ABSTRACT Measurements of γ-rays from mass analyzed nuclear recoils produced in the102Pd +54Fe rea... more ABSTRACT Measurements of γ-rays from mass analyzed nuclear recoils produced in the102Pd +54Fe reaction at 245MeV have allowed us to characterize the decay of a 35 μs isomer in154Lu. The rates of E2 transitions de-exciting isomeric levels in proton-rich N=82, 83 isotones are discussed.
Advances in Experimental Medicine and Biology, 2001
... Treatment and Outcomes Edited by Aubie Angel et a/.. Kluwer Academic/Plenum Publishers, 2001 ... more ... Treatment and Outcomes Edited by Aubie Angel et a/.. Kluwer Academic/Plenum Publishers, 2001 133 Page 148. ... Dr. Subodh Verma is an MRC Fellow. We thank Ms. Mary Battell and Ms.Sylvia Chan for technical and secretarial assistance respectively. ...
ABSTRACT Thesis (M.S.)--Michigan State University. Dept. of Pharmacology, 1971. Includes bibliogr... more ABSTRACT Thesis (M.S.)--Michigan State University. Dept. of Pharmacology, 1971. Includes bibliographical references (leaves 74-81).
American Journal of Physiology-Heart and Circulatory Physiology, 1986
Ventricular hypertrophy and hypothyroidism are each characterized by impaired cardiac muscle rela... more Ventricular hypertrophy and hypothyroidism are each characterized by impaired cardiac muscle relaxation and sarcoplasmic reticulum (SR) calcium uptake activity. A previous report also showed that hypothyroidism does not reverse ventricular hypertrophy (left-to-right ventricular weight ratios) of spontaneously hypertensive rats (SHR). We characterized the effects of thyroidectomy of 8 wk duration on relaxation of ejecting hearts and on SR calcium uptake activity from SHR and nonhypertrophic Wistar-Kyoto rat (WKY) controls. Relaxation was quantified by plotting maximum left ventricular pulse pressure (Pmax) vs. the area under the falling phase of the left ventricular pressure wave at three different pressure loads. Ventricles of euthyroid SHR were characterized by impaired relaxation and depressed SR calcium uptake activity compared with those of euthyroid WKY, confirming earlier studies. Thyroidectomy reduced ventricular relaxation and SR calcium uptake activities to about the same e...
American Journal of Physiology-Cell Physiology, 1979
The influence of alteration in the Ca2+ environment of the tissue on isoproterenol-induced increa... more The influence of alteration in the Ca2+ environment of the tissue on isoproterenol-induced increases in cAMP levels and relaxation was studied in rat uterus. In muscles depolarized with 47.5 mM K+ (with or without Na+), the ability of isoproterenol to increase cAMP levels and to produce relaxation was found to be inversely related to external calcium concentration. The pretreatment of the muscle with D600 or EGTA restored the cAMP response to isoproterenol in the depolarized uterus to a level observed in nondepolarized muscle. The study with Ro 20-1724, a phosphodiesterase (PDE) inhibitor indicated that the failure of isoproterenol to elevate cAMP levels in the depolarized uterus could not be related to the activation of PDE by Ca2+. The exposure of rat uterus to a zero-Ca2+ solution accentuated the increases in cAMP levels produced by isoproterenol. These results have raised the question of a possible regulatory role of Ca2+ in beta-adrenoceptor-induced increases in cAMP levels in ...
Research communications in chemical pathology and pharmacology, 1980
The effect of aprotinine, a natural non-specific protease inhibitor, on cyclic AMP accumulation i... more The effect of aprotinine, a natural non-specific protease inhibitor, on cyclic AMP accumulation in a dog heart washed particle preparation was studied. Aprotinine inhibited GTP-stimulated cyclic AMP accumulation at concentrations equal to or higher than 40 KIU/ml (8 x 10(-7) M). Aprotinine inhibited epinephrine (10(-4) M)-stimulated cyclic AMP accumulation to a greater degree than fluoride (10(-2) M)-stimulated activity. Trypsin stimulated cyclic AMP accumulation at low concentrations (0.5 to 2.5 microgram/ml) and inhibited at higher concentrations. Aprotinine at low concentrations (4 KIU/ml) inhibited the trypsin (1 microgram/ml) stimulation of cyclic AMP accumulation. We conclude that aprotinine may act on the regulator rather than on the catalytic sub-unit of adenylate cyclase and that its mechanism of action is not due only to its antiprotease activity.
