PubMed Health⌕ Search

Biomedical subjects

A K Sinha

Publications and source records attributed to A K Sinha.

At least 19 recordsLinked to original sources
PubMed1996

Loss of high-affinity prostacyclin receptors in platelets and the lack of prostaglandin-induced inhibition of platelet-stimulated thrombin generation in subjects with spinal cord injury.

Coronary artery disease is a leading cause of death in individuals with chronic spinal cord injury (SCI). However, platelets of those with SCI (n = 30) showed neither increased aggregation nor resistance to the antiaggregatory effects of prostacyclin when compared with normal controls (n = 30). Prostanoid-induced cAMP synthesis was similar in both groups. In contrast, prostacyclin, which completely inhibited the platelet-stimulated thrombin generation in normal controls, failed to do so in those with SCI. Scatchard analysis of the binding of [3H]prostaglandin E1, used as a prostacyclin receptor probe, showed the presence of one high-affinity (Kd1 = 8.11 +/- 2.80 nM; n1 = 172 +/- 32 sites per cell) and one low-affinity (Kd2 = 1.01 +/- 0.3 microM; n2 = 1772 +/- 226 sites per cell) prostacyclin receptor in normal platelets. In contrast, the same analysis in subjects with SCI showed significant loss (P < 0.001) of high-affinity receptor sites (Kd1 = 6.34 +/- 1.91 nM; n1 = 43 +/- 10 sites per cell) with no significant change in the low affinity-receptors (Kd2 = 1.22 +/- 0.23; n2 = 1820 +/- 421). Treatment of these platelets with insulin, which has been demonstrated to restore both of the high- and low-affinity prostaglandin receptor numbers to within normal ranges in coronary artery disease, increased high-affinity receptor numbers and restored the prostacyclin effect on thrombin generation. These results demonstrate that the loss of the inhibitory effect of prostacyclin on the stimulation of thrombin generation was due to the loss of platelet high-affinity prostanoid receptors, which may contribute to atherogenesis in individuals with chronic SCI.

Adult↗
PubMed1995

Severe motorcycle injury in Mersey region and North Wales.

Ninety-three patients were involved in serious motorcycle accidents (death or Injury Severity Score more than 15) during a 1-year period among a total of 554 victims of serious road traffic accidents studied at 16 district general and teaching hospitals. There were 91 males and two females. The average age was 29 years (range 15-81 years). Of these, 32 per cent died at the scene of the accident or in transit; 68 per cent arrived alive at the above hospitals. Of the latter, 30 per cent died in hospital. The commonest cause of death was multiple injuries. The Injury Severity Score of patients admitted to hospital was a mean of 32.1. The Glasgow Coma Score was below 9 in 33.8 per cent. Of those admitted to hospital, the average length of stay was 38.7 days. 67 per cent were admitted to intensive therapy unit of whom 41.3 per cent had to be ventilated for an average of 3.55 days. There were four preventable deaths among the patients who died after being admitted to hospital. Many body areas are frequently injured in motorcycle accidents which occur usually in fit males. Careful assessment along with vigorous and aggressive treatment is particularly important for this group. Access to a specialized trauma centre would be beneficial.

Accidents, Traffic↗
PubMed1995

Insulin-induced release of plasminogen activator from human blood platelets.

Incubation of washed platelets in Tyrode buffer, pH 7.5, with insulin (200 microU/ml) and CaCl2 (1.2 mM) at 37 degrees C for 3 h resulted in a threefold increase of plasminogen activator activity in the supernatant over the basal level as determined by both the amidolytic assay and the proteolysis of alpha-casein through the formation of plasmin from plasminogen. This plasminogen activator showed no plasmin-like activity and was inhibited by anti-tissue plasminogen activator antibody as well as by type 1 plasminogen activator inhibitor. The substrate specificity and the inhibition of the enzymic activity by various inhibitors indicated that the platelet plasminogen activator (pPA) was related to tissue-type plasminogen activator of relative molecular weight 56,000. Fibrinolytic activity of pPA and its insulin-dependent release were demonstrated by the shortening of euglobulin lysis time and by the clot lysis time of platelet-rich plasma from normal and type I diabetes mellitus patients. Treatment of platelet membranes with insulin also increased the release of pPA. Increased levels of adenosine 3',5'-cyclic monophosphate (cAMP) in platelets by incubation with various agents completely inhibited the insulin-induced release of the activator. On the other hand, inhibition of platelet aggregation by aspirin had no effect on the release of pPA, indicating that the effect of cAMP was not due to the inhibition of platelet aggregation by the nucleotide.

