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Biomedical subjects

A K Sethi

Publications and source records attributed to A K Sethi.

32 records · Page 2Linked to original sources

Oxidative metabolic status of blood monocytes and alveolar macrophages in the spectrum of human pulmonary tuberculosis.

The oxidative metabolic status of blood monocytes (BM) and alveolar macrophages (AM) in patients with active pulmonary tuberculosis (TB) (n = 40) and in successfully treated patients (n = 40) was assessed and compared with that of healthy control subjects (n = 40). Oxygen free radical (OFR) generation, measured by chemiluminescence (CL) and cytochrome c reduction assay and confirmed by using scavengers of different OFR, was suppressed in AM of the pulmonary TB group compared with healthy controls, whereas it was enhanced in BM. Successfully treated patients showed partial recovery of CL and cytochrome c reduction in AM. There was no significant change in BM of patients after having been treated. The overall capacity to generate OFR was markedly suppressed upon in vitro stimulation with latex in both BM and AM of TB patients. The observed suppressed oxidative metabolic activity in BM and AM was further elucidated by studying the molecular mechanism of respiratory burst. The activities of NADPH oxidase and enzymes of the hexose monophosphate (HMP) shunt were significantly (p less than 0.05) decreased in BM and AM of pulmonary TB patients compared with healthy controls. Patients who had been treated showed marked recovery of NADPH oxidase and HMP shunt activity. The present study suggests that tubercle bacilli escape the microbicidal action of macrophages as a result of suppressed OFR generation caused by decreased activity of HMP shunt, leading to decreased levels of NADPH, thereby preventing NADPH oxidase from working at its full capacity.

Adolescent↗

Colonic motor activity in acute colitis in conscious dogs.

The changes in motor activity of the colon during acute colitis were investigated in six conscious dogs. The motor activity was recorded with seven strain-gauge transducers. Colitis was induced in the entire colon by luminal perfusion of acetic acid. The dogs exhibited urgency and diarrhea with mucus and blood during colitis. The mucosa was diffusely erythematous and friable and there were scattered ulcerations over the mucosal surface. The motor activity of the colon changed in several ways during colitis: (a) the total duration per hour and the mean duration of contractile states decreased significantly; (b) the cycle length of colonic migrating motor complexes was significantly prolonged, and the nonmigrating motor complexes were almost completely absent; and (d) the incidence of giant migrating contractions increased significantly. About half of the giant migrating contractions were followed by defecation. The remaining expelled mucus or gas. Sometimes, a migrating motor complex in the colon was also followed by defecation; this was never observed in the normal state. The motor activity of the colon was still decreased and the cycle length prolonged 21 days after induction of colitis. However, the dogs were asymptomatic at this time and the mucosa looked normal at colonoscopy. The incidence of giant migrating contractions was also normal at this time. It was concluded that the dog is a good model for the study of colitis because of the similarity of symptoms with human ulcerative colitis. The phasic contractions of the colon decreases during colitis but the incidence of giant migrating contractions is increased. The diarrhea in colitis may primarily be due to the large number of giant migrating contractions in the middle and the distal colon.

Acute Disease↗

Colonic motor response to a meal in acute colitis.

The symptoms of urgency, diarrhea, and abdominal discomfort are exaggerated after a meal in inflammatory disorders of the colon, such as ulcerative colitis. The possible motor correlates of these symptoms were investigated in a model of acute colitis in six dogs. Each dog was instrumented with seven strain gauge transducers, two on the proximal, three on the middle, and two on the distal colon. After an overnight fast, 4-hour fasted recordings were made from the normal colon and after the colon had been cleansed on the previous day with Colyte (Reed & Carnrick, Piscataway, NJ). A 1300-kcal meal was then fed, and the recordings were continued for another 8 hours. Acute colitis was then induced by the perfusion of 10 mL of 75% acetic acid and confirmed with colonoscopy and biopsy. The fasted and postprandial recordings were repeated during the next 5 days. In the control state, ingestion of the meal increased the total duration per hour of contractile activity in the early (0-2 hours) and late (2-8 hours) postprandial periods in the distal colon. In the proximal and the middle colon, a significant increase in motor activity occurred only during the late postprandial period. Similar effects were observed in the cleansed colon. By contrast, there was no significant increase in motor activity after a meal during colitis in any of the postprandial periods in the cleansed or the uncleansed colon. During colitis, there was a significant increase in the incidence of giant migrating contractions in the fasted state. The ingestion of a meal further increased the frequency of giant migrating contractions in the uncleansed colon from 0.4 +/- 0.1 to 1.3 +/- 0.5 per hour in the late postprandial period. There was no significant increase during the early postprandial period. The increase in the late postprandial frequency of giant migrating contractions was associated with an increase in defecation frequency. It is concluded that the motor response of the colon to a meal is absent in acute colitis. The entry of new ingesta into the colon during the late postprandial period stimulates enteric mechanisms to initiate an excessive number of giant migrating contractions. These giant migrating contractions may be related to increased postprandial abdominal discomfort and increased frequency of defecation.

