Type 2 diabetes and risk of non-embolic ischaemic stroke in Japanese men and women

Aims/hypothesis The aim of this study was to examine the relationship between type 2 diabetes and risk of ischaemic stroke in Asian populations.Methods We conducted a 17-year prospective cohort study in 10,582 Japanese individuals (4287 men and 6295 women) aged 40–69 years living in five communities in Japan. All subjects were free of stroke and CHD at baseline. Diabetes was defined as a fasting glucose level of 7.0 mmol/l, a non-fasting glucose of 11.1 mmol/l, or receiving medication for diabetes.Results The risk of non-embolic ischaemic stroke was approximately two-fold higher in diabetic subjects than in subjects with normal glucose levels. The multivariate relative risk after adjustment for age, community, hypertensive status, BMI, triceps and subscapular skinfold thickness (TSF and SSF), and other known cardiovascular risk factors was 1.8 (95% CI 1.0–3.2) for men and 2.2 (1.2–4.0) for women. This excess risk was primarily observed among non-hypertensive subjects and individuals with higher values for measures of adiposity (BMI, TSF and SSF values above the median), particularly those with higher values for SSF. The association between non-embolic ischaemic stroke and glucose abnormality was particularly strong among non-hypertensive subjects with higher SSF values: the multivariate relative risk was 1.9 (1.0–3.7) for borderline diabetes and 4.9 (2.5–9.5) for diabetes.Conclusions/interpretation In this cohort, type 2 diabetes was a significant risk factor for non-embolic ischaemic stroke, particularly in non-hypertensive and non-lean individuals. Due to the nationwide decrease in blood pressure and increase in mean BMI among the Japanese population, with current levels approaching those observed in Western countries, the impact of glucose abnormalities on risk of ischaemic stroke represents a forthcoming public health issue in Japan.     

基底节性失语

基底节病变常导致语言功能障碍,其表现彤式复杂,既可出现口语语言障碍,也可出现书面语语言障碍,几乎包括所有失语类型.文章就基底节解剖、基底节失语的定义、特点、机制以及病变部位对语言的影响做了综述.     

Experimental studies on the pathogenesis and prophylaxis of stroke in stroke-prone spontaneously hypertensive rats (SHR).(1) Quantitative estimation of cerebrovascular permeability.

The cerebrovascular permeability quantitatively determined by the retention of 131I-human albumin in the perfused brains was increased in SHR, especially in stroke-prone SHR compared with normotensive Wistar-Kyoto, and confirmed the macroscopical or microscopical findings on the leakage into the brain or trypan blue or peroxidase injected intravenously 2 to 3 hours before sacrifice. The localization of increased vascular permeability in SHR corresponded to the predilection sites of cerebral hemorrhage or softening, which developed likely following the increased cerebrovascular permeability.     

Effects of home-based combined resistance training and walking on metabolic profiles in elderly Japanese

Background: To evaluate the effects of home‐based combined resistance training and walking on metabolic profiles in elderly Japanese subjects. Methods: Two hundred and forty‐four elderly Japanese participants were divided into two groups (184 training group and 60 controls). Each exercise training session consisted of one set of 10 repetitions of 11 different resistance exercises, and the training lasted 12 weeks. Fasting blood samples were obtained for measurements of serum levels of total cholesterol, high‐density lipoprotein cholesterol (HDL‐C), triglycerides, hemoglobin A_1c, insulin and plasma glucose, before and after the training period. We estimated insulin resistance using the homeostasis model assessment. Five subjects further underwent a two‐step hyperinsulinemic‐euglycemic clamp to evaluate insulin action directly before and after the training. Results: Training resulted in a significant increase in HDL‐C (60 ± 1–62 ± 1 mg/dL, mean ± SE, P < 0.01) and a significant decrease in triglycerides (115 ± 5–106 ± 4 mg/dL, P < 0.05), while no significant changes were observed for total cholesterol, plasma glucose, insulin, homeostasis model assessment or hemoglobin A_1c. Glucose infusion rates during the hyperinsulinemic‐euglycemic clamp increased by 30% (P < 0.05) at the 40 mU/m² per min infusion rate, from 5.4 ± 0.9 to 7.0 ± 1.1 mg/kg per min and by 15% (P < 0.01) at the 400 mU/m² per min infusion rate, from 9.4 ± 1.0 to 10.8 ± 1.2 mg/kg per min. In the control group, no significant changes were noted except for a significant decrease in HDL‐C. Conclusions: Our home‐based exercise program for elderly is safe and effective for improving metabolic profiles.     

