An efficient cyclocondensation reactions, antimicrobial activity and molecular orbital calculations of α-benzopyrone derivatives

An efficient synthesis of 4,6,8-trimethyl-2-oxo-2H-chromene-3-carbonitrile (2) via Claisen condensation of 3,5-dimethyl-2-hydroxyacetophenone with ethyl cyanoacetate in the presence of sodium metal is reported. Cyclocondensation reactions of compound (2) with ethyl acetate or with ethyl cyanoacetate in the presence of ethoxide gave sodium salt of 7-amino-9-hydroxy-2,4-dimethyl-6H-benzo[c]chromen-6-one derivatives (3) and (4) respectively, which upon neutralization with 10 % hydrochloric acid gave 7-amino-9-hydroxy-2,4-dimethyl-6H-benzo[c]chromen-6-one (5). Hydrolysis of compound (2) with ethanolic sodium hydroxide solution gave 4,6,8-trimethyl-2-oxo-2H-chromene-3-carboxylic acid (6). Treatment of compound (2) with Vilsmier reagent using excess POCl3 gave 4-(chloro(formyl)methyl-6,8-dimethyl-2-oxo-2H-chromene-3-carbonitrile (7). Also, conden-sation of compound (2) with DMF-DMA in xylene or with POCl3/DMF in pyridine gave the same product 4-((E)-2-(dimethylamino)vinyl)-6,8-dimethyl-2-oxo-2H-chromene-3-carbo-nitrile (8). The cyclocondensation reactions of compound (8) with hydroxylamine hydrochloride, urea, and with hydrazinecarbodithioic acid gave 3,4-dihydro-3-hydroxy-4-imino-7,9-dimethylchromeno[3,4-c]pyridin-5-one (9), 4-imino-7,9-dimethyl-5-oxo-4H-chro-meno[3,4-c]pyridine-3(5H)-carboxamide (10) and 3-amino-3,4-dihydro-4-imino-7,9-dimethyl chromeno[3,4-c]pyridin-5-one (11), respectively. Also, acid hydrolysis of compound (8) gave 7,9-dimethyl-3H-chromeno[3,4-c]pyridine-4,5-dione (12). Structures of the products were established on the basis of elemental analysis, IR, 1H and 13C NMR, mass spectra and semi-empirical AM1-MO calculations. The antimicrobial activities of the synthesized products were also studied

Evaluation of adipokine chemerin in hypertensive obese

Chemerin is an adipokine secreted by adiopose tissue and has a role in obesity and hypertension. This study aims at assessing the level of the adipokine chemerin in obesity and/or hypertension and correlating its level with the inflammatory marker hs-CRP and predictors of atherosclerosis as lipid profile, insulin resistance, systolic (SBP) and diastolic blood pressure (DBP).Volunteers were divided into 4 equal groups according to body mass index (BMI) and blood pressure: normal weight group (BMI ≤ 24.9 kg/m2), overweight group (BMI = 25.0 – 29.9 kg/m2), normotensive obese group (BMI ≥ 30.0 kg/m2) and hypertensive obese group (BMI ≥ 30.0 kg/m2). Chemerin, high-sensitivity C-reactive protein (hs-CRP), lipid profile, fasting blood glucose (FBG) and fasting insulin (FI) were evaluated in the mentioned groups.The results showed that there were significant increases of chemerin, hs-CRP, low density lipoprotein (LDL), SBP and DBP in hypertensive obese group compared to normotensive obese , overweight and normal weight groups. Moreover the only significant positive correlation between chemerin and hs-CRP was observed in the obese hypertensive group. The normotensive obese group showed significant increases of hs-CRP, LDL, triglyceride (TG), FBG, FI and the homeostasis model assessment-insulin resistance index (HOMA-IR) compared to the overweight and normal weight groups. Regarding the overweight group, there were significant increases in chemerin, hs-CRP, cholesterol, LDL, TG compared to the normal weight group, while the HDL levels were significantly lower compared to the two obese groups. These results revealed that the pro-inflammatory adipokine chemerin increases in obesity associated with hypertension, leading to the suggestion that there is a definite dysregulation of the pro-inflammatory and anti-inflammatory parameters towards the pro-inflammatory when hypertension and obesity are associated

