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991.
G. Sathaiah A. Ravi Kumar A. Chandra Shekhar K. Raju P. Shanthan Rao B. Narsaiah A. Raghuram Reddy D. Lakshmi B. Sridhar 《Medicinal chemistry research》2013,22(3):1229-1237
A series of novel positional isomers of 1-alkyl-2-trifluoromethyl benzimidazole derivatives 3a–j and 4a–j have been synthesized and screened for antibacterial activity against gram positive bacteria viz, Bacillus subtilis, Staphylococcus aureus and gram negative bacteria viz., Escherichia coli, Pseudomonas aeruginosa and antifungal activity against Candida albicans, Aspergillus niger, Rhizopus oryzae and Saccharomyces cerevisiae. Results indicate that compounds 3b, 4b were having promising antibacterial and antifungal activity. 相似文献
992.
Cheng Ji Li Zhang Yan Cheng Raj Patel Hao Wu Yi Zhang Mian Wang Shundong Ji Chandra P Belani Jin-Ming Yang Xingcong Ren 《Cancer biology & therapy》2014,15(5):570-577
Use of the inhibitor of ALK fusion onco-protein, crizotinib (PF02341066), has achieved impressive clinical efficacy in patients with ALK-positive non-small cell lung cancer. Nevertheless, acquired resistance to this drug occurs inevitably in approximately a year, limiting the therapeutic benefits of this novel targeted therapy. In this study, we found that autophagy was induced in crizonitib-resistant lung cancer cells and contributed to drug resistance. We observed that ALK was downregulated in the crizotinib-resistant lung cancer cell line, H3122CR-1, and this was causally associated with autophagy induction. The degree of crizotinib resistance correlated with autophagic activity. Activation of autophagy in crizotinib-resistant H3122CR-1 cells involved alteration of the Akt/mTOR signaling pathway. Furthermore, we demonstrated that chloroquine, an inhibitor of autophagy, could restore sensitivity of H3122CR-1 to crizotinib and enhance its efficacy against drug-resistant lung cancer. Thus, modulating autophagy may be worth exploring as a new strategy to overcome acquired crizonitib resistance in ALK-positive lung cancer. 相似文献
993.
Mandeep Singh Yi Ding Li-Ying Zhang Dong Song Yun Gong Sylvia Adams Dara S Ross Jin-Hua Wang Shruti Grover Dinesh Chandra Doval Charles Shao Zi-Li He Victor Chang Warren W Chin Fang-Ming Deng Baljit Singh David Zhang Ru-Liang Xu Peng Lee 《American journal of cancer research》2014,4(4):337-352
Background: Racial disparities among breast cancer (BCa) patients are known but not well studied in early-onset BCa. We analyzed molecular subtypes in early-onset BCa across five major races. Methods: A total of 2120 cases were included from non-Hispanic White (NHW), African American (AA) and Hispanic, Chinese and Indian. Based on ER, PR and HER-2 status, BCa was classified into 4 intrinsic subtypes as Luminal A, Luminal B, HER2/neu overexpression and Triple negative BCa (TNBC) subtypes. Data was stratified according to race and age as younger/early-onset group (40-years and younger) and older group (50-years and older). Results: In early-onset BCa, incidence of TNBC was significantly higher (p = 0.0369) in Indian women followed by AA, Hispanic, NHW and Chinese women. Incidence of Her2 over-expression subtype also was highest in Indian women, followed by Hispanic, Chinese, AA and NHW women. In contrast, Luminal B subtype was most significantly higher in AA women (p = 0.0000) followed by NHW (p = 0.0002), Chinese (p = 0.0003), Hispanic (0.0128) and Indian (p = 0.0468) women. Luminal A subtype was most significantly reduced in Indian women (p = 0.0113) followed by Hispanic, AA, NHW and Chinese women. These results were based on statistical analysis with the mean of older group populations. Conclusions: These results show significant disparities in receptor subtypes across races. This study will contribute in developing optimal clinical trial protocols and personalized management strategies for early-onset BCa patients. 相似文献
994.
