Paraoxonase (PON1) activity in north west Indian Punjabis with coronary artery disease & type 2 diabetes mellitus.

BACKGROUND & OBJECTIVE: Paraoxonase (PON1), an arylesterase is associated with high density lipoprotein cholesterol (HDL-C). PON1 prevents low density lipo-protein cholesterol (LDL-C) from peroxidation and can also hydrolyze lipid peroxides, thereby providing protection against atherosclerosis and coronary artery disease (CAD). The incidence of CAD is known to be high in north western Indian Punjabis. Though many factors may play a role in its pathogenesis, low PON1 activity could be an independent risk factor. We carried out this study to determine PON1 activity in north-west Indian Punjabi patients with CAD with and without type 2 diabetes mellitus and compared with healthy individuals. METHODS: A total of 120 patients with angiographically proven CAD (57 with and 63 without type II diabetes mellitus) and 19 healthy controls were studied for plasma PON1 activity and lipid variables. Comparison was undertaken between CAD patients and healthy controls and between CAD patients with and without type II DM. RESULTS: Significantly lower plasma PON1 activity (P<0.05) along with lower HDL-C (P<0.001) and higher LDL-C (P<0.05) levels were observed in CAD patients as compared to healthy controls. On univariate analysis of variance after adjusting for age and sex, no significant difference could be observed between PON1 activity and age and sex. On discriminant analysis, no clear cut-off could be observed in PON1 activity between patients CAD and controls. Similarly between CAD with and without patients type II diabetes mellitus, there was no significant difference in PON1 activity and lipids. INTERPRETATION & CONCLUSION: The low plasma PON1 activity irrespective of being diabetic may be an independent risk factor for CAD in north-western Indian Punjabi population. Similar studies involving larger samples in different ethnic groups in India need to be done to find out the role of PON1 activity in CAD.

Aspirin esterases in North-West Indians: the influence of age and nutrition.

OBJECTIVE: To determine the activity of aspirin esterases in North-West Indian population and to find the effect of age and nutrition on it. SUBJECTS, MATERIAL AND METHODS: The serum albumin, plasma cholinesterase (PChE), aspirin esterase (ASPES) and phenyl acetate esterase (PAE) were determined in 175 subjects: young (< 40 years) and healthy (BMI > 19) = 74; elderly (> 50 years) and healthy (BMI > 19) = 32; young (< 40 years) and emaciated (BMI < 19) = 44; elderly (> 50 years) and emaciated (BMI < 19) = 25). RESULTS: The serum albumin levels significantly decreased with increase in age (r = -0.384, p < 0.01) and with decrease in body mass index (r = 0.457, p < 0.01). When the activity of esterases in four groups was compared, the PAE activity was not found to be affected by age or nutrition and the ASPES and PChE activity were significantly lower only in elderly emaciated (p < 0.01). CONCLUSION: As elderly emaciated have decreased serum albumin, ASPES and PChE activity, they may need a lower dose of aspirin to achieve the desired antiplatelet and analgesic effect. The young emaciated subjects, in spite of their lower serum albumin levels, may not require a lower dose of aspirin.

Isoniazid- and rifampicin-induced oxidative hepatic injury--protection by N-acetylcysteine.

The role of N-acetylcysteine (NAC), a glutathione (GSH) precursor, was investigated in protection against isoniazid- (INH) and rifampicin- (RIF) induced oxidative hepatic injury in young Wistar rats. The hepatotoxic dose of INH and RIF was 50 mg kg(-1) day(-1) each and the hepatoprotective dose of NAC was 100 mg kg(-1) day(-1). All drugs were administered intraperitoneally (i.p.) in sterile water (4.0 ml kg(-1) day(-1)) over a period of 3 weeks. Status of oxidative/antioxidative profiles was the mechanistic approach to assess the hepatotoxicity and/or hepatoprotection. The oxidative injury in INH-RIF co-exposed animals was closely associated with significant decline of GSH and related thiols, as well as with compromised antioxidant enzyme system. The oxidative stress was further supported by increased lipid peroxidation observed in these animals. The co-administration of NAC prevented the induction of oxidative stress in INH-RIF co-exposed animals. The amelioration of oxidative stress by NAC was faithfully reflected as normal morphology in these animals, except the presence of mild degree of portal triaditis in one animal co-exposed to INH-RIF and NAC. In contrast, the animals co-exposed to INH-RIF alone showed histological lesions which ranged from intralobular inflammation to patchy necrosis. These results suggest that INH-RIF-induced oxidative injury can be prevented by supporting the cellular antioxidant defense mechanism by NAC.

