The potential antiepileptic activity of astaxanthin in epileptic rats treated with valproic acid

ObjectivesEpilepsy is a neurological disease characterized by sudden, abnormal, and hyper- discharges in the central nervous system (CNS). Valproic acid (VPA) is commonly used as a broad-spectrum antiepileptic therapeutic. However, in many cases, patients develop resistance to VPA treatment due to overwhelming oxidative stress, which in turn might be a major catalyst for disease progression. Therefore, antioxidants can potentially become therapeutic agents by counteracting reactive oxygen species (ROS)-mediated damage. The present study is aimed to evaluate the potential antiepileptic effect of astaxanthin (ASTA) in pentylenetetrazol (PTZ) induced epileptic model rats that are chronically treated with VPA for 8 weeks.MethodFifty-male Wistar rats were randomly divided into five groups: Non-PTZ group, PTZ, PTZ/VPA, PTZ/ASTA, and PTZ/VPA/ASTA treated groups.ResultsPTZ/VPA treated group showed a neuroprotective effect with improvement in antioxidant levels, behavioral test, and histopathological changes induced by PTZ. VPA also exhibited an anti-inflammatory effect as its treatment resulted in the reduction of tumor necrosis factor-α (TNF-α). ASTA exhibited an anticonvulsant effect and enhanced anti-inflammatory effect as compared to VPA. During the combined therapy, ASTA potentiated the antiepileptic effect of the VPA by reducing the oxidative stress and TNF-α as well as increased the glutathione (GSH) levels. Also, there were substantial improvements in the behavioral and histopathological changes in the VPA/ASTA treated group as compared to the VPA treated group.ConclusionASTA could have an antiepileptic and anti-inflammatory effect by reducing ROS generation. Therefore, co-administration of both the therapeutics (VPA/ASTA) has a synergistic effect in treating epilepsy and could potentially minimize recurrence and/or exacerbation of seizures.     

Possible role of angiotensin-converting enzyme polymorphism on progression of hepatic fibrosis in chronic hepatitis C virus infection

Many functional polymorphisms in the rennin-angiotensin system (RAS) have been described; these polymorphisms have been postulated to contribute to fibrosis in several diseases. Our aim was to study the frequency of ACE I/D polymorphism in chronic hepatitis C virus (HCV) infection and its association with liver fibrosis and response to treatment. This study included 90 patients with chronic hepatitis C. All patients received antiviral therapy in the form of pegylated interferon and ribavirin. Patients were grouped according to the stage of liver fibrosis by biopsy into: group 1 (fibrosis: 0 or 1); group 2 (fibrosis: 2 or 3) and group 3 (fibrosis: 4 or 5). The study included also 170 healthy subjects, as a control group. Polymerase chain reaction was carried out to detect the different ACE genotypes. The D/D genotype was significantly more prevalent among HCV patients compared to controls (65.6% vs 48.2%, P = 0.006). Degree of necroinflammation was significantly higher among patients with I/I genotype when compared to patients with D/D genotype (P = 0.04). No significant difference in the distribution of the ACE I/D genotypes between the fibrosis groups and between responders and non responders to interferon therapy. The D/D genotype may increase the susceptibility to infection with hepatitis C.     

Elementary school practices and children's objectively measured physical activity during school

Objective

To examine the relation of physical activity practices covering physical education (PE), recess, and classroom time in elementary schools to children's objectively measured physical activity during school.

Methods

Participants were 172 children from 97 elementary schools in the San Diego, CA and Seattle, WA USA regions recruited in 2009–2010. Children's moderate-to-vigorous physical activity (MVPA) during school was assessed via accelerometry, and school practices were assessed via survey of school informants. Multivariate linear mixed models were adjusted for participant demographics and unstandardized regression coefficients are reported. The 5 practices with the strongest associations with physical activity were combined into an index to investigate additive effects of these practices on children's MVPA.

Results

Providing ≥ 100 min/week of PE (B = 6.7 more min/day; p = .049), having ≤ 75 students/supervisor in recess (B = 6.4 fewer min/day; p = .031), and having a PE teacher (B = 5.8 more min/day; p = .089) were related to children's MVPA during school. Children at schools with 4 of the 5 practices in the index had 20 more min/day of MVPA during school than children at schools with 0 or 1 of the 5 practices (p < .001).

