The appropriate neuroimaging study in persons with epilepsy

This article presents the appropriate neuroimaging for persons with epilepsy (PWE) in resource-limited facilities. PWE from the Epilepsy Clinic, Srinagarind Hospital between November 1, 2003 and January 30, 2005 were enrolled. The inclusion criteria were PWE aged more than 15 years who underwent computed tomography (CT) or magnetic resonance imaging (MRI) of the brain. We compared the abnormal neuroimaging findings by both imaging modalities. A total of 180 out of 370 PWE met the inclusion criteria, comprising 101 men (56.1%) and 79 women (43.9%). There were 75 PWE who underwent only CT imagings, 85 PWE who underwent only MRI and 20 PWE who underwent both CT and MRI studies. CT scan significantly detected brain abnormalities more than MRI in PWE (P = 0.0131). It was also found that CT scan was superior than MRI in detecting stroke and cysticercosis in PWE, whereas MRI was significantly better in the diagnosis of hippocampal sclerosis. Clinicians should be able to choose appropriate brain imaging for PWE, particularly in resource-limited countries. MRI should be preserved for particular brain lesion owing to availability and cost effectiveness.     

Risk factors for sexually transmitted diseases in northern Thai adolescents: an audio-computer-assisted self-interview with noninvasive specimen collection

BACKGROUND: Previous studies of sexual behavior and sexually transmitted diseases (STDs) in Thai adolescents may have been limited by participation bias and underreporting of stigmatized behaviors. GOAL: The goal was to increase knowledge about risk behaviors and STDs among youths in Thailand. STUDY DESIGN: Students aged 15 to 21 years completed an audio-computer-assisted self-interview. Oral fluid was tested for HIV antibodies and urine was tested for Chlamydia trachomatis and Neisseria gonorrhoeae nucleic acids with polymerase chain reaction. RESULTS: Of 1736 invited students, 1725 (99.4%) agreed to participate. Overall, C trachomatis infection was detected in 49 (2.8%), and there were five cases (0.3%) each of infection with N gonorrhoeae and HIV. Among those who reported sexual intercourse, the prevalence of chlamydial infection was 3.7% among men and 6.1% among women. Logistic regression analysis showed age-adjusted factors associated with chlamydial infection among men to be parents' occupation in agriculture, having sold sex, having a sex partner who had been pregnant, and the number of casual sex partners during lifetime. Among women, age-adjusted factors were parents' occupation in agriculture, number of casual partners during lifetime, having an older sex partner, and perception of higher HIV infection risk. CONCLUSION: These adolescents had high rates of unprotected intercourse and are at risk for STDs. Prevention programs should emphasize use of effective contraceptive methods, including condom use; reducing the number of sex partners (stressing the risk a partner of older age may pose to female adolescents); and reducing engagement in commercial sex.     

Bidirectional alterations of hippocampal cannabinoid 1 receptors and their endogenous ligands in a rat model of alcohol withdrawal and dependence

BACKGROUND: The hippocampus is strongly implicated in memory processes and contains high concentrations of both cannabinoid receptors and their endogenous ligands. Chronic alcohol consumption impairs a variety of cognitive and performance tasks, including memory and learning. As the activation of cannabinoid receptors by their endogenous ligands modulates hippocampal neurotransmission, we hypothesized that the impaired memory and learning in alcoholism may be due to alterations in the hippocampal endocannabinoid system. METHODS: We used the rat chronic intermittent ethanol (CIE) model for alcohol withdrawal and dependence which involves intermittent episodes of ethanol intoxication (60 doses) and withdrawal (approximating binge drinking episodes in humans). We measured the levels of cannabinoid 1 receptor (CB1R) protein (Western blot using a C-terminal-directed antibody), CB1R mRNA (real-time RT-PCR), CB1R localization (immunocytochemistry), tissue levels of the endocannabinoids N-arachidonoylethanolamine/anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and function (patch-clamp recordings of depolarization-induced suppression of inhibition (DSI), as well as effects of CB1R agonist WIN 55,212-2 on inhibitory currents) in the hippocampus of CIE rats and their saline-treated controls. RESULTS: Results were obtained in saline and CIE-treated rats after 2 and 40 days of withdrawal (DW) from their respective treatments. In 2 DW CIE rats, CB1R mRNA and protein levels were decreased by 27% (p<0.05) compared with saline controls. Surprisingly, in 40 DW CIE rats, CB1R mRNA increased by 100% and protein increased by 21%, confirmed by immunohistochemistry. Hippocampal [2-AG] increased in both 2 and 40 DW CIE rats; [AEA] increased only at 40 DW. Hippocampal DSI of CIE rats was significantly reduced at 2 DW but not at 40 DW. The CB1R agonist WIN 55,212-2 (0.5 microM) produced a significantly greater decrease in the frequency of spontaneous inhibitory currents from saline-treated rats compared with CIE rats at 2 DW, but not at 40 DW. CONCLUSIONS: These data demonstrate that CIE treatment and withdrawal transiently down-regulates hippocampal CB1 Rs followed by a long-term up-regulation, including increased levels of endogenous cannabinoids. These findings are consistent with our hypothesis and suggest that long-term up-regulation of hippocampal CB1Rs may contribute to the long-term cognitive impairments in alcoholism. The data further suggest that the effectiveness of CB1R blockade in decreasing alcohol consumption may be greater after protracted abstinence from alcohol.     