Mahesh Chandra Hegde Abhijit Kumar Gopalkrishna Bhat Suja Sreedharan 《Indian journal of otolaryngology and head and neck surgery》2014,66(1):126-132
The study was designed to compare the oral microbiota in normal and HIV-infected individuals. The study tries to establish a significant shift in oral microflora in HIV-infected patients. Antibiotic sensitivity testing was performed to establish any rise in resistance against the antibiotics. It was a two and half year prospective study conducted in a tertiary care centre. The study group consisted of eighty subjects divided into two groups of control and HIV. The age range for this group was 9–75 years. The mean age in this group was 39.7 years. The male:female ratio was 2.75:1. Tuberculosis was the most common opportunistic infection in patients with HIV infection. The most common commensal micro organism isolated was the Viridans streptococci in 60% followed by Streptococcus pneumoniae in 23.33%. HIV Group: The most common commensal micro organism isolated was the Viridans streptococci in 42%; this was followed by the Micrococci spp. in 22% cases. S. pneumoniae was isolated in 6% of cases. The colony count for Viridans streptococci showed a heavy growth in 55.56% of cases in controls whereas the same in HIV group was 62.5%. Micrococcus spp. was isolated from 11 subjects in HIV group while it was not isolated from the controls. 50% subjects in the HIV group showed a heavy growth of Klebsiella spp. whereas controls showed only moderate and scanty growth. In patients with CD4+ T cell count less than 50 cells/μl we found a heavy colonization of the oral cavity with Micrococcus spp., Acinetobacter and Klebsiella spp. Viridans streptococcus was not isolated in any of the patients with CD4+ T cell count less than 50 cells/μl. As CD4+ T cells counts improved to 51–100 cells/μl Viridans streptococcus colonies returned and 37.5% patients showed a heavy growth. Micrococcus spp. colonies were isolated till the CD4+ T cells improved up to 300 cells/μl. At counts > 300 cells/μl the oral microbiota became comparable to that of the controls. Many of the opportunistic infections in HIV are caused by commensal bacteria which are otherwise harmless in a normal individual. Our study is unique in that such a study of the oral commensals in HIV patients has never been reported. We found an increased colonization of the oral cavity by Micrococcus spp. which is a normal commensal of the skin. 相似文献
995.
R Chandra G K Haines B G Bentz P Shah A M Robinson J A Radosevich 《Otolaryngology--head and neck surgery》2001,124(4):442-447
BACKGROUND: The expression of endothelial constitutive nitric oxide synthase (NOS3) by squamous dysplasia and carcinomas of the head and neck has previously been described. We sought to compare NOS3 expression in squamous mucosa, glandular metaplasia, and adenocarcinoma of the esophagus. METHODS: Forty paraffin-embedded specimens from 20 patients with adenocarcinoma were stained with anti-NOS3 monoclonal antibody. The percentage of cells stained and the intensity of staining were determined for squamous epithelium, metaplasia, and adenocarcinoma. Staining characteristics were statistically analyzed according to clinical variables. RESULTS: NOS3 expression was significantly higher in adenocarcinoma and squamous epithelium compared with glandular metaplasia. Among the carcinomas, larger tumor size (T3/4), nodal positivity, and advanced TNM stage (III/IV) significantly correlated with increased NOS3 expression. CONCLUSIONS: NOS3 is expressed in reflux-induced lesions of the esophagus. Glandular metaplasia shows basal levels of NOS3 that significantly increase with malignant transformation and tumor progression. The role of free radicals in carcinogenesis is being actively studied. 相似文献
996.
Nikhil S Choudhari P Krishna Moorthy Vinod B Tungikar Mohan Kumar Ronnie George Harsha L Rao Sirisha Senthil Lingam Vijaya Chandra Sekhar Garudadri 《Indian journal of ophthalmology》2014,62(11):1082-1085
Purpose:
Goldmann applanation tonometer (GAT) is the current Gold standard tonometer. However, its calibration error is common and can go unnoticed in clinics. Its company repair has limitations. The purpose of this report is to describe a self-taught technique of rectifying calibration error of GAT.Materials and Methods:
Twenty-nine slit-lamp-mounted Haag-Streit Goldmann tonometers (Model AT 900 C/M; Haag-Streit, Switzerland) were included in this cross-sectional interventional pilot study. The technique of rectification of calibration error of the tonometer involved cleaning and lubrication of the instrument followed by alignment of weights when lubrication alone didn’t suffice. We followed the South East Asia Glaucoma Interest Group''s definition of calibration error tolerance (acceptable GAT calibration error within ±2, ±3 and ±4 mm Hg at the 0, 20 and 60-mm Hg testing levels, respectively).Results:
Twelve out of 29 (41.3%) GATs were out of calibration. The range of positive and negative calibration error at the clinically most important 20-mm Hg testing level was 0.5 to 20 mm Hg and -0.5 to -18 mm Hg, respectively. Cleaning and lubrication alone sufficed to rectify calibration error of 11 (91.6%) faulty instruments. Only one (8.3%) faulty GAT required alignment of the counter-weight.Conclusions:
Rectification of calibration error of GAT is possible in-house. Cleaning and lubrication of GAT can be carried out even by eye care professionals and may suffice to rectify calibration error in the majority of faulty instruments. Such an exercise may drastically reduce the downtime of the Gold standard tonometer. 相似文献997.
