Search PubMed⌕ Search

Biomedical subjects

R Sankar

Publications and source records attributed to R Sankar.

At least 73 records · Page 4Linked to original sources

Lipids and lipoprotein profile in doxorubicin treated rats: influence of alpha-tocopherol administration.

The effect of doxorubicin (DXR) on the levels of heart, liver and plasma lipids and plasma lipoproteins were studied in rats. Rats were treated with DXR (2.5 mg/kg body weight weekly for 8 weeks, iv) with or without alpha-tocopherol (alpha-TPL) (400 mg/kg body wt daily for 60 days) co-administration. DXR treated rats showed increase in plasma total cholesterol, triglycerides and phospholipids. The activities of lecithin cholesterol-acyl transferase and hepatic and extrahepatic lipoprotein lipase were lowered significantly with concomitant increase in liver and heart lipid peroxide levels in DXR treatment. HDL cholesterol level was found to be decreased significantly in DXR treated rats as a result of which there was an increase of LDLc/HDLc ratio. alpha-TPL coadministration brought back the enzyme activity to near normal and reduced the level of lipid peroxides. The lipid changes were minimum in rats treated with both alpha-TPL and DXR. This study suggests that the toxicity of DXR is reflected in lipids and lipoprotein profile.

Animals↗

Octanoic acid inhibits astrocyte volume control: implications for cerebral edema in Reye's syndrome.

Octanoic acid has been implicated in the pathogenesis of cytotoxic cerebral edema in Reye's syndrome. Using astrocytes from primary culture, we studied the dose-dependent effects of octanoate on cellular volume regulation and metabolism. Astrocyte volume recovery following hypoosmotic swelling was stimulated by 1.0 mM octanoate and inhibited by 3.0 mM octanoate. Parallel effects were obtained at these concentrations on the activity of the Na+,K+-dependent ATPase. Cellular ATP concentrations also were reduced 36% with the higher octanoate concentration. These effects of octanoate may contribute to the severe astrocyte swelling observed in the brains of Reye's syndrome patients.

Adenosine Triphosphate↗

Effect of alpha-tocopherol on peroxidative membrane damage caused by doxorubicin: an in vitro study in human erythrocytes.

Level of lipid peroxidation in doxorubicin treated human erythrocytes was studied and compared with that of cells pretreated with alpha-tocopherol. Erythrocytes treated with alpha-tocopherol had reduced level of lipid peroxidation with concomitantly lowered membrane damage. The membrane damage was monitored by the levels of conjugated diene absorption, lipid hydroperoxides and lipid peroxides. alpha-tocopherol was not effective in inhibiting the conjugated diene formation, but the lipid hydroperoxides and the lipid peroxide levels were significantly decreased. Methemoglobin level was found to be increased in alpha-tocopherol pretreated cells, which protects the membrane from damage. Erythrocyte membrane lipids were found to be decreased during doxorubicin treatment and alpha-tocopherol significantly reduced the membrane lipid breakdown. Level of reduced glutathione was maintained in alpha-tocopherol pretreated cells. These results are discussed with reference to the antioxidant property of alpha-tocopherol.

Cells, Cultured↗

Energy-dependent volume regulation in primary cultured cerebral astrocytes.

Cell volume regulation and energy metabolism were studied in primary cultured cerebral astrocytes during exposure to media of altered osmolarity. Cells suspended in medium containing 1/2 the normal concentration of NaCl (hypoosmotic) swell immediately to a volume 40-50% larger than cells suspended in isoosmotic medium. The cell volume in hypoosmotic medium then decreases over 30 min to a volume approximately 25% larger than cells in isoosmotic medium. In hyperosmotic medium (containing twice the normal concentration of NaCl), astrocytes shrink by 29%. Little volume change occurs following this initial shrinkage. Cells resuspended in isoosmotic medium after a 30 min incubation in hypoosmotic medium shrink immediately to a volume 10% less than the volume of cells incubated continuously in isoosmotic medium. Thus, the regulatory volume decrease (RVD) in hypoosmotic medium involves a net reduction of intracellular osmoles. The RVD is partially blocked by inhibitors of mitochondrial electron transport but is unaffected by an inhibitor of glycolysis or by an uncoupler of oxidative phosphorylation. Inhibition of RVD by these metabolic agents is correlated with decreased cellular ATP levels. Ouabain, added immediately after hypoosmotic induced swelling, completely inhibits RVD, but does not alter cell volume if added after RVD has taken place. Ouabain also inhibits cell respiration 27% more in hypoosmotic medium than in isoosmotic medium indicating that the (Na,K)-ATPase-coupled ion pump is more active in the hypoosmotic medium. These data suggest that the cell volume response of astrocytes in hypoosmotic medium involves the net movement of osmoles by a mechanism dependent on cellular energy and tightly coupled to the (Na,K)-ATPase ion pump. This process may be important in the energy-dependent osmoregulation in the brain, a critical role attributed to the astrocyte in vivo.

