Assessing the Efficacy of the ARMOR Tool-Based Deprescribing Intervention for Fall Risk Reduction in Older Patients Taking Fall Risk-Increasing Drugs (DeFRID Trial): Protocol for a Randomized Controlled Trial.

BACKGROUND: Falls in older patients can lead to serious health complications and increased health care costs. Fall risk-increasing drugs (FRIDs) are a group of drugs that may induce falls or increase the tendency to fall (ie, fall risk). Deprescribing is the process of withdrawal from an inappropriate medication, supervised by a health care professional, with the goal of managing polypharmacy and improving outcomes. OBJECTIVE: This study aims to assess the effectiveness of a deprescribing intervention based on the Assess, Review, Minimize, Optimize, and Reassess (ARMOR) tool in reducing the risk of falls in older patients and evaluate the cost-effectiveness of deprescribing FRIDs. METHODS: This is an open-label, parallel-group randomized controlled academic trial. Individuals aged 60-80 years who are currently taking 5 or more prescribed drugs, including at least 1 FRID, will be recruited. Demographic data, medical conditions, medication lists, orthostatic hypotension, and fall history details will be collected. Fall concern will be assessed using the Fall Efficacy Scale, and fall risk will be assessed by the Timed Up and Go test and Tinetti Performance-Oriented Mobility Assessment tool. In this study, all treating physicians will be randomized using a stratified randomization method based on seniority. Randomized physicians will do deprescribing with the ARMOR tool for patients on FRIDs. Participants will maintain diaries, and monthly phone follow-ups will be undertaken to monitor falls and adverse events. Physical assessments will be performed to evaluate fall risk every 3 months for a year. The rationality of prescription drugs will be evaluated using the World Health Organization's core indicators. RESULTS: The study received a grant from the Indian Council of Medical Research-Safe and Rational Use of Medicine in October 2023. The study is scheduled to commence in April 2024 and conclude by 2026. Efficacy will be measured by fall frequency and changes in fall risk scores. Cost-effectiveness analysis will also include the incremental cost-effectiveness ratio calculation. Adverse events related to deprescription will be recorded. CONCLUSIONS: This trial will provide essential insights into the efficacy of the ARMOR tool in reducing falls among the geriatric population who are taking FRIDs. Additionally, it will provide valuable information on the cost-effectiveness of deprescribing practices, offering significant implications for improving the well-being of older patients and optimizing health care resource allocation. The findings from this study will be pertinent for health care professionals, policy makers, and researchers focused on geriatric care and fall prevention strategies. TRIAL REGISTRATION: Clinical Trials Registry - India CTRI/2023/12/060516; https://ctri.nic.in/Clinicaltrials/pubview2.php. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55638.

A Longitudinal Analysis of Black Box Warnings: Trends and Implications for Drug Safety.

A black box warning, signaling potential life-threatening adverse effects of medications or medical devices, is crucial for public and healthcare professional awareness. Comprehending and adhering to these warnings can prevent serious harm. This review aims to elucidate their significance. Data on drugs with black box warnings were collected from the Food and Drug Administration's (FDA's) official website using the search term 'Boxed warnings' from January 1, 2015, to January 31, 2024. A Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, WA, USA) containing black box warnings for this period was downloaded from the FDA's website. Additional parameters, such as drug class and whether the warnings were new or existing, were added to the downloaded spreadsheet. The collected data were organized by year, categorizing new and existing warnings, along with details on the evidence source, system-wise classification, and black box warnings for commonly used drugs, including their clinical significance. Results show that in the past decade, 40% of black box warnings were issued in 2023, followed by 12% in 2022. Most warnings (67%) comprised existing ones with minor revisions while 29% were new. Nine existing warnings were removed during the period. Post-marketing studies predominantly provided evidence for these warnings. Neuropsychiatric concerns like addiction potential (31%), suicidal tendency (7%), and hypersensitivity reactions (12%) were the frequently encountered black box warnings. Black box warnings play a crucial role in highlighting the serious adverse effects of medications. Neuropsychiatric warnings have been frequent over the past decade. Awareness of these warnings is essential to prevent adverse effects and enhance patient care, especially concerning drugs like guaifenesin/hydrocodone bitartrate, zolpidem, and montelukast commonly encountered in clinical practice.

