Therapeutic audit of patients on warfarin in an anticoagulation clinic of a tertiary care hospital.

Background: Studies have reported huge variations in the prescribing practice of warfarin. We carried out a clinical audit of warfarin use in an anticoagulation clinic of a tertiary care hospital. Methods: Patients receiving warfarin for at least 6 months were recruited and the following details were collected: demographics (age, body weight and gender); diagnoses; concomitant drugs. We calcula-ted CHA2DS2-VASc, HASBLED and SAMe-TT2R2 scores for each study participant. Statins, proton pump inhibitors, carbamazepine and amiodarone were the concomitant drugs identified with potential drug interaction with warfarin in patients. Results: Two hundred and three patients were recruited. Almost one-third of the study population had poor anticoagulation status. CHA2DS2-VASc and HASBLED scores were the significant predictors of appropriate anticoagulation. Poor anticoagulation status was observed more commonly in the first 6 months following which improvements were seen. Nearly half-of the time abnormal PT-INR was observed to be either between 2 to 2.4 (for patients with heart valve replacements) or 1.5 to 1.9 (for other indications). Significant number of patients without any potentially interacting drugs was observed with higher risk of supra-therapeutic PT-INR. Conclusion: We observed a similar proportion of patients with adequate anticoagulation in our study participants as reported in other populations; and have identified categories at risk for poor anticoagulation. It is the need of the hour to develop in-house algorithm in compliance to international standards for dose titration of warfarin.

Biomarkers in neonates receiving potential nephrotoxic drugs.

OBJECTIVE: Novel biomarkers, such as kidney injury molecule-1 (KIM-1), cystatin, and neutrophil gelatinase-associated lipocalin (NGAL) were shown to predict acute kidney injury (AKI) earlier than serum creatinine in critically ill. We carried out the present study to evaluate these biomarkers in addition to conventional in our neonates. PATIENTS AND METHODS: We recruited 70 neonates of various gestational age groups receiving one or more potential nephrotoxic drug/s. Daily urine samples were collected for estimating KIM-1, cystatin, and NGAL. Modified neonatal kidney disease improving global outcomes (mKDIGO) classification was used in defining AKI. RESULTS: A significant trend in increased urine concentrations of KIM-1, cystatin, and NGAL were observed as we proceed from term to preterm categories. Strong positive correlation was observed between urine albumin and urine albumin creatinine ratio (ACR), and strong negative correlations between urine creatinine and urine cystatin, and between urine creatinine with urine NGAL. A moderate positive correlation was observed between urine KIM-1 and urine cystatin, between urine KIM-1 and urine NGAL, and between urine cystatin and urine NGAL; and a moderate negative correlation was observed between urine creatinine and urine KIM-1. Seven neonates met the mKDIGO criteria for AKI and ROC plot revealed that baseline KIM-1 and NGAL can significantly predict possible drug-induced AKI in neonates. CONCLUSIONS: Urine KIM-1, cystatin, and NGAL are significantly correlated with several other conventional biomarkers that reflect renal function in critically ill neonates. Baseline urine KIM-1 and NGAL concentrations can predict the AKI following potential nephrotoxic drug use in this population.

Topical preparations for the treatment of mild-to-moderate acne vulgaris: systematic review and network meta-analysis.

BACKGROUND: Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective. OBJECTIVES: To identify the most effective and best tolerated topical treatments for acne using network meta-analysis. METHODS: CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA. RESULTS: A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low. CONCLUSIONS: Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.

Interventions for oral lichen planus: A systematic review and network meta-analysis of randomized clinical trials.

