D-2 but not D-1 dopamine agonists produce augmented behavioral response in rats after subchronic treatment with methamphetamine or cocaine

A study was performed to examine behavioral response to a challenge of selective dopamine D-1 and D-2 agonists in rats previously sensitized by subchronic administration of methamphetamine or cocaine. Rats in three groups received repeated injections (IP) of saline, methamphetamine (4 mg/kg/day) or cocaine (20 mg/kg/day), respectively, for 14 days. After an abstinence period of 7–13 days, all groups were challenged with either a selective D-1 agonist (SKF 38393) or D-2 agonists (quinpirole or RU 24213). The ability of SKF 38393 (6 mg/kg or 18 mg/kg) to produce grooming behavior did not differ significantly among the saline-, methamphetamine-and cocaine-treated groups. In contrast, quinpirole (1 mg/kg) and RU 24213 (3 mg/kg) produced more intense stereotypy consisting of rearing, sniffing and repetitive head movement in the two psychostimulant-treated groups than in the saline-treated group. Such augmented response to selective D-2 agonists was observed even after a 1-month abstinence period. These results suggest that the enduring behavioral sensitization induced by two pharmacologically distinct psychostimulant agents, methamphetamine and cocaine, occurs through a common neurobiological mechanism of lasting supersensitivity in postsynaptic D-2, but not D-1 dopamine receptors.     

Cerebral and myocardial infarcts due to deterioration of cloth-cover of Starr-Edwards mitral valve 16 years after replacement

A 55 year-old woman whose mitral valve had been replaced 16 years previously with a Starr-Edwards cloth-covered ball valve was admitted to our hospital, complaining of memory disturbance and bilateral pretibial edema. Her CT scan findings showed a low density area in the left anterior and temporal lobes, hippocampus, and insula. A right coronary angiogram demonstrated total obstruction at the midportion. In addition to these cerebral and myocardial infarctions due to cloth-wear of the Starr-Edwards ball valve, her laboratory data indicated intravascular hemolysis. Her malfunctioning Starr-Edwards valve was successfully replaced with a Bj?rk-Shiley valve. An aggressive attitude toward urgent replacement is suggested in cases of suspected cloth-wear.     

MALIGNANT CHEMODECTOMA (PARAGANGLIOMA) OF THE LARYNX A Case Report with Electron Microscopy and Biochemical Assay

This report presents a case of malignant chemodectoma In the epiglottic region of a 47-year-old man. His initial complaint was laryngeal discomfort and he expired from generalized metastases of the tumor about one year after operation. The tumor was detected by laryngoscopy and laryngogram. The yellow parenchymatous tumor, 2.8×2.5×1.5 cm in size, was resected together with two enlarged regional lymph nodes. The mass was subjected to a histopathological study and biochemical assay. Microscopically, the tumor was located in the submucosa of the epiglottis and showed an alveolar growth pattern of comparatively uniform tumor cells. Neurosecretory granules were clearly demonstrated by Grimelius'method and by electron microscopy. The biochemical assay revealed that the tumor contained small amounts of serotonine, epinephrine, norepinephrine, and dopamine. The distribution of paraganglia as the source of these tumors, the clinicopathological review of the previous reports and significance of neurosecretory granules are discussed.     

Collagen synthesis in human skin fibroblasts is stimulated by a stable form of ascorbate, 2-O-alpha-D-glucopyranosyl-L-ascorbic acid.

