Comparative Clinical Trial of Paracetamol alone and Vitamin C and E as an Add on Therapy in Patients Suffering From Primary Knee Osteoarthritis.

A randomized observational blind comparative clinical study was conducted to compare the antioxidant effect of vitamin C and E with paracetamol in patients of primary knee osteoarthritis.Subjects presenting with sign, symptoms of primary knee osteoarthritis were given paracetamol 1 gm (n=50) twice daily for 8 weeks and combinations of paracetamol 1gm bid with vitamin C (500 mg ) and E (200 IU) (n=50) twice daily for 8 weeks. Subjects completed an over all evaluation of symptoms relief on 2nd, 4th and 8th weeks of completed treatment were evaluated by clinical, routine laboratory and radiographic investigations for improvement of disease conditions, also for adverse drug reaction. On completion of 8 weeks of treatment it was observed that both the treatment group patients showed significant efficacy with better results with patients receiving antioxidant therapy in primary knee osteoarthritis patients (p<0.001) and adverse drug reaction were minor and none of patients complain of any severe adverse drug reaction. Present study indicate that antioxidant therapy can be used as an effective add on therapy in primary knee osteoarthritis.

Effect of combination of thalidomide and sulfasalazine in experimentally induced inflammatory bowel disease in rats.

Thalidomide provided significant protection against tri nitro benzene sulfonic acid induced colitis. Combination therapy also reduced colonic inflammation and all the biochemical parameters (myeloperoxidase assay, malondialdehyde assay and tumor necrosis factor- , estimation) were significant as compared to control as well as thalidomide alone treated group. Combination therapy showed additive effect of thalidomide which restored lipid peroxidation as well as reduced myeloperoxidase and TNF- towards the normal levels. Morphological and histological scores were significantly reduced in combination groups. In experimental model of colitis, oral administration of thalidomide (150 mg/kg) alone as well as its combination with sulfasalazine (360 mg/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of thalidomide with sulfasalazine in rat colitis model which requires further confirmation in human studies.

Effect of Manuka honey and sulfasalazine in combination to promote antioxidant defense system in experimentally induced ulcerative colitis model in rats.

Manuka honey (MH, 5g/kg) provided protection against trinitro-benzo-sulphonic acid induced colonic damage. Combination therapy (MH+sulfasalazine) also reduced colonic inflammation and all the biochemical parameters were significant compared to control and MH alone treated group. Combination therapy showed additive effect of the MH which restored lipid peroxidation and improvement of antioxidant parameters. Morphological and histological scores were significantly reduced in combination groups. In inflammatory model of colitis, oral administration of MH (5g/kg) and combination with sulfasalazine (360 mg/kg) with MH (5g/kg) significantly reduced the colonic inflammation. The results indicate the additive effect of Manuka honey with sulfasalazine in colitis.

Association of anticardiolipin antibodies levels with instent restenosis in patients with coronary artery disease.

Present study was conducted to evaluate the association of IgG anticardiolipin antibodies with instent restenosis in patients having undergone percutaneous intervention with bare metal or drug eluting stents. Coronary artery disease patients with stent placement at least 6 months prior were screened for eligibility. 26 satisfied the inclusion/exclusion criteria. 10 patients with symptoms of restenosis, confirmed on check angiography served as cases and 16 without symptoms of restenosis served as control. Unpaired t- test was applied to ascertain the significance of any difference between control and study groups. Antibody levels were estimated on ELISA reader. The mean (±SD) anticardiolipin antibodies levels in cases and controls were 11.8±5.1 GPL/U/ml and 14.3±10.2 GPL/U/ml, respectively. The difference was not statistically significant (P>0.05). In conclusion, we did not observe any significant correlation between the level of IgG aCL and instent restenosis.

Study of association between use of complementary and alternative medicine and non-compliance with modern medicine in patients presenting to the emergency department.