Adenosine Triphosphate↗

Age-associated changes in the effects of amphetamine on the blood-brain barrier of rats.

The effects of varying doses of amphetamine on the permeability of the blood-brain barrier (BBB) to albumin were studied in young and aged Fischer 344 rats. There was no change in the permeability of the BBB associated with aging as revealed by saline-treated control experiments. The changes in the permeability of the BBB did not correlate with the changes in blood pressure produced by corresponding doses of amphetamine in the young or aged animals. In the dose range reported the young and aged rats showed similar pressor responses to amphetamine. The aged rats showed a greater increase in the permeability of the BBB than the young, and this effect was seen with a lower dose of amphetamine in the aged rats. At the highest doses tested the permeability was restored to control levels in both the young and the aged rats. The enhanced vulnerability of the BBB of the aged rats may be related to a deterioration of the noradrenergic control of cerebrovascular permeability.

Aging↗

Dissociation of changes in the permeability of the blood-brain barrier from catecholamine-induced changes in blood pressure of normotensive and spontaneously hypertensive rats.

We have studied the effects of the pressor catecholamine, dopamine, and the depressor catecholamine, isoproterenol, on the systemic blood pressure and the permeability of the blood-brain barrier (BBB) to albumin in normotensive (WKY) and spontaneously hypertensive (SHR) rats. The rats were anesthetized with pentobarbital. The permeability of the BBB to protein was measured by the extravasation of radioiodinated serum albumin (RISA). The permeability was decreased by both catecholamines despite the dose-dependent, yet opposite, changes in blood pressure in the WKY rats. The blood pressure response to both of the catecholamines was enhanced in the SHR rats. Isoproterenol caused a decrease in the permeability of the BBB in the SHR but dopamine did not. Results with both WKY and SHR rats are suggestive of an adrenergically-mediated decrease in movement across the BBB of compounds of large molecular weight, regardless of changes in blood pressure.

Animals↗

Effects of acute hypertension on the extravasation of macromolecule in the temporal bone--the possible involvement of the blood-inner ear barrier.

In guinea pigs the radioactivity in the vascular beds was washed out by a cardiac perfusion of saline 15 min after the injection of 50 microCi of radioiodinated human serum albumin (RISA). The brain and temporal bones were dissected and a blood sample was obtained. To examine the degree of extravasation of RISA, the extravascular radioactivity in the tissues was measured and expressed as a ratio to that of the blood. Intravenous injection of amphetamine sulfate increased the extravasation in the brain and the temporal bone of the rat but did not increase it in either tissue of the guinea pig. It was proposed that this was because amphetamine did not cause the blood pressure of the guinea pig to reach the "critical level" which would cause the opening of the blood-tissue barrier. In the rat the degrees of extravasation in both the brain and the temporal bone paralleled the maximal mean arterial pressure caused by amphetamine. It is proposed on the basis of these data that there may exist a blood-inner ear barrier and that this barrier has the same characteristics as the blood-brain barrier.

Acute Disease↗

Selective effects of alpha-MSH and MIF-1 on the blood-brain barrier.

The effects of intravenously-injected alpha-MSH and MIF-1 (Pro-Leu-Gly-NH2) on the permeability of the blood-brain barrier (BBB) to a large protein and a small anion were studied using radioiodinated serum albumin (RISA) and 99mTc-labeled sodium pertechnetate. The permeability of the BBB to RISA was unaltered by either peptide. Permeability to the inorganic pertechnetate anion, however, was significantly increased by alpha-MSH but not by MIF-1 at doses known to evoke EEG and behavioral responses. The peptides did not cause a change in the systemic blood pressure. It is possible, therefore, that at least some CNS effects of peripherally administered peptides are exerted by alteration of the permeability of the BBB to other substances.

