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Biomedical subjects

P Gathiram

Publications and source records attributed to P Gathiram.

At least 19 recordsLinked to original sources
PubMed2001

Immunolocalisation and endothelin-1 values In pre-eclampsia: an immunocytochemical study.

Maternal plasma ET-1 levels and the immunolocalisation of ET1 in the fetal membranes of pre-eclamptic primigravidae at >/=28 weeks, gestation were studied. The levels of maternal plasma ET1 and immunoreactive ET-1 were increased in pre-eclampsia. Immunoreactive ET-1 was localised in the amnion, chorion and decidua of normal pregnant women as well as those with preeclampsia-eclampsia. Intense labelling was observed in moderate pre-eclampsia (BP 140/90 - 170/110 mmHg) with very intense labelling in severe pre-eclampsia (BP >170/110 mmHg), especially in the amniotic epithelium, chorionic villi, maternal blood vessels, cytotrophoblasts and giant cells of the decidua. The increased ET-1 levels demonstrated in fetal membranes of pre-eclamptic women are probably produced in a paracrine and/or autocrine manner, contributing to the hypertension, vasospasm and fetal growth restriction characteristic of the syndrome. A larger study would be required to show significant change in endothelin production in pre-eclampsia.

Journal Article↗
PubMed1999

Endothelin-1 and endothelin receptor status in kidney transplants undergoing acute rejection.

Endothelin-1 (ET-1) is a potent vasoconstrictor with vasopressor and mitogenic effects. Blood samples were collected from 21 renal transplant patients undergoing acute rejection at the time of diagnostic kidney biopsy: there were 20 men and one woman, mean age 35.6 years. All patients were on triple immunosuppressive therapy with cyclosporine A, azathioprine and methylprednisolone. Twenty living kidney donors pre-uninephrectomy (11 men and nine women, mean age 34 years) served as controls. Control kidney was obtained from fresh autopsy material and normal kidney tissue from nephrectomies for malignancy. Mean plasma ET-1 was significantly increased at 1.56 +/- 0.2 pg ml(-1) during acute rejection compared to 0.74 +/- 0.06 pg ml(-1) in donors (p = 0.0009 unpaired t-test). ET(A) receptor immunolabelling was visualised in distal tubules and collecting ducts with minimal labelling in the glomeruli and blood vessels of control kidney tissue ET(A) receptor labelling was similar in kidney biopsies with acute rejection. ET(B) receptor immunolabelling was significantly increased in glomeruli (p = 0.002) and decreased in distal tubules (p = 0.004) in kidneys with acute rejection compared to control kidney tissue. While these findings may account for the oedema and hypertension observed during acute rejection, the exact significance needs to be studied further.

Acute Disease↗
PubMed1997

Zinc status in vitamin B6 deficiency.

Three groups of young male Wistar rats were maintained on diets consisting of 7 mg pyridoxine hydrochloride/kg diet (control and pair-fed groups) and 0 mg pyridoxine hydrochloride/ kg diet (deficient group) for six weeks. The zinc status of all rats was assessed by measuring their erythrocyte zinc-metallothionein-1 (Zn-Mt-1) and plasma zinc levels. A significant difference (p < 0.001) in plasma zinc levels was observed between the deficient group and the control and pair-fed groups (1.35 micrograms/ml +/- 0.08, 1.99 micrograms/ml +/- 0.06 and 2.03 micrograms/ml +/- 0.07 respectively). Erythrocyte Zn-Mt-1 levels were significantly lower in vitamin B6 deficient rats when compared to control animals. No significant difference in Zn-Mt-1 levels existed between vitamin B6 deficient and pair-fed groups suggesting that the reduced Zn-Mt-1 levels in vitamin B6 deficient rats may be due entirely to their decreased food intake (8.9 g/day compared to 15 g/day of control rats).

