Suparna Chatterjee

The role of antioxidant properties of Nardostachys jatamansi in alleviation of the symptoms of the chronic fatigue syndrome.

An experimental model of chronic fatigue syndrome (CFS) is utilized for evaluation of antidepressant, anti-stress effects, wherein the rat is forced to swim in water for 15 min/day on 21 consecutive days. Rats were divided into stressed control, stressed plus standard drug (Panax ginseng) and stressed plus 200 and 500 mg/kg of test drug, i.e., Nardostachys jatamansi extract (NJE) given orally. The immobility during each 5 min periods of 0-5, 5-10 and 10-15 min of stress were noted. Similarly the climbing (struggling) behaviour was noted in the above four groups of rats in intervals of 5 min. The locomotor activity and also the anxiety state in animals were evaluated in an elevated plus maze after CFS in all the four groups. There was a significant increase in despair behaviour and anxiety in stressed control animals on successive days of CFS. Locomotor activity gradually decreased in stressed control group. Treatment with NJE (200 and 500 mg/kg) significantly reversed both paradigms. Biochemical analysis showed that CFS significantly increased lipid peroxidation, nitrite and superoxide dismutase levels and decreased catalase level in rat brain. Administration of NJE (200 and 500 mg/kg) tended to normalize both augmented lipid peroxidation, nitrite, superoxide dismutase activities and catalase level significantly. NJE per se has an antioxidant effect. The results indicate that CFS may lead to oxidative stress, which is mitigated by NJE and so its antioxidant property may be responsible for anti-stress effect of NJE.

Multi-drug resistant gram negative bacilli causing early neonatal sepsis in India

Objective To study the organisms causing early and late onset neonatal sepsis, with special reference to multi-drug resistant gram negative bacilli, at two neonatal units (one urban, one rural) in India. Methods Prospective surveillance study. Results There were 159 episodes of sepsis (81 urban and 77 rural) affecting 158 babies. Gram negative bacilli caused 117 infections (68%) and predominated at both centres in both early and late sepsis. Klebsiella pneumoniae was the commonest organism, causing 61 infections (38.3%). In early sepsis (0–2 days), non-fermenting gram negative bacilli caused 42.1% of infections at the urban centre; there were no cases of early Group B Streptococcus sepsis. Late onset sepsis was mainly caused by gram negative bacilli at both centres. Multi-drug resistance of over 80% of early-onset gram negative organisms to ampicillin, third generation cephalosporins and gentamicin indicates that these multi-resistant organisms are almost certainly circulating widely in the community. The overall mortality from early sepsis was 27.3% (9 of 33) and from late sepsis was 26.2% (33 of 126). Gram negative bacilli caused all deaths from early sepsis and 87.5% of deaths from late sepsis. Conclusion This study shows that multi-drug resistant gram negative bacilli are a major cause of early and late neonatal sepsis in India and are almost certainly widespread in the community.

Clinical effectiveness and safety of escitalopram and desvenlafaxine in patients of depression with anxiety: A randomized, open-label controlled trial

Aim: Selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) are effective in treating anxiety disorders associated with major depressive disorder (MDD). This randomized, controlled, parallel-group, open-label, phase 4 trial (CTRI/2012/08/002895) was undertaken to compare the effectiveness and safety of desvenlafaxine versus escitalopram, a standard antidepressant. Materials and Methods: Effectiveness was assessed using the Hamilton Depression Rating Scale (HAM-D17) and Hamilton Anxiety Rating Scale (HAM-A). Response to treatment was assessed by ≥50% decrease of baseline scores (responder rate). Safety and tolerability was evaluated by changes in routine laboratory parameters, vital signs, and adverse events reported by the subject and/or observed by the clinician. Results: Responder rates for both HAM-A and HAM-D scores at 8 weeks were better in the escitalopram group compared to the desvenlafaxine group (HAM-A 76.92% vs. 71.05%; HAM-D 79.48% vs 73.68%) but the differences were not statistically significant (P = 0.59 and P = 0.61). Within group changes of both scores, from baseline to subsequent visits in both treatment arms were statistically significant (P < 0.01). Conclusion: The effectiveness of desvenlafaxine was comparable to escitalopram, but escitalopram was better tolerated.