Possible protective effect of olive leaves extract on paracetamol induced hepatotoxicity in male albino rats

Paracetamol (PCM) overdose can cause hepatotoxicity with oxidative stress; the present study was carried out to establish the possible protective effect of olive leaves extract (OLE) on toxicity induced by paracetamol in adult male rats. Twenty four adult male rats were divided into four equal groups; control, olive leaves extract group, paracetamol group and olive leaves extract plus paracetamol group. Some biochemical parameters and liver histopathology were evaluated. PCM treatment significantly increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, gamma-glutamyltransferase (GGT), lactate dehydrogenase (LDH), urea, creatinine and alpha-fetoprotein. Paracetamol was found to significantly increase malonaldehyde (MDA) and decrease glutathione reductase (GR) activity in tissue and significantly decrease total antioxidant capacity (TAC) and superoxide dismutase (SOD) in serum. Administration of OLE caused a significant decrease serum AST, ALT enzyme, total bilirubin, GGT, LDH, creatinine, urea, alpha-fetoprotein. Also, amelioration of oxidant – antioxidant status with olive leaves extract was observed in addition to a significant decrease in MDA and a significant increase in TAC in liver tissue with a significant increase in glutathione reductase (GR) and SOD in serum compared to paracetamol treated group The chemical pathological changes were in step with histopathological observation suggesting marked hepatoprotective result of olive leaves extract. It could be concluded that olive leaves extract (OLE) treatment may be effective in decreasing hepatic injury and oxidative stress induced by paracetamol overdose in male albino rats

HyCAD-OCT: A Hybrid Computer-Aided Diagnosis of Retinopathy by Optical Coherence Tomography Integrating Machine Learning and Feature Maps Localization

Optical Coherence Tomography (OCT) imaging has major advantages in effectively identifying the presence of various ocular pathologies and detecting a wide range of macular diseases. OCT examinations can aid in the detection of many retina disorders in early stages that could not be detected in traditional retina images. In this paper, a new hybrid computer-aided OCT diagnostic system (HyCAD) is proposed for classification of Diabetic Macular Edema (DME), Choroidal Neovascularization (CNV) and drusen disorders, while separating them from Normal OCT images. The proposed HyCAD hybrid learning system integrates the segmentation of Region of Interest (RoI), based on central serious chorioretinopathy (CSC) in Spectral Domain Optical Coherence Tomography (SD-OCT) images, with deep learning architectures for effective diagnosis of retinal disorders. The proposed system assimilates a range of techniques including RoI localization and feature extraction, followed by classification and diagnosis. An efficient feature fusion phase has been introduced for combining the OCT image features, extracted by Deep Convolutional Neural Network (CNN), with the features extracted from the RoI segmentation phase. This fused feature set is used to predict multiclass OCT retina disorders. The proposed segmentation phase of retinal RoI regions adds substantial contribution as it draws attention to the most significant areas that are candidate for diagnosis. A new modified deep learning architecture (Norm-VGG16) is introduced integrating a kernel regularizer. Norm-VGG16 is trained from scratch on a large benchmark dataset and used in RoI localization and segmentation. Various experiments have been carried out to illustrate the performance of the proposed system. Large Dataset of Labeled Optical Coherence Tomography (OCT) v3 benchmark is used to validate the efficiency of the model compared with others in literature. The experimental results show that the proposed model achieves relatively high-performance in terms of accuracy, sensitivity and specificity. An average accuracy, sensitivity and specificity of 98.8%, 99.4% and 98.2% is achieved, respectively. The remarkable performance achieved reflects that the fusion phase can effectively improve the identification ratio of the urgent patients’ diagnostic images and clinical data. In addition, an outstanding performance is achieved compared to others in literature

