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T Kuzuya

Publications and source records attributed to T Kuzuya.

At least 19 recordsLinked to original sources
PubMed1997

Vascular angiotensin-converting enzyme activity in cholesterol-fed rabbits: effects of enalapril.

Many reports have shown inhibitory effects of angiotensin-converting enzyme (ACE) inhibitors on the progression of atherosclerotic plaque lesions in vascular tissue of experimental models. However, no report has shown alterations of ACE activity in vascular tissue during the process of atherosclerosis. We measured ACE activity in plasma and aortic tissue in rabbits fed a cholesterol-rich (1%) or normal diet for 10 weeks. We also evaluated the blood pressure response to angiotensin (Ang) I and II. These data were compared in untreated rabbits and in rabbits receiving chronic treatment with an ACE inhibitor, enalapril (3 mg/kg/day for 10 weeks). ACE activity in aortic tissue, but not in plasma, in cholesterol-fed rabbits was gradually but significantly increased compared with that in noncholesterol-fed rabbits even after the 4-week feeding period, when no atherosclerotic lesion was observed in the aortic tissue. Treatment with enalapril for 10 weeks, but not 4 weeks, significantly reduced the ACE activity in aortic tissue in association with the reductions in the elevated Ang II level and the atherosclerotic plaque area of the aortic tissue. These results indicated that ACE activity in aortic tissue was increased during the early phase of atherosclerotic process.

Angiotensin I↗
PubMed1996

Cloning and characterization of the 5'-upstream regulatory region of the Ca(2+)-release channel gene of cardiac sarcoplasmic reticulum.

To elucidate the transcriptional regulation mechanism for the Ca(2+)-release channel gene of the cardiac sarcoplasmic reticulum (RYR2), we isolated and analyzed the 5'-upstream flanking region of the gene. Sequence analysis indicated that the core promoter region lacks canonical TATA and CAAT boxes, but contains three overlapping GC boxes. A gel shift assay indicated that Sp1 binds to the region containing the GC boxes. Different 5'-deletion constructs in the 5'-flanking region of the RYR2 gene were fused to the luciferase gene, and their promoter activity in rat neonatal cardiac myocytes was subsequently determined. The results revealed the presence of a region containing positive regulatory elements in the 5'-flanking region. Analyses of substitutional mutations introduced into the GC boxes and the regulatory region indicated that in addition to the GC box located at -56 to -51, two regulatory elements (RYR2P1 and RYR2P2) are essential for the promoter activity. These results indicated that Sp1 and transcription factors that bind to RYR2P1 and RYR2P2 cooperatively enhance the expression of the RYR2 gene. In a transient transfection experiment involving promoter-luciferase gene constructs in skeletal muscle cells, we identified a negative regulatory region between positions -209 and -90 that represses the expression of the RYR2 gene in skeletal muscle cells.

Animals↗
PubMed1996

Amelioration of severity of myocardial injury by a nitric oxide donor in rabbits fed a cholesterol-rich diet.

OBJECTIVES: This study compared the effect of a nitric oxide donor on limiting the size of infarct resulting from myocardial ischemia-reperfusion between atherosclerotic and nonatherosclerotic models. BACKGROUND: Endothelial-derived relaxation in coronary arteries affected by ischemia is substantially impaired after reperfusion, and this impairment may exacerbate the myocardial ischemia-reperfusion injury. In animals with experimental atherosclerosis, release of endothelial-derived relaxing factor is also decreased, and the propagation of myocardial infarction could be exacerbated. METHODS: We examined the extent of myocardial injury induced by ischemia (30 min) and reperfusion (48 hr) in rabbits fed a cholesterol-rich (1%) or normal diet for 10 weeks. We also evaluated the effect of a nitric oxide donor (S-nitroso-N-acetylpenicillamine [SNAP], a nitric oxide precursor (L-arginine) or a degradation product of SNAP (N-acetylpenicillamine) on infarct size in these models. RESULTS: Severity of myocardial injury was significantly exacerbated in cholesterol-fed rabbits (75.2 +/- 4.4% [mean +/- SEM]) compared with that in non-cholesterol-fed rabbits (53.2 +/- 5.2%). This exacerbation was prevented by treatment with SNAP (50.2 +/- 6.4%) but not with L-arginine (70.5 +/- 6.0%) or N-acetylpenicillamine (70.4 +/- 4.8%) in cholesterol-fed-rabbits. However, SNAP did not limit infarct size in non-cholesterol-fed rabbits (60.8 +/- 4.2%). The rate-pressure product was similar during the course of the experiment in all the groups. CONCLUSIONS: Myocardial damage induced by ischemia-reperfusion was significantly exacerbated in rabbits fed a long-term cholesterol-rich diet but was effectively reversed by treatment with a nitric oxide donor. However, this agent did not limit infarct size in normal rabbits. Thus, a nitric oxide donor reduces myocardial infarct size in atherosclerotic but not in nonatherosclerotic rabbits.