Effect of phorbol esters on glucagon secretion from a glucagon-secreting clonal cell line. Synergistic effects of A23187 and theophylline

The cell line In-R1-G9 is one of the clones from the hamster insulinoma cell line, In-111-R1, and it produces glucagon. Phorbol esters markedly enhanced glucagon secretion and the stimulatory effect was found to be correlated to their biological activity as tumor promoters. At a concentration of 200 nM, 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulated glucagon secretion 13-fold more than the control in 10 min. The effect of TPA was not influenced by actinomycin D, cycloheximide, colchicine or vincristine. Depletion of calcium from the incubation medium inhibited TPA-induced glucagon secretion by approximately 50% and dibucaine also suppressed glucagon secretion to 67.4%. An addition of A23187 to TPA induced 150% enhancement over the TPA-stimulated glucagon level, and the maximum secretory response was observed when the cells were stimulated with the simultaneous addition of TPA, A23187 and theophylline.     

Effect of Alcohol Drinking on Gene Expression of Hepatic O6-Methylguanine DNA Methyltransferase in Chronic Liver Diseases

O⁶-methylguanine DNA methyltransferase (MGMT) is a repair protein that transfers methyl groups from O⁶-methylguanine to a cysteine acceptor in its own molecule, and restores DNA to its undamaged state. If left unrepaired, O⁶-methylguanine can pair with either a thymine or a cytosine, causing a C-G to T-A transition, which is considered to be one of the molecular mechanisms of both mutagenesis and carcinogenesis. The expression of MGMT mRNA in liver tissue was quantitatively assessed by the competitive reverse transcrip-tion-polymerase chain reaction method in patients with chronic liver diseases with or without alcohol drinking. MGMT mRNA expression was 1.4 ± 0.9 pg/μg RNA in control livers. Its expression in chronic hepatitis was 3.8 ± 0.7 in alcoholics and 2.7 ± 0.8 in nonalcoholics, which were not statistically different. MGMT mRNA expression in liver cirrhosis was significantly low, compared with that in chronic hepatitis, and 0.8 ± 0.3 in alcoholics and 0.5 ± 0.1 in nonalcoholics, which also were not significantly different. The present study shows that MGMT mRNA was not decreased in patients with chronic liver diseases with alcohol drinking, compared with those without alcohol drinking.     

L-arginine availability is not limiting for nitric oxide generation from recombinant endothelial nitric oxide synthase

L-arginine (L-Arg) may be limiting for inducible nitric oxide synthase (NOS) activity and under certain circumstances, such as increased concentrations of a NOS inhibitor, may also be limiting for endothelial NOS activity. It is unknown if L-Arg is limiting for recombinant eNOS activity in the vascular wall after adenoviral mediated gene transfer. Our aim was to examine, if L-Arg is limiting for recombinant eNOS activity in the normal or atherosclerotic vessel wall. Rings of rabbit aorta from chow or cholesterol fed animals were transduced with adenovirus vector encoding eNOS (AdeNOS) or beta-galactosidase (AdbetaGal). After 24 h, transgene expression was confirmed and vasomotor studies were performed in the absence or presence of L-Arg. During maximal contractions to phenylephrine (10(-5) M), L-Arg (3 mM) was added to the organ chamber for 30 min. Subsequently, relaxations to acetylcholine during half-maximal contractions were obtained. In the chow- and cholesterol-fed animals, relaxations were significantly enhanced in the NOS and NOS + L-Arg groups compared to the betaGal and betaGal + L-Arg groups. There was no difference between NOS and NOS + L-Arg or betaGal and betaGal + L-Arg rings from chow- or cholesterol-fed animals. While gene transfer of eNOS enhances endothelium-dependent vasorelaxation in the normal and atherosclerotic vessel wall, L-arginine is not limiting for recombinant eNOS activity.