Is ciprofloxacin a panacea or do we need a 'use-restricted' drug?
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Biomedical subjects
Publications and source records attributed to D Kumar.
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Erythrocytes of diabetic subjects (non-insulin dependent) were found to have eight- to ten-fold higher levels of endogenously formed thiobarbituric acid reactive malonyldialdehyde (MDA), thirteen-fold higher levels of phospholipid-MDA adduct, 15-20% reduced Na(+)-K(+)-ATPase activity with unchanged Ca+2-ATPase activity, as compared with the erythrocytes from normal healthy individuals. Incubation of normal erythrocytes with elevated concentrations (15-35 mM) of glucose, similar to that present in diabetic plasma, led to the increased lipid peroxidation, phospholipid-MDA adduct formation, reduction of Na(+)-K(+)-ATPase (25-50%) and Ca+2-ATPase (50%) activities. 2-doxy-glucose was 80% as effective as glucose in the lipid peroxidation and lipid adduct formation. However, other sugars, such as fructose, galactose, mannose, fucose, glucosamine and 3-O-methylmannoside, and sucrose, tested at a concentration of 35 mM, resulted in reduced (20-30%) lipid peroxidation without the formation of lipid-MDA adduct. Kinetic studies show that reductions in Na(+)-K(+)-ATPase and Ca+2-ATPase activities precede the lipid peroxidation as the enzyme inactivation occur within 30 min of incubation of erythrocytes with high concentration (15-35 mM) of glucose, while lipid peroxidation product, MDA appears at 4 hr and lipid-MDA adducts at 8 hr. The lipoxygenase pathway inhibitors, 5,8,11-eicosatriynoic acid and Baicalein (5,6,7-trihydroxyflavone), reduced the glucose-induced lipid peroxidation by 30% and MDA-lipid adduct formation by 26%. Indomethacin, a cyclooxygenase pathway inhibitor, had no discernible effect on the lipid peroxidation in erythrocytes. However, the inhibitors of lipid peroxidation, 3-phenylpyrazolidone, metyrapone, and the inhibitors of lipoxygenase pathways did not ablate the glucose-induced reduction of Na(+)-K(+)-ATPase and Ca+2-ATPase activities in erythrocytes. Erythrocytes produce 15-HETE (15-hydroxy-eicosatetraenoic acid), which is augmented by glucose. These results suggest that the formation of lipoxygenase metabolites potentiate the glucose-induced lipid peroxidation and that the inactivation of Na(+)-K(+)-ATPase and Ca+2-ATPase occurs as a result of non-covalent interaction of glucose with these enzymes.
The effect of daily oral administration of ethanol (2.5, 5, or 10% in drinking water for 8 wk), lead (10 mg/kg, po, once daily for 8 wk), or their combination on tissue trace-metal concentration and hematopoietic and hepatic biochemical indices was investigated in male rats. Ethanol (10%) ingestion enhanced the hepatic lipid peroxidation and decreased the calcium and magnesium content of blood and liver. Coexposure to lead and ethanol (5 and 10%) produced a more pronounced elevation of blood zinc protoporphyrin (ZPP) and hepatic lipid peroxidation. Combined lead-ethanol exposure also lowered the concentration of blood and hepatic magnesium and calcium and increased the amount of lead in the blood, liver, and brain compared to a group treated with lead alone. The results suggest that chronic alcohol ingestion results in calcium and magnesium loss. However, coexposure to lead and ethanol could result in more serious depletion of calcium and magnesium, and this could be the cause of suspected synergism between alcohol consumption and lead poisoning.
The ability of zinc, methionine or their combination given by gavage to prevent or treat experimental oral lead intoxication in rats was investigated. Simultaneous oral supplementation with zinc plus methionine was found to be most effective in reducing lead induced inhibition of delta-aminolevulinic acid dehydratase (ALAD) activity in blood, elevation of urinary delta-aminolevulinic acid (ALA) excretion and in enhancing the hepatic glutathione (GSH) contents. The combination was also most effective in reducing the accumulation of lead in blood, liver and kidney compared to zinc or methionine alone. Prevention was more effective than treatment after lead exposure which may be caused by a decrease in the absorption of lead in the gastrointestinal tract in the presence of zinc and/or methionine.
