Cytotoxic activity of alkaloids isolated from Stephania rotunda in vitro cytotoxic activity of cepharanthine

Three major alkaloids: cepharanthine (1), tetrahydropalmatine (2) and xylopinine (3) isolated from Stephania rotunda tuber were investigated for their cytotoxic activity in a panel of human cancer cells (HT29, LS174T, SW620 and HepG2) using MTT assay. In the present study, cepharanthine (1) exerted potent cytotoxicity against colon and hepatoma cancer cell lines with IC₅₀ values between 2.4 and 5.3 µM while tetrahydropalmatine (2) and xylopinine (3) displayed weak cytotoxicity. In addition, the mutagenic activity of cepharanthine (1) was investigated using a modified liquid incubation technique of the Salmonella/microsomal assay. This alkaloid (1) was found to be non‐mutagenic for doses up to 8.2 µM. Copyright © 2008 John Wiley & Sons, Ltd.     

Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned.     

妇科腹腔镜手术时血气P_(ET)CO_2的变化

55例择期妇科腹腔镜手术，按疾病不同分为宫外孕组20例，单纯卵巢或输卵管囊肿组20例，盆腔粘连组15例。术中连续监测PETCO2，并于全麻诱导后CO2气腹建立前、CO2气腹30min后、改变通气量30min后测血气。结果表明，所有患者在CO2气腹建立30min后PaCO2、HCO3、pH、PETCO2均较气腹前有明显变化，改变通气量30min后，上述值较30min前又有明显变化。但pH值仍表现为酸血症。宫外孕组和盆腔粘连组与单纯卵巢或输卵管囊肿组相比，全麻诱导后CO2气腹建立前，血气主要指标数值、PETCO2三组无显著差异，而CO2气腹30min后，改变通气量30min后，前两组与后组有差异。提示CO2吸收量可能同手术野创面情况有关。     

Improved Phenotype-Based Definition for Identifying Carbapenemase Producers among Carbapenem-Resistant Enterobacteriaceae

Preventing transmission of carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) is a public health priority. A phenotype-based definition that reliably identifies CP-CRE while minimizing misclassification of non–CP-CRE could help prevention efforts. To assess possible definitions, we evaluated enterobacterial isolates that had been tested and deemed nonsusceptible to >1 carbapenem at US Emerging Infections Program sites. We determined the number of non-CP isolates that met (false positives) and CP isolates that did not meet (false negatives) the Centers for Disease Control and Prevention CRE definition in use during our study: 30% (94/312) of CRE had carbapenemase genes, and 21% (14/67) of Klebsiella pneumoniae carbapenemase–producing Klebsiella isolates had been misclassified as non-CP. A new definition requiring resistance to 1 carbapenem rarely missed CP strains, but 55% of results were false positive; adding the modified Hodge test to the definition decreased false positives to 12%. This definition should be considered for use in carbapenemase-producing CRE surveillance and prevention.     

International investigation of neurocognitive and behavioral phenotype in 47,XXY (Klinefelter syndrome): Predicting individual differences

47,XXY (KS) occurs in 1:650 male births, though less than 25% are ever identified. We assessed stability of neurocognitive features across diverse populations and quantified factors mediating outcome. Forty‐four boys from the Netherlands (NL) and 54 boys from the United States (US) participated. The Wechsler Intelligence Scales assessed intellectual functioning; the ANT program evaluated cognitive function; and the CBCL assessed behavioral functioning. ANOVA was used for group comparisons. Hierarchical regressions assessed variance explained by each independent variable: parental education, timing of diagnosis, testosterone, age, and nationality. Parental education, timing of diagnosis, and hormonal treatment all played an important role in neurocognitive performance. The observed higher IQ and better attention regulation in the US group as compared to the NL group was observed with decreased levels of behavioral problems in the US group. Cognitive measures that were different between the NL and US groups, i.e., attention regulation and IQ scores, were also significantly influenced by external factors including timing of diagnosis, testosterone treatment, and parental education. On the ANT, a cognitive phenotype of 47,XXY was observed, with similar scores on 9 out of the 10 ANT subtests for the NL and US groups. This study lays additional features to the foundation for an algorithm linking external variables to outcome on various neurodevelopmental measures.

     

应用三种酶联免疫吸附试验（ELISA）诊断肺螨病的比较观察

应用三种酶联免疫吸附试验:Dot——ELlSA、ABC——ELISA和SPA——ELISA分别检测相同类型45份肺螨病患者血清尘螨性抗体,结果阳性率分别为93.33％,83.24％和51.11％(同Dot——ELISA比P<0.05)。肺螨病患者阳性血清的几何平均滴度分别为295.43,191.12和112.54。因而Dot——ELISA的敏感度为ABC——ELISA和SPA——ELISA的1.70倍和2.88倍。实验结果证明Dot—ELISA在诊断肺螨病中有较高的敏感性和特异性。     

Comparative evaluation of simian, simian-human, and human immunodeficiency virus infections in the pigtail macaque (Macaca nemestrina) model

The global impact of HIV/AIDS intensifies the need for a preventive vaccine and nonhuman primate models can help provide critical insights into effective immunity. Pigtail macaques (Macaca nemestrina) are increasingly studied as a nonhuman primate model for AIDS. We compared the virologic and immunologic characteristics of HIV-1, SIV, and SHIV infection of naive pigtail macaques across a series of preclinical HIV vaccine studies. SIVmac251 and SIVmac239 infection of naive pigtail macaques resulted in a gradual decline in peripheral CD4+ T cells in the setting of high levels of viremia, approximating most closely human infection of HIV-1. In contrast, the CXCR4-utilizing SHIVmn229 virus resulted in rapid depletion of CD4+ T cells and minimal generation of humoral or cellular immune responses, similar to that observed with SHIV89.6P infection of rhesus macaques. Infection with the CCR5-utilizing, rhesus macaque passaged, SHIVSF162P3 resulted in some overall CD4+ T cell decline, however, three of eight macaques naturally control SHIVSF162P3 viremia to very low levels in the setting of robust adaptive immunity. Despite attempts at infecting pigtail macaques with HIV-1 strains passaged in juvenile pigtail macaques in vivo or in PBMC isolated from pigtail macaques in vitro, only lower nonsustained levels of viral replication were observed. Our results provide a series of virologic models with which to evaluate potential AIDS vaccines in pigtail macaques.     

Metastatic lung and pleural malignancy presenting as bilateral acute anterior uveitis

Anterior uveitis is associated with a variety of underlying systemic diseases but the association between bilateral acute anterior uveitis (BAAU) and lung and pleural malignancy is not widely recognized. The case is described here of a 61-year-old woman presenting to an eye clinic with BAAU. A routine chest radiograph performed principally to exclude pulmonary sarcoidosis revealed an intrapulmonary mass and she was subsequently found to have widespread lung and pleural malignancies. Evidence is discussed that suggests a link and potential aetiology between BAAU and lung and pleural malignancies. The present case shows the virtue of requesting a chest radiograph in patients presenting with BAAU, even in the absence of other symptoms or clinical findings.