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.

Drug utilization study in medical emergency unit of a tertiary care hospital in north India.

Objective. To generate data on the drug utilization pattern and cost of drug treatment and to determine the rationality of prescriptions. Methods. A retrospective cross-sectional drug utilization study was conducted in the medical emergency unit of our hospital. Patient case records were reviewed to extract data on the pattern of drug use. Cost of drug treatment for the emergency visit was calculated by referring to the cost mentioned in Monthly Index of Medical Specialties and the rationality of prescriptions was evaluated using WHO core indicators of drug utilization. Results. 1100 case records were reviewed. Majority of patients received proton pump inhibitors followed by multivitamins. The median cost per prescription was 119.23$ (7.32$-7663.46$). Majority (49.9%) of drug cost was driven by antibiotics alone. An average of 4.9 drugs was prescribed per prescription. There were 14.89% encounters with antibiotics. 75.17% of the drugs were given as injectables and only 29.27% of the drugs were prescribed as generics. Conclusion. There is need to rationalize the drug therapy in terms of increasing prescribing of drugs by generic name and to avoid overuse of PPIs and multivitamins in emergency unit. Also the hospital pharmacy should be encouraged to procure more cost effective alternative antibiotics in future.

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.

Effect of levofloxacin on lithium - a pharmacokinetic study in rabbits.

The aim of this study was to evaluate potential drug-drug interaction between lithium and levofloxacin. The study was conducted on New Zealand white rabbits with three groups having two subgroups each (n = 12). The first group compared the pharmacokinetic (Pk) parameters of lithium when lithium was given as a single dose (56 mg/kg) and when lithium was co-administered with levofloxacin (35 mg/kg). The second group compared the Pk parameters of lithium when lithium was given for 6 days alone and when levofloxacin was given on the sixth day after lithium steady-state levels were achieved. The third group compared the Pk parameters of lithium when lithium was given alone for 8 days and levofloxacin was given on days 6, 7, and 8 along with lithium. Apart from this, creatinine levels were also measured to detect nephrotoxicity effects because of this co-administration. It was found that there was increase in lithium levels in all three groups. The increase was significant when a single dose of levofloxacin was administered with steady-state level of lithium (C(max) of lithium: 2.54 ± 0.15 vs 2.79 ± 0.12 mm, P < 0.001 and AUC(0-α) of lithium: 24.36 ± 3.68 vs 31.88 ± 4.83 mmol/mL h, P < 0.001). The increase in lithium levels was also significant when levofloxacin was coprescribed for 3 days after lithium steady-state levels were achieved (C(max) increased from 2.72 ± 0.29 to 3.96 ± 0.29 mm, P < 0.001 and AUC(0-α) increased from 27.1 ± 4.96 to 42.64 ± 4.94 mmol/mL h). Levofloxacin increases lithium levels when they are co-administered, and this interaction might be clinically significant as they may be coprescribed.

A prospective observational study on different poisoning cases and their outcomes in a tertiary care hospital.

OBJECTIVES: Poisonings and snake bites constitute major health-care problems worldwide. This observational study was conducted to identify factors associated with outcomes in such cases and to suggest strategies to improve them. METHODS: This is a prospective study conducted in the emergency medicine department of a tertiary care hospital. The study included 102 poisoning and 64 snake bite cases. Data regarding demographics, mode of poisoning, lag time in treatment, first aid, outside and indoor treatment, co-morbid illness, duration of hospitalisation and final outcome were collected in a prestructured proforma. RESULTS: The age of the patients ranged from 11 to 68 years and incidence was more common among males (69.9%) compared to females (30.1%). The major types of poisonings included organophosphorus compounds (16.3%), aluminium phosphide (12%), drug overdose (10.8%) and corrosives (6%). There were 18 (18.6%) and 1 (1.6%) deaths in poisoning and snake bite cases, respectively. In poisoning cases, the duration of hospitalisation was significantly decreased if patient received outside treatment (p = 0.02) and if he or she had lesser lag time in reaching the hospital (p = 0.009). CONCLUSIONS: Measures to reduce lag time and provide immediate treatment at initial encounter may be effective in reducing duration of hospitalisation and possibly mortality in poisoning and snake bite cases.

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.

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.

Toxic Epidermal Necrolysis induced by rarely implicated drugs.

