Preprocesamiento de los fármacos antivirales candidatos contra COVID-19 en modelos de SARS cov2. Objetivos / Preprocessing of the candidate antiviral drugs against COVID-19 in models of SARS cov2 targets

Although many viral infections are self-limiting, other are real health challenges like COVID-19 since many viruses possess just few drug gable targets to be treated with small drug molecules. Corona virus genome encodes for up to 17 main proteins. Orf1ab encodes for polyprotein. COVID-19 structural proteins are the spike S, membrane M, envelope E and the nucleocapsid N protein while other are non-structural proteins designated as NSP1-13 for non-structural proteins. Among NSP the most important corona virus targets for developing antiviral drugs are the papain-like protease, PDB ID: 6m03 and RNA polymerase NSP12, PDB ID: 6nur. NCBI, NIH Genbank, Uniprot, PDB, DrugBank, ChemSpider databases and bioinformatics editor softwares like ICM Mol soft pro and Swiss Dock were used in addition to the in vitro lab model of viral protease were integrated to retrieve and analyze corona virus targets and to select the candidate ligands in an attempt to evaluate the inhibitory efficacy of different experimental and approved drugs which were further optimized and searched for the highly similar approved drug. This step aims to adopt drug repurposing to speed the development of antiviral drugs and recommend rational in vivo and clinical studies. After COVID-19 targets had been analyzed the drugs that shared > 70% similarity to the binding sites of those targets were reversin, pentagastrin, remdesivir, norfloxacin and nitazoxanide against COVID-19 papain-like protease whereas benzyl glutathione, lopinavir and hydroxymethylglutathione against RNA polymerase. The anti-resistance reversin showed the highest inhibitory efficacy against COVID-19 papain-like protease as indicated by the ligand-protease binding energy with Mol soft pro analysis. The calculated inhibitory binding was -137.30 kJ/mol z > 1.9 as compared with the tetrazapentadecanoate -129.57 kJ/mol z = 4.0, whereas remdesivir, pentagastrin, nitazoxanide and norfloxacin had a moderate antiprotease activity (>- 100 kJ/mol). Norfloxacin shoresults showed a slight consistency between in vitro and in silico models. Although benzyl glutathione is an experimental compound, however it had the highest RNA polymerase inhibiting efficacy with -129 kJ/mol binding energy which is even higher than lopinavir and Favinavir. From the overall results, reversin, oligopeptides, quinolones and antiviral drugs may widen the treatment options for COVID-19 if further evaluated in clinical studies

Combinación de bardoxolona y DMF Mejora la isquemia cerebral/reperfusión Lesión en ratas macho / Combination of Bardoxolone and DMF Ameliorates Cerebral Ischemia / Reperfusion Injury in Male Rats

Background: Ischemic stroke has been ranked as the second cause of death in patients worldwide. Inflammation which is activated during cerebral ischemia/reperfusion (I/R) is an important mechanism leading to brain injury. The present study aimed to investigate the effect of Berberine on cerebral I/R injury and the role of inflammation in this process. Material and Methods: The study was carried out on 36 Wistar-albino rats, divided into four groups including: Sham group, I/R group, I/R+ (control-vehicle DMSO) and I/R+ Berberine 5 mg/kg injected intraperitoneally 1 hour before induction of ischemia. Measurement of brain tissue IL-1ß, ICAM1, caspase-3, Notch 1 and Jagged 1 was done after one hour of reperfusion in addition to assessment of the brain infracted area and histopathological analysis. Results: Berberine attenuates cerebral I/R injury induced increase in inflammatory cytokine (IL-1ß), adhesion molecule (ICAM-1) and proapoptotic enzyme (caspase-3). Additionally, it reduces the size of infracted area and histopathological damage; such protective effect could be mediated by Notch 1 signaling pathway since Berberine further unregulated the increased levels of Notch 1 and Jagged 1 seen in brain with I/R injury. Conclusions: Berberine has a neurocytoprotective outcome against cerebral I/R injury which is manifested as anti-inflammatory anti-apoptotic effect that preserved cell structure and viability, in the meantime this effect could be mediated by Notch 1 signaling pathway.

Cytomegalovirus colitis masquerading as rectal malignancy in an immunocompetent patient.

Gastrointestinal tract (GIT) involvement by cytomegalovirus (CMV) infection is well-recognized in immunosuppressed patients but is uncommon in immunocompetent hosts. The colon and esophagus are the most frequently affected sites with punched out ulcers being the characteristic mucosal lesion. CMV-induced pseudotumor is an exceptionally rare presentation, especially in immunocompetent hosts. A 76-year-old immunocompetent female presented with abdominal pain and constipation. Colonoscopy revealed an ulcerated polypoidal tumor-like mass in the anorectal region. Biopsy of the lesion showed large basophilic intranuclear inclusions which were positive for CMV on immunohistochemical staining. The patient responded to 2 weeks of antiviral therapy with complete resolution of the mass. Although rare, pseudotumors associated with CMV infection should be considered in the differential diagnosis of tumorous lesions of the GIT.

