Inhibitory effect of spiradoline, a kappa opioid receptor agonist, on Ca2+ induced contraction and the intracellular Ca2+ concentration in porcine coronary artery.

STUDY OBJECTIVE--The aim was to clarify the inhibitory effect of the selective kappa agonist, spiradoline, on coronary arterial smooth muscle in relation to the intracellular Ca2+ concentration. DESIGN--The inhibitory effect of spiradoline was investigated (1) on the contractile response of pig coronary artery to the readmission of Ca2+, following initial exposure to Ca2+ free medium and depolarisation with 40 mM K+; (2) on the intracellular Ca2+ concentration as assessed using the fluorescent calcium indicator fura-2. Relaxant responses to spiradoline in isolated porcine coronary artery strips contracted with K+ and prostaglandin F2 alpha were also examined. EXPERIMENTAL MATERIAL--Coronary arteries isolated from pigs of both sexes were used. The right and left circumflex coronary arteries were cut into 3 mm wide strips which were used to measure the change in contractile force and the intracellular Ca2+ concentration. MEASUREMENTS AND MAIN RESULTS--Prior treatment with spiradoline at 2 x 10(-6) mol.litre-1 or more inhibited the contractile response to the readmission of Ca2+ in porcine coronary artery exposed to Ca2+ free medium in the presence of high K+. Naloxone at 3 x 10(-4) mol.litre-1 did not reverse the inhibitory action of 2 x 10(-5) M spiradoline. Ca2+ induced contraction was inhibited completely by 10(-4) M spiradoline. Moreover, spiradoline caused relaxation in arterial preparations that had been contracted with K+ (15 to 25 mmol.litre-1) or prostaglandin F2 alpha (10(-6) to 3 x 10(-6) mol litre-1), greater relaxation being seen in the K+ induced contraction. The intracellular Ca2+ concentration was significantly lowered by 2 x 10(-5) M spiradoline. CONCLUSIONS--The relaxant response of coronary artery to spiradoline is, in part, attributable to interference with Ca2+ entry into the arterial smooth muscle.     

Significance of low perfusion with increased oxygen extraction fraction in a case of internal carotid artery stenosis.

BACKGROUND AND PURPOSE: Decreased cerebral blood flow with an increased oxygen extraction fraction, the so-called misery perfusion syndrome, suggests a vulnerability to reduction in cerebral perfusion pressure and a tendency to develop cerebral infarction. It is uncertain, however, whether the infarct would occur in the brain region specifically exhibiting this condition. CASE DESCRIPTION: We report the case of a patient with right intracranial internal carotid artery stenosis who presented with mild left hemiparesis resulting from a right frontal watershed infarct. Positron emission tomography 2 months after the stroke showed decreased cerebral blood flow with an increased oxygen extraction fraction in noninfarcted areas of the affected hemisphere. Maximal changes were detected in the watershed area between the middle cerebral artery and the posterior cerebral artery. Three months later, while on antiplatelet therapy, he suffered a new infarct in the right temporo-occipital watershed area that had shown the highest oxygen extraction fraction value on the first positron emission tomographic study. One month after the recurrence of stroke, a second study showed that low perfusion with increased oxygen extraction fraction persisted in the affected hemisphere to a lesser degree than in the first study. CONCLUSIONS: This observation suggests that the area of low perfusion exhibiting the highest oxygen extraction fraction has the highest risk for infarction. Increased oxygen extraction fraction may be an important factor in the development of hemodynamic infarction.     

Spontaneous mesenteric hemorrhage associated with ehlers-danlos syndrome

The vascular type of Ehlers-Danlos syndrome is a genetic disorder of connective tissue and is frequently associated with catastrophic arterial complications. Its surgical treatment is extremely difficult because of the fragility of vessels. This article describes three patients with vascular type of Ehlers-Danlos syndrome who developed mesenteric hemorrhage due to spontaneous arterial rupture. The clinical and molecular characteristics of the disease are briefly reviewed.     

Effects of herbal medicine Dai-Kenchu-to on anorectal function in children with severe constipation.

AIM: We administered the herbal medicine Dai-Kenchu-To (DKT) to children with severe chronic constipation or with severe constipation after surgery for anorectal malformations. We then objectively assessed the effect of DKT on anorectal function by manometric study in addition to using a clinical scoring system. PATIENTS AND METHODS: Ten children with severe chronic constipation and 5 children with severe constipation after surgery for anorectal malformations were assessed. These 15 children received 0.3 g/kg/day of DKT for periods ranging from 3 months to 1 year. We objectively assessed their bowel function, sphincter function and rectal reservoir function by anorectal manometry and clinical scoring. RESULTS: In 10 children with severe chronic constipation, the clinical score after administration of DKT (7.2 +/- 0.8) improved significantly compared with that before administration of DKT (4.6 +/- 2.9) (p < 0.02). The threshold sensation volume and the maximum tolerable volume after administration of DKT significantly (p < 0.05; p < 0.01) decreased (128 +/- 63 ml vs. 69 +/- 18 ml; 229 +/- 99 ml vs. 144 +/- 47 ml), and rectal compliance after administration of DKT also significantly (p < 0.05) decreased (12.4 +/- 10.9 ml/cmH(2)O vs. 4.7 +/- 3.9 ml/cmH(2)O). CONCLUSION: The present study demonstrated that DKT had a favorable clinical effect on severe constipation in children, and anorectal manometry showed an improvement in their rectal reservoir functions. It appears that the results were secondary to DKT-stimulated peristalsis of the intestine, which promoted regular bowel habits.     

The relationship between testosterone levels and cognitive ability patterns.

The cognitive performance of normal men and women was studied, grouped according to whether the subjects had relatively high or low salivary testosterone (T) concentrations. Men with lower T performed better than other groups on measures of spatial/mathematical ability, tasks at which men normally excel. Women with high T scored higher than low-T women on these same measures. T concentrations did not relate significantly to scores on tests that usually favor women or that do not typically show a sex difference. These results support suggestions of a nonlinear relationship between T concentrations and spatial ability, and demonstrate some task specificity in this respect.