Medical Sector

Background: Hepatitis C virus (HCV) infection is a well-documented etiological factor for hepatocellular carcinoma (HCC). As HCV shows remarkable genetic diversity, an interesting and important issue is whether such a high viral genetic diversity plays a role in the incidence of HCC. Prior data on this subject are conflicting.

This study aims at evaluating the deformation changes on three types of root canal rotary instruments with different designs; the Pro-Taper Universal, the V-Taper, and the Liberator systems after clinical use.

Background$ Pneumonia is the most common cause of community-acquired infection requiring ICU admission'/+&U/ S/VHU/of patients with severe community acquired pneumonia; CAPD/admitted to the ICU develops respiratory failure and require mechanical ventilation ;MVD'/Objectives$ To assess the efficacy and safety of adjunctive low dose hydrocortisone infusion treatment in Egyptian ICU patients with CAP' Methods$ Hospitalized patientsK clinically and radiologically diagnosed with CAPK were randomized to receive hydrocortisone %)'W mg,h IV infusion for H/days or placeboK/along with antibiotics' The end-points of the study were improvement in PaO)$FIO) ;PaO)$FIO)/X/*&&/":/!%&& increase from study entryD and SOFA score by study day V and the development of delayed septic shock' Results$/V& patients were recruitedK/ (& of them received hydrocortisone and the remaining (& received placebo' By study day VK hydrocortisone treated patients showed a significant improvement in PaO)$FIO) and chest radiograph scoreK and a significant reduction in C-reactive protein ;CRPD levelsK Sepsis-related Organ Failure Assessment ;SOFAD/ scoreK and

Introduction: Treatment with fixed orthodontic appliances in the corrosive environment of the oral cavity warrants in-vivo investigations of biocompatibility.

Background: To investigate the prevalence of cumulative organ damage among Egyptian children with juvenileonset systemic lupus erythematosus (jSLE) and the relationships between the organ damage and the demographic data, clinical variables, and disease activity.

Objective: To investigate daptomycin pharmacokinetics in critically ill patients receiving continuous venovenous hemodialysis to develop dosing recommendations.

The receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of RA through its ability to amplify inflammatory pathways. Aims of the work: (1) To evaluate the levels of soluble receptors of advanced glycated end products (sRAGE) as well as the gene variant among patients with rheumatoid arthritis (RA). (2) To assess the association between the sRAGE level and the RAGE gene variants and to correlate the findings.

The ciliopathy Joubert syndrome is marked by cerebellar vermis hypoplasia, a phenotype for which the pathogenic mechanism is unclear. To investigate Joubert syndrome pathogenesis, we have examined mice with mutated Ahi1, the first identified Joubert syndrome-associated gene. These mice show cerebellar hypoplasia with a vermis-midline fusion defect early in development. This defect is concomitant with expansion of the roof plate and is also evident in a mouse mutant for another Joubert syndrome-associated gene, Cep290. Furthermore, fetal magnetic resonance imaging (MRI) of human subjects with Joubert syndrome reveals a similar midline cleft, suggesting parallel pathogenic mechanisms. Previous evidence has suggested a role for Jouberin (Jbn), the protein encoded by Ahi1, in canonical Wnt signaling. Consistent with this, we found decreased Wnt reporter activity at the site of hemisphere fusion in the developing cerebellum of Ahi1-mutant mice. This decrease was accompanied by reduced proliferation at the site of fusion. Finally, treatment with lithium, a Wnt pathway agonist, partially rescued this phenotype. Our findings implicate a defect in Wnt signaling in the cerebellar midline phenotype seen in Joubert syndrome that can be overcome with Wnt stimulation.

Acridine and quinazoline derivatives represent important classes for the treatment of cancer. Many derivatives of them found to be tyrosine kinase inhibitors. In this work novel eight acridine-4-carboxamide and acridine-4- carboxylate derivatives were synthesized from quinazoline and acridine scaffolds. Six of the newly synthesized compounds were chosen by NCI for screening as anticancer. The activity of six compounds (8a-d, 9a and 9d) was tested using the national cancer institute NCI disease oriented antitumor screen protocol. Compound 8c was proved to be the most active member in this study. This acridine analog 8c could be considered as useful template for further development to obtain more potent antitumor agents. [Gehan H.Hegazy, Maha S. Almutairi, Ebtehal S. Al Abdullah. Design and Synthesis of Acridine-4-Carboxamide and Acridine-4- Carboxylate Derivatives as Tyrosine Kinase Inhibitors.

Design and synthesis of some pyrazole derivatives 4-11 of expected anti-inflammatory and analgesic activities. In addition, docking of the tested compounds into cycloxygenase II using (MOE) was performed in order to rationalize the obtained biological results and their mechanism of action. The structures of the new compounds were elucidated by spectral and elemental analyses. All the new synthesized compounds were evaluated for their anti-inflammatory activity using the carrageenan-induced rat paw oedema method. Analgesic activity of the target compounds was measured using the p-benzoquinone writhing induced method and their ability to induce gastric toxicity was also evaluated. Results showed that the new synthesized compounds exhibited weak to good activities compared to ibuprofen and celecoxib as reference drugs. Some compounds, such 4a and 11b exhibited significant anti-inflammatory activity with gastric ulcerogenic potential less than that of ibuprofen. Analgesic activity' results showed that compounds possessing good anti-inflammatory activity showed also good analgesic. Substitution of pyrazole ring with at least one aryl moiety was found to be essential for anti-inflammatory and analgesic activities. Free NH (of pyrazole ring) and/or acidic group (COOH) will improve the anti-inflammatory activity.

