Trends of Antimicrobial Resistance of Sepsis Pathogens at a University Hospital in New Delhi, India.

Knowledge of the aetiological agents and its susceptibility to antimicrobial agents enables the clinician to initiate appropriate empirical antimicrobial therapy and guides diagnostic procedures. The aims of the study were to identify prevalence of bacterial pathogens causing sepsis and observe their antimicrobial resistance trends in hospitalized patients. A prospective cohort study was conducted on patients of sepsis admitted at a university hospital over a period of six months. Pathogens were identified by morphological, biochemical and serological tests as per the American Society for Microbiology. Antibacterial sensitivity of bacterial strains isolated from clinically diagnosed sepsis was carried out by Kirby-Bauer disk diffusion method and interpreted according Clinical and Laboratory Standards Institute guidelines. The data were analyzed by using Statistical Package for Social Sciences, version 16.0 (SPSS 16.0, Chicago, IL, USA). Coagulase negative Staphylococcus (63.5%) and Staphylococcus aureus (23.1%) were the most frequently isolated Gram positive bacteria. Acinetobacter species (31%) and Salmonella typhi (24.1%) were the most frequently isolated Gram negative bacteria. Coagulase negative Staphylococcus showed significant resistance to ciprofloxacin and tetracycline. Acinetobacter species showed significant resistance to ampicillin, amoxicillin and amoxiclav. Salmonella typhi showed significant resistance to ampicillin, amoxicillin, cefotaxime, netilmicin and, tetracycline. Escherichia coli showed significant resistance to ampicillin and netilmicin. All the stains of Staphylococcus aureus were resistant to amoxicillin. Coagulase negative Staphylococcus and Acinetobacter species were predominant Gram positive and Gram negative bacteria, respectively, causing sepsis. Increasing rates of bacterial resistance to commonly use antimicrobial agents were observed.

Adverse drug reaction monitoring during antimicrobial therapy for septicemia patients at a university hospital in New Delhi.

BACKGROUND/AIMS: Adverse drug reaction (ADR) is an appreciably harmful or unpleasant reaction, resulting from an intervention related to the use of a medicinal product. The present study was conducted in order to monitor the frequency and severity of ADR during antimicrobial therapy of septicemia. METHODS: A prospective, observational, and noncomparative study was conducted over a period of 6 months on patients of septicemia admitted at a university hospital. Naranjo algorithm scale was used for causality assessment. Severity assessment was done by Hartwig severity scale. RESULTS: ADRs in selected hospitalized patients of septicemia was found to be in 26.5% of the study population. During the study period, 12 ADRs were confirmed occurring in 9, out of 34 admitted patients. Pediatric patients experienced maximum ADRs, 44.4%. Females experienced a significantly higher incidence of ADRs, 66.7%. According to Naranjo's probability scale, 8.3% of ADRs were found to be definite, 58.3% as probable, and 33.3% as possible. A higher proportion of these ADRs, 66.7% were preventable in nature. Severity assessment showed that more than half of ADRs were moderate. Teicoplanin was found to be the commonest antimicrobial agent associated with ADRs, followed by gemifloxacin and ofloxacin. CONCLUSION: The incidence and severity of ADRs observed in the present study was substantially high indicating the need of extra vigilant during the antimicrobial therapy of septicemia.

Levosimendan reduces myocardial damage and improves cardiodynamics in streptozotocin induced diabetic cardiomyopathy via SERCA2a/NCX1 pathway.

AIMS: Diabetic cardiomyopathy (DCM) is one of the most common causes of mortality. Its pathophysiology is not fully understood and involve number of factors including, cardiovascular and metabolic disorders. The present study was designed to study the pathogenesis of DCM and to explore the effects of levosimendan along with either ramipril or insulin in the long term management of DCM. MATERIALS AND METHODS: Streptozotocin (STZ) was used to develop DCM in Wistar rats at the dose of 25mg/kg body weight for three consecutive days. Rats were randomly divided into 9 groups and treatments were started after 2weeks of STZ administration. KEY FINDINGS: Persistent hyperglycemia was observed in STZ treated rats, leading to significant contractile dysfunction as evidenced by decreased left ventricular pressure (LVP), +LV (dp/dt), -LV (dp/dt) as well as elevated Tau and LVEDP. Marked myocardial damage such as fibrosis, increased wall tension, depletion of contractile proteins were observed as evidenced by increased levels of TGF-ß, BNP, cTroponin-I, as well as decreased expression of SERCA2a and NCX1 proteins in diabetic rats. The levosimendan alone and also in combination with either ramipril or insulin significantly normalized the myocardial dysfunctions developed during the course of persistent hyperglycemia. SIGNIFICANCE: The study suggests that levosimendan treatment improves cardiac dysfunction significantly. Its combined use with ramipril proves better than with insulin in correcting myocardial performance as well as reduction in myocardial damage.

