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Rheumatoid arthritis (RA) is a chronic multisystem disease. A characteristic feature of RA is persistent inflammatory synovitis, usually involving the peripheral joints in a symmetric distribution. The prevalence of RA is approximately 0.8% of the population (range: 0.3–2.1%); women are affected approximately 3 times more often than men. The current therapeutic approach is to start a disease-modifying agent early in the illness to prevent eventual joint damage. Older disease-modifying anti-rheumatic drugs include methotrexate, sulphasalazine and hydroxychloroquine. Newer ones such as leflunomide and cyclosporin are also used. A recent advance in the management of rheumatoid arthritis is the use of biological agents, which block certain key molecules involved in the pathogenesis of the illness. They include tumour-necrosis-factor-α-blocking agents such as infliximab, etanercept and adalimumab, the anti-CD-20 agent, rituximab, and CTLA-4 Ig abatacept. The present study was planned with the aim of evaluating the efficacy of such newer biological therapies in refractory RA at various time points. Databases including Medline, Embase and the Cochrane Library were searched for all relevant studies up to January 2007. A total of 26 studies were included in present meta-analysis. The method of DerSimonian and Laird [Control Clin Trials 1986;7:177–188] was used to calculated a pooled odds ratio (OR) for the American College of Rheumatology (ACR) criteria 20, 50 and 70, at 24, 54 and 96 weeks. The overall pooled OR were found to be significantly more than the placebo at all 3 time points for all 3 criteria (ACR 20, 50 70). In conclusion, biologicals as a group are highly effective in the treatment of RA. Biologicals were efficacious both in treatment naïve and methotrexate-refractory patients.

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.

The current study investigated the hepatoprotective effect of trans-Chalcone in carbon tetrachloride (CCl4) and paracetamol (PCM) induced liver damage in rats. Administration of CCl4 and PCM (1 mL/kg, i.p., 3 days, and 2 g/kg, p.o., single dose, respectively) produced hepatic injury. Ponderal changes (percent change in body mass and relative liver mass) and biochemical parameters (serum ALT, AST, ALP, bilirubin) were estimated. The markers of oxidative and nitrosative stress (TBARS, reduced GSH, nitrite and nitrate), hepatic fibrosis (TGF-β1, collagen content), hepatic inflammation (TNF-α), and histopathological study were evaluated. trans-Chalcone (5, 10, and 20 mg/kg, i.p.) was found to be beneficial as demonstrated by significant reversal of liver histology by perceptible reduction of inflammatory cell infiltration with regenerative changes in hepatocytes. Improvement in percent change in body mass and significant reduction in relative liver mass were observed. Marked reduction in serum levels of ALT, AST, ALP, and bilirubin were noted. Decreases in TBARS and nitrites and nitrates and increases in reduced GSH levels were noted. Hepatic fibrosis and inflammation were significantly decreased. The findings indicate a novel hepatoprotective role for trans-Chalcone by improving hepatic injury by possible actions such as anti-oxidant, anti-nitrosative, anti-fibrotic, and anti-inflammatory. Hence, it can be used as promising hepatoprotective agent.

Context: β-Aescin has anti-inflammatory, anti-oxidant and antiedematous properties.Objective: The present study investigated the hepatoprotective effect and underlying mechanisms of β-aescin in CCl4-induced liver damage.Materials and methods: Thirty-five Wistar rats were divided into six groups: normal control, CCl4 control, silymarin (50 mg/kg, p.o) and β-aescin (0.9, 1.8 and 3.6 mg/kg, i.p.) treatment for 14 d. CCl4 (1 mL/kg, i.p. for 3 d) was administered to produce hepatic damage. Ponderal changes and liver marker enzymes were estimated. Hepatic oxidative and nitrosative stress was estimated by levels of thiobarbituric acid reactive substances (TBARS), glutathione (GSH) and nitrite/nitrate. Serum TGF-β1 and TNF-α were estimated by ELISA technique. Hepatic collagen and histopathological studies were carried out.Results: β-Aescin (3.6 mg/kg) markedly decreased CCl4-induced increased levels of ALT, AST, ALP (71.77 versus 206.7, 71.39 versus 171.82, 121.20 versus 259 IU/L, respectively), total bilirubin (0.41 versus 1.35 mg/dL), TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 μg/mL) and increased CCl4-induced decreased GSH levels (0.095 versus 0.048 μmol/mg protein). β-Aescin (3.6 mg/kg) induced focal regenerative changes in liver and markedly decreased TBARS (2.0 versus 8.83 nmol MDA/mg protein), nitrite/nitrate (352.50 versus 745.15 μg/mL), TGF-β1 (92.28 versus 152.1 pg/mL), collagen content (110.75 versus 301.74 μmol/100 mg tissue) and TNF-α (92.82 versus 170.56 pg/mL) when compared with CCl4 control.Discussion and conclusion: The findings suggest that β-aescin has a protective effect on CCl4-induced liver injury, exhibited via its anti-inflammatory, antioxidative, antinitrosative and antifibrotic properties inducing repair regeneration of liver. Hence, it can be used as a promising hepatoprotective agent.

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.

Background:The National Coordination Centre-Pharmacovigilance Programme of India (NCC-PvPI), Indian Pharmacopoeia Commission works under the aegis of Ministry of Health and Family Welfare, Government of India. It promotes patient safety in India and also supports postmarketing surveillance programs. Currently, almost hundred thousand case reports are submitted to NCC-PvPI each year through its 250 ADR Monitoring Centers (AMCs) located across India, and India is the one of the top ten contributor countries under WHO-Uppsala Monitoring Centre since 2012 and start issuing drug safety alerts from March 2016.Aim:This study aims to highlight the drug safety alerts issued by NCC-PvPI from March 2016 to June 2017 and urgent need for further monitoring by adopting targeted spontaneous reporting (TSR) methodology at AMCs and its impact on the NCC's drug safety database, i.e., VigiFlow in India.Methodology:A retrospective analysis was done for the reported unlisted ADRs by various AMCs to PvPI through VigiFlow, i.e., individual case safety report (ICSR) management system at NCC, where these unlisted drug-ADR combinations considered and issued as drug safety alerts for further reporting these to NCC, if any detected at healthcare settings during routine clinical practice by healthcare professionals.Results:From July 2011 to June 2017, NCC-PvPI was collated 250,787 ICSRs and contributed to WHO international drug safety database, i.e., VigiBase, from these ICSRs; NCC-PvPI was issued 56 drug safety alerts from March 2016 to June 2017.Conclusion:In India, spontaneous reporting of ADRs existed since 1998 under passive surveillance method, but there is an urgent need to initiate TSR, which is a complementary method to spontaneous reporting on these drug safety alerts for further regulatory action by Central Drugs Standard Control Organization.

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