Widespread non-adherence to evidence-based maternity care guidelines: a population-based cluster randomised household survey.

OBJECTIVE: To assess the quality of maternity care in an Indian metropolitan city. STUDY DESIGN: Three-stage cluster randomised cross-sectional survey. SETTING: Sixty selected colonies of Delhi. POPULATION: One thousand eight hundred and one subjects (of 2286 eligible) were enrolled from 118 446 houses. Women who had delivered a live viable birth in the past 6 months were selected for the study. METHODS: In stage 1, 20 wards (of 150) were selected using a probability-proportionate-to-size systematic method. In stage 2, one colony from each income stratum (high, middle and low) was selected from each ward by simple random sampling. In stage 3, a house-to-house survey was conducted to recruit 30 women for administering a peer-reviewed and pilot-trialled questionnaire. MAIN OUTCOME MEASURES: Caesarean section rate, induction rate and episiotomy rate. RESULTS: National health targets such as iron supplementation advice (>96%), tetanus vaccination (>81%), and ≥3 antenatal visits (>90%) were largely achieved across health care facilities but not in home deliveries. Interventions were lower in public than private hospitals: caesarean section [23.7% (20.2-27.7) versus 53.8% (49.3-58.3)], induction [20.6% (17.5-24.25) versus 30.8% (26.8-33.2)] and episiotomy [57.8% (52.3-63.1) versus 79.4% (71.0-85.9)]. Private hospitals achieved better labour support rates [1.1% (0.5-2.2) versus 14.6% (8.5-24.1)] and pain relief [0.9% (0.4-2.0) versus 9.9 (6.5-14.8)]. Pubic hair shaving [16.2% (11.5-22.5) versus 36.4% (29.9-43.4)], enema [20.2% (15.5-26.0) versus 57.3% (49.5-64.8)], and IV fluids during labour [44.0% (36.2-52.2) versus 38.7% (29.3-49.1)] were widely prevalent in public and private hospitals. CONCLUSION: Present practices fall short of evidence-based guidelines, with relative overuse of interventions in private hospitals and deficiency of patient-centred practices such as labour support in public hospitals.

Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools.

Optogenetic tools have become indispensable in neuroscience to stimulate or inhibit excitable cells by light. Channelrhodopsin-2 (ChR2) variants have been established by mutating the opsin backbone or by mining related algal genomes. As an alternative strategy, we surveyed synthetic retinal analogues combined with microbial rhodopsins for functional and spectral properties, capitalizing on assays in C. elegans, HEK cells and larval Drosophila. Compared with all-trans retinal (ATR), Dimethylamino-retinal (DMAR) shifts the action spectra maxima of ChR2 variants H134R and H134R/T159C from 480 to 520 nm. Moreover, DMAR decelerates the photocycle of ChR2(H134R) and (H134R/T159C), thereby reducing the light intensity required for persistent channel activation. In hyperpolarizing archaerhodopsin-3 and Mac, naphthyl-retinal and thiophene-retinal support activity alike ATR, yet at altered peak wavelengths. Our experiments enable applications of retinal analogues in colour tuning and altering photocycle characteristics of optogenetic tools, thereby increasing the operational light sensitivity of existing cell lines or transgenic animals.

Targeting miRNAs for drug discovery: a new paradigm.

The discovery of miRNAs and the establishment of it's clinical links with multiple diseases has led to a paradigm shift in the drug development pipeline of major pharmaceutical companies and has given birth to several biotechnology enterprises revolving around these magic molecules. The miRNA profiling studies over the last few years have indicated implicit involvement of miRNAs in the pathobiology of cancer, diabetes, infectious diseases as well as cardiovascular, neurological and immune system disorders. This information is currently being translated into tools for diagnosis, prognosis and predicting response to treatment. In addition, active and vigorous investigations are ongoing in several laboratories across academia and industry to decipher the precise molecular functions and mechanism of action for key miRNAs with therapeutic potential. Knowledge gained from these efforts will surely pave the way for designing effective R&D strategies and will revolutionize the way we diagnose and treat various diseases. The present review attempts to track the evolutionary progression of microRNA research from it's early infancy years to its maturity into a dynamic field of drug discovery.

Meta-analysis: efficacy of bovine lactoferrin in Helicobacter pylori eradication.