Analysis of Variance↗
PubMed1996

Heme oxygenase-1 expression and its relation to oxidative stress during primary culture of cardiomyocytes.

The inducible form of heme oxygenase (heme oxygenase-1) is a heat shock protein 32 (HSP32) whose expression is induced by numerous agents, including heme compounds and heavy metals, and during oxidative stress. The purpose of this study was to examine whether heme oxygenase-1 is induced during primary cell culture of cardiomyocytes and the relation of heme oxygenase-1 expression to oxidative stress levels. Western blot analysis and reverse transcription-polymerase chain reaction analysis showed heme oxygenase-1 expression 12-48 h after isolation of rat neonatal cardiomyocyte for culture. Its expression was barely detected immediately after isolation. Actinomycin D or cycloheximide completely suppressed such expression. Myocardial cells were exposed to oxidative stress during the first 12 h after isolation as assessed by their glutathione redox state; the ratio of reduced glutathione/oxidized glutathione was less than 10. The expression of heme oxygenase-1 was significantly reduced by treatment with reduced glutathione (58% reduction, P < 0.05), but markedly increased by treatment with hydrogen peroxide (65% increase, P < 0.05) 12 h after isolation. Expression of heat shock protein 70 was not significantly changed during primary culture incubation. Results indicate that heme oxygenase-1 is expressed during primary culture of cardiomyocytes. Its expression is closely related to the oxidative stress level of the cultured cells.

Animals↗
PubMed1996

Alpha 1-adrenergic stimulation induces cardiac tolerance to hypoxia via induction and activation of Mn-SOD.

We examined whether or not alpha 1-adrenergic stimulation increases the tolerance of the heart to ischemia using a hypoxia-reoxygenation model of cardiac myocytes. After exposure to norepinephrine (NE; 0.2 microM) for 24 h, the manganese superoxide dismutase (Mn-SOD) content and activity in the cells were increased from 0.61 +/- 0.03 to 0.87 +/- 0.04 microgram/dish and 22 +/- 1 to 55 +/- 4 U/dish, respectively. The specific activity of Mn-SOD was also increased from 36 to 63 U/microgram Mn-SOD protein after the stimulation with NE. Prazosin (2 microM) abolished the increase in Mn-SOD activity (U/mg total protein). Creatine kinase (CK) release after hypoxia (PO2 7 mmHg; 3 h)-reoxygenation (1 h) from cells pretreated with NE in the presence of propranolol and yohimbine for 24 h was attenuated by 48% compared with that from cells without NE stimulation. When antisense oligodeoxyribonucleotides to Mn-SOD were added to myocyte cultures, the increase in Mn-SOD activity (U/mg total protein) and the attenuation of CK release after the addition of NE in the presence of propranolol and yohimbine were not observed. These results suggest that alpha 1-adrenergic stimulation increases the tolerance of myocytes to hypoxia through induction and activation of Mn-SOD.

Adrenergic alpha-Agonists↗
PubMed1996

Effects of troglitazone: a new hypoglycemic agent in patients with NIDDM poorly controlled by diet therapy.

