Physiologic and Morphologic Characteristics of Granule Cell Circuitry in Human Epileptic Hippocampus

Summary: Morphological and electrophysiological techiques were used to examine granule cells and their mossy fiber axons in nine surgically resected hippocampal specimens from temporal lobe epilepsy (TLE) patients. Timm histochemistry showed mossy fiber sprouting into the inner molecular layer (IML) of the dentate in a subset of tissue samples. In slices from five tissue samples, stimulus-induced bursting activity could be induced with a low concentration (2.5 μM) of bicuculline; bursts were sensitive to the N -methyl- d -aspartate (NMDA) blocker, APV. There was a general correlation between such sprouting and experimentally induced yperexcit ability. Fourteen granule cells from five tissue samples were intracellularly stained [with lucifer yellow (LY) or neurobiotin]. Axons from a subset of these neurons showed axon collaterals reaching into the IML, but this axon projection pattern for single cells was not directly correlated with degree of mossy fiber sprouting shown grossly by Timm staining. Electron microscopic examination of intracellularly stained elements showed mossy fiber axon terminals making asymmetric synaptic contacts (including autapses on the granule cell dendrite) with dendritic shafts and spines in both apical and basal domains. These data are consistent with the hypothesis that mossy fiber sprouting provides a structural basis for recurrent excitation of granule cells, but does not provide direct support of the hypothesis that mossy fiber sprouting causes hyperexcitability. The data suggest that granule cell bursting activity is at least in part a function of compromised synaptic inhibition, since levels of γ-aminobutyric acid (GABA) blockade that are generally subthreshold for burst induction were epileptogenic in some tissue samples from human epileptic hippocampus.     

Vasorelaxant activity of some oxime derivatives

Several non-aromatic substituted oxime derivatives (formamidoxime, acetaldoxime, acetone oxime, acetohydroxamic acid, formaldoxime) function as vasorelaxant NO donors when added to precontracted aortic rings in vitro. This study was aimed to evaluate whether these substances posses vasodilator properties under in vivo conditions. We studied blood pressure changes elicited by administration of these compounds to conscious chronically catheterized Wistar rats in which endogenous NO synthesis was acutely inhibited by N(omega)-nitro-L-arginine methyl ester (L-NAME) pretreatment (30 mg/kg i.v.). Three of the tested substances (formaldoxime, acetohydroxamic acid and formamidoxime) induced pronounced dose-dependent blood pressure reduction which was further augmented when baroreflex operation was interrupted by ganglionic blockade (5 mg/kg pentolinium). Pretreatment of rats with methylene blue (soluble guanylate cyclase inhibitor) was used to estimate the contribution of NO to observed blood pressure lowering effects of the above compounds. Nitric oxide seems to be responsible for the entire formaldoxime-induced blood pressure decrease and for a considerable part of blood pressure changes elicited by formamidoxime. On the contrary, we did not find a significant NO contribution to blood pressure reduction caused by acetohydroxamic acid. In conclusion, our study confirmed in vivo vasodilator effects of three above mentioned compounds which were earlier demonstrated to induce in vitro vasorelaxation. It indicated a variable contribution of nitric oxide to blood pressure changes elicited by particular compounds. Substances with hydrophilic character (formamidoxime, acetohydroxamic acid, formaldoxime) were effective, whereas less hydrophilic substance (acetaldoxime) or slightly hydrophobic one (acetone oxime) were ineffective.     

