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Heterogeneity of HDL particles in hyperinsulinemic men with coronary artery disease
Wednesday 12 October 1994: Poster Abstracts 242
Diabetes
(2371 Treatment
of severe angiopathy with imipenem/ cllastatin versus piperaciiliiciindamycln NKP. Visseren FJL, Banga JD, Verkooyen R, Bartelink K, Diepersloot RJA, Bosch MediCentre, Deutersestraat 2, 5223 GV ‘s-Hertogenhosch, The Netherlands
In order to compare the clinical and microbiological efficacy of irnipenemlcilastatin (IC) with those of piperaciilin/clindamycin (PCL) 30 patients with diabetic foot infections were enrolled in an ongoing multicenter open, randomized study. Inclusion criteria: diabetic foot Wagner 2-4, ankle arm index 0.4-l. Five men and 11 women received IC (mean age 73.4 & 7.5 years) while 7 men and 7 women (mean age 68.6 f 11 years) were treated with PCL. One patient in the IC group turned out not evaluable. The treatment regimen was IC 500 mg q 6 h or PCL 3 g q 6 h/600 mg q 8 h. In the IC group all patients (15/U) were considered clinically cured or improved while in the PCL group IO/14 were clinically cured or improved and four patients were considered a clinical failure (1) or died during therapy while the infection was still present (3) (P < 0.05, Fisher’s exact test). The micro-organisms isolated were eradicated in similar proportions in the two patient groups. In the PCL group bacteria resistant to the combination were observed thrice while a super-infection was noted in two patients. The IC treatment failed to eradicate bacteria sensitive to the drug combination once while a relapse was observed in one and super-infection in two patients. Adverse events were noted in 2ptients receiving IC and in 8 patients receiving PCL (P < 0.05 x with Yates correction). From the preliminary results of this study it can be concluded that in spite of severe angiopathy there is a tendency for the IC combination to be superior to treatment with PCL with respect to clinical outcome and the occurrence of adverse events in patients with diabetic foot infections.
12381Simvastatin, giutaryi-CoA
an inhibitor of 3-hydroxy-3-methyireductase, inhibits the insulin secretagogues-induced cytosoiic Ca*+ activities in rat pancreatic @ceils
Dept. of Physiol., Kagoshima Univ. Sch. of Med., 8-35-l Sakuragaoka, Kagoshima 890, Japan
m,
Inhibitors of 3-hydroxy-3-methylglutaryi-CoA (HMG-CoA) re.ductase are widely used for treating the patients with hyperchoiesterolemia. Since hypercholesteroiemia often occurs in diabetic patients, a possible effect of the drug on insulin release is an issue of great importance. It is well established that insulin release from islet B-cells is determined by the cytosolic free Ca’+ concentration -([Ca2+]i). The present study attempted, therefore, to examine the effect of simvastatin. a linonhilic HMG-CoA reductase inhibitor, and pravastatin, a hydrophilic one, on [Ca2+]i in /5cells. [Ca*+]i in single pancreatic /J-cells from normal Wistar rats was measured by dual-wavelength fura- microfluorometry, and the HMG-CoA reductase inhibitors were. administered under superfusion conditions. A rise in glucose from basal (2.8, 5 mM) to stimulatory concentrations (8.3, 16.7 mM) for insulin release elicited an increase in [Ca*+]l. In the presence of 5.0 and 8.3 n&l glucose, 10 rnM arginine also evoked an increase in [Ca*+]i. The glucose- and arginine-induced increases in [Ca*+]i were inhibited under Ca*+ -deprived conditions and by nitmndipine, an inhibitor of the L-type Ca*’ channel, indicating that glucose and arginine stimulate Ca*+ influx through the B-cell plasma membrane. Simvastatin at 0.3pmg/ml partially and at 3pmg/ml almost completely inhibited both the glucose- and arginine-induced increases in [Ca*+]l, while pravastatin over the concentration range was without effect. Pravastatin at high concentrations over 60ymg/ml partially inhibited the [Ca*+]i response to arginine. Simvastatin
Na+, an acid form with a reduced hydrophobicity, was less potent than simvastatin. Atter washing out inhibitors of the HMG-CoA reductase, the [Ca2+]i responses to glucose and arginine were restored, which suggests that the acute effect of the drugs on [Ca*+]l is reversible. The results demonstrate that inhibitors of the HMG-CoA reductase block the /?-cell [Ca*qi responses to insulin secretagogues glucose and arginine, suggesting an inhibitory action on insulin release. A counteraction of Ca*+ influx through L-type Ca*+ channels in the p-cell plasma membrane is likely to be involved. Moreover, the blocking effect of simvastatin is more potent (about 3 logs) and effective than pravastatin, and the greater effect of simvastatin may be related to the higher hydrophobic&y of the drug. Heterogeneity of HDL particles in hyperinsuiinemic men with coronary artery disease Q&&&&Q, Iwauejko J, KwaSniak M, Wybranska I, Guevara I, Miszczuk-JamskaB, Kruszelnicka-Kwiatkowska 0*, Piwowarska W*, Dembidska-KleC A, Dept. of Clin. Biochem., *Clinic of
