Extended administration of the association of zidovudine plus ritonavir during rat pregnancy: maternal and fetal effects

The purpose of the study was to evaluate at term, the effects of the association of zidovudine/ritonavir administered during the entire period of rat pregnancy. Forty pregnant EPM-1 Wistar rats were divided randomly into four groups: one control (drug vehicle control, n=10) and three experimental treated with an oral solution of zidovudine/ritonavir (Exp 1 = 10/20 mg/kg bw, n = 10; Exp 2 = 30/60 mg/kg bw, n=10; Exp 3 = 90/180 mg/kg bw, n=10) from day 0 up to day 20 of pregnancy. Maternal body weights were recorded at the start of the experiment and at the 7th, 14th and the 20th day thereafter. At term (20th day) the rats were anesthetized and, upon laparotomy and hysterotomy, the number of implantations, resorptions, living fetuses, placentae and intrauterine deaths were recorded. The collected fetuses and placentae were weighed, and the concepts were examined under a stereoscopic microscope for external malformations. The maternal body gain and the mean fetal weight at term were both significantly lower (p < 0.01 and p < 0.0001, respectively) in the experimental groups compared to the control. The recorded resorptions were higher in Exp 2 and Exp 3 groups than in the control group. The other parameters were not affected. The exposure of pregnant rats at term to a 1:2 association of zidovudine plus ritonavir resulted in a significant reduction in maternal body weight gain and increased rate of fetal resorption.     

Morphological and biochemical appraisal of the liver and renal effects of indinavir on rat pregnancy

Since indinavir is currently used in combination with other antiretroviral agents, there is a scarcity of studies in the literature on its single-drug perinatal safety. Thus, we decided to examine the gross maternal and fetal effects of indinavir administered alone during the entire period of rat pregnancy. Forty pregnant animals were assigned at random to four groups (C = control) treated with the drug vehicle (distilled water); the experimental groups were treated with indinavir as follows: E1 = 40 mg/kg; E2 = 120 mg/kg; E3 = 360 mg/kg from "zero" up to the 20th day of gestation. Drug or vehicle were administered daily by gavage. Each group consisted of ten animals. At term-pregnancy, the rats were deeply anesthetized and blood samples were collected for alanine aminotransferase (ALT) and aspartate aminotransferase (AST), creatinine and urea determinations. Fragments of maternal and fetal livers and kidneys were taken and routinely processed for histopathological study. Serum ALT activity in the E2 group was significantly higher (p < 0.01) than that of the other groups. The concentration of creatinine in blood was lower in the E2 and E3 groups than in group E1 (p < 0.01), whereas blood urea in group E3 was significantly lower than in the other groups (p < 0.01). Morphological (light microscopy) studies revealed that no significant effects of the drug could be detected regarding either maternal or fetal organs of the E1 and E2 groups. However, the maternal hepatocytes in the E3 group showed heterochromatic nuclei. In addition, there was some fatty infiltration, congested sinusoids and portal dilation. Maternal kidneys in the E2 and E3 groups revealed vascular dilation around the convoluted tubules. Regarding the biochemical determinations, the alterations observed were mild, without biological relevance, thus indicating that the treatment with indinavir during the entire gestation was essentially devoid of hepatic or renal effects which could result in altered metabolic parameters. It is concluded that indinavir was well tolerated in therapeutic and even in 9-fold higher doses. Notwithstanding, discrete morphological alterations occurred in the maternal compartment, but with no functional expression that could indicate deleterious effects on mothers and/or fetuses.     

培养创新型临床医学人才的思考

文章从创新及创新型人才的概念入手，通过调研指出，目前临床医学人才培养存在的主要问题，提出在新时期要转变教育教学观念、强化创新意识教育、增强创新思维训练、着力创新人格塑造，以培养创新型临床医学人才。     

YD383、YD439对JAK-STAT6信号传导通路作用的特异性研究

目的:探讨化合物YD383和YD439对STAT6信号传导通路的作用是否具有特异性.方法:通过瞬时转染的方法将分别依赖于STAT1和STAT6活性的带有荧光素酶报告基因的质粒转染至HeLa细胞株,两种细胞株在各自相应的细胞因子(IFN-γ或IL-4)刺激下激活JAK-STAT1或JAK-STAT6信号传导通路.通过测定荧光素酶的活性来评价细胞株在化合物存在的情况下报告基因的表达.结果:YD383和YD439均能降低相应细胞因子刺激引起的报告基因的表达,并且具有剂量依赖性.随着化合物剂量的增加,报告基因的表达降低(P＜0.05).但化合物引起的两种转染细胞报告基因表达降低的差异比较无统计学意义(P＞0.05).结论:两种化合物对JAK-STAT1和JAK-STAT6信号传导通路均有抑制作用,对JAK-STAT6通路的抑制不具有特异性.     

