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Biomedical subjects

S Ramanadham

Publications and source records attributed to S Ramanadham.

At least 55 records · Page 3Linked to original sources
PubMed1991

The distribution and half-life for retention of vanadium in the organs of normal and diabetic rats orally fed vanadium(IV) and vanadium(V).

The concentration of vanadium in organs of diabetic rats that had been fed vanadium, either as V(IV) or V(V), in their drinking water has been determined. The kidney was found to have the highest concentration, about 185 nmol/g wet tissue. This averages about three times higher than for the liver or spleen, for which concentrations were comparable. The lung, blood plasma, and blood cells tended to have the lowest accumulations of vanadium. A time-course study indicated that the half-life for elimination of vanadium from the bodies of vanadium-fed rats is about 12 d.

Animals↗
PubMed1990

Toxicological aspects of vanadyl sulphate on diabetic rats: effects on vanadium levels and pancreatic B-cell morphology.

This study explored some toxicological aspects of vanadyl sulphate (VOSO4) treatment of rats made diabetic with a single intravenous injection of streptozotocin (60 mg/kg). Administered in drinking water (0.25, 0.5, 0.75 or 1 mg of VOSO4, 5H2O ml) VOSO4 treatment partially or totally corrected some of the alterations associated with the diabetic state (hyperglycaemia, polydipsia, polyphagia, high cholesterol and triglycerides levels) and did not produce any changes in various plasma or blood cell parameters which were not previously altered by diabetes. Measurement of vanadium levels indicated that tissues accumulated vanadium in the following order of concentrations: bone greater than kidney greater than spleen greater than liver greater than lung greater than or equal to muscle greater than blood. Histopathological studies did not reveal any difference in liver, stomach, ileum, spleen, heart and lung from control, non-treated diabetic or VOSO4-treated diabetic animals. Kidney of all non-treated diabetic animals showed an epithelial cellular swelling of distal tubules while only 2 of 6 VOSO4-treated diabetic animals showed this alteration. Cellular degeneration of pancreas B-cells was less marked in VOSO4-treated that in non-treated diabetic animals. The study indicates that VOSO4 may be a potential antidiabetic agent.

Animals↗
PubMed1990

Enhanced in vivo sensitivity of vanadyl-treated diabetic rats to insulin.

Vanadium has been reported to have insulin-like properties and has recently been demonstrated to be beneficial in the treatment of diabetic animals. In the present study, concentration dependence of the therapeutic effects of vanadium and the nature of interaction under in vivo conditions between vanadium and insulin were examined in streptozotocin-diabetic rats. During a 2-week period, blood glucose levels in all treated animals were decreased. At higher concentrations of vanadyl this decrease was greater and more rapid, and remained consistently lower for the entire treatment period. Daily intake of vanadyl, however, reached a similar steady state in all groups. Acute administration of submaximal doses of insulin, which had minimal effects in untreated diabetic rats, lowered blood glucose concentrations in vanadyl-treated and vanadyl-withdrawn animals to control levels. Chronic treatment of streptozotocin-diabetic rats with submaximal levels of vanadyl and insulin, ineffective alone, also produced significant decreases in blood glucose levels when used in combination. Finally, the insulin dosage required to maintain a nonglycosuric state in spontaneously diabetic (BB) rats was reduced in the presence of vanadyl. These studies indicate that chronic oral vanadyl treatment (a) produces a concentration-related lowering of blood glucose in diabetic rats, (b) potentiates the in vivo glucose lowering effects of acute and chronic administrations of insulin in streptozotocin-diabetic rats, and (c) substitutes for, or potentiates, the effects of chronic insulin therapy in spontaneously diabetic BB rats.

Animals↗
PubMed1990

Myocardial and metabolic abnormalities in streptozotocin-diabetic Wistar and Wistar-Kyoto rats.