Meteorin is a chemokinetic factor in neuroblast migration and promotes stroke-induced striatal neurogenesis

Ischemic stroke affecting the adult brain causes increased progenitor proliferation in the subventricular zone (SVZ) and generation of neuroblasts, which migrate into the damaged striatum and differentiate to mature neurons. Meteorin (METRN), a newly discovered neurotrophic factor, is highly expressed in neural progenitor cells and immature neurons during development, suggesting that it may be involved in neurogenesis. Here, we show that METRN promotes migration of neuroblasts from SVZ explants of postnatal rats and stroke-subjected adult rats via a chemokinetic mechanism, and reduces N-methyl-D-asparate-induced apoptotic cell death in SVZ cells in vitro. Stroke induced by middle cerebral artery occlusion upregulates the expression of endogenous METRN in cells with neuronal phenotype in striatum. Recombinant METRN infused into the stroke-damaged brain stimulates cell proliferation in SVZ, promotes neuroblast migration, and increases the number of immature and mature neurons in the ischemic striatum. Our findings identify METRN as a new factor promoting neurogenesis both in vitro and in vivo by multiple mechanisms. Further work will be needed to translate METRN's actions on endogenous neurogenesis into improved recovery after stroke.     

Anti‐HIV‐1 Integrase Activity and Molecular Docking Study of Compounds from Caesalpinia sappan L.

Caesalpinia sappan L. (Caesalpiniaceae) has been traditionally used as blood tonic, expectorant, and astringent by boiling with water. Searching for HIV‐1 integrase (IN) inhibitors from this plant is a promising approach. The EtOH extract of C. sappan and its isolated compounds were tested for their anti‐HIV‐1 IN effect using the multiplate integration assay, and the active compounds were determined for their mechanisms by molecular docking technique. Extraction from the heartwoods and roots of C. sappan led to the isolation of nine compounds. Among the compounds tested, sappanchalcone (2) displayed the strongest effect against HIV‐1 IN with an IC₅₀ value of 2.3 μM followed by protosappanin A (9, IC₅₀ = 12.6 μM). Structure‐activity relationships of compounds from C. sappan were found, in which the vicinal hydroxyl moiety were essential for anti‐HIV‐1 IN effect of compounds 2 and 9 by binding with the amino acid residues Gln148 and Thr66 in the core domain of the HIV‐ 1 IN enzyme, respectively. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis and cytotoxicity of novel 4-(4-(substituted)-1H-1,2,3-triazol-1-yl)-N-phenethylbenzenesulfonamides

A new series of 4-(4-(substituted)-1H-1,2,3-triazol-1-yl)-N-phenethylbenzenesulfonamide derivatives 5 were synthesized through the Click approach and evaluated for their cytotoxic activity against four cancer cell lines (HuCCA-1, HepG2, A549, and MOLT-3). Most of the synthesized triazoles 5 displayed cytotoxicity against MOLT-3 cell line, except for analogs 5a–c and 5e. Significantly, 4-phenyltriazoles (5a and 5n), 4-(naphthalen-2-yloxy)methyltriazole 5d, as well as 4-((2-oxo-2H-chromen-7-yl)oxy)methyltriazole 5l showed higher cytotoxic activity against HepG2 cells than the reference drug, etoposide. Interestingly, the 4-phenyltriazole 5a was the most potent and promising compound with IC₅₀ value of 9.07 μM against HepG2 cell line. The analog 5a also exerted the highest cytotoxic activity against HuCCA-1 cells. This finding provides the novel lead molecules for further development.     

Transformation of temporomandibular joint disc configuration in internal derangement patients using magnetic resonance imaging

PurposeThe normal disc configuration is biconcave; however, the deformed disc can be found in internal derangement (ID) of the temporomandibular joint (TMJ). The purpose of this study was to evaluate the relationship between the transformation patterns of TMJ disc configuration during mouth opening and disc displacement status, disc reduction ability and TMJ clinical symptoms.MethodsTMJ MR images from volunteers and ID patients were analyzed for closed and open mouth positions. MR images of ID patients were classified into 4 groups: symptomatic joint with anterior disc displacement with or without reduction (ADW or ADWo) and asymptomatic joint with ADW or ADWo. The disc configurations in both positions were categorized as biconcave, biplanar, convex or folded; then the patterns of transformation were observed.ResultsFor the ADW group, the most common disc configuration for closed and open mouth positions were biplanar (66.7%) and biconcave (86.3%). The transformation pattern was significantly related to disc reduction ability (p < 0.05).ConclusionsThe transformation patterns of disc configuration during opening were related to anterior disc displacement and disc reduction ability.     

Transcranial Direct Current Stimulation for Treatment of Refractory Childhood Focal Epilepsy

BackgroundCathodal transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation method for suppressing regional cortical excitability. We examine the safety and antiepileptic efficacy of cathodal tDCS in children with refractory focal epilepsy. Although a prior cathodal tDCS trial in adults with epilepsy revealed EEG improvement, neither the antiepileptic potential nor the safety and tolerability of tDCS has been tested in children.MethodThe study consisted of three phases: 1) a 4-week pre-treatment monitoring period with vital sign measures, EEG, seizure diary, and baseline quality of life (QOL) questionnaire; 2) a single treatment with 1 mA cathodal tDCS for 20 min with cathode positioned over the seizure focus and anode on the contralateral shoulder; 3) follow-ups immediately after stimulation, and at 24, 48 h, and 4 weeks after tDCS with continued seizure diary and epileptic discharge counts on EEG; the QOL questionnaire was also repeated 4 weeks after stimulation. Patients were randomized to receive either single session active or sham tDCS 1 mA, 20 min.ResultsThirty six children (6–15 years) with focal epilepsy were enrolled, 27 in active and 9 in sham group. All patients tolerated tDCS well. No serious adverse events occurred. Active tDCS treatment was associated with significant reductions in epileptic discharge frequency immediately and 24 and 48 h after tDCS. Four weeks after treatment, a small (clinically negligible but statistically significant) decrease in seizure frequency was also detected.ConclusionA single session of cathodal tDCS improves epileptic EEG abnormalities for 48 h and is well-tolerated in children.