Alprostadil↗
PubMed1995

Electrophysiological studies in children with paralytic poliomyelitis.

H-reflex latency (H-RL) and H/M ratio were measured in normal children and children with paralytic poliomyelitis of 1-3 years of age. The H-RL was considerably increased in both the involved and uninvolved limbs of the patients, whereas the H/M ratio did not differ. The Mmax value in the involved limb was very low, and therefore, a corrected H/M ratio was calculated for that side only. The corrected H/M ratio was significantly less than the H/M ratio observed in the uninvolved and control limbs. The distal motor latency was also increased in the involved side.

Child, Preschool↗
PubMed1995

Assessment of long-term glycaemic control in diabetic patients attending Port Moresby General Hospital.

Good glycaemic control is important in preventing the acute and long-term complications of diabetes mellitus. We assessed long-term glycaemic control using glycosylated haemoglobins in 83 diabetic patients, of mean age 47 years and of mean known duration 4.5 years, attending Port Moresby General Hospital over a one-year period. Significant improvement in glycaemic control was observed in only 11 (13%) of the patients. Glycaemic control worsened in 13 (16%) and no change was observed in the remainder (71%). Mean glycosylated haemoglobin and fasting plasma glucose levels were similar at the beginning and end of the study period. Over a one-year period 53 patients (64%) exhibited poor control with mean glycosylated haemoglobin levels exceeding 10%. Among the 19 newly diagnosed diabetic patients (23% of the total) glycaemic control improved in only 2 (11%). Glycaemic control was not influenced by sex, treatment, obesity or duration of diabetes. The demonstration of poor metabolic control in the majority of patients suggests that urgent measures are needed to reevaluate the management of diabetic patients, particularly with respect to education and diet. This may improve the poor survival rates reported in diabetic patients from Papua New Guinea.

Adult↗
PubMed1994

Transient decrease of binding of insulin to platelets in acute ischemic heart disease.

The specific binding sites of 125I-insulin in platelets from nondiabetic patients with acute myocardial infarction and unstable angina pectoris was significantly decreased (192 +/- 84/cell) during the acute ischemic condition when compared with normal platelets (496 +/- 76/cell; p < 0.001, n = 9). A relatively low mean plasma insulin level (20 microU/mL) with an elevated mean glucose level (130 mg/dL) was noted. The decreased binding of insulin and the relatively low mean plasma insulin level during the acute ischemic condition improved into the normal range during 8 to 12 weeks of recuperation. The decrease of insulin binding sites in the acute phase and their subsequent increase during recovery were directly related to the hormone-induced increase in sensitivity to prostaglandin E1 through the stimulation of adenosine 3',5'-cyclic monophosphate formation in platelets by the prostanoid.

Acute Disease↗
PubMed1994

Effects of inhibition of nitric oxide synthase on blood-brain barrier transport in focal cerebral ischemia.

This study was performed to determine whether nitric oxide (NO) alters the transport of small hydrophilic molecules across the blood-brain barrier in focal cerebral ischemia by administering an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and by measuring the blood-brain barrier transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB) in the rats with middle cerebral artery occluded under isoflurane anesthesia. L-NAME increased the mean arterial blood pressure from 91 +/- 9 to 134 +/- 13 mm Hg. The Ki of the ischemic cortex (ICO) was 26% higher than that of the contralateral cortex (CCO) in the control animals without the L-NAME treatment. However, in the L-NAME-treated animals, Ki was 33% lower in the ICO than in the CCO. The Ki of ICO in the L-NAME group was significantly lower (-54%) than that of the control group. L-NAME did not affect Ki significantly in the nonischemic brain regions. Our data demonstrate that focal ischemia increased Ki of 14C-AIB, but L-NAME significantly decreased the Ki in the focal ischemic area of the brain without causing significant changes in the nonischemic tissue. Our results suggest that NO may participate in increasing transport of small hydrophilic molecules across the blood-brain barrier in focal ischemia.

