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991.
Trimurti L. Lambat Ahmed A. Abdala Sami Mahmood Pankaj V. Ledade Ratiram G. Chaudhary Subhash Banerjee 《RSC advances》2019,9(68):39735
We report an efficient and facile one-pot synthesis of 4-oxo-tetrahydroindoles using sulfamic acid under ball milling conditions. The present protocol for preparation of biologically important 4-oxo-tetrahydroindoles offers several advantages such as mild reaction conditions, improved selectivity and higher isolated yields. Moreover, solvent-free reaction conditions and the use of ball milling make the present protocol environmentally friendly in nature.We report an efficient and facile one-pot synthesis of 4-oxo-tetrahydroindoles using sulfamic acid under ball milling conditions. 相似文献
992.
Muhammad Imran Sobia Manzoor Nasir Mahmood Khattak Madiha Khalid Qazi Laeeque Ahmed Fahed Parvaiz Muqddas Tariq Javed Ashraf Waseem Ashraf Sikandar Azam Muhammad Ashraf 《Archives of virology》2014,159(5):831-846
Hepatitis C virus (HCV) infection is the most important problem across the world. It causes acute and chronic liver infection. Different approaches are in use to inhibit HCV infection, including small organic compounds, siRNA, shRNA and peptide inhibitors. This review article summarizes the current and future therapies for HCV infection. PubMed and Google Scholar were searched for articles published in English to give an insight into the current inhibitors against this life-threatening virus. HCV NS3/4A protease inhibitors and nucleoside/nucleotide inhibitors of NS5B polymerase are presently in the most progressive stage of clinical development, but they are linked with the development of resistance and viral breakthrough. Boceprevir and telaprevir are the two most important protease inhibitors that have been approved recently for the treatment of HCV infection. These two drugs are now the part of standard-of-care treatment (SOC). There are also many other drugs in phase III of clinical development. When exploring the various host-cell-targeting compounds, the most hopeful results have been demonstrated by cyclophilin inhibitors. The current SOC treatment of HCV infection is Peg-interferon, ribavirin and protease inhibitors (boceprevir or telaprevir). The future treatment of this life-threatening disease must involve combinations of therapies hitting multiple targets of HCV and host factors. It is strongly expected that the near future, treatment of HCV infection will be a combination of direct-acting agents (DAA) without the involvement of interferon to eliminate its side effects. 相似文献
993.
Our working years increasingly extend into the late 60s and may soon include the 70s for some people. Thus the question whether work stress has a cumulative effect in older age, and whether older employees are more vulnerable to certain sources of work stress, such as bullying in the work place, is becoming increasingly relevant. We review some of the mechanisms, which translate cumulative stress at work into ill health, particularly in older age, and summarise what is known about the effect of age-specific stress, taking age-related bullying as an example. 相似文献
994.
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996.
Hannaneh Wahhabaghai Bahram Rasoulian Mansour Esmaili Hossein Ali Mehrani Hassan Mohammadhosseniakbari Mahmood Mofid 《Renal failure》2013,35(6):514-521
Background. Pre-exposure to hyperoxic gas (≥ 95%) has been shown to protect the heart and central nervous system from ischemia-reperfusion injury. In the present study, we investigated whether oxygen pretreatment induces delayed renal protection in rats. The possible role of some renal antioxidant agents was also investigated. Materials and methods. Adult male Wistar rats were kept in a hyperoxic (HO) (≥ 95% O2) environment for 0.5 h, 1 h, 2 h, 3 h, 6 h, and 2 h/day for three consecutive days and 4 h/day for six consecutive days, and control group (IR) animals were kept in the cage with no HO, one day before subjecting their kidney to 40 minutes of ischemia and 24h of reperfusion. Renal function was assessed by comparing plasma creatinine (Cr), blood urea nitrogen (BUN), creatinine clearance (CLCr), and fractional excretion of sodium (FENa%). Histopathological injury score was also determined according to the Jablonski method. To examine the antioxidant system induction by hyperoxia, we measured renal catalase and superoxide dismutase activity, and renal glutathione and malondialdehyde content. Results. Our data demonstrated that only in 4 h/day HO for six consecutive days, the renal function tests (Cr, CLCr, BUN, and FENa%) and Jablonski histological injury were better than control group (p < 0.05). The beneficial effect of oxygen pretreatment in this group was associated with increased renal catalase activity compared with those obtained from control group (p < 0.05). Conclusion. The present study demonstrates that repeated exposure to hyperoxic (≥ 95% O2) environment can reduce subsequent rat's renal ischemia-reperfusion damage. Induction of endogenous antioxidant system may partially explain this beneficial effect of hyperoxic preconditioning. 相似文献
997.