BACKGROUND: Corticosteroids, calcineurin inhibitors, vitamin D, photodynamic therapy, herbal drugs are some of the interventions tried in clinical trials for treating oral lichen planus. We carried out the present network meta-analysis to compare the above-mentioned interventions. METHODS: Electronic databases were searched for randomized clinical trials evaluating interventions in patients with symptomatic oral lichen planus. Clinical resolution, clinical score, pain resolution, pain score, and adverse effects were the outcomes evaluated. RESULTS: Fifty-five (2831 patients) trials were included. Corticosteroids (OR: 13.6; 95% CI: 1.2, 155.4), pimecrolimus (OR: 14.7; 95% CI: 1.7, 125), purslane (OR: 18.4; 95% CI: 3.5, 97), and ozonized water/corticosteroids (OR: 52; 95% CI: 1.4, 1882.6) had better rates of clinical resolution compared to placebo. Corticosteroids (OR: 3.18; 95% CI: 1.2, 8.43), ozonized water/corticosteroids (OR: 9.9; 95% CI: 2.7, 36.2), aloe vera (OR: 13; 95%: 1.5, 111.8), pimecrolimus (OR: 18.8; 95% CI: 2, 177.4) and hyaluronic acid (OR: 24.8; 95% CI: 1.3, 457.6) were significantly associated with superior rates of pain resolution compared to placebo. Pimecrolimus and cyclosporine were associated with significantly higher risk of adverse effects than placebo. CONCLUSION: Topical corticosteroids were the most effective drug class for treating oral lichen planus.

Intravenous frusemide does not interact pharmacodynamically with acetaminophen in critically ill preterm neonates with patent ductus arteriosus.

OBJECTIVE: Evidence is controversial regarding the effect of concomitant frusemide with acetaminophen therapy in neonates with patent ductus arteriosus (PDA). PATIENTS AND METHODS: Critically ill neonates diagnosed with hemodynamically significant PDA by echocardiography and receiving intravenous acetaminophen were recruited. Dosing regimens of frusemide, and acetaminophen, and the sizes of ductus arteriosus following treatment, were evaluated. RESULTS: Fifty-one neonates were recruited. Forty-six (90.2%) had moderate-sized, and five (9.8%) had large-sized ductus arteriosus. Forty (78.4%) neonates had a successful closure. Twenty-four received concomitant frusemide with a median (range) cumulative dose of 3 (0.8-13) mg; duration of 2 (1-13) days; and a fraction of overlapping days with acetaminophen therapy of 0.4 (0.2-1). Twenty-one (87.5%) neonates that received frusemide had a successful ductal closure compared to 70.4% of those without (p >0.05). CONCLUSIONS: We did not observe any significant influence in the outcomes of acetaminophen therapy with concomitant frusemide in preterm neonates with PDA.

Powered toothbrushes for plaque control in fixed orthodontic patients: a network meta-analysis.

BACKGROUND: Orthodontic patients are at greater risk due to the inability to clean around the components directly bonded to teeth. Hence, the aim of the present network meta-analysis is to compare the utility of powered toothbrushes in plaque control in patients with orthodontic brackets compared with manual tooth brushing. METHODOLOGY: Necessary data were extracted and analysed for Risk of Bias. Heterogeneity was assessed using Chi-square and I2 tests. Random effects model was used for both direct and mixed treatment comparisons. Standardized mean difference with 95% confidence interval was the effect estimate for plaque and bleeding scores and mean difference for pocket depth. Inconsistencies between the direct and indirect estimates were evaluated by H-statistics. GRADE approach was used to assess the quality of evidence. RESULTS: Pooled results from 14 studies showed significantly higher plaque scores in patients using manual toothbrushes. Pooled results from 13 studies showed significant higher bleeding scores as well with manual brushes. There was a significant reduction in pocket depth with electric toothbrushes. CONCLUSION: Powered toothbrushes are a promising alternative for plaque control in patients with fixed orthodontic brackets. Stronger evidence can be established with addition of long-term clinical trials based on the recommendations.

Patient preference and operating time for digital versus conventional impressions: a network meta-analysis.

