血清Cys C对原发性高血压患者心、肾功能损害的评估价值

【目的】探讨血清胱抑素C（CysC）对原发性高血压患者心、肾功能损害的评估价值。【方法】选取2011年1月至2014年9月本院收治的186例原发性高血压患者,并分为合并心、肾功能损害组（A组,n=63）与不合并心、肾功能损害组（B组,n=123）,随机选择同期来本院体检的健康成人80例为对照组（C组）。比较三组的性别、年龄、血清CysC水平及其他临床指标。采用简单线性相关和多重线性回归探讨原发性高血压患者的血清CysC与各临床指标的关系,并采用受试者工作特征（ROc）曲线下面积评价血清CysC水平及其他指标对原发性高血压患者肾功能损害的诊断价值。【结果】三组在收缩压（SBP）、舒张压（DBP）、CysC、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、血尿素氮（BUN）、血肌酐（SCr）、肾小球滤过率（GFR）、尿微量白蛋白（mALB）、左心室射血分数（LVEF）、左心室质量指数（LVMI）等指标比较,差异均有统计学意义（P〈0．05）。血清CysC水平与SCr、mALB、LVMI等指标呈正相关（P〈0．05）,与GFR、LVEF等指标呈负相关（P〈0．05）。CysC、BUN、SCr、mALB的曲线下面积分别为0．752、0．673、0．688、0．620。【结论】原发性高血压合并心、肾功能损害患者的血清CysC水平明显升高,血清CysC水平可作为评估心、肾损害的相关指标之一。     

Studies in the diabetic mutant mouse: III. Physiological factors associated with alterations in beta cell proliferation

Summary Beta cell replication was studied in normal (C 57 BL/Ks) and diabetic mutant (C 57 BL/Ks-db/db) mice following thymidine-³H administration. The specific activity of DNA of isolated islets (DPM/g islet DNA) was used as an index of proliferative activity and correlated with labeling determined by radioautography. Although thymidine-³H incorporation in islets of prehyperglycemic 5 to 6 week old mutants was limited, it was significantly greater than that in normal mice. With the elevation of blood glucose values, incorporation rose sharply, reaching a maximum level above 130 mg glucose/100 ml blood. Sustained, severe hyperglycemia subsequently correlated with a decline in islet DNA synthesis. Food restriction early in the syndrome reduced hyperglycemia and resulted in low incorporation of label. Animals refed ad lib for periods of 1, 2, or 3 weeks showed significant increases in labeling, with maximal values after 1 week of refeeding. Electron microscopic radioautographs of the islets revealed labeled beta cells but no labeled alpha cells, suggesting that proliferative activity is predominantly restricted to the beta cell population.USPHS Research Career Development Awardee, Grant K4-AM-7394.     

The Alcohol Deprivation Effect in C57BL/6J Mice is Observed Using Operant Self-Administration Procedures and is Modulated by CRF-1 Receptor Signaling

Background: The alcohol deprivation effect (ADE) is characterized by transient excessive alcohol consumption upon reinstatement of ethanol following a period of ethanol deprivation. While this phenomenon has been observed in rats using both bottle drinking (consummatory behavior) and operant self‐administration (consummatory and appetitive “ethanol‐seeking” behavior) procedures, ADE studies in mice have primarily relied on bottle drinking measures. Furthermore, the neurochemical pathways that modulate the ADE are not well understood. Therefore, we determined whether the ADE can be observed in C57BL/6J mice using operant self‐administration procedures and if expression of the ADE is modulated by the corticotropin releasing factor‐1 (CRF‐1) receptor. Methods: C57BL/6J mice were trained in a 2‐hour operant self‐administration paradigm to lever press for 10% ethanol or water on separate response keys. Between operant sessions, mice had access to ethanol in their homecage. Once stable responding occurred, mice were deprived of ethanol for 4 days and were then retested with ethanol in the operant paradigm for 3 consecutive days. Next, to assess the role of the CRF‐1 receptor, mice were given intraperitoneal (i.p.) injection (0, 10, or 20 mg/kg) of the CRF‐1 receptor antagonist CP‐154,526 30 minutes before ADE testing. Additional experiments assessed (i) ADE responding in which the alternate response lever was inactive, (ii) the effects of CP‐154,526 on self‐administration of a 1% sucrose solution following 4 days of deprivation, and (iii) ADE responding in which mice did not received i.p. injections throughout the experiment. Results: Mice exhibited a significant increase in postdeprivation lever responding for ethanol with either a water reinforced or inactive alternate lever. Interestingly, i.p. injection of a 10 mg/kg dose of CP‐154,526 protected against the ADE while not affecting lever responding for a sucrose solution. Finally, baseline and deprivation‐induced increases of ethanol reinforced lever responding were greater in mice not given i.p. injections. Conclusions: The ADE in C57BL/6J mice can be modeled using the operant self‐administration paradigm and increased ethanol self‐administration associated with the ADE is modulated by CRF‐1 receptor signaling.     

