Pharmacokinetics of Rifabutin in Japanese HIV-Infected Patients with or without Antiretroviral Therapy

Objective

Based on drug-drug interaction, dose reduction of rifabutin is recommended when co-administered with HIV protease inhibitors for human immunodeficiency virus (HIV)-associated mycobacterial infection. The aim of this study was to compare the pharmacokinetics of rifabutin administered at 300 mg/day alone to that at 150 mg every other day combined with lopinavir-ritonavir in Japanese patients with HIV/mycobacterium co-infection.

Methods

Plasma concentrations of rifabutin and its biologically active metabolite, 25-O-desacetyl rifabutin were measured in 16 cases with HIV-mycobacterial coinfection. Nine were treated with 300 mg/day rifabutin and 7 with 150 mg rifabutin every other day combined with lopinavir-ritonavir antiretroviral therapy (ART). Samples were collected at a median of 15 days (range, 5–63) of rifabutin use.

Results

The mean C_max and AUC_0–24 of rifabutin in patients on rifabutin 150 mg every other day were 36% and 26% lower than on 300 mg/day rifabutin, while the mean C_max and AUC_0–24 of 25–O-desacetyl rifabutin were 186% and 152% higher, respectively. The plasma concentrations of rifabutin plus its metabolite were similar between the groups within the first 24 hours, but it remained low during subsequent 24 to 48 hours under rifabutin 150 mg alternate day dosing.

Conclusion

Rifabutin dose of 150 mg every other day combined with lopinavir-ritonavir seems to be associated with lower exposure to rifabutin and its metabolite compared with rifabutin 300 mg/day alone in Japanese patients. Further studies are needed to establish the optimal rifabutin dose during ART. The results highlight the importance of monitoring rifabutin plasma concentration during ART.

Trial registration

UMIN-CTR (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=search&action=input&language=E) UMIN000001102     

High Efficacy of 14‐Day Triple Therapy‐Based,Bismuth‐Containing Quadruple Therapy for Initial Helicobacter pylori Eradication

Background: The success rate of currently recommended 7‐day triple therapy with a PPI plus amoxicillin and clarithromycin has fallen into the unacceptable range. It is urgent to look for a new strategy to treat the infection of Helicobacter pylori. Aims: To observe the efficacy of triple therapy‐based, bismuth‐containing quadruple therapy for H. pylori treatment. Methods: A total of 160 patients with functional dyspepsia who were Hp+ were randomly assigned into two groups. Regimen: Omeprazole 20 mg, Amoxicillin 1.0 g, Clarithromycin 500 mg and Bismuth Potassium Citrate 220 mg, twice a day. Eighty patients received 7‐day quadruple therapy and 80 patients received the same therapy for 14 days. Six weeks after treatment, H. pylori eradication was assessed by ¹³C‐urea breath test. Minimal inhibitory concentrations of metronidazole, clarithromycin and amoxicillin of clinical isolates were determined by the twofold agar dilution method. Results: Fourteen‐day therapy led to a significant increase of H. pylori eradication success when compared to 7‐day therapy in the intention‐to‐treat analysis (93.7 vs 80.0%; p = .01), and the per‐protocol analysis (97.4 vs 82.0%; p = .0016). The H. pylori resistance rates to metronidazole, clarithromycin and amoxicillin were 42.1, 18.0 and 0%. Fourteen‐day therapy was significantly more effective in patients with clarithromycin‐resistant strains. Incidences of adverse events were comparable. Conclusions: Addition bismuth and prolonging treatment duration can overcome H. pylori resistance to clarithromycin and decrease the bacterial load. Fourteen‐day triple therapy‐based, bismuth‐containing quadruple therapy achieved ITT success rate 93% and could be recommended as the first line eradication regimen.     

免疫毒素的抗肿瘤研究

免疫毒素是由具有导向能力的载体（抗体或细胞因子）和具有细胞毒性的分子（毒素）偶联而成的具有特异性细胞杀伤能力的杂合分子,是一种靶向药物。免疫毒素首先利用肿瘤细胞上导向分子的受体与细胞结合,然后进入细胞,再由毒素发挥蛋白质合成抑制作用,最终导致靶细胞死亡。与其他抗肿瘤药物相比,免疫毒素具有毒性强和特异性高的优点,在肿瘤治疗中显示出巨大的应用前景。简要概述了免疫毒素的作用机理、制备及其抗肿瘤研究进展。     