The Journal of pharmacology and experimental therapeutics, 1985
The responses of guinea-pig isolated cardiac tissues to carbachol were examined. Tension response... more The responses of guinea-pig isolated cardiac tissues to carbachol were examined. Tension responses of paced left atria and right ventricular papillary muscles, rate responses of spontaneously beating right atria and working hearts and contractility (+dP/dt) of paced and unpaced working hearts were obtained at 38 degrees C. Carbachol induced negative inotropic and chronotropic responses of atria, abolishing tension and rate at the maxima. The spontaneously beating heart also exhibited negative chronotropy. The papillary muscles displayed partial inhibition of tension but, in tissues from reserpine-pretreated animals, negative inotropy was absent. Similarly, no reduction of contractility of paced working hearts was obtained. It was concluded that muscarinic receptors mediating a direct inhibition of ventricular muscle are virtually absent and that the small response obtained in untreated tissue may be due either to inhibition of endogenous catecholamine release via presynaptic recepto...
ABSTRACT 1. The effect of omega-3 fatty acid supplementation on α1-adrenergic receptor-mediated p... more ABSTRACT 1. The effect of omega-3 fatty acid supplementation on α1-adrenergic receptor-mediated phosphoinositide turnover in the hearts of 6-week streptozotocin diabetic rats was studied.2. The diabetic state was characterized by decreased body weight gain, hypoinsuilinemia and hyperglycemia. Omega-3 fatty acid treatment did not have any significant effects on the above parameters.3. Plasma triglyceride and cholesterol levels were significantly higher in diabetic rats compared with controls.4. Omega-3 fatty acid treatment reduced the plasma triglyceride levels in the diabetic rats, whereas plasma cholesterol levels remained unaffected.5. Norepinephrine (10 and 100 μM) stimulated inositol monophosphate (IP1) formation was significantly decreased in the diabetic rat heart compared with controls. Omega-3 fatty acid treatment had no significant effect on the norepinephrine-mediated IP1 formation in these rats.6. Inositol bisphosphate (IP2) formation in response to 100 μM of norepinephrine was significantly lower in the diabetic rat heart; which was also not affected by omega-3 fatty acid treatment.
The PI-3 kinase signalling pathway is an important pathway in mediating the glucoregulatory effec... more The PI-3 kinase signalling pathway is an important pathway in mediating the glucoregulatory effects of insulin and skeletal muscle (SKM) is the major tissue involved in glucose utilization. In diabetes this pathway is impaired, either due to lack of insulin as in Type 1 diabetes, or due to insulin resistance as in Type 2 diabetes. Bis(maltolato)-oxovanadium IV (BMOV), an insulin
The effect of hypothyroidism on isolated rat cardiac sarcoplasmic reticulum (SR) calcium transpor... more The effect of hypothyroidism on isolated rat cardiac sarcoplasmic reticulum (SR) calcium transport activity was determined. Cardiac SR was studied 2, 4 and 6 weeks following surgical removal of the thyroid gland. Thyroidectomized rats had reduced body weight and left ventricular weight 4 and 6 weeks after thyroidectomy. The rate of SR calcium transport activity was not affected 2 weeks after thyroidectomy, but was reduced 4 and 6 weeks after thyroidectomy. To elucidate the mechanism responsible for altered calcium transport activity, the roles of endogenous SR acylcarnitine and SR calcium pump protein were determined. Thyroidectomy did not affect the level of endogenous acylcarnitine associated with the SR membranes isolated at the time points studied. The level of acylphosphoprotein, putatively the SR calcium pump protein, was not affected 2 weeks following thyroidectomy, but was significantly reduced in SR 4 weeks postthyroidectomy. These studies suggest that the quantity of SR calcium pump sites is reduced in hypothyroidism and that this reduction may explain the altered SR calcium transport activity observed.
