Restraint stress and ethanol consumption in two mouse strains

Background: This study examined the interaction between restraint stress and ethanol drinking in mice that consume low and high amounts of ethanol. Methods: Two strains of mice (129SVEV and C57BL/6J) underwent 1 hour of restraint stress twice per day for 4 days in the presence of a CRF‐1 receptor antagonist, a glucocorticoid receptor antagonist or vehicle. Ethanol preference and consumption were assessed using a two bottle choice design. In another study, mice were implanted with pellets containing corticosterone; ethanol preference and consumption were assessed using a two bottle choice design. Results: Restraint stress significantly increased ethanol preference and consumption in 129SVEV mice but not in C57BL/6J mice. Then 129SVEV mice underwent the identical stress procedure; however, mice received either the CRF‐1 receptor antagonist, R121919 (15 or 20 mg/kg, ip) or vehicle 30 minutes prior to stress. R121919 did not block the stress‐induced change in ethanol preference despite causing a significant blunting in the HPA axis. Negative results were also obtained using the CRF‐1 receptor antagonist, Antalarmin (20 mg/kg, ip). In another study, 129SVEV mice were administered either the glucocorticoid receptor antagonist Mifepristone (25, 50 or 100 μg/kg, ip) or vehicle under the same procedure. Mifepristone did not alter ethanol preference. Moreover, the three receptor antagonist did not alter nonstress ethanol consumption either. In the last study, both mouse strains underwent active or sham adrenalectomy, then pellets containing corticosterone or placebo were implanted and preference for ethanol versus water was tested. Corticosterone administration decreased ethanol consumption in a strain‐dependent manner. Conclusion: These data show the restraint model for stress can modestly increase ethanol consumption in 129SVEV mice but not in C57BL/6J mice. Pharmacologic manipulation of CRF and corticosterone did not blunt baseline or stress‐induced change in ethanol preference nor did administration of corticosterone mimic the effects of restraint stress on ethanol consumption. These findings suggest the mechanism responsible for increasing ethanol consumption in this model is independent of the HPA axis and extra‐hypothalamic CRF.     

Fertility awareness and attitudes among resident physicians across different specialties

Journal of Assisted Reproduction and Genetics - To evaluate knowledge of age-related fertility decline and oocyte cryopreservation among resident physicians in obstetrics and gynecology (ob-gyn)...     

Promoter hypermethylation in sentinel lymph nodes as a marker for breast cancer recurrence

Purpose Promoter methylation of tumor suppressor genes in histologically negative sentinel lymph nodes (HNSN) of early stage breast cancer patients has not been extensively studied. This study evaluates the methylation frequency and pattern in HNSN to determine if detection of hypermethylation of one or more genes is associated with an increased recurrence risk in node negative breast cancer. Experimental design In 1998, a prospective study of patients with early stage breast cancer and HNSN was initiated in order to correlate sentinel node analysis with clinical outcome. Nodal tissue was selected from 120 HNSN patients for methylation analysis in at least one and up to six sentinel nodes using a panel of nine genes. Corresponding primary breast tumors from 79 patients were also evaluated for hypermethylation. Methylation analysis was performed using nested Methylation Sensitive PCR (n-MSP). Logistical regression was used to evaluate the relationship between clinical recurrence and methylation status. Results Over a median follow-up of 79 months, 13 of the 120 patients had clinical recurrence. Hypermethylation of genes was frequently observed in HNSN, but there was no correlation of methylation pattern and clinical recurrence. However, increased frequency of gene methylation of the primary tumor correlated with clinical recurrence. Conclusions Although hypermethylation of multiple genes occurs frequently in HNSN of breast cancer patients, it is not associated with breast cancer recurrence in the first 7 years of clinical follow-up. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. An invited commentary to this article can be found at doi:.     

Biochemical and Cellular Analysis of Human Variants of the DYT1 Dystonia Protein,TorsinA/TOR1A

Early‐onset dystonia is associated with the deletion of one of a pair of glutamic acid residues (c.904_906delGAG/c.907_909delGAG; p.Glu302del/Glu303del; ΔE 302/303) near the carboxyl‐terminus of torsinA, a member of the AAA⁺ protein family that localizes to the endoplasmic reticulum lumen and nuclear envelope. This deletion commonly underlies early‐onset DYT1 dystonia. While the role of the disease‐causing mutation, torsinAΔE, has been established through genetic association studies, it is much less clear whether other rare human variants of torsinA are pathogenic. Two missense variations have been described in single patients: R288Q (c.863G>A; p.Arg288Gln; R288Q) identified in a patient with onset of severe generalized dystonia and myoclonus since infancy and F205I (c.613T>A, p.Phe205Ile; F205I) in a psychiatric patient with late‐onset focal dystonia. In this study, we have undertaken a series of analyses comparing the biochemical and cellular effects of these rare variants to torsinAΔE and wild‐type (wt) torsinA to reveal whether there are common dysfunctional features. The results revealed that the variants, R288Q and F205I, are more similar in their properties to torsinAΔE protein than to torsinAwt. These findings provide functional evidence for the potential pathogenic nature of these rare sequence variants in the TOR1A gene, thus implicating these pathologies in the development of dystonia.     

