Incidence of Echinococcus granulosus in Domestic Dogs in Palestine as Revealed by Copro-PCR

Hydatidosis or echinococcosisis considered a neglected zoonotic disease despite its high burden in the livestock industry and the high risk of infection by humans in endemic areas. In a cross-sectional study we estimated the copro-Incidence and also genotyped Echinococcus granulosus isolates from domestic dogs using polymerase chain reaction (PCR). Medical archives in nine major hospitals in Palestine were reviewed to determine incidence of E. granulosus infection detected in humans during surgery. Faecal samples were collected from 93 domestic dogs in three districts with the highest number of human cases: Al-Khalil (Hebron), Tubas and Jenin. Genomic DNA was extracted from dog faecal samples and amplified by PCR targeting the repeat DNA sequence (EgG1 Hae III) followed by sequencing of five positive samples. Genotyping was determined by sequencing and BLAST searching of mitochondrial cytochrome c oxidase subunit (CO1). The incidence of E. granulosus infection detected in humans at surgery was 1.2 per 100,000 in the West Bank and 1.0 per 100,000 in Gaza Strip. Seventeen of 93 domestic dogs (18%) were positive, based upon comparison with the Echinococcus DNA control. The five sequenced samples were confirmed to be E. granulosus. Successfully genotyped sample belonged to E.granulosus sensu stricto (formerly G1-G3 complex, sheep strain). For domestic dogs, age group (13-24 months) and sex were identified as two risk factors for contracting E. granulosus. The study identified the high incidence of E. granulosus sensu stricto in dogs in Palestine.     

The Knoevenagel reactions of pregnenolone with cyanomethylene reagents: Synthesis of thiophene,thieno[2,3-b]pyridine,thieno[3,2-d]isoxazole derivatives of pregnenolone and their in vitro cytotoxicity towards tumor and normal cell lines

The reaction of pregnenolone with either 2-aminoprop-1-ene-1,1,3-tricarbonitrile or 3-oxo-3-phenylpropanenitrile gave the Knoevenagel condensation products 3 and 6, respectively. Separation of the E and Z isomeric compounds of 3 and 6 together with their structure elucidation were carried out. Some chemical transformations of the latter products were carried out and the cytotoxicity of the newly obtained products was evaluated against some cancer cell lines and a human normal cell line. The results indicated that compounds 15, 17a, 18 and 20e among the tested compounds showed the highest cytotoxicity against the cancer cell lines.     

Antimetabolites: Design,synthesis, and cytotoxic evaluation of novel dihydropyridine thioglycosides and pyridine thioglycosides

A convenient synthesis of a novel series of dihydropyridine and pyridine thioglycosides was developed. The evaluation of anti-proliferative activity against HepG-2 cell lines (liver carcinoma cell lines) shows that most of the compounds have antitumor activity, especially 5b, 5f, 5j, 5n, 7b, 7f, 7j, 7n, 8b, 8f, and 8j. The results of molecular docking reveal that these compounds have high binding affinity by hydrogen bond formation with the binding pocket of thymidylate synthase dihydrofolate reductase (TS-DHFR).     

Frequency of chromosomal aberrations in the rainbow trout, Salmo gairdneri Rich., exposed to five pollutants

This work presents the results of investigations of cytogenetic changes produced by pollutants of a water ecosystem (phenol, decamethrine, Malathion, Neguvon and crude oil). The changes have been measured by observing frequency of chromosomal aberrations in the tissues of gills and kidney of rainbow trout exposed to pollutants. The fish were exposed to two dose levels of the pollutants, the lowest being the legislative maximum permissible concentration in the waters of Yugoslavia, which were used as a dose-response for the highest investigated concentrations. Exposure to the water polluted by chemical pollutants under investigation, raised the frequency of aberrations compared to the controls.     

Chromosomal studies by blood leukocyte culture technique on three salmonids from Yugoslavian waters

Three species of salmonids, rainbow trout, Salmo gairdneri , brown trout, S. trutta , and marble trout, S. marmoratus , have been studied for their karyotypes. In rainbow trout 316 metaphases were studied and recorded 2 n of 60 with 44 meta- to submetacentric and 16 subtelo- to telo-centric chromosomes, and the number of chromosome arms (NF) of 104. Observation on 243 metaphases of brown trout showed 2 n of 80 with 20 meta- to submetacentric, 60 telocentric chromosomes and the nf of 100. While in 164 metaphases from the marble trout 2 n was of the order of 80 out of which 22 were meta to submetacentric and 58 telocentric chromosomes with nf of 108.     

