Homocysteine, folic acid and vitamin B12 levels in serum of epileptic children

The relationship between increased homocysteine (Hcy) level and epileptic seizure remains controversial in human, despite a growing evidence of the pro-convulsive effect of the hyperhomocysteinemia (HHcy) observed in the animal studies. The mechanism of this association with epileptogenesis has not been clearly understood, although there is emerging evidence to support the unfavorable effects of some anti-epileptic drugs (AEDs) on the plasma homocysteine (Hcy) concentrations. The aim of this study was to uncover the relationship between the levels of homocysteine (Hcy), the cofactors involved in its metabolism as folic acid and vitamin B12 and anti-epileptic drugs (AEDs) in epileptic patients. Serum level of homocysteine (Hcy), folic acid and vitamin B12 was measured in 60 patients with idiopathic epilepsy; and its level was compared to 30 healthy children serving as control group. No significant difference was found regarding the plasma homocysteine (Hcy) levels between patients (both receiving anti-epileptics and non anti-epileptic drug users) and controls. Epileptic patients on polytherapy showed higher mean serum levels of homocysteine (Hcy) and lower mean serum levels of folic acid compared to those on monotherapy. However, the mean serum levels of homocysteine (Hcy), vitamin B12 and folic acid showed non significant differences between patients using valproic acid (VPA) or carbamazepine (CBZ). Duration of AED therapy showed a significant positive correlation with mean serum levels of homocysteine (Hcy) and a significant negative correlation with mean serum levels of folic acid. To conclude; AEDs upset the homeostatic balance of homocysteine (Hcy) and its cofactors and cause abnormalities in their serum levels.Keywords: Homocysteine; Epilepsy; Folic acid; Vitamin B12; Anti-epileptic dru

Josephson effects in MgB2 meta masked ion damage junctions

Ion beam damage combined with nanoscale focused ion beam direct milling was used to create manufacturable SNS type Josephson junctions in 100 nm thick MgB$_{2}$ with T$_{C}$ of 38 K. The junctions show non-hysteretic current - voltage characteristics between 36 and 4.2 K. Experimental evidence for the dc and ac Josephson effects in MgB$_{2}$ metal masked ion damage junctions are presented. This technique is particularly useful for prototyping devices due to its simplicity and flexibility of fabrication and has a great potential for high-density integration.Comment: 12 pages, 4 figures, RevTeX4, submitted to AP

Multiple molecular markers MAGE-1, MAGE-3 and AFP mRNAs expression nested PCR assay for sensitive and specific detection of circulating hepatoma cells: Enhanced detection of hepatocellular carcinoma

Hepatocellular Carcinoma is a multifactorial, multistep and complex process. Its prognosis is poor and early diagnosis and monitoring of metastasis of HCC is of utmost importance. Circulating alpha-fetoprotien mRNA has been proposed as a marker of HCC cells disseminatedinto the circulation but the specificity of this molecular marker and its correlation with the main HCC clinico-pathological parameters remain controversial. In recent years; several different multi-marker assays have been developed for the detection of hepatoma cells in the peripheral bloodof patients with HCC. In this study 58 patients and 15 matched healthy volunteers were included; the patients were divided into three groups; group A: patients with primary HCC (n =32), group B: patients withcirrhosis with no evidence of HCC (n= 12), group C: patients with metastatic cancer in liver (n= 14). Group D: 15 healthy volunteers age and sex matched. The staging of HCC was carried out according to the Tumor/Node/Metastasis (TNM) classification. Peripheral blood samples were obtained from all subjects; MAGE-1 and MAGE-3 and AFP mRNAs were detected by nested RT-PCR. The positive rates of MAGE-1, MAGE-3 and AFP mRNAs were 18/32 (56.3%), 15/32 (46.9%) and 19/32 (59.4%) respectively in the primary HCC patients. In the cirrhotic group only 4/12 (33.3%) patients were positive for AFP mRNA, whereas in the metastatic group 5/14 (35.7%) and 4/14 (28.6%) were positive to MAGE-1 and MAGE-3 mRNAs respectively. MAGE-1 and MAGE-3 mRNAs were correlated with TNM clinical stages; tumor number and tumor size (p<0.05).Our results indicate that a multi-marker nested RT-PCR assay with cancer-specific markers such as MAGE-1 and MAGE-3 in combination with a hepatocyte-specific AFP marker may be a promising diagnostic tool for monitoring hepatocellular carcinoma patients. Nested PCR exhibits highersensitivity, stronger specificity and lower false-positive occurrence as compared to single RT

Age-Related Differences in Susceptibility to Carcinogenesis. II. Approaches for Application and Uncertainty Analyses for Individual Genetically Acting Carcinogens

In an earlier report we developed a quantitative likelihood-based analysis of the differences in sensitivity of rodents to mutagenic carcinogens across three life stages (fetal, birth to weaning, and weaning to 60 days) relative to exposures in adult life. Here we draw implications for assessing human risks for full lifetime exposures, taking into account three types of uncertainties in making projections from the rodent data: uncertainty in the central estimates of the life-stage–specific sensitivity factors estimated earlier, uncertainty from chemical-to-chemical differences in life-stage–specific sensitivities for carcinogenesis, and uncertainty in the mapping of rodent life stages to human ages/exposure periods. Among the uncertainties analyzed, the mapping of rodent life stages to human ages/exposure periods is most important quantitatively (a range of several-fold in estimates of the duration of the human equivalent of the highest sensitivity “birth to weaning” period in rodents). The combined effects of these uncertainties are estimated with Monte Carlo analyses. Overall, the estimated population arithmetic mean risk from lifetime exposures at a constant milligrams per kilogram body weight level to a generic mutagenic carcinogen is about 2.8-fold larger than expected from adult-only exposure with 5–95% confidence limits of 1.5-to 6-fold. The mean estimates for the 0- to 2-year and 2- to 15-year periods are about 35–55% larger than the 10- and 3-fold sensitivity factor adjustments recently proposed by the U.S. Environmental Protection Agency. The present results are based on data for only nine chemicals, including five mutagens. Risk inferences will be altered as data become available for other chemicals