Cissampelos pareira Linn. ameliorates thyroxin-induced cardiac hypertrophy in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Cissampelos pareira extract has been traditionally used in ayruveda as cardiotonic, diuretics and in heart complains but its pharmacological evaluation in thyroxin-induced cardiac hypertrophy has not yet been explored. AIM OF THE STUDY: The aim of this study was to assess the cardioprotective effect of C. pareira root extract in experimentally induced hyperthyroidism in rats. MATERIALS AND METHODS: Male Wistar rats were treated with (i) thyroxin (0.1 mg/kg/day, i.p.) for 30 days, (ii) C. pareira extract (200 mg/kg/day, p.o.) alone for 60 days, (iii) C. pareira extract (100 and 200 mg/kg/day, p.o., respectively) for 30 days then with thyroxin for another 30 days, (iv) thyroxin for 30 days then C. pareira extract (100 and 200 mg/kg/day, p.o., respectively) for another 30 days. At the end of experiment, serum calcineurin, nitric oxide, lactate dehydrogenase, and thiobarbituric acid reactive substance as well as serum and/or myocardial antioxidant enzymes activity were estimated. RESULTS: Hyperthyroid induced cardiotoxicity was characterized by a significant (P<0.001) increase in heart weight/body weight ratio, serum calcineurin, nitric oxide, lactate dehydrogenase and thiobarbituric acid reactive substance levels as well as a significant decrease in serum reduced glutathione, myocardial glutathione peroxidase, glutathione reductase and glutathione-S-transferase levels, which were significantly (P<0.05 and P<0.01) reverted by C. pareira extract treatment. Reversal of histological changes on treatment with C. pareira extract was also supported the biochemical parameters. These results were quite comparable with amlodipine, the standard drug taken in this study. CONCLUSIONS: Treatment with C. pareira extract ameliorates thyroxin-induced oxidative stress and cardiac hypertrophy, probably through amelioration of calcineurin activity and augmentation of antioxidant enzyme activities.

Levosimendan suppresses oxidative injury, apoptotic signaling and mitochondrial degeneration in streptozotocin-induced diabetic cardiomyopathy.

Diabetic cardiomyopathy plays a major role in morbidity and mortality among cardiovascular disorder-related complications. This study was designed to explore long-term benefits of Levosimendan (LEVO) along with Ramipril and Insulin. Diabetic cardiomyopathy was induced using streptozotocin (STZ) at the dose of 25 mg/kg/body weight/day for three consecutive days in Wistar rats. Rats were randomly divided into 10 groups and treatments were started after 2 weeks of STZ administration. A gradual but severe hyperglycemia ((§§§)p < 0.001) was observed in all STZ-treated groups except those received insulin (2 U/day). LEVO alone and in combination with Ramipril and Insulin normalized (**p < 0.01) mean arterial pressure and heart rate, restored catalase, superoxide dismutase, malondialdehyde, glutathione level and also attenuated (***p < 0.001) the raised serum levels of creatine kinase-heart type, lactate dehydrogenase, tumor necrosis factor-alpha, C-reactive protein, and caspase-3 level in heart tissue altered after STZ treatment. Myofibril degeneration, mitochondrial fibrosis and vacuolization occurred after STZ treatment, were also reversed by LEVO in combination with Ramipril and Insulin. The combination of LEVO with Ramipril and Insulin improved hemodynamic functions, maintained cardiac enzymes and ameliorated myofibril damage in diabetic cardiomyopathy.

Assessment of nonsteroidal anti-inflammatory drug-induced cardiotoxicity.