A series of 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine cyclin-dependent kinase (CDK2) inhibitors is designed and synthesized. 6-Amino-2-thiouracil is reacted with an aldehyde and thiourea to prepare the pyrimido[4,5-d]-pyrimidines. Alkylation and amination of the latter ones give different amino derivatives. These compounds show potent and selective CDK inhibitory activities and inhibit in vitro cellular proliferation in cultured human tumor cells.

A number of 2-substituted and 2,3-disubstitutedquinazolinone analogues have been synthesized. Their structures have been elucidated on the basis of elemental analyses and spectroscopic studies (IR, 1H NMR, and MS). An evaluation of the anticonvulsant activity of the prepared compounds has indicated that some of them exhibit moderate to significant activity, compared to diazepam and phenobarbital standards.

Two series of novel non acidic 3, 5-diarylpyrazoline and 3, 5-diarylisoxazoline derivatives were designed to be synthesized and screened for anti-inflammatory and analgesic activities. In addition, molecular modelling and docking of the designed compounds into cyclooxygenase II (COX-II) using Molsoft ICM 3.4-8C program was performed in order to predict the affinity and orientation of the designed compounds at the active site compared with its binding inhibitor celecoxib. The ICM score values show good agreement with predicted binding affinities,

A hexane extract of the flower-heads of Euryops pectinatus L. (Cass.) was formulated into local anti-inflammatory implantation patches with controlled release. Cross-linked sodium hyaluronate patches (F1-F3) and chitosan patches (F4-F6) were prepared by a casting/solvent evaporation technique. Morphological and mechanical characterizations including the components ratio, surfactant and the loaded amount of the hexane extract (50, 100, and 200 mg/kg b.wt.) were investigated. Release studies were performed during 24 h using a diffusion cell. Films with optimum in vitro release rate have been investigated for testing the anti-inflammatory activity and the sustaining effect of the formulations. The sustained anti-inflammatory effect of the hexane extract of E. pectinatus flower-heads from the selected films was studied by inducing paw edema in rats with 1% (w/v) carrageenan solution. The results indicated the compatibility of hexane extract with both sodium hyaluronate and chitosan patches forming yellowish transparent films. Based on variations in drug release profiles throughout the 24-h among the formulations (F1-F6) studies, F3 and F6 were selected for further investigation. When the films were applied 1 h before the subplantar injection of carrageenan in the hind paw of male Albino rats, formulation (F3) provided its maximum inhibition of paw edema in rats (91.3%) 4 h after edema induction whereas, formulation (F6) showed less inhibition after 4 h (70.6%). The previous two formulations (F3 and F6) produced potent results (95.3 and 89.5%, respectively) after 24 h when compared with a local market preparation containing 25% ?-sitosterol used as positive control. Histophathological investigation was conducted for 1, 4, and 12 weeks to study the tissue response for the two formulations (F3 and F6) at the implantation site. Chemical investigation of the hexane extract was achieved for both unsaponifiable matter (USM) and fatty acid methyl esters (FAME) using gas liquid chromatography (GLC). The USM was dominated by n-pentacosane (14.40%), phytosterols (Cholesterol, Campesterol, Stigmasterol, ?-sitosterol, ?-amyrin) reached 33.44% and the FAME was dominated by Linoleinic (49.97%). Quality control of the local implantation was evaluated by GLC using cholesterol as an analytical marker and phytosterols as an active marker compared to the plain extract.

Sustained release matrix pellets of the freely water soluble drug, betahistine dihydrochloride (BH), were prepared using freeze pelletization technique. Different waxes and lipids (cetyl alcohol, beeswax, glyceryl tripalmitate (GTP) and glyceryl tristearate) were evaluated for the preparation of matrix pellets. A D-optimal design was employed for the optimization and to explore the effect of drug loading (X1), concentration of lipophilic surfactant (X2), concentration of co-surfactant (X3) and wax type (X4) on the release extent of the drug from matrix pellets. The entrapment efficiency (Y1), pellet diameter (Y2), and the percentage drug released at given times were selected as dependent variables. Results revealed a significant impact of all independent variables on drug release from the formulated pellets. The lipophilic surfactant significantly increased both the entrapment efficiency and the in vitro drug release and significantly decreased the pellet size. The optimized BH-loaded pellets were composed of 19.95% drug loading, 9.95% Span® 80 (surfactant), 0.25% Capmul® (co-surfactant) using glyceryl tripalmitate as a matrix former. The release profiles of the drug from hard gelatin capsule containing optimized pellets equivalent to 32 mg BH was similar to that of target release model for once-daily administration based on similarity factor. It could be concluded that a promising once-daily capsule containing sustained release pellets of BH was successfully designed.