Effect of a deacyl gymnemic acid on glucose homeostasis & metabolic parameters in a rat model of metabolic syndrome.

BACKGROUND & OBJECTIVES: Metabolic syndrome (MS) comprises several cardio-metabolic risk factors, which include obesity, hypertension, hyperglycaemia, hypertriglyceridaemia and decreased HDL cholesterol. Leaf extract of Gymnema sylvestre has been shown to possess glucose lowering activity in animal models. This study was carried out to evaluate the efficacy of deacyl gymnemic acid (DAGA), active constituent of G. sylvestre, in a rat model of MS. METHODS: Six groups consisting of six wistar rats in each, were studied. Group I received the normal diet, while the remaining five groups received high fructose diet (HFD ) for 20 days to induce MS. HFD was continued in these five groups for the next 20 days along with group II received vehicle solution, group III received pioglitazone and groups IV- VI received DAGA in variable doses. Systolic blood pressure (SBP) was measured using tail-cuff method. Oral glucose tolerance test (OGTT) was done at baseline and at days 20 and 40. Blood samples were collected for glucose, insulin and lipid profile. RESULTS: Administration of HFD for 20 days resulted in weight gain (>10%), increase in SBP, fasting plasma glucose (FPG) and triglycerides fulfilling the criteria for MS. Administration of DAGA (200 mg/kg) reduced SBP and significantly improved the FPG and HOMA-IR (homeostatis model assessment-insulin resistance) with modest improvement in lipid profile without decrease in body weight similar to pioglitazone. INTERPRETATION & CONCLUSIONS: Our findings show that DAGA decreases SBP and improves parameters of glucose-insulin homeostasis in a rat model of MS induced by HFD. Further studies are required to elucidate the mechanism of action.

Comparison of alternate-day atorvastatin treatment to daily treatment in maintaining LDL-cholesterol targets in patients with variable coronary risk profile.

3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity of atorvastatin lasts upto 20-30 hours. This study aimed at comparing the maintenance of National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) goal by the alternate-day therapy to daily treatment. This randomized, open-label trial included 300 patients of dyslipidemia or coronary artery disease on stable doses of atorvastatin. These patients met their respective NCEP-ATPIII cholesterol goals and were randomized to receive the same doses of atorvastatin every day (QD) or every other day (QOD) in a 1:1 ratio for 12 weeks. The efficacy criteria were (1) proportion of patients maintaining the low-density lipoprotein-cholesterol (LDL-C) goal, (2) comparison of changes in the total cholesterol, LDL-C, high-density lipoprotein cholesterol, and triglyceride levels from baseline. The proportions of patients maintaining their LDL-C goals in QD and QOD groups at 6 weeks were 83.9% (60.3-97.5) versus 70.9% (59.3-82.5) (P < 0.01) and at 12 weeks were 84.6% (70.9-98.3) versus 73.8% (63.8-83.8) (P < 0.05). Per-protocol analysis showed 95.5% (80.0-111.0) versus 79.1% (66.2-92.0) (P < 0.001) patients at 6 weeks and 91.9% (82.0-106.8) versus 77.4% (64.8-90) (P < 0.05) patients at 12 weeks had maintained their LDL-C goals in the QD and QOD groups. A significant increase was observed in the levels of total cholesterol, LDL-C, and triglyceride at 6 and 12 weeks compared with baseline values in the QOD group. Alternate-day treatment of atorvastatin was inferior to daily treatment in maintaining the NCEP-ATPIII goal.

Differential expression of heat shock protein (HSP) 70-2 gene polymorphism in benign and malignant pancreatic disorders and its relationship with disease severity and complications.

