二甲基甲酰胺生物接触限值的研究

目的研究我国职业接触二甲基甲酰胺(DMF)的生物限值。方法气相色谱法检测工作场所空气中二甲基甲酰胺浓度和作业工人班末尿中甲基甲酰胺(NMF)浓度,同时研究两者的相关性。结果 DMF接触者班末尿中NMF浓度与工作场所空气中DMF浓度有密切正相关(Y=0.3389X+3.0297,r=0.9986,P0.01)。根据作业场所空气中DMF的国家职业卫生标准,按回归方程推导出职业接触DMF的生物限值。结论 DMF接触者生物接触限值推荐值:班末尿中NMF为12.0 mg/gCr。     

Relationship Between Blood Lead Levels and Hematological Indices in Pregnant Women

Several studies have revealed a negative association between blood lead levels and hematological impairment. In this cross-sectional study, we examined the relationship between blood lead levels and hematological indices in 292 pregnant women from Durango, Mexico. Apparently healthy pregnant women, aged 14–41 years and at 3–41 weeks of gestation, were recruited between June 2007 and May 2008. Blood lead and hematological indices were measured. The mean blood lead was 2.79 ± 2.16 μg/dL, and lead levels ≥5 μg/dL were detected in 25 women (8.6%). Hemoglobin, hematocrit, and red blood cells count were significantly higher in pregnant women with a blood lead concentration of ≥5 μg/dL than the group with lower blood lead levels (p < .05). Mean corpuscular volume and mean corpuscular hemoglobin were not significantly related to lead levels. Hemoglobin and hematocrit showed a non-significant positive correlation with blood lead, but the correlation between red blood cell count and blood lead levels was statistically significant (r = 0.185, p = .002). The findings suggest that a positive association between blood lead and some hematological indices may occur at relatively low blood lead concentration (mean < 5 μg/dL).     

平静呼吸状态下肺通气功能测试

目的：介绍用于平静呼吸时各项呼吸指标测试系统的设计。方法：系统太要由Fleisch流量换能器、压力换能器、放大器、A/D转换器和486微机组成，系统软件是用汇编语言对流量信号进行采样，用C语言计算各项指标[呼吸频率（RR）、潮气量（TV）、潮气峰值流量（PTEF）、吸气时间/总呼吸时间（TiTtot到达呼气峰流量时间/呼气时间（TPF）、到达静态呼气峰流量时的呼出气量/潮气量（VPF）、呼出75%潮气量时的呼气流量（PE25）、平静呼吸中期流量/静态吸气中期流量（MEF/MIF），静态流量-容量环]，结果：经测试，同一正常男子测试TV的相对误差为1%；Fleisch型流量换能器，在整个量程内（0-8L），非线性误差不大于2%。结论：肺量计与浮筒式肺量计比较具有阻力小，精度高的优点，临床适用范围大，易于临床推广使用。     

Instrumental set-up as a factor influencing the variability of retention index values in high pressure liquid chromatography

Summary The influence of different laboratory set-ups on HPLC retention index values of selected acidic and basic drugs was investigated. The RI values of drugs were calculated using the alkyrarylketone scale. Two columns filled with different batches of the same Hypersil ODS phase were consecutively used in two laboratories under identical conditions, but using different instrumentation. The study showed that the different laboratory set-ups influence the precision of RI values, and the differences in column filling affect the accuracy.     

Umbilical Artery Doppler Indices in Small for Gestational Age Fetuses

Objective. The purpose of this study was to compare the screening efficiency of the umbilical artery systolic to diastolic ratio (S/D), pulsatility index (PI), and absent end-diastolic flow (AEDF) for adverse pregnancy outcomes and placental abnormalities in small for gestational age (SGA) fetuses. Methods. We conducted a retrospective cohort study of Doppler examinations of 161 nonanomalous SGA fetuses. The reliability of the S/D and PI were quantified by intraclass correlation coefficients. The association of the S/D, PI, and AEDF with adverse outcomes and placental abnormalities was compared by the χ² test. Results. There was a simple association of Doppler results with adverse outcomes, which was mitigated when controlled for gestational age. For all measures of adverse outcomes, the specificity of abnormal Doppler results exceeded the sensitivity, and the negative predictive value was greater than the positive predictive value. Comparing the S/D with the PI, there was no significant difference in the sensitivity; however, the specificity of the PI was at least 90% and exceeded that of the S/D for all outcomes. The intraclass correlation coefficients of the S/D and PI were similar, indicating no difference in reliability. Placental abnormalities were significantly more common in cases with abnormal Doppler values (positive predictive value, 94%) with no overlap in the types of placental lesions in most cases. Conclusions. As an initial screen for adverse outcomes in SGA fetuses, the umbilical artery Doppler S/D, PI, and AEDF were imprecise. However, these measures were all strongly and similarly predictive of placental abnormalities, especially lesions of maternal underperfusion and fetal vascular obstruction.     