Four-week-old Wistar and Wistar-Kyoto (WKY) and 12-year-old Wistar rats treated with streptozotocin (55 or 65 mg/kg) were studied to assess the relationship between diabetes-induced alterations in lipid and thyroid hormone concentrations and myocardial tissue function. In the Wistar rats, both doses of streptozotocin resulted in hyperlipidemia and hypothyroidism. However, the higher dose was associated with: greater increases in plasma lipid levels in both age groups; larger increases in plasma lipid levels in older rats; and decreases in myocardial sensitivity to isoproterenol and beta-adrenoceptor density. The diabetic state in WKY rats, while also accompanied by hypothyroidism, was not differentially affected by the two doses of streptozotocin, nor associated with severe hyperlipidemia, nor associated with alterations in the myocardial beta-adrenoceptor system. These findings, as expected, reveal that the dose of streptozotocin and the age and strain of rat influence the diabetic state. Furthermore, these data do not suggest a direct correlation between diabetes-induced alterations in myocardial inotropic sensitivity and associated changes in plasma lipid or thyroid hormone concentrations.

Animals↗
PubMed1989

Sustained prevention of myocardial and metabolic abnormalities in diabetic rats following withdrawal from oral vanadyl treatment.

Earlier studies revealed a general amelioration of diabetes-induced alterations in the rat following chronic oral vanadyl treatment. Recently, some streptozotocin-diabetic animals treated similarly were observed to remain euglycemic after withdrawal from vanadyl. In the present study, the diabetic profile of these animals (STZ-T) was investigated. After 3 weeks of treatment with vanadyl followed by 13 weeks of withdrawal, plasma concentrations of glucose, insulin, lipids, and thyroid hormones in the STZ-T animals were returned to control levels. Myocardial dysfunction and increased glycerol output from adipose tissue in untreated-diabetic (STZ) rats were also found to be normalized in the STZ-T group. Furthermore, there was no evidence of cataracts in these animals compared with age-matched STZ rats. These findings indicate that short-term oral treatment of diabetic rats with vanadyl induces beneficial changes that persist following withdrawal of the treatment. The results of these studies may suggest a possible new treatment protocol that could be incorporated into the management of diabetes.

Adipose Tissue↗
PubMed1989

Chronotropic function in spontaneously diabetic BB rats.

In the present study, isolated atrial function in spontaneously diabetic BB Wistar rats maintained for 12 weeks on a low (BB-LI) and a high (BB-HI) dosage of insulin was examined. Basal atrial rates were unchanged in the diabetic animals, relative to nondiabetic littermates (ND-BB) or Wistar controls. The BB-HI animals were euglycemic and responded to isoproterenol in a similar manner to the ND-BB and Wistar control animals. In contrast, BB-LI animals remained hyperglycemic and exhibited lower responses to the maximum chronotropic effects of isoproterenol. Plasma thyroid hormone levels were unaltered in the BB-diabetic animals. These results therefore reveal an absence of bradycardia and hypothyroidism in spontaneously diabetic BB rats, in contrast to previous observations in streptozotocin diabetic rats. However, a decrease in chronotropic response to isoproterenol was still noted in the BB-LI animals. These findings suggest that decreased positive chronotropic effect of isoproterenol in diabetes may not be a direct consequence of altered thyroid status.

Animals↗
PubMed1989

Oral vanadyl sulfate in treatment of diabetes mellitus in rats.

Recent reports have suggested that vanadium in the form of vanadyl (+IV) possesses insulin-like activity. Therefore, in the present study we examined the effects of administering oral vanadyl to diabetic animals. Wistar rats made diabetic with streptozotocin and age-matched controls were maintained for 10 wk in the absence and presence of vanadyl sulfate trihydrate in the drinking water. In the presence of vanadyl, decreases in rate of growth and circulating levels of insulin were the only significant alterations recorded in control animals. In contrast, diabetic animals treated with vanadyl, despite having lower body weights and insulin levels, had normal plasma concentrations of glucose, lipid, creatinine, and thyroid hormone. In addition, abnormalities in isolated working heart function and glycerol output from adipose tissue of diabetic animals were also corrected after vanadyl treatment. These results suggest that vanadium when used in the vanadyl form is effective in diminishing the diabetic state in the rat by substituting for and replacing insulin or possibly by enhancing the effects of endogenous insulin.