Animals↗

Iodine loss from iodised salt on heating.

Iodine deficiency disorders constitute a major public health problem in India. The national IDD control programme (NIDDCP) relies solely on iodine supplementation through fortification of common salt with potassium iodate. However, data regarding iodine loss due to high temperatures of cooking procedure is scarce. Using iodometric titration methods, we calculated iodine content of iodised salt samples subjected to incremental heat up to 350 degree Celsius. The results of the study indicate a gradual but minimal loss of iodine content from the iodised salt samples when subjected to high temperature with a maximum loss noticed being 18.5% at 350 degree Celsius. We conclude that there is minimal loss of iodine from the salt fortified with potassium iodate when subjected to heating (temperature normally attained during cooling process).

Administration, Oral↗

Iodine deficiency disorders in school children of Sikkim.

Sikkim is a small state in the eastern Himalayas. A survey was conducted to determine the prevalence of iodine deficiency disorders in the state. A two stage sampling procedure was adopted. In stage one, all villages in the state were listed and 249 were randomly selected for the survey. In stage two, households, were randomly selected from the selected villages using the electoral lists. The basic sampling unit was a household and all members of the households were studied. A total of 17,837 subjects were studied from 3,197 households of 249 villages. Overall prevalence of goitre and cretinism in the community as a whole, were 54.03% and 3.46% respectively. Of the population studied, 5939 were children in the age group of 5 to 16 years. There were 3,005 boys and 2,934 girls. Goitre was detected in 3,381 (56.9%). Goitre prevalence in the boys was 55.4% and in girls it was 58.5% (p = < 0.05). Grade I goitre was seen in 2,472 (73.1%), grade II in 888 (26.3%) and grade III in 21 (0.6%). Endemic cretinism was diagnosed in 175 subjects (2.9%). Cretinism prevalence in the boys was 3.1%, and in girls in was 2.8% and this difference was not significant. Neurological; cretinism was the predominant form (98.3%). Estimation of urinary iodine concentration in 167 subjects revealed the mean concentration to be 3.64 u/dl (SD 2.47). The median value was ug/dl indicating the skewed distribution of the urinary iodine concentration. The study shows the existence of severe iodine deficiency in the school-aged children of Sikkim.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Intellectual and motor functions in school children from severely iodine deficient region in Sikkim.

High prevalence of endemic goitre (54%) and endemic cretinism (3.5%) exist in Sikkim. The level of intellectual functioning and motor performance were assessed in 90 school children in the age group of 10 to 12 years selected randomly from four severely iodine-deficient villages. Bender Visual Motor Gestalt Test, Binet-Kamat Test for mental ability and Raven's Coloured Progressive Matrices were the tests used. The results show an impairment in intellectual and other neuropsychological functions in a high percentage of the children. Visuomotor coordination was poor in 62 (69%). Binet-Kamat test results showed that 19 (21%) children were intellectually subnormal (IQ < 70). Majority of the children (> 80%) had significant impairment in language, meaningful memory, non-meaningful memory, conceptual thinking, numerical reasoning and motor skills. The children did better on non-verbal reasoning and social intelligence. Goitre was detected in 82 (91.1%). Urine samples for iodine estimations was collected from every second child examined. The mean urinary iodine concentration was 4.23 micrograms/dl (SD 2.16). Urinary iodine concentration was less than 2 micro gm/dl in 26.1% (11 children) and less than 5 micro gm/dl in 84.8% (39 children) indicating severe iodine deficiency. The test results show impairment of psychomotor development in children born and brought up in iodine-deficient environment.

Child↗

Epidemiology of endemic cretinism in Sikkim, India.

