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991.
Billah MM Cooper N Minnicozzi M Warneck J Wang P Hey JA Kreutner W Rizzo CA Smith SR Young S Chapman RW Dyke H Shih NY Piwinski JJ Cuss FM Montana J Ganguly AK Egan RW 《The Journal of pharmacology and experimental therapeutics》2002,302(1):127-137
N-(3,5-Dichloro-1-oxido-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 351591) has been identified as a potent (IC(50) = 58 nM) and highly selective type 4 phosphodiesterase (PDE4) inhibitor with oral bioactivity in several animal models of lung inflammation. N-(3,5-Dichloro-4-pyridinyl)-8-methoxy-2-(trifluoromethyl)-5-quinoline carboxamide (SCH 365351), the only significant in vivo metabolite, is also a potent and highly selective PDE4 inhibitor (IC(50) = 20 nM). Both SCH 351591 and SCH 365351 inhibited cytokine production in human blood mononuclear cell preparations. Oral SCH 351591 significantly attenuated allergen-induced eosinophilia and airway hyperreactivity in allergic guinea pigs at doses as low as 1 mg/kg. In this model, oral SCH 365351 showed similar potency. When SCH 351591 was administered orally to allergic cynomolgus monkeys at 3 mg/kg, Ascaris suum-induced lung eosinophilia was blocked. Hyperventilation-induced bronchospasm in nonallergic guinea pigs, a model for exercise-induced asthma, was also suppressed significantly by oral SCH 351591 at 0.3 mg/kg. Cilomilast (SB 207499; Ariflo), a PDE4 inhibitor currently being developed for asthma and chronic obstructive pulmonary disease (COPD), was 10- to 30-fold less potent than SCH 351591 at inhibiting guinea pig lung eosinophilia and hyperventilation-induced bronchospasm. In a ferret model of emesis, maximum nonemetic oral doses of SCH 351591 and cilomilast were 5 and 1 mg/kg, respectively. Comparison of plasma levels at these nonemetic doses in ferrets to those at doses inhibiting hyperventilation-induced bronchospasm in guinea pigs gave a therapeutic ratio of 16 for SCH 351591 and 4 for cilomilast. Thus, SCH 351591 exhibits a promising preclinical profile as a treatment for asthma and COPD. 相似文献
992.
Gonadal dysfunction is a common problem in end-stage renal disease. We decided to test the ability of the male gonads to respond to exogenous stimuli. The patients receiving chronic hemodialysis showed abnormally low levels of total testosterone and free testosterone in the presence of normal testosterone-binding globulin. Furthermore, the exogenous administration of human chorionic gonadotropin failed to elicit a normal response from the male gonads of hemodialyzed patients. Although basal serum prolactin levels are elevated, we do not believe that elevation is of the magnitude expected to produce testicular failure. Thus we believe that the primary testicular failure is part of the uremic syndrome, and is not corrected by dialysis. 相似文献
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995.
Sujoy Ganguly Lucy S. Williams Isabel M. Palacios Raymond E. Goldstein 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(38):15109-15114
Cells can localize molecules asymmetrically through the combined action of cytoplasmic streaming, which circulates their fluid contents, and specific anchoring mechanisms. Streaming also contributes to the distribution of nutrients and organelles such as chloroplasts in plants, the asymmetric position of the meiotic spindle in mammalian embryos, and the developmental potential of the zygote, yet little is known quantitatively about the relationship between streaming and the motor activity which drives it. Here we use Particle Image Velocimetry to quantify the statistical properties of Kinesin-dependent streaming during mid-oogenesis in Drosophila. We find that streaming can be used to detect subtle changes in Kinesin activity and that the flows reflect the architecture of the microtubule cytoskeleton. Furthermore, based on characterization of the rheology of the cytoplasm in vivo, we establish estimates of the number of Kinesins required to drive the observed streaming. Using this in vivo data as the basis of a model for transport, we suggest that the disordered character of transport at mid-oogenesis, as revealed by streaming, is an important component of the localization dynamics of the body plan determinant oskar mRNA. 相似文献
996.
Murugan Veerapandian Mohana Marimuthu Ponnilavarasan Ilangovan Swastika Ganguly Kyu-Sik Yun Sanghyo Kim Jeongho An 《Medicinal chemistry research》2010,19(3):283-298
A number of organic compounds obtained by chemical synthesis as model compounds have useful antimicrobial activities. Quinazoline
ring is an aromatic benzopyrimidine system; many of its derivatives possess interesting biological activities, such as analgesic,
anti-inflammatory, anti-microbial, and anti-tumor. In our study, the biological activity of synthesized quinazoline semicarbazone
derivatives were characterized by antimicrobial screening against several gram-positive, gram-negative bacteria, and fungus.
