A randomized trial of Chinese herbal medicines for the treatment of symptomatic hepatitis C

BACKGROUND: Many patients with the hepatitis C virus (HCV) cannot be successfully treated with interferon-based regimens. Chinese herbal medicines have been widely prescribed for HCV in Asia, and many infected patients in the United States have used these agents. However, data to support the efficacy of these medications are limited and, to our knowledge, no published trials have been conducted in a US population. METHODS: In a double-blinded design, 45 patients with HCV and fatigue were randomized to receive a combination of Chinese herbal medications or a matched placebo for 12 weeks. The main outcome measures were changes in health-related quality of life using the role physical and vitality scale scores from the validated Hepatitis Quality of Life Questionnaire and alanine aminotransferase levels. In addition, other Hepatitis Quality of Life Questionnaire variables, HCV load, and adverse effects were monitored. RESULTS: In patients with HCV, the herbal medications had no effect on any quality-of-life variables, as measured by the Hepatitis Quality of Life Questionnaire. In addition, no significant changes in alanine aminotransferase or serum HCV RNA levels were noted. No significant adverse effects were observed. CONCLUSIONS: In this study, a regimen of Chinese herbal medicines did not improve quality of life, liver chemistry results, or viral load in a cohort of patients with HCV. Patients and practitioners should remain cautious about the use of herbal medicines for HCV, because studies have not shown a clear benefit of these agents.     

TLIF术式在布氏杆菌性脊柱炎病人中的临床疗效及安全性分析

目的 对比分析单纯后路内固定+一期经腰椎间孔病椎间病灶清除(TLIF)与经典的前后联合手术在布氏杆菌性脊柱炎患者中的临床疗效及安全性。 方法 对我院2015年1月至2017年12月收治的93例布病性脊柱炎患者的临床资料进行分析。按手术方式分为观察组(45例)和对照组(48例)。对两组患者的基础数据、临床指标、术前术后各项指标水平以及术后并发症、植骨治愈情况。 结果 观察组与对照组基础数据比较,差异无统计学意义(P>0.05)。观察组患者的手术时间、住院天数、术中出血量及术后下床时间均明显低于对照组(P<0.01)。两组患者术后3个月的ODI、VAS、CRP、ESR及Cobb角均明显低于术前(P<0.05);术后3个月,观察组患者的ODI、VAS、CRP、ESR及Cobb角均明显低于对照组(P<0.05)。观察组术后并发症发生率(4.4%)明显低于对照组(25.0%)(Χ²=7.674,P<0.01)。 结论 TLIF治疗布氏杆菌性脊柱炎患者的临床疗效突出,安全性较好,更有利于患者术后身体的恢复。     

Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo that directs pulsatile secretion. FSH containing this heptapeptide enters the regulated pathway in gonadotropes of transgenic mice, and is released in response to gonadotropin-releasing hormone, similar to LH. FSH released from the LH secretory pathway rescued ovarian defects in Fshb-null mice as efficiently as constitutively secreted FSH. Interestingly, the rerouted FSH enhanced ovarian follicle survival, caused a dramatic increase in number of ovulations, and prolonged female reproductive lifespan. Furthermore, the rerouted FSH vastly improved the in vivo fertilization competency of eggs, their subsequent development in vitro and when transplanted, the ability to produce offspring. Our study demonstrates the feasibility to fine-tune the target tissue responses by modifying the intracellular trafficking and secretory fate of a pituitary trophic hormone. The approach to interconvert the secretory fate of proteins in vivo has pathophysiological significance, and could explain the etiology of several hormone hyperstimulation and resistance syndromes.During vertebrate evolution, the female reproductive pattern underwent a remarkable transition from spawning of large number of eggs in primitive species under favorable conditions to more tightly controlled ovarian cycles in higher vertebrates, such that only a limited number (rodents) or a single (human and nonhuman primates) egg is released per cycle (1, 2). Coincident with this event, the single pituitary gonadotropic hormone that exists in primitive vertebrates has given rise to two gonadotropins, FSH and luteinizing hormone (LH), which coordinate gametogenesis and steroidogenesis (3–7). FSH and LH are heterodimeric glycoproteins that contain a common α-subunit and a hormone-specific β-subunit (3). Although synthesized in the same cell, the gonadotrope, FSH is mostly constitutively released in many species, whereas LH is stored in dense core granules (DCGs) and secreted in pulses via the regulated pathway in response to gonadotropin-releasing hormone (GnRH) (8, 9). Although this pattern is evolutionarily conserved, how distinct modes of gonadotropin secretion affect ovarian development and target cell responses remain unclear. Although models in which variations in secretion of gonadotropins have been achieved in vivo (10) and in vitro, including basolateral and apically polarized secretion (11), the in vivo consequences of altered mode of gonadotropin trafficking and release (constitutive vs. regulated) from pituitary are untested. We sought to identify why the two gonadotropins, LH and FSH, expressed in the same pituitary cell have evolved to exit via different routes to regulate ovarian physiology.     