Animals↗
PubMed1993

11 beta-Hydroxysteroid dehydrogenase activity in mesenteric arteries of spontaneously hypertensive rats.

1. 11 beta-Hydroxysteroid dehydrogenase (11-HSD) activity in mesenteric arteries of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was determined and expressed as the percentage conversion of [3H]-corticosterone to [3H]-11-dehydrocorticosterone. 2. 11-HSD activity was significantly decreased in mesenteric arteries of both 4 and 9 week old SHR (8.4 +/- 0.8%, 5.0 +/- 1.5%, respectively) compared with WKY rats (12.4 +/- 0.6%, 15.8 +/- 0.7%, respectively; P < 0.05). 3. Total RNA from rat vascular smooth muscle cells (VSMC) and endothelial cells (EC) were prepared with selective precipitation in 3 mol/L LiCl/6 mol/L urea. The expression of 11-HSD mRNA was confirmed in the rat VSMC but its mRNA expression was not detected in EC, using northern blot analysis. 4. The results in this study indicate that 11-HSD in the vascular wall may play a role in the pathogenesis of hypertension in SHR.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1989

Changes in lipopolysaccharide concentrations in hepatic portal and systemic arterial plasma during intestinal ischemia in monkeys.

The time course of changes in the level of plasma lipopolysaccharides (LPS) in both the hepatic portal and the systemic arterial circulations, together with changes in cardiovascular parameters, was ascertained during a 1 hr occlusion of the superior mesenteric artery (SMA) in six primates. The LPS concentrations before occlusion of the SMA in the hepatic portal and systemic arterial circulation were 0.051 +/- 0.009 and 0.065 +/- 0.011 ng/ml, respectively (NS). At the end of the occlusion period, there was no significant increase in either the hepatic portal or systemic arterial plasma LPS concentrations. Immediately on removal of the occlusion, however, the LPS concentration in the portal plasma increased and peaked at 0.431 +/- 0.124 ng/ml (P less than 0.01) within 17.5 +/- 1.71 min, whereas in the systemic arterial circulation the LPS concentration began to rise but only after a delay of approximately 10 min to peak at 0.287 +/- 0.126 ng/ml (P less than 0.05) within 32.5 +/- 4.23 min of reperfusion. The mean arterial pressure (MAP) declined during the reperfusion period from 98.6 +/- 6.89 to 65.0 +/- 9.5 mm Hg (P less than 0.05). The heart rate showed a small but not significant increase (P greater than 0.2) after about 80 min of reperfusion. These data indicate that the gut is the source of the increased plasma LPS concentration following occlusion of the SMA.

Animals↗
PubMed1988

Endotoxaemia in exhausted runners after a long-distance race.

The extent to which plasma endotoxin concentrations increased was measured in 89 randomly selected exhausted runners who required admission to the medical tent for treatment in the 1986 Comrades Marathon (89,4 km). Eighty-one per cent had concentrations above the upper limit of 0,1 ng/ml ('endotoxaemic'), including 2% above 1 ng/ml (the reported lethal level in humans), and only 19% had normal levels. There was a negative correlation between plasma endotoxin and plasma anti-endotoxin IgG concentration (P less than 0,025). Those runners completing the race in less than 8 hours had a significantly lower average endotoxin value than those taking longer than 8 hours (P less than 0,025). Also 80,6% of runners (58/72) with high plasma endotoxin values reported nausea, vomiting and/or diarrhoea, compared with 17,7% (3/17; P less than 0,001) with low endotoxin values. Elevated plasma endotoxin concentrations of 32 randomly selected endotoxaemic runners had returned to normal 1-3 weeks later, and most of them (25/32) had increased anti-endotoxin IgG concentrations (P less than 0,02). Fifty-nine runners randomly selected in a short run (21,1 km) 3 weeks after the 89,4 km run completed the race without problems and none showed any increase in endotoxin levels. Further studies in this field are warranted, especially the measurement of endotoxin and anti-endotoxin values from commencement of training to full fitness. It is possible that these measurements may prove useful as predictors of an athlete's or combat soldier's performance.