OBJECTIVE: To investigate the clinical efficacy of troglitazone, a newly developed oral hypoglycemic agent, in patients with NIDDM. RESEARCH DESIGN AND METHODS: There were 284 NIDDM patients (20-82 years of age) whose glycemic control while on a diet was judged stable but was judged unsatisfactory (fasting plasma glucose [FPG] > or = 8.3 mmol/l) when entered into a multicenter and double-blind study with parallel groups study. They were randomly allocated into two groups, the troglitazone group (the T group: 400 mg/day p.o.) and the placebo group (the P group), and were treated with test drugs for 12 weeks. RESULTS: We evaluated efficacy in 136 patients of the T group and 126 patients of the P group. There was no significant difference in any of baseline characteristics between the T and P groups. In the T group, FPG and HbA1c decreased significantly after treatment (before versus after, FPG 10.1 +/- 1.6 vs. 8.8 +/- 1.9 mmol/l, P < 0.001; HbA1c: 8.6 +/- 1.5 vs 8.1 +/- 1.7%, P < 0.001). FPG and HbA1c did not change after treatment in the P group (before versus after, FPG 10.1 +/- 1.8 vs. 9.9 +/- 2.1 mmol/l; HbA1c 8.5 +/- 1.5 vs. 8.6 +/- 1.6%). Of 136 patients in the T group, 62 (45.6%) were classified as responders. Serum triglyceride level also decreased in the T group but not in the P group. Body weight increased slightly only in the T group. There were no differences in changes in blood pressure between the two groups. No serious adverse events occurred in either group. CONCLUSIONS: Troglitazone at 400 mg/day decreased FPG and HbA1c significantly in NIDDM patients who had failed to respond to diet therapy. Troglitazone, developed as a drug to enhance insulin action, can be a useful hypoglycemic agent for the treatment of NIDDM.

Adult↗
PubMed1996

A nitric oxide donor reverses myocardial injury in rabbits with acute hypercholesterolemia.

We evaluated the propagation of myocardial injury in a model of coronary artery occlusion and reperfusion in control and hypercholesterolemic rabbits. This was done by examining the differences in the infarct size and in the extent of leukocyte accumulation resulting from coronary artery occlusion (30 min) followed by reperfusion (2 or 48 hr) in rabbits fed 1% cholesterol for 4 days vs. controls not fed cholesterol. There was no significant difference in the infarct size in the 2-hr (45.7 +/- 6.7%, n = 8) vs. 48-hr (48.8 +/- 5.8%, n = 9) models of reperfusion in control rabbits. However, infarct size in the cholesterol-fed rabbits at 2 hr (64.0 +/- 4.1%, n = 6) or 48 hr (72.3 +/- 3.0%, n = 8) of reperfusion significantly exceeded that in the corresponding controls (P < .05). The infarct in cholesterol-fed rabbits at 2 hr of reperfusion was smaller than that at 48 hr of reperfusion, but not significantly. Treatment with S-nitroso-N-acetylpenicillamine, a nitric oxide donor, effectively reduced the size of infarct in the cholesterol-fed rabbits. However, treatment with N-acetylpenicillamine had no infarct-limiting effect. When we evaluated the extent of leukocyte accumulation in the ischemic myocardium, as assessed by myeloperoxidase activity, a positive correlation was observed between myeloperoxidase activity and infarct size at 48 hr of reperfusion. Results indicate that the propagation of myocardial ischemia and reperfusion injury in acutely hypercholesterolemic rabbits differed from that in controls. An exogenous nitric oxide donor effectively reduced the size of infarct associated with the reduction in the accumulation of leukocytes 48 hr after reperfusion, which suggests that a reduction in the production of endogenous nitric oxide during ischemia and reperfusion may aggravate the severity of myocardial injury in acutely hypercholesterolemic rabbits.

Animals↗
PubMed1996

The prevalence of low insulin responders to oral glucose load among groups with various patterns of family history of diabetes.