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Amplification of a variable region 3' to the human type II collagen gene (COL2A1) has permitted segregation analysis in a three generation Stickler syndrome pedigree. This family had previously proved uninformative for the known restriction fragment length dimorphisms. Amplification of the variable region revealed five distinguishable alleles, of which three were segregating in this family. The lod score in favour of linkage was 2.86 at zero recombination.
We have developed a method for prolonged combined anorectal manometry and electromyography (EMG) of the external anal sphincter in ambulant subjects. Fourteen healthy volunteers were studied for a total of 284 hr (mean of 20.3 hr/subject). Anorectal manometry was performed using a probe with twin pressure sensors. EMG was recorded by one indifferent and two differential silver-silver chloride surface electrodes positioned 0.5-0.75 cm from the anus on either side. The sampling reflex occurred frequently and was significantly (P less than 0.001) more common during wakefulness than during sleep and also following meals than during fasting (P less than 0.01). The passage of flatus was associated with transient relaxation of the anal canal in 19% of episodes. In contrast, there was a contractile episode with no preceding relaxation in 75% of episodes. The anal sphincter had significantly (P less than 0.05) more action potentials (APs) during the day (12.8 +/- 3.2 APs/10 min) than at night (1.6 +/- 1.3 APs/10 min). During micturition, anal canal pressure rose (mean 15 mm Hg) in association with powerful external anal sphincter contractions. Our data show that, normally, contractile activity both in the anal canal and external anal sphincter maintains fecal continence during micturition and the passage of flatus. The technique should lead to a better understanding of the normal mechanisms of fecal continence during waking and sleep and of the pathophysiology of disorders of anorectal function.
Toxic cardiovascular effects of allylamine and beta-aminopropionitrile were studied in adult male Sprague-Dawley rats given allylamine alone (AA), 100 mg/kg/day, beta-aminopropionitrile alone (beta APN), 1 g/kg/day, or both chemicals (AA + beta APN) by gavage. Rats were given a total of 10 doses in 11 days. Rats given AA + beta APN showed extensive smooth muscle cell necrosis of the aortic media not seen when either toxin was given alone. Lingual artery lesions in the form of small intracellular eosinophilic globules were seen in animals given AA and AA + beta APN treatments, but were more numerous and larger in the latter group by morphometric analysis (p less than 0.03). Myocardial necrosis was much less severe in the AA + beta APN treatment group than in rats given only AA. A long-term follow-up (47 and 180 days) after the AA + beta APN protocol above showed that rats had persistent aortic medial necrosis with striking intimal cartilaginous metaplasia. Cultured porcine aortic smooth muscle cells exposed in vitro to combined AA and beta APN showed markedly decreased viability and increased cell injury when compared to cells exposed to only one toxin, thus supporting the synergistic toxic effect seen in vivo. Our studies show a synergistic necrotizing effect of AA and beta APN on aortic vascular smooth muscle cells. A hypothesis concerning these compounds' effects on vascular amine oxidases is made to explain this toxic synergism. Synergistic toxic interactions may be important in other forms of vascular injury.
