Exogenous insulin-like growth factor II enhances post-infarction regional myocardial function in swine

OBJECTIVES: Insulin-like growth factor II (IGF-II) promotes cardiac myocytegrowth and contractility in vitro. This study was designed toinvestigate the effect of exogenous IGF-II on regional myocardialfun ction at the area of infarct in the pig. METHODS: Myocardial infarction was induced in 12 female anoesthetizedpigs by affigel blue beads, embolizing microvessels of the leftanterior descending coronary artery distribution. In the experimentalgroup (n=6), IGF-II (0.12 µg. kg^–1 in two animalsand 0.6 µg. kg^–1 in four) was incorporated intothe beads and delivered by them to the infarct area. Myocardialfunction was followed echocardiographically, and the excisedheart was analysed immunohistochemically and histopathologically. RESULTS: Myocardial function in injured zones, inversely related to anechocardiographic segmental wall motion score (mean ±SEM), was similar between the two groups at baseline, but at4 weeks post-infarction was significantly (P=0.008) reducedin the control group (0.58± 0.38 vs 3.42 ± 0.84),in contrast to nearly baseline values in the experimental group(0.58 ± 0.33 vs 1.17 ± 0.42, P=0.41). Cardiacperformance in injured segments was sign better after myocardialinjury in the experimental group (P=0.04). Tissue samples fromboth groups (4 weeks post-infarction), stained with haematoxylinand eosin demonstrated pen-infarct myocyte hypertrophy, correspondingto regions selectively stained by an antibody for CD56, whichhighlights growing cardiac myocytes. By image analysis semi-quantification,staining for CD56 was significantly (P=0.04) higher in the peri-infarctregion of the experimental group, as compared with controls(106.5 ± 2.8 vs 92 ± 4.4 gray level units). Microvesselsstained for von-Willebrand factor were similar in nwnber inboth groups (P=0.8), as were mesenchymal cells stained for vimentin(P=0.7). CONCLUSIONS: Exogenous IGF-II, delivered to the infarct area amelioratesregional cardiac function in the pig, perhaps by inducing peri-infarctmyocyte growth.     

喘可治注射液对大鼠抗炎和免疫调节机制的研究

目的:探讨喘可治注射液治疗支气管哮喘(简称哮喘)的作用机制.方法:60只雄性Wistar大鼠随机分为正常组、模型组、地塞米松组(0.5 ml·kg-1 ·d-1,肌内注射),高、中、低剂量(10、5、2.5 ml·kg-1·d-1,腹腔注射)喘可治注射液组.以2％卵蛋白为激发液,雾化吸入致敏,建立哮喘模型.治疗后,大鼠肺叶经HE染色后行病理切片,采用酶联免疫吸附(ELISA)法分别测定大鼠外周血中白介素-4(IL-4)和γ-干扰素(IFN-γ)浓度,采用流式细胞仪测定大鼠外周血中CD4+ CD25+T调节细胞和CD3- CD161a+自然杀伤(NK)细胞占淋巴细胞的百分比.结果:各剂量喘可治注射液组大鼠肺叶局部炎症反应均较模型组轻,IL-4浓度均明显下降,与模型组相比差异有显著性(P＜0.01),但各治疗组间、治疗组和正常组间IL-4浓度无显著差异.各治疗组IFN-γ的浓度均较模型组有所上升,其中高剂量组上升最为明显,与模型组比较有显著差异(P＜0.01).高、中、低剂量喘可治注射液组CD4+ CD25+T调节细胞百分比均明显上升,与模型组相比有显著差异(P＜0.05).CD3- CD161.+ NK细胞的百分比各组间比较无显著性差异.结论:喘可治注射液可增加血中IL-4、IFN-γ浓度,及CD4+ CD25+T调节细胞含量,纠正免疫失衡,这可能是其治疗哮喘的机制之一.     

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain.     

Risk of opportunistic infections in patients treated with alemtuzumab for multiple sclerosis

Introduction: Alemtuzumab is a monoclonal anti CD-52 antibody recently approved for use in relapsing-remitting multiple sclerosis(MS). Given that the targeted antigen is primarily expressed on B and T lymphocytes, the administration of this biological drug is associated with rapid but protracted peripheral lymphopenia.

Areas covered: The impact on infective risk of this immune impairment is still to be fully understood. In this review, we attempt to summarize all the available literature concerning opportunistic infections occurring in patients with MS receiving alemtuzumab. Infective adverse events were observed in more than 70% of patients in phase 2/3 RCTs, mainly of mild-to-moderate severity. Nevertheless, several post-marketing reports documented cases of serious, rare, and unexpected infections.

Expert Opinion: Predictive risk factors and prognostic features of opportunistic infections in this setting still need to be exactly assessed. At present, the only recommended preventive measures consist in anti-herpetic prophylaxis, Listeria-free diet, Tuberculosis prophylaxis and annual Papillomavirus screening. Given the non-negligible risk of unpredicted infective events, we advise physicians to take into account patients’ history of infectious diseases and vaccine status and to consider supplementary prophylactic strategies, including screening for Toxoplasma gondii and viral hepatitis serostatus as well as pre-emptive approaches to avert CMV reactivation and Pneumocystosis.     