Joshi S Singh AR Kumar A Misra PC Siddiqi MI Saxena JK 《Molecular and biochemical parasitology》2008,160(1):32-41
The pentose phosphate pathway (PPP) is an important metabolic pathway for yielding reducing power in the form of NADPH and production of pentose sugar needed for nucleic acid synthesis. Transketolase, the key enzyme of non-oxidative arm of PPP, plays a vital role in the survival/replication of the malarial parasite. This enzyme in Plasmodium falciparum is a novel drug target as it has least homology with the human host. In the present study, the P. falciparum transketolase (PfTk) was expressed, localized and biochemically characterized. The recombinant PfTk harboring transketolase activity catalyzed the oxidation of donor substrates, fructose-6-phosphate (F6P) and hydroxypyruvate (HP), with K(m)(app) values of 2.25 and 4.78 mM, respectively. p-Hydroxyphenylpyruvate (HPP) was a potent inhibitor of PfTk, when hydroxypyruvate was used as a substrate, exhibiting a K(i) value of 305 microM. At the same time, noncompetitive inhibition was observed with F6P. The native PfTk is a hexamer with subunit molecular weight of 70kDa, which on treatment with low concentrations of guanidine hydrochloride (GdmCl) dissociated into functionally active dimers. This protein was localized in the cytosol and nucleus of the parasite as studied by confocal microscopy. A model structure of PfTk was constructed based on the crystal structure of the transketolases of Saccharomyces cerevisae, Leishmania mexicana and Escherichia coli to assess the structural homology. Consistent with the homology modeling predictions, CD analysis indicated that PfTk is composed of 39% alpha-helices and 26% beta-sheets. The availability of a structural model of PfTk and the observed differences in its kinetic properties compared to the host enzyme may facilitate designing of novel inhibitors of PfTk with potential anti-malarial activity. 相似文献
998.
Scavenging action of zinc and green tea polyphenol on cisplatin and nickel induced nitric oxide generation and lipid peroxidation in rats 总被引:3,自引:1,他引:2
Joshi S Hasan SK Chandra R Husain MM Srivastava RC 《Biomedical and environmental sciences : BES》2004,17(4):402-409
Objective Toxic metal ions have been implicated in the generation of reactive oxygen species (ROS) and nitric oxide (NO). Metallothionines (MT) and plant flavonoids have been reported in the intervention against oxidative damage. We investigated the effect of zinc induced MT and green tea polyphenol (GTP) in reducing the oxidative responses induced by nickel and platinum. Methods Zinc (10 mg/kg b. wt, sc) was administered to rats twice at a gap of 24hrs and GTP (10 mg/100 mL in drinking water) was fed ad libitum for 8 days. Nickel chloride (150 umol/kgb.wt, ip) and cisplatin (50 umol/kg b.wt, sc) was administered to rats 24 h after Zn or GTP pre-treatment. Animals of all the groups were sacrificed 16 hrs after treatment and biochemical markers for toxicity were monitored. Results Zinc or GTP pre-treatment caused significant protection against nickel or cisplatin enhanced mortality in rats, and reduction in lipid peroxidation and NO. Conclusion It is proposed that inhibition of ROS and NO by GTP and zinc may prove useful as a selective pharmacological agent in the amelioration of metal toxicity. 相似文献
999.
The failure of Leishmania, an intracellular pathogen, to stimulate a pro-inflammatory response following entry into macrophages has been well reported. This occurs in spite of the fact that ligands for the toll-like receptors (TLR) have been recently shown on the parasite surface and their role in disease protection well documented. The outcome of infection in leishmaniasis is determined by the Th1 versus Th2 nature of the effector response and the generation of IL-12 and IL-10 by the infected macrophages is important for this decision. We evaluated the effect of L. donovani infection of monocytes (cell line THP-1, and monocytes derived from human peripheral blood) on Pam3cys (TLR2 ligand) and lipopolysaccharide (TLR4 ligand) stimulated production of IL-12p40 and IL-10. L. donovani infection caused suppression of TLR2 and TLR4-stimulated IL-12p40, with an increase in IL-10 production. Parasites also modulated the TLR2-stimulated mitogen-activated protein kinase (MAPK) pathway by suppressing MAPK P(38) phosphorylation and activating extracellular regulated kinase (ERK)1/2 phosphorylation. These effects could be reversed either by using a MAPK P(38) activator, anisomycin, or ERK1/2 inhibitor, U0126. L. donovani caused modulation of TLR2-stimulated MAPK pathways in a contact-dependent mechanism. In addition parasite structural integrity but not viability was required for suppression of TLR2-stimulated IL-12p40 and activation of IL-10. These observations suggest that L. donovani has evolved survival strategies that subvert the pro-inflammatory response generated through TLRs. 相似文献
1000.
Systemic lupus erythematosus (SLE) is an autoimmune disease that results in immune-mediated damage to multiple organs. Among
these, kidney involvement is the most common and fatal. Spontaneous lupus nephritis (SLN) in mouse models has provided valuable
insights into the underlying mechanisms of human lupus nephritis. However, SLN in mouse models takes 6–12 months to manifest;
hence there is clearly the need for a mouse model that can be used to unveil the pathogenic processes that lead to immune
nephritis over a shorter time frame. In this article more than 25 different molecules are reviewed that have been studied
both in the anti-glomerular basement membrane (anti-GBM) model and in SLN and it was found that these molecules influence
both diseases in a parallel fashion, suggesting that the two disease settings share common molecular mechanisms. Based on
these observations, the authors believe the experimental anti-GBM disease model might be one of the best tools currently available
for uncovering the downstream molecular mechanisms leading to SLN. 相似文献