Animal-Assisted Therapy in Psychiatric Rehabilitation

ABSTRACT

Reviews of animal-assisted therapy (AAT) research suggest the need for better controlled and designed research studies to supplement the many case studies and anecdotal reports. This study reports the results of such an investigation where sixty-nine male and female psychiatric inpatients were randomized to either an AAT psychiatric rehabilitation group or a similarly conducted control group without AAT, to test if AAT can improve prosocial behaviors. The Social Behavior Scale was scored daily by an independent rater and patients were monitored for four weeks. A two-group by weeks repeated measure analysis of variance was conducted for each outcome measure. There were no baseline differences between the two groups on demographics or any of the measures, but by week four, patients in the AAT group were significantly more interactive with other patients, scored higher on measures of smiles and pleasure, were more sociable and helpful with others, and were more active and responsive to surroundings. These data suggest that AAT plays an important role in enhancing the benefits of conventional therapy, and demonstrates the benefit of including a non-AAT group for comparison. The study also demonstrates the importance of using longitudinal, repeated measure designs. Previous studies may have failed to find significant effects because they were restricted to shorter intervals for measuring outcomes.     

Metal–Organic Frameworks for Photodynamic Therapy: Emerging Synergistic Cancer Therapy

Photodynamic therapy (PDT) conducted by photosensitizers producing cytotoxic reactive oxygen species (ROS) under light irradiation is widely used in cancer treatment. A great number of photoactive nanoscale metal–organic frameworks (NMOFs) have been prepared for PDT. With the development of biomedicine and nanotechnology, many synergistic cancer therapies have emerged. In this mini-review, an overview on the latest progress in the application of NMOFs in PDT is provided, with emphasis on the recent emergence of some synergistic therapies.     

原发性肝癌的介入治疗现状与进展

原发性肝癌(Hepatocellular carcinoma,HCC)是肝脏最常见的恶性肿瘤,具有高发病率、死亡率及预后差的特点,大多数患者确诊时为进展期,已失去手术机会,严重危及患者生命。虽然目前相关的治疗方法较多,但预后仍较差,介入治疗作为一种微创疗法在提高患者生存期、改善患者生活质量等方面取得显著效果。本文就原发性肝癌的介入治疗现状与进展进行综述。     

Meta-Analysis: Lactobacillus Containing Quadruple Therapy Versus Standard Triple First-Line Therapy for Helicobacter pylori Eradication

Background:  Recent evidence showed that Lactobacilli could exert an inhibitory effect on Helicobacter pylori both in vitro and in vivo models. To systematically evaluate whether adding Lactobacilli to H. pylori eradication regimens could improve eradication rates and reduce side effects during anti- H. pylori treatment.
Materials and Methods:  Eligible articles were identified by searches of electronic databases. We included all randomized trials comparing Lactobacilli supplementation to placebo or no treatment during anti- H. pylori regimens. Statistical analysis was performed with Review Manager 5.0.10. Subanalysis analysis was also performed.
Results:  We identified eight randomized trials (n = 1372). Pooled H. pylori eradication rates were 82.26% (95% CI = 78.01–86.51%) and 76.97% (95% CI = 73.11–80.83%) for patients with or without Lactobacilli by intention-to-treat analysis, respectively, the odds ratio (OR) was 1.78 (95% CI = 1.21–2.62). The occurrence of total side effects had no significant difference and were 30.84% (95% CI = 24.82–36.86%) and 42.24% (95% CI = 35.89%–48.59%) for two groups, the summary OR was 0.49 (95% CI = 0.24–1.02); However, Lactobacilli supplementation group had lower occurrence of diarrhoea, bloating and taste disturbance.
Conclusions:  Our review suggests that supplementation with Lactobacilli could be effective in increasing eradication rates of anti- H. pylori therapy for first-treated patients. Furthermore, Lactobacilli showed a positive impact on some H. pylori therapy-related side effects.     

二维过渡金属碳/氮化物在肿瘤治疗中的应用

二维过渡金属碳/氮化物（MXenes）具有优异的光热转换性能,丰富的表面基团,良好的生物相容性、亲水性和粒径可调性,这使得应用MXenes作为肿瘤诊疗过程中的治疗剂和造影剂具有巨大潜力。本文综述了基于MXenes的肿瘤单一治疗和联合治疗的相关研究,同时介绍了MXenes在肿瘤主动靶向治疗领域的研究,最后阐述了目前MXenes在制备和肿瘤治疗研究中存在的挑战和对未来的展望。     

以雷贝拉唑、左氧氟沙星为基础的三联补救疗法的临床观察

目的:观察以雷贝拉唑、左氧氟沙星为基础的三联疗法对幽门螺杆菌根除失败的补救疗法的临床疗效.方法:幽门螺杆菌根除失败的患者50例,予雷贝拉唑20mg,阿莫西林1.0,一天两次;左氧氟沙星0.5,一天一次;口服一周.停药1个月后行13C呼气试验检测来判断幽门螺杆菌根除率.结果:49例完成了整个研究过程,意向处理分析(ITT)根除率为82.00％,完成治疗分析(PP)根除率为83.67％,总的副作用发生率为12.00％,症状缓解率95.92％.结论:以雷贝拉唑、左氧氟沙星为基础的短程三联疗法对根治失败的幽门螺旋杆菌感染患者是一种安全、有效的治疗方案.     