Enhanced Bone Regeneration Using Porcine Small Intestinal Submucosa

Small instestinal submucosa (SIS) is an easily produced material that has been used experimentally for tissue engineering. To evaluate the ability of SIS to facilitate bone growth within a long-bone defect, a segment of the radius was surgically removed in adult, female Sprague-Dawley rats. The defect was either left unfilled or implanted with SIS, demineralized cortical bone (DMCB), or ovalbumin. The defect was evaluated radiographically and histologically after 3, 6, 12, and 24 weeks. Tissue remodeling within the defect was evident by week 3 in SIS- and DMCB-treated rats. Filling was characterized initially by infiltration of mononuclear cells and extracellular material in SIS-implanted rats and multifocal remodeling bone particles and cartilage formation in DMCB implanted rats. Cartilage was observed as early as 3 weeks and bone as early as 6 weeks in SIS-implanted rats. Filling of the defect arose from multiple foci in DMCB-implanted rats, but was contiguous with and parallel to the ulnar shaft in SIS-implanted rats, suggesting that defect repair by SIS may be conductive rather than inductive. Rats in which the defect was left unfilled demonstrated slow but progressive filling of the defect, characterized by mononuclear cell infiltrates and fibrous extracellular material. In summary, SIS facilitated rapid filling of a longbone defect. These results suggest that SIS may be useful as a bone repair material.     

The Quality of Life of Family Caregivers of Eating Disorder Patients

Having a relative with an eating disorder (ED) affects the life of family caregivers and may thus affect their quality of life. To study this aspect, 40 caregivers of ED patients filled out a health-related quality of life questionnaire (Short Form-36) and a questionnaire on the impact of the ED on various areas of life domains, and on the relationship with the ED patient and the need for professional support. Quality of life of caregivers was worse than in a normal reference group. Specifically, mental health, vitality and emotional role functioning were reported to be most impaired. ED appeared to affect families’ lives substantially. In response to the ED, caregivers felt anxious, powerless, sad, or desperate. The relationship of the caregiver with the ED patient had also changed. Caregivers were more worried, lost their trust, and reported more conflicts. Seventy five percent welcomed professional support. Caregivers need practical advice, information on ED, and emotional support. Quality of life of caregivers should be addressed in the treatment of ED.     

Surrogate markers for cerebral blood flow correlate with [18F]‐fallypride binding potential at dopamine D2/3 receptors in human striatum

Positron emission tomography (PET) with the high affinity dopamine D_2/3 receptor ligand [¹⁸F]‐fallypride affords estimates of the binding potential (BP_ND) in extra‐striatal regions of low receptor abundance, but the sufficient recording time for accurate measurements in striatum has been called into question. We have earlier argued that transient equilibrium measurements are obtained in striatum with [¹⁸F]‐fallypride PET recordings of 3 h duration, which may be the practical limit for clinical investigations without interrupted scanning. However, the high extraction fraction of [¹⁸F]‐fallypride predicts flow‐dependence of tracer delivery to brain, which may be a source of variance of the apparent BP_ND in regions of high binding. To test this prediction, we conducted a retrospective analysis of [¹⁸F]‐fallypride PET data from a group of 50 healthy volunteers (age 18–58 years [mean ± SD: 32.6 ± 10.6), who had participated in clinical studies without arterial input measurements. We used the initial 120‐s integral (AUC) of the venous confluence (VC) as a surrogate marker for cerebral blood flow (CBF) and tested for correlations between regional estimates of BP_ND calculated by the simplified reference tissue model (SRTM) and the individual VC‐AUC. The magnitude of BP_ND in a high binding region (putamen), but not in a low binding region (thalamus) correlated positively with VC‐AUC, suggesting that approximately 9% of the variance in the [¹⁸F]‐fallypride BP_ND in putamen can be attributed to individual differences in this surrogate marker for CBF, a contribution equal in magnitude to the effects of age on BP_ND in putamen of the present healthy control group. Synapse, 2013. © 2012 Wiley Periodicals, Inc.     