恶性肿瘤患者外周血调节性T细胞及Th1、Th2细胞的检测和临床意义

目的:通过检测恶性肿瘤患者外周血中的淋巴细胞亚群、CD4+CD25+调节性T细胞(Treg细胞)以及Th1、Th2细胞的数量,了解恶性肿瘤患者的免疫状态。方法:采用流式细胞仪检测90例恶性肿瘤患者(肿瘤组)及60例健康体检者(对照组)外周血中的淋巴细胞亚群、Treg细胞和以及Th1和Th2细胞数量。结果:肿瘤组外周血CD3+T细胞、CD4+T细胞和NK细胞的数量均显著低于对照组(P<0.05),而Treg细胞显著高于对照组(P<0.05)。肿瘤组分泌IFN-γ的Th1细胞显著低于对照组(P<0.05),而分泌IL-4的Th2细胞显著高于对照组(P<0.05)。结论:恶性肿瘤患者Treg细胞数量增多,Th1细胞数量减少,Th2细胞数量增加,这可能是其免疫功能处于抑制状态的重要原因。     

老年人抗生素相关性肠道菌群失调的防治

目的观察肠道微生态调节剂培菲康胶囊对老年人抗生素相关性肠道菌群失调的防治作用.方法将幽门螺杆菌(Helicobacter pylori)感染的十二指肠溃疡及胃溃疡患者随机分至A组(阿莫西林、甲硝唑、奥美拉唑、果胶铋四联治疗组)和B组(四联加培菲康治疗组),疗程均为2周,治疗结束4周后复查13C-尿素呼气试验及快速尿素酶试验判断根除H.pylori疗效.依据腹泻症状、粪便常规及镜检结果判定肠道菌群失调.结果A、B两组疗法均有较理想根除H.pylori疗效,根除率分别为92.19%、96.88%,两组比较差异无显著性(P＞0.05).单纯四联治疗组抗生素相关性肠道菌群失调发生率明显高于四联加培菲康组(P＜0.05).A组中55岁以上患者肠道菌群失调发生率(35.29%)明显高于55岁以下患者(12.77%,P＜0.05);与A组比较,B组老年患者肠道菌群失调发生率明显下降(10.53%,P＜0.05).结论培菲康胶囊能有效地防治老年人根除HP治疗所致抗生素相关性肠道菌群失调的发生.     

胃癌的现代诊断和治疗

胃癌是消化道最常见的恶性肿瘤,近年来,该病的发生率逐渐上升,这一方面是因为环境等因素的改变使人们接触的有害因子增多,精神压力增大,胃癌的实际发病率上升.另一方面,胃镜的普及应用以及人们卫生保健意识的提高,使胃癌的发现率提高.根据其发展阶段可分为早期胃癌(癌肿尚未侵及肌层)和进展期胃癌.     

胃癌的现代诊断和治疗

胃癌是消化道最常见的恶性肿瘤,近年来,该病的发生率逐渐上升,这一方面是因为环境等因素的改变使人们接触的有害因子增多,精神压力增大,胃癌的实际发病率上升。另一方面,胃镜的普及应用以及人们卫生保健意识的提高,使胃癌的发现率提高。根据其发展阶段可分为早期胃癌(癌肿尚未侵     

内镜下注射A型肉毒毒素治疗贲门失弛缓症

目的介绍内镜下注射 A型肉毒毒素（ BTXA）治疗贲门失弛缓症 (AC)的方法,探讨其近期疗效。方法原发性 AC患者 13例,于治疗前和治疗后 1周做症状计分和食管造影（测量贲门开口、 5分钟食管存留造影剂的高度和平均宽度）。内镜下于贲门齿状线上 0.5cm分 4点各注射 BTXA 20U至下食管括约肌。结果治疗次日症状即明显缓解,咽下困难频度、咽下困难程度、反食频度、胸骨后疼痛频度计分均明显减少;贲门开口由治疗前的 (1.5± 1.8)mm增大至 (4.4± 2.4)mm, P< 0.001; 5分钟食管碘柱高度和平均宽度分别由治疗前的 (89.5± 37.4)mm和 (31.9± 11.3)mm降至治疗后的 (14.4± 22.0)mm和 (8.4± 9.4)mm, P< 0.001。结论内镜下注射 BTXA治疗 AC安全、经济、简便易行,近期效果良好。