Effect of aqueous extract of Cochlospermum planchonii rhizome on some kidney and liver functional indicies of albino rats

Aqueous extract of Cochlospermum planchonii Hook. Ef. x Planch rhizome was investigated for its toxic effects in albino rats using some liver and kidney functional indices as 'markers'. Thirty six albino rats weighing 200.08 ± 10.21 were randomly assinged into six groups (A-F) of six animals each. Animals in groups A-E were orally administered on daily basis with 1 ml of the extract corresponding to 50 mg/kg body weight of the extract for 1, 3, 5, 10 and 15 days while those in the control group received orally 1 ml of distilled water. Rats in all the groups were sacrificed 24 hours after the completion of their respective doses. The extract significantly (P<0.05) decreased alkaline phosphatase (ALP) activities in the liver leading to 80.95% loss by the end of the experimental period. While there was no consistent pattern in the kidney ALP activity and serum bilirubin level, the serum enzyme compared well (P>0.05) with the control value. There was no effect (P>0.05) on the acid phosphatase activity of the tissues and serum of the animals. The extract also reduced the urea, albumin and creatinine content in the serum of the animals. The alterations in the biochemical parameters by the aqueous extract of Cochlospermum planchoni may have consequential effects on the normal functioning of the liver and kidney of the animals. Therefore, the 50 mg/kg body weight of the aqueous extract of Cochlospermum planchoni rhizome may not be completley safe as an oral remedy.     

3D-QSAR studies of JNK1 inhibitors utilizing various alignment methods

We report our three-dimensional quantitative structure activity relationship (3D-QSAR) studies of the series of anilinopyrimidine derivatives of JNK1 inhibitors. The comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were applied using different alignment methods. The ligand-based atom-by-atom matching alignment has produced better values for CoMFA (q(2) = 0.646 and r(2) = 0.983), while in CoMSIA it has achieved only lower statistical values. The pharmacophore-based model has produced (q(2) = 0.568, r(2) = 0.938) and (q(2) = 0.670, r(2) = 0.982) for CoMFA and CoMSIA models, respectively. As the model was based on the receptor-guided alignment, all the compounds were optimized within the receptor, resulting in q(2) = 0.605 and r(2) = 0.944 for CoMFA, and q(2) = 0.587 and r(2) = 0.863 for CoMSIA. Molecular Dynamic simulation studies suggested that the generated models were consistent with the low-energy protein ligand conformation. The CoMFA and CoMSIA contour maps indicated that the substitutions of the electropositive groups in the phenyl ring, and an addition of hydrophobic groups in the pyrimidine ring, are important to enhance the activity of this series. Moreover, the virtual screening analysis against NCI database yields potentials hits, and the results obtained would be useful to synthesize selective and highly potent c-Jun N-terminal kinase 1 analogs.     

In silico identification of anthropogenic chemicals as ligands of zebrafish sex hormone binding globulin

Anthropogenic compounds with the capacity to interact with the steroid-binding site of sex hormone binding globulin (SHBG) pose health risks to humans and other vertebrates including fish. Building on studies of human SHBG, we have applied in silico drug discovery methods to identify potential binders for SHBG in zebrafish (Danio rerio) as a model aquatic organism. Computational methods, including; homology modeling, molecular dynamics simulations, virtual screening, and 3D QSAR analysis, successfully identified 6 non-steroidal substances from the ZINC chemical database that bind to zebrafish SHBG (zfSHBG) with low-micromolar to nanomolar affinities, as determined by a competitive ligand-binding assay. We also screened 80,000 commercial substances listed by the European Chemicals Bureau and Environment Canada, and 6 non-steroidal hits from this in silico screen were tested experimentally for zfSHBG binding. All 6 of these compounds displaced the [³H]5α-dihydrotestosterone used as labeled ligand in the zfSHBG screening assay when tested at a 33 μM concentration, and 3 of them (hexestrol, 4-tert-octylcatechol, and dihydrobenzo(a)pyren-7(8H)-one) bind to zfSHBG in the micromolar range. The study demonstrates the feasibility of large-scale in silico screening of anthropogenic compounds that may disrupt or highjack functionally important protein:ligand interactions. Such studies could increase the awareness of hazards posed by existing commercial chemicals at relatively low cost.