Clinico-pathological and Immunological Changes in Chickens Infected with Chicken Anemia Virus

Chicken infectious anemia virus (CIAV) is an immunosuppressive viral disease causing high economic losses in poultry industry. In this study, 20 farms were represented for a prevalence study of the disease in Ismailia governorate, Egypt.ON532690.1 and ON532691.1 Isolates from bone marrow, thymus loops, liver, and spleen of broiler farms exhibiting some clinical and postmortem signs were used for reverse transcription polymerase chain reaction assay. RT-PCR was used to amplify a 418bp product of the CIAV VP1 gene. Three farms out of 20 (15%) were positive. Phylogenetic tree of partial vp1 amino acids were classified into three groups according to change in H/22/N-Q amino acid indicated that there are three CIAV different strains circulating in Egypt. Hematological investigation revealed significant decrease in RBCs count, hemoglobin concentration, and packed cell volume declared normocytic normochromic anemia.The immunological studies revealed a significant decrease in serum lysozyme, nitric oxide (NO), antioxidants (CAT and GSH), total protein,and in the majority of serum protein fractions in infected chickens (G2) compared to apparently healthy (G1) while there were marked increase in G2 than G1 in A: Gratio. This result guides to review the vaccination programs against CIAV in Egypt forimproving the immune response against the infection.

Left atrial deformation analysis as a predictor of severity of coronary artery disease

Background: Two-dimensional (2D) speckle-tracking strain imaging is a novel method for assessment of regional myocardial deformation that uses tracking of acoustic speckles or kernels rather than Doppler myocardial velocities. It has been suggested that Left atrial (LA) strain as measured by 2D speckle tracking can be used to evaluate dynamic LA function. Objective: To study the relation between left atrial deformation and the severity of coronary artery stenosis in patients with stable coronary artery disease (CAD). Study design: 30 patients with stable coronary artery disease (SCAD) with coronary artery stenosis (>50%) who were admitted for elective coronary angiography at Ain Shams University hospitals and AlAzhar University hospitals were included in the study. Measurements of conventional echocardiographic parameters as well as LA strain and strain rate parameters were obtained, Syntax (SX) score was calculated for all patients. Results: Patients were categorized into 3 groups: low Syntax score of <23 (Group I), moderate syntax score 23–32 (Group II) and high syntax score of ≥33 (Group III). Peak atrial longitudinal strain (PALS) (Group I: 29.80 ± 4.48, Group II: 22.44 ± 1.42, Group III: 19.53 ± 4.46; p < 0.001) and Peak atrial contraction strain (PACS) (Group I: 13.43 ± 4.05, Group II: 10.84 ± 2.47, Group III: 7.19 ± 0.71; p < 0.022) were significantly lower in high syntax group. Significant negative correlation was found between SX score level and LA strain parameters (PALS and PACS) (r = 0.861; p < 0.001). Conclusion: Left atrial deformation analysis by 2D Speckle tracking Doppler Echocardiography can predict the severity of coronary affection in patients with stable CAD. Keywords: Left atrium, Deformation, Strain, Speckle trackin

Effect of Celecoxib and Infliximab against Multiple Organ Damage Induced by Sepsis in Rats: A Comparative Study

