DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NEW SUCCINIMIDE, 2-IMINOTHIAZOLINE AND OXAZINE DERIVATIVES BASED BENZOPYRONE AS ANTICONVULSANT AGENTS

Objective: The objective of the present study was to synthesize novel benzopyrone derivatives with potential and safer anticonvulsant activity.Methods: New benzopyrone derivatives have been synthesized and characterized by spectral and elemental analysis. These compounds tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens (phase 1), which are the most widely employed seizure models for early identification of new anticonvulsant agents. Phase 2 including, neurotoxicity screening and quantitative determination of the median effective dose (ED50), median lethal dose (LD50) and protective index (PI) for the active compounds from phase 1.Results: Compound 12b possessed potent anticonvulsant activity with ED50 values of 94.75 and 70.7 mg/kg in the MES and scPTZ screens respectively, and had LD50 value of 2546 mg/kg after intraperitoneal injection to mice, which provide compound 12b with a wide protective index of 26.87 and 36.01 for MES and scPTZ screens respectively compared to the reference drug Phenobarbital with PI of 12.16 and 20.08, respectively. In addition, compound 12b exhibited mild neurotoxicity at the maximum administrated dose (200 mg/kg).Conclusion: Compound 12b possessed broad spectrum activity for the treatment of all types of seizures, with a wide protective index compared to Phenobarbital. Consequently, compound 12b can be selected as a new bio candidate lead for further study.Keywords: Benzopyrone, Succinimide, 2-Iminothiazoline, Oxazine; Anticonvulsant

Why do consumers trust online travel websites? Drivers and outcomes of consumer trust toward online travel websites

Egypt is currently one of the leading nations especially in the Middle East region with a well-established e-commerce environment and advanced IT infrastructure, but rapid growth of e-commerce will soon occur in other nations with similar consumption patterns. This study tests a model of antecedents (consumer experience, propensity to trust, reputation, perceived website size, ease of use, perceived usefulness, and website quality) and consequences of consumers’ trust toward online travel websites. Trust is expected to predict consumer attitude, perceived risk, and intention to purchase travel online. Data of 1,431 users of online travel websites were selected from the Supreme Council of Universities Database–Egypt (SCU) and analyzed through structural equation modeling. The findings show that all the aforementioned factors with the exception of consumer experience influence consumer trust toward online travel websites. Trust influences consumers’ attitude, perceived risk, and intention to purchase travel online

The Rose Bengal Test in Human Brucellosis: A Neglected Test for the Diagnosis of a Neglected Disease

Brucellosis is a highly contagious zoonosis affecting livestock and human beings. The human disease lacks pathognomonic symptoms and laboratory tests are essential for its diagnosis. However, most tests are difficult to implement in the areas and countries were brucellosis is endemic. Here, we compared the simple and cheap Rose Bengal Test (RBT) with serum agglutination, Coombs, competitive ELISA, Brucellacapt, lateral flow immunochromatography for IgM and IgG detection and immunoprecipitation with Brucella proteins. We tested 208 sera from patients with brucellosis proved by bacteriological isolation, 20 contacts with no brucellosis, and 1559 sera of persons with no recent contact or brucellosis symptoms. RBT was highly sensitive in acute and long evolution brucellosis cases and this related to its ability to detect IgM, IgG and IgA, to the absence of prozones, and to the agglutinating activity of blocking IgA at the pH of the test. RBT was also highly specific in the sera of persons with no contact with Brucella. No test in this study outperformed RBT, and none was fully satisfactory in distinguishing contacts from infected patients. When modified to test serum dilutions, a diagnostic titer >4 in RBT resulted in 87.4% sensitivity (infected patients) and 100% specificity (contacts). We discuss the limitations of serological tests in the diagnosis of human brucellosis, particularly in the more chronic forms, and conclude that simplicity and affordability of RBT make it close to the ideal test for small and understaffed hospitals and laboratories

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD

Microbiome to Brain:Unravelling the Multidirectional Axes of Communication

The gut microbiome plays a crucial role in host physiology. Disruption of its community structure and function can have wide-ranging effects making it critical to understand exactly how the interactive dialogue between the host and its microbiota is regulated to maintain homeostasis. An array of multidirectional signalling molecules is clearly involved in the host-microbiome communication. This interactive signalling not only impacts the gastrointestinal tract, where the majority of microbiota resides, but also extends to affect other host systems including the brain and liver as well as the microbiome itself. Understanding the mechanistic principles of this inter-kingdom signalling is fundamental to unravelling how our supraorganism function to maintain wellbeing, subsequently opening up new avenues for microbiome manipulation to favour desirable mental health outcome