The prevalence of low insulin responders was assessed in non-diabetic subjects with various patterns of family history of diabetes. Subjects were divided into five groups: group A, without any family history of diabetes among all known relatives; group B, with diabetes among parents and/or siblings; group C, with one diabetic parent; group D, with two diabetic parents; and group E, non-diabetic co-twins of monozygotic twins with diabetes. Except twins, the type of diabetes in the family was not defined. They were examined by 100 g oral glucose tolerance test (OGTT) except for group E in which 50 g or 75 g OGTT were also used. Insulin response was evaluated by the insulinogenic index, the ratio of increment of serum insulin to that of plasma glucose (mg dl-1) 30 min after the oral glucose load. The low insulin responders had a lower insulinogenic index below 0.5 in the case of 100 g OGTT, and below 0.35 and 0.4 in the case of 50 g and 75 g OGTT. Groups with a family history of diabetes (B, C, and D) had significantly lower insulinogenic indices than group A without a family history of diabetes. The prevalence of low insulin responders was significantly higher in subjects with a strong family history of non-insulin-dependent diabetes mellitus (NIDDM), such as subjects with two diabetic parents and monozygotic co-twins of NIDDM patients. In group A, low insulin responders were more prevalent in older subjects, while in group D, they were also frequent in younger subjects. These results suggest that a low insulin response has a genetic basis and is a preclinical feature in subjects with genetic pre-disposition to NIDDM.

Adolescent↗
PubMed1996

Insulin response to oral glucose load is consistently decreased in established non-insulin-dependent diabetes mellitus: the usefulness of decreased early insulin response as a predictor of non-insulin-dependent diabetes mellitus.

We studied the plasma insulin response during a 100 g oral glucose tolerance test (OGTT) in subjects with NIDDM and various other conditions associated with glucose intolerance. The criteria for definite diabetes and previously definite diabetes is proposed for those whose fasting blood glucose (FBG) is, or has been, greater than 140 mg dl-1 in the past. A diabetic type glucose tolerance with FBG lower than 140 mg dl-1 was called 'equivocal diabetes'. Insulin response was almost invariably lower in definite diabetes and previously definite diabetes compared to control groups with similar degree of glucose intolerance even in the states of non-diabetic glucose tolerance. This was in contrast to other conditions which are often associated with glucose intolerance such as corticosteroid treatment, post-gastrectomy, liver diseases, in which insulin response is increased with the impairment of glucose tolerance as far as the FBG remains below 140 mg dl-1. The low insulin response in definite diabetes can be represented by a decreased insulinogenic index, the ratio of increment of plasma insulin (muU ml-1) to that of blood glucose (mg dl-1) 30 min after the glucose load. Insulin response was judged to be low when this index was less than 0.5. Low insulin response was a reproducible feature, better than the category of glucose tolerance. It was highly correlated with acute insulin response (AIR) elicited by intravenous glucose injection. The prevalence of low insulin responders was high among groups with a family history of NIDDM. Diabetes with elevated FBG occurred more frequently in low insulin responders than in normal insulin responders. Fasting and 2-h insulin levels are lower in definite diabetes than in control groups with similar blood glucose levels. The so-called inverted-U shape relationship of plasma insulin to blood glucose was not so apparent in definite diabetes. We conclude that a low insulin response to oral glucose, as represented by a low insulinogenic index, is an important inherent characteristic in definite diabetes and probably plays a predominant role in the pathogenesis of NIDDM in most Japanese patients.

Blood Glucose↗
PubMed1996

A prospective study of health check examinees for the development of non-insulin-dependent diabetes mellitus: relationship of the incidence of diabetes with the initial insulinogenic index and degree of obesity.

A total of 1788 non-diabetic subjects, screened by a general health check, had either glycosuria or marginal elevation of fasting blood glucose and/or HbA1c. They were followed by repeated 100 g oral glucose tolerance tests for up to 8 years. Their initial mean age was 52 years and the mean BMI was 23.2. Low insulin secretory response was defined when the insulinogenic index, a ratio of increment of plasma insulin to that of plasma glucose 30 min after oral glucose load, was lower than 0.5. Cumulative incidence of diabetes with fasting blood glucose (FBG) exceeding 120 mg dl-1 was significantly higher in impaired glucose tolerance (IGT) than in non-IGT, and in each of IGT and non-IGT groups, the incidence was significantly higher for low than normal insulin responders. The mean initial plasma insulin response in subjects who developed diabetes was significantly lower than in those who remained non-diabetic with the same category of glucose tolerance at baseline irrespective of the degree of glucose intolerance. The mean baseline BMI did not differ whether or not they developed diabetes, but a few cases who developed diabetes despite normal initial insulin response were much more obese. Fasting insulin levels did not correlate with FBG during the course of development of diabetes. We suggest that defective insulin secretion plays a predominant role in the non-obese subtype of NIDDM which includes the majority of Japanese patients, while both insulin resistance and insulin secretory defect are important in the obese subtype for the development of diabetes.