12391
Coronary Disease, Collegium Medicum, Jagiellonian University, Cracow. Poland
The insulin resistance syndrome refers to a constellation of disorders associated with increased insulin concentration. These include tendencies towards hypertension, NIDDM, central obesity, hyperuricemia, renal dysfunction and atherosclerosis. While each of these symptoms separately occurs rather rarely, dyslipidemia appears to be one of the most consistent traits with hyperinsulinemia. The association between the action of insulin and trigiyceride metabolism is well recognized. Insulin is also essential for the regulation of HDL metabolism. HDL composition was investigated in 60 normolipidemic, non-obese, male subjects with normal glucose tolerance and CAD proven by coronary angiography. Subjects were divided into lowinsulin (LI) and high-insulin (HI) groups according to their insulin response to an oral glucose tolerance test. The HI group had lower apo A-I and apo E, but not apo A-II, concentrations, as well as low concentrations of free and esterified cholesterol, especially in HDh. HDL2 but not HDL3 from HI patients had lower concentrations of triglycerides and phosphoiipids. Additionally, investigation of the predominant peak diameter of HDL showed that HDL from HI subjects were mom frequently larger, although no difference between HI and LI patients in the HDL protein/lipid ratio was observed. The results suggest that HDL obtained from normolipidemic patients with HI could be less good cholesterol scavengers than HDL from LI men. Overexpression of heparin-binding epidermai growth factor-like growth factor (HJ&EGF) in vascular smooth muscle ceils from streptozotocin-induced diabetic rats @B& Kawata S, Inui Y, Fukuda K, Maeda Y, Yoshida S, Matsuzawa Y, 2nd Dept. of Int. Med., Osaka Univ. Med. Sch., 2-2
12401
Yamadaoka, Suita 565, Japan
Diabetes mellitus is a known risk factor for atherosclerosis in which proliferation of vascular smooth muscle cells (SMC) plays an important role. Proliferation of SMC from diabetic animals was faster than that of control SMCs. HB-EGF is a potent mitogen for SMC and fibroblasts. We studied gene expression of HB-EGF in SMC from streptozotocin-induced diabetic rats (STZ-rats) to evaluate how HB-EGF modulates the proliferation of SMC from STZ-rats. Male Wistar rats (250 g) were made diabetic with a single intravenous injection of streptozotocin 70 mg/kg. After 4 weeks, thoracic aorta was removed and medical SMC were subsequently
Atherosclerosis X, Montreal, October 1994
Diabetes
(2371 Treatment
of severe angiopathy with imipenem/ cllastatin versus piperaciiliiciindamycln NKP. Visseren FJL, Banga JD, Verkooyen R, Bartelink K, Diepersloot RJA, Bosch MediCentre, Deutersestraat 2, 5223 GV ‘s-Hertogenhosch, The Netherlands
In order to compare the clinical and microbiological efficacy of irnipenemlcilastatin (IC) with those of piperaciilin/clindamycin (PCL) 30 patients with diabetic foot infections were enrolled in an ongoing multicenter open, randomized study. Inclusion criteria: diabetic foot Wagner 2-4, ankle arm index 0.4-l. Five men and 11 women received IC (mean age 73.4 & 7.5 years) while 7 men and 7 women (mean age 68.6 f 11 years) were treated with PCL. One patient in the IC group turned out not evaluable. The treatment regimen was IC 500 mg q 6 h or PCL 3 g q 6 h/600 mg q 8 h. In the IC group all patients (15/U) were considered clinically cured or improved while in the PCL group IO/14 were clinically cured or improved and four patients were considered a clinical failure (1) or died during therapy while the infection was still present (3) (P < 0.05, Fisher’s exact test). The micro-organisms isolated were eradicated in similar proportions in the two patient groups. In the PCL group bacteria resistant to the combination were observed thrice while a super-infection was noted in two patients. The IC treatment failed to eradicate bacteria sensitive to the drug combination once while a relapse was observed in one and super-infection in two patients. Adverse events were noted in 2ptients receiving IC and in 8 patients receiving PCL (P < 0.05 x with Yates correction). From the preliminary results of this study it can be concluded that in spite of severe angiopathy there is a tendency for the IC combination to be superior to treatment with PCL with respect to clinical outcome and the occurrence of adverse events in patients with diabetic foot infections.