Pregnancy and its outcome in patients with noncirrhotic portal hypertension.

There is paucity of data in the literature on the occurrence of pregnancy and its outcome in patients with noncirrhotic portal hypertension. The present study was undertaken to assess the fertility pattern, fetal loss, and consequences of variceal bleeding during pregnancy in these patients. Fifty-five women of child-bearing age with a diagnosis of noncirrhotic portal hypertension (including 32 with noncirrhotic portal fibrosis and 23 with extrahepatic portal venous obstruction) and 44 age-matched controls were studied. A detailed history of obstetric events and bleeding episodes was recorded in all patients. Any complication of portal hypertension was managed accordingly. Patients were classified into three groups for analysis: group 1-obstetric events after the diagnosis of portal hypertension in patients; group II-obstetric events before the diagnosis of portal hypertension in patients; and group III-obstetric events in controls. A total of 116 pregnancies took place in 44 patients. Of these, 36 occurred after and 80 before the diagnosis of portal hypertension was made. In the 44 controls, 118 pregnancies took place. The mean fertility rates of groups I, II and III were 0.20+/-0.24, 0.18+/-0.21, and 0.22+/-0.12 pregnancies per year, respectively, which were not statistically different (P>0.05). The numbers of fetal losses in groups I, II and III were 3/36 (8.3%), 6/80 (7.5%), and 12/118 (10.17%) pregnancies, respectively. Menstrual irregularities were found in 7/55 (12.72%) patients and 6/44 (13.6%) controls (P>0.05). Five episodes of variceal bleeding occurred in 36 pregnancies after the diagnosis of portal hypertension (13.88%). All five were successfully managed with endoscopic sclerotherapy. In conclusion, noncirrhotic portal hypertensive patients have normal fertility and outcome of pregnancy. Variceal bleeding episodes are not common and endoscopic sclerotherapy is safe and effective in pregnancy.

Natural history of late radiation proctosigmoiditis treated with topical sucralfate suspension.

Rectal bleeding due to radiation proctosigmoiditis is often difficult to manage. We had earlier shown the efficacy of short-term therapy with topical sucralfate in controlling bleeding in the radiation proctosigmoiditis. We now report our long-term results with this form of therapy. The study comprised 26 patients with radiation proctosigmoiditis. Sigmoidoscopically, 9 (34.6%) patients had severe changes, 15 (57.69%) had moderate, and 2 (7.69%) had mild changes. Severity of bleeding was graded as severe (> 15 episodes per week), moderate (8-14 episodes per week), mild (2-7 episodes per week), negligible (< or = 1 episode per week), or nil (no bleeding). Ten patients had moderate rectal bleeding, while 16 had severe bleeding. All patients were treated with 20 ml of 10% rectal sucralfate suspension enemas twice a day until bleeding per rectum ceased or failure of therapy was acknowledged. Response to therapy was considered good whenever the severity of bleeding showed improvement by a change of two grades. Rectally administered sucralfate achieved good response in 20 (76.9%) patients at 4 weeks, 22 (84.6%) patients at 8 weeks, and 24 (92.3%) patients at 16 weeks. This change was significant by Wilcoxon matched-pairs signed-ranks test. Two patients required surgery due to poor response. Over a median follow-up of 45.5 months (range 5-73 months) after cessation of bleeding, 17 (70.8%) patients had no further bleeding while 7 (22.2%) had recurrence of bleeding. All recurrences responded to short-term reinstitution of therapy. No treatment-related complications were observed. Ten patients had other associated late toxicity due to pelvic irradiation in the form of asymptomatic rectal stricture (N = 3), rectovaginal fistula (N = 1), intestinal stricture (N = 1), vaginal stenosis (N = 1), and hematuria (N = 6). Three patients had progression of the primary disease in the form of pelvic recurrence (N = 2) and hepatic metastases (N = 1). We conclude that topical sucralfate induces a lasting remission in a majority of patients with moderate to severe rectal bleeding due to radiation proctosigmoiditis.