BACKGROUND: Several randomized-controlled trials (RCTs) have sought to determine the efficacy of bovine lactoferrin in Helicobacter pylori eradication with equivocal results. AIM: To evaluate the effect of bovine lactoferrin supplementation in H. pylori eradication. METHODS: Electronic databases, reviews, bibliographies, abstracts and conference proceedings were searched. Included trials had to be randomized or quasi-randomized and controlled, using bovine lactoferrin in the intervention group, treating Helicobacter-infected subjects and evaluating eradication of H. pylori as an outcome. RESULTS: The search identified five eligible RCTs (of 169). Data were available for 682 subjects (bovine lactoferrin group-n = 316; control group-n = 366). The pooled odds ratio (five studies) for eradication by intention-to-treat analysis was 2.22 (95% CI 1.44-3.44; P = 0.0003) using the fixed effects model (FEM) and 2.24 (95% CI 1.15-4.35; P = 0.0003) using the random effects model (REM) (Cochran's Q = 6.83; P = 0.145). The pooled risk difference was 0.11 (95% CI 0.05-0.16; P = 0.0001) by FEM (Cochran's Q = 6.67; P = 0.154) and 0.10 (95% CI 0.04-0.17; P = 0.0023) by REM. There was no significant difference in incidence of adverse effects. CONCLUSION: Bovine lactoferrin potentially improves H. pylori eradication rates without any impact on adverse effects, but available evidence is limited and further research is necessary to confirm the findings.

A double-blind, randomized, placebo-controlled trial of the short-term effect of vitamin D3 supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men.

AIM: To determine the short-term effect of vitamin D(3) supplementation on insulin sensitivity in apparently healthy, middle-aged, centrally obese men. SUBJECTS AND METHODS: A double-blind randomized controlled trial was conducted at a tertiary care facility in which 100 male volunteers aged > or = 35 years received three doses of vitamin D(3) (120,000 IU each; supplemented group) fortnightly or placebo (control group). Hepatic fasting insulin sensitivity [homeostasis model assessment (HOMA), quantitative insulin-sensitivity check index, HOMA-2], postprandial insulin sensitivity [oral glucose insulin sensitivity (OGIS)], insulin secretion (HOMA%B, HOMA2-%B), lipid profile and blood pressure were measured at baseline and at 6 weeks' follow-up. RESULTS: Seventy-one of the recruited subjects completed the study (35 in supplemented group, 36 in control group). There was an increase in OGIS with supplementation by per protocol analysis (P = 0.038; intention-to-treat analysis P = 0.055). The age- and baseline 25-hydroxyvitamin D level-adjusted difference in change in OGIS was highly significant (mean difference 41.1 +/- 15.5; P = 0.01). No changes in secondary outcome measures (insulin secretion, basal indices of insulin sensitivity, blood pressure or lipid profile) were found with supplementation. CONCLUSION: The trial indicates that vitamin D(3) supplementation improves postprandial insulin sensitivity (OGIS) in apparently healthy men likely to have insulin resistance (centrally obese but non-diabetic).

Direct cost of ambulatory care of type 2 diabetes in the middle and high income group populace of Delhi: the DEDICOM survey.

OBJECTIVE: To estimate the direct cost of ambulatory care in diabetes patients in the middle and high income group populace of Delhi. RESEARCH DESIGN AND METHODS: We analyzed the drugs, investigations, consultation and monitoring related data available from a survey of 35- 65-year-old known diabetes patients conducted using a probability-proportionate-to-size 2-stage cluster design to calculate the direct cost of ambulatory diabetes care. RESULTS: A total of 819 subjects were enrolled from 20,666 houses. The average estimate of direct annual expenditure on ambulatory care of diabetes was approximately Rs. 6000 (approximately US$ 150). Time elapsed since diagnosis (p<0.001), education (p=0.011), gross family income (p=0.002), presence of co-morbidities (p=0.009) and requirement for useof oral hypoglycemic agents (p<0.001) or insulin (p<0.001) were significant correlates. Direct ambulatory cost of care comprised 1-3% of the gross family income of the subjects. CONCLUSION: Despite the limitations of the present study it may be concluded that a majority of the diabetes patients spend a significant proportion of their family income on diabetes related expenditure. The cost is higher for subjects with longer duration since diagnosis, those with higher education or income, those with co-morbidities and those requiring oral hypoglycemic agents or insulin.