CONTEXT: The role of heat shock protein (HSP) 70-2 gene polymorphism (at position 1267, A to G transition) in patients with pancreatic disorders is not clear. OBJECTIVE: To evaluate HSP 70-2 gene polymorphism (at position 1267, A to G transition) in patients with acute and chronic pancreatitis as well as pancreatic carcinoma, and to find any association of this polymorphism with disease complications and severity. METHODS: One-hundred and fifty patients (50 each of acute, chronic pancreatitis, and pancreatic carcinoma) and 50 healthy blood donors as controls were prospectively studied. Three alleles (AA, AG and GG) of HSP 70-2 gene determined by PstI restriction fragment length polymorphism. RESULTS: There was a statistically significant difference in the distribution pattern of HSP 70-2 gene polymorphism in patients with acute pancreatitis (P=0.001) and pancreatic carcinoma (P<0.001) as compared to controls. The frequency of mutant allele (G allele) was significantly higher in diseased group as compared to control group (19% in control group, 40% in acute pancreatitis, 33% in chronic pancreatitis and 45% in pancreatic carcinoma). No association of this polymorphism was found with disease severity in patients with acute and chronic pancreatitis or pancreatic carcinoma. CONCLUSIONS: In our patient sample the frequency of mutant allele (G allele) of HSP 70-2 gene is significantly higher in patients with acute pancreatitis and pancreatic carcinoma compared to controls (50 healthy blood donors). However, this polymorphism was not associated with disease severity and complications.

Effect of aceclofenac on pharmacokinetic of phenytoin.

Aceclofenac is presently most commonly prescribed analgesic for chronic pain and inflammatory conditions. In clinical practice, phenytoin and aceclofenac are used in a chronic condition of generalized seizure with concomitant chronic pain. Hence there are chances of drug-drug interaction because modulations of isoenzymes involved in metabolism of phenytoin and aceclofenac are CYP2C9/10 and CYP2C19. It is important to maintain the therapeutic level of phenytoin in plasma for effective control of seizure. So, the aim of the study was to determine the effect of aceclofenac on the pharmacokinetics of phenytoin in rabbits. In a parallel design study, phenytoin 30 mg/kg/day per oral was given daily for seven days. On day 7, blood samples were taken at various time intervals between 0-24 hours. In aceclofenac group, phenytoin was administered for seven days as above. On day 8, aceclofenac 14 mg/kg along with phenytoin 30 mg/kg/day was administered and blood samples drawn as above. Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated. In aceclofenac group, there was decrease in t½el than phenytoin group significant changes were observed in the pharmacokinetic parameters in aceclofenac treated group. These results suggest that aceclofenac alter the pharmacokinetics of phenytoin. Confirmation of these results in human studies will warrant changes in phenytoin dose or frequency when aceclofenac is co-administered with it.

Pharmacotherapy of heart failure with normal ejection fraction (HFNEF)--a systematic review.

AIM: The pharmacotherapy for heart failure with normal ejection fraction (HFNEF) is not as well defined as that for the treatment for heart failure with reduced ejection fraction (HFREF). Studies of the various drugs given for HFNEF have revealed conflicting results. The aim of this systematic review was to determine whether there is any benefit with pharmacotherapy in HFNEF in terms of cardiac outcomes. METHODS: Electronic and printed sources were searched until August 2010 for randomized controlled clinical trials (RCTs) comparing drug therapy with placebo in HFNEF. Weighted mean difference and pooled odds ratio (OR) with 95% confidence intervals were calculated. RESULTS: A total of six RCTs including 8410 patients with a mean follow-up period of 21 months were included in the analysis. Although there were no significant differences in all cause mortality between the two groups (pooled OR 0.95, 95% CI 0.79, 1.13, P= 0.55), the subgroup analysis revealed a slight but non significant advantage with the ß-adrenoceptor blocker group. There was no significant difference between the two groups in terms of cardiovascular mortality, hospitalization, worsening heart failure, ejection fraction, E : A ratio, deceleration time and E : E' ratio. CONCLUSION: There was no significant benefit of pharmacotherapy in HFNEF. This might have been because of a lack of stringent inclusion criteria for patients in the trials and lower power of the studies. Hence trials with well defined inclusion criteria, better power, longer follow-up periods and with echocardiographic parameters as endpoints are required to shed further light on this topic.

In vitro physicochemical characterization and short term in vivo tolerability study of ethionamide loaded PLGA nanoparticles: potentially effective agent for multidrug resistant tuberculosis.