INTRODUCTION: Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (coxibs) and traditional NSAIDs (tNSAIDs), have been widely used for the treatment of pain and rheumatic disease. The use of NSAIDs has been linked to increased cardiovascular toxicity in both healthy individuals and patients with established cardiovascular disease. Various recently published studies have raised concerns about the cardiovascular safety of NSAIDs; this review is focused on the cardiotoxic effects of NSAIDs. AREAS COVERED: This review focuses on arthritis trials, placebo-controlled trials, meta-analyses, preclinical and observational studies associated with the use of NSAIDs-induced cardiotoxicity. It analyses the data given in these studies and discusses the cardiotoxic risk of NSAIDs. EXPERT OPINION: Analysis of various clinical, preclinical, meta-analysis and observational studies showed that coxibs and tNSAIDs increase the risk of cardiotoxicity. Cardiotoxic risk depends on dose, duration and frequency of NSAID administration. Most studies were based on large medical databases with miscellaneous populations and pointed to an increase risk of cardiotoxicity under NSAID medication. The cardiotoxicity associated with use of NSAIDs might be due to inhibition of prostacyclin synthesis, oxidative stress, increase in blood pressure and impaired endothelial function.

Protective effect of a direct renin inhibitor in acute murine model of cardiotoxicity and nephrotoxicity.

This study aimed to investigate the possible protective effects of aliskiren against doxorubicin (DXR)-induced cardiorenal injury and to identify the mechanisms involved. Intraperitoneal administration of DXR (15 mg/kg, body weight, as a single dose) caused significant induction in the levels of angiotensin I, caspase-3, lactate dehydrogenase (LDH), lipid peroxidation malondialdehyde (MDA), urea, and creatinine. Concomitant decline in the levels of albumin and total protein in plasma, reduction in reduced glutathione (GSH), and antiperoxidative enzyme superoxide dismutase (SOD) levels followed by ultrastructural alterations in the myocardial and renal tissues were also observed. Oral administration of aliskiren (100 mg/kg, for a period of 14 days) significantly prevented all these DXR-induced adverse effects and maintained the rats near to normal status. However, telmisartan (10 mg/kg) pretreatment has shown slight protection in DXR-induced renal injury as evidenced by broadening of podocyte foot process and narrowing of slit pore diameter. The results of aliskiren were compared with telmisartan which was used as reference in this study. These results suggested that aliskiren has protective effects against acute model of DXR-induced cardiotoxicity and nephrotoxicity, implying that plasma renin activity plays a role in DXR-induced cardio-renal injury.

Effects of pioglitazone and vildagliptin on coagulation cascade in diabetes mellitus--targeting thrombogenesis.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is intricately allied with an increased risk of atherothrombotic disease. Thrombosis is the cause of mortality in 80% of patients with diabetes mellitus. Endothelial abnormalities lead to elevated inflammatory and coagulation biomarkers as seen in diabetes. Progression of atherothrombotic disease in diabetes has been linked with elevated levels of various coagulation factors including fibrinogen, plasminogen activator inhibitor-1, and von Willebrand factor. AREAS COVERED: We review the existing evidence and most recent data elucidating the various inflammatory and coagulation biomarkers that are elevated in T2DM leading to thrombosis as well as the anti-inflammatory, anticoagulant and antithrombotic mechanisms of pioglitazone and vildagliptin in addition to their effect on glucose metabolism that may halt the progression of atherothrombotic disease. EXPERT OPINION: The review highlights the pleiotropic effects of pioglitazone and vildagliptin on metabolic, inflammatory and coagulation processes that have the potential to influence cardiovascular disease progression at various points in the disease process, including hemostatic disturbances, inflammation, plaque rupture and atherogenesis in T2DM. Finally, the paper suggests a possible decline in T2DM-associated cardiovascular comorbidities once the antithrombotic potential of pioglitazone and vildagliptin is established through clinical investigation.

Effect of Cissampelos pareira root extract on isoproterenol-induced cardiac dysfunction.

The aim of this study was to assess the cardioprotective effect of Cissampelos pareira root extract on isoproterenol-induced cardiac dysfunction in rats. Male albino Wistar rats were randomly divided into eight groups and received either normal saline (0.5 ml/kg, intraperitoneally), isoproterenol (5 mg/kg, intraperitoneally), C. pareira (100 and 200 mg/kg, by gavage, respectively) alone, amlodipine (9 mg/kg, by gavage) alone, C. pareira (100 and 200 mg/kg, respectively) + isoproterenol and amlodipine (9 mg/kg) + isoproterenol, once a day for 30 days, respectively. Isoproterenol-induced cardiac dysfunction was characterized by a significant (P < 0.001) increase in the heart weigh/body weight ratio, serum calcineurin, nitric oxide, lactate dehydrogenase, and thiobarbituric acid reactive substance levels, as well as a significant decrease in serum-reduced glutathione, cardiac glutathione peroxidase, glutathione reductase, and glutathione-S-transferase levels, which were significantly (P < 0.05 and P < 0.01) improved by C. pareira treatment. No significant alteration was observed in the group treated with C. pareira alone compared with the control. C. pareira treatment also restored histopathological changes observed in isoproterenol-induced rats. Amlodipine is used as standard drug in this study. Thus, these results suggest that the attenuation of isoproterenol-induced cardiac dysfunction by treatment with ethanolic root extract of C. pareira may be due to amelioration of calcineurin activity and free radical formation, and by augmentation of antioxidant enzymes activities.

