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891.
Takhi M Murugan C Munikumar M Bhaskarreddy KM Singh G Sreenivas K Sitaramkumar M Selvakumar N Das J Trehan S Iqbal J 《Bioorganic & medicinal chemistry letters》2006,16(9):2391-2395
Novel oxazolidinone antibacterials containing N-hydroxyacetamidine moiety are synthesized with the diversity at C-5 terminus. These compounds have been evaluated against a panel of clinically relevant gram-positive and gram-negative pathogens. Most of the analogs in this series displayed activity superior to Linezolid and in vivo efficacies of selected oxazolidinones are also disclosed herein. 相似文献
892.
Das J Sitaram Kumar M Subrahmanyam D Sastry TV Prasad Narasimhulu C Laxman Rao CV Kannan M Roshaiah M Awasthi R Patil SN Sarnaik HM Rao Mamidi NV Selvakumar N Iqbal J 《Bioorganic & medicinal chemistry》2006,14(23):8032-8042
In an effort to discover potent antibacterials based on the entropically favored 'bioactive conformation' approach, a series of novel tricyclic molecules mimicking the conformationally constrained structure of Linezolid is reported. Based on the initial tricyclic molecule 1, the benzazepine derivative 2 was designed where the tricyclic structure had more flexibility around C-N bond compared to 1. While, the molecule 2 was less active, the molecule 3 showed promising antibacterial activity presumably after having obtained rigidity due to pyrrole ring. The syntheses, SAR studies, and evaluation of 3 as a lead compound are reported. 相似文献
893.
Madhavan GR Chakrabarti R Reddy KA Rajesh BM Balraju V Rao PB Rajagopalan R Iqbal J 《Bioorganic & medicinal chemistry》2006,14(2):584-591
2,4-Thiazolidinedione derivatives of 1,3-benzoxazinone were synthesized and evaluated for their PPAR-alpha and -gamma dual activation. DRF-2519, a compound obtained through SAR of TZD derivatives of benzoxazinone, has shown potent dual PPAR activation. In ob/ob mice, it showed better efficacy than the comparator molecules. In fat fed rat model, it showed significant improvement in lipid parameters, which was better than fibrates. 相似文献
894.
Sun AQ Balasubramaniyan N Chen H Shahid M Suchy FJ 《The Journal of biological chemistry》2006,281(24):16410-16418
The mechanisms underlying the transport of bile acids by apical sodium-dependent bile acid transporter (Asbt) are not well defined. To further identify the functionally relevant residues, thirteen conserved negatively (Asp and Glu) and positively (Lys and Arg) charged residues plus Cys-270 of rat Asbt were replaced with Ala or Gln by site-directed mutagenesis. Seven of the fourteen residues of rat Asbt were identified as functionally important by taurocholate transport studies, substrate inhibition assays, confocal microscopy, and electrophysiological methods. The results showed that Asp-122, Lys-191, Lys-225, Lys-256, Glu-261, and Lys-312,Lys-313 residues of rat Asbt are critical for transport function and may determine substrate specificity. Arg-64 may be located at a different binding site to assist in interaction with non-bile acid organic anions. For bile acid transport by Asbt, Na(+) ion movement is a voltage-dependent process that tightly companied with taurocholate movement. Asp-122 and Glu-261 play a critical role in the interaction of a Na(+) ion and ligand with Asbt. Cys-270 is not essential for the transport process. These studies provide new details about the amino acid residues of Asbt involved in binding and transport of bile acids and Na(+). 相似文献
895.
Anthelmintic resistance: the state of play revisited 总被引:1,自引:0,他引:1
Helminthosis is one of the major constraints in the successful wool and mutton industry throughout the world. Anthelmintic Resistance (AR) is said to have been established when previously effective drug ceases to kill exposed parasitic population at the therapeutically recommended dosages. Anthelmintic resistance is almost cosmopolitan in distribution and it has been reported in almost all species of domestic animals and even in some parasites of human beings. Some of the most important species of parasites of small ruminants in which AR has been reported include: Haemonchus spp., Trichostrongylus spp. Teladorsagia spp., Cooperia spp. Nematodirus spp., and Oesophagostomum spp. All the major groups of anthelmintics have been reported for development of variable degrees of resistance in different species of gastrointestinal nematodes. This paper describes the global scenario of prevalence and methods used for detection of AR in small ruminants. Different mechanisms and contributory factors for the development of AR are discussed. Various options and alternate strategies for the control and/or delay in the onset of AR are suggested in the light of available information. 相似文献
896.
897.