ABSTRACT Cardiac effects of ω-3 fatty acid treatment were studied in streptozocin (STZ)-induced (... more ABSTRACT Cardiac effects of ω-3 fatty acid treatment were studied in streptozocin (STZ)-induced (55 mg/kg intravenously [IV]) diabetic male Wistar rats. Nondiabetic control and STZ-diabetic animals were treated with Promega (0.5 mL/kg/d; Warner-Lambert, Morris Plains, NJ) for a period of 4 weeks beginning 2 weeks after either vehicle or STZ injection. Plasma glucose, triglyceride, and cholesterol concentrations were significantly (P < .05) elevated in diabetic animals; ω-3 fatty acid treatment did not significantly affect these parameters. An isolated working heart preparation was used to determine aortic and coronary flow rates in control, diabetic, treated control, and treated diabetic animals. Aortic and coronary flow rates of untreated STZ-diabetic rats were significantly (P < .05) lower than those of controls over a range of left atrial filling pressures (7.5 to 20 cm water). Both aortic and coronary flow rates of ω-3 fatty acid-treated diabetic animals were significantly (P < .05) increased above those of untreated diabetic rats. Aortic and coronary flow rates of treated diabetic rats paralleled those of control animal; ω-3 fatty acid treatment did not affect aortic or coronary flow rates of control animals. Cardiac phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and sarcoplasmic reticulum (SR) total phospholipid were isolated and the acyl composition was determined. Stearic acid and C22:4, n-6 were significantly reduced in cardiac PE of diabetic animals. Relative to PE acyl species of untreated nondiabetic controls, treated diabetic PE had increased eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA) and reduced C22:4, n-6 levels. Compared with respective untreated groups, there was a significant increase in the amount of PE EPA in ω-3 fatty acid-treated control and diabetic animals. Alterations in acyl content of PC were restricted to ω-3 fatty acid-treated controls; compared with untreated controls, reductions in C18:2, n-6 and C22:4, n-6 and an increase in EPA levels were found. EPA, which is not detectable in cardiac SR of untreated animals, accounted for 1.6% and 0.7% of the total acyl species of treated control and treated diabetic animals, respectively. DHA levels increased by 22% and 16% to account for 14.3% and 16.6% of ω-3 fatty acid-treated control and diabetic SR acyl species, respectively. The changes in SR DHA content were not significant. These data suggest that mechanisms in addition to membrane phospholipid alterations may be responsible for the ω-3 fatty acid-mediated effect on aortic and coronary flow in STZ-diabetic rats.
ABSTRACT Measurements of γ-rays from mass analyzed nuclear recoils produced in the102Pd +54Fe rea... more ABSTRACT Measurements of γ-rays from mass analyzed nuclear recoils produced in the102Pd +54Fe reaction at 245MeV have allowed us to characterize the decay of a 35 μs isomer in154Lu. The rates of E2 transitions de-exciting isomeric levels in proton-rich N=82, 83 isotones are discussed.
Advances in Experimental Medicine and Biology, 2001
... Treatment and Outcomes Edited by Aubie Angel et a/.. Kluwer Academic/Plenum Publishers, 2001 ... more ... Treatment and Outcomes Edited by Aubie Angel et a/.. Kluwer Academic/Plenum Publishers, 2001 133 Page 148. ... Dr. Subodh Verma is an MRC Fellow. We thank Ms. Mary Battell and Ms.Sylvia Chan for technical and secretarial assistance respectively. ...
ABSTRACT Thesis (M.S.)--Michigan State University. Dept. of Pharmacology, 1971. Includes bibliogr... more ABSTRACT Thesis (M.S.)--Michigan State University. Dept. of Pharmacology, 1971. Includes bibliographical references (leaves 74-81).
American Journal of Physiology-Heart and Circulatory Physiology, 1986
Ventricular hypertrophy and hypothyroidism are each characterized by impaired cardiac muscle rela... more Ventricular hypertrophy and hypothyroidism are each characterized by impaired cardiac muscle relaxation and sarcoplasmic reticulum (SR) calcium uptake activity. A previous report also showed that hypothyroidism does not reverse ventricular hypertrophy (left-to-right ventricular weight ratios) of spontaneously hypertensive rats (SHR). We characterized the effects of thyroidectomy of 8 wk duration on relaxation of ejecting hearts and on SR calcium uptake activity from SHR and nonhypertrophic Wistar-Kyoto rat (WKY) controls. Relaxation was quantified by plotting maximum left ventricular pulse pressure (Pmax) vs. the area under the falling phase of the left ventricular pressure wave at three different pressure loads. Ventricles of euthyroid SHR were characterized by impaired relaxation and depressed SR calcium uptake activity compared with those of euthyroid WKY, confirming earlier studies. Thyroidectomy reduced ventricular relaxation and SR calcium uptake activities to about the same e...