Arizona↗
PubMed1995

Inactivation of glutathione peroxidase by nitric oxide. Implication for cytotoxicity.

S-nitro-N-acetyl-DL-penicillamine (SNAP), a nitric oxide (NO) donor, inactivated bovine glutathione peroxidase (GPx) in a dose- and time-dependent manner. The IC50 of SNAP for GPx was 2 microM at 1 h of incubation and was 20% of the IC50 for another thiol enzyme, glyceraldehyde-3-phosphate dehydrogenase, in which a specific cysteine residue is known to be nitrosylated. Incubation of the inactivated GPx with 5 mM dithiothreitol within 1 h restored about 50% of activity of the start of the SNAP incubation. A longer exposure to NO donors, however, irreversibly inactivated the enzyme. The similarity of the inactivation with SNAP and reactivation with dithiothreitol of GPx to that of glyceraldehyde-3-phosphate dehydrogenase, suggested that NO released from SNAP modified a cysteine-like essential residue on GPx. When U937 cells were incubated with 100 microM SNAP for 1 h, a significant decrease in GPx activity was observed although the change was less dramatic than that with the purified enzyme, and intracellular peroxide levels increased as judged by flow cytometric analysis using a peroxide-sensitive dye. Other major antioxidative enzymes, copper/zinc superoxide dismutase, manganese superoxide dismutase, and catalase, were not affected by SNAP, which suggested that the increased accumulation of peroxides in SNAP-treated cells was due to inhibition of GPx activity by NO. Moreover, stimulation with lipopolysaccharide significantly decreased intracellular GPx activity in RAW 264.7 cells, and this effect was blocked by NO synthase inhibitor N omega-methyl-L-arginine. This indicated that GPx was also inactivated by endogenous NO. This mechanism may at least in part explain the cytotoxic effects of NO on cells and NO-induced apoptotic cell death.

Animals↗
PubMed1995

Elevated ratio of summed serum proinsulin to insulin response after oral glucose load in type 2 diabetes decreases following sulfonylurea treatment.

We showed previously that the disproportionate elevation of serum proinsulin at fasting and after glucose ingestion in Type 2 diabetes is reduced to nearly normal after improvement of glycemic control by diet therapy. In this study, we investigated the effect of sulfonylurea (SU) treatment on serum proinsulin levels and proinsulin/insulin ratio (PI/I) during oral glucose tolerance test in patients with Type 2 diabetes. Thirteen diabetic patients (age 56 +/- 9 years, body mass index 22.4 +/- 1.9 kg/m2, mean +/- SD) were examined by 75 g oral glucose tolerance test (OGTT) before and after glycemic control by SU therapy. Mean interval of two OGTTs was 126 days. Serum proinsulin was measured by the radioimmunoassay using a human proinsulin-specific antiserum. When glycemic control improved after SU therapy (mean fasting plasma glucose 11.5 and 6.0 mmol/l, before and after SU treatment), fasting insulin, proinsulin and PI/I ratio did not change significantly. Insulin response during OGTT markedly increased after SU therapy. Summed value of insulin (sigma I) increased from 634 to 1064 pmol/l after SU (P < 0.01), whereas summed proinsulin (sigma PI) did not change significantly (146 and 159 pmol/l), resulting in a significant decrease in sigma PI/sigma I (23.6-15.1%, P < 0.05). We conclude that the disproportionate elevation of proinsulin during OGTT in patients with Type 2 diabetes can be reduced after glycemic control by SU treatment, chiefly by a selective increase in insulin response.