PURPOSE: To achieve prolonged drug release for the treatment of multidrug resistant tuberculosis and to improve the patient compliance, ethionamide loaded PLGA nanoparticles were developed. MATERIAL AND METHODS: They were developed by solvent evaporation method and optimized. The optimized formulation was subjected to various physico-chemical characterization, in vitro release studies and in vivo tolerability study. RESULTS AND DISCUSSION: There was no significant drug-polymer interaction and drug was encapsulated as crystalline form in nanoparticles. In vitro release was sustained up to 15 days in various media. Ethionamide loaded nanoparticles in mice did not reveal any statistically significant treatment related effects on body weight gain and clinical signs. Likewise, no treatment-related toxic effect was found in hematology, clinical chemistry and histopathology. Our results indicate the development of an orally effective safe formulation of ethionamide with sustained release property. CONCLUSION: Hence, ethionamide loaded nanoparticles offer excellent potential for further preclinical and clinical studies.

Effects of three different doses of a fruit extract of Terminalia chebula on metabolic components of metabolic syndrome, in a rat model.

There is documented evidence of the use of Terminalia chebula for various ailments in the Ayurvedic literature. The extract has been shown to possess glucose lowering activity and to improve insulin sensitivity in animal models of type 2 diabetes mellitus. The present study was carried out to study the dose response relationship of this extract in a rat model of metabolic syndrome. Six groups of rats were fed a high fructose diet (HFD) for a period of 20 days to induce metabolic syndrome. Three doses of fruit extract of T. chebula 50, 100 and 200 mg/kg were administered orally and pioglitazone 2.7 mg/kg was used as a positive control. Blood samples were collected at days 0, 20 and 40 from the tail vein. Systolic blood pressure (SBP) was measured using the tail cuff method and an oral glucose tolerance test (OGTT) was done on the day of blood collection. Administration of HFD for 20 days significantly increased fasting blood glucose (FBG), SBP and the area under the curve of OGTT. On day 40 the FBG in the 50, 100 and 200 mg/kg group was 97.33 +/- 5.82 (NS), 86.83 +/- 5.08 (p = 0.038) and 85.67 +/- 6.74 (p = 0.15), respectively. These results show that the fruit extract of T. chebula exerts a significant and dose-dependent glucose lowering effect in the rat model of metabolic syndrome.

Evaluation of cost of treatment of drug-related events in a tertiary care public sector hospital in Northern India: a prospective study.

AIMS: Drug related events (DREs) contribute significantly to hospital admissions. These are largely preventable events and require optimum use of the therapeutic agents. The study was conducted to analyze the cost of treatment of DREs. PATIENTS & METHODS: All visits to medical emergency department of a tertiary care public sector hospital in northern India were recorded in a prospective, non-interventional manner over a period of 4 months. DREs were recognized and were followed up till their stay in the hospital. Data about the cost generating components of direct and indirect costs of treatment of DREs were collected. The projected cost of treatment of the same DREs in a private sector hospital was estimated and compared. RESULTS: Out of 1833 admissions, 92(5.01%) were due to DREs. Maximum cases were due to non compliance (66%) followed by ADR (28%) and drug overdose (6%). The common DREs leading to ED visits were cerebrovascular accident (19.44%), followed by accelerated hypertension (18.36%) and diabetic ketoacidosis(14.04%). Total cost of management of all the 92 DREs in our hospital was calculated to be INR17,37,339(Euro 30,215). The direct cost was INR1,72,961 (Euro 3008) and the approximate indirect cost was INR15,64,378 (Euro 27,206). The projected cost of management of all the 92 DREs was estimated to be INR63,63,872(Euro 1,01, 676) in a private sector hospital. CONCLUSION: The study shows that ADEs leading to emergency department visits and hospitalizations constitute a significant economic burden. Training of the patients and the prescribers may lessen the economic burden on the patient as well as the health care system.

Triple antiplatelet therapy vs. dual antiplatelet therapy in patients undergoing percutaneous coronary intervention: an evidence-based approach to answering a clinical query.

