic side effects. Compounds 7m and 7r increased PPAR-γ gene expression by 2.10 and 2.00 folds, respectively in comparison to the standard drugs Pioglitazone (1.5 fold) and Rosiglitazone (1.0 fold). Therefore the compounds 7m and 7r may be considered as potential candidates for development of new antidiabetic agents.

Thiazolidine-2,4-diones derivatives as PPAR-γ agonists: synthesis, molecular docking, in vitro and in vivo antidiabetic activity with hepatotoxicity risk evaluation and effect on PPAR-γ gene expression.

A library of conjugates of chromones and 2,4-thiazolidinedione has been synthesized by Knoevenagel condensation followed by reduction using hydrogen gas and Pd/C as a catalyst. Compounds 5c and 5e were most effective in lowering the blood glucose level comparable to standard drug pioglitazone. Compound 5e exhibited potent PPAR-γ transactivation of 48.72% in comparison to pioglitazone (62.48%). All the molecules showed good glide score against the PPAR-γ target in molecular docking study. PPAR-γ gene expression was significantly increased by compound 5e (2.56-fold) in comparison to standard drug pioglitazone. Compounds 5e and 5c did not cause any damage to the liver and may be considered as promising candidates for the development of new antidiabetic agents.

Effect of escitalopram on cardiomyopathy-induced anxiety in mice.

The present study was aimed to evaluate the effect of escitalopram on anxiety following doxorubicin (DOX)-induced cardiomyopathy, a rodent model for heart failure (HF), in mice. The study was carried out in Swiss albino mice. DOX was used at a dose of 10 mg/kg intravenously. Escitalopram was administered at the doses of 10 and 20 mg/kg orally for 7 days pre- and 7 days post-DOX. Anxiety was measured on day 8 and on day 14 using elevated plus maze and Vogel's conflict test. On day 14, serum lactate dehydrogenase (LDH) was estimated. The mice were then killed and their hearts were dissected out for the estimation of malondialdehyde (MDA) and for the transmission electron microscopic (TEM) studies. Our results showed that the DOX administration induced cardiomyopathy in mice. This was evidenced by the increased levels of serum LDH and tissue MDA and was also confirmed by TEM. Escitalopram (20 mg/kg) not only reversed the anxiety-like effects induced by DOX but also DOX-induced increase in LDH and MDA as well as the morphological alterations induced by DOX in TEM studies. Escitalopram, thus, appears to be a good candidate for alleviating anxiety in patients with HF.

Combination therapy of piperine and phenytoin in maximal electroshock induced seizures in mice: isobolographic and biochemical analysis.

The present study was aimed to characterize the anticonvulsant effects of piperine in combination with well established antiepileptic drug (AED) phenytoin, in the mouse maximal electroshock (MES)-induced seizure model by using the type I isobolographic analysis for non-parallel dose-response relationship curves (DRRCs). Potential adverse-effect profiles of interactions of phenytoin with piperine at the fixed-ratio of 1:1 from the MES test with respect to long-term memory and skeletal muscular strength were evaluated along with free plasma concentration of piperine and phenytoin. Parameters of oxidative stress (glutathione, malondialdehyde), brain serotonin and serum calcium levels were also determined to probe the mechanism involved in the interaction. Test of parallelism revealed that 2 drugs were associated with non-parallel dose response effects, hence only one fixed ratio combination (1:1) was evaluated which displayed additive interaction between the 2 drugs with a slight tendency towards superadditivity. Free plasma concentrations of piperine and phenytoin revealed no significant changes in their concentrations when the drugs were combined at the fixed-ratio of 1:1. In combination, neither long-term memory nor skeletal muscular strength was impaired. Analysis of biochemical parameters showed that the piperine alone or in combination with phenytoin successfully reversed the parameters of oxidative stress and increased brain serotonin levels as compared to MES group. However, no significant alteration in the serum calcium levels was observed by any treatment. In conclusion, the combination displayed additive interaction and slight tendency towards synergistic potential with protection towards side effects associated with AED therapy and is worthy of consideration for further investigations.

Medicine utilization review at a university teaching hospital in New Delhi.