BACKGROUND: Digital impression techniques have seen many advancements, with new hardware and software being developed each year. The technical advantages of these systems are real-time visualization, evaluation and archive, segmental capture, ease of recapture if necessary, economical in terms of no use of impression material or trays or disinfection, easy file transfer and communication with the laboratory. However patient satisfaction is one major factor that might influence the choice of impression technique. The aim of this network meta-analysis was to identify statistically the evidence on overall patient preferences relative to digital versus conventional impression techniques, in addition to the time taken in making these impressions. METHODOLOGY: Randomized or prospective clinical studies were identified based on the inclusion criteria in PUBMED, DARE and COCHRANE databases; subsequently pertinent data were extracted. Risk of bias of the included studies was assessed using the Cochrane risk of bias tool and Newcastle-Ottawa scale. Heterogeneity amongst the studies in direct comparison was assessed by Chi-square and I2 tests using the Inverse variance heterogeneity model. Direct comparison estimates were derived by pooling the data from studies that compared the same intervention. Indirect comparison pooled estimates were derived by using the data amongst the studies, through a common comparator, using MetaXL software. Mean differences and Odds ratio at 95% confidence interval were used as the effect estimates, while inconsistencies were evaluated by H-statistics. GRADE working group approach was used to assess the quality of available evidence. RESULTS: Fourteen studies were included. Results from 11 studies  on 471 patients (236-Digital; 235-conventional) were pooled for patient preference with 95% confidence interval. The Forest plot showed a pooled estimate of 31.23 [5.95, 163.87], showing a statistically significant number of patients favouring digital impressions. Results from 11 studies reported the time taken in 589 patients (278-digital; 311 conventional). The pooled estimate (2.72 [0.08, 5.32]) (95% confidence interval) showed a statistically significant increase in the time required to make digital impressions. The overall time taken in minutes for the interventions in the digital group in decreasing order were: LAVA Cos (8.14[3.64,12,26] (statistically significant); I tero (4.11[-1.02,9.24]; CEREC (0.34[-4.14,4.82]). CONCLUSION: There was an overall preference for digital impressions, although the time required is longer. The factors related to the digital system, the operator and the patient were studied, with recommendations forming a basis for possible hardware and software upgrades of the digital systems that can produce significant improvement in the acceptance rate for both the patient and the clinician.

Pulmonary Infections Caused by Emerging Pathogenic Species of Nocardia.

Pulmonary infections are the most common clinical manifestations of Nocardia species. There is an increase in cases of nocardial infections occurring worldwide attributable to the increase in the immunosuppressed population. The availability of molecular methods has aided the detection of more number of cases as well as unusual species. Still, it remains one of the most underdiagnosed pathogens. Recognition of drug resistance in this organism has now mandated early and precise identification with speciation for effective treatment and management. Nocardial species identity can predict antimicrobial susceptibility and guide clinical management. Here, we report two cases of pulmonary nocardiosis caused by unusual species of Nocardia, namely, N. cyriacigeorgica and N. beijingensis identified by 16S rRNA gene-based sequencing. These cases are being reported for their rarity.

Effect of metformin on thyroid function tests in patients with subclinical hypothyroidism: an open-label randomised controlled trial.

PURPOSE: Though most of the observational studies have shown that metformin can reduce serum thyroid stimulating hormone (TSH) level in patients of hypothyroidism with diabetes or polycystic ovarian disease, randomised controlled trials are sparse. The primary objective of this study was to evaluate the effect of metformin on thyroid function tests (TSH, free T4, and free T3) in patients with subclinical hypothyroidism (SCH). METHODOLOGY: In this open label, parallel arm, randomised controlled trial, 60 patients of SCH (TSH 5.5-10 mIU/L) were randomised to either metformin group (1500 mg/day) or control group. RESULT: A total of 46 patients (23 in each group) completed the study and no significant difference in serum TSH, free T4 or free T3 was found in between the 2 groups. Neither there was any significant change in serum TSH, free T4 or free T3 (pre and post 6 months) within the individual groups. However, the rate of normalisation of serum TSH in patients with negative thyroid antibody was significantly higher than patients with positive thyroid antibody (71.4% vs. 18.8%; P = 0.026) in metformin group in post hoc analysis. Fasting plasma glucose, serum high-density lipoprotein and indices of insulin sensitivity significantly improved in metformin group. Four patients (17%) had mild gastrointestinal adverse effects in the metformin group. CONCLUSION: We did not find any significant change in thyroid function test in patients with SCH with metformin therapy.

Force Decay Characteristics of commonly used Elastomeric Chains on Exposure to various Mouth Rinses with different Alcohol Concentration: An in vitro Study.