12381Simvastatin, giutaryi-CoA
an inhibitor of 3-hydroxy-3-methyireductase, inhibits the insulin secretagogues-induced cytosoiic Ca*+ activities in rat pancreatic @ceils
Dept. of Physiol., Kagoshima Univ. Sch. of Med., 8-35-l Sakuragaoka, Kagoshima 890, Japan
m,
Inhibitors of 3-hydroxy-3-methylglutaryi-CoA (HMG-CoA) re.ductase are widely used for treating the patients with hyperchoiesterolemia. Since hypercholesteroiemia often occurs in diabetic patients, a possible effect of the drug on insulin release is an issue of great importance. It is well established that insulin release from islet B-cells is determined by the cytosolic free Ca’+ concentration -([Ca2+]i). The present study attempted, therefore, to examine the effect of simvastatin. a linonhilic HMG-CoA reductase inhibitor, and pravastatin, a hydrophilic one, on [Ca2+]i in /5cells. [Ca*+]i in single pancreatic /J-cells from normal Wistar rats was measured by dual-wavelength fura- microfluorometry, and the HMG-CoA reductase inhibitors were. administered under superfusion conditions. A rise in glucose from basal (2.8, 5 mM) to stimulatory concentrations (8.3, 16.7 mM) for insulin release elicited an increase in [Ca*+]l. In the presence of 5.0 and 8.3 n&l glucose, 10 rnM arginine also evoked an increase in [Ca*+]i. The glucose- and arginine-induced increases in [Ca*+]i were inhibited under Ca*+ -deprived conditions and by nitmndipine, an inhibitor of the L-type Ca*’ channel, indicating that glucose and arginine stimulate Ca*+ influx through the B-cell plasma membrane. Simvastatin at 0.3pmg/ml partially and at 3pmg/ml almost completely inhibited both the glucose- and arginine-induced increases in [Ca*+]l, while pravastatin over the concentration range was without effect. Pravastatin at high concentrations over 60ymg/ml partially inhibited the [Ca*+]i response to arginine. Simvastatin
Na+, an acid form with a reduced hydrophobicity, was less potent than simvastatin. Atter washing out inhibitors of the HMG-CoA reductase, the [Ca2+]i responses to glucose and arginine were restored, which suggests that the acute effect of the drugs on [Ca*+]l is reversible. The results demonstrate that inhibitors of the HMG-CoA reductase block the /?-cell [Ca*qi responses to insulin secretagogues glucose and arginine, suggesting an inhibitory action on insulin release. A counteraction of Ca*+ influx through L-type Ca*+ channels in the p-cell plasma membrane is likely to be involved. Moreover, the blocking effect of simvastatin is more potent (about 3 logs) and effective than pravastatin, and the greater effect of simvastatin may be related to the higher hydrophobic&y of the drug. Heterogeneity of HDL particles in hyperinsuiinemic men with coronary artery disease Q&&&&Q, Iwauejko J, KwaSniak M, Wybranska I, Guevara I, Miszczuk-JamskaB, Kruszelnicka-Kwiatkowska 0*, Piwowarska W*, Dembidska-KleC A, Dept. of Clin. Biochem., *Clinic of
12391
Coronary Disease, Collegium Medicum, Jagiellonian University, Cracow. Poland
The insulin resistance syndrome refers to a constellation of disorders associated with increased insulin concentration. These include tendencies towards hypertension, NIDDM, central obesity, hyperuricemia, renal dysfunction and atherosclerosis. While each of these symptoms separately occurs rather rarely, dyslipidemia appears to be one of the most consistent traits with hyperinsulinemia. The association between the action of insulin and trigiyceride metabolism is well recognized. Insulin is also essential for the regulation of HDL metabolism. HDL composition was investigated in 60 normolipidemic, non-obese, male subjects with normal glucose tolerance and CAD proven by coronary angiography. Subjects were divided into lowinsulin (LI) and high-insulin (HI) groups according to their insulin response to an oral glucose tolerance test. The HI group had lower apo A-I and apo E, but not apo A-II, concentrations, as well as low concentrations of free and esterified cholesterol, especially in HDh. HDL2 but not HDL3 from HI patients had lower concentrations of triglycerides and phosphoiipids. Additionally, investigation of the predominant peak diameter of HDL showed that HDL from HI subjects were mom frequently larger, although no difference between HI and LI patients in the HDL protein/lipid ratio was observed. The results suggest that HDL obtained from normolipidemic patients with HI could be less good cholesterol scavengers than HDL from LI men. Overexpression of heparin-binding epidermai growth factor-like growth factor (HJ&EGF) in vascular smooth muscle ceils from streptozotocin-induced diabetic rats @B& Kawata S, Inui Y, Fukuda K, Maeda Y, Yoshida S, Matsuzawa Y, 2nd Dept. of Int. Med., Osaka Univ. Med. Sch., 2-2
12401
Yamadaoka, Suita 565, Japan
Diabetes mellitus is a known risk factor for atherosclerosis in which proliferation of vascular smooth muscle cells (SMC) plays an important role. Proliferation of SMC from diabetic animals was faster than that of control SMCs. HB-EGF is a potent mitogen for SMC and fibroblasts. We studied gene expression of HB-EGF in SMC from streptozotocin-induced diabetic rats (STZ-rats) to evaluate how HB-EGF modulates the proliferation of SMC from STZ-rats. Male Wistar rats (250 g) were made diabetic with a single intravenous injection of streptozotocin 70 mg/kg. After 4 weeks, thoracic aorta was removed and medical SMC were subsequently
Atherosclerosis X, Montreal, October 1994