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Subtotal colectomy with ileorectal anastomosis is now frequently offered to patients with slow transit constipation who have severe symptoms and no response to more conventional medical treatment. If this operation is to be successful, the underlying problem should be delay in the progress of contents through the colon but no mechanical or functional obstruction in the small bowel or rectum. We have used a recently described technique of prolonged ambulant manometry and electromyography to investigate anorectal function in these patients. Pressure data were collected using a 2 mm diameter intrarectal probe carrying microtransducers, and external anal sphincter activity was assessed by a pair of silver-silver chloride surface electrodes. Fourteen control subjects and eight patients with colonic inertia were studied. Sampling reflexes, indicative of rectal filling, occurred at mean (SEM) rates of 7.4 (2.0)/hour in controls but were significantly reduced in patients (2.4 (0.3)/hour (p less than 0.01]. Recurrent rectal motor complexes were seen to occur in both groups at intervals of 76 (1.8) minutes in controls and 64.9 (7.2) minutes in patients (p less than 0.1), and with amplitudes of 42.4 (2.1) mmHg and 9.2 (0.7) mmHg (p less than 0.001), respectively. External sphincter electromyographic spike activity did not differ between groups. Our results support the concept of reduced transit of faeces to the rectum from the colon over a 24 hour period in slow transit constipation and suggest that a motor neuropathy may also be present in the rectum.
Both the human small intestine and rectum exhibit motor activity in which relatively brief bursts of powerful regular contractions recur with a similar periodicity. We used prolonged ambulant manometry to test the hypothesis that these activities are synchronous. Pressure activity from the duodenojejunum and the rectum was recorded continuously for 24 h in eight freely ambulant healthy adults. A total of 61 migrating motor complexes and 61 rectal motor complexes occurred in the group; the median periodicities of the two rhythms differed significantly (P = 0.025). There was no evidence of synchrony between the two biorhythms. We conclude that they are independent oscillations.
To address the question of synchrony between two major biorhythms with a similar periodicity, the cortical rapid eye movement (REM)/non-REM sleep cycle and the enteric migrating motor complex (MMC cycle), we recorded upper small bowel motor activity and sleep activity during nocturnal and diurnal sleep in six healthy subjects. Motility was measured continuously using a fine (2.2 mm OD) and relatively comfortable nasojejunal probe with two pressure-sensitive microtransducers positioned under fluoroscopic control on either side of the ligament of Treitz. Sleep stages were recorded while the subjects slept in a sleep laboratory. Each subject was studied twice; once during normal nocturnal sleep and then after acute reversal of sleep by advancing the time of going to bed by 4 h each night for three nights. The total duration of sleep was similar for diurnal and nocturnal sleep. There was a significantly higher number of REM episodes (P less than 0.001) and REM sleep stage shifts (P less than 0.02) during diurnal (reversed) sleep. During sleep (both diurnal and nocturnal) there was a significant reduction in the MMC cycle length (P less than 0.02, P less than 0.03) and the duration of phase II of the MMC (P less than 0.009, P less than 0.02). The distribution of MMCs among sleep stages and REM sleep was consistent with a random distribution. These data show that periodic activity in the gut is modulated by the presence or absence of sleep, but they also are consistent with the hypothesis that the two cycles are independent and that one is not contingent upon the other.
Our study was designed to test the hypothesis that psychoneurosis in irritable bowel syndrome (IBS) may be the secondary effects of the unsatisfactory nature of the medical transactions (diagnosis, explanation, prognosis, and therapy) in IBS rather than a primary cause of the syndrome. We carried out psychometric assessments on three groups of subjects: 10 healthy volunteers, 12 patients diagnosed as suffering from benign gastrointestinal disease, and 18 patients with IBS. We found a significantly raised incidence of psychoneurosis in IBS, but the components of this were predominantly anxiety and obsession; the incidence of depression in all 3 groups was similar. We argue that the data support our hypothesis that the psychoneurotic manifestations are secondary components of IBS; the data do not support the hypothesis that IBS is a manifestation of depression.
The effect of chandonium iodide (as a non-depolarising muscle relaxant) was studied in 50 patients of ASA grade I or II who were scheduled for surgery. The patients were divided into 2 groups according to the dose of chandonium iodide (0.2 and 0.25 mg/kg respectively). The onset and duration of action was found to be dose dependent. Intubation characteristics were good to fair in all the patients, the reaction to intubation being either absent or mild. There was mild and transient rise in pulse and blood pressure. No allergic reaction was observed in any patient and reversal characteristics were good in all the cases.
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