AIM: The aim of this study was to test the effect of varying alcohol concentrations of various commercially available mouth-washes on force decay of elastomeric chains in prestretched and unstretched condition. MATERIALS AND METHODS: A total of five specimen groups were tested with a total sample size of 180 specimens. A specimen is described as a three-link, short module, clear elastomeric chain (3M Unitek, Ortho Plus, Ortho Organizer). The control and test groups were independently submerged in separate 37°C artificial saliva to simulate the oral conditions. Effects of different solution groups and time (initial, 1, 7, 14, 21, and 28 days) on three different elastomeric chains and force (cN) are analyzed with two-way analysis of variance; pair-wise comparisons are done by t-test. RESULTS: Higher mean force was recorded initially followed by 24 hours >7 days >14 days >21 days and 28 days respectively. The difference in mean force decay among the different time intervals was found to be statistically significant (p < 0.001). Among the different solutions, higher mean force was recorded in 21.6% alcohol mixture > Listerine 8.38% > Wokadine > alcohol mixture 8.38% > artificial saliva. CONCLUSION: In conclusion, alcohol-containing mouth rinses cause an increase in force decay of elastomeric chain over time. CLINICAL SIGNIFICANCE: These mouth rinses are commonly recommended during orthodontic treatment. The orthodontist can know better that the alcohol content of the mouth rinses and the structural and molecular modification results in the decay of elastomeric chain.

An in vitro Evaluation of Friction Characteristics of Conventional Stainless Steel and Self-ligating Stainless Steel Brackets with different Dimensions of Archwires in Various Bracket-archwire Combination.

AIM: The purpose of this research is to compare the frictional attributes of stainless steel conventional brackets and self-ligating stainless steel brackets with different dimensions of archwires. MATERIALS AND METHODS: The test was carried with two sets of maxillary brackets: (1) Conventional stainless steel (Victory Series), (2) stainless steel self-ligating (SmartClip) without first premolar brackets. Stainless steel, nickel-titanium (NiTi), and beta-Ti which are the types of orthodontic wire alloys were tested in this study. To monitor the frictional force, a universal testing machine (Instron 33R 4467) that comprises 10 kg tension load cell was assigned on a range of 1 kg and determined from 0 to 2 kg, which allows moving of an archwire along the brackets. One-way analysis of variance was used to test the difference between groups. To analyze the statistical difference between the two groups, Student's t-test was used. RESULTS: For Victory Series in static friction, p-value was 0.946 and for kinetic friction it was 0.944; at the same time for SmartClip, the p value for static and kinetic frictional resistance was 0.497 and 0.518 respectively. Hence, there was no statistically significant difference between the NiTi and stainless steel archwires. CONCLUSION: It is concluded that when compared with conventional brackets with stainless steel ligatures, self-ligating brackets can produce significantly less friction during sliding. Beta-Ti archwires expressed high amount of frictional resistance and the stainless steel archwires comprise low frictional resistance among all the archwire materials. CLINICAL SIGNIFICANCE: In orthodontics, frictional resistance has always had a major role. Its ability to impair tooth movement leads to the need for higher forces to move the teeth and it extends the treatment time which results in loss of posterior anchorage. Friction in orthodontics is related with sliding mechanics when a wire is moving through one or a series of bracket slots.

Radiation endurance in Al2O3 nanoceramics.

The lack of suitable materials solutions stands as a major challenge for the development of advanced nuclear systems. Most issues are related to the simultaneous action of high temperatures, corrosive environments and radiation damage. Oxide nanoceramics are a promising class of materials which may benefit from the radiation tolerance of nanomaterials and the chemical compatibility of ceramics with many highly corrosive environments. Here, using thin films as a model system, we provide new insights into the radiation tolerance of oxide nanoceramics exposed to increasing damage levels at 600 °C -namely 20, 40 and 150 displacements per atom. Specifically, we investigate the evolution of the structural features, the mechanical properties, and the response to impact loading of Al2O3 thin films. Initially, the thin films contain a homogeneous dispersion of nanocrystals in an amorphous matrix. Irradiation induces crystallization of the amorphous phase, followed by grain growth. Crystallization brings along an enhancement of hardness, while grain growth induces softening according to the Hall-Petch effect. During grain growth, the excess mechanical energy is dissipated by twinning. The main energy dissipation mechanisms available upon impact loading are lattice plasticity and localized amorphization. These mechanisms are available in the irradiated material, but not in the as-deposited films.