Performance in a Balance Test and Prediction of All-Cause Mortality in Community-Dwelling Elderly Ambulatory Individuals: A Systematic Review and Meta-analysis.

Objective: This systematic review and meta-analysis was performed to evaluate the association between an inability to perform a static balance test and mortality in community-dwelling older ambulatory individuals. Methods: PubMed, Embase, and Scopus were searched for relevant cohort studies. Hazard ratios (HR) were pooled (random-effect model). Meta-regression was performed with independent demographic variables (PROSPERO ID: CRD42022381137). Results: A total of 11,713 articles were screened and 15 were included. An inability to perform a static balance test was significantly associated with a higher risk of mortality irrespective of whether confounding variables were considered [HR, 1.14 (95% CI: 1.07-1.21); p < .001; i2, 87.96% (p < .01)] or not [HR, 1.11 (95% CI: 1.03-1.20); p = .01; i2, 95.28% (p < .01)] (both moderate GRADE evidence). Also, this association was correlated with progressive age. Conclusion: An inability to successfully complete a static balance test was significantly associated with a higher risk of mortality among community-dwelling older ambulatory individuals.

Clinical and immunological responses to COVID-19 vaccination in rheumatoid arthritis patients on disease modifying antirheumatic drugs: a cross-sectional study.

Objective: This study was conducted to investigate the immunological and clinical response to COVID-19 vaccination in rheumatoid arthritis (RA) patients receiving disease modifying antirheumatic drugs (DMARDs). Methods: A cross-sectional study was conducted among RA patients who received two doses of COVID-19 vaccine within 6 months to one year. Demographic information, comorbidities, vaccination details, and past COVID-19 infection details were collected. Hemoglobin (Hb), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and interleukin-6 (IL-6) levels were estimated. Disease Activity Score-28 (DAS-28) was calculated for RA patients. Anti-spike antibody (ASA) concentrations were measured, and compared with a healthy control population. Correlations of ASA with age, sex, disease parameters, medication use, and comorbidities were assessed. Results: A total of 103 RA patients and 185 controls were included in the study. RA patients had higher mean age, lower mean Hb, higher ESR, and elevated IL-6 levels. Both groups showed positive results for anti-spike antibodies, with a higher percentage in controls. Among RA patients majority had low DAS-28 score. The number of DMARDs used showed a negative correlation with antibody levels. There was a slight positive correlation between ASA concentration and DAS-28 score. Comorbidities did not significantly influence antibody concentration. No significant differences were found in antibody levels based on the type of COVID-19 vaccine or previous COVID-19 infection or booster dose vaccination among RA patients. Conclusion: The study revealed that RA patients showed a reduced antibody response following COVID-19 vaccination compared to the control group and potentially influenced by immunosuppressive treatments and disease-related factors.

Efficacy and safety of bempedoic acid lipid-lowering therapy: a systematic review and meta-analysis of randomized controlled trials.

AIM: This systematic review and meta-analysis was conducted to synthesize the efficacy and safety of bempedoic acid in patients requiring lipid-lowering therapy. METHODS: PubMed, Embase, and Scopus databases were searched for randomized controlled trials from inception till June 2023. The primary outcome was major adverse cardiovascular events (MACE), and secondary outcomes were all-cause mortality, serum lipid profile, and adverse events between bempedoic acid and comparators. ROB2 was used for risk of bias assessment. We pooled mean differences or relative risks (RR) along with 95% confidence intervals (random-effects model). RESULTS: Five-hundred and thirty-one studies were screened and 17 (n = 21,131) were included for review. There was a significant reduction in the risk of MACE [RR, 0.88 (95% CI: 0.77 to 0.99), p = 0.03)] and all-cause mortality [RR, 0.90 (95% CI: 0.82 to 0.98), p = 0.02] following bempedoic acid treatment. Treatment with bempedoic acid led to a significant reduction in the mean serum total cholesterol [- 34.41 mg/dl (95% CI: - 42.43 to - 26.39), p < 0.001], low-density lipoprotein cholesterol (LDL-C) [- 33.91 mg/dl (95% CI: - 39.66 to - 28.17), p < 0.001], as well as high-density lipoprotein cholesterol (HDL-C) [- 2.40 mg/dl (95% CI: - 3.09 to - 1.71), p < 0.001] levels. However, there was a significant increase in the risk of hyperuricemia [RR, 2.05 (95% CI: 1.81 to 2.33), p < 0.001] following bempedoic acid treatment. The number needed to harm was large for all safety outcomes. The GRADE of evidence was moderate for all outcomes. CONCLUSION: Bempedoic acid reduces the risk of MACE and all-cause mortality, lowers serum total cholesterol and LDL-C levels, and has a favorable safety profile. Trial registration ClinicalTrial.gov Identifier: CRD42023412837.