microRNA调控NK细胞KIR3DL1表达初探

目的初步探寻人外周血自然杀伤细胞（Nature Killer,NK）杀伤细胞免疫球蛋白样受体（Killer Cell Immnoglobulin-Like Receptor,KIR3DL1）表达可能存在的microRNA（miR）调控机制。方法利用生物信息学方法,从miR信息库中筛选出可能与KIR3DL1相关的miRs,构建含KIR3DL1 3’非翻译区（UTR）的PGL3质粒,分别将含相应miR的PcDNA3.0质粒与前者共转染293T细胞,通过荧光素酶报告实验及之后的突变实验筛选出可能调控KIR3DL1的miR。结果通过TARGET SCAN信息库筛选了miR-146b等10个miR;转染miR-146b后,荧光素酶活性下降最多（61.3%）,突变其KIR3DL1 3’UTR靶位点后荧光素酶活性恢复（91.4%）。结论 miR-146b可与KIR3DL1’UTR在靶位点特异结合,很可能参与KIR3DL1表达的调控。     

Effect of a Boarding Restriction Protocol on Emergency Department Crowding

PurposeAccess block due to the lack of hospital beds causes crowding of emergency departments (ED). We initiated the “boarding restriction protocol” that limits the time of stay in the ED for patients awaiting hospitalization to 24 hours from arrival. The purpose of this study was to determine the effect of the boarding restriction protocol on ED crowding.Materials and MethodsThe primary outcome was ED occupancy rate, which was calculated as the ratio of the number of occupying patients to the total number of ED beds. Time factors, such as length of stay (LOS), treatment time, and boarding time, were investigated.ResultsThe mean of the ED occupancy rate decreased from 1.532±0.432 prior to implementation of the protocol to 1.273±0.353 after (p<0.001). According to time series analysis, the absolute effect caused by the protocol was -0.189 (-0.277 to -0.110) (p=0.001). The proportion of patients with LOS exceeding 24 hours decreased from 7.6% to 4.0% (p<0.001). Among admitted patients, ED LOS decreased from 770.7 (421.4–1587.1) minutes to 630.2 (398.0–1156.8) minutes (p<0.001); treatment time increased from 319.6 (198.5–482.8) minutes to 344.7 (213.4–519.5) minutes (p<0.001); and boarding time decreased from 298.9 (109.5–1149.0) minutes to 204.1 (98.7–545.7) minutes (p<0.001). In pre-protocol period, boarding patients accumulated in the ED during the weekdays and resolved on Friday, but this pattern was alleviated in post-period.ConclusionThe boarding restriction protocol was effective in alleviating ED crowding by reducing the accumulation of boarding patients in the ED during the weekdays.     

Thyroid disorders in hemodialysis patients in an iodine-deficient community

There are various changes in the thyroid gland and its function in chronic renal failure (CRF). These changes include lower levels of circulating thyroid hormone, altered peripheral hormone metabolism, decreased binding to carrier proteins, possible reduction in tissue hormone content, and increased iodine storage in the thyroid gland. The decrease of excretion of urinary iodine in CRF increases serum inorganic iodine level and iodine content of the thyroid, which consequently enlarges the gland. This study is designed to investigate the prevalence of goiter and thyroid dysfunction in patients with end-stage renal disease (ESRD) on hemodialysis (HD) in an iodine-deficient community. Eighty-seven (40 females and 47 males) HD patients and 169 (79 females and 90 males) healthy individuals as controls are included. Sex ratios for the patient and control groups are 0.85 and 0.88, respectively. Mean ages for the patient and control groups are 42.94 +/- 11.88 and 40.20 +/- 10.72 years, respectively. Examination of the thyroid gland using ultrasonography along with simultaneous measurement of blood levels of free-T4 (FT4), free-T3 (FT3), and thyrotropin (TSH) are made for every individual. The presence of goiter demonstrable by ultrasonography is found in 32.2% of the uremic patients and in 23.5% of the controls and its prevalence increases with age (P = 0.01). In 32 (36.8%) of the patients and 29 (17.1%) of the controls at least one thyroid nodule is found in ultrasonography. Between patients with or without a nodular goiter the authors could not observe any difference for duration of dialysis and serum levels of TSH, FT4, FT3, calcium, and albumin. In ESRD patients the prevalence of nodular goiter is higher for females (47.5% vs. 27.7%, P = 0.045) and increases with age (P = 0.04). Though incidence of hyperthyroidism is found to be similar for the two groups (1.14% in ESRD patients vs. 1.10% in controls), hypothyroidism is observed in 3.4% of ESRD patients but only 0.6% of controls. This high incidence of hypothyroidism and nodular goiter in ESRD patients shows that screening for thyroid dysfunction and goiter, using appropriate laboratory tests and ultrasonography, should be considered in evaluation of every ESRD patient.