Paraoxonase (PON1) polymorphism & its relation with lipids in north west Indian Punjabis.

We investigated 190 healthy, unrelated and randomly selected, north-west Indian Punjabis (M:102; F:88) for paraoxonase (PON1) polymorphism by dual substrate method and also determined lipid variables i.e., total cholesterol (TC), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL) and triglycerides (TG) in them to determine any relationship between PON1 activity, PON1 phenotypes and lipids. The basal plasma paraoxonase (PON) activity, and PON activity in presence of 1 Mol NaCl (salt activated paraoxonase i.e., SAP) were estimated by using paraoxon as substrate whereas the, phenyl acetate esterase (A) activity was estimated by using phenylacetate as substrate. Based on the ratio of SAP/A activity, three distinct phenotypes of PON1 could be determined with gene frequencies of PON*A (low activity) and PON*B (high activity) allele being 0.847 and 0.153 respectively. In the whole population on partial correlation after normalising the variables and after adjusting the lipids for age and body mass index (BMI), a significant negative correlation was observed between SAP/A ratio and TC (r = -0.290; P < 0.01) and LDL (r = -0.154; P < 0.05). However, on analysis of covariance (ANCOVA) after normalizing the lipid variables and adjusting these for age and body mass index (BMI), no significant difference could be observed in lipid profile of these three phenotypes. The lack of a significant relationship between lipids and PON1 phenotypes, suggests that PON phenotype does not significantly influence the lipid profile in north-west Indian Punjabis. However, a significant negative correlation between the PON activity and TC and LDL suggests that low PON activity could be a risk factor for atherosclerosis in these subjects.

Paraoxonase polymorphism in northwestern Indians.

OBJECTIVE: The aim of this study was to distinguish paraoxonase phenotypes by dual substrate method. SUBJECTS AND METHODS: 166 unrelated healthy northwestern Indian Punjabis were studied for basal paraoxonase activity (P), in presence of 1 M NaCl (salt-activated) using paraoxon as substrate and arylesterase activity (A) using phenylacetate as substrate. RESULTS: The mean (+ SD) activity of these in population was 70.43 (+/-30.41), 103.11 (+/-42.87) nmol/min/ml plasma and 36.81 (+/- 9.87) micromol/min/ml plasma, respectively, with no significant difference in sexes. Based on the ratio of SAP activity to A activity, 3 distinct phenotypes could be determined with gene frequencies of PON*A and PON*B being 0.845 and 0.155, respectively. Between P and A, and SAP and A in both A and AB phenotypes, significant correlation was observed (A = r 0.34 and 0.62, p < 0.01; B = r 0.31 and 0.81, p > 0.01), suggesting that both enzymes belong to the same group. CONCLUSIONS: Though northwestern Indian Punjabis have trimodal paraoxonase activity, the majority is either low homozygous (AA) or heterozygous (AB) type with enzyme activity lower than Europids.

Red cell acetyl cholinesterase and plasma cholinesterase activity and genetic variants of plasma cholinesterase in northwest Indian adults.

The plasma cholinesterase (PChE) and red cell acetyl cholinesterase (AChE) activities are indicators of exposure to organophosphates. We studied their distribution in unexposed Northwest Indian adults by measuring them in 120 men and 111 women by Ellman's and Kalow's method, respectively. We also determined genetic variability of plasma cholinesterase in 193 subjects (male = 111, female = 82). The mean +/- (SD) AChE levels in population, men and women, were 34.97 +/- 13.66, 35.05 +/- 12.42, 34.88 +/- 14.89 nmol/mg Hb/min, whereas PChE was 0.448 +/- 0.173, 0.435 +/- 0.163, 0.462 +/- 0.183 ku/l, respectively. When compared for sex, no significant difference could be found for red cell AChE and PChE activity. However, on 2-way analysis of variance (ANOVA) adjusted for age classification, the levels of both AChE and PChE were significantly higher in groups above the age of 30 years as compared to below 30 years (t = 3.08, p < 0.01, t = 2.82, p < 0.05), respectively. Seven genetic variants of PChE could be detected in males, whereas in females 6 genetic variants were found.

Study of oxidative-stress in rifampicin-induced hepatic injury in growing rats with and without protein-energy malnutrition.