Antitoxins↗
PubMed1988

Oral administered nonabsorbable antibiotics prevent endotoxemia in primates following intestinal ischemia.

Plasma lipopolysaccharide (LPS) concentrations have been found to increase during a temporary occlusion of the superior mesenteric artery (SMA). We have attempted to show, by a prophylactic oral administration of a nonabsorbable antibiotic to monkeys subjected to an SMA occlusion shock, that the increased LPS is intestinal in origin. A total of eight monkeys were subjected to a temporary occlusion of the SMA. Four monkeys received prophylactic oral administration of a nonabsorbable antibiotic, while the rest acted as controls. The plasma LPS concentrations before occlusion in the control and the kanamycin group were 0.069 +/- 0.006 and 0.092 +/- 0.005 ng/ml, respectively. At the end of the 1-hr occlusion period the plasma LPS concentration in the controls increased to 0.09 +/- 0.009 ng/ml (P less than 0.1) and peaked to 0.378 +/- 0.103 ng/ml (P less than .001) within 20 min of reperfusion. Thereafter, the plasma LPS concentration returned slowly to baseline. In the kanamycin group the plasma LPS concentration remained at baseline throughout both the occlusion and reperfusion periods. These data suggest that the origin of the increased plasma LPS concentration seen following temporary occlusion of the SMA is from the gut, and is information of possible importance in patients about to undergo intestinal surgery.

Administration, Oral↗
PubMed1988

Plasma endotoxin concentration in healthy primates and during E. coli-induced shock.

The normal range for circulating plasma endotoxin concentration was determined in 62 healthy primates (vervet monkeys, Cerecopithecus aethiops) by the chromogenic substrate modification of the Limulus amoebocyte lysate test, and found to have a mean of 0.076 +/- 0.004 ng/ml (range 0.000 to 0.0127). Four anesthetized primates received an LD100 iv infusion of Escherichia coli over one hour. Plasma concentrations of endotoxin (lipopolysaccharide, LPS) and anti-LPS IgG, and viable E. coli colonies in circulating whole blood samples were determined at specified intervals. Plasma antiendotoxin IgG concentration was determined by an enzyme-linked immuno-absorbent assay, and viable bacterial counts were assayed by standard plate count techniques. LPS concentration increased during E. coli infusion to a mean of 1.13 +/- 0.068 ng/ml (p less than .001) with a concomitant decrease in the concentration of anti-LPS IgG to 59 +/- 5% of control values (p less than .005). Viable circulating E. coli colonies increased during the infusion to a maximum of 425 X 10(6) cfu/ml 10 min after the completion of the infusion, but fell precipitously 20 min later to 10.1 X 10(6) cfu/ml. When each animal succumbed, their respective plasma LPS concentrations were still raised, whereas no viable circulating E. coli colonies were present at a dilution of 10(2). Elevated plasma LPS could prove to be a significant circulating pathogen during Gram-negative bacterial shock and supports the possible association between plasma LPS and morbidity, and mortality in septic shock.

Animals↗
PubMed1988

Portal and systemic plasma lipopolysaccharide concentrations in heat-stressed primates.