Delta DNMT3B variants regulate DNA methylation in a promoter-specific manner

DNA methyltransferase 3B (DNMT3B) is critical in de novo DNA methylation during development and tumorigenesis. We recently reported the identification of a DNMT3B subfamily, DeltaDNMT3B, which contains at least seven variants, resulting from alternative pre-mRNA splicing. DeltaDNMT3Bs are the predominant expression forms of DNMT3B in human lung cancer. A strong correlation was observed between the promoter methylation of RASSF1A gene but not p16 gene (both frequently inactivated by promoter methylation in lung cancer) and expression of DeltaDNMT3B4 in primary lung cancer, suggesting a role of DeltaDNMT3B in regulating promoter-specific methylation of common tumor suppressor genes in tumorigenesis. In this report, we provide first experimental evidence showing a direct involvement of DeltaDNMT3B4 in regulating RASSF1A promoter methylation in human lung cancer cells. Knockdown of DeltaDNMT3B4 expression by small interfering RNA resulted in a rapid demethylation of RASSF1A promoter and reexpression of RASSF1A mRNA but had no effect on p16 promoter in the lung cancer cells. Conversely, normal bronchial epithelial cells with stably transfected DeltaDNMT3B4 gained an increased DNA methylation in RASSF1A promoter but not p16 promoter. We conclude that promoter DNA methylation can be differentially regulated and DeltaDNMT3Bs are involved in regulation of such promoter-specific de novo DNA methylation.     

Perceived health status as measured by the SF-36 in patients with multiple sclerosis: a review

This review of literature gives an overview of recent studies about perceived health status as measured by the Short-Form-36 (SF-36) Health Survey in patients with multiple sclerosis (MS). The SF-36 is one of the tools measuring health status in patients used in international research and clinical practice. It measures two main health concepts – physical and mental. The SF-36 represents a valid instrument able to detect differences in perceived health status in patients. A computer-aided search in Medline and PsycINFO resulted in 504 articles in English published from 1996 to August 2006. After the screening process on the basis of abstracts, eight articles consisting of empirical studies remained in which perceived health status was evaluated using the SF-36 Health Survey. Seven studies focused on disability and perceived health status in the SF-36. Two studies focused on the relationship between depression and perceived health status. These studies showed that MS patients with low disability and minor depression scored significantly better than patients with high disability and major depression in the SF-36 health dimensions. Gender seems to have no influence on perceived health status in MS patients. The longer the disease duration and the more severe the disease, the lower the patients scored in perceived health status. The more disabled, the more depressive and the older the patients, the poorer their perceived health status was. Health providers supporting appropriate treatment might pay more attention to more disabled and more depressive patients, with longer disease duration. Perceived health status can be a predictor of prognosis and intervention outcomes. The study shows the importance of measuring perceived health status in MS patients with implications for their quality of life and provision of care.     

End-state comfort and joint configuration variance during reaching

This study joined two approaches to motor control. The first approach comes from cognitive psychology and is based on the idea that goal postures and movements are chosen to satisfy task-specific constraints. The second approach comes from the principle of motor abundance and is based on the idea that control of apparently redundant systems is associated with the creation of multi-element synergies stabilizing important performance variables. The first approach has been tested by relying on psychophysical ratings of comfort. The second approach has been tested by estimating variance along different directions in the space of elemental variables such as joint postures. The two approaches were joined here. Standing subjects performed series of movements in which they brought a hand-held pointer to each of four targets oriented within a frontal plane, close to or far from the body. The subjects were asked to rate the comfort of the final postures, and the variance of their joint configurations during the steady state following pointing was quantified with respect to pointer endpoint position and pointer orientation. The subjects showed consistent patterns of comfort ratings among the targets, and all movements were characterized by multi-joint synergies stabilizing both pointer endpoint position and orientation. Contrary to what was expected, less comfortable postures had higher joint configuration variance than did more comfortable postures without major changes in the synergy indices. Multi-joint synergies stabilized the pointer position and orientation similarly across a range of comfortable/uncomfortable postures. The results are interpreted in terms conducive to the two theoretical frameworks underlying this work, one focusing on comfort ratings reflecting mean postures adopted for different targets and the other focusing on indices of joint configuration variance.     

Envenoming by the viperid snake Proatheris superciliaris: A case report

Snake bites caused by viperid snakes of Atheris genus are extremely rare, envenoming of a bite of related viper Proatheris superciliaris was described only once in the literature. The present case study depicts the envenoming of a 57 years old Czech man, a private herpetologist, who was bitten to his finger. He developed painful local reaction, nausea, hematuria, hypertension, chest and lumbar pain. Coagulopathy and thrombocytopenia subsequently developed as well as acute renal failure, hepatic and lung lesion. Intensive care therapy was purely symptomatic and supportive as no antisera exists. Treatment included haemodialysis, substitution of fresh frozen plasma and platelets. Patient completely recovered during 1 month.     

