Perspectivas futuras del tratamiento de la hepatitis C, ¿sin interferón y sin ribavirina?

The hepatitis C virus is an important health problem worldwide. Currently, the standard treatment of genotype 1 chronic hepatitis C is the combination of pegylated interferon, ribavirin and a first-generation protease inhibitor: telaprevir or boceprevir. This triple therapy has improved the efficacy of treatment but has also increased regimen complexity, costs, and the number of adverse effects (mainly hematological and cutaneous). Unfortunately, viral response rates are still suboptimal in patients with cirrhosis, particularly those with a prior null response. Moreover, studies carried out in clinical practice have shown that the presence of advanced fibrosis confers a high risk of developing severe adverse effects during treatment (infection, decompensation and even death). It is therefore essential to select candidates for triple therapy according to their risk of complications and possibilities for cure. In this scenario, interferon (and ribavirin)-free combinations are very safe and well tolerated first-line treatments.     

序贯疗法与三联疗法治疗幽门螺杆菌性消化性溃疡疗效分析

目的：分析序贯疗法与三联疗法治疗幽门螺杆菌性消化性溃疡的治疗效果。方法选择我院近1年来82例幽门螺杆菌性消化性溃疡患者,随机分为两组,甲组患者采用序贯疗法,乙组患者采用传统的三联疗法,对比分析两种治疗方法的治疗效果。结果甲组患者的幽门螺杆菌（Hp）根除率为92.7%、不良反应发生率为7.3%,与乙组 Hp 根除率80.5%、不良反应发生率26.8%相比差异有统计学意义（P ＜0.05）。结论给予幽门螺杆菌性消化性溃疡患者采用10d 序贯疗法,安全有效,可显著提高患者依从性,应在临床治疗中广泛推广。     

The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1.     

Immunomodulation of Fungal β-Glucan in Host Defense Signaling by Dectin-1

During the course of evolution, animals encountered the harmful effects of fungi, which are strong pathogens. Therefore, they have developed powerful mechanisms to protect themselves against these fungal invaders. β-Glucans are glucose polymers of a linear β(1,3)-glucan backbone with β(1,6)-linked side chains. The immunostimulatory and antitumor activities of β-glucans have been reported; however, their mechanisms have only begun to be elucidated. Fungal and particulate β-glucans, despite their large size, can be taken up by the M cells of Peyer''s patches, and interact with macrophages or dendritic cells (DCs) and activate systemic immune responses to overcome the fungal infection. The sampled β-glucans function as pathogen-associated molecular patterns (PAMPs) and are recognized by pattern recognition receptors (PRRs) on innate immune cells. Dectin-1 receptor systems have been incorporated as the PRRs of β-glucans in the innate immune cells of higher animal systems, which function on the front line against fungal infection, and have been exploited in cancer treatments to enhance systemic immune function. Dectin-1 on macrophages and DCs performs dual functions: internalization of β-glucan-containing particles and transmittance of its signals into the nucleus. This review will depict in detail how the physicochemical nature of β-glucan contributes to its immunostimulating effect in hosts and the potential uses of β-glucan by elucidating the dectin-1 signal transduction pathway. The elucidation of β-glucan and its signaling pathway will undoubtedly open a new research area on its potential therapeutic applications, including as immunostimulants for antifungal and anti-cancer regimens.     

Expanding hepatocytes in vitro before cell transplantation: donor age‐dependent proliferative capacity of cultured human hepatocytes

Background: We have previously reported mixed infection with wild-type (sensitive) and mutant (resistant) Helicobacter pylori strains using a PCR-based preferential homo-duplex formation assay (PCR-PHFA) to detect gene mutations associated with clarithromycin resistance. Half of the cases with mixed infection were determined as sensitive by conventional MIC assessment and yet failed to respond to clarithromycin-based therapy. The aim of this study is to assess the efficacy of clarithromycin-based triple therapy in patients infected exclusively with wild-type strains as determined by PCR-PHFA. Methods: Ninety patients who had pure wild-type H. pylori infection were randomly assigned to receive clarithromycin (200 mg b.i.d.), amoxicillin (500 mg q.i.d.) and lansoprazole (30 mg b.i.d.) for either 5 days or 7 days (n = 48 and n = 42, respectively). The outcome of eradication was assessed by [13C] urea breath test. Results: Eradication was achieved in 36/48 (75%) versus 39/42 (93%) by intention-to-treat analysis (P = 0.02), and in 36/45 (80%) versus 39/40 (98%) by per protocol analysis (P = 0.01), for the 5- day and 7-day protocols, respectively. Compliance and the incidence of untoward effects were similar in both groups. Conclusions: Seven-day administration is necessary and sufficient for the triple therapy with clarithromycin, amoxicillin and lansoprazole in patients with pure wild-type H. pylori infection.     