Protective effects of histamine H3-receptor ligands in schizophrenic behaviors in experimental models.

Schizophrenia (SCZ) afflicts around 1% of the world's population with characteristic symptoms such as hallucinations, delusions, and cognitive disorders. Several experimental studies in the past have indicted brain histaminergic neuronal system involvement in the pathogenesis of psychotic disorders including SCZ. Present study investigates anti-schizophrenic activity using two histamine H(3)-receptor (H(3)R)-antagonists/inverse agonists, ciproxifan (3.0 mg/kg, i.p.) and clobenpropit (15 mg/kg, i.p.), on some of the established animal model of schizophrenia, for example, amphetamine (AMPH) and dizocilpine (MK-801)-induced hyperactivity, apomorphine (APO)-induced climbing behavior, scopolamine and MK-801-induced learning and memory deficits and haloperidol-induced catalepsy including determination of acetylcholinesterase (AChE) activity. Results of the present study demonstrate that ciproxifan and clobenpropitwere able to control AMPH and MK-801-induced hyperlocomotor activities demonstrated as reduced horizontal activity and reduced number of movements made by rats. Further, there was overall reduction in APO-induced climbing behavior. Learning and memory deficits, as evaluated on elevated plus maze, followed by estimation of brain AChE activity demonstrated positive results with these protypical imidazole H(3)R-antagonists/inverse agonists.

Aliskiren as a novel therapeutic agent for hypertension and cardio-renal diseases.

OBJECTIVES: High blood pressure (BP) is a major risk factor for cardiovascular and renal complications. A majority of treated hypertensive patients still complain of high BP. The renin-angiotensin aldosterone system (RAAS) has been a centre-stage target for all the cardiovascular and cardio-renal complications. Aliskiren, is the first direct renin inhibitor (DRI) to be approved by the US FDA. Renin controls the rate-limiting step in the RAAS cascade and hence is the most favorable target for RAAS suppression. KEY FINDINGS: This review article strives to summarize the pharmacokinetic, preclinical and clinical studies done so far pertaining to the efficacy of aliskiren. Further, the pharmacology of aliskiren has been comprehensively dealt with to enhance understanding so as to further research in this unfathomed area in the multitude of cardiovascular disorders and renal diseases. SUMMARY: Aliskiren has been shown to have comparable BP-lowering effects to other RAAS inhibitors. Recent clinical trials have indicated that it might contribute significantly in combination with other agents for the protection of end-organ diseases.

Aliskiren attenuates myocardial apoptosis and oxidative stress in chronic murine model of cardiomyopathy.

Doxorubicin (DXR) is one of the most effective antineoplastic agents. However, the optimal clinical use of this agent is limited because of marked cardiomyopathy and congestive heart failure. Renin angiotensin system (RAS) plays an important role in the development of cardiac hypertrophy, reperfusion injury and congestive heart failure. Aliskiren (ALK) is a direct inhibitor of renin and does not affect other systems involved in cardiovascular regulation. This study was designed to explore the possible protective effects of ALK (30 and 100 mg/kg, per oral [p.o.] respectively for 42 days) in chronic model of DXR (1.25 mg/kg, intraperitoneally (i.p.) sixteen equal cumulative doses) induced cardiomyopathy in rats. DXR treatment significantly (P<0.01) increased the activities of serum creatine kinase (CK-MB), lactate dehydrogenase (LDH), cardiomyocyte caspase-3 and catalase (CAT). ALK (100 mg/kg) treatment prevented the animals significantly (P<0.01) from rise in the above indices. Furthermore ALK (100 mg/kg) significantly restores the DXR-induced decrease in antioxidant defense, reduced glutathione (GSH) and superoxide dismutase (SOD). Transmission electron microscopic studies showed that DXR caused apoptosis in myocardium, manifested as condensation of chromatin network at the margins and rupture of nuclear membrane which was well protected by ALK (100 mg/kg) treatment. The present study indicates that ALK protected rats from DXR-induced cardiomyopathy.