Toxic Epidermal Necrolysis (TEN) and Steven-Johnson Syndrome (SJS) are serious disorders commonly caused as idiosyncratic reactions to drugs, the most common ones being oxicams, anticonvulsants, allopurinol, and sulfonamides. We present a case of TEN in a patient who developed the lesions after ingesting multiple drugs including paracetamol, metoclopramide, antihistamines, and multivitamins. These drugs have rarely been implicated in this disorder. The suspected drugs in this case were paracetamol and metoclopramide. However, the role of other drugs could not be ruled out definitely. The patient was managed with antibiotics, corticosteroids, and parenteral fluids and recovered well.

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.

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.

Safety and efficacy of vitamin-based antioxidant therapy in patients with severe acute pancreatitis: a randomized controlled trial.

BACKGROUND/AIM: Oxidative stress plays a major role in the pathogenesis of pancreatitis. Antioxidant therapy in the form of high-dose vitamin has been used for the treatment of severe acute pancreatitis with equivocal results. We wished to evaluate the efficacy and safety of antioxidant (vitamin A, vitamin C, vitamin E) therapy in patients with severe acute pancreatitis. SETTING AND DESIGN: This was a single-center, prospective, randomized, open-label with blinded endpoint assessment study of antioxidant therapy, conducted in the emergency department attached to our hospital. MATERIALS AND METHODS: Thirty-nine patients with severe acute pancreatitis were randomly assigned to antioxidant treatment group (n=19) or a control group (n=20) within 96 hours of developing symptoms. Patients in the antioxidant group received antioxidants (vitamin A, vitamin E, vitamin C) in addition to the standard treatment provided to both the groups for a period of 14 days. The primary outcome variable was presence of organ dysfunction at day 7. The secondary outcome variables were length of hospital stay, multiorgan dysfunction (MODS) at day 7, recovery at the end of 4 weeks, complications, and mortality. The change in markers of oxidative stress from baseline was also measured. RESULTS: We demonstrated no significant difference in organ dysfunction (P=1.0), MODS (P=0.8), and length of hospital stay (P=0.29) between the two groups. All the patients survived in the antioxidant-treated group, whereas two patients died in the control group. The change in the levels of malondialdehyde, superoxide dismutase, and reduced glutathione were not significantly different in the two groups at day 7. Univariate analysis showed marginal benefit with antioxidant treatment (P=0.034) in patients with severe acute pancreatitis. CONCLUSIONS: This randomized study demonstrates that there is no significant benefit from antioxidant therapy in patients with established severe acute pancreatitis.

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.

Pharmacokinetics and tissue distribution studies of orally administered nanoparticles encapsulated ethionamide used as potential drug delivery system in management of multi-drug resistant tuberculosis.

Sustained release nanoformulations of second line anti-tubercular drugs can help in reducing their dosing frequency and improve patient's compliance in multi-drug resistant tuberculosis (MDR TB). The objective of the current study was to investigate the pharmacokinetics and tissues distribution of ethionamide encapsulated in poly (DL-lactide-co-glycolide) (PLGA) nanoparticles. The drug loaded nanoparticles were 286 ± 26 nm in size with narrow size distribution, and zeta-potential was -13 ± 2.5 mV. The drug encapsulation efficiency and loading capacity were 35.2 ± 3.1%w/w and 38.6 ± 2.3%w/w, respectively. Ethionamide-loaded nanoparticles were administered orally to mice at two different doses and the control group received free (unencapsulated) ethionamide. Ethionamide-loaded PLGA nanoparticles produced sustained release of ethionamide for 6 days in plasma against 6 h for free ethionamide. The Ethionamide was detected in organs (lung, liver, and spleen) for up to 5-7 days in the case of encapsulated ethionamide, whereas free ethionamide was cleared within 12 h. Ethionamide-loaded PLGA nanoparticles exhibited significant improvement in pharmacokinetic parameters, i.e. C(max), t(max), AUC0₋∞, AUMC0₋∞, and MRT of encapsulated ethionamide as compared with free ethionamide. Drug in nanoparticles also exhibited a dose proportional increase in the AUC0₋∞ values. The pharmacodynamic parameters such as AUC0₋24/MIC, C(max)/MIC, and Time > MIC were also improved. PLGA nanoparticles of ethionamide have great potential in reducing dosing frequency of ethionamide in treatment of MDR TB.

Painful diabetic neuropathy: an update.