OBJECTIVE: A prospective medicine usage evaluation based on prescription monitoring was conducted in the medicine OPD of our university teaching hospital to know prescribing trends of different categories of medicines. MATERIALS AND METHODS: A total of 600 patients were included in the study comprising of 339 (56.5%) males and 261 (43.5%) females. The data were recorded within the OPD by a registered pharmacist on a medicine usage evaluation form, approved by The University Institutional Review Board (IRB). RESULTS: A total of 2365 medicines were prescribed to 600 patients during the 3 months study period. The mean number of medicines per prescription were found to be 3.94. Medicines were most frequently prescribed as solid dosage forms (85.62%), especially tablets (70.82%), and liquid formulations (14.12%). Oral route (96.17%) was the most preferred mode of administration, followed by topical (2.11%) and parenteral (1.60%) routes. Combination therapy (94.33%) was more prevalent than monotherapy (5.66%). An overwhelming tendency for prescribing medicines by brand names (99%) was observed by the physicians. The most frequently prescribed class of medicines were antimicrobials > analgesics > cardiovascular > gastrointestinal agents. The most prescribed individual medicines among various therapeutic classes included isoniazid (antimicrobial), amlodipine (cardiovascular), metformin (hypoglycemic), cetirizine (antiallergic), rabeprazole (GI medicine), atorvastatin (hypolipidemic), dextromethorphan (respiratory medicine), alprazolam (sedative-hypnotic), paracetamol (analgesic). CONCLUSIONS: There is a considerable scope of improvement in the existing prescribing practice, especially prescribing by generic names, needs to be encouraged and a hospital formulary has to be developed for the purpose. The number of medicines to be included per prescription should be judged rationally and polypharmacy ought to be curbed. Use of antimicrobial also needs to be rationalized as over usage of antibiotics may lead to the problems such as medicine resistance and noncompliance.

Evaluation of antimicrobial activity of ethanol extract and compounds isolated from Trichodesma indicum (Linn.) R. Br. root.

ETHNOPHARMACOLOGICAL RELEVANCE: The roots are reportedly used to treat diarrhoea, dysentery, leprosy, skin diseases and fever. AIM OF STUDY: The aim of present study was to investigate the in vitro antimicrobial potential of ethanol extract of Trichdesma indicum root, and its purified compounds and to validate scientifically its use in traditional medicine. MATERIAL AND METHODS: The root of Trichdesma indicum was extracted with ethanol and subjected to chromatographic separation for isolation of phytochemical compounds. Structures of isolated compounds were elucidated by spectroscopic methods. The antimicrobial activities of the ethanol extract of T. indicum and isolated compounds were primarily evaluated by a disc diffusion test. The anti-microbial efficacy of the ethanol extract or isolated compounds was then assessed in vitro by determining minimal inhibition concentration (MIC) and minimal bactericidal or fungicidal concentration (MBC/MFC). RESULTS: n-Decanyl laurate (1), n-tetradecanyl laurate (2), n-nonacosanyl palmitate (3), stigmast-5-en-3ß-ol-21(24)-olide (4), n-pentacos-9-one (5), n-dotriacont-9-one-13-ene (6), stigmast-5-en-3ß-ol-23-one (7) and lanast-5-en-3ß-D-glucopyranosyl-21 (24)-olide (8) were isolated from ethanol extract of T.indicum. The ethanol extract and isolated compounds (1-8) showed varying degrees of antimicrobial activities. The ethanol extract exhibited potent growth inhibitory activity against S. aureus, B. subtilis and C. albicans with an MIC value of 19.2 µg/ml. Among all the isolated compounds, lanast-5-en-3ß-D-glucopyranosyl-21 (24)-olide (8) displayed strongest antibacterial activity against S. aureus with MIC value of 2.4 µg/ml. CONCLUSIONS: The results of present study provide ground basis for the potential use of the ethanol extract Trichodesma indicum root as well as the some of the isolated compounds in the treatment of infections associated with the studied microorganisms.

Effect of rosuvastatin on obesity-induced cardiac oxidative stress in Wistar rats--a preliminary study.

