Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva

IntroductionThe sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking.MethodsA retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment.ResultsOverall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported.ConclusionTreatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.     

脑络康缓释胶囊的制备工艺和体外释放度的研究

以羟丙甲基纤维素作为主要的缓释辅料,采用正交设计方法优化处方研制成脑络康缓释胶囊.以人参皂苷的累积释放量作为考察指标,按照<药典>规定的缓释制剂的释放度进行优选.结果:最佳的处方工艺即羟丙甲基纤维素216 mg,乙基纤维素24 mg,混合稀释剂132 mg,释放曲线符合Higuchi动力学模型.     

Recent Ⅳ-drug users with chronic hepatitis C can be efficiently treated with daily high dose induction therapy using consensus interferon:An open-label pilot study

INTRODUCTION Under physiological conditions, interferon-α (IFN-α) is a key cytokine produced by virtually all cells in the mammalian organism in response to a variety of bacterial and viral stimuli. In response to viral infection, IFN-α produced by the infected target cells induces a number of cellular genes involved in inhibition of viral replication. In addition, IFN-α is secreted by stimulated NK-cells and T-cells and exerts a multitude of immune stimulatory effects of innate a…     

盐酸维拉帕米自乳化缓释片的研制及释药行为的探讨

目的：探索固体自乳化释放药系统，研制自乳化缓释片，考察体外释药行为。方法：以盐酸维拉帕米（Verpamil Hydrochloride,VH)为模型药物，以吐温80（Tween80），豆磷脂（sbpc)为乳化剂，以羟丙甲纤维素（HPMC），卡波普（carbopol)为骨架材料，制备自乳化缓释片。结果：以含吐温80和豆磷脂10％，羟丙甲纤维素和卡波普30％的处方乳化效果好，体外释药符合要求。结论：通过调节乳化剂和骨架材料的比例，可以获得理想的自乳化固体缓释制剂。     

Inhibition of IL-2 synthesis by donor-pecific suppressor T cells in a renal transplant recipient

Abstract A study was conducted to elucidate the mechanism of donor-pecific Mixed Lymphocyte Reaction (MLR and Cell Mediated Lymphotoxicity (CML) unresponsiveness in a renal transplant recipient with a long-term well-functioning kidney. The peripheral blood lymphocytes (PBL) of the recipient, who had not shown rejection since his transplantation 5 years previously, and those of his mother (donor), his father and two healthy third parties were examined. MLR, CML, semimicro MLR in a double chamber, interleukin-2 (IL-2) synthesis assay and limiting dilution assay were performed. This recipient showed donor-pecific MLR and CML unresponsiveness. IL-2 assay showed that the PBL of the recipient produced less IL-2 against the donor than against the father and the third parties. The addition of exogenous recombinant IL-2 (rIL-2; Takeda Co.) to the priming MLR caused a recovery of CML against the donor. A limiting dilution assay indicated that cytotoxic T cell precursor (CTLp) frequencies against the donor and father did not differ. The suppressor assay in a double chamber indicated that the PBL of the recipient stimulated by the donor PBL had a non-pecific suppressive effect on MLR, CML and IL-2 synthesis of the PBL across the Major Histocompatibility Complex (MHC) barrier. This suppressive effect was abolished by OKT3 or OKT8 monoclonal antibody and complement. Thus, the recipient had donor-pecific suppressor T cells that produced a humoral non-pecific suppressive factor only when stimulated by the donor PBL, and this factor suppressed PLR and CML by inhibiting IL-2 synthesis of the PBL.     

The sustained inward current in sino-atrial node cells of guinea-pig heart

 Single myocytes were dissociated from the sino-atrial (SA) node of guinea-pig hearts. Only a quite small fraction of the cell population showed spontaneous action potentials and these cells were characterized by the presence of the hyperpolarization-activated cation current I _f , the delayed rectifier K⁺ current I _K and the L-type Ca²⁺ current I _Ca,L as well as by the absence of both the transient outward current I _to and the inward rectifier K⁺ current I _K,1. After blocking I _f and I _K, depolarizing pulses from –80 mV revealed a large nicardipine-sensitive late current (NSLC). The NSLC was scarcely affected by decreasing extracellular [Ca²⁺] ([Ca²⁺]_o) from 1.8 to 0.1 mM, while it was decreased significantly by depleting [Na⁺]_o, differently from I _Ca,L. NSLC was blocked by nicardipine and was increased by Bay K 8644. NSLC was increased by isoprenaline and the additional application of acetylcholine reversed the increase of this current. We conclude that NSLC is largely composed of I _st described in the rabbit SA node pacemaker cells, and that I _st is unique for the pacemaker cells in mammalian SA node cells. Most of the quiescent cells showed neither I _f nor I _st. Received: 22 July 1996 / Received after revision: 30 September 1996 / Accepted: 9 October 1996     

Predicting development of sustained unresponsiveness to milk oral immunotherapy using epitope-specific antibody binding profiles

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Monovalent cation conductance of the sustained inward current in rabbit sinoatrial node cells

 Under the whole cell clamp, superfusion of the rabbit sinoatrial node cells with a Na⁺-free solution suppressed the sustained inward current (I_st), and the L-type Ca²⁺ current (I_Ca,L) could be recorded on depolarization less negative than –40 mV from the holding potential of –80 mV. On the other hand, replacement of Ca²⁺ with Mg²⁺ in the external solution suppressed inward-going I_Ca,L and isolated I_st. Under this condition, I_st measured as a nicardipine-sensitive current showed an activation threshold between –60 and –70 mV. The conductance sequence of I_st for monovalent ions was determined as Na⁺ > Li⁺ >> K⁺ @ Cs⁺ by replacing the external Na⁺ with these alkali metal ions. The contribution of I_st to the diastolic depolarization is discussed. Received: 12 June 1996 / Received after revision: 31 July 1996 / Accepted: 7 August 1996     

Cardiac vagal tone and sustained attention in school-age children

Three hypotheses tested relationships between cardiac responses mediated via the vagus and sustained attention in a population of normal school-age children. These hypotheses addressed the theoretical relationships among resting cardiac vagal tone (using the Porges estimate of respiratory sinus arrhythmia, V), performance measures of sustained attention, and cardiac reactivity during sustained attention. Thirty-two fourth and fifth grade children performed a continuous performance task while their electrocardiograms were monitored. Children with higher resting levels of V performed better on the first 3-min block of the continuous performance task. Additionally, levels of V were significantly reduced across the blocks of the 9-min task for all children. No relationships were found between resting levels of V and change in either V or heart period during task performance. These findings support two of the three hypotheses proposed by Porges regarding individual differences in cardiac vagal tone and sustained attention.     

ERP modulations indicate the selective processing of visual stimuli as a result of transient and sustained spatial attention

Two experiments investigated selective processing as a result of transient and sustained visual-spatial attention. In Experiment 1, attention was cued on a trial-by-trial basis and event-related brain potentials were measured to stimuli preceded by valid, invalid, or neutral symbolic precues. Trial validity had only small effects on posterior PI and N1 components. At midline electrodes, an enhanced negativity for valid as compared with invalid trials was present, which appeared to reflect initial processing costs for invalid trials followed by an additional processing benefit for valid trials. Experiment 2 investigated whether these effects are specific for transient spatial attention by comparing transient and sustained attention conditions. No indication of early processing costs was found in the latter case.