AIMS: Outcomes of patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare metal stents (BMS) have not been evaluated separately for specific dual and triple antiplatelet agent use. The purpose of this meta-analysis was to determine whether triple antiplatelet therapy (combination of clopidogrel, aspirin and cilostazol) has any advantage in efficacy compared with standard dual antiplatelet therapy (aspirin and clopidogrel) in patients undergoing PCI. METHODS: Electronic and printed sources were searched till May 2008 for randomized controlled clinical trials (RCTs) of cilostazol in combination with aspirin and clopidogrel. Pooled weighted mean difference (WMD) and pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of four RCTs including 1457 patients with a median follow-up period of 6-9 months were included in the analysis. The rates of major adverse cardiac and/or cerebrovascular events (MACE/MACCE), stent thrombosis and bleeding were not significantly different between triple and dual antiplatelet therapy groups. Pooled analysis showed that cilostazol was associated with significantly decreased incidence of in segment restenosis (ISR) (OR 0.51, 95% CI 0.38, 0.68; P < 0.00001), increased minimum luminal diameter (MLD) (WMD 0.16, 95% CI 0.10, 0.22; P < 0.00001) for both DES and BMS and also individually. However, the rates of target vessel revascularization (OR 0.45, 95% CI 0.25, 0.83; P = 0.01 and late lumen loss (pooled WMD 0.14, 95% CI 0.2, 0.07; P = 0.001) were decreased significantly only in the DES group receiving triple therapy. CONCLUSIONS: Cilostazol appears to be effective in reducing the rates of ISR without any significant benefit for MACE/MACCE.

Pancreatic enzymes for chronic pancreatitis.

BACKGROUND: The efficacy of pancreatic enzymes in reducing pain and improving steatorrhoea is debatable and the evidence base for their utility needs to be determined. OBJECTIVES: To evaluate the efficacy of pancreatic enzymes in patients with chronic pancreatitis. The specific objectives were to compare the following: 1) pancreatic enzyme versus placebo; 2) different pancreatic enzyme preparations and 3) different dosage schedules of the enzyme preparations. We evaluated the following outcomes: change in frequency of abdominal pain, duration of pain episodes, intensity of pain, weight loss, steatorrhoea, faecal fat and quality of life. SEARCH STRATEGY: We devised a search strategy to detect all published and unpublished literature and the search included CENTRAL (The Cochrane Library 2009, issue 1), MEDLINE (1965 to February 2009) and EMBASE (1974 to Feburary 2009). We handsearched reference lists and published abstracts from conference proceedings to identify further relevant trials. The date of the last search was April 2009. SELECTION CRITERIA: Randomised controlled trials with or without blinding. We included abstracts or unpublished data if sufficient information was available. DATA COLLECTION AND ANALYSIS: Two authors independently extracted and pooled the data pertinent to study outcomes. We combined continuous data using standardised mean difference (SMD) with 95% confidence interval (CI) and calculated the odds ratio (OR) for dichotomous data (95% CI). MAIN RESULTS: Ten trials, involving 361 participants, satisfied the inclusion criteria. All the trials were randomised; two had a parallel design while the remainder had a cross-over design. Although some individual studies reported a beneficial effect of pancreatic enzyme over placebo in improving pain, incidence of steatorrhoea and analgesic consumption, the results of the studies could not be pooled for these outcomes. With the use of pancreatic enzymes, we observed a non-significant benefit for weight loss (kg) (SMD 0.06; 95% CI -0.23 to 0.34); a significant reduction in faecal fat (g/day) (SMD -1.03; 95% CI -1.60 to -0.46) and non-significant difference in subjects' Clinical Global Impression of Disease Symptom Scale (SMD -0.63; 95% CI -1.41 to 0.14). We found no significant benefit in reducing faecal fat with any particular schedule of enzyme preparation or type of enzyme.Another small study did not show any significant benefit of timing the administration of enzyme preparations in relation to meals on faecal fat. AUTHORS' CONCLUSIONS: The role of pancreatic enzymes for abdominal pain, weight loss, steatorrhoea, analgesic use and quality of life in patients with chronic pancreatitis remains equivocal. Good quality, adequately powered studies are much warranted.