Lipopolysaccharide (LPS) concentrations in hepatic portal and systemic arterial plasma were determined in five anesthetised monkeys heat-stressed by an environmental temperature of 41.0 +/- 0.3 degrees C and 100% relative humidity. As the rectal temperature (Tr) rose, the LPS concentrations in both the portal and systemic arterial plasma remained at the pre-heat-stress levels of 0.088 +/- 0.017 and 0.078 +/- 0.021 ng/ml (N.S.), respectively, until a Tr of 42.5-43.0 degrees C, when the LPS concentration increased slowly, first in the portal plasma and then in the systemic plasma. On the other hand, the concentration of plasma anti-LPS IgG antibodies began to decline at temperatures as low as 40 degrees C from 20.66 +/- 7.35 micrograms/ml (portal) and 22.14 +/- 7.43 micrograms/ml (arterial) to 5.51 +/- 1.28 micrograms/ml (portal) (P less than .05) and 4.6 +/- 1.69 micrograms/ml (arterial) (P less than .05) just prior to death. Above a Tr of 43 degrees C, the LPS concentration increased rapidly to a maximum of 0.244 +/- 0.05 ng/ml (portal) (P less than .01) and 0.224 +/- 0.06 ng/ml (arterial) (P less than .01). The mean arterial pressure remained more or less constant at 112 +/- 17.03 mm Hg until a Tr of 41.5 degrees C and then rapidly declined as Tr rose (P less than .01). The heart rate rose gradually from 154 +/- 14 min-1 as Tr increased and then rapidly after a Tr of 41.5 degrees C to a maximum of 307 +/- 13 min-1 at 43.0 degrees C. Thereafter it declined rapidly until death.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Prophylactic corticosteroid suppresses endotoxemia in heat-stressed primates.

We previously found that lipopolysaccharides (LPS) leak from the gut lumen into the hepatic portal vein during heat stroke. Furthermore, we found that prophylactic corticosteroid administration could prevent a rise in plasma LPS concentration in superior mesenteric artery occlusion shock. In this study, we found that treatment prior to heat-stress with corticosteroids could prevent any rise in plasma LPS concentration in heat-stressed primates. Two groups of primates, one of which received a prophylactic dose of methylprednisolone sodium succinate (MPSS) (n = 4) were subjected to heat-stress (41 +/- 0.3 degrees C). Their arterial blood pressure, heart rate and rectal temperature (Tr) were continuously recorded. In the untreated control group (n = 8), the plasma LPS concentration tended to increase slowly at a Tr of 41.5 degrees C from an initial 0.06 +/- 0.013 ng.ml-1. Above a Tr of 43 degrees C, the plasma LPS level rose rapidly until at a Tr of 44.4 +/- 0.1 degrees C, the mean LPS level was 0.315 +/- 0.03 ng.ml-1 (p less than 0.001). Prophylactic treatment with MPSS suppressed the increase in plasma LPS levels to 0.066 +/- 0.01 ng.ml-1 before heat-stress and 0.03 +/- 0.01 ng.ml-1 at Tr 44.4 degrees C just before primate demise. The mean arterial pressure of the control group was lower than the treated group for any given Tr; between Tr 42-43 degrees this difference was significant (p less than 0.05). Moreover, the cardiovascular parameters began to deteriorate at a lower Tr in the control group.

Animals↗
PubMed1988

Prophylactic corticosteroid increases survival in experimental heat stroke in primates.

It has been suggested that endotoxins or lipopolysaccharides (LPS), may contribute to heat stroke pathophysiology. In this study, 11 anesthetised monkeys were divided into 2 groups. The steroid group (n = 5) had received a dose of MPSS (30 mg.kg-1, i.v.) before being heat-stressed and the control animals (n = 6) received saline equivolumetrically. The animals were heat-stressed to a rectal temperature of 43.5 degrees C in an environmental temperature of 41 +/- 0.3 degrees C and 100% relative humidity and then allowed to recover at room temperature. Blood samples for LPS and anti-LPS IgG analyses were taken both before treatment and before and after heat-stress. The administration of prophylactic MPSS increased the survival rate significantly from 33% to 100% (p less than 0.05). The plasma LPS level in the steroid group showed very little change after heat-stress, whereas in the non-surviving controls there was a significant increase in plasma LPS level (from 0.089 +/- 0.007 to 0.257 +/- 0.031 ng.ml-1) (p less than 0.005). The control animals that survived showed very little increase in plasma LPS levels, but had about 300% greater plasma Anti-LPS IgG levels. We conclude that pretreatment with MPSS improves the survival rate during heat stroke, possibly by suppressing the rise in plasma LPS concentration.