亚麻子水提液对DPP-4及α-葡萄糖苷酶活性抑制实验研究

目的通过观察亚麻子水提液对二肽基肽酶-4（DPP-4）、α-葡萄糖苷酶抑制作用,为该药防治糖尿病提供实验依据。方法①以DPP-4酶、缓冲液、底物建立DPP-4抑制剂的体外筛选体系,对亚麻子水提液进行抑制实验,采用发色底物法测定吸光度（OD）,计算DPP-4抑制率及IC50值;②以蔗糖为底物建立α-葡萄糖苷酶活性抑制模型,采用葡萄糖氧化酶法测定亚麻子水提液对α-葡萄糖苷酶的抑制作用,计算其抑制率和IC50值。结果①亚麻子具有轻度DPP-4抑制作用,其IC50值738.20mg/L;②亚麻子具有α-葡萄糖苷酶抑制作用,其IC50值为365.9mg/mL。结论亚麻子水提液可一定程度地抑制DPP-4及α-葡萄糖苷酶活性。     

Heterologous Expression and Functional Characterization of the Exogenously Acquired Aminoglycoside Resistance Methyltransferases RmtD,RmtD2, and RmtG

The exogenously acquired 16S rRNA methyltransferases RmtD, RmtD2, and RmtG were cloned and heterologously expressed in Escherichia coli, and the recombinant proteins were purified to near homogeneity. Each methyltransferase conferred an aminoglycoside resistance profile consistent with m⁷G1405 modification, and this activity was confirmed by in vitro 30S methylation assays. Analyses of protein structure and interaction with S-adenosyl-l-methionine suggest that the molecular mechanisms of substrate recognition and catalysis are conserved across the 16S rRNA (m⁷G1405) methyltransferase family.     

A selective allosteric potentiator of metabotropic glutamate (mGlu) 2 receptors has effects similar to an orthosteric mGlu2/3 receptor agonist in mouse models predictive of antipsychotic activity

Recent studies suggest that agonists of group II metabotropic glutamate (mGlu) receptors (mGlu2/3) have potential utility as novel therapeutic agents for treatment of psychiatric disorders such as anxiety and schizophrenia. Agonists of mGlu2/3 receptors block amphetamine- and phencyclidine (PCP)-induced hyperlocomotor activity in rodents, two actions that may predict potential antipsychotic activity of these compounds. We now report that LY487379 [N-(4-(2-methoxyphenoxy)phenyl)-N-(2,2,2-trifluoroethylsulfonyl)pyrid-3-ylmethylamine], a recently described selective allosteric potentiator of mGlu2 receptor, has behavioral effects similar to mGlu2/3 receptor agonists. LY487379 and LY379268 [(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate], an ortho-steric mGlu2/3 receptor agonist, induced similar dose-dependent reductions in PCP- and amphetamine-induced hyperlocomotor activity in C57BL6/J mice at doses that did not significantly alter spontaneous locomotor activity. These effects were blocked by the mGlu2/3 receptor antagonist LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid]. LY487379 had a short duration of action compared with LY379268. Furthermore, unlike the mGlu2/3 agonist, LY487379 reversed amphetamine-induced disruption of prepulse inhibition of the acoustic startle reflex. When LY379268 was given chronically, it failed to block amphetamine- and PCP-induced hyperlocomotor activity. The finding that the effects of an orthosteric mGlu2/3 receptor agonist in these models can be mimicked by a selective allosteric potentiator of mGlu2 suggests that these effects are mediated by the mGlu2 receptor subtype. Furthermore, these data raise the possibility that a selective allosteric potentiator of mGlu2 receptor could have utility as a novel approach for the treatment of schizophrenia.     

Fresh water drowning and near-drowning-an update

Canadian Journal of Anesthesia/Journal canadien d'anesthésie - The current status of fresh water near-drowning including some recent advances has been reviewed, with particular emphasis on...