Blockade of the corticotropin releasing factor type 1 receptor attenuates elevated ethanol drinking associated with drinking in the dark procedures

Background: Drinking in the dark (DID) procedures have recently been developed to induce high levels of ethanol drinking in C57BL/6J mice, which result in blood ethanol concentrations (BECs) reaching levels that have measurable affects on physiology and/or behavior. The present experiments determined whether the increased ethanol drinking caused by DID procedures can be attenuated by pretreatment with CP‐154,526; a corticotropin releasing factor type‐1 (CRF₁) receptor antagonist. Methods: In Experiment 1, male C57BL/6J mice received ethanol (20% v/v) in place of water for 4 hours, beginning with 3 hours into the dark cycle. On the fourth day, mice were given an intraperitoneal injection of one of the 4 doses of CP‐154,526 (0, 1, 3, 10 mg/kg) 30 minutes before receiving their ethanol bottle. In Experiment 2, C57BL/6J mice had 2 hours of access to the 20% ethanol solution, beginning with 3 hours into the dark cycle on days 1 to 3, and 4 hours of access to the ethanol bottle on day 4 of DID procedures. Mice were given an intraperitoneal injection of one of the 4 doses of CP‐154,526 (0, 1, 3, 10 mg/kg) 30 minutes before receiving their ethanol bottle on day 4. Tail blood samples were collected immediately after the 4‐hour ethanol access period on the fourth day of each experiment. Additional control experiments assessed the effects of CP‐154,526 on 4‐hour consumption of a 10% (w/v) sucrose solution and open‐field locomotor activity. Results: In Experiment 1, the vehicle‐treated group consumed approximately 4.0 g/kg/4 h of ethanol and achieved BECs of approximately 30 mg%. Furthermore, pretreatment with the CRF₁ receptor antagonist did not alter ethanol consumption. On the other hand, procedures used in Experiment 2 resulted in vehicle‐treated mice consuming approximately 6.0 g/kg/4 h of ethanol with BECs of about 80 mg%. Additionally, the 10 mg/kg dose of CP‐154,526 significantly reduced ethanol consumption and BECs to approximately 3.0 g/kg/4 h and 27 mg%, respectively, relative to vehicle‐treated mice. Importantly, the 10 mg/kg dose of the CRF₁R antagonist did not significantly alter 4‐hour sucrose consumption or locomotor activity. Conclusions: These data indicate that CRF₁R signaling modulates high, but not moderate, levels of ethanol drinking associated with DID procedures.     

The usefulness of p57 immunohistochemical staining and genotyping test in the diagnosis of the hydatidiform mole