Targeting human 8-oxoguanine DNA glycosylase to mitochondria protects cells from 2-methoxyestradiol-induced-mitochondria-dependent apoptosis.

2-Methoxyestradiol (2-ME), an endogenous estrogen metabolite of 17beta-estradiol, is known to induce mitochondria-mediated apoptosis through several mechanisms. We sought to study the effect of mitochondrialy targeted hOGG1 (MTS-hOGG1) on HeLa cells exposed to 2-ME. MTS-hOGG1-expressing cells exposed to 2-ME showed increased cellular survival and had significantly less G(2)/M cell cycle arrest compared to vector-only-transfected cells. In addition, 2-ME exposure resulted in an increase in mitochondrial membrane potential, increased apoptosis, accompanied by higher activation of caspase-3, -9, cleavage of Bid to tBid and protein poly(ADP-ribose) polymerase (PARP) cleavage in HeLa cells lacking MTS-hOGG1. Fas inhibitors cerulenin or C75 inhibited 2-ME-induced caspase activation, PARP cleavage, apoptosis and reversed mitochondrial membrane hyperpolarization, thereby recapitulating the increased expression of MTS-hOGG1. Hence, MTS-hOGG1 plays an important protective role against 2-ME-mediated mitochondrial damage by blocking apoptosis induced through the Fas pathway.

Aberrant promoter methylation and tumor suppressive activity of the DFNA5 gene in colorectal carcinoma.

To identify novel methylated gene promoters, we compared differential RNA expression profiles of colorectal cancer (CRC) cell lines with or without treatment of 5-aza-2'-deoxycytidine (5-aza-dC). Out of 1776 genes that were initially 'absent (that is, silenced)' by gene expression array analysis, we selected 163 genes that were increased after 5-aza-dC treatment in at least two of three CRC cell lines. The microarray results were confirmed by Reverse Transcription-PCR, and CpG island of the gene promoters were amplified and sequenced for examination of cancer-specific methylation. Among the genes identified, the deafness, autosomal dominant 5 gene, DFNA5, promoter was found to be methylated in primary tumor tissues with high frequency (65%, 65/100). Quantitative methylation-specific PCR of DFNA5 clearly discriminated primary CRC tissues from normal colon tissues (3%, 3/100). The mRNA expression of DFNA5 in four of five colon cancer tissues was significantly downregulated as compared to normal tissues. Moreover, forced expression of full-length DFNA5 in CRC cell lines markedly decreased the cell growth and colony-forming ability whereas knockdown of DFNA5 increased cell growth in culture. Our data implicate DFNA5 as a novel tumor suppressor gene in CRC and a valuable molecular marker for human cancer.

Cardiovascular risk profile of subjects with known diabetes from the middle- and high-income group population of Delhi: the DEDICOM survey.

AIMS: To determine the cardiovascular risk profile of known diabetic patients from the middle- and high-income group populace of Delhi. METHODS: A cross-sectional survey was conducted using a probability proportionate to size (systematic) two-stage cluster design. Thirty areas were selected for a house-to-house survey to recruit a minimum of 25 subjects (known diabetes > or = 1 year; 35-65 years of age) per area. Data were collected by interview, blood sampling and from medical records. Scores from the Framingham, Joint British Society, United Kingdom Prospective Diabetes Study, Systematic Coronary Risk Evaluation, and Diabetes Epidemiology: Collaborative Analysis Of Diagnostic Criteria in Europe studies were used to calculate summary estimates of risk for coronary heart disease (CHD) and stroke. RESULTS: Eight hundred and nineteen subjects (25-30 per cluster) were enrolled. The mean age of the subjects was 53.6 years, the mean duration since diagnosis was 8.1 years, the mean body mass index was 28.1 kg/m(2), with 50.7% women; 74.3% had hypertension, 75.1% dyslipidaemia and 41.8% had poor glycaemic control (HbA(1c) > 8.0%); 8.4% had already had a myocardial infarction, whereas 2.3% had suffered a stroke. Only 17.6% were taking aspirin, 3.4% were on lipid-lowering drugs and 11.6% were taking antihypertensive agents. The risk engines estimated a 10-year CHD risk of 12.6-13.9% and a stroke risk of 5.1-5.7%. CONCLUSION: The study documents that the cardiovascular profile of known diabetes patients from the middle and higher income groups of Delhi is poor, strengthening the case for targeting interventions at patients, providers and other stakeholders for improvement.