Ocular adverse effects of Topiramate: Two case reports

Topiramate, an antiepileptic drug is reported to cause various ocular adverse effects like acute onset myopia, glaucoma. Visual field defect is an uncommon, serious treatment emergent adverse effect. We are reporting two cases of suspected topiramate induced visual field defects. Both the cases were on topiramate for more than 6 months as add-on therapy at daily doses ranging from 100-150mg. The presenting complaints were insidious onset visual disturbances. Diagnosis was based of temporal association with drug intake, clinical examination and investigations. Automated perimetry revealed bilateral superior quadrantic and arcuate field defects in the two cases respectively. Marked improvement with drug dechallenge was noted which was also corroborated by perimetry. Using Naranjos ADR Probability Scale, both cases revealed a “probable” association with topiramate. This report intends to improve awareness amongst clinicians to facilitate early diagnosis and intervention.

Multi-drug-resistant, non-fermenting, gram-negative bacilli in neonatal sepsis in Kolkata, India: a 4-year study

Abstract Background: Non-fermenting gram-negative bacilli (NFGNB) are an emerging problem in neonatal sepsis. A major concern is multi-drug resistance which severely limits treatment options. Aims and Objectives: A retrospective observational study was conducted to analyse the role of non-fermenters in neonatal sepsis over a 4-year period, the factors leading to this trend and the pattern of antibiotic resistance. Methods: Demographic and clinical data were collected for all neonates with blood culture-positive sepsis during the study period, January 2007 to December 2010. Results: Blood cultures were positive in 186 (13%) of 1402 neonates, in 44 (32·1%) of whom the cause was NFGNB. Acinetobacter spp was the most common organism (n = 30). Infection by NFGNB showed a steady increase (P<0·0001), and was fairly evenly distributed between early- and late-onset sepsis. The infection rate was significantly higher in inborn neonates (P = 0·04) and those delivered vaginally (P = 0·002). Multi-drug resistance (MDR) occurred in 50% and carbapenem resistance in 30% of Acinetobacter spp isolates. In five cases there was panresistance of Acinetobacter spp to all antibiotics tested. Conclusion: The trend of increasing numbers of cases of NFGNB in neonatal sepsis compounded by MDR is of great concern. It is necessary to administer antibiotics judiciously, strengthen surveillance and laboratory services in neonatal intensive care units, and re-evaluate treatment guidelines for management of infection by these organisms.

Levels of oxidative damage and proinflammatory cytokines are enhanced in patients with active vitiligo

Abstract Vitiligo is an autoimmune depigmenting skin disease characterised by loss of melanocytes wherein oxidative stress is proposed to be the initial triggering factor with subsequent immune dysregulation. This study aimed to evaluate the relationship, if any, between the generation of reactive oxygen species (ROS), markers of oxidative damage and circulating cytokines in patients with active vitiligo. The generation of ROS in erythrocytes and neutrophils was significantly higher in patients with active vitiligo than healthy controls. Alongside, markers of oxidative stress-mediated damage namely lipid peroxidation, DNA damage and protein carbonylation were evaluated. Patients with active vitiligo demonstrated increased lipid and DNA damage but minimal protein damage. There was a significant decline in the free radical scavenging capacity of active vitiligo cases. A positive correlation existed between baseline levels of ROS and lipid peroxidation as also DNA damage. Patients with active vitiligo demonstrated an increase in several proinflammatory (IL-6, TNF-α, IL-1β, IFN-γ and IL-8) and some anti-inflammatory/immunoregulatory (IL-5 and IL-10) cytokines. Importantly, the levels of IFN-γ and IL-10 consistently correlated with the generation of ROS, markers of damage and their free radical scavenging capacity. Taken together, patients with active vitiligo demonstrated an enhanced generation of ROS in erythrocytes and neutrophils which mediated lipid peroxidation, DNA damage and coupled with a decline in their antioxidant capacity created a pro-oxidant milieu that favoured tissue damage and potential generation of neoantigens, accounting for disease progression.

Drug safety monitoring in patients of movement disorders of a tertiary care hospital.

