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1.
Auda A. Eltahla Fabio Luciani Peter A. White Andrew R. Lloyd Rowena A. Bull 《Viruses》2015,7(10):5206-5224
The hepatitis C virus (HCV) is a pandemic human pathogen posing a substantial health and economic burden in both developing and developed countries. Controlling the spread of HCV through behavioural prevention strategies has met with limited success and vaccine development remains slow. The development of antiviral therapeutic agents has also been challenging, primarily due to the lack of efficient cell culture and animal models for all HCV genotypes, as well as the large genetic diversity between HCV strains. On the other hand, the use of interferon-α-based treatments in combination with the guanosine analogue, ribavirin, achieved limited success, and widespread use of these therapies has been hampered by prevalent side effects. For more than a decade, the HCV RNA-dependent RNA polymerase (RdRp) has been targeted for antiviral development. Direct acting antivirals (DAA) have been identified which bind to one of at least six RdRp inhibitor-binding sites, and are now becoming a mainstay of highly effective and well tolerated antiviral treatment for HCV infection. Here we review the different classes of RdRp inhibitors and their mode of action against HCV. Furthermore, the mechanism of antiviral resistance to each class is described, including naturally occurring resistance-associated variants (RAVs) in different viral strains and genotypes. Finally, we review the impact of these RAVs on treatment outcomes with the newly developed regimens. 相似文献
2.
非胰岛素依赖型糖尿病患者血清唾液酸的改变 总被引:2,自引:0,他引:2
测定20例NIDDM伴有心脑血管病变的患者、20例单纯NIDDM患者的血清唾液酸(SA)水平,并与20例正常人进行比较。结果发现所有NIDDM患者的血清SA水平均显著增高(P<0.01),其中伴有心脑血管疾病患者的血清SA水平显著高于单纯NIDDM患者(P<0.05),同时血清SA水平与血清胰岛素及C肽水平、收好压之间存在相关。提示血清SA水平与NIDDM患者的心脑血管疾病关系密切,可能是心脑血管并发症发生的一个危险因素。 相似文献
3.
目的:为了探讨非依赖型糖尿病全血低切变率粘度值测定的临床意义。方法:对91例非依赖型糖尿病血液流变学低切率粘度值进行了检测,并对其结果及形成机制进行了分析讨论。结果:91例非依赖型糖尿病低切变率粘度值和对照组相比有显著性差异,p<0.01。结论:非依赖型糖尿病全血低切变率粘度增高,可造成微血管循环障碍,是非依赖型糖尿病易形成心梗、脑梗及其他微血管病的一种重要因素。 相似文献
4.
H. Iwata T. Otoshi N. Takada T. Murai S. Tamano T. Watanabe Y. Katsura S. Fukushima 《Urological research》1995,23(1):27-32
A series of 8 rat and 16 mouse invasive bladder carcinomas were investigated for the presence of silverstained nucleolar organizer regions (AgNORs) to clarify whether this parameter is applicable to the estimation of their invasive character. With regard to number of AgNORs per cell, neither rat nor mouse carcinomas showed any difference between invasive and noninvasive sites within the same tumor. However, the frequency of cancer cells bearing bizarre dots, irregular in size and shape, was significantly higher at sites of actual invasion. Quantitative data generated using an image analyzer revealed significantly lower values for NOR roundness and significantly larger NOR size in invasive sites than in noninvasive sites in all groups. Double staining for the proliferation marker proliferating cell nuclear antigen (PCNA) and AgNORs was performed on eight rat carcinomas and a close correlation between the two was confirmed. Thus the number of AgNORs in PCNA-positive cells was significantly greater than in PCNA-negative cells. Furthermore, a particularly strong correlation was observed for incidences of PCNA-positive cells and bizarre dots (P<0.01). The quantitative data also demonstrated significant differences in size and shape of dots. It is concluded that AgNORs have diagnostic value for the invasive character of bladder carcinomas. 相似文献
5.