"Effect of COVID-19 Vaccination on Menstrual Cycle Patterns of Reproductive-Age Women: A Multi-centric Observational Study."

AIM: The study was conducted to know the impact of COVID-19 vaccination on menstrual cycle patterns and pre- and post-menstrual symptoms in women aged 18-45 years. BACKGROUND: COVID-19 vaccination was introduced to combat the dreadful impacts of human coronavirus infection. The two indigenously developed COVID-19 vaccines approved for use in India are COVISHILED and COVAXIN. OBJECTIVES: To investigate the effects of COVID-19 vaccination on the menstrual cycle, pre- and post-menstrual symptoms and to establish the correlation with the type of vaccine received. METHODS: Multi-centric observational study conducted in six institutes of national importance in different states of India over one year. A total of 5709 female participants fulfilling inclusion criteria were enrolled. Data about the impact of vaccines (COVISHIELD and COVAXIN) and prior COVID-19 infection on the menstrual cycle and its associated symptoms were obtained using all participants' online and offline interviews. RESULTS: Of 5709 participants, 78.2% received COVISHIELD and 21.8% COVAXIN. Of the total 5709 participants, 333(5.8%) developed post-vaccination menstrual disturbances, with 32.7% having frequent cycles, 63.7% prolonged cycles, and 3.6% inter-menstrual bleeding. A total of 301 participants noticed changes in the amount of bleeding, with 50.2% excessive, 48.8% scanty, and 0.99% amenorrhea followed by heavy bleeding. Furthermore, the irregularities of the menstrual cycle (p=0.011) and length (0.001) were significantly higher in the COVAXIN group (7.2%) as compared to the COVISHIELD (5.3%) group. A total of 721 participants complained of newly developed/worsening pre- and post-menstrual symptoms. These symptoms were significantly higher in the COVISHIELD group (p=0.031), with generalized weakness and body pains as the main complaints (p=0.001). No significant difference was observed in the incidence of COVID-19 infection with these vaccines. No significant associations were observed when comparing menstrual abnormalities among those with COVID-19 infection (p>0.05). CONCLUSIONS: COVISHILED and COVAXIN vaccines were associated with menstrual cycle disturbances and pre-and post-menstrual symptoms in a small proportion of participants, with 94.7% having no change in the amount of bleeding during menstruation post-vaccination. The menstrual irregularities observed were significantly higher with the COVAXIN vaccine. Others: Further, long-term studies are required to confirm that the impact of COVID-19 vaccination on the menstrual cycle may be short-lasting, with no severe effects on women's menstrual health.

Anti-spike Antibody Status in Pre-vaccinated Healthy Participants and Rheumatoid Arthritis Patients During the Third Wave of COVID-19.