We evaluated the effect of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid (AA-2G) on collagen synthesis in cultured human skin fibroblasts and on proliferation of fibroblasts. At concentrations of 0.1-0.5 mmol/L, AA-2G effectively stimulated collagen synthesis with an effectiveness comparable to that of L-ascorbic acid. On the other hand, 6-O-alpha-D-glucopyranosyl-L-ascorbic acid showed a weak effect. The stimulation of collagen synthesis by AA-2G was attenuated by the addition of a collagen synthesis inhibitor, L-azetidine 2-carboxylic acid, in a dose-dependent manner. In addition, AA-2G-induced stimulation of collagen synthesis could be completely inhibited by the addition of castanospermine, an inhibitor of neutral alpha-glucosidase. Relatively high alpha-glucosidase activity, which would contribute to release of ascorbic acid from AA-2G, could be detected in the lysate of cultured fibroblasts. The stimulatory activity of AA-2G on collagen synthesis was observed after 5 d in culture, whereas L-ascorbic acid tended to lose its stimulatory activity. Continuous supplementation of AA-2G (0.25 mmol/L) to culture medium for 24 d enhanced the cell growth four times that of the control. These results indicate that AA-2G is gradually cleaved by the cellular alpha-glucosidase to release L-ascorbic acid, which adequately stimulates collagen synthesis and proliferation of human skin fibroblasts.     

Thrombin accumulation in brains of patients with Alzheimer's disease.

Thrombin was detected immunohistochemically in brain tissue of Alzheimer's disease (AD) patients and age-matched controls. Positive staining was restricted to vessels and residual plasma in controls but was also present in senile plaques, some diffuse amyloid deposits and neurofibrillary tangles in AD. Positive staining was abolished by absorption of antibody with purified human thrombin but not by absorption with prothrombin. The data suggest that thrombin formation from prothrombin probably takes place in AD brain.     

Electrophysiological effects of magnesium sulfate on human conduction system

Electrophysiological studies were performed to evaluate the effects of MgSO4 on human conduction system. Nine patients who received 20 mg/kg of MgSO4 did not show any significant changes in the electrophysiological parameters except for prolongations in the PR and AH intervals. After the infusion of 40 mg/kg of MgSO4 in eleven patients, sinus cycle length and corrected sinus node recovery time were increased but statistically insignificantly. Sinoatrial conduction time, the PR interval and AH interval were increased. The effective refractory period (ERP) of right atrium, ERP of atrioventricular node (AV node), ERP of right ventricule and ERP/QTc were increased significantly. These findings suggests that the antiarrhythmic effects of magnesium were due to (1) suppression of the functions of the sinus and AV nodes, and (2) shortening of the duration of the ventricular vulnerable period during the cardiac cycle and prevention of ventricular arrhythmias related reentry mechanism.     

Experimental studies on an artificial esophagus using a collagen-silicone copolymer

An artificial esophagus consisting of a collagen-silicone copolymer prepared by special chemical and physical procedures proved to be advantageous by both physical and histological examination. The adherence to the host tissue was satisfactory when collagen was used. The esophageal prosthesis was anastomosed to the jejunum in 5 dogs and no leakage occurred during 10-30 days. In subsequent experiments, use of the artificial prosthesis in the thoracic esophagus was followed by leakage in 5 of 14 cases (35 per cent). Five of these dogs survived for over 30 days, and the longest survival was 212 days. The incidence of leakage was acceptable but stricture was a common long-term complication. Further studies are underway to refine the prosthesis, the method of anastomosis, and post-operative management.     

Morphologic hippocampal asymmetry in male and female rats

Our findings indicate that the hippocampus of the rat varies in structure in the right and left hemispheres and in males and females. A morphologic study of the thickness of the dorsal hippocampus was carried out on celloidin-embedded histologic sections from male, Long-Evans rats of the following ages: 6, 10, 14, 26, 41, 55, 77, 90, 108, 185, 300, 400, and 650 days. Between 15 and 25 rats per age group were used, a total of 225 male rats. In addition, the hippocampi were measured on 47 Long-Evans female, 90-day-old rats: 11 normal and 36 animals ovariectomized one day after birth. We found that in males the right hippocampus was significantly thicker than the left for some but not all age groups. In the female at 90 days of age, the left hippocampus was thicker than the right. This left-right pattern in the female hippocampus did not reverse, as it did in the cerebral cortex after ovariectomy at birth.