Partitioned polymerization, 4. Seeded emulsion polymerization of methyl methacrylate

The shape of the conversion curves and the rates of the emulsion polymerization in batch of methyl methacrylate (MMA) in the presence of seed particles of poly(butyl acrylate) (PBA) depend on the mass ratio of methyl methacrylate/poly(butyl acrylate) MMA/PBA and on the presence or absence of 2,2,6,6-tetramethyl-4-octadecanoyloxypiperidinyl-1-oxyl (STMPO). Irrespective of the presence and/or absence of STMPO in the reaction system, the diameter of a polumer particle experimentally found and calculated on the assumption that no new crop of polymer particles is formed, agrees well for systems with “low” (0,632) mass ratio of MMA/PBA. For systems with “high” (3,160) mass ratio of MMA/PBA, the calculated diameter is higher than that experimentally measured. This indicates that for “low” values of MMA/PBA, all poly(methyl methacrylate) formed was only used for building up shells of poly(butyl acrylate) particles. For “high” values of MMA/PBA, about 37 mass-% (in the absence of STMPO) or 57 mass-% (in the presence of STMPO) of poly(methyl methacrylate) formed was used for generating a crop of poly(methyl methacrylate) particles. Retardation of the polymerization rate in the presence of STMPO is more pronounced for systems characterized by a “low” value of the mass ratio MMA/PBA. Only short inhibition periods (up to five minutes) were observed for both “low” and “high” MMA/PBA ratios. It is shown that for the “low” mass ratio of MMA/PBA the “inner” monomer transport (from PBA particles swollen with MMA) to the locus of propagation is decisive. For systems with a “hugh” mass ratio MMA/PBA, the “outer” monomer transport from monomer droplets and micelles swollen by monomer to the locus of propagation is of primary importance. To explain the experimental results a reaction mechanism for the seeded emulsion polymerization is proposed.     

Influence of Antioxidants on the Quality of Stored Blood

Background and objectives: Blood is exposed to oxidation stress and therefore has a high antioxidant capacity (AOC). With the many factors increasing the demands on the AOC, there may be damage to erythrocytes by free radicals. This study was to investigate evidence of erythrocyte damage in stored donor blood and to affect this by premedication of blood donors. Materials and methods: Blood samples of 15 healthy donors were collected in CPDA-1 solution and analyzed immediately, and then again after 10 days of incubation at 4 °C and 1 day of incubation at 37 °C. Prior to incubation, the following parameters were evaluated: Na⁺, K⁺, malondialdehyde (MDA), hemoglobin (Hb), AOC in the supernatant, superoxide dismutase (SOD) in erythrocytes, and glutathione peroxidase (GSHPx) in whole blood. Blood donors of group 1 were not given any drugs or vitamins before blood sampling. The same blood donors were then supplemented with the following daily doses of antioxidants for 10 days before the next blood sampling: 36 mg of β-carotene, 300 mg of vitamin E, 200 mg of vitamin C, and 40 mg of selenium. Results: The blood from donors of group 2 had a significantly smaller increase in MDA, K⁺, and Hb, and a smaller decrease in Na⁺ and AOC in the supernatant compared with that of group 1, while the activity of SOD and GSHPx did not change during blood storage. Conclusions: These results suggest that antioxidants given to blood donors can improve red cell storage parameters by reducing cell damage caused by free radicals.     

Anionic polymerization of 6-hexanelactam, 62. Fast catalytic systems in the anionic polymerization of 6-hexanelactam

With magnesium 6-hexanelactamate bromide (LMgBr) as a catalyst and the N-acyllactam as initiator an exceptionally high rate of polymerization of 6-hexanelactam is observed. Side reactions decreasing the concentrations of growth centres and activated monomer (lactam anion) are not affected to such an extent as to explain this acceleration. In the presence of poly(propylene oxide), the side reactions are largely suppressed with LMgBr. The results corroborate the assumption that the reactivity of the N-acyllactam growth centre is increased by coordination of a magnesium bromide ligand.