Acute Disease↗

Role of oxygen free radicals generated by blood monocytes and neutrophils in the pathogenesis of rheumatic fever and rheumatic heart disease.

The generation of oxygen free radicals by peripheral blood monocytes and neutrophils of patients with rheumatic fever and rheumatic heart disease has been studied using luminol enhanced chemiluminescence technique. Five groups of patients; acute rheumatic fever, recurrence of rheumatic activity, chronic rheumatic heart disease, acute pharyngitis and normal controls were studied. In all groups except the controls, measurements were made on 0, 15, 90 and 180 days. The chemiluminescence was measured in response to streptococcal membrane antigen, carbohydrate antigen and latex as triggering agents. Chemiluminescent response of monocytes, as well as, neutrophils was significantly higher (P less than 0.01) in acute rheumatic fever and recurrence of rheumatic heart disease as compared to patients with acute pharyngitis and chronic rheumatic heart disease through the study period and with all the triggering agents. A significant decline (P less than 0.001) in chemiluminescence was observed from day 0 to day 180 in the acute rheumatic fever, recurrence of rheumatic heart disease and pharyngitis patients while no such change, was observed in the chronic rheumatic heart disease group. This study raises the possibility that these phagocytic cells, which infiltrate the myocardium, may have a role in the pathogenesis of cardiac disease seen in patients with rheumatic heart disease, through the generation of oxygen free radicals.

Acute Disease↗

Changes in the superoxide anion generating capacity and respiratory burst enzymes of peripheral blood monocytes of monkeys during acute Plasmodium knowlesi infection.

The superoxide anion generation profile of peripheral blood monocytes of rhesus monkeys was investigated during the different stages of an acute Plasmodium knowlesi infection. An initial increase in superoxide anion was followed by a significant decline (P less than 0.001), paralleled by a drop in NADPH oxidase activity; there was no alteration in the activity of the hexose monophosphate shunt enzymes. This lowered activity of the NADPH oxidase, with the resulting decreased O2 generation, might be responsible for the failure of the animals to control the parasitaemia; as a result they succumbed to the infection.

Animals↗

Concentration dependent function of superoxide dismutase in oxygen free radicals mediated tissue injury in renal brush border membrane.

The dose dependent effect of superoxide dismutase in providing protection against oxygen free radicals mediated tissue damage was investigated. Xanthine-xanthine oxidase system was used to generate oxygen free radicals in vitro and damage renal brush border membrane of mice. At lower concentrations, superoxide dismutase was found to rather aggravate renal brush border membrane damage as shown by significant increase (p less than 0.05) in the malondialdehyde levels and corresponding decrease (p less than .05) in the activities of marker enzymes of renal tissue injury i.e. alkaline phosphatase, gamma-glutamyl transpeptidase and leucine aminopeptidase except maltase whose activity increased correspondingly. At higher doses of superoxide dismutase, significant protection (p less than .05) was observed against tissue damage in a dose dependent manner. On the other hand, catalase and mannitol provided dose dependent protection and their combinations with superoxide dismutase could alleviate the enhanced tissue damage produced by lower doses of superoxide dismutase. The implications of these findings have been discussed.

Animals↗

The resting surface electrocardiogram as a predictor of future hypertension.

Resting supine and post-provocation (dynamic exercise, isometric exercise and cold pressor) levels of blood pressure were measured in 80 normotensive offspring of normotensive parents (control) and 55 normotensive offspring of parents with essential hypertension. The surface electrocardiogram (including conventional twelve leads, posterior chest leads, right-sided chest leads and bipolar precordial leads) was also recorded in all subjects. Twenty-eight offspring of parents with essential hypertension had their resting and/or post-provocation blood pressure above the upper limit of standard deviation in age- and sex-matched control group. Flat or upright T waves, with either S waves less than 0.2 mV, or S/R ratio less than 2, or T waves equal to or higher than the accompanying R waves in lead V4R, could identify these potential hypertensives with nearly 90% specificity and nearly 75% sensitivity. The criterion had been derived, however, by analysis of the data achieved retrospectively. Therefore, the exact discriminating value of this criterion can be assessed only by a long-term prospective study.

Adolescent↗

Effect of various oxygen free radical scavengers in preventing tissue injury caused by Escherichia coli in pyelonephritic mice.

