Prostate cancer susceptibility is mediated by interactions between exposure to ultraviolet radiation and polymorphisms in the 5' haplotype block of the vitamin D receptor gene

Vitamin D receptor (VDR) polymorphisms are prostate cancer risk candidates. We determined if SNPs in haplotype block sub-regions C2 (SNPs C2-1, G/C(3436), C2-2, A/G(3944)) or C1 (C1-1, C/T(20965), C1-2, C/T(30056)) are associated with risk in an ultraviolet radiation (UVR)-dependent manner. In men with very low exposure, SNPs in both sub-regions were associated with risk. Various haplotypes in haplotype block C including G(3436)-A(3944)-C(20965)-C(30056), (G or C)-A-C-C and G-A-(C or T)-C were significantly associated with increased risk (odds ratios between 1.95 and 2.37). These findings suggest various block C SNPs are associated with prostate cancer risk via a mechanism involving exposure to sunlight.     

Intermedin/Adrenomedullin-2 inhibits growth hormone release from cultured, primary anterior pituitary cells

Intermedin (IMD), a novel member of the adrenomedullin (AM), calcitonin gene-related peptide (CGRP), amylin (AMY) peptide family, has been reported to act promiscuously at all the known receptors for these peptides. Like AM and CGRP, IMD acts in the circulation to decrease blood pressure and in the brain to inhibit food intake, effects that could be explained by activation of the known CGRP, AM, or AMY receptors. Because AM, CGRP, and AMY have been reported to affect hormone secretion from the anterior pituitary gland, we examined the effects of IMD on GH, ACTH, and prolactin secretion from dispersed anterior pituitary cells harvested from adult male rats. IMD, in log molar concentrations ranging from 1.0 pm to 100 nm, failed to significantly alter basal release of the three hormones. Similarly, IMD failed to significantly alter CRH-stimulated ACTH or TRH-stimulated prolactin secretion in vitro. However, IMD concentration-dependently inhibited GHRH-stimulated GH release from these cell cultures. The effects of IMD, although requiring higher concentrations, were as efficacious as those of somatostatin and, like somatostatin, may be mediated, at least in part, by decreasing cAMP accumulation. These actions of IMD were not shared by other members of the AM-CGRP-AMY family of peptides, suggesting the presence of a novel, unique IMD receptor in the anterior pituitary gland and a potential neuroendocrine action of IMD to interact with the hypothalamic mechanisms controlling growth and metabolism.     

Evaluation of three different measurement methods for dural ectasia in Marfan syndrome

AIM: Dural ectasia is a major diagnostic criterion for Marfan syndrome using the Ghent nosology. Our aim was to evaluate the efficacy of three different radiological methods previously proposed for the assessment of dural sac diameter in Marfan syndrome. METHODS: Marfan syndrome was diagnosed in our study using the Ghent criteria, disregarding dural ectasia as a criterion. Three proposed radiological methods were applied to measure dural sac diameter, examined for 41 patients (18 patients with and 23 without Marfan syndrome) by computed tomography or magnetic resonance imaging. RESULTS: Using Oosterhof's method, 94% of the patients with and 44% of the patients without Marfan syndrome fulfilled the criteria of dural ectasia. According to Villeirs, dural ectasia was diagnosed in 18% of the patients with and in none of the patients without Marfan syndrome. With Ahn's method, dural ectasia was found in 72% of the patients with and in 44% of the patients without Marfan syndrome. In only two patients with Marfan syndrome was dural ectasia diagnosed by all three methods. CONCLUSION: Our results reveal overt discrepancy between the three methods of assessing dural ectasia. Considering the key role played by dural ectasia in reinforcing the diagnosis of Marfan syndrome according to the Ghent nosology, a standardized and reliable method should be sought.     

Effect of central administration of ondansetron, a 5-hydroxytryptamine-3 receptor antagonist on gastric and duodenal ulcers

The effect of central administration of ondansetron, a 5-hydroxytryptamine-3 (5-HT₃) receptor antagonist on gastric secretion and gastric cytoprotection was evaluated using four different models of gastric ulcers and cysteamine induced duodenal ulcer. Ondansetron was administered at two different doses of 20 μg/kg, intracerebroventricular (i.c.v.) and 40 μg/kg, i.c.v. Both doses of ondansetron showed significant increase in healing of acetic acid induced gastric ulcers and reduced the formation of ethanol-induced and pylorus ligation-induced gastric ulcers and cysteamine-induced duodenal ulcer. High dose of ondansetron (40 μg/kg, i.c.v.) was more effective compared with the low dose (20 μg/kg, i.c.v.). However, both doses of ondansetron did not influence the development of cold restraint stress induced gastric ulcers. It was concluded that blocking of 5-HT₃ receptors in brain decreases gastric acid secretion and increases gastric mucus secretion.     

The effects of microinjection of d-amphetamine into the n. accumbens during the late maintenance phase of an ethanol consumption bout.

The microinjection of d-amphetamine into the n. accumbens of rats, prior to the start of an operant ethanol self-administration session, increases operant behavior and the amounts of ethanol presented as the reinforcer. Although this effect could result by blocking termination processes regulating a consummatory bout, it could also be a result of enhancing the stimulus control regulating the maintenance of a drinking bout. To explore this issue, rats were trained to self-administer 10% ethanol in an operant situation. Following establishment of stable behavior, they were surgically instrumented so that the n. accumbens could be microinjected with d-amphetamine during a drinking bout, without having to handle the animal. The microinjection of d-amphetamine in the rats self-administering ethanol at the late phase of the drinking bout resulted in a prolonged bout and increased self-administration. During extinction testing, a reinstatement of responding was found following the amphetamine microinjection. The data suggest the most likely action of the amphetamine microinjection was to alter stimulus control factors, which normally regulate the maintenance of drinking, thereby prolonging the bout and increasing intake.     

Impaired Knowledge of Visual and Non-visual Attributes in a Patient with a Semantic Impairment for Living Entities: A Case of a True Category-specific Deficit

Abstract

We report a single case study of a 22-year-old, brain-damaged patient, Jennifer, who showed a semantic deficit affecting living entities (animals and fruit and vegetables) to a greater extent than non-living ones (implements and means of transport). We first show that this category effect was reliable both across time and naming conditions and that it was not an artefact of uncontrolled stimulus factors. We then show that Jennifer had no impairment at the visual or structural processing level and that her deficit was probably located at a semantic processing level. Specific semantic deficits for living entities have usually been explained by damage to the visual semantic system. However, when Jennifer's access to visual and non-visual semantics was assessed through an attribute-verification task, no evidence of an attribute-specific impairment was found: Jennifer was equally impaired in retrieving visual and non-visual attributes of living entities and she was not at all impaired in retrieving visual attributes of non-living entities. Thus, the hypothesis of damage to visual semantics cannot account for the pattern of living things impairment found in this patient. Rather, this pattern seems to require the assumption that the semantic system is organized according to the living/non-living dimension.