Pharmacokinetic interaction of single dose of piperine with steady-state carbamazepine in epilepsy patients.

Piperine, the active principle of piper species, is commonly used as a spice and adjuvant in various traditional systems of medicine. It has been known as a bioavailability-enhancer. The present study aimed at evaluating the effect of piperine on the steady-state pharmacokinetics of a single dose of carbamazepine in poorly controlled epilepsy patients on carbamazepine monotherapy. Patients (n = 10 each) receiving either 300 mg or 500 mg dose of carbamazepine twice daily were selected. After administration of carbamazepine, venous blood samples were collected at 0, 0.5, 1, 2, 4, 6, 9, 12 h. Subsequently, piperine (20 mg p.o.) was administered along with carbamazepine and samples were collected similarly. The pharmacokinetic parameters were compared by Students t-test. Piperine significantly increased the mean plasma concentrations of carbamazepine at most of the time points in both dose groups. There was a significant increase in AUC(0-12hr) (p < 0.001), average C(ss) (p < 0.001), t(1\2el) (p < 0.05) and a decrease in K(el) (p < 0.05), in both the dose groups, whereas changes in K(a) and t(1\2a) were not significant. Cmax (p < 0.01) and t(max) (p < 0.01) were increased significantly following piperine administration in the 500 mg dose group; however, these parameters were not significant in the lower dose group. Piperine could significantly enhance the oral bioavailability of carbamazepine, possibly by decreasing the elimination and/or by increasing its absorption.

Randomised Comparison of Safety Profile and Short Term Response of Itraconazole, Voriconazole and Amphotericin B in the Management of Chronic Invasive Fungal Rhinosinusitis.

Chronic invasive fungal rhino sinusitis (CIFS) is a well described clinical entity characterized by mucosal and sub mucosal infiltration of mycotic organisms and angio-centric extension into orbital and intracranial structures. Itraconazole, Voriconazole and Amphotericin B are commonly used for CIFS. In the present study we have evaluated short term clinical response of these drugs. Thirty diagnosed patients of CIFS who presented to us from January 2011 to December 2015 were divided into three groups randomly. Group A, B and C received Itraconazole, Voriconazole and Amphotericin respectively. Visual Analogue scale (VAS), Lund Mackay (LM) radiological scores and Kupferberg's nasal endoscopic grades were seen and compared in all patients before treatment, after primary surgical debridement and biopsy and after post biopsy antifungal drug treatment. We assessed the serum drug levels using HPLC assay at 4 and 8 weeks of therapy and correlated them for efficacy and safety. All the groups had significant improvement after treatment compared to beginning of study. Inter group comparison showed that mean LM, NE and VAS scores were significantly better in Voriconazole group compared to Itraconazole and amphotericin B therapy. The reduction of these objective parameters with treatment was also significantly high in Voriconazole group compared to the other two groups. Voriconazole has shown to be the most effective treatment modality for chronic invasive fungal sinusitis compared to other commonly used drugs such as Itraconazole and Amphotericin B.

Bacopa monniera exerts antiamnesic effect on diazepam-induced anterograde amnesia in mice.

RATIONALE: As Benzodiazepines are known to produce amnesia by involvement of the GABAergic system, we examined Bacopa monniera, an herb known for memory enhancement for reversal of memory deficits caused by diazepam. OBJECTIVES: The objective of the study was to study the effect of standardized extract of B. monniera on diazepam-induced amnesia in mice using Morris water maze. MATERIALS AND METHODS: We used the rota rod test as a screening measure for muscle incoordination followed by the Morris water maze scale to evaluate the effect of B. monniera on amnesia. The index of acquisition and retrieval was recorded with varying doses of Bacopa. RESULTS: The results revealed antiamnesic effects of B. monniera (120 mg kg(-1) oral) on diazepam (1.75 mg kg(-1) intraperitoneal)-induced amnesia. The degree of reversal by Bacopa was significant as it progressively reduced escape latency time when mice treated with diazepam were subjected to acquisition trials. CONCLUSIONS: The antiamnesic effects of Bacopa suggest likely a gamma-aminobutyric acid-benzodiazepine pathway possibly affecting long-term potentiation.