Protective effect of Withania somnifera against oxidative stress and pancreatic beta-cell damage in type 2 diabetic rats.

The aim of the present study was to investigate the effects of Withania somnifera (WS) on lipid peroxidation (LPO), activities of both non-enzymatic and enzymatic antioxidants and histopathological examination of pancreas in type 2 diabetic rats. Type 2 diabetes was induced by single intraperitoneal injection of STZ (100 mg/kg) to 2 days old rat pups. Oxidative stress was measured by tissue LPO levels, reduced glutathione (GSH) contents and by enzymatic activities of glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT). Administration of WS to type 2 diabetic rats caused a significant decrease in blood glucose and tissue LPO levels with significant increase in GSH contents when compared with the type 2 diabetic control rats. In addition, WS treated rats also showed a significant increase in the activities of antioxidant enzymes namely GPx, GR, GST, SOD and CAT when compared with type 2 diabetic control rats. Significant reduction in the number and size of pancreatic beta-cells were preserved to near normal morphology by the administration of WS in type 2 diabetic rats as evident from histopathological examination. The results obtained clearly indicate that WS has shown strong free radical scavenging activity and helped in improving the non-enzymatic and enzymatic antioxidants in type 2 diabetic rats.

Isoproterenol-induced cardiomyopathy in rats: influence of Acorus calamus Linn.: A. calamus attenuates cardiomyopathy.

Acorus calamus has been used as a traditional remedy since ancient days but its cardioprotective effect is not yet well characterized. The aim of this study was to assess the effect of A. calamus rhizome extract in isoproterenol-induced cardiomyopathy in rats. Male Wistar rats were treated with normal saline (0.5 ml/kg, i.p.), isoproterenol (5 mg/kg, i.p.), A. calamus (100 and 200 mg/kg, respectively, by gavage) alone, amlodipine (9.0 mg/kg, by gavage) alone, A. calamus (100 and 200 mg/kg, respectively) + isoproterenol and amlodipine (9.0 mg/kg) + isoproterenol, single dose/day for 30 days, respectively. Isoproterenol-induced cardiomyopathy was characterized by a significant (P < 0.001) increase in heart weigh/body weight ratio, calcineurin, nitric oxide, lactate dehydrogenase, and thiobarbituric acid-reactive substance levels as well as a significant (P < 0.001) decrease in reduced glutathione, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase levels. Treatment with A. calamus significantly (P < 0.05 and P < 0.01) attenuated isoproterenol-induced cardiomyopathy. No significant alteration was found in A. calamus-alone groups compared with the vehicle. Amlodipine is used as standard drug in this study. Thus, the result shows that A. calamus attenuates isoproterenol-induced cardiomyopathy. This could be due to attenuating calcineurin activity and oxidative stress.

Protective effects of 'Khamira Abresham Hakim Arshad Wala', a unani formulation against doxorubicin-induced cardiotoxicity and nephrotoxicity.

Doxorubicin is one of the most active cytotoxic agents in current use. The clinical usefulness of the doxorubicin has been precluded by its marked cardiotoxicity. The aim of the present study was to investigate the effect of Khamira Abresham Hakim Arshadwala, a well known unani cardiac tonic formulation, pre-treatment on doxorubicin-induced cardiotoxicity, and nephrotoxicity in rats. Twenty-four Wistar albino rats, divided into four groups, were used. Khamira Abresham Hakim Arshadwala was administered daily, for 7 days, and a single dose of doxorubicin (10 mg/kg, i.v.) on day 5. After 48 h of doxorubicin injection, animals were sacrificed. Lactate dehydrogenase (LDH), aspartate transaminase (AST), blood urea nitrogen (BUN), and creatinine were estimated in the serum. Heart specimens were used for biochemical estimations of lipid peroxides (MDA), reduced glutathione (GSH), catalase, and for microscopic examination of histopathological changes. Doxorubicin showed cardiotoxicity and nephrotoxicity, as evidenced by elevated activities of AST, LDH, BUN, creatinine, and MDA, depletion in GSH level, and catalase activity. Histopathological studies showed disruption of cardiac tissues in doxorubicin groups. Khamira Abresham Hakim Arshadwala pre-treatment showed a protective effect against the enzymatic changes in serum as well as cardiac and kidney tissue damage, significantly. The present findings suggest that Khamira Abresham Hakim Arshadwala significantly (p < 0.01) improved the state of markers for cardiac and kidney damage investigated in this model of doxorubicin-induced experimental cardiotoxicity and nephrotoxicity; indicating its potential in limiting doxorubicin toxicity.