Improve Markers of Oxidative Stress and Coagulation Parameters in Response to Atorvastatin Therapy.

Aims: This study was undertaken to investigate the antioxidant effects of atorvastatin in treating cases of atherosclerosis associated with hyperlipidemia. Methodology: Forty local domestic rabbits were assigned to five groups (eight rabbits in each group): After two weeks acclimatization period, a group of 8 rabbits (Group I) were used as the baseline values of the study parameters. Another 8 rabbits were selected and maintained on standard chow diet (4% fat, 18% protein, 60% carbohydrate, and 4% fibers) throughout the experiment (12 weeks) and served as a normal diet control (Group II). The rest 24 rabbits were fed on an atherogenic diet for 8 weeks to induce atherogenesis. At the end of 8th week, a group of 8 atherogenic rabbits (Group III) were separated and sacrificed and served as an atherogenic-baseline group. The remaining 16 atherogenic rabbits were randomly allocated into two groups; first group received atherogenic diet only for the next four weeks and served as an atherogenic control (Group IV). The other group received atorvastatin (Group V). Results: Blood samples were collected for serum lipids, coagulation parameters and oxidation parameters. Results showed a significant improvement in the coagulation parameters and oxidation parameters in the atorvastatin treated group compared to the atherogenic control group (P= .01). Conclusion: This study illustrated the beneficial anti-oxidant effects of atorvastatin in treating atherosclerosis associated with hyperlipidemia.

Benign signet ring cells in pseudomembranous colitis: A diagnostic trap.

A 71-year-old female patient was admitted with intractable diarrhea and abdominal distention following several courses of broad spectrum antibiotic therapy. Colonic biopsy revealed pseudomembranous colitis with foci of signet ring cell (SRC) change. The SRCs possessed bland nuclei and were confi ned to the basement membranes of the crypts with no infi ltration into the lamina propria. Benign SRCs in pseudomembranous colitis is an uncommon phenomenon. Awareness of this rare, but potential pitfall is of utmost importance to avoid a misdiagnosis of SRC carcinoma.

Rheological studies on different oily vehicles for pharmaceutical preparations

The rheological properties of oily vehicles based on patents of non-aqueous vehicles for pharmaceutical suspensions were studied. The effects of different concentrations of suspending agents and different excipients on the flow curves were also investigated. A Rotovisko viscometer [Haake] fitted with concentric cylinder sensors, NV measuring head- 500 and a temperature controlled water jacket at 37°C was used. The results showed that Fractionated Coconut Oil [FCO] alone and with 0.7% w/v lecithin exhibited Newtonian behavior. Dispersions of aluminium stearate, hydrogenated castor oil, Cab-o-sil and sucrose in FCO exhibited pseudoplastic behavior. Aluminium stearate 1% w/v and above and the oily vehicle containing aluminium stearate, hydrogenated castor oil, lecithin and sucrose exhibited thixotropic pseudoplastic properties. The omission of lecithin from the later vehicle resulted in a decrease in the apparent viscosity and the loss of thixotropy. The thixotropic pseudoplastic behavior of oily vehicles is a desirable property in liquid pharmaceutical systems that ideally should have a high consistency in the container, yet pour or spread easily after they had been stirred vigorously. Possible reasoning and suggestions were discussed

Kyste amygdaloide oropharynge : a propos d'un cas

Le kyste amygdaloide est une tumeur kystique latero-cervicale haute rare; issue de la 2eme fente branchiale. Il represente 2 des tumeurs latero-cervicales du cou; et 6;1a 85;2 des anomalies de la deuxieme fente. La forme oropharyngee est tres rare. Nous rapportons une observation d'un kyste amygdaloide oropharynge; chez une femme de 56 ans. Aucune symptomatologie particuliere n'a ete notee. L'examen clinique a revele une tumefaction de la loge amygdalienne droite; refoulant le pilier anterieur. La TDM a objective un processus expansif necrose de l'amygdale palatine droite comblant l'espace parapharynge droit; en contact avec la base de la langue et le muscle pterygoidien medial homolateral. Une resection complete et sans rupture du kyste a ete pratiquee par voie transorale; le geste a ete complete par une amyg- dalectomie droite. L'histologie a confirme le diagnostic par la co-existence d'un revetement epithelial et d'une infiltration de tissu lymphoide. Le recul est de 6 mois sans recidive

Familial mediterranean fever in the Arabian Peninsula: case report and review of literature

Familial Mediterranean Fever [FMF] is an inherited disease which manifests with attacks of fever and serosal inflammation, and is complicated in 26% of patients with secondary amyloidosis. In this paper the author reports a series of five patients, including the first Bahraini with this disease; and reviews the clinical course, pathology, theories of pathogenesis and treatment of this disease