Pathotypic diversity of Hyaloperonospora brassicae collected from Brassica oleracea

Downy mildew caused by Hyaloperonospora brassicae is an economically destructive disease of brassica crops in many growing regions throughout the world. Specialised pathogenicity of downy mildews from different Brassica species and closely related ornamental or wild relatives has been described from host range studies. Pathotypic variation amongst Hyaloperonospora brassicae isolates from Brassica oleracea has also been described; however, a standard set of B. oleracea lines that could enable reproducible classification of H. brassicae pathotypes was poorly developed. For this purpose, we examined the use of eight genetically refined host lines derived from our previous collaborative work on downy mildew resistance as a differential set to characterise pathotypes in the European population of H. brassicae. Interaction phenotypes for each combination of isolate and host line were assessed following drop inoculation of cotyledons and a spectrum of seven phenotypes was observed based on the level of sporulation on cotyledons and visible host responses. Two host lines were resistant or moderately resistant to the entire collection of isolates, and another was universally susceptible. Five lines showed differential responses to the H. brassicae isolates. A minimum of six pathotypes and five major effect resistance genes are proposed to explain all of the observed interaction phenotypes. The B. oleracea lines from this study can be useful for monitoring pathotype frequencies in H. brassicae populations in the same or other vegetable growing regions, and to assess the potential durability of disease control from different combinations of the predicted downy mildew resistance genes

Seiberg-Witten prepotential for E-string theory and global symmetries

We obtain Nekrasov-type expressions for the Seiberg-Witten prepotential for the six-dimensional (1,0) supersymmetric E-string theory compactified on T^2 with nontrivial Wilson lines. We consider compactification with four general Wilson line parameters, which partially break the E_8 global symmetry. In particular, we investigate in detail the cases where the Lie algebra of the unbroken global symmetry is E_n + A_{8-n} with n=8,7,6,5 or D_8. All our Nekrasov-type expressions can be viewed as special cases of the elliptic analogue of the Nekrasov partition function for the SU(N) gauge theory with N_f=2N flavors. We also present a new expression for the Seiberg-Witten curve for the E-string theory with four Wilson line parameters, clarifying the connection between the E-string theory and the SU(2) Seiberg-Witten theory with N_f=4 flavors.Comment: 22 pages. v2: comments and a reference added, version to appear in JHE

Antralization at the edge of proximal gastric ulcers: Does Helicobacter pylori infection play a role?

Aim: To determine the prevalence of antralization at the edge of proximal gastric ulcers, and the effect of H. pylori eradication on the mucosal appearances. Methods: Biopsies were taken from the antrum, body and the ulcer edge of patients with benign proximal gastric ulcers before and one year after treatment. Gastric mucosa was classified as antral, transitional or body type. H. pylori positive patients received either triple therapy, or omeprazole. Results: Patients with index ulcers in the incisura, body or fundus (n=116) were analyzed. Antral-type mucosa was more prevalent at the ulcer edge in H. pylori-positive patients than H. pylori-negative patients (93 % vs 60 %, OR=8.95, 95 %CI: 2.47-32.4, P=0.001). At one year, there was a significant reduction in the prevalence of antralization (from 93 % to 61 %, P=0.004) at the ulcer edge in patients with H. pylori being eradicated. However, there was no difference in the prevalence of antralization at the ulcer edge in those with persistent infection. Conclusion: H. pylori infection is associated with antralization at the edge of proximal gastric ulcers, which may be reversible in some patients after eradication of the infection.published_or_final_versio

Can We “Hedge” against the Development of Antiviral Resistance among Pandemic Influenza Viruses?

David K. Shay and Benjamin Ridenhour discuss a modeling study predicting that stockpiling a secondary antiviral for use early in a flu pandemic can forestall resistance to the primary stockpiled drug

The time-dependent rearrangement of the epithelial basement membrane in human skin wounds

In 62 human skin wounds (surgical wounds, stab wounds and lacerations after surgical treatment) we analyzed the immunohistochemical localization of collagen IV in the epithelial basement membrane. In 27 of these wounds the distribution of collagen VII, which represents a specific component of the basement membrane of stratified epithelia, was also analyzed. We were able to demonstrate a virtually identical co-distribution of both collagen IV and VII in the wound area with no significant time-dependent differences in the appearance of both collagen types. Fragments of the epithelial basement membrane could be detected in the wound area from as early as 4 days after wounding and after 8 days a complete restitution of the epithelial basement membrane was observed. In all cases with a wound age of more than 21 days the basement membrane was completely reformed over the former lesional area. The period between 8 and 21 days after wounding was characterized by a wide variability ranging from complete restitution to deposition of basement membrane fragments or total lack of the epidermal basement membrane