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141.
Mahajan A Kumar V Mansour NR Bickle Q Chibale K 《Bioorganic & medicinal chemistry letters》2008,18(7):2333-2336
New analogues of the potent antihelmintic meclonazepam were prepared and evaluated against Schistosoma mansoni. The biological data suggests substitution at positions 2 and 4 of meclonazepam could provide promising analogues for prophylactic and therapeutic activity against S. mansoni. 相似文献
142.
El Sayed H. El Ashry Ahmed A. Kassem Hamida M. Abdel-Hamid Farida Louis Mohamed R. Aouad 《Carbohydrate research》2009,344(6):725-733
The glycosylation of 5-(3-chlorobenzo[b]thien-2-yl)-4H-1,2,4-triazole-3-thiol (1) and its 3-benzylsulfanyl and 3-methylsulfanyl derivatives with different glycosyl halides 2-4 has been studied in presence of base. The S-glycosides 5-7 were obtained in the presence of triethylamine, whereas the respective S,N4-bis(glycosyl) derivatives 8-10 were synthesized in the presence of potassium carbonate; the S,N2-bis(glycosyl) isomer 11 could also be isolated in the case of the galactosyl analog. Similarly, after protecting 1 as 3-benzyl(methyl)sulfanyl derivatives 12 or 13, the N4-glycosyl analogs 14-19 as well as minor amounts of S,N2-bis(galactosyl) isomers 20 and 21 were formed. The theoretical calculations using AM1 semiempirical methods agreed with the experimental results. Microwave irradiation (MWI) led to higher yields in much less time than the conventional methods, and no change in regioselectivity has been noticed. 相似文献
143.
F. C. Connell P. Ostergaard C. Carver G. Brice N. Williams S. Mansour P. S. Mortimer Steve Jeffery Lymphoedema Consortium 《Human genetics》2009,124(6):625-631
Milroy disease (hereditary lymphoedema type I, MIM 153100) is a congenital onset primary lymphoedema with autosomal dominant
inheritance. Mutations in the gene, vascular endothelial growth factor receptor 3, VEGFR3 (FLT4), are known to cause Milroy disease, but there is uncertainty about the prevalence of VEGFR3 mutations in patients with primary lymphoedema and more specifically in those with a phenotype that resembles Milroy disease.
This study aims to address this issue and thereby delineate the Milroy disease phenotype. Fifty-two patients with primary
lymphoedema were analysed for mutations in the coding regions of VEGFR3. Patients were divided into four groups: Typical Milroy disease with family history (group I), typical Milroy disease with
no family history (group II), atypical Milroy disease (group III), and complex primary lymphoedema (group IV). Results demonstrated
that with rigorous phenotyping the likelihood of detecting VEGFR3 mutations is optimised. Mutation prevalence is 75% in typical Milroy patients with a family history (group I) and 68% if
positive family history is not a diagnostic criterion. A positive family history is not essential in Milroy disease. The likelihood
of detecting VEGFR3 mutations in patients who have a phenotype which is not typical of Milroy disease is very small (<5%). For the 22 mutation
positive patients, 14 novel VEGFR3 mutations were identified, two of which were in exon 22 and one in exon 17, confirming that these exons should be included
in VEGFR3 analysis. No mutations were found outside the kinase domains, showing that analysis of this part of the gene is not useful
for Milroy disease patients. VEGFC, which encodes the ligand for VEGFR3, was sequenced in all patients with typical Milroy disease (groups I and II) and no
mutations were identified.
F. C. Connell and P. Ostergaard contributed equally to this work.
An erratum to this article can be found at 相似文献
144.