Background: Movement disorders (MD) are neurological conditions that affect the speed, fluency, quality, and ease of movement and commonly include Parkinson’s disease, tremor and dystonias. Drugs are important causes of MD, and the incidence and prevalence of such disorders are possibly underappreciated because of the lack of recognition. Objectives: To assess the incidence of all adverse drug reactions (ADRs) and estimate the prevalence of drug-induced MD among patients attending the clinic. Materials and Methods: This prospective observational study was conducted at an outpatient referral MD clinic of a tertiary care hospital for 1 year. The demographic data, drug intake, diagnosis, and ADRs experienced by the subjects were recorded. Causality assessment was done by Naranjo’s scale. Results: Incidence of ADR among patients who attended this clinic was 19.7% (151 out of 768 patients experienced at least one ADR). A total of 299 ADRs were detected out of which 30.8% were gastrointestinal, 28.4% psychiatric, and 26% MD effects. The commonly implicated suspect drugs were levodopa (37.8%) and trihexyphenidyl (25.1%). The prevalence of drug-induced MD was 10.15% and drug-induced dyskinesias and dystonias were the most common. Conclusion: MDs are clinically important neurological disorders which are often caused by drugs and interestingly drugs used for its management are also associated with high incidence of ADRs. Hence these ADRs should be carefully monitored.

Hepatic and hematological adverse effects of long-term low-dose methotrexate therapy in rheumatoid arthritis: An observational study

Objectives: Methotrexate (MTX) is the most commonly used cost-effective disease-modifying antirheumatoid drug (DMARD). Its main dose-limiting adverse effects are hepatic and hematopoietic. This cross-sectional, observational study evaluated the prevalence of hepatic and hematological adverse effects with long-term low-dose MTX therapy. Materials and Methods: Rheumatoid arthritis (RA) patients taking ≤15 mg/week MTX for at least 2 years were enrolled from the rheumatology outpatient department. Demographic, disease, drug treatment profiles, and hematological and hepatic enzyme levels were noted. Results: Of the 204 patients enrolled, the frequency of raised alanine transaminase level (≥3-fold rise above the upper limit of normal) was 6.37% (95% confidence interval of 3.76–10.59) including two biopsy-proven hepatic fibrosis cases. About 5.4% had severe anemia (<8 g/dl) and 4.4% had leukopenia. Conclusion: Long-term low-dose MTX is safe in RA patients in the Indian population. The patterns of adverse effects were similar to those documented in earlier studies. However, our study results suggest that disease duration, cumulative MTX dose, concomitant DMARD intake are not risk factors associated with hepatic or hematological adverse effects.

Myopathy induced by statin-ezetimibe combination: Evaluation of potential risk factors.

Although both atorvastatin and ezetimibe may cause myopathy, statin-induced myopathy is less likely at low doses, and ezetimibe is only rarely reported to induce myopathy. Also, ezetimibe is not usually known to potentiate statin-induced myopathy. We report a case of myalgia with elevated serum creatinine phosphokinase in a patient after 2 months of therapy with fixed dose combination of atorvastatin and ezetimibe (10 mg each). At the time of the event, patient was undertaking moderate physical exertion in the form of brisk walking for 30–40 min a day and was detected to have low serum Vitamin D levels. The adverse event resolved after stopping atorvastatin-ezetimibe combination therapy. Potential risk factors, such as physical exertion and Vitamin D deficiency, co-existent in dyslipidemic patients, may exacerbate myopathy potential of these drugs, and precipitate muscular symptoms even at a low-dose.

Acute and sub-chronic oral toxicity study of black tea in rodents

Objectives: Systematic oral toxicity study for black tea (Camellia sinensis), the most commonly consumed variety of tea, is lacking. The present study was undertaken to assess the iron load on black tea (Camellia sinensis) and its safety aspects in animals. Materials and Methods: The analysis of iron was done in six tea samples as per American Public Health Association method using flame atomic absorption spectrophotometer. Maximum physical iron-loaded tea sample was identified on black tea sample 2 (BTS-2), and this was further studied for acute and 90-day sub-chronic toxicity following Organisation for Economic Co-operation and Development guidelines. Results: Black tea sample 2 did not show any signs of toxicity or mortality at up to 2 g/kg per oral dose in Swiss albino mice. 90-day toxicity studies in Wistar rats did not reveal any evidence of toxicity at up to 250 mg/kg/day (2.5% infusion of BTS-2) oral dose as exhibited by regular observations, body weight, food consumption, hematology, serum chemistry, organ weights, and histopathology. Further, serum iron, total iron binding capacity, unsaturated iron binding capacity, and ferritin were not altered after 90 days of treatment. Masson trichrome staining and Perls’ staining did not reveal any abnormalities in hepatic tissue following 90-day treatment of high iron-loaded BTS-2. Conclusions: This safety study provides evidence that BTSs, in spite of relatively high iron content, show no significant iron-related toxicity on acute or sub-chronic oral administration in animals.