Administration, Oral↗
PubMed1989

Long-term effects of vanadyl treatment on streptozocin-induced diabetes in rats.

The vanadate and vanadyl forms of vanadium have been shown by many investigators to have insulinlike effects on glucose metabolism. Many investigators have shown that vanadium, or its salts, counteracts the hyperglycemia associated with streptozocin-induced diabetes (STZ-D) in the rat, although insulin secretion remains depressed. Studies of the action of vanadate on insulin secretion and glucose metabolism have not addressed the question of possible long-term effects of this compound on glucose metabolism extending beyond the period of oral administration. This study was undertaken to assess the effects of treatment (3 wk) and withdrawal of vanadyl sulfate (13 wk) on glucose metabolism, insulin secretion, and islet insulin content of STZ-D rats. Our results indicate that STZ-D rats that have had blood glucose levels normalized by 3 wk of vanadyl treatment remain normoglycemic after 13 wk of withdrawal from treatment. Normal glucose tolerance was observed in vanadyl-treated diabetic animals despite depressed fasting and glucose-stimulated plasma insulin levels. Insulin secretion from the isolated perfused pancreas was greater after vanadyl treatment than in untreated diabetic rats, although it was only 12% of values from controls. Three weeks of vanadyl treatment of STZ-D rats, followed by 13 wk of withdrawal, yielded islets close in size and insulin content of control islets, even though in vivo and in vitro insulin secretion was impaired. This study has shown that short-term vanadyl treatment of STZ-D rats yields normalization of glucose tolerance and protection of islets from destruction by STZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Nonspecific supersensitivity induced by reserpine in guinea pig cardiac ventricle tissue.

The depletion of norepinephrine stores by chronic reserpine pretreatment is thought to be responsible for the development of supersensitivity in cardiac tissue. The present study was designed to determine if reserpine-induced supersensitivity could be demonstrated in isolated guinea pig right ventricular strips, if it was associated with beta adrenoceptor proliferation and was specific for beta adrenoceptor agonists. In addition, reserpine dose-dependency of the phenomenon was tested for by using two pretreatment regimens to determine if supersensitivity was the result of direct or possibly toxic effects of reserpine. Pretreatment of guinea pigs with reserpine (0.1 mg/kg/day) for 7 days resulted in over 90% depletion of cardiac norepinephrine stores. Supersensitivity to the inotropic effects of isoproterenol, impromidine and forskolin was demonstrated. Associated with the supersensitivity was a significant increase in beta adrenoceptor density. Muscarinic receptor density was actually decreased. This pretreatment regimen also was associated with a significant (30%) drop in body weight suggesting that the phenomenon might be the result of a direct toxic effect of reserpine. Pretreatment of guinea pigs with a lower dose of reserpine (0.03 mg/kg/day) for 7 days produced the same degree of norepinephrine depletion, nonspecific inotropic supersensitivity and beta adrenoceptor proliferation in the absence of a significant reduction in body weight. The degree of supersensitivity induced by the two pretreatment regimens was between 2- to 3-fold for all three agonists tested.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Alterations in the myocardial beta-adrenoceptor system of streptozotocin-diabetic rats.

Previous investigations in our laboratory revealed subsensitivity of right ventricular tissue, isolated from one month STZ-diabetic rats, to the inotropic effects of isoproterenol. The present study was concerned with the characterization of this subsensitivity phenomenon. Observations of supersensitivity to methoxamine accompanied by decreased responsiveness to glucagon without a change in responsiveness to forskolin suggested a specific effect of diabetes on pathways involving receptor-mediated activation of adenylate cyclase. Radioligand binding analysis further revealed a specific decrease in the population of the high affinity state of the beta-adrenoceptor. Since the high affinity receptor state is a necessary intermediate for adenylate cyclase activation and enhanced myocardial contractility, it is proposed that the specific decrease in the high affinity population of the beta-adrenoceptor contributes to myocardial subsensitivity to isoproterenol observed in the diabetic animals. It is further proposed that the decrease in receptor population is related to increases in circulating epinephrine levels which were evident in the diabetic animals.

