Genetic polymorphisms of CYP2E1 and GSTM1 loci and susceptibility to anti-tuberculosis drug-induced hepatotoxicity.

BACKGROUND: Host genetic factors that influence predisposition to anti-tuberculosis drug-induced hepatotoxicity (DIH) are not clear in the Indian population. OBJECTIVE: To investigate the possible association of DIH with polymorphism at the RsaI site of the 5-prime untranslated region of CYP2E1 and GSTM1 'null' mutations. METHODS: In this prospective study, 113 tuberculosis (TB) patients with DIH and 201 TB patients receiving anti-tuberculosis treatment without developing hepatotoxicity (non-DIH) constituted cases and controls, respectively. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to analyse genetic polymorphisms of CYP450 2E1 at the RsaI site and 'null' GSTM1 mutations. PCR-RFLP results were compared between 185 non-DIH and 105 DIH patients RESULTS: A high frequency of c1c1 genotypes of CYP2E1 was commonly encountered, and the difference between DIH and non-DIH patients was not significant (75.14% vs. 77.14%). The genotypic distribution of c2c2 was significantly higher in the DIH than in the non-DIH group (4.8% vs. 0.5%, OR 8.58, P = 0.03). However, adjustment for age, sex and serum albumin differences yielded an OR of 2.75, making it non-significant (P = 0.26). Homozygous 'null' mutation frequencies at the GSTM1 gene in DIH and non-DIH patients were observed that were not significantly different (40% and 37%, respectively, P = 0.61). CONCLUSION: RsaI variants of the CYP2E1 gene and GSTM1 'null' mutation were not associated with risk of DIH in a north Indian population.

Angiotensin-converting enzyme gene polymorphism in north Indian population with obstructive sleep apnea.

BACKGROUND: A deletion of 287-bp Alu repeat of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene is associated with hypertension. PURPOSE: The aim of this study is to determine the frequency of ACE (I/D) polymorphism in patients with obstructive sleep apnea (OSA). METHODS: Genotyping of ACE (I/D) gene polymorphism and estimation of serum angiotensin-converting enzyme (SACE) activity were done in 813 subjects who underwent polysomnography. Of these, 395 were apneics and 418 were non-apneics. RESULTS: The frequencies of II genotype (OR = 1.8, 95 % CI 1.26-2.60, p = 0.001) and I allele (OR = 1.4, 95 % CI 1.13-1.69, p = 0.001) of ACE gene were found to be significantly increased in patients with OSA as compared to patients without OSA. Frequency of II genotype was significantly decreased (OR = 0.46, 95 % CI 0.28-0.77, p = 0.003) in OSA patients with hypertension. In contrast, the frequencies of ID (OR = 1.80, 95 % CI 1.08-2.99, p = 0.024) and DD genotypes (OR = 2.15, 95 % CI 1.30-3.57, p = 0.003) were significantly increased in this group. The activity of SACE was significantly decreased in the apneic group as compared to the non-apneic group (OR = 0.99, 95 % CI 0.98-1.00, p = 0.04). CONCLUSIONS: The findings suggest that II genotype confers susceptibility towards development of OSA whereas DD genotype confers susceptibility towards hypertension irrespective of OSA.

Proton magnetic resonance spectroscopy of brain in obstructive sleep apnoea in north Indian Asian subjects.

BACKGROUND & OBJECTIVES: Repeated apnoeic/hypoapnoeic episodes during sleep may produce cerebral damage in patients with obstructive sleep apnoea (OSA). The aim of this study was to determine the absolute concentration of cerebral metabolites in apnoeic and non-apnoeic subjects from different regions of the brain to monitor the regional variation of cerebral metabolites. METHODS: Absolute concentration of cerebral metabolites was determined by using early morning proton magnetic resonance spectroscopy ((1)H MRS) in 18 apnoeic patients with OSA (apnoeics) having apnoea/hypopnoea index (AHI) >5/h, while 32 were non-apnoeic subjects with AHI< 5/h. RESULTS: The absolute concentration of tNAA [(N-acetylaspartate (NAA)+N-acetylaspartylglutamate (NAAG)] was observed to be statistically significantly lower (P<0.05) in apnoeics in the left temporal and left frontal gray regions compared to non-apnoeics. The Glx (glutamine, Gln + glutamate, Glu) resonance showed higher concentration (but not statistically significant) in the left temporal and left frontal regions of the brain in apnoeics compared to non-apnoeics. The absolute concentration of myo-inositol (mI) was significantly high (P<0.03) in apnoeics in the occipital region compared to non-apnoeics. INTERPRETATION & CONCLUSIONS: Reduction in the absolute concentration of tNAA in apnoeics is suggestive of neuronal damage, probably caused by repeated apnoeic episodes in these patients. NAA showed negative correlation with AHI in the left frontal region, while Cho and mI were positively correlated in the occipital region and Glx showed positive correlation in the left temporal region of the brain. Overall, our results demonstrate that the variation in metabolites concentrations is not uniform across various regions of the brain studied in patients with OSA. Further studies with a large cohort of patients to substantiate these observations are required.

