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31.
Sui Z Guan J Macielag MJ Jiang W Zhang S Qiu Y Kraft P Bhattacharjee S John TM Haynes-Johnson D Clancy J 《Journal of medicinal chemistry》2002,45(19):4094-4096
A series of N-pyrimidinylpyrroloquinolones were discovered as extremely potent and selective PDE5 inhibitors. Representative compounds demonstrated in vivo efficacy in dog erectile dysfunction models and are orally bioavailable. 相似文献
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33.
Differential activity of NO synthase inhibitors as chemopreventive agents in a primary rat tracheal epithelial cell transformation system 下载免费PDF全文
A model to study the effectiveness of potential chemopreventive agents that inhibit neoplastic process by different mechanisms has been used to test the efficacy of seven nitric oxide synthase (NOS) inhibitors. Five selective inducible NOS (iNOS) inhibitors: S-methyl isothiourea (S-MITU), S-2-aminoethyl isothiourea (S-2-AEITU), S-ethyl isothiourea (S-EITU), aminoguanidine (AG), 2-amino-4-methyl pyridine (2-AMP), and two non selective general NOS inhibitors: l-N(6)-(1-iminoethyl) lysine (IEL) and N(omega)-nitro-l-arginine (NNLA), were tested for efficacy against a carcinogen, benzo[a]pyrene (B[a]P)-induced primary rat tracheal epithelial (RTE) cell transformation assay. RTE cells were treated with B[a]P alone or with five nontoxic concentrations of an NOS inhibitor and the resulting foci at the end of 30 days were scored for inhibition of transformation. The results indicate that all three isothiourea compounds inhibited B[a]P-induced RTE foci in a dose-dependent manner. S-AEITU was the most effective inhibitor with an IC(50) (the molar concentration that inhibits transformation by 50%) of 9.1 microM and 100% inhibition at the highest dose tested (30 microM). However, both S-EITU and S-MITU showed a maximum percent inhibition of 81% and 100% at 1 mM with an IC(50) of 84 and 110 microM, respectively. 2-AMP did not show any dose-dependent response, but was highly effective (57% inhibition) at an intermediate dose of 30 microM and an IC(50) of 25 microM. Similar to thiourea compounds, AG exhibited good dose-dependent inhibition with a maximum inhibition of 86% at 1 mM. NNLA and IEL were negative in this assay. Based on the IC(50) values, NOS inhibitors were rated for efficacy from high to low as follows: S-2-AEITU<2-AMP相似文献
34.
Michelle T Paulsen Adrienne M Starks Frederick A Derheimer Sheela Hanasoge Liwu Li Jack E Dixon Mats Ljungman 《Molecular cancer》2006,5(1):25-11
Background
The evolutionary conserved cyclin-dependent kinase phosphatase hCdc14A has been shown to play potential roles in the regulation of mitotic exit and in the centrosome duplication cycle. We have recently shown that hCdc14A also can interact with the tumor suppressor p53 both in vitro and in vivo and specifically dephosphorylates the ser315 site of p53 in vitro. In this study we developed antibodies against hCdc14A to investigate the expression and regulation of hCdc14A in human tissues and cancer cells. 相似文献35.
Samson J Sheela Devi R Ravindran R Senthilvelan M 《Environmental toxicology and pharmacology》2005,20(1):142-148
The levels of free radical scavenging enzymes in six discrete brain regions (cerebral cortex, cerebellum, midbrain, pons medulla, hippocampus and hypothalamus), after exposure to three different durations of noise stress (broadband white noise, 100dB, 4h/day, in acute: 1 day, sub acute: 15 days and chronic stress: 30 days) was studied in Wister strain male albino rats. Acute noise stress significantly increases the levels of superoxide dismutase (SOD: EC 1.15.1.1), catalase (EC 1.11.1.6), glutathione peroxidase (GPx: EC 1.11.1.9), oxidized glutathione (GSSG) and lipid peroxidation (LPO) and decreases the levels of reduced glutathione (GSH), GSH/GSSG ratio and protein thiols. The free radical scavenging enzymes levels, in sub acute and chronic noise stress also showed marked deviation in certain regions from the controls within the study duration. The results indicate that adaptation to noise stress does not occur immediately in all the brain regions. The noise induced alterations in free radicals may be assumed to serve as a linkage between the environmental noise and the manifestation of multifactorial diseases attributed to noise exposure. Moreover the quantification of the health effects of noise by the alterations in free radicals seems inappropriate in chronic noise stress. 相似文献
36.