Amino Acid Oxidoreductases↗
PubMed1994

Nitric oxide synthase inhibition alters cerebral blood flow and oxygen balance in focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: This study investigated whether the nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) would alter blood flow and oxygen balance in the ischemic cerebrocortex of isoflurane-anesthetized Long-Evans rats. METHODS: Fifteen minutes after middle cerebral artery occlusion, L-NAME (1.5 mg/min per kilogram) was infused intravenously to the L-NAME group (n = 14), and normal saline was given to the control group (n = 14) for 45 minutes. In each group, regional cerebral blood flow was determined with [14C]iodoantipyrine, and arterial and venous oxygen saturations were determined by microspectrophotometry. RESULTS: In both groups regional cerebral blood flow of the ischemic cortex was significantly lower than that of the contralateral cortex ([mean +/- SD] 55 +/- 13 versus 110 +/- 29 mL/min per 100 g in the control group and 35 +/- 13 versus 90 +/- 24 mL/min per 100 g in the L-NAME group). Compared with the blood flow in the ischemic cortex of the control group, L-NAME significantly reduced ischemic blood flow by 36%. Venous oxygen saturation was significantly increased in the ischemic cortex (41 +/- 1% versus 44 +/- 3%) but decreased in the contralateral cortex (65 +/- 3% versus 61 +/- 4%) by L-NAME. Calculated ischemic cortical oxygen consumption in the L-NAME group was 39% lower than that in the corresponding control group, whereas the difference was only 11% in the contralateral sides between groups. In both groups, the ratio of oxygen supply to consumption was lower in the ischemic than in the nonischemic regions. In the ischemic cortex, this ratio was significantly lower in the control group than in the L-NAME group (1.7 +/- 0.1 versus 1.9 +/- 0.1). In contrast, the ratio tended to be decreased by L-NAME in nonischemic regions. CONCLUSIONS: These observations suggest that despite a decrease in cerebral blood flow, inhibition of nitric oxide synthesis mildly improves the oxygen supply and consumption balance in the ischemic cortex.

Amino Acid Oxidoreductases↗
PubMed1994

Transport of thyroid hormones to target tissues.

Endemic iodine deficiency is associated with maternal hypothyroxinemia and a relatively high incidence of neurological disorders in the offspring. The previous assumption that the placenta is impermeable to maternal thyroid hormone, has resulted in the erroneous suggestion that iodine per se has an essential role in brain development. Furthermore, the observed factorial rise in thyroxine-binding globulin (TBG) in pregnancy has often been misinterpreted as preventing thyroid hormone loss to either the fetal compartment or excretory systems. However, physiochemical analysis of the role of specific binding proteins in hormone delivery, combined with epidemiological evidence and evolutionary considerations has led us to postulate that a) maternal thyroxine (T4) is transported to the fetus, and is of crucial importance in early fetal development, and b) TBG forms part of a control system specifically designed to maintain at an optimal level the T4 environment to which the developing fetus is exposed. Placental transfer of maternal T4 in a variety of mammalian species (including humans) is now well established. Further experimental studies in rats have shown that perturbation of the intrauterine thyroid hormone environment during critical phases of brain development results in a spectrum of biochemical dysgenesis. For example, in fetal brains deriving from hypothyroxinemic (Tx) rat dams, severe disruption of phosphate metabolism is observed and the ontogenesis of two enzyme activities associated with growth control, protein kinase C and ornithine decarboxylase, are compromised. Development of brain function is also impaired, as evidenced by the dysgenesis of certain neurotransmitter metabolic activities (choline acetyltransferase and DOPA decarboxylase).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Perturbation of thyroid hormone homeostasis in the adult and brain function.

Although a critical role of thyroid hormones in mammalian brain development is well established and extensively documented, the adult CNS is often thought to be a thyroid hormone-insensitive organ. The presence in the adult brain of thyroid hormone, along with high levels of nuclear T3 receptors and the strict regulation of intracerebral T3 levels, coupled with overt psychomotor and cognitive dysfunctions in adult-onset dysthyroidism, casts doubt upon this assumption. We have therefore investigated the influence of thyroid hormones on the biochemistry, metabolism and molecular biology of adult rat brain regions and confluent neurons and astrocytes in culture. Our results and those in the literature show that brain nuclear T3 receptor and angiotensinogen mRNA levels and 5'D-II activity are dependent upon normal thyroid hormone concentrations. Several subfractions of cell signalling proteins (G protein alpha subunits) are compromised in hypo- and hyperthyroidism and the activities of protein kinases A and C are up-regulated in the hypothyroid state in a brain region-specific manner. The activities of acid phosphatase and aryl sulphatase A are compromised in the brain of hypothyroid rats, indicating a degree of lysosomal dysfunction, and several neurotransmitter metabolic enzymes and receptor systems are also affected. Metabolic experiments indicate that glutamate and acetate metabolism are compromised in the hypothyroid state, although glucose metabolism remains normal. Primary cultures of confluent neurons and astrocytes also strongly indicate a critical role for thyroid hormones in the control of amino acid uptake, protein synthesis, glycoprotein synthesis and 2-deoxyglucose uptake, in a cell-specific manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Diminished effect of inhibition of nitric oxide synthase on regional cerebral vascular resistance in conscious and in isoflurane anesthetized rats during hemorrhage.