Reactive oxygen species have been found to be responsible for the tissue injury caused in experimental pyelonephritis in mice. The extent of lipid peroxidation (as assayed by malondialdehyde formation) was found to be increased significantly (p less than .001) in the infected group as compared to the normal mice. Superoxide dismutase and catalase (oxygen free radical scavengers) showed a significant decrease (p less than .001) in the extent of lipid peroxidation even in the presence of infection. Dimethyl sulfoxide, a hydroxyl ion scavenger, was however found to be effective only at 4 and 7 days postinfection (p less than .001). Allopurinol, an inhibitor of xanthine oxidase, did not significantly (p greater than .05) inhibit the formation of lipid peroxides, even upto 7 days postinfection. There was a significant decrease (p less than .05) in the activities of renal brush border membrane enzymes used as markers of renal tissue damage (i.e. alkaline phosphatase, leucine amino-peptidase and gamma-glutamyl transpeptidase) in the infected group as compared to the normal group. In the presence of superoxide dismutase, dimethylsulfoxide and catalase except allopurinol, the activities of all the enzymes but maltase were found to be increased significantly (p less than .05) as compared to the infected group. There was a significant increase (p less than .01) in the bacterial count in the presence of superoxide dismutase and DMSO in infected mice as compared to the infected control mice. However, no significant difference was observed in the catalase and allopurinol treated groups.

Allopurinol↗

The role of oesophageal electrocardiography in the diagnosis of right ventricular hypertrophy in chronic obstructive pulmonary disease.

Oesophageal electrocardiograms were recorded in 25 normal persons, 20 patients with chronic bronchitis and predominant emphysema without right ventricular hypertrophy and 25 patients with chronic cor pulmonale as an end result of chronic obstructive pulmonary disease. At ventricular level, patients with chronic cor pulmonale had higher P wave height, lower Q wave depth, lower R wave height, deeper S waves and lower R/S ratio as compared to the group with emphysema. In terms of the transitional zone, patients with cor pulmonale had smaller Q waves and a lower Q/R ratio. At atrial level, the patients with cor pulmonale had higher heights of the P and R waves and a lower Q/R ratio. All these differences were highly significant statistically (P less than 0.001). An R/S ratio of less than 2.5 at ventricular level had high sensitivity (96.0%), specificity (100%) and accuracy (98%) in diagnosing right ventricular hypertrophy in cases of chronic obstructive pulmonary disease. This criterion obtained from the oesophageal electrocardiogram is much more sensitive and accurate than those obtained routinely from the surface electrocardiogram in diagnosing right ventricular hypertrophy in cases of chronic obstructive pulmonary disease.

Asthma↗

Biosynthetic growth hormone therapy in children with growth hormone deficiency: experience at AIIMS, New Delhi.

A total of 20 previously untreated children with growth hormone deficiency (GHD) were treated for one year with biosynthetic human growth hormone (hGH). The mean chronologic age was 9.43 +/- 3.52 years with a height age of 5.02 years, and bone age 9.43 +/- 3.52 (TW2-RUS) 6.42 years. The mean pretreatment growth velocity was 2.43 +/- 0.90 cm/year. Of these 14 children had complete GHD (peak GH levels less than 5 ng/ml) and 6 had partial GHD. They were treated with recombinant GH in a dose of 0.5 IU/kg/week divided into 6-7 injections per week subcutaneously at night. The mean growth velocity increased to 8.88 +/- 2.10 cm/yr at the end of 6 months and 8.00 +/- 2.21 cm/yr at 12 months. The actual gain ranged from 6-11 cm in a year. There were no local adverse reactions. One child developed vitiligo of the face and another transient hyperglycemia.

Academies and Institutes↗

Congenital adrenal hyperplasia: experience at intersex clinic, AIIMS.

During 1981-88, 63 cases of female pseudohermaphroditism (FPH) were seen at the Intersex clinic at AIIMS, of whom 34 (54%) were diagnosed as due to congenital adrenal hyperplasia (CAH). Though ambiguity was present at birth in most cases, only one child was brought immediately after birth, while 14 presented after one year. Family history of affected siblings and fetal wastage was present in 10. Salt wasting symptoms were present in 13 (38.2%), evidence of early virilization in 10 (29.4%) and generalised hyperpigmentation in 7 (20.6%). Clitoromegaly was present in 30 children with labial fusion in 10 and scrotalisation of labia in 6. The urogenital opening was single in 25 (73.5%). Buccal smear was positive for sex chromatin in 19. Chromosomal pattern showed 46 XX in 33. Dyselectrolytemia was present in 16 children. Bone age was advanced in all. Adrenal hyperplasia could be documented in 3 on CT scan. All the girls were put on hydrocortisone or prednisolone, and fluodrocortisone was given only to children with salt wasting CAH. Children with CAH are being brought to medical attention much too late and investigative and therapeutic facilities are grossly inadequate. There is a need to educate primary care physicians for early case detection and provide minimum diagnostic and therapeutic facilities in regional centres.

Adrenal Hyperplasia, Congenital↗

Effect of venoruton on hypoxic stress-induced neurotoxicity in mice and oxygen free radical generation by human neutrophils.

Venoruton offers a protection against hypoxic stress-induced neurotoxicity (convulsions and death) in mice. It also inhibits free radical generation, since it produces a concentration-dependent (5-160 micrograms/10(6) cells/ml) decrease of chemiluminescence response from human neutrophils. The maximum inhibition was observed at 140 micrograms/10(6) cells/ml. The in vivo protective effect against hypoxic stress-induced neurotoxicity has been correlated to the inhibitory action of venoruton on oxygen free radical generation.

Animals↗