Caerulein-and xenopsin-related peptides with insulin-releasing activities from skin secretions of the clawed frogs, Xenopus borealis and Xenopus amieti (Pipidae)

Caerulein-related peptides were identified in norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus borealis and the octoploid frog Xenopus amieti using negative ion electrospray mass spectrometry and their primary structures determined by positive ion tandem (MS/MS) mass spectrometry. X. borealis caerulein-B1 (pGlu-Gln-Asp-Tyr(SO₃)-Gly-Thr-Gly-Trp-Met-Asp-Phe.NH2) contains an additional Gly⁵ residue compared with X. laevis caerulein and caerulein-B2 (pGlu-Asp-Tyr(SO₃)-Thr-Gly-Trp-Met-Asp-Phe.NH2) contains a Gln² deletion. X. amieti caerulein was identical to the X. laevis peptide. In addition, xenopsin, identical to the peptide from X. laevis, together with xenopsin-AM2 (pGlu-Gly-Arg-Arg-Pro-Trp-Ile- Leu) that contains the substitution Lys³ → Arg were isolated from X. amieti secretions. X. borealis caerulein-B1, and X. amieti xenopsin and xenopsin-AM2 produced significant (P < 0.05) and concentration-dependent stimulations of insulin release from the rat BRIN-BD11 clonal β cell line at concentrations ?30 nM. The peptides did not stimulate the release of lactate dehydrogenase at concentrations up to 3 μM demonstrating that the integrity of the plasma membrane had been preserved. While their precise biological role is unclear, the caerulein- and xenopsin-related peptides may constitute a component of the animal’s chemical defenses against predators.     

Secrets,shame and guilt: HIV disclosure in rural Chinese families from the perspective of caregivers

This in-depth ethnographic study examines the processes, barriers and impacts experienced by Mainland Chinese caregivers residing in rural Yunnan for disclosing HIV status to their adolescents born with the infection and other community members. In particular, highlighted are their associated personal, social, relational and cultural vulnerabilities. A purposeful sample of 13 pairs of HIV-born adolescents between the ages of 11–19 years and their primary caregivers were recruited in December 2014. The Conceptual Model Sexual Health Disclosure (CMSHD) was modified with Chinese culturally specific adaptation to guide the exploration of the complex aspects of the adolescents and caregiver’s relationships. All interviews were audiotaped, transcribed verbatim and then translated into English.

Complex sociocultural interactions emerging in these dyadic interviews included guilt, shame, unintended disclosure, the need for secrecy, perceived stigma, ‘loss of face’, protection of parents, inability to support their families and deep concerns over lineage and future marriage prospects amongst the parents, which had significant psychosocial and even physical impacts for these adolescents born with HIV and their families. Frontline health-care workers and HIV peer support programs are recommended to counteract China’s current top-down biomedical disease-related approach to health services. It is crucial to provide instrumental avenues of confidential psychosocial support including disclosure approaches for caregivers of HIV positive adolescents within a uniquely Chinese cultural context.     

Expression of interleukin 1β converting enzyme in 5-FU induced apoptosis in esophageal carcinoma cells

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Effect of HCV NS3 protein on P53 protein expression in hepatocarcinogenesis

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肝硬变和肝细胞癌组织中CD54,CD80,CD86和HLA-ABC的表达

目的探讨CD54,CD80,CD86和HLA-ABC在肝硬变的免疫损伤和抗肝癌免疫中的意义.方法用免疫组化方法检测CD54,CD80,CD86和HLA-ABC在肝硬变(n=30)和肝癌(n=48)中的表达、定位和分布.结果在LC中,CD54阳性率为40%(12/30),CD80为50%(15/30),CD86为37%(11/30),HLA-ABC为63%(19/30);在HCC中,CD54阳性率为77%(37/48),CD80为19%(9/47),CD86为13%(6/47),HLA-ABC为30%(12/40);在癌周围组织(PCT)中,CD54为阴性,CD80阳性率为44%(14/32),CD86为47%(15/32),HLA-ABC为53%(17/32).统计学处理显示,在LC中,CD54阳性率显著低于HCC(P＜0.01);CD80(P＜0.01),CD86(P＜0.05)和HLA-ABC(P＜0.01)均显著高于HCC;而与PCT无显著差别.在HCC中,CD80(P＜0.05),CD86(P＜0.01),HLA-ABC(P＜0.05),均显著低于PCT.结论 CD54,CD80,CD86和HLA-ABC在LC和HCC中的同时足量表达有可能引起肝细胞损伤和有效抗肿瘤免疫应答,而CD80,CD86表达的缺失或不足可能是HCC产生免疫逃避的主要原因.     