Effects of a nitric oxide (NO) synthase inhibitor on regional cerebral vascular resistance (rCVR) and regional cerebral blood flow (rCBF) were studied during a severe hemorrhage in conscious and in isoflurane anesthetized groups of rats. Half of each group was infused with NG-nitro-L-arginine-methyl ester (L-NAME), a NO synthase inhibitor, at a rate of 2 mg.kg-1.min-1 for 30 min. Half of the L-NAME infused and half of the normal saline infused rats were bled to reduce the mean arterial blood pressure (MAP) to 44-49 mmHg. rCBF was measured using [14C]iodoantipyrine. rCVR was calculated as the ratio of MAP to rCBF. In the conscious non-hemorrhagic rats, L-NAME markedly increased rCVR in all the brain regions that we studied. In the conscious rats without L-NAME treatment, hemorrhage decreased rCVR in most of the brain regions. With L-NAME treatment in this group, hemorrhage increased rCVR only in the rostral part of the brain. Isoflurane decreased rCVR in most of the brain regions except the cortical area. L-NAME markedly increased rCVR in all the brain regions that we studied in the isoflurane anesthetized rats. In the isoflurane anesthetized rats, hemorrhage did not reduce rCVR in any of the brain regions. In the isoflurane anesthetized hemorrhagic rats, L-NAME did not significantly affect rCVR in any of the brain regions that we studied. We found that L-NAME increased rCVR to a greater extent in the non-hemorrhagic rats than in the hemorrhagic rats in both the conscious and in the isoflurane anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1993

Laser-induced stimulation of thromboxane B2 synthesis in human blood platelets: role of superoxide radicals.

Exposure of platelet-rich plasma to laser radiation at 3.5 W for 30 seconds reduced the threshold concentrations of adenosine diphosphate and L-epinephrine needed from complete platelet aggregation by 20% to 60% and by 30% to 50%, respectively. The irradiation of platelet-rich plasma with laser also increased the basal level of thromboxane A2 from < 0.5 pmol/10(8) platelets for each second of exposure. In contrast, the exposure of gel-filtered platelets to laser produced no effect on the prostanoid formation. However, the addition of laser-exposed platelet-free plasma to gel-filtered platelets stimulated the synthesis of thromboxane A2 in these cells. The effect of laser was completely blocked by adding superoxide dismutase or catalase to the platelet-rich plasma, indicating that the radiation-induced stimulation of thromboxane A2 production was mediated through the generation of superoxide radicals. Electron microscopic studies indicated that the laser-induced stimulation of thromboxane A2 production in platelet can occur without any noticeable damage in the cellular structure.

Blood Platelets↗
PubMed1993

Imbalance of regional cerebral blood flow and oxygen consumption: effect of vascular alpha adrenoceptor blockade.

This study tested the hypothesis that local cerebral O2 supply and consumption are not precisely balanced and that vascular alpha adrenoceptors affect this equilibrium. Twenty-two male Long-Evans rats were used in this study. Cerebral blood flow was determined in six regions, using 4-iodo [N-methyl-14C]antipyrine. Oxygen saturation was determined microspectrophotometrically in small veins draining three regions of the brain of the rat. Comparisons were made between a control group and a group given N-methyl chlorpromazine, an alpha adrenergic blocker that does not affect central neuronal alpha adrenoceptors. Under control conditions, no regional differences in flow were found. With N-methyl chlorpromazine, cerebral blood flow in the basal ganglia was greater than all other regions, except the frontal cortex. Cerebral O2 consumption was higher in the frontal cortex than the medulla under control conditions and this difference was not statistically significant after N-methyl chlorpromazine. Cerebral venous O2 saturations (a measure of cerebral O2 supply/consumption balance) were found to be significantly heterogeneous under control conditions. The coefficient of variation (CV = 100 x SD/mean) averaged 18%. The average cerebral venous O2 saturation was 59 +/- 11%. Administration of N-methyl chlorpromazine significantly reduced this heterogeneity through a reduction in the number of veins with low O2 saturations (CV = 11%). The average value increased slightly but significantly to 62 +/- 8%. Thus, N-methyl chlorpromazine eliminated many microregions of high O2 extraction. This indicated that vascular alpha adrenoceptors limit cerebral blood flow to some of the brain regions.