CONTEXT: Complementary and alternative medicines (CAMs) are extensively used by the public. Noncompliance is an important cause of therapy failure. AIM: This study was done to determine prevalence of emergency admission due to noncompliance with modern medicine following switching over to CAM and to identify any significant association for CAM use among noncompliers. SETTING AND DESIGN: This cross-sectional study was conducted in the emergency unit of a tertiary healthcare institute. MATERIALS AND METHODS: Demographic factors and system affected were compared between compliers and noncompliers. Prevalence, reasons and nature of noncompliance were determined. Age, gender, outcome, relation strength and potential preventability of noncompliance, precipitating and previous disease and noncompliant drugs were compared for significant association between CAM using and other noncompliers. STATISTICAL ANALYSIS: Student's 't' test, Chi square test and odds ratio were used. Results: Of the 506 patients interviewed 168 (33%) were noncompliant. In 160 (95%) patients noncompliance was due to under-dosing. Lack of knowledge and CAM use constituted 144 (86%) noncompliance-related admissions. Thirty-three (7%) admissions were strongly related to noncompliance and CAM use. Age, gender, outcome, drug use and diseases except chronic obstructive pulmonary disease (COPD) and asthma showed no association while relation strength and potential preventability of emergency admission was less with CAM-using noncompliers. Noncompliance was observed for hypertension, diabetes, COPD and asthma, seizure disorder, tuberculosis and hemophilia besides hepatic and renal failure. The CAM noncompliers used CAM more for modern medicine incurable or unaffordable than curable diseases. CONCLUSION: Advice for regular treatment and frequent monitoring can decrease CAM use-related noncompliance admissions.

Honey--a remedy rediscovered and its therapeutic utility.

Honey is a common household product with many medicinal uses described in traditional medicine. Modern system of medicine is also finding the honey efficacious in various medical and surgical conditions. Antimicrobial, antioxidant and wound healing properties of honey are being evaluated with successful outcome. Prevention and treatment of various infections due to a wide variety of organisms and promoting surgical wound healing are some of the areas where honey is making its mark.

Comparative gastrointestinal toxicity of selective cyclooxygenase (COX-2) inhibitors.

Cyclooxygenase (COX-2) inhibitors were developed with the hope that they will cause fewer gastrointestinal adverse effects. Ability of selective as well as nonselective COX inhibitors to alter ischemia-reperfusion induced damage of gastric mucosa and hapten-induced colitis in rats has been compared. Celecoxib (10, 20 and 40 mg/kg(-l)) was significantly more potent at aggravating ischemia-reperfusion injury as compared to nimesulide. Similarly, celecoxib was found to maximally potentiate TNBS-induced colitis, followed by nimesulide and indomethacin. Celecoxib at its highest dose produced maximum deep histological injury. This paradoxic ulcer and colitis aggravating effect of selective COX-2 inhibitors may be explained by suppression of protective prostaglandins generated as a consequence of COX-2 induction in inflammatory states.

Effect of nimesulide co-administration on pharmacokinetics of lithium.

In a crossover study, lithium was given orally at a dose of 56 mg/kg, prepared as suspension (0.5%) in carboxymethyl cellulose (CMC) and blood samples (1 ml) collected after 0-24 hr after drug administration. After a washout period of two weeks, nimesulide (10 mg/kg) was administered alongwith lithium (56 mg/kg) and blood samples were drawn at the same time intervals (0-24 hr) after drug administration. Plasma was separated and assayed for lithium by M 654 Na+/K+/Li+ analyzer and various pharmacokinetic parameters were calculated. C(max), K(el), t(1/2el) and AUC(0-alpha) of lithium were significantly increased when nimesulide was administered along with lithium as compared to control group.

Investigation of central mechanism of insulin induced hypoglycemic convulsions in mice.

Insulin produces seizures in healthy and diabetic animals. Amongst suggested mechanisms, the role of neuromodulators and neurotransmitters is not clear. The present study explores the mechanisms involved in insulin-induced convulsions. Convulsions were induced in Swiss male albino mice with graded doses of insulin. Blood sugar levels were measured prior to and after the first convulsion. Drugs like 5-HTP (5-HT precursor), pCPA (5-HT depletor), ondansetron (5-HT3 antagonist), ketanserin (5-HT, antagonist), ketamine (NMDA antagonist), 1-dopa (dopamine precursor) and reserpine (amine depletor) were studied for interaction with convulsive behaviour induced by insulin. Insulin in 2 IU/kg dose did not produce convulsions while 4 and 8 IU/kg doses produced convulsions in 50% and 100% of animals respectively. 5-HTP, ondansetron, ketanserin, ketamine and l-dopa significantly protected/inhibited animals from convulsions at all studied doses of insulin. On the contrary, pCPA and reserpine potentiated insulin induced convulsions. Insulin caused mortality in 40 and 100% animals with 4 and 8 IU/kg doses respectively. pCPA and reserpine treatments caused mortality at all doses of insulin, while other drugs did not influence insulin induced mortality. Blood sugar levels were reduced in all groups irrespective of the presence or absence of convulsions. A definitive link of serotonergic, dopaminergic and excitatory amino acid pathways in mediating insulin-induced hypoglycemic convulsions is suggested.