Kielmann K Deshmukh D Deshpande S Datye V Porter J Rangan S 《Social science & medicine (1982)》2005,61(7):1540-1550
Changing epidemiological patterns and the advent of new rapid diagnostic technologies and therapies have created considerable uncertainty for providers working in HIV. In India, the demand for HIV care is increasingly being met by private practitioners (PPs), yet little is known about how they deal with the challenges of managing HIV patients. To explore HIV management practices in the private medical sector, a survey was conducted with 215PPs in Pune, India, followed by in-depth interviews focusing on the social context of practice among a sub-set of 27PPs. Drawing primarily on interview data, this paper illustrates a number of uncertainties that underlie the reported actions of providers in a competitive medical market. PPs perceive HIV as a 'new' and challenging disease for which they lack adequate knowledge and skills. Combined with the perceived high cost and complexity of antiretroviral treatment, preconceptions about HIV patients' social, financial and mental capacity lead to highly individualistic management practices. While these fall short of clinical 'best practice' guidelines, they reflect adaptive responses to the wider uncertainties surrounding HIV care in urban India. By highlighting contextual issues in PPs' management of HIV patients, the paper suggests the need to explicitly acknowledge the social, moral and economic bases of uncertainty beyond the clinical setting. 相似文献
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38.
Narayan K Dail D Li L Cadavid D Amrute S Fitzgerald-Bocarsly P Pachner AR 《Annals of neurology》2005,57(6):813-823
Lyme neuroborreliosis (LNB) is a chronic infection in which B-cell activation, plasma cell infiltration, and enhanced Ig production in infected tissue are prominent feature. However, little is known about how B cells and plasma cells invade and persist in target organs. To assess this issue, we developed real-time PCR measurements of IgG and CXCL13 production. We used these RNA assays and specific enzyme-linked immunosorbent assays for protein and demonstrated that human peripheral blood mononuclear cells (PBMCs), stimulated by Borrelia burgdorferi sonicate, produced CXCL13 and IgG. Magnetic separation of PBMC populations and flow cytometry showed that CXCL13 is produced by dendritic cells. We then measure the expression of CXCL13 and IgG in tissues and correlated the expression of these host genes with spirochetal load. We also measured expression of dbpA and BBK32, two spirochetal genes important in chronic infection. There was a strong correlation between host immune response gene expression (CXCL13 and IgG) and spirochetal load. Immunohistochemistry of infected nonhuman primates tissue confirmed that CXCL13 is expressed in the nervous system. We conclude that persistent production of CXCL13 and IgG within infected tissue, two characteristics of ectopic germinal centers, are definitive features of LNB. 相似文献
39.
Sheela H Seela S Caldwell C Boyer JL Jain D 《Journal of clinical gastroenterology》2005,39(7):603-610
Since the origination of the liver biopsy, the technique has evolved into an essential diagnostic tool, with very few complications. In addition to the percutaneous approach, a liver biopsy can also be obtained via transjugular, laparoscopic, or intraoperative approach. While in the early 1960s and 1970s the liver biopsy was used for making a diagnosis in cases of clinically suspected medical liver disease, today it is more often performed to assess disease prognosis and evaluate therapeutic strategies. As a result, indications for the liver biopsy have evolved over the past 2 decades. However with advances in serologic diagnosis of viral/autoimmune hepatitis and laboratory tests for genetic disorders, the role of liver biopsy in certain clinical settings is currently debated. This review discusses the technique, indications, contraindications, and the changing role of liver biopsy in some of the common disorders and the associated controversies. 相似文献
40.
Millis SR Campagnolo DI Kirshblum S Elovic E Jain SS DeLisa JA 《The journal of spinal cord medicine》2004,27(5):428-433
OBJECTIVE: This study describes a research training program that implemented several processes and structures with the aim of increasing the quality and quantity of resident research in physical medicine and rehabilitation. Another aim of the program was to address the Accreditation Council for Graduate Medical Education (ACGME) Practice-Based Learning and Improvement competency. DESIGN: Educational program. RESULTS: Data on resident research activity for 11 years before the implementation of the research program were compared with 4 years of data after implementation. There were statistically significant increases in both the total number of publications (P = 0.03) and the number of empirical, data-based publications after implementation of the program (P = 0.03). CONCLUSIONS: The findings from this study suggest that a structured research training program may have a salutary effect on increasing the quality and quantity of resident research. 相似文献