Adrenergic alpha-Antagonists↗
PubMed1993

Effect of constant load training on skeletal muscle histochemistry of thoroughbred horses.

Skeletal muscle adaptations to training of differing intensities were examined in 10 thoroughbred horses that underwent six weeks of treadmill training followed by six weeks of detraining. The horses were randomly assigned to either a slow group exercised at 40 per cent maximum oxygen uptake (VO2max) or a fast group at 80 per cent VO2max. Resting muscle biopsies were taken before training, after six weeks of training and after six weeks of detraining, from m gluteus medius and m biceps femoris. Muscle was analysed histochemically for fibre type composition (myosin ATPase) and capillary supply (PAS amylase). Cross sectional area and lesser fibre diameter were measured by planimetry and image analysis. No alterations were found in the proportions of different muscle fibre types during training or detraining. Capillary density increased by 54 per cent in m biceps femoris of the fast group during training and decreased to the pretraining level following detraining. Few changes in fibre size occurred as a result of training and detraining. It was not possible to draw conclusions as to the effects of detraining because of the small number of training induced changes. The results suggest that for major adaptations in skeletal muscle, an increasing exercise intensity throughout training may be more significant than the degree of exercise load, when exercise intensity is submaximal.

Adaptation, Physiological↗
PubMed1993

Evaluation of the efficacy of different antibiotics in inhibiting colonisation of Vibrio cholerae O1 in the rabbit intestine.

The efficacy of ciprofloxacin, norfloxacin and tetracycline in prevention of colonisation of V. cholerae O1 in the rabbit intestine were tested. V. cholerae O1 highly colonised the gut of rabbits which did not receive any antibiotic. All antibiotics tested inhibited the colonisation of V. cholerae O1 within the rabbit intestine. Moreover, ciprofloxacin and norfloxacin were found to be as effective as tetracycline suggesting that these drugs should be subjected to clinical trials for the treatment of cholera in comparison with tetracycline.

Animals↗
PubMed1993

Effect of cervical sympathectomy and hypoxia on the heterogeneity of O2 saturation of small cerebrocortical veins.

This study evaluated the hypothesis that the sympathetic nervous system was one of the factors increasing the heterogeneity of cerebrocortical venous O2 saturation and this heterogeneity would be greater during hypoxia when cervical sympathetic activity was elevated. Thirty-two male Long-Evans rats were either sham operated (n = 16) or received bilateral cervical sympathectomy (n = 16). One-half of the animals (n = 8) in each treatment were challenged by hypoxia (8% O2 in N2). Cerebral blood flow was determined in five brain regions with [14C]iodoantipyrine. Oxygen saturation was measured microspectrophotometrically in small cerebrocortical arteries and veins. The degree of hypoxic hyperemia was not significantly different between sham-operated and sympathectomized rats. Cortical venous O2 saturations, indicating the balance between O2 supply and consumption, were significantly more heterogeneous in the sham-operated group under both normoxic and hypoxic conditions. The coefficient of variation (CV = 100 x SD/mean) for the normoxic sham-operated animals was 24.9% and the average venous O2 saturation was 53.8%. During hypoxia, venous O2 saturation was significantly decreased to 43.1% without a change in CV (24.5%). Sympathectomy significantly reduced this heterogeneity through a reduction in the number of low O2 saturation veins (CV = 13.2%) under normoxic conditions and the effect was similar under hypoxic conditions (CV = 15.3%). In both sham-operated and sympathectomized groups, hypoxia elicited a significantly higher cerebrocortical O2 consumption. Thus, bilateral cervical sympathectomy improved the O2 supply in selective cerebrocortical regions with high O2 extraction. However, the effect of sympathetic innervation on the heterogeneity of cerebrocortical venous O2 saturation was not potentiated by hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