Biologics in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic progressive disease of the joints associated with significant morbidity, deformity, and impaired quality of life. A satisfactory remission of disease is seldom achieved, so therapy is aimed at controlling joint damage and pain with preservation of joint mobility. Until recently, NSAIDs, followed by DMARDs, was considered the treatment of choice. However, many patients fail to gain a satisfactory response to DMARDs or response declines over time. Biologics such as IL-1 receptor antagonist (anakinra), and anti TNF-alpha agents (Etanercept, Infliximab, and Adalimumab) are now available. The anti TNF and IL-1 therapies exert their anti-inflammatory action by neutralizing the activities of TNF-alpha and IL-1 respectively. In contrast to older DMARDs, these agents have rapid onset of action with fewer side effects and have pronounced disease reducing activity in patients who have previously been treated with other DMARDs, when administered as monotherapy or in combination with methotrexate. They have been shown to be at least as effective as methotrexate in reducing clinical disease activity and reducing radiographic progression. Biological agents are generally well tolerated, although their long-term safety needs to be determined. Some concerns have been raised that anti TNF-alpha therapy can increase the risk of serious infections, since TNF-alpha plays an important role in host defense. In light of limitations of cost and lack of long-term safety and efficacy data, newer agents for the time being are used as second- or third-line agents in patients with active RA. The dilemma is that which patients with RA are most suitable for such therapy, since it is still not possible to accurately predict which patient with RA will develop severe disease. One alternative approach may be to limit the use in patients who can afford it, and who are at high risk of radiographic progression and disability.

Prehospital delay in patients hospitalized with acute myocardial infarction in the emergency unit of a North Indian tertiary care hospital.

BACKGROUND: Prompt treatment of patients presenting with acute myocardial infarction decreases the incidence of death from early arrhythmia, and maximizes the potential benefit of thrombolytic therapy. Prehospital delay has been identified as a major obstacle to the widespread use of thrombolytic therapy. The aim of the present study was to examine the extent of, and factors associated with, delay in seeking medical care (usually thrombolytic therapy) in patients with acute myocardial infarction. METHODS AND RESULTS: The study was conducted in patients visiting the medical emergency unit of the Nehru Hospital, Post Graduate Institute of Medical Education and Research, Chandigarh. A total of 104 patients diagnosed with acute myocardial infarction were interviewed using a pre-designed proforma. Pain-to-door, and door-to-drug times, were the main outcome measures. The corrected mean (SEM) and median (range) pain-to-door times were 8.5 (0.8) hours and 5.2 (0.5-24) hours, respectively. Out of 104 patients, 38 did not receive thrombolytic therapy. In those who did not receive thrombolytic therapy, prior therapy at local health centers, lack of knowledge of symptoms, and transportation problems were the main reasons for hospital delay. The mean (SEM) and median (range) of door-to-drug times were 1.2 (0.1) hours and 1 (0.2-3.5) hours, respectively.

Effect of oral magnesium supplementation on experimental pre-eclampsia induced by prolonged blockade of nitric oxide synthesis in pregnant rats.

Nitric oxide inhibitor L-NAME when given alone caused a significant rise in both systolic and diastolic pressure, an increase in 24 hr urinary protein excretion and reduction in weight of the litter as compared to control group. Supplementation of MgSO4 at lower dose (250 mg/kg) did not inhibit this pre-eclamptic effect of L-NAME; but in higher doses (500 and 750 mg/kg), it inhibited the pre-eclamptic action of L-NAME. The results suggest that administration of MgSO4 improves the foetal outcome and significantly prevents the development of symptoms of pre-eclampsia like hypertension and proteinuria.

A meta-analysis of controlled clinical trials comparing low-molecular weight heparins with unfractionated heparin in unstable angina.