The prevalence of obesity has been rising alarmingly and it has now become a global concern causing an enormous economic burden on the health care system. Obesity is generally linked to complications in lipid metabolism and oxidative stress. The aim of the present study was to investigate the effect of rosuvastatin (10 mg/kg, po) on obesity-induced oxidative stress in high fat-fed Wistar rats. Oral administration of rosuvastatin (10 mg/kg) for 21 days along with high fat diet brought about significant elevation in serum high density lipoprotein and cardiac antioxidant enzymes levels (superoxide dismutase, catalase, glutathione, glutathione peroxidase, glutathione peroxidase-, glutathione reductase- and glutathione-S-transferase) while decreasing in serum lactate dehydrogenase, apolipoprotein-B, lipids (triglycerides, total cholesterol, low density lipoprotein-cholesterol, very low density lipoprotein-cholesterol and atherogenic index) and cardiac thiobarbituric acid reactive substances levels. The results were comparable with orlistat, a standard antiobesity drug. These preliminary results for the first time demonstrate that administration of rosuvastatin can be beneficial for the suppression of obesity-induced oxidative stress and dyslipidemia in high fat-fed Wistar rats.

Antimicrobial therapy and outcome of septicemia patients admitted to a University Hospital in Delhi.

Septicemia is a common clinical condition encountered in most of the hospitals in this region of the world. However, limited information is available in the Indian literature on antimicrobial usage in patients with suspected or proven cases of septicemia. The aim of the present study is on the one hand to describe the clinical characteristics of septicemia, the causative pathogens, the current pattern of antimicrobial use, the clinical outcome, the acquisition cost of commonly used antimicrobial regimens and on the other hand to monitor adverse drug reactions (ADRs) during therapy of septicemia patients admitted to a University Hospital in Delhi. We prospectively reviewed the antimicrobial therapy in 34 clinically diagnosed septicemia cases admitted to a University Hospital from July 2009 to December 2009. All study patients presented various clinical signs and symptoms, fever, diarrhoea and vomiting were most commonly reported. Microorganisms could be identified in 13 (38.2%) of the patients. Escherichia coli (41.2%) constituted the most prevalent bacterial pathogen. Among culture positive patients, 15.4% received ceftriaxone as the most common empirical antimicrobial therapy; among culture negative patients, 19% received cefotaxime plus amikacin as the most common empirical antimicrobial therapy. The average acquisition cost of the 1st line antimicrobial regimen was higher in culture positive than in culture negative patients, but it was reversed for the 2nd line therapy. Overall, 67.6% patients were discharged after recovery, 23.5% were transferred out and 8.8% died during the course of therapy. 9 (26.5%) patients experienced ADRs during the antimicrobial therapy. These findings may have an important implication for developing comprehensive, evidence-based guidelines for the practical treatment of septicemia, adherence to which may lead to a more rational antimicrobial therapy, to cost reduction and to an improved level of care of patients with septicemia.

Reversal of oxidative stress by histamine H3 receptor-ligands in experimental models of schizophrenia.

Schizophrenia (SCZ) is a debilitating disorder afflicting around 1% of the world population. Recent literature reveals oxidative injuries contribute enormously to the pathophysiology of SCZ alongside other psychopathological disturbances. Histamine H3R-antagonists have shown dual mechanism of action in experimental models of SCZ. Firstly it prevents oxidative stress and secondly alleviates schizophrenic symptoms, particularly the negative symptoms and cognitive deficits. In the present study, histamine H3R-antagonists used were ciproxifan (3.0 mg/kg, ip) and clobenpropit (15 mg/kg, ip) markedly controlled the elevated levels of various oxidative stress markers, for example, thiobarbituric acid reactive substance (TBARS), glutathione (GSH), superoxide dismutase, catalase, etc., as a result of augmented oxidative stress in the experimental models of SCZ such as amphetamine (0.5 mg/kg, sc) and dizocilpine (MK-801) (0.2 mg/kg, ip) induced locomotor hyperactivity, apomorphine (1.5 mg/kg, sc) induced climbing behavior and haloperidol (2.0 mg/kg, po) induced catalepsy. The results of the present study revealed that H3R-antagonists possess antioxidant activity and could serve with dual mechanism by supplementing antioxidant needs of SCZ and at the same time controlling symptoms of SCZ.