Comparison of implant supported mandibular overdentures and conventional dentures on quality of life: a systematic review and meta-analysis of randomized controlled studies.

BACKGROUND: Conventional complete dentures and implant supported overdentures are commonly used by dentists to treat completely edentulous mandibular arches. There have been problems associated with retention and stability while treating completely edentulous mandibular arches compared to maxillary arches. Many factors have been attributed to this, primarily focusing on the decreased area available for support and increased resorption. Implant supported overdentures have increased the treatment options for resorbed ridges, especially the mandible. However, no reports have proved the superiority of one treatment option over the other, especially in terms of patient-centric outcome measures such as the Oral Health Impact Profile (OHIP). Hence, this meta-analysis was conducted. METHODS: A literature search of Medline (via PubMed), the Cochrane Central Register of Clinical Trials (CENTRAL) and the Database of Abstracts of Reviews of Effects (DARE) was performed. The reviewers screened titles, abstracts and performed full-text screening of eligible studies. The references from these studies were further screened for additional relevant studies. A random effects model was applied to measure the significance of the per cent mean difference in OHIP scale improvement between implant and conventional dentures. The Cochrane Risk of Bias Tool was applied to assess the selection, ascertainment and selective reporting biases. RESULTS: Five studies were reviewed and identified. Results of 441 patients (228 implant and 213 conventional) were pooled for analysis of primary outcome and other secondary outcomes. A forest plot of total OHIP scores and for secondary outcomes were obtained between the interventions. Results of 441 patients (228 implant and 213 conventional) were pooled for analysis of primary outcome with a mean difference [95% confidence interval] in the score of -30.72[-48.39, -13.05]; mean difference [95% confidence interval] in the score of -26.45[-43.56, -9.35] for functional limitation; -29.16[-60.89, 2.56] for physical pain; -77.61[-154.63, -0.60] for psychological discomfort; -33.70[-47.96, -19.44] for physical disability; -41.17[-55.93, -26.40] for psychological disability; -17.27[-29.44, 5.10] for social disability; and -28.45[-33.97, -22.92] for handicap. A statistically significant difference favouring the implant group was obtained except for physical pain. CONCLUSIONS: The implant overdenture group performed better in regard to patient satisfaction as measured using the OHIP questionnaire. Further studies are required to identify superiority between the two treatment options.

Malignant mesothelioma, hypoalbuminaemia and the effect of carboplatin/pemetrexed on survival.

AIMS: The incidence of malignant mesothelioma in the UK is increasing. The aim of this study was to determine the prognostic factors and assess the effect of carboplatin/pemetrexed chemotherapy on survival. MATERIALS AND METHODS: Cases of malignant mesothelioma diagnosed between 1998 and 2011 were stratified by year of diagnosis. Factors affecting survival were assessed by Cox's proportional hazards regression. RESULTS: In total, there were 202 new cases of malignant mesothelioma between 1998 and 2011. The age-standardised rate (95% confidence interval) increased from 2.84 (2.06-3.60) to 4.44 (3.50-5.4); P = 0.025. Chemotherapy use has increased since 2006: 52% versus 34% (P = 0.007). The median survival (interquartile range) by year diagnosed was 9 (4.0-21.9) versus 10 (3.8-20.1) months for 1998-2005 versus 2006-2011. Independent predictors of survival [hazard ratio (95% confidence interval)] were: histology, sarcomatoid 2.22 (1.49-3.31) and unspecified non-epithelioid 1.50 (1.06-2.14); Eastern Cooperative Oncology Group performance status ≥3 2.86 (1.64-5.00); hypoalbuminaemia 2.07 (1.47-2.92), carboplatin/pemetrexed chemotherapy 0.56 (0.38-0.80). CONCLUSION: The incidence of mesothelioma is increasing. Adverse prognostic factors include non-epithelioid histology, performance status and hypoalbuminaemia. Overall survival has not improved significantly, but treatment with carboplatin/pemetrexed chemotherapy is associated with a significant survival benefit.