Administration, Oral↗
PubMed1995

Effect of angina pectoris on myocardial protection in patients with reperfused anterior wall myocardial infarction: retrospective clinical evidence of "preconditioning".

OBJECTIVES: We examined whether angina pectoris occurring shortly before the onset of acute myocardial infarction can actually preserve postischemic left ventricular function in humans. BACKGROUND: Experimental studies indicate that brief, transient episodes of ischemia render the heart very resistant to infarction from a subsequent sustained ischemic insult, an effect termed ischemic preconditioning. However, no clinical data are available concerning the implications of angina pectoris shortly before the onset of infarction in humans. METHODS: We studied 84 patients with an acute anterior myocardial infarction. All patients had total occlusion of the proximal or medial portion of the left anterior descending coronary artery and achieved reflow within 6 h of onset. Patients were classified into three groups on the basis of duration of antecedent angina pectoris: group 1 = no angina (37 patients); group 2 = new angina pectoris occurring < or = 7 days of onset of infarction (22 patients); group 3 = angina pectoris beginning > 7 days before onset of infarction (25 patients). All patients underwent left ventriculography on the day of, and 28 days after, onset of infarction to determine ejection fraction and regional wall motion in the territory of the left anterior descending coronary artery by the centerline method. RESULTS: Angiographic collateral flow grade was higher in group 3 than in groups 1 and 2 ([mean +/- SD] group 1 = 0.08 +/- 0.7, group 2 = 0.7 +/- 0.7, group 3 = 1.5 +/- 0.8). Although there were no differences in baseline ejection fraction and regional wall motion among the three groups, the degree of improvement was significantly greater in groups 2 and 3 than in group 1 (late minus baseline ejection fraction: group 1 = 0 +/- 8%, group 2 = 7 +/- 10% group 3 = 6 +/- 10% [p < 0.05 group 1 vs. groups 2 and 3]; late minus baseline regional wall motion: group 1 = 0.2 +/- 0.4, group 2 = 0.6 +/- 0.5, group 3 = 0.5 +/- 0.6 SD/chord [p < 0.05, group 1 vs. group 2]). When the study was limited to those patients with no or poor collateral flow (31 in group 1, 19 in group 2, 10 in group 3), only group 2 patients had a significant improvement in wall motion. Angina pectoris within 24 h before onset of infarction was more frequent in group 2 (82%) than group 3 (28%, p < 0.05). CONCLUSIONS: Episodes of angina pectoris occurring shortly before the onset of infarction may preserve myocardial contractile function in reperfused myocardial infarction despite less support from collateral flow channels, although these are suggestive results in a limited number of patients.

Angina Pectoris↗
PubMed1995

Nitric oxide synthase protects the heart against ischemia-reperfusion injury in rabbits.

The role of nitric oxide (NO) in myocardial ischemia-reperfusion injury is still controversial. To determine the role of NO in the propagation of myocardial injury in a coronary artery occlusion-reperfusion model, we examined the effect of a competitive NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), with and without L-arginine, on the size of the infarct resulting from coronary artery occlusion (30 min) followed by reperfusion (48 hr) in rabbits. L-NAME (300 micrograms/kg, as a bolus, and 100 micrograms/kg/min, i.v.) with and without L-arginine (30 mg/kg, as a bolus, and 10 mg/kg/min, i.v.) was administered immediately before coronary occlusion to 60 min after reperfusion. The infarct size in the L-NAME-treated rabbits (75.1% +/- 5.0%, n = 7), assessed as a percentage of infarcted region/ischemic region, was significantly larger than that of control rabbits (51.2% +/- 7.4%, n = 7; P < .05). The increase in infarct size was significantly attenuated by the treatment with L-NAME and L-arginine (62.0% +/- 4.0%, n = 7). However, the infarct size for the treatment with L-NAME and D-arginine (76.7% +/- 5.7%, n = 6) did not differ from that in the L-NAME-treated rabbits. There was no significant difference in the infarct size between L-arginine-treated (60.1% +/- 7.3%, n = 6) and control rabbits. Rate-pressure products, as an index of myocardial oxygen consumption, were comparable in all the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Relationship between obesity and concordance rate for type 2 (non-insulin-dependent) diabetes mellitus among twins.