The Quest for New Anticoagulants: From Clinical Development to Clinical Practice

The Vitamin K antagonists (VKAs) have been the standard treatment of thromboembolic diseases for more than 50 years. They have been proved effective and safe under optimal settings; however, the long‐term application of VKAs has been considered problematic and challenging for both patients and physicians due to their narrow therapeutic window, the frequent drug to drug interactions and the need for regular monitoring. Novel anticoagulants that selectively block specific pathways of the coagulation cascade have demonstrated efficacy and safety without the need of intensive monitoring. Several novel anticoagulants are already licensed for the prevention and treatment of thromboembolic disease while others are in advanced stages of clinical development. This review summarizes data derived from recently published clinical trials and discusses the present and the future of oral anticoagulation.     

Stroke Risk Stratification in a “Real‐World” Elderly Anticoagulated Atrial Fibrillation Population

Stroke Risk Stratification . Introduction: Appropriate stroke risk stratification is essential to ensure suitable tailoring of antithrombotic therapy. The objective of this study was to assess the predictive value of stroke risk classification schemes and to identify patients with atrial fibrillation (AF) who are at substantial risk of stroke despite optimal anticoagulant therapy, in a “real world” consecutive elderly AF cohort. Methods: Six hundred and sixty‐two consecutive AF patients (mean [SD] age 74 [7.7] years; 36.1% female) referred to the Anticoagulation Clinic of the Azienda Ospedaliera Careggi of Florence, Italy, were included and followed‐up for a mean 3.6 ± 2.7 years for the incidence of thromboembolic (TE) events. The ability of the new CHA₂DS₂‐VASc schema to predict TE was compared with other contemporary stroke risk schema (including CHADS₂, NICE 2006, ACC/AHA/ESC 2006, and ACCP 2008), by determining the c‐statistic. Results: Univariate predictors of TE events were female gender (odds ratio 1.9; 95%CI [confidence intervals] 1.01–3.70) and previous stroke/transient ischemic attack (TIA)/TE (OR 5.6; 95%CI 2.70–11.45), although after adjustment only previous stroke/TIA/TE was an independent predictor of TE (OR 5.5; 95%CI 2.68–11.31; P = 0.0001). All stroke risk schema had modest discriminating ability, with c‐statistics ranging from 0.54 (atrial fibrillation investigators [AFI]) to 0.72 (CHA₂DS₂‐VASc). The CHADS₂ and CHA₂DS₂‐VASc schemes having the best c‐statistics (0.717 and 0.724, respectively) with significant discriminating value between risk strata (both P < 0.001). The proportion of patients assigned to individual risk categories varied widely across the schema, with those categorized as “moderate‐risk” ranging from 5.3% (CHA₂DS₂‐VASc) to 49.2% (CHADS₂‐classical). Conclusion: In this “real world” cohort, current published risk schemas have modest predictive ability, with the CHADS₂ and CHA₂DS₂‐VASc schemes having the best predictive value for thromboembolism. Future trials could assess the value of alternative strategies for thromboprophylaxis in high‐risk anticoagulated patients identified by these schemes. (J Cardiovasc Electrophysiol, Vol. 22, pp. 25‐30, January 2011)     

Prognostic factors affecting survival and recurrence after hepatic resection for hepatocellular carcinoma in cirrhotic liver

Aim  

Hepatic resections for hepatocellular carcinoma (HCC) in cirrhotic liver are characterized by early recurrence and poor survival. In this study, we analyzed several factors affecting both survival and recurrence after hepatic resection.