Diabetes, a silent killer, is a leading cause of neuropathy. Around 50% of diabetic patients develop peripheral neuropathy in 25 years. Painful diabetic neuropathy manifests as burning, excruciating, stabbing or intractable type of pain or presents with tingling or numbness. The pathophysiology of this condition is due to primarily metabolic and vascular factors. There is increase in sorbitol and fructose, glycated endproducts, reactive oxygen species and activation of protein kinase C in the diabetic state. All these factors lead to direct damage to the nerves. The first step in the management of painful diabetic neuropathy is a tight glycaemic control. Currently there is no drug which can halt or reverse the progression of the disease. Most of the therapies prevalent aim at providing symptomatic relief. Antidepressants like tricyclic antidepressants (TCAs) and selective norepinephrine reuptake inhibitors (SNRIs) have good efficacy in controlling the symptoms. Selective serotonin reuptake inhibitors have not shown the same consistent results. Anticonvulsants including pregabalin, gabapentin and lamotrigine have shown good results in the control of symptoms whereas same was not found with carbamazepine, oxcarbazepine and topiramate. Topical agents (capsaicin, topical nitrates and topical TCAs) and local anaesthetics have also been used with good results. Use of opioids and non steroidal anti-inflammatory drugs although common but is not preferable. The newer therapies under studies are NMDA antagonists, aldose reductase inhibitors, neurotropic factors, vascular endothelial growth factor, Gamma linolenic acid, protein kinase C beta inhibitors, immune therapy, hyperbaric oxygen and alpha lipoic acid.

Rosiglitazone promotes pancreatic regeneration in experimental model of acute pancreatitis.

Acute pancreatitis is an inflammatory disease of the pancreas caused by release of activated digestive enzymes in the pancreas. A number of therapeutic options have been explored for acute pancreatitis, but none has been unambiguously proven to be effective. Rosiglitazone has been shown to be efficacious in acute pancreatitis; thus, the present study was planned to evaluate the effect of rosiglitazone on pancreatic regeneration. Pancreatitis was induced by l-arginine in rats which were divided into three groups: cholecystokinin (CCK-8), rosiglitazone and vehicle. Rats were sacrificed at four time points after induction of pancreatitis i.e. 24h, day 3, day 14 and day 28 for determination of biochemical parameters and histological examination. Rate of DNA synthesis, immunohistochemistry and RT-PCR were performed at day 3 and day 7. Drug administration was started 2h after last L-arginine injection and continued till the day of sacrifice. The lower levels of enzyme in rosiglitazone-treated group compared to vehicle group proved the efficacy of rosiglitazone treatment in reducing severity of acute pancreatitis. The nucleic acid content and rate of DNA synthesis were significantly higher in rosiglitazone group indicating promotion of pancreatic regeneration. The histopathological score were lower in rosiglitazone group. Rosiglitazone treatment promoted pancreatic regeneration after acute injury. Currently, only symptomatic treatment is available, regeneration of pancreatic tissue can be a future strategy in the management of acute pancreatitis. Further studies are required to support the findings of the present study.

Beneficial effects of Emblica officinalis in L-arginine-induced acute pancreatitis in rats.

Acute necrotizing pancreatitis is characterized by focal macroscopic or diffuse necrosis, hemorrhage, and vascular thrombosis of the pancreas. Current treatment options are limited to supportive and symptomatic interventions. A large amount of experimental work is ongoing to identify novel therapeutic agents for acute pancreatitis. The present study was carried out to explore the beneficial effects of Emblica officinalis, a medicinal plant of India, on acute pancreatitis. Ascorbic acid is one of the major chemical components of E. officinalis, so a vitamin C group was included for comparison. Acute pancreatitis was induced by L-arginine. Rats were divided into the following groups: control (saline), arginine + saline, arginine + E. officinalis, and arginine + vitamin C. Animals in each group were sacrificed at 24 hours and 3, 14, and 28 days after pancreatitis induction for determination of biochemical parameters and histological examination. For rate of DNA synthesis and immunohistochemical studies, animals were sacrificed on Day 3 and Day 7. Drug administration was started 2 hours after the last arginine injection and continued until the day of sacrifice. E. officinalis treatment was found to be beneficial for treating acute pancreatitis. Serum levels of lipase and interleukin-10 were significantly lower than in the arginine group. Nucleic acid content, rate of DNA synthesis, pancreatic proteins, and pancreatic amylase content were significantly improved. Histopathological examination showed significantly lower total scores in the Emblica group. Vitamin C was found to be less efficacious than E. officinalis for all outcome parameters. Thus E. officinalis treatment was found to be beneficial in acute necrotizing pancreatitis.

Correlation of seizures and biochemical parameters of oxidative stress in experimentally induced inflammatory rat models.

