Phorbol ester inhibition of ovarian and testicular steroidogenesis in vitro

Possible influences of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) upon gonadal steroidogenesis were investigated in vitro. Granulosa cells from hypophysectomized, estrogen-treated rats were cultured for 2 days in medium containing 0.1 microM androstenedione. Follicle-stimulating hormone (FSH) treatment increased estrogen, progesterone, and 20 alpha-hydroxypregn-4-en-3-one production. Concomitant TPA treatment inhibited FSH-stimulated estrogen production by up to 95% [concentration that induced 50% inhibition of steroid production (ED50), 1.1 ng/ml]. TPA also inhibited FSH-stimulated progesterone (ED50, approximately 0.6 ng/ml) and 20 alpha-hydroxypregn-4-en-3-one (ED50, approximately 1.1 ng/ml) production. N6O2'-dibutyryl cyclic adenosine 3':5'-monophosphate increased steroidogenesis; however, cotreatment with TPA blocked progestin but not estrogen production. The TPA inhibition of progestin biosynthesis was accompanied by decreases in FSH-stimulated pregnenolone biosynthesis and 3 beta-hydroxysteroid dehydrogenase activity without decreasing the activity of 20 alpha-hydroxysteroid dehydrogenase. In primary cultures of rat testicular cells, human chorionic gonadotropin treatment increased testosterone production 44-fold, whereas concomitant treatment with TPA inhibited testosterone production by up to 86% (ED50, 10 ng/ml). Cholera toxin and N6O2'-dibutyryl cyclic adenosine 3':5'-monophosphate also increased testosterone production, while the actions of these agents were decreased by TPA. The TPA suppression of testosterone production was associated with a decrease in accumulation of 17 alpha-hydroxyprogesterone and androstenedione and an increase in progesterone production, suggesting a specific inhibition of 17 alpha-hydroxylase and 17,20-lyase activities. These results demonstrate the inhibitory effects of a tumor promoter upon gonadotropin-stimulated steroidogenesis by cultured rat granulosa and Leydig cells through specific regulation of steroidogenic enzymes. Additional studies may assist in further elucidation of cellular mechanisms associated with carcinogenesis and steroidogenesis.     

Characteristics of cloned cerebrovascular endothelial cells following infection with Theiler's virus I. Acute infection

The present study describes the replication of Theiler's virus in cloned cerebrovascular endothelial cells (CVE) isolated from strains of mice that are either susceptible or resistant to Theiler's virus-induced demyelination (TVID). CVE isolated from all strains of mice were equally permissive to Theiler's virus infection. Interferon-γ and tumor necrosis factor-α were found to inhibit the replication of Theiler's virus in CVE. A correlation between susceptibility to demyelination and the ability of Theiler's virus to induce MHC Class I on CVE was demonstrated.     

Noninvasive assessment of microvessels with the duplex scanner

This study was undertaken to determine if a duplex scanner equipped with a new 10 MHz probe could accurately evaluate microvascular anastomotic patency. The overall predictive accuracy of the duplex scanner was 90% (p less than 0.0001) with no difference noted among the three main anastomotic groups examined--acute artery, acute vein, and long-term artery. There was, however, a statistically significant difference (p less than 0.05) in the ability to interpret vessels that were patent (100%) versus those that were partially occluded (73%) or occluded (88%). It is believed that the duplex scanner has potential applications to preoperatively and intraoperatively study microvessels and postoperatively to supplement other techniques in monitoring acute and long-term anastomotic patency.     

Error-related hyperactivity of the anterior cingulate cortex in obsessive-compulsive disorder.

BACKGROUND: Hyperactivity of the anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been shown to increase with symptom provocation and to normalize with treatment-induced symptom reduction. Although the functional significance of anterior cingulate involvement in OCD remains unknown, electrophysiological evidence has linked this region to error-processing abnormalities in patients with OCD. In this functional magnetic resonance imaging (fMRI) study, we sought to further localize error-processing differences within the ACC of OCD patients compared with healthy subjects. METHODS: Event-related fMRI data were collected for eight OCD patients and seven healthy subjects during the performance of a simple cognitive task designed to elicit errors but not OCD symptoms. RESULTS: Both OCD patients and healthy subjects demonstrated dorsal ACC activation during error commission. The OCD patients exhibited significantly greater error-related activation of the rostral ACC than comparison subjects. Activity in this region was positively correlated with symptom severity in the patients. CONCLUSIONS: Error-processing abnormalities within the rostral anterior cingulate occur in the absence of symptom expression in patients with OCD.     

Quality of life of alcoholics and non-alcoholics: does excessive drinking make a difference in the urban setting?

The current study assessed whether perceived quality of life differed between alcoholics and non-alcoholics. Patients attending an urban-based hospital were screened for alcoholism using the CAGE questionnaire. Patients were recruited from an out-patient clinic setting as well as from an in-patient substance abuse unit. Quality of life scores were based on Chubon's (1987) Life Situation Survey. Results indicated that alcoholics experience a lower quality of life than their non-alcoholic counterparts regardless of setting; however, all patients reported experiencing poor life quality. The impact of alcoholism treatment programmes on patients already experiencing low quality of life is questioned.Study supported by NIAAA-R01-AA08278