The N-methyl-D-aspartate receptor type 2A is frequently methylated in human colorectal carcinoma and suppresses cell growth.

N-methyl-D-aspartate receptors (NMDARs) are the predominant excitatory neurotransmitter receptors in the mammalian brain. We found that among the three NMDARs examined (NMDAR1, NMDAR2A, NMDAR2B), only NMDAR2A was silenced in colorectal carcinoma (CRC) cell lines at basal line and reactivated by the demethylating agent, 5-aza-2'-deoxycytidine. NMDAR2A was expressed in normal colon epithelium, while expression was hardly detectable in colon cancer tissues. Promoter methylation of NMDAR2A was confirmed by bisulfite sequencing and combined bisulfite restriction analysis in the CRC cell lines and primary tumors. Quantitative methylation-specific PCR demonstrated NMDAR2A promoter hypermethylation in 82 of 100 primary human CRC, 15 of 100 normal corresponding epithelial tissues and 1 of 11 (9%) normal colon mucosa samples obtained from patients without cancer. Moreover, forced expression of full-length NMDAR2A in CRC cell lines induced apoptosis and almost abolished the ability of the cells to form colonies in culture, while NMDAR2A knockdown increased cell growth. Thus, NMDAR2A is commonly hypermethylated in primary human CRC and possesses tumor-suppressive activity.

Identification of differentially expressed genes in tobacco chewing-mediated oral cancer by differential display-polymerase chain reaction.

BACKGROUND: Identification of changes in gene expression that occur in oral squamous cell carcinoma (OSCC), after sufficient characterization, may yield novel molecular markers that may be useful in the diagnosis and disease management of oral cancer. MATERIALS AND METHODS: We used differential display-polymerase chain reaction (DD-PCR) to study critically the global gene expression profile of the oral tumour versus normal epithelium. The differential expression of fished out cDNA were confirmed by Northern blot and reverse transcription-PCR. The differentially expressed cDNA were cloned, sequenced and matched for homology in the GenBank database. RESULTS: We identified 13 cDNA that showed differential expression. Out of these we selected four cDNA showing consistent reproducibility. One of the cDNA expressed exclusively in tumour had a homology to DEK, a putative oncogene, and is linked to leukaemia, various cancers, HIV infection and several autoimmune disorders. Another cDNA expressed only in tumour had homology to sorcin protein. Sorcin is a 22-kDa calcium-binding protein and is associated with drug resistance in various cell lines. Apparently, sorcin expression might be responsible for drug resistance of OSCC and poor prognosis. Another cDNA showing 10 times overexpression in cheek tumour as compared to normal had homology to CDK6 gene. Hence, it seems from our results that CDK6 is dysregulated during oral carcinogenesis. The fourth cDNA was overexpressed in normal as compared to cheek tumour, but did not show any match in BLAST search. CONCLUSIONS: We conclude that there is an enormous significance of these differentially expressed cDNA in oral cancer progression as they can serve as cancer markers to be used for diagnosis and therapeutic intervention.

Short-term effect of complementary feeding frequency on total ad libitum consumption in 6- to 10-month-old breast fed Indian infants.

OBJECTIVE: To evaluate the short-term effect of frequency of complementary feeding on total ad libitum consumption in breast fed infants. METHODS: Twenty infants between 6 to 10 months of age were studied in a tertiary hospital in New Delhi for 48 hours. A traditional gruel made of rice and pulses (mean (SD) caloric density 54.22 (7.08) kcal/100 g) was offered in a randomized manner three (n = 10) or four (n = 10) times per day to the subjects over the first 24 hours with the subjects crossing over in the next 24 hours. They were allowed ad libitum breast feeding with no other food or fluid during the study period. Total caloric intake from breast milk and semisolids was computed for each day. RESULTS: There was no difference in the total caloric consumption with a semisolid feeding frequency of three or four times per day. The frequency of breast feeding and the breast feeding duration were also comparable (P > 0.05). However, breast milk intake was lower with a semisolid feeding frequency of 4 times/day (mean difference -61.2 g/d [95% confidence interval (CI) -122.2-0.32]; P = 0.051). The time required for feeding was higher (mean difference 14.75 min; P < 0.001), whereas the per meal intake of semisolids was lower with four semisolid feeds per day (mean difference -5.5 kcal/meal; [95% CI -10.19 to -0.81]; P = 0.024). CONCLUSION: In the short term, a change in semisolid feeding frequency from three to four times per day does not result in enhanced energy consumption because of lower breast milk intake.