In cases of sepsis, the immune system responds with an uncontrolled release of proinflammatory cytokines and reactive oxygen species. The lungs, kidneys, and liver are among the early impacted organs during sepsis and are a direct cause of mortality. The aim of this study was to compare the effects of infliximab (IFX) and celecoxib (CLX) on septic rats that went through a cecal ligation and puncture (CLP) surgery to induce sepsis. This study included four groups: sham, CLP (untreated), and CLP-treated with CLX or IFX. The administration of &ldquo;low dose&rdquo; CLX or IFX was performed after 2 h following the induction of sepsis. Twenty-four hours following the induction of sepsis, the rats were sacrificed and blood samples were collected to evaluate kidney, liver, and lung injuries. MDA and NOx content, in addition to SOD activity and GSH levels, were evaluated in the tissue homogenates of each group. Tissue samples were also investigated histopathologically. In a separate experiment, the same groups were employed to evaluate the survival of septic rats in a 7-day observation period. The results of this study showed that treatment with either CLX or IFX ameliorated the three organs&rsquo; damage compared to septic-untreated rats, decreased oxidative stress, enhanced the antioxidant defense, and reduced serum cytokines. As a result, a higher survival rate resulted: 62.5% and 37.5% after the administration of CLX and IFX, respectively, compared to 0% in the CLP group after 7 days. No significant differences were observed between the two agents in all measured parameters. Histopathological examination confirmed the observed results. In conclusion, CLX and IFX ameliorated lung, kidney, and liver injuries associated with sepsis through anti-inflammatory and antioxidant actions, which correlated to the increase in survival observed with both of them

Synthesis, Biophysical Interaction of DNA/BSA, Equilibrium and Stopped-Flow Kinetic Studies, and Biological Evaluation of bis(2-Picolyl)amine-Based Nickel(II) Complex

Reaction of bis(2-picolyl)amine (BPA) with Ni(II) salt yielded [(BPA)NiCl2(H2O)] (NiBPA). The Ni(II) in NiBPA bound to a BPA ligand, two chloride, and one aqua ligands. Because most medications inhibit biological processes by binding to a specific protein, the stopped-flow technique was used to investigate DNA/protein binding in-vitro, and a mechanism was proposed. NiBPA binds to DNA/protein more strongly than BPA via a static quenching mechanism. Using the stopped-flow technique, a mechanism was proposed. BSA interacts with BPA via a fast reversible step followed by a slow irreversible step, whereas NiBPA interacts via two reversible steps. DNA, on the other hand, binds to BPA and NiBPA via the same mechanism through two reversible steps. Although BSA interacts with NiBPA much faster, NiBPA has a much higher affinity for DNA (2077 M) than BSA (30.3 M). Compared to NiBPA, BPA was found to form a more stable BSA complex. When BPA and NiBPA bind to DNA, the Ni(II) center was found to influence the rate but not the mechanism, whereas, for BSA, the Ni(II) center was found to change both the mechanism and the rate. Additionally, NiBPA exhibited significant cytotoxicity and antibacterial activity, which is consistent with the binding constants but not the kinetic stability. This shows that in our situation, biological activity is significantly more influenced by binding constants than by kinetic stability. Due to its selectivity and cytotoxic activity, complex NiBPA is anticipated to be used in medicine

Multiple sclerosis and fecundity: a study of anti-mullerian hormone level in Egyptian patients

Abstract Background Multiple sclerosis (MS) is a neurological disease that affects people aged 20–40 years on average. It classically affects young females of reproductive age. The prevalence of MS for females to males has increased markedly in recent years (from 2.3 to 3.5:1). Females with MS seem to use infertility treatments more frequently and fecundity could be affected years before making an MS diagnosis. The anti-Müllerian hormone (AMH) level is the strongest marker of ovarian reserve. Although recent studies suggest that patients with MS have lower ovarian reserve, there is no definite data to conclude that females with MS suffer from impaired fertility. This study aimed to investigate fertility and fecundity among female patients with MS by assessing AMH level. This study included 100 patients with MS and 60 healthy controls (HC). Both groups were assessed for AMH levels, activities of daily living (ADL) were assessed using the Kurtzke Expanded Disability Status Scale (EDSS) and the reproductive history of both groups was assessed via a self-administered questionnaire. Results AMH levels among the HCs (0.34–2 ng/ml with a mean of 1.03 ± 0.41 ng/ml) were significantly higher than in patients with MS (0.15–2 ng/ml with a mean of 0.68 ± 0.31 ng/ml). The use of disease-modifying therapies (DMT) was the only predictor of below normal AMH among patients, but there was no significant correlation with age, duration of disease or type of DMT. Conclusions Levels of AMH were significantly lower in MS patients than in healthy controls