In order to analyse the relationship of genetic factors and the role of obesity in the pathogenesis of Type 2 (non-insulin-dependent) diabetes mellitus, we compared body mass index (BMI) and other parameters in 71 monozygotic and 17 dizygotic twins (MZT and DZT) with Type 2 diabetes, and analysed the relationship of maximal BMI in the past (max BMI) with the concordance and discordance for diabetes. Data were collected by mail from the members of the Japan Diabetes Society. Concordance rate for diabetes was higher in MZT than in DZT (72% vs. 41%, P = 0.017). Concordance rate in MZT varied in relation to the max BMI of the index twins who developed diabetes earlier. It was higher in non-obese and slightly obese groups (82% and 80% for those with max BMI < 24 and 24-27.9, respectively) than in obese group (36%, max BMI > or = 28) (P = 0.003). In MZT, diabetic twins of discordant pairs were significantly more obese at the survey and in the past than index twins of concordant pairs (mean BMI: 23.9 vs. 21.7, P = 0.007; mean max BMI, 27.7 vs. 24.3, P = 0.001). A similar tendency of differences in BMI was also observed in DZT. Intrapair comparison in discordant MZT and DZT pairs showed that diabetic twins were more obese than non-diabetic cotwins (mean max BMI, 27.7 vs. 24.7, P = 0.004 for MZT; and 27.3 vs. 23.9, P = 0.002 for DZT). In concordant DZT pairs, index twins with earlier onset of diabetes had been less obese than cotwins (mean max BMI, 23.6 vs. 26.0, P = 0.004). In conclusion, the comparison of the max BMI in twins suggests that the degree of diabetogenic role of obesity varies in heterogeneous genetic background. The index twins of discordant pairs had been more obese than those of concordant pairs, suggesting that obesity plays a more important role in those with weaker genetic susceptibility for diabetes.

Adult↗
PubMed1994

gamma-Glutamylcysteine ethyl ester for myocardial protection in dogs during ischemia and reperfusion.

OBJECTIVES: The aim of this study was to examine the infarct-limiting effects of gamma-glutamylcysteine ethyl ester, a newly discovered synthetic precursor of glutathione biosynthesis, in a canine model of myocardial infarction. BACKGROUND: Reduced glutathione plays an important role in protecting cells against damage induced by reactive oxygen species during myocardial ischemia and reperfusion. Gamma-glutamylcysteine ethyl ester is capable of penetrating into cells in its intact form and increasing intracellular glutathione levels. METHODS: Dogs were subjected to a 90-min coronary occlusion followed by 5 h of reperfusion. An intravenous bolus injection of gamma-glutamylcysteine ethyl ester (3 or 10 mg/kg body weight) was administered immediately before reperfusion. Regional myocardial blood flow was measured with the use of colored microspheres. RESULTS: Gamma-glutamylcysteine ethyl ester effectively reduced infarct size in a dose-dependent manner (mean +/- SEM 26.4 +/- 3.5% in the low dose group [3 mg/kg, n = 10] and 19.0 +/- 3.4% in the high dose group [10 mg/kg, n = 10]; each p < 0.05 vs. the value in the control group [40.6 +/- 4.8%, n = 10]). There were no differences between the control and treated groups in hemodynamic variables or regional myocardial blood flow either during the ischemic period or after reperfusion. The reduced glutathione content of ischemic myocardium in the control group (0.62 +/- 0.11 mumol/g, p < 0.01) was significantly lower than that in nonischemic myocardium (1.46 +/- 0.07 mumol/g), and it was preserved by treatment in a dose-dependent manner (3 mg/kg, 0.83 +/- 0.06 mumol/g; 10 mg/kg, 0.92 +/- 0.14 mumol/g; each p < 0.05 vs. control level). There were no differences in oxidized glutathione content between nonischemic and ischemic myocardium or among the three groups. CONCLUSIONS: Gamma-glutamylcysteine ethyl ester, a precursor of glutathione, significantly attenuates myocardial ischemia and reperfusion injury when administered immediately before reperfusion.

Animals↗