Diclofenac sodium, a nonselective nonsteroidal anti-inflammatory drug aggravates doxorubicin-induced cardiomyopathy in rats.

The cardiotoxic effects of selective cyclo-oxygenase-2 inhibitors are well documented. Recently, concerns have been raised over the cardiovascular safety of nonselective nonsteroidal antiinflammatory drugs. The aim of this study was to assess the cardiac effects of diclofenac sodium on doxorubicin-induced cardiomyopathy in rats. Male Wistar rats were treated with doxorubicin (15 mg/kg intraperitoneally, single dose), diclofenac sodium (2.5 and 10 mg/kg/day, respectively, by gavage for 5 days) alone and doxorubicin + diclofenac sodium treatment, 24 hours after doxorubicin administration. Doxorubicin-induced a significant (P < 0.001) increase in the serum lactate dehydrogenase, cardiac thiobarbituric acid-reactive substance and catalase levels and a significant (P < 0.001) decrease in the cardiac glutathione and superoxide dismutase levels, which were significantly (P < 0.001) aggravated by diclofenac sodium treatment. Diclofenac sodium alone also showed a significant change in these parameters compared with the control. Ultrastructural studies showed that doxorubicin causes apoptosis in myocardium, which was characterized by condensation of chromatin network at the margins of nuclear membrane. Apoptosis induced by doxorubicin was exacerbated by diclofenac sodium treatment. Thus, our study indicates that diclofenac sodium, a nonaspirin nonsteroidal anti-inflammatory drug, is not free from cardiotoxicity and aggravates doxorubicin-induced cardiomyopathy in rats.

RETRACTED: Rosiglitazone and pioglitazone aggravate doxorubicin-induced cardiomyopathy in Wistar rats.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.biomag.2010.12.001 The duplicate article has therefore been withdrawn.

Effect of Withania somnifera on insulin sensitivity in non-insulin-dependent diabetes mellitus rats.

We investigated the effect of an aqueous extract of Withania somnifera (WS) on insulin sensitivity in non-insulin-dependent diabetes mellitus (NIDDM) rats. NIDDM was induced by single intraperitoneal injection of streptozotocin (100 mg/kg) to 2 days old rat pups. WS (200 and 400 mg/kg) was administered orally once a day for 5 weeks after the animals were confirmed diabetic (i.e. 75 days after streptozotocin injection). A group of citrate control rats (group I) were also maintained that has received citrate buffer on the second day of their birth. A significant increase in blood glucose, glycosylated haemoglobin (HbA(1)c) and serum insulin levels were observed in NIDDM control rats. Treatment with WS reduced the elevated levels of blood glucose, HbA(1)c and insulin in the NIDDM rats. An oral glucose tolerance test was also performed in the same groups, in which we found a significant improvement in glucose tolerance in the rats treated with WS. The insulin sensitivity was assessed for both peripheral insulin resistance and hepatic insulin resistance. WS treatment significantly improved insulin sensitivity index (K(ITT)) that was significantly decreased in NIDDM control rats. There was significant rise in homeostasis model assessment of insulin resistance (HOMA-R) in NIDDM control rats whereas WS treatment significantly prevented the rise in HOMA-R in NIDDM-treated rats. Our data suggest that aqueous extract of WS normalizes hyperglycemia in NIDDM rats by improving insulin sensitivity.

Amiloride protects against pentylenetetrazole-induced kindling in mice.

This study was performed to investigate whether or not amiloride, a sodium-hydrogen exchanger (NHE) inhibitor, can protect against seizure development of pentylenetetrazole (PTZ)-induced kindling in mice.Kindling was induced by once every 2 days treatment with PTZ (25 mg kg(-1) i.p.) for 5 weeks. Challenge experiments were carried out after 15 or 30 days of last treatment with PTZ. Administration of amiloride (2 h before PTZ, in doses of 0.65 and 1.3 mg kg(-1), p.o.) significantly prolonged the onset of kindling and reduced the incidence and severity of seizures in a dose-dependent manner. The effect of amiloride on the incidence of PTZ-induced seizures was evident even after 15 or 30 days of last treatment. The results indicate a protective role for amiloride against PTZ-induced kindling in mice. The possibility of mediation of such effects by NHE inhibition is discussed.