Samer S. El-Kamary Michelle D. Shardell Mohamed Abdel-Hamid Soheir Ismail Mohamed El-Ateek Mohamed Metwally Nabiel Mikhail Mohamed Hashem Amr Mousa Amr Aboul-Fotouh Mohamed El-Kassas Gamal Esmat G. Thomas Strickland 《Phytomedicine》2009,16(5):391-400
PurposeMilk thistle or its purified extract, silymarin (Silybum marianum), is widely used in treating acute or chronic hepatitis. Although silymarin is hepatoprotective in animal experiments and some human hepatotoxic exposures, its efficacy in ameliorating the symptoms of acute clinical hepatitis remains inconclusive. In this study, our purpose was to determine whether silymarin improves symptoms, signs and laboratory test results in patients with acute clinical hepatitis, regardless of etiology.MethodsThis is a randomized, placebo-controlled trial in which participants, treating physicians and data management staff were blinded to treatment group. The study was conducted at two fever hospitals in Tanta and Banha, Egypt where patients with symptoms compatible with acute clinical hepatitis and serum alanine aminotransferase (ALT) levels >2.5 times the upper limit of normal were enrolled. The intervention consisted of three times daily ingestion of either a standard recommended dose of 140 mg of silymarin (Legalon®, MADAUS GmbH, Cologne, Germany), or a vitamin placebo for four weeks with an additional four-week follow-up. The primary outcomes were symptoms and signs of acute hepatitis and results of liver function tests on days 2, 4 and 7 and weeks 2, 4, and 8. Side-effects and adverse events were ascertained by self-report.ResultsFrom July 2003 through October 2005, 105 eligible patients were enrolled after providing informed consent. No adverse events were noted and both silymarin and placebo were well tolerated. Patients randomized to the silymarin group had quicker resolution of symptoms related to biliary retention: dark urine (p=0.013), jaundice (p=0.02) and scleral icterus (p=0.043). There was a reduction in indirect bilirubin among those assigned to silymarin (p=0.012), but other variables including direct bilirubin, ALT and aspartate aminotransferase (AST) were not significantly reduced.ConclusionsPatients receiving silymarin had earlier improvement in subjective and clinical markers of biliary excretion. Despite a modest sample size and multiple etiologies for acute clinical hepatitis, our results suggest that standard recommended doses of silymarin are safe and may be potentially effective in improving symptoms of acute clinical hepatitis despite lack of a detectable effect on biomarkers of the underlying hepatocellular inflammatory process. 相似文献
145.
Abdel-Hamid A. Hamdy Elsayed A. Aboutabl Somayah Sameer Ahmed A. Hussein Ana R. Díaz-Marrero Jos Darias Mercedes Cueto 《Steroids》2009,74(12):927-930
Bioassay-guided purification of an ethanolic extract of Cystoseira myrica against HEPG-2 (liver) and HCT116 (colon) human cancer cell lines led to the isolation of 3-keto-22-epi-28-nor-cathasterone, 1 and cholest-4-ene-3,6-dione, 2. This finding allowed us to report for the first time that a brassinosteroid-related metabolite occurs in seaweed. These compounds showed activity in the range of 12.38–1.16 μM with selective activity of compound 2 to liver cancer cell lines. 相似文献
146.
Mansour Djedaini Milou-Daniel Drici Perla Saint-Marc Annie Ladoux 《Biochemical and biophysical research communications》2009,386(1):96-100
HIV-protease inhibitors (PIs) markedly decreased mortality of HIV-infected patients. However, their use has been associated with occurence of metabolic abnormalities the causes of which are not well understood. We report here that lopinavir, one of the most prescribed PI, dose-dependently co-induced insulin resistance and ER stress in human adipocytes obtained from differentiation of precursor cells.Insulin resistance was subsequent to IRS1 phosphorylation defects and resulted in a concentration-dependent decrease of glucose uptake. The major ER stress pathway involved was the phosphorylation of eIF2-α. Salubrinal, a selective eIF2-α dephosphorylation inhibitor, induced insulin resistance by targeting IRS1 phosphorylation at serine 312 and acted synergistically with LPV when both drugs were used in combination.This study points out the key role of eIF2-α phosphorylation in the development of PI-associated insulin resistance and ER stress. Thus, this protein represents a promising therapeutic target for development of new PIs devoid of adverse metabolic effects. 相似文献
147.