The purity of the synthesized compounds was characterized by physicochemical properties, such as solubility, melting point,
and thin layer chromatography (TLC). Elemental analysis for carbon, nitrogen, hydrogen, and oxygen was performed according
to standard procedures. The presence of functional groups was analyzed using FT-IR spectra. Molecular structural information
for the compounds was analyzed by 1H-NMR spectroscopy. The wavelengths of maximum absorbance for all the synthesized compounds were measured by UV-Visible spectroscopy.
Thereby the chemical structures of the synthesized quinazoline derivatives were confirmed. Antimicrobial screening for all
the compounds exhibits characteristic microbial inhibition. A detailed study is in progress to modify the synthetic route,
structural activity, and toxicological barriers for the enhanced pharmacological efficiency of synthetic antibiotics. 相似文献
997.
Pabitra Saha Arindam Naskar Swagata Ganguly Sonali Das Subhasish K Guha Asit Biswas Dilip K Bera Pratip K Kundu Madhusudan Das Shrabanee Mullick Krishnangshu Ray Ardhendu K Maji 《Asian Pacific journal of tropical medicine》2013,6(6):443-448
ObjectiveTo study the in vivo efficacy of these two ACTs in the treatment ofPlasmodium falciparum (P. falciparum malaria) in Kolkata and to determine the prevalence of mutant S769N codon of thePfATPase6 gene among field isolates ofP. falciparum collected from the study area.MethodsA total of 207P. falciparum positive cases were enrolled randomly in two study arms and followed up for 42 days as per WHO (2009) protocol. A portion ofPfATPase6 gene spanning codon S769N was amplified and sequenced by direct sequencing method.ResultsIt was observed that the efficacy of both the ACT regimens were highly effective in the study area and no mutant S769N was detected from any isolate.ConclusionsThe used, combination AS+SP is effective and the other combination AM+LF might be an alternative, if needed. 相似文献
998.
Nyamathi AM William RR Ganguly KK Sinha S Heravian A Albarrán CR Thomas A Greengold B Ekstrand M Ramakrishna P Rao PR 《Journal of HIV/AIDS & social services》2010,9(4):385-404
A community-based participatory research study was conducted using focus groups with 39 women living with AIDS (WLA) in the rural setting of Andhra Pradesh, India. In addition, three nurses, two physicians, and five reproductive health accredited social health activists (ASHAs) took part in focus groups. The WLA offered insight into the benefits of HIV-trained ASHAs including emotional support, assistance with travel to health care providers and antiretroviral therapy medication adherence. Health care providers also identified benefits of using HIV-trained ASHAs and suggested modalities for how to train these individuals. These findings will contribute to the design of a future program of care involving HIV-trained ASHAs. 相似文献
999.
Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy 总被引:2,自引:0,他引:2
Schessl J Zou Y McGrath MJ Cowling BS Maiti B Chin SS Sewry C Battini R Hu Y Cottle DL Rosenblatt M Spruce L Ganguly A Kirschner J Judkins AR Golden JA Goebel HH Muntoni F Flanigan KM Mitchell CA Bönnemann CG 《The Journal of clinical investigation》2008,118(3):904-912
Reducing body myopathy (RBM) is a rare disorder causing progressive muscular weakness characterized by aggresome-like inclusions in the myofibrils. Identification of genes responsible for RBM by traditional genetic approaches has been impossible due to the frequently sporadic occurrence in affected patients and small family sizes. As an alternative approach to gene identification, we used laser microdissection of intracytoplasmic inclusions identified in patient muscle biopsies, followed by nanoflow liquid chromatography-tandem mass spectrometry and proteomic analysis. The most prominent component of the inclusions was the Xq26.3-encoded four and a half LIM domain 1 (FHL1) protein, expressed predominantly in skeletal but also in cardiac muscle. Mutational analysis identified 4 FHL1 mutations in 2 sporadic unrelated females and in 2 families with severely affected boys and less-affected mothers. Transfection of kidney COS-7 and skeletal muscle C2C12 cells with mutant FHL1 induced the formation of aggresome-like inclusions that incorporated both mutant and wild-type FHL1 and trapped other proteins in a dominant-negative manner. Thus, a novel laser microdissection/proteomics approach has helped identify both inherited and de novo mutations in FHL1, thereby defining a new X-linked protein aggregation disorder of muscle. 相似文献
1000.