Introduction Anti-spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced after infection with the coronavirus disease of 2019 (COVID-19) will offer protection and prevent re-infection for a few months. Seroprevalence studies measuring the SARS­CoV-2 immunoglobulin G (IgG) levels will be helpful to know the herd immunity level that prevents community transmission. Very few studies have addressed the antibody titer among healthy participants and rheumatoid arthritis (RA) patients. The present study was conducted to determine the anti-spike SARS-CoV-2 antibody (Ab) status before COVID-19 vaccination in healthy participants and RA patients. Methodology A cross-sectional study was conducted at a tertiary care hospital to estimate the serum anti-spike antibody levels against COVID-19 among the pre-vaccinated healthy participants and patients with RA during the third wave of COVID-19. After receiving written informed consent, participants were recruited as per the inclusion and exclusion criteria. Demographic details, co-morbid status, and medication details were collected. Five milliliters of blood samples were collected, and anti-spike antibodies were estimated. The SARS-CoV-2 Ab positivity rate was expressed in percentage and was correlated with gender and age groups. Ab-positive participants were classified into three categories based on the neutralizing antibody titers (NAT). Results A total of 58 participants (49 healthy volunteers and nine RA patients) were recruited. Out of 58 participants, 40 were males, nine were females among healthy participants, and one male and eight females in the RA group were enrolled. Among the RA patients, one participant was found to have the chronic obstructive pulmonary disease (COPD), and two participants with hypothyroidism. Antibody positivity was found to be 83.6% among the healthy volunteers and 100% in the RA patients. About 48% had NAT between 50 and 90%. There was no significant difference for age and gender-specific positivity for SARS-CoV-2 neutralizing antibodies and neutralizing antibody titers among healthy participants. Conclusion Our study showed 84% positivity for anti-spike SARS-CoV-2 antibodies around the third wave (between November 2021 and February 2022). The majority had high neutralizing antibody titers. The probable reason for the SARS-CoV-2 antibody positivity before vaccination was either asymptomatic infection or herd immunity.

Efficacy and Safety of Anti-SARS-CoV-2 Monoclonal Antibodies: An Updated Review.

Monoclonal antibodies (mAbs) had received emergency use authorization for mild-to-moderate coronavirus disease 2019 (COVID-19) or for prophylaxis against COVID-19, including casirivimab plus imdevimab (C+I), bamlanivimab plus etesevimab (B+E), tixagevimab plus cilgavimab (T+CG), and sotrovimab (S) and bebtelovimab (BEB). This systematic review was done to assess the efficacy and safety of the same. PubMed, Embase, Scopus, medRxiv, bioRxiv, and FDA fact sheets were searched for the studies published between January 2021 and May 2022, and appropriate search terms related to the mentioned mAbs were used for data collection. Review included original research including randomized clinical trials and observational studies published or preprints. Studies included in the review had compared with placebo or standard of care or no treatment or mAbs with each other and also of various doses. Data extraction was done and reviewed the same for both efficacy and safety. Total of 20 studies were included in this review. The rate of hospitalization within 30 days showed ∼2% in comparison to ∼7% with placebo. Significant reduction in viral load was more observed with combination mAbs. Combination therapy showed faster virological cure against the Gamma variant. With C + I as postexposure prophylaxis (PEP), 29.0% of asymptomatic participants developed symptomatic COVID-19. Pre-exposure prophylaxis with T+CG reduced the incidence of infection by 77%. Infusion-related reaction was the most common adverse event (AE). The neutralizing mAbs reduced hospitalization in mild-to-moderate patients with infusion-related reactions as common AE. The response was better in the seronegative patients. Most of these studies were conducted in unvaccinated individuals and against Alpha, Gamma, and Delta variants.

Efficacy and safety of Molnupiravir in COVID-19 patients: a systematic review.

BACKGROUND: Molnupiravir is an oral antiviral drug that received Emergency Use Authorization in three countries for the treatment of mild COVID-19. The aim of this systematic review was to find out the safety and efficacy of Molnupiravir in SARS-COV-2 infections. METHODS: The electronic databases such as PubMed, MedRxiv, BioRxiv, FDA, ClinicalTrials.Gov, ctri.nic.in and Google Scholar were searched for articles from January 2021 to March 2022 using the keywords such as "Molnupiravir", "COVID-19", "Oral antiviral pill", "MK-4482", "EIDD-280", "Efficacy" and "Safety". Details of published, unpublished with interim reports and ongoing studies of Molnupiravir in COVID-19 were retrieved, and a systematic review was performed. RESULTS: A total of 6 articles and 18 ongoing trials data were collected. Out of these, data from 4 published and 2 unpublished with interim reports were extracted. After review of these studies, it was observed that the daily dose of 1600 mg Molnupiravir for 5 days was safe and tolerable with nausea, diarrhea and headache as the common adverse effects. The results also showed significant decrease in time to viral clearance with 800 mg twice daily in mild patients and reduction in the risk of hospitalization or death by 50% in non-hospitalized COVID-19 patients. CONCLUSION: Evidence from clinical studies showed that Molnupiravir caused significant reduction in the risk of hospitalization or death in high-risk mild COVID-19 patients. Molnupiravir was also found to be well tolerated and safe without any major adverse events on short-term use. For confirmative use of this drug in mild-to-moderate COVID-19 disease, further studies are required in vaccinated COVID-19 patients and against emerging variants.