American Journal of Physiology-Cell Physiology, 1979
The influence of alteration in the Ca2+ environment of the tissue on isoproterenol-induced increa... more The influence of alteration in the Ca2+ environment of the tissue on isoproterenol-induced increases in cAMP levels and relaxation was studied in rat uterus. In muscles depolarized with 47.5 mM K+ (with or without Na+), the ability of isoproterenol to increase cAMP levels and to produce relaxation was found to be inversely related to external calcium concentration. The pretreatment of the muscle with D600 or EGTA restored the cAMP response to isoproterenol in the depolarized uterus to a level observed in nondepolarized muscle. The study with Ro 20-1724, a phosphodiesterase (PDE) inhibitor indicated that the failure of isoproterenol to elevate cAMP levels in the depolarized uterus could not be related to the activation of PDE by Ca2+. The exposure of rat uterus to a zero-Ca2+ solution accentuated the increases in cAMP levels produced by isoproterenol. These results have raised the question of a possible regulatory role of Ca2+ in beta-adrenoceptor-induced increases in cAMP levels in ...
Research communications in chemical pathology and pharmacology, 1980
The effect of aprotinine, a natural non-specific protease inhibitor, on cyclic AMP accumulation i... more The effect of aprotinine, a natural non-specific protease inhibitor, on cyclic AMP accumulation in a dog heart washed particle preparation was studied. Aprotinine inhibited GTP-stimulated cyclic AMP accumulation at concentrations equal to or higher than 40 KIU/ml (8 x 10(-7) M). Aprotinine inhibited epinephrine (10(-4) M)-stimulated cyclic AMP accumulation to a greater degree than fluoride (10(-2) M)-stimulated activity. Trypsin stimulated cyclic AMP accumulation at low concentrations (0.5 to 2.5 microgram/ml) and inhibited at higher concentrations. Aprotinine at low concentrations (4 KIU/ml) inhibited the trypsin (1 microgram/ml) stimulation of cyclic AMP accumulation. We conclude that aprotinine may act on the regulator rather than on the catalytic sub-unit of adenylate cyclase and that its mechanism of action is not due only to its antiprotease activity.
The Journal of pharmacology and experimental therapeutics, 1985
The responses of guinea-pig isolated cardiac tissues to carbachol were examined. Tension response... more The responses of guinea-pig isolated cardiac tissues to carbachol were examined. Tension responses of paced left atria and right ventricular papillary muscles, rate responses of spontaneously beating right atria and working hearts and contractility (+dP/dt) of paced and unpaced working hearts were obtained at 38 degrees C. Carbachol induced negative inotropic and chronotropic responses of atria, abolishing tension and rate at the maxima. The spontaneously beating heart also exhibited negative chronotropy. The papillary muscles displayed partial inhibition of tension but, in tissues from reserpine-pretreated animals, negative inotropy was absent. Similarly, no reduction of contractility of paced working hearts was obtained. It was concluded that muscarinic receptors mediating a direct inhibition of ventricular muscle are virtually absent and that the small response obtained in untreated tissue may be due either to inhibition of endogenous catecholamine release via presynaptic recepto...
ABSTRACT 1. The effect of omega-3 fatty acid supplementation on α1-adrenergic receptor-mediated p... more ABSTRACT 1. The effect of omega-3 fatty acid supplementation on α1-adrenergic receptor-mediated phosphoinositide turnover in the hearts of 6-week streptozotocin diabetic rats was studied.2. The diabetic state was characterized by decreased body weight gain, hypoinsuilinemia and hyperglycemia. Omega-3 fatty acid treatment did not have any significant effects on the above parameters.3. Plasma triglyceride and cholesterol levels were significantly higher in diabetic rats compared with controls.4. Omega-3 fatty acid treatment reduced the plasma triglyceride levels in the diabetic rats, whereas plasma cholesterol levels remained unaffected.5. Norepinephrine (10 and 100 μM) stimulated inositol monophosphate (IP1) formation was significantly decreased in the diabetic rat heart compared with controls. Omega-3 fatty acid treatment had no significant effect on the norepinephrine-mediated IP1 formation in these rats.6. Inositol bisphosphate (IP2) formation in response to 100 μM of norepinephrine was significantly lower in the diabetic rat heart; which was also not affected by omega-3 fatty acid treatment.