Effects of etoricoxib on the pharmacokinetics of phenytoin.

Etoricoxib is presently the most commonly prescribed cyclooxygenase-2 (Cox-2) inhibitor for chronic pain and inflammatory conditions. In clinical practice, phenytoin and etoricoxib are used in chronic conditions of generalized seizure with concomitant chronic pain. Hence, there are chances of drug-drug interaction because modulations of isoenzymes involved in metabolism CYP2C9/10 and CYP2C19 which partially inhibited by etoricoxib. It is important to maintain the therapeutic level of phenytoin in plasma for effective control of seizure. So, the aim of the study was to determine the effect of etoricoxib on the pharmacokinetics of phenytoin in rabbits. In a parallel design study, phenytoin (30 mg/kg/day) was given daily for seven days. On day 7, blood samples were taken at various time intervals between 0-24 h. In etoricoxib group, phenytoin was administered for seven days as above. On day 8, etoricoxib (5.6 mg/kg) along with phenytoin (30 mg/kg/day) was administered and blood samples were drawn as above. Plasma phenytoin levels were assayed by HPLC and pharmacokinetic parameters were calculated. In etoricoxib group, there was a decrease in t(1/2)a phenytoin and t(1/2)el decreased significantly as compared to phenytoin group. Significant changes were observed in the pharmacokinetic parameters in etoricoxib-treated group. These results suggest that etoricoxib alters the pharmacokinetics of phenytoin. Confirmation of these results in human studies will warrant changes in phenytoin dose or frequency when etoricoxib is co-administered with it.

Recent advances in the pharmacotherapy of chronic anal fissure: an update.

Surgical sphincterotomy reduces anal tone and sphincter spasm and promotes ulcer healing. Because the surgery is associated with the side effect of faecal incontinence, pharmacological agents to treat chronic anal fissure have been explored recently. Glyceryl trinitrate (GTN) ointment (0.2%) has an efficacy of up to 68% in healing chronic anal fissure, but it is associated with headache as the major and most common side effect. Though botulinum toxin injected into the anal sphincter healed over 80% of chronic anal fissures, it is more invasive and expensive than GTN therapy. Diltiazem ointment achieved healing of chronic anal fissure comparable to 0.2% GTN ointment but was associated with fewer side effects. Other drugs that have been tried are lidocaine, the alpha-adrenergic antagonist indoramin, and the potassium channel opener minoxidil.

Comparison of efficacy, tolerability, and cost of iron polymaltose complex with ferrous sulphate in the treatment of iron deficiency anemia in pregnant women.

BACKGROUND: The efficacy of iron polymaltose complex (IPC) in the treatment of iron deficiency anemia (IDA) during pregnancy has not been well established, and the evidence is inconclusive. AIMS: The aim of the study was to compare efficacy, safety, compliance, and cost-effectiveness of IPC with ferrous sulphate (FS) in pregnant patients. SETTINGS AND DESIGNS: The randomized, double-blind, parallel-group study was conducted in the Department of Pharmacology in collaboration with the Department of Obstetrics and Gynaecology Postgraduate Institute of Medical Education and Research, Chandigarh, India. METHODS: One hundred pregnant women aged 20-40 years at 14 to 27 weeks' gestation, with hemoglobin (Hb) < 9 g/dL, and serum ferritin < 12 mcg/L, were classified into 2 groups. One group received IPC (100 mg elemental iron), and the other group received FS (120 mg elemental iron) daily for 8 weeks. At Week 0 and Week 8, Hb, packed cell volume (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), serum iron, and serum ferritin were measured. Compliance with study medication was determined by pill counting at each visit. Cost minimization analysis was done to compare the costs of the 2 treatments. STATISTICAL ANALYSIS: Data are expressed as mean -/+ SD. Paired and unpaired 't' test were used to analyze differences within groups and between groups. Chi-square (x2) test was used to analyze primary efficacy parameters and adverse drug reactions (ADR). RESULTS: Statistically significant increases in Hb, PCV, MCV, MCH, MCHC, serum iron, and serum ferritin levels were seen at the end of 8 weeks of treatment in both groups. The overall adverse effects were more common in the FS group compared with the IPC group [41 (78%) vs 15 (31%), P < .001]. The compliance rate was significantly (P < .05) higher for the IPC (91%) group than for the FS (87%) group. The average total cost (direct + indirect) of treatment of anemia was comparable between the 2 groups. CONCLUSION: The results of the present study suggest that IPC can be considered as a useful alternative formulation for the treatment of IDA during pregnancy for those patients who cannot tolerate other iron preparations (ferrous form); this is an important finding, as compliance is a significant concern during pregnancy.