Efficacy and safety of baricitinib and tocilizumab in hospitalized patients with COVID-19: A comparison using systematic review and meta-analysis.

Objective: This review was performed to compare the efficacy and safety among hospitalized patients with COVID-19 who received baricitinib and those who received tocilizumab independently with placebo or the standard of care (SOC). Methods: Relevant databases were searched for randomized controlled trials which evaluated the effect of baricitinib or tocilizumab as compared to placebo or the SOC in hospitalized patients with COVID-19. The primary endpoint was the comparison of the 28-day mortality. Risk ratios (RR) and mean differences were compared and pooled for dichotomous and continuous variables, respectively. A two-staged exploratory network meta-analysis using a multivariate meta-analysis was also performed. All analyses were performed in Stata version 16.0. The GRADE approach was used to assess the quality of the generated evidence (PROSPERO ID: CRD42022323363). Results: Treatment with baricitinib [RR, 0.69 (95% CI, 0.50-0.94), p = 0.02, i2 = 64.86%] but not with tocilizumab [RR, 0.87 (95% CI, 0.71-1.07), p = 0.19, i2 = 24.41%] led to a significant improvement in the 28-day mortality as compared to that with the SOC. Treatment with baricitinib or tocilizumab, both independently led to a significant reduction in the duration of hospitalization [baricitinib: mean difference, -1.13 days (95% CI, -1.51 to -0.76), p < 0.001, i2 = 0.00%; tocilizumab: mean difference, -2.80 days (95% CI, -4.17 to -1.43), p < 0.001, i2 = 55.47%] and a significant improvement in the proportion of patients recovering clinically by day 28 [baricitinib: RR, 1.24 (95% CI, 1.03-1.48), p = 0.02, i2 = 27.20%; tocilizumab: RR, 1.41 (95% CI, 1.12-1.78), p < 0.001, i2 = 34.59%] as compared to those with the SOC. From the safety point of view, both these drugs showed similar results. There were fewer patients who experienced any serious adverse event following treatment with barictinib and tocilizumab as compared to those following treatment with the SOC [baricitinib: RR, 0.76 (95% CI, 0.62-0.92), p = 0.01, i2 = 12.63%; tocilizumab: RR, 0.85 (95% CI, 0.72-1.01), p = 0.07, i2 = 0.00%]. Conclusion: As baricitinib and tocilizumab are recommended interchangeably by various guidelines for the management of COVID-19, considering the better 28-day mortality data and other comparable efficacy and safety outcomes, baricitinib may be favored over tocilizumab considering its ease of administration, shorter half-life, and lower cost of treatment.

Adverse events following remdesivir administration in moderately ill COVID-19 patients - A retrospective analysis.

Introduction: Remdesivir, an antiviral drug, received an emergency use authorization for treating coronavirus disease 2019 (COVID-19) patients. Though many studies have reported the safety aspects of this antiviral agent, most of them were observed in severely ill COVID-19 patients, making very less data available in the moderately ill patients. The present study was conducted with an objective of finding the adverse events (AEs) associated with remdesivir in moderately ill COVID-19 patients. Methodology: A retrospective observational study was conducted by collecting data of demographic details and details of remdesivir, laboratory investigations, and AEs from the patient medical records from May to July 2021 and analyzed by using the appropriate statistics. Results: Out of the 160 COVID-19 patients, 32 were moderately ill (males: 29, females: 03) and were treated with remdesivir along with steroids and low molecular weight heparin (LMW) heparin. The average number of administered remdesivir doses was 4, with a loading dose of 200 mg and a maintenance dose of 100 mg. A total of 41 AEs were observed out of which 17 were adverse drug reactions (ADRs) (a significant increase in the alanine transaminase (ALT) [P < 0.001]) and 23 AEs (a significant rise in random blood sugars, RBS [one of the AEs] [P = 0.007]). The AEs were more commonly seen in the hypertensive patients. An increased oxygen requirement was a major serious AE observed in four patients. Conclusion: Remdesivir caused a significant increase in the liver enzymes. Increased blood sugar levels were the most common AE and increased oxygen requirement was the major serious AE observed.