1. Rifampicin (RMP) induced hepatic injury was investigated in growing rats. The interaction of moderate and severe protein-energy malnutrition (PEM) was also investigated. 2. Status of oxidative/antioxidative profile was studied by the mechanistic approach, to enumerate the nature of injury. 3. Successful hepatic injury in rats was produced by giving intraperitoneal injection of RMP (50 mg/kg/day). 4. Hepatic lipid peroxidation was significantly increased in all the RMP treated rats. 5. Superoxide dismutase, catalase and glutathione peroxidase activities in the hepatic tissue decreased with RMP treatment. 6. Hepatic thiols represented as total and protein-bound thiols, showed significant elevation, whereas the non protein thiols remain unchanged with RMP treatment. 7. Glutathione-S-transferases also showed significant elevation against 1,2-dichloro-4 nitrobenzene (DCNB) and ethacrynic acid (EA) as substrates. 8. The oxidative/antioxidative profile was observed to be more severely affected with coexistence of malnutrition. 9. Histopathological correlation showed an additional fatty infiltration of hepatocytes with coexistence of malnutrition. 10. Thus, in conclusion, it can be speculated that an altered oxidative/antioxidative profile is the closely associated with production of RMP induced hepatic injury.

Public awareness, understanding & attitudes toward epilepsy.

The public awareness, understanding and attitudes towards epilepsy were evaluated in a north Indian population in 1992 by personal interview method. The study revealed that 92 per cent of the respondents had read or heard about epilepsy. More than 55 per cent knew someone and had seen a case of seizure. Eighty five per cent of the respondents were not aware of the cause of epilepsy or had wrong beliefs. Eighteen and 15 per cent thought epilepsy to be a hereditary disorder and a form of insanity respectively. About 40 per cent of the respondents felt that children with epilepsy should not be sent to school and also objected to their children's contact with epileptics at school or at play. Two-thirds of the respondents objected to their children marrying a person who had ever had epilepsy. Twenty per cent were ignorant about the manifestation of epilepsy and an equal number were unable to recommend any therapy in case their relatives or friends had epilepsy. Fifty seven per cent did not know what kind of first aid should be given during the epileptic attack. Although the awareness of epilepsy among Indian people was comparable to that of individuals in Western countries, the attitudes of the Indians were much more negative. Better educated people belonging to higher occupational groups were less prejudiced against social contact and schooling of their children with epileptic children compared to low educational and occupational groups.

Evaluation of 14C-urinary excretion and its comparison with 14CO2 in breath after 14C-urea administration in Helicobacter pylori infection.

OBJECTIVES: 1) to estimate levels of 14C-urinary excretion in Helicobacter pylori-infected and noninfected patients after 14C-urea ingestion, 2) to compare 14C-urinary excretion and 14CO2 breath results with biopsy findings, and 3) to find out correlation between 14C-urinary excretion with 14CO2 breath results, if any. METHODS: Twenty-four-hour 14C-urinary excretion was measured in 26 patients of non-ulcer dyspepsia after oral administration of 5 microCi 14C-urea to each patient. One-mmol CO2 breath samples at baseline, 2, 5, 15, and 45 min were collected and 14C content measured. Four gastric biopsies were obtained endoscopically from each patient for histology, culture, Gram staining, and rapid urease test. RESULTS: 14C-urinary excretion in H. pylori-positive patients was 27.38 +/- 13.35% (mean +/- SD) as compared to 67.05 +/- 14.19% in H. pylori-negative patients. Five-, 15-, and 45-min 14CO2 breath values in H. pylori-positive cases were 0.07 +/- 0.041%, 0.063 +/- 0.041%, and 0.028 +/- 0.017% of administered 14C-urea/mmol CO2 exhaled, respectively, which were significantly higher (p < 0.001) from their corresponding values in negative cases. The 14C-urinary excretion data, when compared with biopsies results, discriminated well in 17 of the 18 H. pylori-positive cases, resulting in sensitivity of 94.4%, specificity 100%, and diagnostic accuracy 96.1%, whereas 15 min 14CO2 breath results were 100% accurate. Strong negative correlation between 14C-urinary excretions and 15 min 14CO2 breath was obtained (r = -0.717, p < 0.001). CONCLUSIONS: Measurement of 14C in 24-h urine and in 15-min breath sample may be employed as a cross confirmatory reliable technique for the detection of viable H. pylori colonization.