Gremlin in the pathogenesis of hepatocellular carcinoma complicating chronic hepatitis C: an immunohistochemical and PCR study of human liver biopsies

ABSTRACT: BACKGROUND: The possible role of secretory products of fibrous tissue in the development of hepatocellular carcinoma (HCC) complicating chronic hepatitis C was investigated. Our hypothesis was that gremlin, secreted by fibroblasts, inhibited bone morphogenic protein (BMP), which mediates stem cell maturation into adult functioning hepatocytes, and thus, arrest stem cell maturation and promoted their proliferation in an immature state possibly culminating into development of HCCs. RESULTS: Protein expression of cytokeratin 19 (CK19) and fibroblast growth factor 2 (FGF-2), and mRNA expression of gremlin and BMP-7 were studied in 35 cases of chronic hepatitis, cirrhosis and HCC complicating chronic hepatitis C. CK19 expression was higher in cases of cirrhosis (0.004), which correlated with the grade (r=0.64, p=0.009) and stage (r=0.71, p=0.001). All HCCs were negative for CK19. Stem cell niche activation (as indicated as a ductular reaction) was highest in cases of cirrhosis (p=0.001) and correlated with CK19 expression (r=0.42, p=0.012), the grade(r=0.56, p=0.024) and stage (0.66, p=0.006). FGF-2 expression was highest in HCCs and correlated with the grade (r=0.6, p=0.013), stage (0.72, p=0.002), CK19 expression (r=0.71, p=002) and ductular reaction (0.68, p=0.004) in hepatitis cases. Higher numbers of cirrhosis cases and HCCs (p=0.009) showed gremlin expression, which correlated with the stage (r=0.7, p=0.002). Gremlin expression correlated with that of CK19 (r=0.699, p=0.003) and FGF2 (r=0.75, p=0.001) in hepatitis cases. CONCLUSIONS: Fibrosis promotes carcinogenesis by fibroblast-secreted gremlin that blocks BMP function and promotes stem cell activation and proliferation as well as possibly HCC development.     

S-glycosides in medicinal chemistry: Novel synthesis of cyanoethylene thioglycosides and their pyrazole derivatives

A one-pot reaction of a sodium 2-cyanoethylene-1-thiolate salt with 2,3,4,6-tetra-O-acetyl-α-D-gluco- and galactopyranosyl bromides affords a new class of cyanoethylene thioglycosides. The conversion to the corresponding 5-aminopyrazoles confirms the E-configuration of these cyanoethylene thioglycosides.     

Detection of biomarkers for Hepatocellular Carcinoma using a hybrid univariate gene selection methods

ABSTRACT: BACKGROUND: Discovering new biomarkers has a great role in improving early diagnosis of Hepatocellular carcinoma (HCC). The experimental determination of biomarkers needs a lot of time and money. This motivates this work to use in-silico prediction of biomarkers to reduce the number of experiments required for detecting new ones. This is achieved by extracting the most representative genes in microarrays of HCC. RESULTS: In this work, we provide a method for extracting the differential expressed genes, up regulated ones, that can be considered candidate biomarkers in high throughput microarrays of HCC. We examine the power of several gene selection methods (such as Pearson's correlation coefficient, Cosine coefficient, Euclidean distance, Mutual information and Entropy with different estimators) in selecting informative genes. A biological interpretation of the highly ranked genes is done using KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways, ENTREZ and DAVID (Database for Annotation, Visualization, and Integrated Discovery) databases. The top ten genes selected using Pearson's correlation coefficient and Cosine coefficient contained six genes that have been implicated in cancer (often multiple cancers) genesis in previous studies. A fewer number of genes were obtained by the other methods (4 genes using Mutual information, 3genes using Euclidean distance and only one gene using Entropy). A better result was obtained by the utilization of a hybrid approach based on intersecting the highly ranked genes in the output of all investigated methods. This hybrid combination yielded seven genes (2 genes for HCC and 5 genes in different types of cancer) in the top ten genes of the list of intersected genes. CONCLUSIONS: To strengthen the effectiveness of the univariate selection methods, we propose a hybrid approach by intersecting several of these methods in a cascaded manner. This approach surpasses all of univariate selection methods when used individually according to biological interpretation and the examination of gene expression signal profiles.