Ivermectin in COVID-19 Management: What is the Current Evidence?

Ivermectin (IVM), an approved anthelminthic drug, has been reported to have antiviral, antibacterial, and anticancer activities. Antiviral activity is due to the inhibition of nuclear cargo importin (IMP) protein. The anti-SARS CoV-2 activity through in vitro study was first reported by an Australian team. Later, many studies were conducted, and most of the study results were available as non-peer-reviewed preprints. In this narrative review, literature on the clinical studies conducted with ivermectin from published articles, preprints, and unpublished evidence was collected until 13th June 2021. They are discussed based on the severity of COVID-19 disease. Out of the 23 peer-reviewed published articles, 13 studies were randomized controlled trials. The remaining were either prospective interventional, prospective observational, retrospective cohort, cross-sectional, or case series type of studies; additionally, there were 10 randomized controlled trials available as preprints. In most studies, ivermectin was used in combination with doxycycline, azithromycin, or other drugs. Some studies suggested that a higher dose or increased duration of ivermectin usage was required to achieve favorable effects. In this review, articles on the prophylactic role of ivermectin in COVID-19 are also discussed - wherein the results are more promising. Despite accumulating evidence suggesting the possible use of ivermectin, the final call to incorporate ivermectin in the management of COVID-19 is still inconclusive.

Nephroprotective effects of ethanolic root extract of Azima tetracantha lam in adenine-induced chronic kidney failure in Wistar rats.

OBJECTIVES: To evaluate the effects of ethanolic root Ethanolic extract of Azima tetracantha. Lam roots (EEATR) in adenine-induced chronic kidney failure in Wistar albino rats To assess the antioxidant activity of EEATR. MATERIALS AND METHODS: Thirty rats were selected and allocated to five groups with six animals in each group. Group 1 was given normal saline (control), Group 2 - adenine, 0.75% 40 mg/kg, Group 3 - adenine and 250 mg/kg of EEATR, Group 4 - adenine and 500 mg/kg EEATR, and Group 5 - EEATR 500 mg/kg. Saline, adenine, and EEATR were given orally once daily for 28 days. EEATR was given 60 min before adenine administration. Urine output, blood urea nitrogen (BUN), creatinine, albumin, and total proteins were estimated. The histopathological changes in the kidneys were examined, and antioxidant property of the extract was assessed in the renal tissue. RESULTS: Adenine treated rats had a reduction in urine output (‒45%), food intake (‒46%), body weight (‒28%), total proteins (‒66%) and albumin (‒59%) and an increase in creatinine (950%), BUN (73.6%), and kidney weight (43.75%). Histological examination of the kidneys showed capillary congestion, tubular damage, glomerular distortion, and many oxalate crystals. Rats co-administered with EEATR 250 and 500 mg/kg had marked improvement (P ≤ 0.0001%) in all the above parameters with a marked reduction in size and number of oxalate crystals in the kidney. In the anti-oxidant assays, EEATR exhibited significant antioxidant activity. CONCLUSION: EEATR was found to be an effective nephroprotective agent in adenine-induced chronic renal failure in Wistar albino rats.

Effect of aluminum chloride on blood glucose level and lipid profile in normal, diabetic and treated diabetic rats.