A survey was conducted in Sikkim to determine the prevalence of endemic cretinism in the state. A household was the basic sampling unit. Villages were selected randomly in the state and from these households were selected randomly using the electoral lists. All members of the households were studied. Total of 17,837 individuals from 3,197 households from 249 villages were studied. There were 8,953 males and 8,884 females. A total of 617 endemic cretins were identified: 316 males and 301 females. The overall prevalence of endemic cretinism was 3.46%: (males 3.53% and females 3.39%). Endemic cretinism was observed in 194 (77.9%) villages studied. Neurological cretinism was the predominant form (98.7%). Deaf-mutism was the most salient neurological feature seen in 472 (76.5%) subjects. Motor system examination revealed proximal spasticity and brisk reflexes, both more marked in the lower limbs. Recording of daily life activities revealed 14.1% of the cretins to be totally dependent and another 23% to be requiring considerable assistance for their daily routine activities. The overall prevalence of goitre found in this survey was 54%. Urinary iodine concentration was estimated from a representative sample of the population; mean 4 micrograms/dl (SD 2.68). This survey shows the existence of severe iodine deficiency in Sikkim.

Adolescent↗

Neuropsychiatric aspects of pediatric thyrotoxicosis.

The neurobehavioural and neuropsychiatric changes associated with thyrotoxicosis are multiple and varied. This association is well recognised although the true incidence of neuropsychiatric symptoms in thyrotoxicosis is not known. Review of available literature suggests that frank psychiatric symptoms in thyrotoxicosis may be in the order of 10%. In pediatric thyrotoxicosis the neuropsychiatric symptoms may be pronounced and may antedate the medical diagnosis by six months to one year. One of the classic presentation is deterioration in school performance. Frequently noticed cognitive and behavioural abnormalities in pediatric thyrotoxicosis are hyperactivity, irritability or anxious dysphoria, and problems of attention. Successful treatment of thyrotoxicosis usually leads to resolution of the major mental disturbances associated with it and delayed treatment possibly results in enduring neuropsychiatric problems. Awareness of neuropsychiatric symptomatology can help in early detection and appropriate management of children with thyrotoxicosis.

Adolescent↗

Surgery for intractable infantile spasms: neuroimaging perspectives.

Twenty-three infants and children underwent cortical resection (n = 15) or hemispherectomy (n = 8) for intractable infantile spasms. Infantile spasms were present at the time of surgery in 17 of the 23 patients; in six, spasms had evolved to other seizure types during surgical evaluation. Children with a remote history of infantile spasms were excluded from this study. Focal or hemispheric lesions were identified by magnetic resonance imaging in seven children; an additional two showed focal atrophy without a discrete lesion. Positron emission tomography (PET) showed lateralized or localized abnormalities of cerebral glucose utilization in all patients; in 14, PET was the only neuroimaging modality to identify the epileptogenic cortex. When this occurred, neuropathological examination of resected brain tissue typically showed malformative and dysplastic cortical lesions. Focal interictal and/or ictal electrographic abnormalities were present in all patients, and corresponded well with localization from neuroimaging. None of the patients were subjected to chronic invasive electrographic monitoring with intracranial electrodes. At follow-up (range 4-67 months; mean 28.3 months), 15 children were seizure-free, three had 90% seizure control, one had 75% seizure control, and four failed to benefit from surgery with respect to seizure frequency.

Brain↗

Radioactive iodine therapy in Graves' hyperthyroidism.

Graves' disease is a common condition encountered in clinical practice. The available modes of therapy for Graves' disease are antithyroid drugs, radioiodine and surgery. Radioiodine therapy is indicated in patients with nearly all causes of hyperthyroidism and is considered the treatment of choice for most patients with Graves' hyperthyroidism who are beyond the adolescent years. Pregnancy and breast-feeding are absolute contraindications. Although there are many ways of calculating the dose of radioiodine, fixed dose regimens are gaining acceptance. Hypothyroidism follows sooner or later in nearly all patients treated with radioiodine. Available evidence suggest that patients are best treated by a single thyroablative dose, the aim being elimination of hyperthyroidism, with larger doses accomplishing it with more certainty, and the inevitable hypothyroidism develops under physician control. Radioiodine therapy can lead to exacerbation of infiltrative ophthalmopathy and this can be prevented by the concomitant administration of corticosteroids. Radioiodine therapy for Graves' hyperthyroidism has no adverse effects on the health of the offspring of treated patients. There are no definitive data that provide evidence for increased rates of thyroid cancer, leukaemia, infertility or neonatal abnormality in patients treated with radioiodine. Radioiodine therapy is safe, definitive and cost-effective.

Adult↗