Spontaneous abortions and congenital malformations among women exposed to tetrachloroethylene in dry cleaning.

STUDY OBJECTIVE: The aim of the study was to determine whether exposure to tetrachloroethylene during the first trimester of pregnancy has harmful effects on pregnancy outcome. DESIGN: The study used record linkage identification of cases and case-control comparison. SETTING: The study involved dry cleaner and laundry workers throughout Finland who had become pregnant during the study period. Controls were age matched but otherwise unselected women giving birth to normal babies in the study period. SUBJECTS: Cases were defined as women who had been treated for spontaneous abortion or had delivered a malformed child. Out of 5700 workers nearly half had been pregnant during the study period. One pregnancy only was randomly selected for study per worker, and the final study population was 247 women with spontaneous abortions and 33 with malformed infants. Three age matched controls were selected for each abortion case and five for each malformation case. MEASUREMENTS AND MAIN RESULTS: Three women out of four had worked in early pregnancy. Exposure information was collected from 1108 women by mailed questionnaires, with a 77% response, and was partly confirmed by biological monitoring data. Exposure to tetrachloroethylene was found to be significantly associated with spontaneous abortions (odds ratio 3.6, p less than 0.05). CONCLUSION: The findings, together with other available data, indicate that exposure of pregnant women to tetrachloroethylene needs to be minimised.     

Glucuronidation of Entacapone, Nitecapone, Tolcapone, and Some Other Nitrocatechols by Rat Liver Microsomes

Purpose. Nitrocatechol COMT inhibitors are a new class of bioactive compounds, for which glucuronidation is the most important metabolic pathway. The objective was to characterize the enzyme kinetics of nitrocatechol glucuronidation to improve the understanding and predicting of the pharmacokinetic behavior of this class of compounds. Methods. The glucuronidation kinetics of seven nitrocatechols and 4-nitrophenol, the reference substrate for phenol UDP-glucuronosyltrans-ferase activity, was measured in liver microsomes from creosote-treated rats and determined by non-linear fitting of the experimental data to the Michaelis-Menten equation. A new method that combined densitometric and radioactivity measurement of the glucuronides separated by HPTLC was developed for the quantification. Results. Apparent K_m values for the nitrocatechols varied greatly depending on substitution pattern being comparable with 4-nitrophenol (0.11 mM) only in the case of 4-nitrocatechol (0.19 mM). Simple nitrocatechols showed two-fold V_max values compared with 4-nitrophenol (68.6 nmol min^–1 mg^–1), while all disubstituted catechols exhibited much lower glucuronidation rate. V_max/K_m values were about 10 times higher for monosubstituted catechols compared to disubstituted ones. The kinetic parameters for COMT inhibitors were in the following order: K_m nitecapone >> entacapone > tolcapone; V_max nitecapone > entacapone > tolcapone; V_max/K_m tolcapone > nitecapone > entacapone. Conclusions. Nitrocatechols can in principle be good substrates of UGTs. However, substituents may have a remarkable effect on the enzyme kinetic parameters. The different behaviour of nitecapone compared to the other COMT inhibitors may be due to its hydrophilic 5-substituent. The longer elimination half-life of tolcapone in vivo compared to entacapone could not be explained by glucuronidation kinetics in vitro.     

A rat model of monitoring liver allograft rejection

Rat models are often used to study liver allograft rejection. We have established a model for rat liver allograft rejection, monitored by fine needle aspiration biopsy (FNAB), in the strain combination PVG-to-BN with a mean survival time of 37 ± 20 days. In this model, we observed acute rejection with an intense peak of lymphoid blasts and lymphocyte-dominated inflammation in the FNAB [9.1 ± 3.0 corrected increment units (CIU)], and an eventual increase in macrophages (up to 4.2 ± 4.4 CIU), together with fibrosis and parenchymal necrosis in the graft. Markers of immune activation, such as an increase in IL-2-receptor (from 1 % ± 2 % to 21 % ± 13 %) and class II (from 20 % ± 9 % to 43 % ± 13 %) expressing lymphoid cells and induction of ICAM-1 in the graft, were consistent with the overall cellular response. The FNAB correlated well with parallel graft histology. In this rat model, the atraumatic monitoring makes a close follow-up possible without having to sacrifice the experimental animals. This saves work, animals, and costs in the study of liver rejection. Received: 2 July 1996 Accepted: 28 October 1996     

Peripheral nerve injury and Raynaud's syndrome following electric shock

A truck driver was injured by a high-voltage line of 10,000 volts when holding a metallic bar in both hands. Initially no neurological abnormalities were found, but during the following few weeks increasing sensory and minor motor symptoms developed in the right upper extremity. After one year numbness of the right thigh and leg appeared, as well as attacks of white finger in both hands. Repeated examinations showed progressive abnormalities of the median and ulnar nerves in both hands. No other cause for Raynaud's syndrome was discovered. The late high-voltage effects, presumably indirect, are suggested to be of multifactorial etiology.