Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.     

The participation of adenosine receptors in the adenosine 5''-triphosphate-induced relaxation in the isolated rabbit corpus cavernosum penis

AIM: To investigate the participation of adenosine receptors in the adenosine 5'-triphosphate (ATP)-induced relaxation in the corpus cavernosum penis (CCP) of rabbits. METHODS: The ATP-induced relaxation was assessed on the noradrenaline precontracted CCP of rabbits in the presence and absence of 8-(3-chlorostyryl)caffeine (CSC); an adenosine A(2A) receptor antagonist; alloxazine and MRS1754; adenosine A(2B) receptor antagonists; and ARL67156, an inhibitor of ecto-nucleoside triphosphate diphosphohydrolases. RESULTS: Adenosine and ATP relaxed the noradrenaline precontracted CCP of rabbits in a concentration-dependent manner. The adenosine- and ATP-induced relaxations were suppressed by alloxazine and MRS1754, but not by 8-(3-chlorostyryl)caffeine. ARL67156 potentiated the ATP-induced relaxation but not the adenosine-induced one. MRS1754 suppressed the ATP-induced relaxation potentiated by ARL67156. CONCLUSIONS: The above results suggest that, in the CCP of rabbits, the adenosine receptor mediating adenosine-induced relaxation is of the A(2B) receptor and the ATP directly causes relaxation through the A(2B) receptor on the CCP.     

Warning against the indiscriminate use of a biological half-time model in deriving the critical concentration of metals

For heavy metals, many studies obtained short biological half-times (BHTs) by administrations of heavy metals. Tsuchiya and Sugita, however, first reported the possibility of a long BHT for cadmium (Cd) calculated from Cd accumulations in postmortem human organs and tissues by age using a non-linear regression method employing a differential equation. According to their reports, the Cd BHTs (point estimators) were 12.1-22.7 years by sex, renal cortex and medulla. The minimums and the maximums of the Cd BHTs on the 95% confidence regions of estimators were 6.9-70.2 years by sex and kidney part. It is presumed that the range of the 95% confidence region for the individual BHTs of renal Cd exists in a range from a few years to at least 100 years because of large individual variations in exposure, absorption rate and excretion rate. Point estimators of BHTs, however, include the assumption that all subjects have been exposed to the same level of Cd at the same year of age over a period of decades and have equal absorption and excretion rates of Cd. Therefore, it is not adequate to calculate a safety level for Cd in the industrial environment or foodstuffs using a value of Cd BHT (point estimator) based on Cd accumulation applying a mathematical model. BHTs of metals require careful evaluation and must not be used indiscriminately to derive a critical concentration, for example, using a mathematical model.     

Modified head fixation system for intraoperative CT scanning--technical note.

A head fixation system using four carbon fiber head pins and modified pin supporting devices is described. The fixation system was developed for intraoperative computed tomographic scanning and provides artifact-free images during open-field neurosurgery.     

Effects of STA-MCA anastomosis for ischaemic oculopathy due to occlusion of the internal carotid artery

Summary Effects of STA-MCA anastomosis on two patients with neovascular glaucoma due to occlusion of the internal carotid artery are presented. Both patients improved in visual acuity and central retinal artery pressure as well as in signs of transient ischaemic attack. Postoperative angiography showed a marked decrease in collateral flow through the ophthalmic artery, which is reversed from the normal direction, with the development of blood flow through the anastomosis. Discussion is offered indicating that the lack of collateral flow through both the anterior and posterior communicating arteries is important in addition to occlusion of the internal carotid artery in order to produce full-blown ischaemic oculopathy such as venous stasis retinopathy, neovascular glaucoma or rubeosis iridis. It is stressed that EC-IC bypass surgery should be performed soon after the appearance of ischaemia and before the development of neovascular glaucoma or rubeosis iridis in order to obtain normal vision. In ischaemic oculopathy the results of EC-IC bypass can be evaluated objectively and quantitatively by many noninvasive neuro-ophthalmological tests which are important in discussing the efficacy of the bypass surgery.     

Effects of chronic administration of L-arginine on vasoactive responses induced by endothelin-1 and its plasma level in streptozotocin-induced diabetic rats.

To investigate the mechanism underlying increased endothelin-1 (ET-1) release in diabetic rats, we administered L-arginine chronically to streptozotocin (STZ)-induced diabetic rats. The plasma concentrations of glucose, ET-1 and NOx (NO2- + NO3-) were all significantly raised at 10 weeks after the STZ injection. Chronic administration of L-arginine resulted in a significantly higher plasma NOx concentration and a significantly lower plasma ET-1 level at 10 weeks compared with the untreated diabetic group. ET-1 induced a biphasic vasodilator/vasoconstrictor response in the perfused isolated mesenteric arterial beds from all groups. The vasodilatation was significantly greater in diabetic rats than in age-matched controls. Chronic oral L-arginine administration had no significant effect on the enhanced ET-1-induced vasodilatation seen in the untreated diabetic rats. The vasoconstrictions induced by ET-1 and methoxamine were significantly attenuated in STZ-diabetic rats. The attenuated vasoconstrictor response to ET-1, but not that to methoxamine, was further attenuated by chronic treatment with L-arginine. We conclude that since chronic L-arginine administration not only reduced the increase in plasma ET-1 levels but also further attenuated the ET-1-induced vasoconstriction without affecting the change in vasodilatation, chronic L-arginine administration could be valuable for the treatment of the symptoms of diabetic mellitus related to ET-1.     

Distribution of calcium-activated neutral protease inhibitor in the central nervous system of the rat.

The ubiquitous existence of calcium-activated neutral protease (CANP, calpain), an enzyme whose activity is regulated by calcium ions and a specific endogenous CANP inhibitor (calpastatin), is well known. Although there has been much investigation concerning the distribution and role of CANP, investigations of the distribution of the CANP inhibitor using immunohistochemical techniques are rare. We made antiserum against a 40K fragment of cDNA corresponding to two C-terminal repeats of rat liver CANP inhibitor expressed in Escherichia coli. Using this antiserum, we examined the distribution of CANP inhibitor in the rat central nervous system by the ABC technique and compared it with the distribution of CANP. Neurons and glias were stained, with the cytosol stained diffusely and the cell membranes stained clearly and strongly. Axons and myelin were stained faintly, but nuclei and vessels were not stained. The distribution of CANP inhibitor was thus found to be similar to that of CANP.