Animals↗
PubMed1987

Prevention of endotoxaemia by non-absorbable antibiotics in heat stress.

Four anaesthetised monkeys were given oral kanamycin (15 mg 1 kg 12 hourly) over five consecutive days before being heat stressed. Four other anaesthetised monkeys served as controls. The plasma lipopolysaccharide concentration in control primates increased initially from 0.044 (SEM 0.004) ng/ml to 0.062 (0.006) ng/ml as the rectal temperature increased from 37.5 to 39.5 degrees C. A second increase in lipopolysaccharides started at 42 degrees C and reached 0.308 (0.038) ng/ml (p less than 0.01) at 44.5 degrees C. Before heat stress the plasma lipopolysaccharide concentration in the primates who had been pretreated with kanamycin was 0.007 (0.006) ng/ml, and despite heating these animals to 44.5 degrees C no increase in plasma lipopolysaccharide concentrations were seen in this group. The cardiovascular variable during heat stress were more unstable in the control group and began to deteriorate at a lower temperature than in the group receiving antibiotic. These data suggest that the increased plasma lipopolysaccharide concentration during heat stress originates mainly from the gut.

Animals↗
PubMed1987

Antilipopolysaccharide improves survival in primates subjected to heat stroke.

Recent investigations have suggested that endotoxins or lipopolysaccharides (LPS) may play a role in heat stroke pathophysiology. In this study we wish to investigate whether prophylactic administration of anti-LPS hyperimmune plasma improves survival of experimental heat stroke in primates. Eleven monkeys were anesthetised and heat-stressed to a rectal temperature of 43.5 degrees C (group A) and then allowed to recover at room temperature. Five had received a prophylactic i.v. dose of equine anti-LPS (experimental group), while the other six (control group) received an equivalent i.v. dose of nonimmune equine plasma. All the experimental monkeys survived, while only one out of the six controls survived (chi 2 = 4.65, p less than 0.025). All the control animals that succumbed had significantly elevated plasma LPS levels (p less than 0.05) as compared to the experimental group and the single surviving control. The latter showed very little or no change in plasma LPS levels. A further eight monkeys (group B) were heat-stressed to a rectal temperature of 43.8 degrees C. Of these eight, four had received a prophylactic i.v. dose of equine anti-LPS plasma. Although all eight animals died, the four which were pretreated with anti-LPS plasma had a significantly longer survival time (427.5 +/- 61.39 min) than the untreated group (81.25 +/- 33.94 min) (p less than 0.05). Furthermore, the plasma LPS levels in the treated monkeys remained unchanged whereas in the untreated group, a significantly elevated plasma LPS level was noticed (p less than 0.005). We conclude that LPS may have a role in heat stroke pathophysiology and that prophylactic treatment with anti-LPS antibodies would seem to offer protection against the effects of heat stress.

Animals↗
PubMed1987

Time course of endotoxemia and cardiovascular changes in heat-stressed primates.

Heat stress causes a marked reduction in splanchnic blood flow in order to compensate for the increased flow to the skin. Splanchnic ischemia causes a leakage of endotoxins from the gut lumen into the portal circulation and, especially in the presence of a compromised reticuloendothelial system, may cause severe systemic endotoxemia. Since many of the pathological features of heat stroke are similar to the shock state produced by LPS, we examined whether heat-stress causes endotoxemia. Five anesthetized monkeys were subjected to an environmental temperature of 41 degrees +/- 0.3 degrees C and relative humidity of 100%, until death. Rectal temperatures were recorded continuously, blood pressure and ECG were recorded at 5-min intervals, and arterial blood samples were taken at 15-30 min intervals. A decline in mean arterial pressure and rapid rise in heart rate occurred at about 42 degrees C. Plasma LPS remained at 0.071 +/- 0.006 ng.ml-1 until a rectal temperature of +/- 42 degrees C. Thereafter, it increased slowly until beyond 43 degrees C when it rose rapidly to 0.347 +/- 0.024 prior to death. Endotoxemia may have been a contributing factor in the pathogenesis of heat stroke. If so, then the use of anti-LPS antibodies may be expected to be beneficial.