David P. Kodack Euiheon Chung Hiroshi Yamashita Joao Incio Annique M. M. J. Duyverman Youngchul Song Christian T. Farrar Yuhui Huang Eleanor Ager Walid Kamoun Shom Goel Matija Snuderl Alisha Lussiez Lotte Hiddingh Sidra Mahmood Bakhos A. Tannous April F. Eichler Dai Fukumura Jeffrey A. Engelman Rakesh K. Jain 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(45):E3119
Brain metastases are a serious obstacle in the treatment of patients with human epidermal growth factor receptor-2 (HER2)–amplified breast cancer. Although extracranial disease is controlled with HER2 inhibitors in the majority of patients, brain metastases often develop. Because these brain metastases do not respond to therapy, they are frequently the reason for treatment failure. We developed a mouse model of HER2-amplified breast cancer brain metastasis using an orthotopic xenograft of BT474 cells. As seen in patients, the HER2 inhibitors trastuzumab and lapatinib controlled tumor progression in the breast but failed to contain tumor growth in the brain. We observed that the combination of a HER2 inhibitor with an anti–VEGF receptor-2 (VEGFR2) antibody significantly slows tumor growth in the brain, resulting in a striking survival benefit. This benefit appears largely due to an enhanced antiangiogenic effect: Combination therapy reduced both the total and functional microvascular density in the brain xenografts. In addition, the combination therapy led to a marked increase in necrosis of the brain lesions. Moreover, we observed even better antitumor activity after combining both trastuzumab and lapatinib with the anti-VEGFR2 antibody. This triple-drug combination prolonged the median overall survival fivefold compared with the control-treated group and twofold compared with either two-drug regimen. These findings support the clinical development of this three-drug regimen for the treatment of HER2-amplified breast cancer brain metastases. 相似文献
998.
Jessica Ausborn Riyadh Mahmood Abdeljabbar El Manira 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(52):E3631-E3639
Significance
Spinal neural networks generate locomotion. An adjustment of the locomotion speed entails a precise order of recruitment of excitatory interneurons (e.g., V2a interneurons) within these networks. We show, using the adult zebrafish spinal cord, that the recruitment order of V2a interneurons is not topographic and does not conform to input resistance. The incremental recruitment of these interneurons is determined by scaling the excitatory drive with input resistance. We also show that locomotor networks are composed of multiple microcircuits recruited in a continuum. Thus, we provide insights into the recruitment mechanisms of spinal microcircuits that ensure optimal execution of locomotor movements. 相似文献999.
Khatun I Zeissig S Iqbal J Wang M Curiel D Shelness GS Blumberg RS Hussain MM 《Hepatology (Baltimore, Md.)》2012,55(5):1356-1368
Microsomal triglyceride transfer protein (MTP), essential for apolipoprotein B (apoB) biosynthesis, evolved as a phospholipid transfer protein and acquired triglyceride transfer activity during a transition from invertebrates to vertebrates. But it is unknown whether MTP directly transfers lipids onto apoB in vivo and, if it does, whether both neutral and polar lipid transfer activities of MTP are critical for lipoprotein assembly. The molecular bases for differences in lipid transfer activities with respect to distinct domains in Drosophila MTP (dMTP) and human MTP (hMTP) are not obvious because both proteins have very similar primary, secondary, and tertiary structures. We used an in vivo approach to delineate physiological significance of these distinct lipid transfer activities by expressing dMTP (transfers phospholipids) and hMTP (transfers phospholipids and triglycerides) orthologs using adenoviruses in liver-specific MTP-deficient (L-MTP(-/-)) mice that have low plasma and high hepatic lipids. Both orthologs improved plasma lipids but plasma triglycerides were lower in dMTP mice due to lower hepatic triglyceride and apoB production. Hepatosteatosis in L-MTP(-/-) mice was ameliorated to similar levels by both. Attenuation of hepatosteatosis upon dMTP expression pertained to enhanced β-oxidation with no changes in lipogenesis. Phospholipid transfer activity of MTP promoted biogenesis of both apoB48 and apoB100-containing very low density lipoprotein in addition to a phospholipid-rich apoB48-containing high-density lipoprotein particle. Triglyceride transfer activity augmented the biosynthesis of triglyceride-rich lipoproteins by increasing the formation of these particles in the lumen of the endoplasmic reticulum. CONCLUSION: Based on these findings, we posit that the selective inhibition of MTP triglyceride transfer activity might reduce hyperlipidemia while protecting liver from excess lipid accumulation. 相似文献
1000.
Poorhosseini H Kassaian SE Aghajani H Alidoosti M Hajizeinali AM Salarifar M Nematipour E Amirzadegan AR Sheikhfathollahi M Shafiee N Hakki-Kazazi E Tokaldany ML 《Texas Heart Institute journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital》2012,39(1):24-29
In this retrospective study, we compared the in-hospital and long-term outcomes of the on-label and off-label uses of drug-eluting stents.From April 2003 through June 2007, 1,538 patients underwent percutaneous coronary intervention with a drug-eluting stent (sirolimus or paclitaxel) at Tehran Heart Center. Off-label implantation of the drug-eluting stent was as implemented on the basis of specific clinical and procedural characteristics set forth in our text. There were 708 patients in the on-label group and 830 in the off-label group.Baseline characteristics were not significantly different between the groups. Histories of non-ST-segment-elevation myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting were more prevalent in the off-label group. Both groups had similar procedural and in-hospital complications. The follow-up rate at 1 year was 93.1% in the on-label group and 93.3% in the off-label group. During that period, the occurrence of major adverse cardiac events was not significantly different between the groups. After 1 year between the respective on- and off-label uses of the sirolimus-eluting and paclitaxel-eluting stents, and after adjustment for diabetes mellitus, myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting, there was no remarkable difference in the occurrence of major adverse cardiac events (hazard ratio, 0.688; 95% confidence interval, 0.365-1.295; P=0.2463) or target-vessel revascularization (hazard ratio, 0.69; 95% confidence interval, 0.291-1.636; P=0.3993).We found that off-label use of drug-eluting stents was safe after 1 year and that such use was not associated with increased in-hospital myocardial infarction or death. 相似文献