Philippe Marullo Chantal Mansour Matthieu Dufour Warren Albertin Delphine Sicard Marina Bely & Denis Dubourdieu 《FEMS yeast research》2009,9(8):1148-1160
During red wine fermentation, high temperatures may cause stuck fermentation by affecting the physiology of fermenting yeast. This deleterious effect is the result of the complex interaction of temperature with other physicochemical parameters of grape juice, such as sugar and lipid content. The genetic background of fermenting yeast also interacts with this complex matrix and some strains are more resistant to high temperatures than others. Here, the temperature tolerance of nine commercial starters was evaluated, demonstrating that, at high sugar concentrations, half of them are sensitive to temperature. Using a classical backcross approach, one thermo-sensitive commercial starter was genetically improved by introducing quantitative trait loci conferring resistance to temperature. With this breeding program it is possible to obtain a thermo-resistant strain sharing most of its genome with the initial commercial starter. The parental and improved strains were compared for population growth and fermentation ability in various conditions. Despite their common genetic background, these two strains showed slight physiological differences in response to environmental changes that enable identification of the key physiological parameters influencing stuck fermentation. 相似文献
148.
Background
In view of the current widespread use of and reliance on a single schistosomicide, praziquantel, there is a pressing need to discover and develop alternative drugs for schistosomiasis. One approach to this is to develop High Throughput in vitro whole organism screens (HTS) to identify hits amongst large compound libraries.Methodology/Principal Findings
We have been carrying out low throughput (24-well plate) in vitro testing based on microscopic evaluation of killing of ex-vivo adult S. mansoni worms using selected compound collections mainly provided through the WHO-TDR Helminth Drug Initiative. To increase throughput, we introduced a similar but higher throughput 96-well primary in vitro assay using the schistosomula stage which can be readily produced in vitro in large quantities. In addition to morphological readout of viability we have investigated using fluorometric determination of the reduction of Alamar blue (AB), a redox indicator of enzyme activity widely used in whole organism screening. A panel of 7 known schistosome active compounds including praziquantel, produced diverse effects on larval morphology within 3 days of culture although only two induced marked larval death within 7 days. The AB assay was very effective in detecting these lethal compounds but proved more inconsistent in detecting compounds which damaged but did not kill. The utility of the AB assay in detecting compounds which cause severe morbidity and/or death of schistosomula was confirmed in testing a panel of compounds previously selected in library screening as having activity against the adult worms. Furthermore, in prospective library screening, the AB assay was able to detect all compounds which induced killing and also the majority of compounds designated as hits based on morphological changes.Conclusion
We conclude that an HTS combining AB readout and image-based analysis would provide an efficient and stringent primary assay for schistosome drug discovery. 相似文献149.
El‐Sayed M. El‐Sayed Ahmed M. Mansour Waleed S. El‐Sawy 《Journal of biochemical and molecular toxicology》2017,31(11)
Doxorubicin (DOX) exerts toxic effects in several organs particularly kidney. The present study aimed to assess the protective effect of proanthocyanidins (PAs) against DOX‐induced nephrotoxicity in rats. A single dose of DOX (7.5 mg/kg, i.v.) significantly increased kidney weight, kidney/body weight ratio, serum urea, creatinine, tumor necrosis factor alpha levels, and kidney contents of malondialdehyde, nitric oxide, cyclooxygenase‐2, and caspase‐3 activity with significant reduction in final body weight, serum albumin, kidney contents of reduced glutathione (GSH), and superoxide dismutase activity as compared with control group. In contrast, pretreatment with PAs (200 mg/kg, p.o.) for 14 days before DOX and for 7 days after DOX ameliorated kidney function and oxidative stress parameters. Histopathological evidence confirmed the protective effects of PAs from the tissue damage induced by DOX. In conclusion, PAs have a multi‐nephroprotective effect that might be attributed to its antioxidant, anti‐inflammatory, and antiapoptoic activities. 相似文献
150.