Oblique spatial shifts of subjective visual straight ahead orientation in quadrantic visual field defects

Patients with postchiasmatic visual field defects often show a contralesional bias towards the scotoma in line bisection or when indicating their visual subjective straight ahead (VSSA). Recent evidence suggests a retinotopic misrepresentation of visual space in patients with homonymous quadrantanopia (HQ). We therefore assessed in the present study whether patients with HQ show an oblique shift of their VSSA towards their scotoma, in addition to the known bias in horizontal line bisection. Moreover, we examined whether eccentric fixation contributes to this shift. To this purpose, 15 non-neglecting stroke patients with HQ and 15 matched healthy control subjects were assessed in horizontal line bisection and in the horizontal and vertical dimension of their VSSA. Additionally, perimetric blind spot mapping was performed. Eight out of nine patients with left quadranopia showed the typical leftsided, horizontal line bisection error, while only one out of seven patients with rightsided quadranopia showed a rightsided shift. Normal subjects showed a non-significant leftward shift in line bisection (pseudoneglect). All 15 patients with HQ showed a large oblique shift of their VSSA towards the blind quadrants, while normal subjects showed no systematic left-rightward shift, but a small downward shift of the VSSA. The position of the blind spot was normal in all testable eyes of patients and control subjects, thus excluding eccentric fixation or cyclorotation of the eyes. In conclusion, our study reveals a hitherto unreported oblique spatial shift of subjective visual body orientation towards the blind quadrants in non-neglecting patients with quadranopia.     

Plasmodesmal targeting and intercellular movement of potato mop-top pomovirus is mediated by a membrane anchored tyrosine-based motif on the lumenal side of the endoplasmic reticulum and the C-terminal transmembrane domain in the TGB3 movement protein

Live-cell fluorescence microscopy was used to investigate the third triple gene block protein (TGB3) of potato mop-top pomovirus and its role in assisted targeting of TGB2 to plasmodesmata (PD). Wild-type and mutant TGB3 proteins were expressed under the control of the 35 S promoter or from a virus reporter clone. Assisted targeting of TGB2 to PD was optimal when the proteins were expressed from a bicistronic plasmid in the relative ratios expected in a virus infection, suggesting that excess TGB3 inhibited PD localisation. Contrary to the generally accepted view, bimolecular fluorescence complementation showed that the TGB3 N terminus is located in the cytosol. Mutational analysis to dissect TGB3 sub domain functions showed that PD targeting was mediated by a composite signal comprising an ER-lumenal tyrosine-based motif and the C-terminal transmembrane domain. Mutation of either of these domains also abolished cell-to-cell movement of the virus. The results are discussed in the context of TGB3 membrane topology.     

As2 O3对人胃癌BGC-823 细胞端粒酶的影响

 目的 观察三氧化二砷（As₂ O₃）对人胃癌BGC-823细胞端粒酶活性及端粒酶逆转录酶基因转录的影响。方法 用不同浓度的三氧化二砷作用于人胃癌BGC-823细胞，通过MTT法测定细胞活力；流式细胞术检测细胞凋亡变化；TRAP PCR ELIsA方法检测细胞端粒酶活性的变化；RT-PCR半定量方法检测细胞端粒酶hTEI汀基因mRNA的转录水平。结果 三氧化二砷可明显抑制人胃癌BGC-823细胞的生长，诱导细胞发生凋亡，抑制作用随三氧化二砷浓度的升高及作用时间的延长而增强。细胞的端粒酶活性明显下降，细胞hTERT基因的转录表达显著抑制。BGC-823细胞端粒酶活性的下调与As₂ O₃作用时间和浓度有关，呈现明显的时间-剂量效应关系。结论 As₂ O₃能够抑制人胃癌BGC-823细胞的增殖、促使细胞凋亡、抑制细胞的端粒酶活性。As₂ O₃是一种良好的端粒酶抑制剂，在肿瘤的治疗中具有一定应用价值。     

微生态制剂联合思密达治疗新生儿轮状病毒性肠炎的疗效观察

目的探讨微生态制剂(培菲康)联合思密达治疗新生儿轮状病毒性肠炎的临床疗效。方法对90例新生儿轮状病毒性肠炎患儿随机分为3组,在液疗、纠酸等治疗基础上,A组加用培菲康治疗,B组加用思密达治疗,C组加用培菲康联合思密达治疗,比较三组临床疗效。结果A、B、C组的总有效率分别为63·33%、66·67%、93·33%,平均止泻时间分别为(75·21±3·28)h、(73·33±5·05)h、(57·51±5·72)h。无论总有效率或平均止泻时间,C组与A组或B组相比,差异均有显著性(P<0·05或<0·01)。结论微生态制剂(培菲康)联合思密达治疗新生儿轮状病毒性肠炎的疗效肯定,值得临床推广使用。     

三联疗法治疗股骨头缺血性坏死36例临床观察

目的：观察三联疗法治疗股骨头缺血性坏死的临床疗效；方法：对36例42髋股骨头缺血性坏死均采用股骨头髓芯钻孔减压加植骨术、牵引加功能锻炼、中医辨证施治相结合治疗；结果：优11髋（26．3％），良17髋（40．5％），可9髋（21．2％），差5髋（12％）；结论：三联疗法治疗股骨头缺血性坏死疗效显著，尤其对早、中期及年轻患者疗效佳。