Animals↗
PubMed1987

Prevention of streptozotocin-induced alterations in the rat heart by 3-O-methyl glucose and insulin treatments.

Streptozotocin-induced diabetes has previously been shown to alter the sensitivity and responsiveness of rat myocardial tissues to cardiotonic agonists. The objective of the present study was to determine if these alterations were due to the diabetogenic or possible direct cardiotoxic effects of streptozotocin. One month after streptozotocin treatment the following changes were observed in the rat: decrease in body weight; elevation of blood glucose and glycosylated hemoglobin levels; decrease in spontaneously beating atrial rate; elevation in basal developed force of electrically driven right ventricle; and inotropic subsensitivity of right ventricle to isoproterenol, which was associated with decreased beta-adrenoceptor density and supersensitivity to calcium. Pretreatment with the nonmetabolizable glucose analog 3-O-methyl glucose prevented these alterations. Chronic insulin replenishment also reversed the effects of streptozotocin, with the exception of complete normalization of elevations in blood glucose and basal developed force. Acute exposure to high glucose in the medium preserved the subsensitivity to isoproterenol but resulted in an elevated basal developed force in both control and streptozotocin groups. These observations indicate that myocardial alterations after streptozotocin treatment are not the result of direct cardiotoxic effects but rather a consequence of the drug-induced diabetic state. They also suggest that the increase in basal developed force might be related to elevated glucose concentrations.

3-O-Methylglucose↗
PubMed1986

Chronic effects of streptozotocin diabetes on myocardial sensitivity in the rat.

One month after streptozotocin treatment, basal rate in spontaneously beating right atria was decreased and basal developed force in electrically-driven right ventricular tissue was increased. Atrial sensitivity to the chronotropic effects of isoproterenol was not altered. In contrast, sensitivity in ventricular tissue to the inotropic effects of isoproterenol was decreased while sensitivity to calcium was increased. Associated with these changes was a decrease in myocardial beta-adrenoceptor density. Data obtained 3 and 6 months after streptozotocin treatment were similar to the observed alterations at 1 month. These results suggest that alterations in the chronotropic and inotropic responses that are expressed within 1 month after streptozotocin treatment do not significantly progress during the 6 months following induction of diabetes. They therefore reveal the independence of myocardial alterations from age of the animal and duration of diabetes (up to 6 months).

Animals↗
PubMed1984

Alterations in aortic and tail artery reactivity to agonists after streptozotocin treatment.

In the present study, responses to various agonists in thoracic aorta and tail artery strips, obtained from 4-week streptozotocin (STZ)-treated rats and age-matched controls, were studied. Responses in aorta obtained from diabetic animals to the alpha-agonists, norepinephrine (NE), and methoxamine (MOX), to calcium (Ca2+) and potassium (K+) were found to be depressed relative to control tissue. Responses in tail artery however, were found to be different. While responses to K+ were decreased and to Ca2+ unchanged, tail artery strips obtained from diabetic animals were found to be supersensitive to both alpha-agonists relative to control tissue. Another observed difference between the two tissues was in their catecholamine content. While induction of diabetes did not alter catecholamine levels in the aorta, a significant decrease was produced in the tail artery, relative to control tissue levels. Our results indicate that inherent differences (such as the degree of innervation) may contribute to the differential responses observed in the two tissues studied. They further suggest the possible involvement of alterations in calcium utilization in aorta and the development of postjunctional supersensitivity in tail artery obtained from STZ-treated animals.

Animals↗