Short-term effect of oil supplementation of complementary food on total ad libitum consumption in 6- to 10-month-old breastfed Indian infants.

OBJECTIVES: To evaluate the short term effect of oil supplementation of complementary food on total ad libitum consumption in breastfed infants. METHODS: Twenty infants between 6 to 10 months of age were studied in a tertiary hospital in New Delhi for 48 hours. They were given three semi-solid complementary feeds per day and ad libitum breastfeeding. No other food or fluid was allowed during the study period. A traditional gruel made of rice and pulses with high energy density (oil added; caloric density = 35 kcal/100 g) or low energy density (without oil; caloric density = 20 kcal/100 g) was offered in a randomized manner on consecutive days to all infants. Total caloric intake from breast milk and semi-solids was computed for each day. RESULTS: Infants consumed an equivalent amount of semi-solid (mean difference, 10.75 g/day; 95% confidence interval, 10.56 to 32.06; P = 0.304) and a lower amount of breast milk (mean difference, 121.1 g/day; 95% confidence interval, 35.13 to 207.16; P = 0.008) when high energy density feeds were offered. Although the caloric intake from semi-solids increased significantly (18.9 kcal/day; 95% confidence interval, 12.9 to 24.8; P < 0.001) with the high density diet, the total caloric intake (breast milk and study feeds) decreased (mean difference = 59.6 kcal/day; 95% confidence interval, 5.95 to 113.34; P = 0.031). An inverse relationship was found between caloric density of semi-solids and breast milk intake (r = 0.34, r = 0.12, P = 0.032). CONCLUSION: In the short term, oil supplementation of complementary food in breastfed infants does not translate into enhanced total caloric intake, primarily as a result of breast milk displacement.

Haematological effect of iron supplementation in breast fed term low birth weight infants.

AIMS: To determine the haematological effects of iron supplementation in predominantly breast fed term low birth weight (LBW) infants. METHODS: Seventy three healthy term LBW (<2500 g), predominantly breast fed infants aged 50-80 days were randomised into two groups to receive either iron (3 mg/kg/day) (iron supplemented (IS) group; n = 37) or placebo drops (placebo (P) group; n = 36). Haematological parameters and anthropometry were measured at baseline and repeated after four and eight weeks. RESULTS: A total of 62 subjects (32 in the IS group and 30 in the P group) came for the first follow up and 26 (13 in the IS group and 13 in the P group) reported for the second visit. There were no significant differences in serum ferritin and anthropometry. However, covariates (infant age, haemoglobin, and ferritin, and maternal haemoglobin) adjusted haemoglobin change was significantly higher in the IS group after four weeks (4.6 g/l; 95% CI 0.5 to 8.8) and eight weeks (8.6 g/l; 95% CI 1.8 to 15.4). CONCLUSIONS: Iron supplementation in a therapeutic dose in term breast fed LBW infants results in a marginal increase in haemoglobin. The functional benefit of this haemoglobin rise requires further evaluation.

Open labeled, randomized, switch-over study of two fixed doses (10/15mg) of aripiprazole : to evaluate its safety and efficacy in the treatment of Indian patients of schizophrenia.