The "Statinth" wonder of the world: a panacea for all illnesses or a bubble about to burst.

After the introduction of statins in the market as effective lipid lowering agents, they were shown to have effects other than lipid lowering. These actions were collectively referred to as 'pleiotropic actions of statins.' Pleiotropism of statins formed the basis for evaluating statins for several indications other than lipid lowering. Evidence both in favour and against is available for several of these indications. The current review attempts to critically summarise the available data for each of these indications.

Estimating the diagnostic accuracy of procalcitonin as a marker of the severity of acute pancreatitis: a meta-analytic approach.

CONTEXT: Approximately 15-20% of cases of acute pancreatitis are categorized as severe. There is a lack of accurate predictors of disease severity. Several studies have evaluated the usefulness of procalcitonin as a marker of severe disease. Reports regarding the diagnostic accuracy of procalcitonin are conflicting. OBJECTIVE: The present meta-analysis was carried out to evaluate the relevance of procalcitonin as a predictor of disease severity. METHODS: Two investigators working independently attempted to locate eligible studies by electronic and manual means. Studies in which at least one of the markers of disease severity was procalcitonin were included for analysis. For all the studies included, the following parameters were calculated: true positive, false negative, false positive and true negative. A summary receiver operating characteristic (SROC) curve was generated from these parameters. RESULTS: Four studies were finally included in the analysis. The unweighted regression line parameters b and i were 3.633 and 1.399, respectively. The values for b and i for weighted regression line were 3.637 and 1.428. The SROC curve generated demonstrated that procalcitonin is not a good predictor of the severity of acute pancreatitis. CONCLUSION: The available data indicates that procalcitonin cannot be considered a good marker for assessing the severity of pancreatitis.

Effect of inhaled steroids on bone mineral density: a meta-analysis.

Inhaled corticosteroids are currently considered first-line agents for the treatment of asthma. Medium- to long-term administration of inhaled steroids may be associated with bone loss. Various studies have evaluated their effect on bone mineral density (BMD); some have shown loss of BMD with steroid treatment, but others have failed to do so. The present meta-analysis was undertaken to determine the possible effect of inhaled steroids on bone density. Literature was collected using computerized (MEDLINE) and manual searches using index medicus and checking cross-references of the published articles. The studies identified were screened for inclusion/exclusion criteria. Grouped means (XT/XC) and pooled standard deviations (SDT/SDC) for the treatment group (XT[95% CI] = 1.144 [1.019-1.269]; SDT = 0.163, g/cm2) and control group (XC [95% CI] = 1.193 [1.073-1.313]; SDC = 0.157, g/cm2) were worked out respectively for the selected studies. Finally, a comparison between grouped means of steroid-treated and control groups was done by two-sample t-test at the 5% level of significance. The results of the meta-analysis showed that although the mean BMD of the steroid-treated group was reduced by 4.1% as compared to the control group, this failed to achieve statistical significance (p = 0.8; 95% CI for the mean difference between two groups = 0.028-0.070 g/cm2). It is concluded that inhaled steroids for the treatment of asthma can be considered safe with respect to their effect on bone loss.