A pharmacological appraisal of medicinal plants with antidiabetic potential.

Diabetes mellitus is a complicated metabolic disorder that has gravely troubled the human health and quality of life. Conventional agents are being used to control diabetes along with lifestyle management. However, they are not entirely effective and no one has ever been reported to have fully recovered from diabetes. Numerous medicinal plants have been used for the management of diabetes mellitus in various traditional systems of medicine worldwide as they are a great source of biological constituents and many of them are known to be effective against diabetes. Medicinal plants with antihyperglycemic activities are being more desired, owing to lesser side-effects and low cost. This review focuses on the various plants that have been reported to be effective in diabetes. A record of various medicinal plants with their established antidiabetic and other health benefits has been reported. These include Allium sativa, Eugenia jambolana, Panax ginseng, Gymnema sylvestre, Momrodica charantia, Ocimum sanctum, Phyllanthus amarus, Pterocarpus marsupium, Trigonella foenum graecum and Tinospora cordifolia. All of them have shown a certain degree of antidiabetic activity by different mechanisms of action.

Synthesis and evaluation of anticancer activity of some novel 6-aryl-2-(p-sulfamylphenyl)-pyridazin-3(2H)-ones.

A series of novel pyridazinone derivatives bearing benzenesulfonamide moiety (2a-h) has been synthesized by the condensation of appropriate aroylacrylic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Five derivatives (2a, 2b, 2d, 2g and 2h) were evaluated for their anticancer activity toward human cancer cell lines by the National Cancer Institute. The 2h showed remarkable activity against SR (leukemia) and NCI-H522 (non-small cell lung) with a GI(50) value of less than 0.1 µM. It also displayed good activity against leukemia (CCRF-CEM, HL-60 (TB), K-562, MOLT-4, RPMI-8226), non-small cell lung cancer (NCI-H460), colon (HCT-116, HCT-15, HT29, KMI2, SW-620), CNS (SF-295), melanoma (MALME-3M, M14, MDA-MB-435 SK-MEL-5), ovarian (OVCAR-3, NCI/ADR-RES) and breast (MCF7) cancer cell lines with a GI(50) less than 1.0 µM. The acute toxicity study of 2h indicated that it is well tolerated intra-peritoneally (400 mg/kg) by athymic nude mice. The 2h may possibly be used as lead compound for developing new anticancer agents.

The effects of triple vs. dual and monotherapy with rosiglitazone, glimepiride, and atorvastatin on lipid profile and glycemic control in type 2 diabetes mellitus rats.

The present study was undertaken to investigate the effects of triple oral therapy and different combination of rosiglitazone, atorvastatin, and glimepiride on streptozotocin (STZ)-induced diabetic rats. The various biochemical parameters studied included glycosylated hemoglobin (A1c), fasting plasma sugar levels, triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and very low-density lipoprotein (VLDL) cholesterol in diabetic and normal rats. The present study demonstrates that atorvastatin could increase the effect of rosiglitazone and glimepiride and lipid-lowering effect of combination of rosiglitazone and glimepiride (GLIM). According to our finding, similar results for rosiglitazone plus atorvastatin were obtained in terms of correcting lipid parameters, whereas the suppressive action of triple oral therapy of rosiglitazone and glimepiride, and atorvastatin on blood glucose, total cholesterol, LDL, VLDL, HDL cholesterol, and triglyceride was more beneficial than that of dual therapy of different combinations and monotherapy.

Enhancement of antioxidant defense mechanism by pitavastatin and rosuvastatin on obesity-induced oxidative stress in Wistar rats.