Two-generation reproductive toxicity evaluation of dietary 17beta-estradiol (E2; CAS No. 50-28-2) in CD-1 (Swiss) mice.

No information exists on reproductive/developmental effects in mice exposed to dietary 17beta-estradiol (E2) over multiple generations. Therefore, under OECD Test Guideline 416 with enhancements, CD-1 mice (F0 generation, 25 mice/sex/group) were exposed to dietary E2 at 0, 0.001, 0.005, 0.05, 0.15, or 0.5 ppm ( approximately 0, 0.2, 1, 10, 30, or 100 mug E2/kg body weight/day) for 8 weeks prebreed, 2 weeks mating, approximately 3 weeks gestation, and 3 weeks lactation. At weaning, selected F1 offspring (F1 parents; 25/sex/group) and extra retained F1 males (one per litter) were exposed to the same dietary concentrations and durations as the F0 generation; study termination occurred at F2 weaning; F1/F2 weanlings (up to three per sex per litter) were necropsied with organs weighed. At 0.5 ppm, effects were increased F1/F2 perinatal loss, prolonged F0/F1 gestational length, reduced numbers of F2 (but not F1) litters/group, reduced F1/F2 litter sizes, accelerated vaginal patency (VP) and delayed preputial separation (PPS), increased uterus + cervix + vagina weights (UCVW) in F0/F1 adults and F1/F2 weanlings, and decreased testes and epididymides weights (TEW) in F1/F2 weanlings. At 0.15 ppm, effects were increased UCVW in F0/F1 adults and F1/F2 weanlings, accelerated VP, delayed PPS, and reduced TEW in F1/F2 weanlings. At 0.05 ppm, UCVW were increased in F1/F2 weanlings, and PPS was delayed only in extra retained F1 males. There were no biologically significant or treatment-related effects on F0/F1 parental body weights, feed consumption, or clinical observations, or on F0/F1 estrous cyclicity, F0/F1 andrology, or F1/F2 anogenital distance at any dose. The no observable effect level was 0.005 ppm E2 ( approximately 1 mug/kg/day). Therefore, the mouse model is sensitive to E2 by oral administration, with effects on reproductive development at doses of 10- 100 mug/kg/day.     

CELL-DYN3700血细胞分析仪的使用体会

CELL-DYN3700血细胞分析仪是美国Abbott公司1999年推出的全自动多参数血细胞分析仪。该仪器采用电阻法与激光技术相结合的原理，进行全血细胞计数（Complete Blood Cell Count，CBC）的同时，还可进行网织红细胞分析，为临床及科研提供白细胞系统15项，红细胞系统7项，血小板系统4项。网织红细胞系统3项等多项参数。     

216份冠状动脉支架置入术手术编码错误分析及探讨

目的 对冠状动脉支架置入术手术编码中存在的问题进行分析探讨.方法 收集行冠脉支架置入术的出院病案共216份,按照ICD-9-CM-3编码原则,分析主要手术填写及编码情况,对其中出现的错误进行汇总分析.结果 医师填写该类主要手术时共存在错误69份,总错误率为31.9％.编码员存在的最主要的问题为遗漏血管手术数量,占53.2％.结论 加强对心内科医师有关冠脉支架置入术ICD-9-CM3知识的专项培训,提高编码员自身业务水平及编码能力,双方共同努力才能减少冠状动脉支架置入术编码的错误率.     

The dopamine-depleting effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in CD-1 mice are gender-dependent

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a selective dopaminergic neurotoxin affecting the nigrostriatal system in a variety of species including, rodents, nonhuman primates and humans. There exists, however, a great deal of variability in the sensitivity of different species to the effects of MPTP. The present study was designed to determine whether a significant difference in gender susceptibility to the toxin in CD-1 mice might also exist. A dosing regiment of 30 mg/kg MPTP once a day for 3 days (90 mg/kg total dose) in 4-month-old male and female CD-1 mice led to a significant depletion of striatal dopamine in both sexes. Two way ANOVA analysis of a time-course generated by measuring striatal dopamine at 4, 12 and 24 h after each dose of MPTP revealed that the initial dopamine reduction is significantly greater in male CD-1 mice (P < 0.001). Further, dopamine levels were reduced to a greater extent in male mice 5 days after the last dose (31 % vs. 59% of control; P < 0.02). HPLC analysis using fluorescence detection revealed no difference in the striatal nor the cerebellar levels of MPP+ between the two sexes, however, accumulation of larger amounts of MPP⁺ was observed in the livers of the female mice. These findings suggest that, while female CD-1 mice are more resistant to the dopamine-depleting effects of MPTP, this gender difference is not due to decreased production or accumulation of striatal MPP⁺.