胆管癌的光动力疗法

胆管癌(Cholangiocarcinoma CC)是一种罕见的胆道原发性恶性肿瘤,预后较差。根治性手术只适用于一小部分早期诊断的患者。姑息性的经皮或内镜下支架置入胆管引流术能通过减轻瘙痒,疼痛,和胆管炎的程度从而提高生活质量,但对于延长生存时间作用甚微。光动力疗法(PDT)是对于不能手术切除的CC的一种较新颖的局部微创性的姑息疗法。其原理是PDT中使用的光敏性分子能特异性的聚集在增生组织如肿瘤,在特定波长的光照下光敏剂激活生成活性氧类物质,从而选择性的导致肿瘤细胞的死亡。经过初步的可行性性研究和充满前景的前瞻性II期临床研究后,关于研究比较胆管支架置入联合光动力治疗与单纯胆管内支架置入的两组前瞻性随机对照试验已经发表。其中一组试验结果显示PDT组(493天)与非PDT组(98天)相比在中位生存期方面的显著优势(P0.0001),且PDT组患者的体力状态也明显改善。另一组试验也进一步明确了PDT治疗对于提高生存率方面的优势(PDT组630天而单纯支架置入组210天,P0.01)。整个治疗过程耐受性良好。有报道称PDT作为CC的辅助或新辅助疗法已取得了令人满意的结果,因此PDT可以被看作是治疗不能手术切除的胆管癌的一种标准性姑息治疗方法。     

RNA干扰技术治疗疾病

RNA干扰(RNA interference,RNAi)现象最早发现于秀丽隐杆线虫(Caenorhabditis elegans),随后发现该现象普遍存在于真菌、植物和哺乳动物等真核生物,并行使基因调控和抵御外源基因片段侵袭的作用。目前,RNAi分子机制和RNAi在基因功能方面的研究已经取得了突破性的进展。鉴于RNAi在基因沉默中的特异性、高效性和易操作,其在药物筛选和疾病治疗等方面有着广泛的应用前景。然而,RNAi技术用于治疗疾病的安全性尚待确定,分子传递途径也有待进一步的研究。     

干细胞和产前治疗

干细胞特殊的生物性质为产前治疗的研究和应用带来了新的希望。近年来,借助干细胞进行的产前治疗的基础研究进展迅速,为早日在临床广泛开展产前治疗提供了大量有益的参考和指导。本文就这方面的研究进展作一综述。 Stem Cells and Prenatal Therapy WANG Mo-lin,HUANG Shu-zhen Shanghai Institute of Medical Genetics,Shanghai Children Hospital,Shanghai 200040,China Abstract:The special biological properties of stem cells bring us new hope for the research and application of prenatal therapy.The basic reseach of prenatal therapy utilizing stem cells developed quickly,providing reference and direction for clinical therapy.This review is mainly related to the progress in this field in recent years. Key words：stem cell;prenatal therapy     

肿瘤基因治疗的研究进展

肿瘤是严重影响人类身体健康的重大疾病之一,肿瘤的发生发展是一个复杂的涉及到众多基因的过程,肿瘤的基因治疗也已经成为肿瘤治疗的研究热点之一。目前,肿瘤基因治疗的策略主要包括以下几个方面:基因沉默治疗、抑癌基因治疗、免疫基因治疗、自杀基因疗法、抑制肿瘤血管生成基因治疗、肿瘤多药耐药基因治疗、抗端粒酶疗法和多基因联合疗法等。我们简要地对上述策略及相关研究进展进行综述。     