Septic Arthritis of Hip Caused by Salmonella typhi: A Case Report.

Salmonella typhi usually produces enteric fever and gastroenteritis. The infection may spread through blood stream and present as local suppurative lesions which may involve any site including the bone and joints. We report a case of septic arthritis of hip in a patient with systemic lupus erthematosis. The case is presented for its rarity and to highlight the atypical manifestations of Salmonella typhi in endemic regions.

Fretting wear study of surface modified Ni-Ti shape memory alloy.

A combination of shape memory characteristics, pseudoelasticity, and good damping properties make near-equiatomic nickel-titanium (Ni-Ti) alloy a desirable candidate material for certain biomedical device applications. The alloy has moderately good wear resistance, however, further improvements in this regard would be beneficial from the perspective of reducing wear debris generation, improving biocompatibility, and preventing failure during service. Fretting wear tests of Ni-Ti in both austenitic and martensitic microstructural conditions were performed with the goal of simulating wear which medical devices such as stents may experience during surgical implantation or service. The tests were performed using a stainless steel stylus counter-wearing surface under dry conditions and also with artificial plasma containing 80 g/L albumen protein as lubricant. Additionally, the research explores the feasibility of surface modification by sequential ion implantation with argon and oxygen to enhance the wear characteristics of the Ni-Ti alloy. Each of these implantations was performed to a dose of 3 x 10(17) atom/cm(2) and an energy of 50 kV, using the plasma source ion implantation process. Improvements in wear resistance were observed for the austenitic samples implanted with argon and oxygen. Ion implantation with argon also reduced the surface Ni content with respect to Ti due to differential sputtering rates of the two elements, an effect that points toward improved biocompatibility.

Effect of an antidiabetic extract of Catharanthus roseus on enzymic activities in streptozotocin induced diabetic rats.

Hypoglycemic activity was detected in dichloromethane:methanol extract (1:1) of leaves and twigs of Catharanthus roseus (family Apocynaceae), a traditionally used medicinal plant, using streptozotocin (STZ) induced diabetic rat model. Extract at dose 500 mg/kg given orally for 7 and 15 days showed 48.6 and 57.6% hypoglycemic activity, respectively. Prior treatment at the same dose for 30 days provided complete protection against STZ challenge (75 mg/kg/i.p.x1). Enzymic activities of glycogen synthase, glucose 6-phosphate-dehydrogenase, succinate dehydrogenase and malate dehydrogenase were decreased in liver of diabetic animals in comparison to normal and were significantly improved after treatment with extract at dose 500 mg/kg p.o. for 7 days. Results indicate increased metabolization of glucose in treated rats. Increased levels of lipid peroxidation measured as 2-thiobarbituric acid reactive substances (TBARS) indicative of oxidative stress in diabetic rats were also normalized by treatment with the extract.

Effect of high altitude (7,620 m) exposure on glutathione and related metabolism in rats.

Reduced and oxidised glutathione (GSH and GSSG) contents, and glutathione reductase, and glutathione S-transferase activities were studied in the livers, muscles, and blood/erythrocytes of male Sprague-Dawley rats exposed to intermittent hypoxia (6 h.day-1) at a simulated altitude of 7,620 m for 1, 7, 14, and 21 days. Significant decreases in GSH and increases in GSSG contents were observed in the muscles and blood of hypoxia-exposed rats in comparison to unexposed rats. Significant declines in GSH content by 43% and 45% respectively in muscles and blood were observed in the group exposed for 1 day which tended to recover on subsequent exposure. Glutathione reductase and glutathione S-transferase activities were decreased in the livers and erythrocytes of hypoxia-exposed rats, but were increased significantly in muscle. Lipid peroxidation was also increased in the livers and muscles of exposed rats. The changes were indicative of an increased production of reactive oxygen species and an impairment of drug and xenobiotic metabolism during exposure to high altitude hypoxia.