Conclusions

The presence of multiple school physical activity practices doubled children's physical activity during school.     

Synthesis and antitumor activity of novel pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-5-one derivatives

A series of new pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidines with different substituents at position 3 were synthesized. The effect of the newly synthesized compounds was tested in vitro on human breast adenocarcinoma cell line (MCF7). Some of the synthesized compounds exploited potent antitumor activity, especially the 3-amino derivative 12 which displayed the highest activity among the test compounds with IC50 equal to 3.74 μg/mL.     

Early menarche predicts incidence of asthma in early adulthood

The present study explores the effect of age at menarche on the incidence of asthma during early adulthood. The analysis was based on Canadian girls followed up from 8-11 to 18-21 years of age during the first 6 cycles (1994-2005) of the National Longitudinal Survey of Children and Youth. Early menarche was defined as 1 standard deviation less than the average age at menarche. Asthma occurrence after menarche was measured as asthma that was diagnosed by a health care professional. The authors used logistic regression to investigate the association between early menarche and incidence of asthma, adjusting for possible confounders. A total of 1,176 girls weighted to represent 352,345 Canadian girls were analyzed. The incidence of asthma after menarche was 11.2% (95% confidence interval: 8.3, 14.0). The onset of early menarche (<11.56 years of age) predicted postmenarcheal incidence of asthma; girls who matured early had more than twice the risk of developing asthma during early adulthood than did girls who matured at an average age (odds ratio, 2.34, 95% confidence interval: 1.19, 4.59). The present study provides partial insight into the worldwide rapid increase in asthma rates that coincides with the declining trends in menarcheal timing. Further studies within different contexts are warranted to assess the generalizability of these Canadian findings.     

Splenic arteriovenous fistula and portal hypertension. A case report

The authors report a rare case of portal hypertension following to an arteriovenous fistula. The embolisation of the fistula permitted to treat portal hypertension and liver histologic alterations.     

Natural products inhibiting Candida albicans secreted aspartic proteases from Lycopodium cernuum

Activity-guided fractionation of an ethanol extract of Lycopodium cernuum for Candida albicans secreted aspartic proteases (SAP) inhibition resulted in the identification of six new (1-6) and four known (7-10) serratene triterpenes, along with the known apigenin-4'-O-(2' ',6' '-di-O-p-coumaroyl)-beta-D-glucopyranoside (11). On the basis of spectroscopic analysis, the structures of 1-10 were established as 3beta,14alpha,15alpha,21beta,29-pentahydroxyserratane-24-oic acid (lycernuic acid C, 1), 3beta,14alpha,15alpha,21beta-tetrahydroxyserratane-24-oic acid (lycernuic acid D, 2), 3beta,14beta,21beta-trihydroxyserratane-24-oic acid (lycernuic acid E, 3), 3beta,21beta,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone A, 4), 3alpha,21beta,29-trihydroxy-16-oxoserrat-14-en-24-methyl ester (lycernuic ketone B, 5), 3alpha,21beta,24-trihydroxyserrat-14-en-16-one (lycernuic ketone C, 6), 3beta,21beta-dihydroxyserrat-14-en-24-oic acid (lycernuic acid A, 7), 3beta,21beta,29-trihydroxyserrat-14-en-24-oic acid (lycernuic acid B, 8), serrat-14-en-3beta,21beta-diol (9), and serrat-14-en-3beta,21alpha-diol (10). The 13C NMR data for the known compounds 7 and 8 are reported for the first time. Compounds 1 and 11 showed inhibitory effects against C. albicans secreted aspartic proteases (SAP) with IC50 of 20 and 8.5 microg/mL, respectively, while the other compounds were inactive.     

Characterization of Mycotypha metabolites found to be inhibitors of cell adhesion molecules

Three inhibitors of cell adhesion based on LFA-1/ICAM-1 were isolated from the cultured broth of the fungal strain Mycotypha sp. UMF-006. These compounds were identified by spectroscopy to be cytochalasin E (1), 5,6-dehydro-7-hydroxy derivative of cytochalasin E (2) and delta 6,12-isomer of 2 (3). All these components inhibited adhesion of HL-60 cells to CHO-ICAM-1 cells at IC50 values of 30 micrograms/ml for 1, 75 micrograms/ml for 2, and 90 micrograms/ml for 3.