The role of oxidative stress in the pathogenesis of various conditions including epilepsy, inflammatory bowel disease and rheumatoid arthritis is evolving. The aim of this study was to find out the correlation between various inflammatory models with seizures and antioxidant parameters. Fifty-four male rats were divided into three groups of colitis, adjuvant arthritis and cotton wool granuloma (CWG). Each group had three subgroups of control, model and treatment. Thalidomide was used as treatment in colitis and arthritis group, whereas etoricoxib was used in CWG group. In colitis and arthritis groups, thalidomide was administered for 3 and 17 days, respectively, whereas etoricoxib was administered for 7 days in CWG group. At the end of treatment protocols, a subconvulsive dose of pentylenetetrazole (PTZ) (40 mg/kg i.p.) was injected intraperitoneally to note seizure onset and score. After confirming the presence of inflammation by morphological and histological studies, plasma and brain biochemical parameters of oxidative stress were estimated. The models of colitis, arthritis and CWG were effectively produced as evidenced by morphological scores (P < 0.001). Thalidomide reduced the morphological score (P < 0.002) and seizure grade (P < 0.001), whereas increased seizure onset (P < 0.001) in the arthritis group. There was an increase in malondialdehyde levels in the brain of thalidomide-treated groups (P < 0.002) and a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels. There was neither improvement in seizure nor any significant changes in lipid peroxidation and antioxidant enzyme levels in etoricoxib-treated group. Thalidomide was effective in reducing the extent of arthritis as well as reducing the seizure scoring and increasing seizure onset in the adjuvant arthritis group. As it increased lipid peroxidation and reduced SOD and GPx, further evaluation is necessary with respect to oxidative stress.

Melatonin treatment is beneficial in pancreatic repair process after experimental acute pancreatitis.

Current treatment options for acute pancreatitis are supportive and symptomatic. Due to lack of agents targeting the underlying pathophysiology a large amount of experimental work is going on to identify novel therapeutic agents. The present study was carried out to explore if melatonin can modulate the spontaneous regeneration process of the pancreas after experimentally induced acute pancreatitis. Rats were given two i.p. injections of l-arginine in a dose of 200mg/100g at an interval of 1h for induction of pancreatitis. After this rats were randomly divided into three groups i.e. saline, CCK-8 and melatonin. Drug treatment was started 2h after the last l-arginine injection and continued till the day of sacrifice. An additional only saline treated control group was included for comparison. Animals in each group were sacrificed at 24h, days 3, 14 and 28 after pancreatitis induction for determination of biochemical parameters (serum amylase, lipase and IL-10 and pancreatic amylase, total proteins and nucleic acid content) and histological examination. For rate of DNA synthesis and immunohistochemical studies animals were sacrificed at day 3 and day 7. Melatonin treatment was found to be beneficial in acute pancreatitis. Severity of acute pancreatitis was significantly reduced in melatonin group. Nucleic acid content, rate of DNA synthesis, pancreatic proteins and pancreatic amylase content were significantly improved. Histopathological examination showed significantly lower total scores in melatonin group. Results of melatonin group were comparable to that of positive control, CCK-8 group. Thus melatonin treatment was found to promote the spontaneous regeneration process of pancreatic tissue.

Evaluation of analgesic efficacy, gastrotoxicity and nephrotoxicity of fixed-dose combinations of nonselective, preferential and selective cyclooxygenase inhibitors with paracetamol in rats.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are combined with paracetamol (PCM) with a view to enhance analgesic efficacy and reduce gastric toxicity. However, there are reports of enhanced nephrotoxicity with nonselective NSAID with PCM combinations. The present study investigated the analgesic efficacy, gastrotoxicity and nephrotoxicity of nonselective, preferential and selective cyclooxygenase inhibitors and their combination with PCM in rats. Graded doses of ibuprofen, meloxicam and celecoxib alone and their combination with fixed dose of PCM were administered to the rats by gavage for 14 days. The results showed that PCM potentiated the analgesic effect of all three classes of NSAIDs significantly as evidenced by increase in tail-flick latency in radiant heat method. Dose-dependent gastromucosal damage was produced by all the drugs, which was augmented significantly with PCM in the form of decreased total carbohydrate/protein ratio of mucin and increased gastric ulcer index. It was further confirmed by histopathology of rat's stomach. The renal histopathology was conducted to evaluate inflammation, tubular damage, papillary necrosis, and interstitial changes. Increased nephrotoxicity was observed with all NSAIDs in dose-dependent manner and in combination with PCM. Our study revealed the augmented analgesia as well as enhanced gastrotoxicity and nephrotoxicity with all three major NSAIDs classes when combined with PCM. These findings highlighted the need for large pharmacoepidemiological studies to evaluate the magnitude of gastrotoxicity and nephrotoxicity in population who are on long-term treatment with NSAID combinations.

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.