应用标准微电极技术,研究了关附甲素对豚鼠右心室乳头肌动作电位最大除极速率(Vmax)的频率依赖性抑制作用(RDB),并与美西律,奎尼丁,劳卡尼进行了比较. 在相同刺激间隔(300 ms),产生50%左右RDB的药物浓度下,美西律的RDB开始最快,其第2个Vmax所产生的抑制已占RDB的64%,奎尼丁,劳卡尼和关附甲素的RDB开始速率常数分别为每个动作电位0.165, 0.076和0.136. 美西律,奎尼丁,劳卡尼和关附甲素产生RDB的恢复时间常数分别为1.4, 9.0, 18.2和44.0 s,而且它们的恢复时间常数是不依赖于药物浓度而变化的,结果提示,关附甲素是一个慢动力学钠通道阻滞剂. 相似文献
6.
Haiyung Cheng Jules I. Schwartz Charles Lin Raju D. Amin James R. Seibold Kenneth C. Lasseter David L. Ebel Dominick J. Tocco J. Douglas Rogers 《Biopharmaceutics & drug disposition》1994,15(5):409-418
MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD4-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg 14C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative. 相似文献
7.
Jordi Llorens Cristina Su ol Josep M. Tusell Eduard Rodrí guez-Farr 《Neurotoxicology and teratology》1990,12(6):607-610
The inhibition of [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding to the GABAA receptor by the insecticide γ-hexachlorocyclohexane, lindane, was studied in several brain regions and using different membrane preparation methods, both in vitro and after dosing the animals with the chemical. In the latter studies, the amount of lindane remaining in the membrane suspensions used for binding assays was determined. In vitro data showed values of IC50 from 150 to 1675 nM, varying in function of the membrane preparation method used. This may account for the discrepancies in IC50 values found in the literature. IC50 values within the range of 150–250 nM were determined using extensively washed membranes from several brain regions, so no evidence arose for brain regional differences in the affinity of lindane for the TBPS binding site. After different schedules of acute treatment with lindane, we found a manifest relationship between the extent of the observable inhibition of [35S]TBPS binding and the lindane amount remaining in the membrane suspensions used for binding assays. This relationship was in good agreement with the in vitro data, so no support for an in vivo acute regulation of the binding site was obtained. 相似文献
8.
R. L. Cabrini A. E. Schwint A. Mendez F. Femopase H. Lanfranchi M. E. Itoiz 《Journal of oral pathology & medicine》1992,21(6):275-279
A morphometric study of nucleolar organizer regions (NOR) was performed to analyze their distribution, volume, number and shape in the different strata of human normal oral mucosa epithelium and papilloma and in squamous cell carcinoma employing microphotographs of silver-stained paraffin sections. The different NOR-related parameters evidenced significant differences between normal mucosa, papilloma and squamous cell carcinoma. The functional polarity of normal mucosa epithelium and of papilloma is also evidenced in terms of NOR-related parameters. The discriminative value of certain NOR parameters was demonstrated. 相似文献
9.
扩大经额硬膜外入路切除巨大侵袭性垂体瘤 总被引:1,自引:0,他引:1
目的:探讨采用扩大的经额硬膜外入路切除巨大侵袭性垂体瘤的临床应用.方法:1997年6月至2002年3月采用该入路显微外科切除巨大侵袭性垂体瘤10例,肿瘤主要累及于鞍上、蝶筛窦及上斜坡区.结果:本组10例中,肿瘤全切6例,次全切除3例,大部分切除1例.术后发生颅神经麻痹4例,其中动眼神经障碍3例,外展神经障碍1例.全组无手术死亡.术后影像学随访6~24个月,全切除肿瘤病例未见肿瘤复发,次全切除者无明显增大.结论:该入路可充分显露鞍区肿瘤,术野开阔,对脑组织损伤小,适用于已侵犯蝶筛窦区及上斜坡的侵袭性垂体瘤. 相似文献
10.
We present our experience with twenty children with insulin dependent diabetes mellitus admitted during the past 2 1/2 years.
Sixteen patients were admited with acute onset of ketoacidosis while four were having gradual onset. Active and symptomatic
treatment was started in all diabetic ketoacidotic patients. One patient died during the acute stage. Eleven patients were
followed for 3–6 months or more. Glycosylated hemoglobin was considered as a criteria for control. Three had good control,
two fair and six poor control; six developed diabetic ketoacidosis and three developed hypoglycemia 相似文献