Animals↗
PubMed1986

Effect of corticosteroid prophylaxis on lipopolysaccharide levels associated with intestinal ischemia in cats.

Ischemia of the intestines damages the permeability of the intestinal wall, allowing lipopolysaccharide (LPS) (endotoxin) to leak from the gut lumen into the blood circulation, causing shock and death. We measured LPS levels associated with corticosteroid treatment vs. no treatment in cats whose superior mesenteric artery had been occluded for 60 min. In untreated cats, the preocclusion mean plasma LPS concentration remained stable at 0.069 +/- 0.015 ng/ml. Toward the end of the occlusion period, mean plasma LPS rose to 0.239 +/- 0.032 ng/ml (p less than .01). Release of the clamp and reperfusion with oxygenated blood was followed within 20 min by a large rise in plasma LPS concentration to 0.825 +/- 0.11 ng/ml (p less than .01), which had returned to preocclusion levels about 80 min later. Methylprednisolone (30 mg/kg) was infused into a second group of cats 1.5 h before SMA occlusion. In these cats there was a complete inhibition of the LPS rise both during and after occlusion. These data suggest that the reported beneficial effect of corticosteroids in the treatment of septic shock may be mediated, in part, by reducing LPS leakage from the gut.

Animals↗
PubMed1986

Perspective graphics as a means of portraying the distribution of radiolabelled ligands in the spinal cord--a pilot study using intrathecally administered 3H morphine.

Tritium-labelled morphine sulphate was injected into the lumbar (L4-5) subarachnoid space of an adult male baboon. Three hours after injection, the animal was sacrificed. Using quantitative light microscopic autoradiographic mapping techniques, contour and perspective diagrams were prepared that described the position of radiolabel and by inference the distribution of morphine binding sites within the spinal cord. High concentrations of 3H was found in the medial regions of laminae I, II (substantia gelatinosa) and III of the dorsal horns. Smaller, but significant levels were seen bilaterally in the spinal anterolateral quadrant. Minimal 3H activity was seen in the remainder of the spinal cord with the lowest level being recorded in the spinal canal. Perspective graphics proved a precise and attractive method for locating the position and quantifying the concentration of radiolabel in baboon spinal cord.

Animals↗
PubMed1986

Superior mesenteric artery occlusion shock in cats: modification of the endotoxemia by antilipopolysaccharide antibodies (anti-LPS).

We measured the time course of elevated plasma LPS concentration caused by a temporary intestinal ischemia using the superior mesenteric artery (SMA) occlusion shock model in anesthetized cats. The systemic plasma LPS increased from 0.075 +/- 0.006 ng/cc to 0.219 +/- 0.026 ng/cc (P less than 0.001) during the occlusion period. On release of the clamp, the plasma LPS concentration rose rapidly to 0.716 +/- 0.122 ng/cc (P less than 0.001) within 20 min. Thereafter, it declined to reach baseline levels after 100-120 min reperfusion. A total of 21 animals received IV 1.0 cc/kg antilipopolysaccharide hyperimmune equine plasma (anti-LPS) either 1.5 hr before the occlusion or at 0, 10, or 20 min after release of the occlusion. Prophylactic anti-LPS prevented any rise in plasma LPS both during and after release of the occlusion. The administration of anti-LPS during the reperfusion period completely reversed the endotoxemia caused by intestinal ischemia within 5-10 min. This rapidity of response to anti-LPS may be important in the previously reported therapeutic benefit of anti-LPS.

Animals↗