Weidong Xiong Marianela Candolfi Chunyan Liu A. K. M. Ghulam Muhammad Kader Yagiz Mariana Puntel Peter F. Moore Julie Avalos John D. Young Dorothy Khan Randy Donelson G. Elizabeth Pluhar John R. Ohlfest Kolja Wawrowsky Pedro R. Lowenstein Maria G. Castro 《PloS one》2010,5(6)
Background
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and carries a dismal prognosis. We have developed a conditional cytotoxic/immunotherapeutic approach using adenoviral vectors (Ads) encoding the immunostimulatory cytokine, human soluble fms-like tyrosine kinase 3 ligand (hsFlt3L) and the conditional cytotoxic molecule, i.e., Herpes Simplex Type 1- thymide kinase (TK). This therapy triggers an anti-tumor immune response that leads to tumor regression and anti-tumor immunological memory in intracranial rodent cancer models. We aim to test the efficacy of this immunotherapy in dogs bearing spontaneous GBM. In view of the controversy regarding the effect of human cytokines on dog immune cells, and considering that the efficacy of this treatment depends on hsFlt3L-stimulated dendritic cells (DCs), in the present work we tested the ability of Ad-encoded hsFlt3L to generate DCs from dog peripheral blood and compared its effects with canine IL-4 and GM-CSF.Methodology/Principal Findings
Our results demonstrate that hsFlT3L expressed form an Ad vector, generated DCs from peripheral blood cultures with very similar morphological and phenotypic characteristics to canine IL-4 and GM-CSF-cultured DCs. These include phagocytic activity and expression of CD11c, MHCII, CD80 and CD14. Maturation of DCs cultured under both conditions resulted in increased secretion of IL-6, TNF-α and IFN-γ. Importantly, hsFlt3L-derived antigen presenting cells showed allostimulatory potential highlighting their ability to present antigen to T cells and elicit their proliferation.Conclusions/Significance
These results demonstrate that hsFlt3L induces the proliferation of canine DCs and support its use in upcoming clinical trials for canine GBM. Our data further support the translation of hsFlt3L to be used for dendritic cells'' vaccination and gene therapeutic approaches from rodent models to canine patients and its future implementation in human clinical trials. 相似文献898.
899.
Association of Blood Lead (Pb) and Plasma Homocysteine: A Cross Sectional Survey in Karachi,Pakistan
Background
High blood lead (Pb) and hyperhomocysteinemia have been found to be associated with cardiovascular disease (CVD). Mean blood Pb and mean plasma homocysteine levels have been reported to be high in Pakistani population. The objective of the present study was to assess the relationship of blood Pb to the risk of hyperhomocysteinemia in a low income urban population of Karachi, Pakistan.Methodology/Principal Findings
In a cross sectional survey, 872 healthy adults (355 males, 517 females; age 18–60 years) were recruited from a low income urban population of Karachi. Fasting venous blood was obtained and assessed for blood Pb and plasma/serum homocysteine, folate, pyridoxal phosphate (PLP, a coenzymic form of vitamin B6) and vitamin B12. The study population had median (IQR) blood Pb of 10.82 µg/dL (8.29–13.60). Prevalence of high blood Pb (levels >10 µg/dL) was higher in males compared to females (62.5% males vs 56% females; p value = 0.05). Mean ± SD/median (IQR) value of plasma homocysteine was significantly higher in the highest quartile of blood Pb compared to the lowest quartile 16.13±11.2 µmol/L vs 13.28±9.7µmol/L/13.15 (10.33–17.81) µmol/L vs 11.09 (8.65 14.31) µmol/L (p value<0.001). Daily consumption of fruit juice had a positive influence on both levels of plasma homocysteine and blood Pb. Compared with the lowest quartile of blood Pb, the OR for hyperhomocysteinemia was 1.69 (95% CI, 1.00 to 2.85) for the fourth quartile when the model was adjusted for age, gender, folate and vitamin B12.Conclusions/Significance
This study showed a relationship between blood Pb and hyperhomocysteinemia in a general population of Karachi, Pakistan. The harmful effect of Pb on cardiovascular system could be due to its association with hyperhomocysteinemia. 相似文献900.
Irin Parvin Abu Sadat Mohammad Sayeem Bin Shahid Subhasish Das Lubaba Shahrin Mst. Mahmuda Ackhter Tahmina Alam Soroar Hossain Khan Mohammod Jobayer Chisti John D. Clemens Tahmeed Ahmed David A. Sack Abu Syed Golam Faruque 《PLoS neglected tropical diseases》2021,15(9)
BackgroundAfter a multi-country Asian outbreak of cholera due to Vibrio cholerae serogroup O139 which started in 1992, it is rarely detected from any country in Asia and has not been detected from patients in Africa.Methodology/Principal findingsWe extracted surveillance data from the Dhaka and Matlab Hospitals of International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) to review trends in isolation of Vibrio cholerae O139 in Bangladesh. Data from the Dhaka Hospital is a 2% sample of > 100,000 diarrhoeal patients treated annually. Data from the Matlab Hospital includes all diarrhoeal patients who hail from the villages included in the Matlab Health and Demographic Surveillance System. Vibrio cholerae O139 was first isolated in Dhaka in 1993 and had been isolated every year since then except for a gap between 2005 and 2008. An average of thirteen isolates was detected annually from the Dhaka Hospital during the last ten years, yielding an estimated 650 cases annually at this hospital. During the last ten years, cases due to serogroup O139 represented 0.47% of all cholera cases; the others being due to serogroup O1. No cases with serogroup O139 were identified at Matlab since 2006. Clinical signs and symptoms of cholera due to serogroup O139 were similar to cases due to serogroup O1 though more of the O139 cases were not dehydrated. Most isolates of O139 remained sensitive to tetracycline, ciprofloxacin, and azithromycin, but they became resistant to erythromycin starting in 2009.Conclusions/SignificanceCholera due to Vibrio cholerae serogroup O139 continues to cause typical cholera in Dhaka, Bangladesh. 相似文献