替诺福韦酯相关性肾毒性的研究进展

替诺福韦酯是替诺福韦的前药,是一种与阿德福韦酯相似的单磷酸腺苷类似物,具有抑制人免疫缺陷病毒（HIV）逆转录酶的活性的作用。随着临床应用的日益广泛,替诺福韦酯相关性肾毒性的报道也越来越多。本文综述替诺福韦酯相关性肾毒性在国内外不同人群的临床表现、作用机制、潜在风险及处理措施等研究进展。     

富马酸喹硫平在大鼠体内的药动学研究

目的:测定富马酸喹硫平在大鼠体内的血药浓度,并研究其药动学特征。方法:取6只大鼠灌胃给予富马酸喹硫平40mg/kg,与给药前和给药后5、15、30、45 min和1、1.5、2、4、6、8、12、24 h静脉采血0.5 ml,离心后取血浆,用乙腈沉淀蛋白后直接进样,以卡马西平为内标物,反相高效液相色谱法测定血药浓度,采用DAS2.0软件分析药动学参数。结果:富马酸喹硫平在大鼠体内的药动学特征呈二室模型,主要药动学参数t1/2α为(20.132±1.198)min、t1/2β为(62.883±11.120)min、tmax为(40.00±8.66)min、cmax为(2.21±0.066)μg/ml、AUC0-24 h为(687.453±12.026)mg·min/L、V1/F为(8.244±0.679)L/kg、K10为(0.183±0.028)min-1、K12为(1.764±0.161)min-1、K21为(0.189±0.018)min-1。结论:富马酸喹硫平在大鼠体内的分布和消除均比较快,且分布不广泛。     

Bioinspired tissue engineering: the great promise of protein delivery technologies

The concept of developing a tissue either in vitro or in vivo taking inspiration from physiological events has prompted toward the integration of molecular signals such as growth factors (GFs) in tissue engineering strategies with the aim to guide cell proliferation, differentiation and migration. After the first studies, the awareness emerged that a fine tuning of GF levels in the scaffold, when present, and at boundary with healthy tissue was needed to give successful results. Thus, the modality of GF presentation to cells has been recognized as a key fundamental in many tissue engineering applications and applied through different approaches. In this scenario the potential of particulate systems for GF delivery was promptly perceived as a mean to protect GFs during tissue regrowth and to offer adequate control over release rate. The use of tissue engineering constructs based on GF-loaded particles integrated in different scaffold types has impressively grown in recent years and led to significant advances in the field. Release of more than one GF at rates mimicking in vivo situation has become possible as well as to exert a fine control over GF spatial concentration by developing constructs with specific areas of bioactivities. However, if we consider the strategies for protein delivery currently applied in tissue engineering, it is soon realized that much more can be done. Thus, the aim here is to review some tissue engineering approaches involving the use of GFs by the point of view of delivery issues trying to highlight the remarkable impact that particulate systems can have in the next future.     

Tenofovir plus lamivudine as rescue therapy for adefovir‐resistant chronic hepatitis B in hepatitis B e antigen‐positive patients with liver cirrhosis

Background/Aims: There is no consensus on the management of patients with adefovir (ADV)‐resistant hepatitis B virus (HBV) infection. The aim of this study was to investigate whether tenofovir disoproxil fumarate (TDF) combined with lamivudine (LMV) is effective and safe in patients with resistance to or non‐response to ADV. Methods: Six patients with HBV‐related cirrhosis, viral breakthrough during LMV therapy and viral breakthrough or non‐response during ADV therapy were treated daily with TDF plus LMV for at least 6 months. The HBV DNA level, alanine aminotransferase (ALT), the Child–Pugh score and serum creatinine were monitored. Genotypic LMV‐ or ADV‐resistant mutations were measured in stored samples. Results: In five of six patients, ADV‐resistant mutations at rt181 or rt236 were detected during ADV therapy. At 6 months of starting TDF/LMV combination, HBV DNA levels became undetectable (detection limit, 400 copies/ml) in four of six patients. Within 12 months, HBV DNA levels became undetectable in all patients, and ALT levels were normalized in four of six patients. These responses persisted up to the end of the observation period (median duration 16.5 months, range 6–21 months). The Child–Pugh scores improved in two of three patients with hepatic decompensation. No significant changes in serum creatinine were observed. Conclusion: Our data demonstrated that TDF plus LMV safely and markedly suppressed HBV replication in patients with resistance to or non‐response to ADV. This study suggests that this combination may be a promising rescue therapy for these patients, particularly those with liver cirrhosis or pre‐existing LMV resistance.     

Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B

1. Download high-res image (217KB)
2. Download full-size image

     

Multiple Sclerosis: Current and Emerging Disease-Modifying Therapies and Treatment Strategies

Multiple sclerosis (MS) is a chronic inflammatory demyelinating central nervous system disease that typically strikes young adults, especially women. The pathobiology of MS includes inflammatory and neurodegenerative mechanisms that affect both white and gray matter. These mechanisms underlie the relapsing, and often eventually progressive, course of MS, which is heterogeneous; confident prediction of long-term individual prognosis is not yet possible. However, because revised MS diagnostic criteria that incorporate neuroimaging data facilitate early diagnosis, most patients are faced with making important long-term treatment decisions, most notably the use and selection of disease-modifying therapy (DMT). Currently, there are 10 approved MS DMTs with varying degrees of efficacy for reducing relapse risk and preserving neurological function, but their long-term benefits remain unclear. Moreover, available DMTs differ with respect to the route and frequency of administration, tolerability and likelihood of treatment adherence, common adverse effects, risk of major toxicity, and pregnancy-related risks. Thorough understanding of the benefit-risk profiles of these therapies is necessary to establish logical and safe treatment plans for individuals with MS. We review the available evidence supporting risk-benefit profiles for available and emerging DMTs. We also assess the place of individual DMTs within the context of several different MS management strategies, including those currently in use (sequential monotherapy, escalation therapy, and induction and maintenance therapy) and others that may soon become feasible (combination approaches and “personalized medicine”). We conducted this review using a comprehensive search of MEDLINE, PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, from January 1, 1990, to August 31, 2013. The following search terms were used: multiple sclerosis, randomized controlled trials, interferon-beta, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, BG-12, alemtuzumab, rituximab, ocrelizumab, daclizumab, neutralizing antibodies, progressive multifocal leukoencephalopathy.     

S聚丙烯网片在污染切口应用的大鼠实验研究

目的通过动物实验研究污染伤口植入聚丙烯网片后切口感染率和病理学变化,探讨嵌顿性腹股沟疝患者应用聚丙烯网片行疝修补术的可行性。方法大鼠分成3组,每组40只,分别为清洁植入网片组(A组)、大肠杆菌污染不植入网片组(B组)和大肠杆菌污染植入网片组(C组)。在大鼠左右背部切口3 cm,A组直接植入聚丙烯网片,B组应用大肠杆菌悬浊液污染切口30 min后0.25%稀释碘伏冲洗切口后局部用咽拭子浸蘸做细菌培养然后直接缝合,C组如B组处理后植入聚丙烯网片。术后观察A、B、C三组伤口愈合情况和感染率,并分别于术后1、2、4、8周取出网片作病理检查。结果所有实验动物无死亡。A组切口1期愈合,切口感染率为0;1周时网片网孔内已有纤维母细胞和纤维细胞增生,部分区域已有肉芽形成,8周时纤维细胞和胶原细胞已经排列规则致密;B、C组细菌培养无细菌生长;B组切口感染率7.5%(3/40),感染切口经引流换药2期愈合;C组切口感染率10.0%(4/40),未感染之网片较清洁切口之网片同期病理有较多巨噬细胞存在;感染切口未去除网片经引流换药2期愈合,术后8周取出网片作病理检查纤维细胞和胶原细胞较规则排列,有巨噬细胞存在。结论动物实验结果表明:切口污染状态下经稀释碘伏冲洗后,植入聚丙烯网片并不增加切口感染率。提示对于嵌顿性腹股沟疝甚至发生肠坏死行肠切除肠吻合患者可以应用聚丙烯网片行疝修补术。     

Combined anterior vaginal wall mesh with sacrospinous ligament fixation or with posterior intravaginal slingplasty for uterovaginal or vaginal vault prolapse

Objective

To evaluate outcomes of anterior vaginal wall mesh augmentation with concomitant sacrospinous ligament fixation (SSLF) or with concomitant posterior intravaginal slingplasty (IVS) for uterovaginal or vaginal vault prolapse.

Study design

Women with symptomatic uterovaginal or vaginal vault prolapse were randomly allocated to SSLF or IVS. All underwent concomitant anterior repair augmented with self-tailored multifilament polypropylene and polyglactin composite mesh. Before and 2, 12, 24 and 36 months after surgery, the outcome was assessed by examination and standard questions. The primary endpoint was anatomic recurrence of pelvic organ prolapse at stage II or beyond (−1 cm or greater) at any site of the vaginal wall. Secondary outcomes included perioperative and postoperative complications, symptom resolution, reoperation and mesh exposure.

Results

Twenty-two women were recruited from March 2003 to December 2005. At 3-year follow-up3 (2 posterior and 1 apical) out of 14 (21%) in the IVS group had anatomic recurrences of pelvic organ prolapse, and 1 anterior out of 8 (13%) in the SSLF group. Severe operative complications or reoperations did not occur. The proportions of symptomatic patients, including those with dyspareunia, did not differ between the groups. Erosion of the anterior multifilament mesh was found in 2 out of 22 cases (9%; 95% CI 3-28%).

Conclusion

At 3-year follow-up anterior repair reinforced with a composite mesh with concomitant sacrospinous ligament fixation or with concomitant posterior intravaginal slingplasty allowed feasible support in patients with severe pelvic organ prolapse.