Classification of molar gestations into complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM) and their differentiation from nonmolar hydropic abortions (HA) are traditionally accomplished by morphology alone. Sometimes, the process may be inaccurate or inconclusive especially in early diagnosed cases. With the availability of p57^KIP2 immunostaining (the product of a strongly paternally imprinted and maternally expressed gene), it may be possible to classify these lesions objectively. P57^KIP2 immunostaining is absent in CHM because it lacks a maternal genome, whereas PHM and HA show positive staining. The aims of this study were to evaluate the results of routine histopathological examination and p57^KIP2 immunoreactivity in a large series of molar and nonmolar HA in Tunisia, and to compare the accuracy of p57^KIP2 immunohistochemistry with that of nuclear DNA microsatellite polymorphism in identifying CHM. The immunohistochemical expression of p57^KIP2 protein was investigated in 220 specimens of first trimester hydropic abortuses, and it was compared with the original diagnosis based on morphology, including 132 CHM, 49 PHM, and 39 HA. Concordant results were obtained in 210 cases. In 9 of 10 cases with a discordant diagnosis (negative immunostaining in 8 cases morphologically diagnosed as PHM and one case diagnosed as HA), microsatellite DNA genotyping analysis agreed with the results of p57^KIP2 staining, confirming the diagnosis of CHM in these cases. Twenty cases of CHM with negative p57^KIP2 immunostaining were also analyzed by genotyping and indicated the absence of maternal contribution and the homozygosity for a single paternal allele in concordance with the androgenetic and monospermic origin of CHM in these cases. We confirm that for distinguishing CHM from its mimics, p57^KIP2 immunohistochemistry can be used as successfully as DNA microsatellite genotyping. However, molecular techniques are still required for the evaluation of some difficult cases with discordant positive p57^KIP2 staining.     

Bidirectional Relationships Between Weight Change and Sleep Apnea in a Behavioral Weight Loss Intervention

Objective

To examine the bidirectional relationship between weight change and obstructive sleep apnea (OSA) in the context of a behavioral weight loss intervention.

Clinical hematological and biochemical parameters in Swiss,BALB/c,C57BL/6 and B6D2F1 Mus musculus

BackgroundAnimal models are widely used in scientific research in order to obtain information from a whole organism under a specific set of experimental conditions. Various lineages of mice have been used to investigate diseases and new therapeutic strategies, and, consequently, hematological and biochemical tests in these laboratory animals are essential to validate scientific studies. Our study seeks to establish reference values for hematological and biochemical parameters of four lineages of mice.MethodsWe evaluated the hematological and biochemical profiles of 20 males and 20 females from the lineages Swiss (heterogeneous), BALB/c and C57BL/6 (isogenic), and B6D2F1 (hybrid), totaling 160 mice. Analysis were standardized using the systems pocH‐100iV Diff™ for 19 hematological parameters and VITROS^® 350 for 12 biochemical parameters.ResultsResults are shown as means and standard deviation, grouped by lineage and genre. Comparing the values obtained in this study with the values from previous studies, some variations were detected, which could be explained by differences in methodologies or individual variability.ConclusionThus our study shows that knowledge and disclosure of the values of physiological parameters of laboratory animals is necessary, and emphasises the importance of considering variations influenced by gender, lineage and genotype in the choice of the best experimental model.     

血清巨噬细胞移动抑制因子与急性脑梗死的相关性研究

【目的】探讨急性脑梗死（ACI）患者血清巨噬细胞移动抑制因子（MIF）水平与病情严重程度和短期预后的关系。【方法】选择ACI患者106例,采用美国国立卫生研究院卒中量表NIHSS评分分为轻型脑梗死组（A组,NIHSS评分＜4分）40例、中型脑梗死组（B组,NIHSS评分4～15分）38例、重型脑梗死组（C组, NIHSS评分＞15分）28例。同期住院48例有动脉粥样硬化（Atherosclerosis ,AS）危险因素非急性脑梗死患者为对照组（D组）。酶联免疫吸附法（ELISA ）测定各组患者血清中M IF水平,对ACI患者随访,评估90 d改良Ranking量表（ mRS）评分,进行统计学分析。【结果】A、B、C与D组血清MIF存在差异,数值上A组、B组、C组大于D组,具有统计学意义（ P ＜0．05）。相关性分析,MIF与高敏C反应蛋白（hs‐CRP）、同型半胱氨酸（Hcy）、白细胞（WBC）、中性粒细胞百分比（NEUT％）呈正相关,与单核细胞百分比（MONO％）呈负相关。Logistic回归分析,收缩压（SBP ）、M IF、低密度脂蛋白胆固醇（LDL‐C ）、Hcy、WBC水平与患者90 d的mRS评分呈正相关。【结论】急性脑梗死患者血清 M IF水平升高,与病情严重程度及90 d预后相关,说明M IF可能参与了ACI的炎症反应过程。