Aripiprazole is a new anti psychotic with a unique receptor binding profile that combines partial agonistic activity at D2 receptor and 5-HT 1A receptor and potent antagonism at 5-HT 2A receptor. This receptor profile makes it possible for it to act as a dopamine system stabilizer. Based on various short term and long term studies, aripiprazole has been found to be effective in schizophrenia and has no significant adverse effect on QTc prolongation, prolactin, serum lipids, and has a low potential for weight gain. Present study aims to evaluate the efficacy and tolerability of aripiprazole (10-15mg/day) in the treatment of Indian patients of schizophrenia and to see its effect on QTc interval, prolactin levels, serum lipids, plasma sugar and weight gain in these patients. Outpatients with an ongoing/newly diagnosed ICD-10 Schizophrenia (n=136) were randomly assigned to 10 or 15 mg dose of Aripiprazole for a period of six weeks. Clinical response was evaluated by the Positive And Negative Symptoms Scale (PANSS), Clinical Global Impression (CGI) scale and safety was evaluated by observing spontaneously reported adverse events and changes in various laboratory parameters. Switching schizophrenic patients to aripiprazole (10/15 mg) from both conventional and atypical anti-psychotics was safe and well tolerated. Six weeks after switching to aripiprazole, patients showed improvements in PANSS scores (P< 0.001), EPS, prolactin levels and weight over the baseline levels. No difference was seen in the 10 or 15mg dose groups. One hospitalization was reported (due to hepatitis E). Common side effects reported were insomnia, somnolence, nausea, vomiting and diarrhea. Aripiprazole is a safe and effective anti psychotic in Indian patients - both in newly diagnosed, as well as, in patients not responding to or intolerant to other available typical and atypical antipsychotics.

P53 codon 72 polymorphism and susceptibility to development of human papilloma virus-associated cervical cancer in Indian women.

BACKGROUND: Infection with human papilloma virus (HPV) is an important etiological factor in the development of cervical cancer and it has been proposed that individuals homozygous for Arg/Arg at codon-72 of p53 are seven times more susceptible to HPV-mediated cancer. In this study, we have analyzed the genetic predisposition of the India population to HPV infection and cervical carcinogenesis. METHODS: We investigated 71 cases of squamous cell carcinoma of the cervix, 14 cases of low-grade squamous intraepithelial lesions, 25 cases of high-grade squamous intraepithelial lesions and 29 noncancer controls for presence of HPV16/18 infections by L-1-specific PCR assay and Southern hybridization, and its association with polymorphism at p53 codon 72. RESULTS: We observed that 69.1% (76/110) of the cervical cancer patients were HPV positive, among which the presence of HPV16, 18 and 16/18 coinfection was 40.9%, 8.2% and 13.6%, respectively. The allele frequencies of the three p53 genotypes Arg/Arg, Arg/Pro and Pro/Pro in the HPV-positive tumour samples were 0.34, 0.57 and 0.09 in comparison with frequencies of 0.18, 0.44 and 0.38 for HPV-negative tumours. Hence, there is a significant difference in the allelic frequency of p53 Arg/Arg in high-risk HPV-infected cervical carcinoma cases (0.34) and HPV-negative carcinomas (0.18). CONCLUSION: Our results indicate a striking over-representation of homozygous arginine at codon 72 of p53 in HPV-associated cervical carcinogenesis. We conclude that women with Arg/Arg homozygous allele are more prone to infection by HPV16/18, which leads to cervical carcinomas having poor prognosis.

Inhibition of D-glucose uptake by isatin in rat intestine: effect of harmaline and various sulfhydryl reagents.

The effect of isatin (indole-2,3-dione) on D-glucose uptake has been studied in rat intestine. Isatin at 6 mM concentration significantly inhibited both the sugar uptake and transmural (mucosal to serosal side) transport in the intestine. The suppression of glucose uptake by isatin was irreversible. Similar to the action of various SH-group-reacting agents, isatin inhibited the sugar uptake, presumably by binding to membrane sulfhydryl groups through a covalent linkage. Isatin-induced reduction in glucose uptake was unaffected by pH (between 5.5 and 8.4) and by DTT addition to incubation medium. Inhibition of sugar uptake by isatin and harmaline was additive in nature; this suggested that these compounds interact at different sites on the microvillus membrane surface.

The effect of medroxyprogesterone acetate on the hepatic drug-metabolizing enzymes in normal and protein-deficient female rats.

Effect of depot medroxyprogesterone acetate on the hepatic drug-metabolizing enzymes was studied in female protein-deficient and normal pair-fed rats. Treatment with this drug did not cause any change in organ weight, microsomal protein, and soluble protein yield per gram of tissue in both groups. MPA administration resulted in significant increases in the content of cytochrome P-450 and b5, and activities of benzo[a]pyrene hydroxylase, UDP-glucuronosyltransferase, and NADPH-Cyt c reductase in both pair-fed control and protein-deficient rats. However, the content of glutathione and activity of glutathione-S-transferase were not affected appreciably. The present study suggests that MPA treatment induces drug-metabolizing enzymes in liver to almost the same extent in both protein-deficient and normal pair-fed rats.