BACKGROUND: Unfractionated heparin has been used extensively for the treatment of unstable angina/non-Q wave myocardial infarction but it has several disadvantages. Low-molecular weight heparins are now recommended although they are 3-5 times costlier than unfractionated heparin since they are convinient to administer and do not require activated thromboplastin time monitoring. Whereas enoxaparin, a low-molecular weight heparin, has been demonstrated to be superior to unfractionated heparin, the results of other low-molecular weight heparins have not been so convincing. METHOD AND RESULTS: Through manual, MEDLINE and EMBASE search, we identified five randomized trials (excluding enoxaparin trials) that compared low-molecular weight heparins with unfractionated heparin in unstable angina. The prespecified efficacy end point of interest included a composite of death, myocardial infarction, recurrent angina and urgent revascularization. The safety end point was taken as a composite of major hemorrhage, minor hemorrhage, thrombocytopenia, allergic reaction and any other adverse event. We calculated odds ratio (95% confidence interval) for each trial for the composite end point, and the pooled odds ratio (95%) confidence interval) was calculated using two established methods of meta-analysis, the Mantel-Haenszel-Peto method and the DerSirmonian-Laird method. Both the methods yielded similar odds ratio (95% confidence interval). Separate odds ratio were calculated for efficacy and safety end points. There was a nonsignificant reduction in the incidence of the composite efficacy end point: the odds ratio (95% confidence interval) was 0.83 (0.70-0.99: p=0.08). The odds ratio (95% confidence interval) for the safety data was 0.78 (0.69-1.26: p=0.33). CONCLUSIONS: No statistically significant difference was observed when the efficacy and safety of low-molecular weight heparins were compared with those of unfractionated heparin. A cost-effectiveness analysis of low-molecular weight heparins versus unfractionated heparin must be done urgently to establish more firmly the place of low-molecular weight heparins in the management of unstable angina.

Analgesics for pediatric use.

The use of nimesulide is increasing and recently, concerns have been raised regarding its hepatotoxicity, especially in children. At least two deaths due to fulminant hepatic failure have been attributed to nimesulide. In India, nimesulide has been approved and about twelve pediatric preparations are available. Lack of effective postmarketing surveillance means that adverse drug reactions may not be picked or reported. Therefore, quick approval of those drugs for which substitutes are available may not be desirable in India and in other developing countries.

Effect of acute and chronic administration of L-arginine on morphine induced inhibition of gastrointestinal motility.

Effect of acute and chronic administration of L-arginine on morphine induced gastrointestinal inhibition was tested in rats. In the test for acute effect, L-arginine (200 mg/kg, i.v.) was given 10 minutes before the charcoal meal test. In the test for chronic effects, L-arginine (200 mg/kg, i.v.) was given twice a day for 4 days. Charcoal meal test was done on the fifth day. Morphine was administered 45 minutes before the charcoal meal test. Results showed that acute administration of L-arginine did not affect the morphine's action on the GIT. In contrast, chronic administration of L-arginine reversed the morphine induced decrease in gastrointestinal motility. The reversal was however, not complete. This data suggests that inhibition of NO may be one of the mechanism of morphine induced constipation.

Cognitive dysfunction induced by phenytoin and valproate in rats: effect of nitric oxide.

Phenytoin (PHT) and Valproate (VPA) are known to induce cognitive dysfunction, in terms of long term memory loss. Nitric oxide (NO) on the other hand is said to help in long term potentiation and hence enhance memory. The effects of nitric oxide donor L-arginine (L-Arg) and nitric oxide synthase inhibitor N-W-L-Nitroarginine (L-NOARG) were studied on the cognitive dysfunction, induced by PHT and VPA in normal healthy rats, using the step-through passive avoidance test (PAT). It was observed that combining L-Arg with PHT significantly enhanced long term memory while, combining PHT with L-NOARG decreased it, as compared to PHT alone. When combined with VPA, L-Arg and L-NOARG increased the retention latency as compared to PVA alone but this was not statistically significant. We conclude that the No donor L-Arg is able to increase the difference in LTE in acquisition and retention trials with both PHT and VPA, but with VPA the increase is not statistically significant.

Anticonvulsant profile of nimodipine and nitrendipine against pentylenetetrazole induced seizures in rats.

The activity of nimodipine and nitrendipine against pentylenetetrazole (PTZ) induced seizures in Albino rats was studied alone and in combination with valproate. The median effective dose [ED50] of valproate, nimodipine and nitrendipine were initially determined. All the 3 drugs were injected i.p. 30 min before the induction of seizures. Seizures were induced by PTZ 85 mg/kg i.p., and subsequently the effect of combining ED50 doses of nimodipine and nitrendipine with ED50 dose of valproate was evaluated. ED50 of valproate and nitrendipine were 129 and 2.5 mg/kg respectively. ED50 of nimodipine could not be established since a dose-response relationship was not obtained. Hence, for the purpose of combination studies, 4 mg/kg of nimodipine was used. Both nimodipine (4 mg/kg) and nitrendipine (2.5 mg/kg) decreased the ED50 of valproate from 129 to 40 mg/kg. Both nimodipine and nitrendipine potentiate the activity of valproate against PTZ induced seizures and can be considered as potential adjuvant anticonvulsants which merit further study.