The PI-3 kinase signalling pathway is an important pathway in mediating the glucoregulatory effec... more The PI-3 kinase signalling pathway is an important pathway in mediating the glucoregulatory effects of insulin and skeletal muscle (SKM) is the major tissue involved in glucose utilization. In diabetes this pathway is impaired, either due to lack of insulin as in Type 1 diabetes, or due to insulin resistance as in Type 2 diabetes. Bis(maltolato)-oxovanadium IV (BMOV), an insulin
The effect of hypothyroidism on isolated rat cardiac sarcoplasmic reticulum (SR) calcium transpor... more The effect of hypothyroidism on isolated rat cardiac sarcoplasmic reticulum (SR) calcium transport activity was determined. Cardiac SR was studied 2, 4 and 6 weeks following surgical removal of the thyroid gland. Thyroidectomized rats had reduced body weight and left ventricular weight 4 and 6 weeks after thyroidectomy. The rate of SR calcium transport activity was not affected 2 weeks after thyroidectomy, but was reduced 4 and 6 weeks after thyroidectomy. To elucidate the mechanism responsible for altered calcium transport activity, the roles of endogenous SR acylcarnitine and SR calcium pump protein were determined. Thyroidectomy did not affect the level of endogenous acylcarnitine associated with the SR membranes isolated at the time points studied. The level of acylphosphoprotein, putatively the SR calcium pump protein, was not affected 2 weeks following thyroidectomy, but was significantly reduced in SR 4 weeks postthyroidectomy. These studies suggest that the quantity of SR calcium pump sites is reduced in hypothyroidism and that this reduction may explain the altered SR calcium transport activity observed.
ABSTRACT Cardiac effects of ω-3 fatty acid treatment were studied in streptozocin (STZ)-induced (... more ABSTRACT Cardiac effects of ω-3 fatty acid treatment were studied in streptozocin (STZ)-induced (55 mg/kg intravenously [IV]) diabetic male Wistar rats. Nondiabetic control and STZ-diabetic animals were treated with Promega (0.5 mL/kg/d; Warner-Lambert, Morris Plains, NJ) for a period of 4 weeks beginning 2 weeks after either vehicle or STZ injection. Plasma glucose, triglyceride, and cholesterol concentrations were significantly (P < .05) elevated in diabetic animals; ω-3 fatty acid treatment did not significantly affect these parameters. An isolated working heart preparation was used to determine aortic and coronary flow rates in control, diabetic, treated control, and treated diabetic animals. Aortic and coronary flow rates of untreated STZ-diabetic rats were significantly (P < .05) lower than those of controls over a range of left atrial filling pressures (7.5 to 20 cm water). Both aortic and coronary flow rates of ω-3 fatty acid-treated diabetic animals were significantly (P < .05) increased above those of untreated diabetic rats. Aortic and coronary flow rates of treated diabetic rats paralleled those of control animal; ω-3 fatty acid treatment did not affect aortic or coronary flow rates of control animals. Cardiac phosphatidylcholine (PC) and phosphatidylethanolamine (PE) and sarcoplasmic reticulum (SR) total phospholipid were isolated and the acyl composition was determined. Stearic acid and C22:4, n-6 were significantly reduced in cardiac PE of diabetic animals. Relative to PE acyl species of untreated nondiabetic controls, treated diabetic PE had increased eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA) and reduced C22:4, n-6 levels. Compared with respective untreated groups, there was a significant increase in the amount of PE EPA in ω-3 fatty acid-treated control and diabetic animals. Alterations in acyl content of PC were restricted to ω-3 fatty acid-treated controls; compared with untreated controls, reductions in C18:2, n-6 and C22:4, n-6 and an increase in EPA levels were found. EPA, which is not detectable in cardiac SR of untreated animals, accounted for 1.6% and 0.7% of the total acyl species of treated control and treated diabetic animals, respectively. DHA levels increased by 22% and 16% to account for 14.3% and 16.6% of ω-3 fatty acid-treated control and diabetic SR acyl species, respectively. The changes in SR DHA content were not significant. These data suggest that mechanisms in addition to membrane phospholipid alterations may be responsible for the ω-3 fatty acid-mediated effect on aortic and coronary flow in STZ-diabetic rats.
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