OBJECTIVES: The objectives of the study were to assess evaluate the effects of aluminum chloride (AlCl3) on blood glucose and lipid levels in normal, diabetic, and glibenclamide-treated diabetic rats. MATERIALS AND METHODS: Forty-two male Wistar rats were divided into seven groups of six each. Group I was normal control, Groups II and III were given AlCl350 and 100 mg/kg, and Group IV to VII were administered with streptozotocin (STZ) (60 mg/kg) intraperitoneally. Group IV was diabetic control, Group V in addition was given AlCl350 mg/kg, Group VI glibenclamide (10 mg/kg), and Group VII glibenclamide and AlCl3(50 mg/kg) per-oral daily for 28 days. Blood glucose and lipid levels were estimated at base line, after diabetes was set in and on the last day of study. Histopathological changes in pancreas, liver, and kidney were studied. RESULTS: No significant change was observed in blood glucose and lipid levels in Group I. Group II and III showed a dose-dependent significant increase in blood glucose was observed. Group V had a reduction in blood glucose but not to the nondiabetic level. Group VI had significant reduction in blood sugar. In Group VII, treated with glibenclamide and AlCl3, there was no significant change in blood glucose reduction compared to Group VI. Lipid levels were reduced in groups treated with AlCl3 and glibenclamide and not in other groups. Gross tissue damage was seen in pancreas in STZ group and in liver and kidney in AlCl3 groups. CONCLUSION: AlCl3 administration in Wistar rats caused in significant hyperglycemia in normal rats, hypoglycemia in diabetic rats, and did not influenced hypoglycemic effect of glibenclamide and in addition, resulted in reduction in lipid levels.

Antioxidant and Nephroprotective Activities of Aconitum heterophyllum Root in Glycerol Induced Acute Renal Failure in Rats.

AIM: The present study was to evaluate the antioxidant and nephroprotective activities of ethanolic extract of Aconitum heterophyllum root (EEAHR) in glycerol induced acute renal failure (ARF) in Wistar albino rats. MATERIALS AND METHODS: In vitro antioxidant activity of EEAHR was assessed using the 2, 2-diphenyl-picrylhydrazyl (DPPH assay), nitric oxide radical scavenging (NO assay), hydrogen peroxide (H2O2 assay) and ferric reducing antioxidant power (FRAP) scavenging activity assays. In vivo study, rats were divided into four groups of six each for assessing the nephroprotective activity. Group-1 received normal saline, group-2 received 50% glycerol (10 ml/kg) alone, group-3 received glycerol and 250 mg/kg of EEAHR and group-4 received glycerol and 500 mg/kg of EEAHR. The renal injury and recovery was measured by serum creatinine, blood urea nitrogen (BUN), total proteins, albumin, urine output and histopathological changes. RESULTS: In vitro antioxidant activity of root extract was found to be equal to Vitamin C and in an in vivo study root extract treated animals showed significant attenuation of biochemical parameters and histopathological changes of the kidney compared to glycerol treated group and it was found to be more significant with the extract at 500 mg/kg than 250mg/kg. CONCLUSION: The present study revealed that Aconitum heterophyllum root has shown antioxidant and nephroprotective activities.

Nephroprotective effect of ethanolic extract of Azima tetracantha root in glycerol induced acute renal failure in Wistar albino rats.

The gravity of the impact of renal failure on human health is well known and as there is no specific pharmacotherapy for renal failure, the current study was undertaken to evaluate the effect of root extract of Azima tetracantha, an ancient medicinal plant used in Siddha and Ayurvedhic systems of medicine. The experiment was done in glycerol-induced acute renal failure in Wistar albino rats. Thirty rats were divided into five groups. Group 1 was given normal saline (10 ml/kg) per oral, group 2 with single dose of hypertonic glycerol (8 ml/kg) by intramuscular injection into the hind limbs, group 3 with glycerol and ethanolic extract of A. tetracantha root (ATR) 250 mg/kg, group 4, glycerol and ATR 500 mg/kg and group 5, 500 mg/kg ATR. Extract was given orally 60 min prior to glycerol injection. 24 h urine output, serum creatinine, blood urea nitrogen, total proteins and albumin were measured for all the groups. Kidneys were examined for histopathological changes. The antioxidant activity of the extract was tested in vitro and in vivo. Rats treated with ATR showed significant improvement in biochemical parameters and histopathological changes compared to glycerol treated group. The protective effect was highly significant at 500 mg/kg. Both in vitro and in vivo assays showed significant antioxidant activity. The in vitro activity was comparable to vitamin-C. The ethanolic extract of ATR has nephroprotective effect in glycerol-induced acute renal failure and the mechanism of action could be the antioxidant effect.