The brain‐derived neutrophic factor val66met polymorphism and sudden unexpected infant death

Aim: Findings of hypoxia prior to death and involvement of a dysregulation of the serotonergic network in sudden infant death syndrome (SIDS) may indicate that brain‐derived neutrophic factor (BDNF) also is of importance with regard to sudden unexpected infant death. Based on this, the purpose of this study was to investigate the BDNF val66met polymorphism in SIDS cases, cases of infectious death and controls. Methods: The polymorphism was investigated in 163 SIDS cases, 34 cases of infectious death and 121 controls, using real‐time PCR and fluorescence melting curve analysis. Results: There were no differences in val66met genotype distribution between neither the SIDS cases nor the cases of infectious death and controls (p = 0.95 and p = 0.52, respectively). Conclusion: The study indicates that the val66met polymorphism is not important for sudden unexpected infant death. However, several other SNPs in the BDNF gene, as well as in other genes involved in this pathway, including G‐protein, have to be investigated to fully exclude any involvement of BDNF in SIDS.     

Hyperglycemia in aneurysmal subarachnoid hemorrhage: a potentially modifiable risk factor for poor outcome

Hyperglycemia after aneurysmal subarachnoid hemorrhage (aSAH) occurs frequently and is associated with delayed cerebral ischemia (DCI) and poor clinical outcome. In this review, we highlight the mechanisms that cause hyperglycemia after aSAH, and we discuss how hyperglycemia may contribute to poor clinical outcome in these patients. As hyperglycemia is potentially modifiable with intensive insulin therapy (IIT), we systematically reviewed the literature on IIT in aSAH patients. In these patients, IIT seems to be difficult to achieve in terms of lowering blood glucose levels substantially without an increased risk of (serious) hypoglycemia. Therefore, before initiating a large-scale randomized trial to investigate the clinical benefit of IIT, phase II studies, possibly with the help of cerebral blood glucose monitoring by microdialysis, will first have to improve this therapy in terms of both safety and adequacy.     

Focal up-regulation of E-cadherin-catenin complex in inflamed bowel mucosa but reduced expression in ulcer-associated cell lineage

The E-cadherin-catenin complex is important for the maintenance of epithelial architecture. We studied its expression in Crohn disease, ulcerative colitis, acute ileitis, and controls. Immunohistochemical stainings for E-cadherin, alpha-catenin, beta-catenin and gamma-catenin were performed. E-cadherin messenger RNA (mRNA) was detected using riboprobes. In active inflammation, there was up-regulation of the complex. In particular, epithelium adjacent to ulcers showed increased expression of protein and mRNA, but in ulcer-associated cell lineage, the intensity of staining was weak to negative. In focal inflammation, up-regulation was found in affected areas. Reparative epithelium growing over denuded areas showed weaker expression. Since structural or functional perturbation in any of the molecules of the E-cadherin-catenin complex results in loss of intercellular adhesion, the preexistent epithelium may benefit from up-regulation to try to maintain its normal architecture under inflammatory conditions. Reduced expression in reparative epithelium and ulcer-associated cell lineage could facilitate the motility of these cells.     

An anatomic basis for ultrasound images of the human placenta

Placentas after uneventful pregnancies were perfused under physiologic pressure in the fetal vessels, expanded to their predelivery volume, fixated with 4% formaldehyde, and compared to their ultrasound images in pregnancy. The placentas showed a side arrangement of the fetal cotyledons in contact with the basal plate. The centers of the cotyledons showed an empty space in which the spiral arteries ended. These spaces in the placenta corresponded with transsonic areas of ultrasound. The central spaces were surrounded by a relatively dense shell of villi containing the more or less fibrotic stem villi. This explained the areas of increased echo-density, as seen by ultrasound during the last trimester of pregnancy. The fetal cotyledons, composed of a central cavity and a dense villous shell, were separated by a reticular area. The veins ended at the basal plate in these intercotyledonary areas.     

Accuracy of sperm characteristics in predicting the in vitro fertilizing capacity of semen

Based on the results of in vitro fertilization (IVF) in 56 couples, the power was assessed of traditional sperm characteristics of native semen to discriminate between in vitro fertile and in vitro infertile semen. The number per ejaculate of spermatozoa with regular oval heads was the best discriminant, followed by the concentration of progressively motile spermatozoa. This contrasts with the in vivo fertilizing capacity, which depends mostly on the proportion and concentration of spermatozoa with rapid linear progression. The lower limit of sperm characteristics was assessed as the fifth percentile of in vitro fertile semen and was compared with the lower limit of semen of fertile men and of subfertile men who achieved spontaneous or treatment-related conception in vivo. It appeared that the semen quality needed for in vitro fertilization is inferior to that of fertile men but not remarkably different from that of subfertile men who achieved spontaneous conception during 1-year follow-up after consultation. If conventional methods for semen preparation are used, there seems to be no major advantage in favor of IVF for the treatment of male infertility due to sperm deficiency. An increased success rate may, however, be attained, thanks to improved techniques of semen collection, semen preparation, and oocyte insemination.     