肿瘤干细胞的光动力治疗研究进展

肿瘤干细胞(cancerstem cells,CSCs)是在肿瘤组织中具有干细胞特性的细胞亚群,它具有正常干细胞的多向分化潜能,能够无限增值和自主分化为各种具有异质性的肿瘤细胞。CSCs在肿瘤的发生、生长、转移中起着重要作用。同时,CSCs对目前大多数治疗如化疗、放疗不敏感,甚至具有耐药性,这也就导致了恶性肿瘤在治疗后容易复发。鉴于此,针对肿瘤干细胞的治疗日益受到关注,光动力疗法(photodynamictherapy,PDT)由于其微创性,不良反应少,靶向性强等特点在肿瘤的治疗研究中不断得到发展。本文将从CSCs的特性入手,结合PDT治疗的最新进展,探讨PDT治疗在肿瘤干细胞治疗中的应用。     

端粒生物学与肿瘤治疗

端粒的生物学功能主要是保护染色体末端,避免核酸酶对染色体末端的降解,防止染色体之间发生融合和重排。大多数人类肿瘤细胞通常通过端粒酶活性的重新激活来延长端粒,从而稳定染色体端粒DNA的长度。端粒酶是由端粒酶逆转录酶和端粒酶RNA模板组成的具有特殊逆转录活性的核糖核蛋白复合物。抑制端粒酶阳性细胞中的端粒酶活性会导致细胞凋亡或衰老。目前有多种以端粒和端粒酶为靶点来进行肿瘤治疗的策略。     

CAR-T联合疗法治疗实体瘤的研究进展

CAR-T疗法(chimeric antigen receptor T-cell immunotherapy)即嵌合抗原受体T细胞免疫疗法,是目前肿瘤免疫治疗中较有潜力的策略之一^[1],已成功应用于多种血液肿瘤的治疗。但CAR-T疗法在治疗实体瘤领域进展缓慢,存在肿瘤微环境的限制、细胞因子释放综合征以及严重的脱靶效应等诸多挑战^[2]。与单一靶向治疗相比,CAR-T联合疗法为改进肿瘤治疗方法提供了新的方向。综述目前常用的CAR-T联合治疗策略,针对CAR-T疗法在实体瘤治疗领域面临的主要挑战,探讨提高CAR-T疗效的潜在方案。     

视网膜色素变性治疗的临床前研究进展

人视网膜在组织学上分为十层,色素上皮(ＲＰＥ)和感光细胞(ＰＲＣ,包括视锥细胞ｃｏｎｅ和视杆细胞ｒｏｄ)是位于视网膜最外面的两层细胞。视网膜色素变性(ｒｅｔｉｎｉｔｉｓｐｉｇｍｅｎｔｏｓａ,ＲＰ)是一组以进行性感光细胞及色素上皮功能丧失为共同表现的遗传性视网膜变性疾病,主要临床特征为夜盲、进行性视野损害、眼底色素沉着和视网膜电图(ＥＲＧ)异常或无波。ＲＰ是遗传性视觉损害和失明的最常见原因之一,发病....     

肿瘤的分子治疗新进展

肿瘤的发生、发展是一个多步骤、多基因参与的、复杂的系统性过程.分子治疗作为21世纪最有希望根治人类肿瘤的技术,其治疗技术的关键在于靶分子的选择,寻找合适的靶分子一直是分子治疗肿瘤的重要方向.针对近年来肿瘤治疗研究中发现的端粒酶靶标、抗血管生成基因靶标、apoptin、survivin、stathmin、autophagy、PUMA、转铁蛋白受体靶标和相应的治疗策略作一综述.     

细胞衰老与癌症治疗

细胞衰老是生物界普遍存在的现象。肿瘤细胞是一类摆脱细胞周期束缚,突破Hayflick界限,能够无限增殖而不衰老的细胞。癌症是一种与细胞衰老密切相关的疾病。从进化的角度来看,衰老对于生物体是有益的,可以导致细胞不可逆的周期阻滞,被认为是一种自主的肿瘤抑制机制。在恶性增殖的癌细胞中,在胞外及胞内多种刺激下,如端粒缩短、DNA损伤、氧化应激以及化疗药物的处理等,都会出现细胞周期阻滞,生长迟缓等细胞衰老现象。诱导肿瘤细胞衰老也被认为是一种治疗癌症的有效手段。衰老细胞可以向胞外分泌数十种因子,维持细胞自身衰老表型,并影响周围细胞的生长,这种特性被称为衰老相关的分泌表型(SASP)。本文详细综述细胞衰老的形态学特征与分子标记物及检测方法,细胞衰老的信号调控通路（p53-p21,p16-pRB和PTEN-p27）,以及细胞衰老与恶性肿瘤发生发展的关系等。尤其是应激压力诱导下的细胞衰老在癌症治疗中的潜在作用,并进一步讨论当下流行的促衰老癌症治疗的靶点与药物以及存在的问题,以期为今后的研究提供新思路和新方向。