Anionic polymerizations of 2-[(trimethylsilyl)oxy]ethyl methacrylate (l), 2-[(tert-butyldimethylsilyl)oxy]ethy1 methacrylate (2), and 2-[(methoxymethyl)oxy]ethyl methacrylate (3), the protected forms of 2-hydroxyethyl methacrylate (HEMA), were carried out in THF at -78 "C with 1 ,l -diphenylhexyllithium or 1,l -diphenyl-3-methylpentyllithium in the presence of LiCl. The resulting poly(1-3)s were found to possess predictable molecular weights and very narrow molecular weight distributions. The sequential polymerizations of tert-butyl methacrylate with the anionic propagating ends of poly(1-3) gave block copolymers in quantitative efficiency. Thus, the anionic polymerizations of 1-3 proceeded without transfer and termination reactions to afford stable living polymers. Complete hydrolysis of the protective groups of poly(1-3)s produced linear poly(HEMA) quantitatively. Novel well-defined di-and triblock copolymers containing hydrophobic [polystyrene, poly(4-octylstyrene), polyisoprene] and hydrophilic segments [poly(HEMA)] were also prepared by sequential polymerization of the corresponding hydrophobic comonomers with 1, followed by deprotection.

No abstract

No abstract

It has been shown that orally administered geranylgeranylacetone (GGA), an anti-ulcer drug, induces expression of heat shock protein 72 (HSP72) and provides protection against ischemia-reperfusion in rat hearts. The underlying protective mechanisms, however, remain unknown. Mitochondria have been shown to be a selective target for heat stress-induced cardioprotection. Therefore, we hypothesized that preservation of mitochondrial function, owing to an opening of a putative channel in the inner mitochondrial membrane, the mitochondrial ATP-sensitive potassium (mitoKATP) channel, could be involved in GGA- or heat stress-induced cardioprotection against ischemia-reperfusion. Rats were treated with oral GGA or vehicle. Twenty-four hours later, each heart was isolated and perfused with a Langendorff apparatus. GGA-treated hearts showed better functional recovery, and less creatine kinase was released during a 30-min reperfusion period, after 20 min of no-flow ischemia. Concomitant perfusion with 5-hydroxydecanoate (5-HD, 100 μM) or glibenclamide (10 μM) abolished the GGA-induced cardioprotective effect. GGA also showed preserved mitochondrial respiratory function, isolated at the end of the reperfusion period, which was abolished with 5-HD treatment. GGA prevented destruction of the mitochondrial structure by ischemia-reperfusion, as shown by electron microscopy. In cultured cardiomyocytes, GGA induced HSP72 expression and resulted in less damage to cells, including less apoptosis in response to hypoxia-reoxygenation. Treatment with 5-HD abolished the GGA-induced cardioprotective effects but did not affect HSP72 expression. Our results indicate that preserved mitochondrial respiratory function, owing to GGA-induced HSP72 expression, may, at least in part, have a role in cardioprotection against ischemia-reperfusion. These processes may involve opening of the mitoKATP channel.

Background: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM). However, the relationship between cardiovascular autonomic neuropathy and the incidence of cardiovascular events has been poorly investigated in type 2 DM. The present study aimed to assess the long-term cardiovascular predictive value of baroreflex sensitivity (BRS) in Japanese patients with type 2 DM without structural heart disease. Methods and Results:BRS was evaluated using the phenylephrine method in 210 patients with type 2 DM who did not have structural heart disease or other severe complications. BRS was considered depressed if <6 ms/mmHg. Accurate follow-up information for 3-10 years (mean 4.7 years) was obtained in 184 patients (90 females, 94 males; mean age 58±12 years). The initial onset of a major adverse cardiovascular event (MACE) was investigated. During follow-up, 19 patients presented with a MACE (4 cardiovascular deaths, 3 nonfatal myocardial infarctions, 4 coronary revascularizations, 5 strokes, 2 congestive heart failures). Cox proportional hazards regression analysis revealed that depressed BRS was independently associated with the incidence of MACE (hazard ratio 1.93, 95% confidence interval 1.09-3.82, P=0.0236). Conclusions:Depressed BRS at baseline has long-term cardiovascular predictive value in Japanese patients with type 2 DM without structural heart disease. (Circ J 2010; 74: 1379 - 1383

No abstract

No abstract

Background: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM), and baroreflex sensitivity (BRS) reportedly can predict cardiovascular prognosis in type 2 DM patients. The hypothesis that cardiovascular events are associated with gender differences in BRS was tested in the present study. Methods and Results:From 1998, we have evaluated BRS by phenylephrine methods in 185 consecutive type 2 DM patients. The long-term prognostic value of BRS was compared between 91 female (58±12 years) and 94 male patients (58±11 years). There was no significant difference in age or severity and duration of DM between the 2 groups. When compared to male, the BRS value in female patients was significantly lower (9.26±6.0 vs. 5.97±5.0 ms/mmHg, P<0.0001). During a mean of 62.7 months of follow-up, 16 female patients developed cardiovascular events (17.6%) including stroke, acute myocardial infarction, angina pectoris requiring percutaneous coronary intervention or coronary artery bypass grafting and congestive heart failure requiring admission, while only 4 male patients developed events (4.3%, P<0.005). In females, the Kaplan-Meier curves revealed that those with depressed BRS (<6 ms/mmHg) had a higher incidence of cardiovascular events than those with preserved BRS (P<0.05), but this relationship was not observed in male patients. Conclusions:Although the reason why females had a more depressed BRS remains unclear, our findings demonstrated that a depressed BRS value can accurately predict cardiovascular events, especially in female patients with type 2 DM. (Circ J 2011; 75: 1418 - 1423