Comparative study on the bioactivation mechanisms and cytotoxicity of Te-phenyl-L-tellurocysteine,Se-phenyl-L-selenocysteine,and S-phenyl-L-cysteine

Tellurium compounds are effective antioxidants and chemoprotectors, even more active than their selenium and sulfur analogues. In addition to these properties, some selenium compounds, such as selenocysteine Se-conjugates, possess significant chemopreventive and antitumor activities, and selenol metabolites are considered as active species. In the present study, we have synthesized Te-phenyl-L-tellurocysteine and evaluated its bioactivation and cytotoxicity. The activities of this compound were compared with those of the corresponding selenium and sulfur analogues. Te-Phenyl-L-tellurocysteine is bioactivated into its corresponding tellurol, as detected by GC-MS, by cysteine conjugate beta-lyase and amino acid oxidase, analogously to what has been shown previously for Se-phenyl-L-selenocysteine. The rate of beta-elimination may reflect the bond strength of the corresponding C-S, C-Se, and C-Te bond. Bioactivation of Te-phenyl-L-tellurocysteine and its selenium and sulfur analogues by oxidative enzymes was evaluated by measuring NADPH-dependent activation of hepatic mGST and inhibition of EROD. Te-Phenyl-L-tellurocysteine and Se-phenyl-L-selenocysteine displayed strong and time-dependent mGST activation, while S-phenyl-L-cysteine resulted in no significant activation. Te-Phenyl-L-tellurocysteine was also a strong inhibitor of EROD activity. In addition to EROD inhibition, Te-phenyl-L-tellurocysteine was the strongest inhibitor of several human cytochrome P450 isoenzymes followed by Se-phenyl-L-selenocysteine, while S-phenyl-L-cysteine was the weakest inhibitor. Interestingly, Te-phenyl-L-tellurocysteine selectively inhibited cytochrome P450 1A1 directly, which is, for example, responsible for the activation of several procarcinogens. Preliminary cytotoxicity studies with Te-phenyl-L-tellurocysteine in freshly isolated rat hepatocytes showed a time-dependent depletion of GSH and LDH leakage comparable with the relatively nontoxic drug paracetamol, while the selenium and sulfur analogues were nontoxic toward rat hepatocytes. In conclusion, because the chemopreventive and antitumor activities of selenium compounds are thought to be mediated via their selenol metabolites and tellurium compounds might be even more active than selenium compounds, tellurocysteine Te-conjugates might be an interesting novel class of prodrugs for the formation of biologically active tellurols.     

Usefulness of language and memory testing during intracarotid amobarbital testing: observations from an fMRI study

BACKGROUND: Several procedures for testing language lateralization and memory function exist during the intracarotid amobarbital test (IAT). The use of functional magnetic resonance imaging (fMRI) gives the opportunity to assess the validity of some of these procedures, or at least to inspect the neuronal correlates. A comprehensive fMRI protocol was tested, aimed at addressing aspects of lateralization of language, as well as testing memory in relation to activation of mesiotemporal regions. Here we report observations with possible consequences for the current IAT procedures. MATERIALS AND METHODS: The protocol consisted of three language tasks (overt naming, semantic decision and silent word generation) and two memory tasks (encoding and retrieving visual scenes). The paradigms used a block-related procedure in nine right-handed normal volunteers. During the procedure dynamic weighted full brain images were acquired which are sensitive to the blood oxygenation activation effect. RESULTS : Encoding showed symmetrical bilateral activation in the mesiotemporal regions, specifically the hippocampus, parahippocampal gyrus and fusiform gyrus. With a retrieval task activation of the mesiotemporal areas was restricted to the posterior hippocampal area. Overt object naming showed results, similar to encoding tasks with bilateral activation of hippocampal areas. Silent word generation showed much stronger ability to lateralize than the other two language-related tasks and especially object naming. CONCLUSION: Activation revealed by fMRI activation shows that IAT procedures, using active semantic language processing or comprehensive procedures with multiple language tasks have the highest guarantee for individual activation lateralization. Simple object naming does not guarantee a lateralized language fMRI activation pattern. Of the different memory procedures during IAT, the procedures (Interview and the Montreal) demanding encoding processing will be related to larger areas of bilateral hippocampal activation than procedures (Seattle) exclusively requiring retrieval. Moreover, tasks using recognition of previously presented language items (naming objects) are equally effective for assessing hippocampal activation compared with presenting separate memory items.