CONTEXT: There has been a steady increase in the epidemiology of obesity over the last 30 years with developed countries leading the way. Oxidative stress was believed to be the principle contributor to the development of cardiovascular disorders that linked with obesity. OBJECTIVE: To evaluate the enhancement of antioxidant defense mechanism by Pitavastatin (PTV) and Rosuvastatin (RSV) on obesity-induced oxidative stress in Wistar rats. METHODS: Fifty Wistar albino rats were divided into five groups. High fat diet (HFD, 20 g/day/rat) pellets were given for 28 days to produce obesity-induced oxidative stress in Wistar rats. Oral administration of HFD along with PTV, RSV and Orlistat [(HFD for 28 days + from 8th day PTV (1 mg/kg), RSV (5 mg/kg) and Orlistat (10 mg/kg) to 28th day] were given respectively. RESULTS: Both PTV and RSV produced significant (p < 0.01) reduction in serum apolipoprotein-B (Apo-B), total cholesterol (TC), triglycerides (TGs), cardiac-lipid peroxides (TBARS) levels and elevation in serum high density lipoprotein (HDL-C), cardiac antioxidant enzymes [glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catase (CAT)] levels. DISCUSSION AND CONCLUSION: Results were comparable with Orlistat, a standard antiobesity drug and present initial evidence that Pitavastatin and Rosuvastatin are useful for the treatment of obesity by enhancing the antioxidant defense mechanism. However, the effects of PTV were more prominent than RSV. The present findings of Pitavastatin and Rosuvastatin raise the possibility of a new application as an antiobesity therapeutic modality.

Pharmacokinetic-pharmacodynamic equivalence of three gliclazide formulations in healthy human male subjects.

AIMS: To find out the pharmacokinetic (PK) and pharmacodynamic (PD) parameters for assessing the bioequivalence of three marketed products. To study the relationship between the pharmacokinetics of gliclazide and pharmacodynamic effect in healthy male volunteers. METHODS: This was an open label, balanced, randomized, 3-treatment, 3-sequence, 3 period, single-dose, cross-over bioavailability study in which 18 healthy adults were randomized to receive gliclazide 80 mg with 7 days wash out between treatments. The drug was administered with 240 ml of 20% glucose solution after a 10 h overnight fasting. Pharmacokinetic parameters like t(max), C(max), AUC(0-t), AUC(0-∞), AUC(0-t) / AUC(0-∞) and t(1/2) and pharmacodynamic parameters like maximum effect (minimum glucose level in the body, C(minglu)), time to minimum glucose level in the body (T(cminglu)) and partial AUC were calculated for all the products. RESULTS: The values for mean ± SD for age, height and weight of the volunteers were 28.00 ± 22.68, 165.78 ± 5.56 and 56.78 ± 13.37 respectively. There were total 4 withdrawn subjects and 1 drop out. Within batch accuracy of the method were in the range of 95.5 - 101.7%, 99.1 - 106.1% and 96.2 - 104.2% for three consecutive batches. The 90% CI for log transformed data of the PK and PD were within the acceptance range of 80.0 - 125.0%. CONCLUSIONS: This population PKPD analysis has characterized the relationship between the exposure to gliclazide and its hypoglycemic effect. The test products A & B compared to reference product R were bioequivalent on the basis of pharmacokinetic and pharmacodynamic parameters. Finally it is recommended that the more costly product R can be safely switched with less costly products i.e. A and B.

Effect of aloe vera (Aloe barbadensis Miller) gel on doxorubicin-induced myocardial oxidative stress and calcium overload in albino rats.

Administration of a single dose of doxorubicin (DOX) (7.5 mg/kg, i.v.) produces cardiotoxicity, manifested biochemically by significant decrease in blood glutathione (GSH) and tissue GSH along with elevated levels of serum lactate dehydrogenase (LDH) and serum creatine phosphokinase (CPK). In addition, cardiotoxicity was further confirmed by significant increase in lipid peroxides expressed as malondialdehyde (MDA, secondary indicator of lipid peroxidation), tissue catalase and tissue superoxide dismutase (SOD). Administration ofA. vera gel (100 and 200 mg/kg) orally for 10 days produced a significant protection against cardiotoxicity induced by DOX evidenced by significant reductions in serum LDH, serum CPK, cardiac lipid peroxides, tissue catalase and tissue SOD along with increased levels of blood and tissue GSH. The results revealed that A. vera gel produced a dose dependent protection against DOX induced cardiotoxiaty.