Sulfated nanozirconia: an investigation on acid-base properties and n-butane isomerization activity.

Hydrated zirconia was synthesized by an organo-inorganic route employing surfactant and was sulfated using aqueous ammonium persulfate, followed by drying at 110 degrees C. The sample thus obtained was calcined at 600 degrees C to obtain sulfated zirconia and was characterized by several physicochemical methods. Crystallite sizes of sulfated zirconia were calculated from X-ray line broadening using the Debye-Scherer equation and were found to be in the range of 25 nm. When pretreated in air, the catalyst was found to exhibit butane isomerization activity at a temperature as low as 35 degrees C under atmospheric pressure. It showed conversion as high as 37% at 100 degrees C under normal pressure when pretreated in air, whereas nitrogen-pretreated catalyst showed zero activity under similar conditions. NH(3) and CO(2) temperature-programmed desorption studies on air- and helium-pretreated samples indicated that the catalyst surface changes appreciably during air pretreatment. Results on butane isomerization in conjunction with TPD studies suggest that zirconium-oxy sites play an important role in butane activation during the reaction.

Synthesis and characterization of vegetable oil derived esters: evaluation for their diesel additive properties.

Trans-esterification of four vegetable oils; canola oil, greenseed canola oil from heat-damaged seeds, processed waste fryer grease and unprocessed waste fryer grease, was carried out using methanol, and KOH as catalyst. The methyl esters of the corresponding oils were separated from the crude glycerol, purified, and characterized by various methods to evaluate their densities, viscosities, iodine values, acid numbers, cloud points, pour points and gross heat of combustion, fatty acid and lipid compositions, lubricity properties, and thermal properties. The fatty acid composition suggests that 80-85% of the ester was from unsaturated acids. Substantial decrease in density and viscosity of the methyl esters compared to their corresponding oils suggested that the oils were in their mono or di glyceride form. The lubricity of the methyl esters, when blended at 1 vol% treat rate with ISOPAR M reference fuel, showed that the canola methyl ester enhanced the fuel's lubricity number. From the analyses performed, it was determined that the ester with the most potential for being an additive or a substitute for diesel fuel is the canola methyl ester, whose physical and chemical characteristics are similar to diesel fuel.

Studies on platinum-promoted sulfated zirconia alumina: effects of pretreatment environment and carrier gas on n-butane isomerization and benzene alkylation activities.

A series of platinum-promoted sulfated zirconia alumina catalysts (SZA) with different amounts of platinum (0.5, 1, and 2 wt%) were synthesized. Two other catalysts were prepared by mechanically mixing different proportions of the Al-promoted sulfated zirconia with Pt/Al(2)O(3). The 650 degrees C calcined catalysts were characterized by N(2) adsorption/desorption (BET), TPR, and TPD analysis. Butane isomerization activity of the catalysts was studied at 270 degrees C, varying the pretreatment environment and carrier gases. Though the textural properties of the catalysts did not change significantly with platinum loading, the maximum surface area of 116 m(2)/g was exhibited by the catalyst with 1 wt% Pt loading. Under the studied reaction conditions, the air-pretreated catalysts (sulfated zirconia alumina (SZA) and platinated SZA) showed higher n-butane conversion than the N(2)-pretreated catalyst. However, nitrogen was a better carrier gas than H(2), CO(2) or air, and CO(2) and air deactivated the catalyst very fast. Unlike the platinated SZA catalysts, the mechanically mixed catalysts showed an induction phenomenon. A redox mechanism is suggested for butane isomerization over these catalysts. The catalyst SZA was also found to be active for alkylation of benzene with isopropanol, which gave 93% selectivity toward cumene.

Acquired Cystic Renal Disease in Patients Receiving Long-term Hemodialysis.

Thirty seven patients with End Stage Renal Disease (ESRD) on maintenance hemodialysis at our center were studied for prevalence of Acquired Cystic Renal Disease (ACRD). Eighteen (49%) patients had documented ACRD. The mean age was 50.4 years. The proportion of patients with ACRD rose with increasing duration of dialysis. In our study, ACRD was found in 71.4% of patients who had dialysis for more than four years and in 43.3% of patients who underwent dialysis for less than four years. All of our patients with ACRD remained asymptomatic except one who had flank pain and macro-hematuria. There was no clinical or ultrasonographic evidence of renal neoplasm in any of these patients.