Ethanol Increases K+ Conductance in Human T-Cells

Ethanol increased the open probability of a K channel in cultured human T-cells. Single-channel currents were studied using the patch-clamp technique in cell-attached configuration. Ethanol increased the number of simultaneously active channels and subsequent current maxima at concentrations of 35 and 50 mM from control levels of 3.2 to 4.6 pA and 8.4 PA, respectively. Current responses were elicited by a 80 mV hyperpolarizing pulse following adjustment to the same resting potential. The channel was K-selective as determined by the reversal potentials under different Na-K gradients. When the pipette contained 155 mM K, single-channel currents had a slope conductance of 28 pS and a reversal potential of -4.3 mV. Baseline current levels often shifted in a negative direction during the application of ethanol, indicating a hyperpolarization of the membrane potential and an increase in channel activity.     

Effects of calcium and magnesium acetates on the carcinogenicity of cadmium chloride in Wistar rats

The effects of calcium and magnesium acetates on the formation of injection site and testicular tumors in male Wistar rats over 2 years following s.c. injections of cadmium chloride (CdCl2) were determined. The rats (25/group) received a single s.c. dose of CdCl2 (0.02 or 0.04 mmol/kg; 0.9% NaCl solutions). Calcium and magnesium acetates were administered as 3% dietary supplements for 2 weeks prior to and 2 weeks after the CdCl2 injection, or as three daily s.c. injections (0.16 mmol calcium acetate per kg, 4 mmol magnesium acetate per kg; 0.9% NaCl solutions) at the same site as CdCl2 on the day before, the day of, and the day after CdCl2 dosing. Control groups were given 0.9% NaCl solution instead of CdCl2 plus s.c. or dietary calcium and magnesium acetates. In rats given injections of CdCl2 alone, the final tumor yields were 33 and 34% of rats at risk at the injection site (mostly fibrosarcomas) and 86 and 85% of rats at risk in the testes (mostly interstitial cell tumors), respectively, for the low- and high-CdCl2 doses. In control rats, the corresponding tumor yields were 0% at the site of 0.9% NaCl solution injection and 30% in the testes. Dietary calcium and magnesium acetates or s.c. calcium acetate did not affect significantly the tumor yields and latent periods. Simultaneous injections of magnesium acetate at the same site completely prevented the development of injection site tumors for both CdCl2 doses but had no effect on the final yields of testicular tumors. CdCl2 injection also caused significant elevation of incidence of the pancreatic islet cell tumors (8.5 versus 2.2%) regardless of any other experimental treatment. These results provide further evidence that the divalent carcinogenic metals may exert their activity through an antagonism with the physiologically essential divalent metals.     

Analysis of macrophage interactions with cryopreserved amastigotes of Leishmania tropica.

Amastigotes of Leishmania tropica were harvested from infected footpads of BALB/cJ mice and cryopreserved, using a controlled-rate freezer. This technique produced inocula with reproducible viability and infectivity for peritoneal macrophages from C3H/HeN mice. Cryopreserved amastigotes, stored for up to 17 weeks in a liquid nitrogen freezer, were similar to freshly harvested parasites in susceptibility to lymphokine-induced intracellular killing. Interactions of cryopreserved parasites with macrophages were best evaluated at 72 h, since macrophages preferentially ingested viable amastigotes and rapidly cleared ingested nonviable parasites.     

Trophoblast sampling by blind transcervical aspiration

Summary. Blind transcervical aspiration for trophoblast was carried out on 137 patients undergoing elective termination of early pregnancies. Trophoblast was obtained from 45 patients (33%) usually at the first attempt. Collection was not necessarily more successful between 8 and 11 weeks of gestation. In only 13 patients (9%) was trophoblast collected without contamination by maternal tissue, or blood. Perforation of the amniotic sac in one patient (1%), bleeding either observed, or detected histologically (34%) and introduction of infection (4%) constitutes a real threat to fetal survival. Maternal serum a-fetoprotein estimation appears useful and may forewarn likelihood of fetal damage. Although transcervical aspiration should encounter ready acceptability as an outpatient procedure, modifications in the technique are essential before clinical application for detection of gene, or chromosome anomalies can be considered.     

Antagonism of androgen and estrogen effects in guinea pig seminal vesicle epithelium and fibromuscular stroma by keoxifene (LY156758)

Using separated epithelium (SVE) and fibromuscular stroma (SVM) of guinea pig seminal vesicle, the antihormonal effects of daily subcutaneous administration (14 and 28 days) of the benzothiophene keoxifene (LY156758; [6-hydroxy-2-(4-hydroxyphenyl)benzo(b) thien-3-yl] [4-(2-1-piperidinyl) ethoxyl] phenyl) methanone hydrochloride) in intact, castrate, and androgen/estrogen-maintained castrate animals was evaluated. The compound was devoid of agonist activity in castrated males, in that the compound had no stimulatory effect on SVM wet weight or DNA content. In vitro cytosolic binding of [3H]estradiol (E2) in the SVM was decreased in a concentration-dependent manner by keoxifene, but the compound did not perturb the binding of [3H]dihydrotestosterone (DHT) in the SVM or SVE. Likewise, keoxifene administration to castrated males treated with exogenous steroids antagonized the estrogen-induced hyperplastic response of the SVM, whereas no interference with androgen-induced growth of the SVM or SVE was observed. Keoxifene treatment of intact male guinea pigs produced regression of the androgen-sensitive SVE as well as the androgen/estrogen-sensitive SVM. Keoxifene-induced decreases in guinea pig serum testosterone levels were associated with this activity. Histological analysis of the seminal vesicle under these conditions suggests androgen deprivation. These findings indicate that keoxifene is a physiological antagonist of androgen action in the intact male guinea pig. The pure estrogen antagonist properties of keoxifene and its ability to decrease accessory sex organ epithelium and fibromuscular stroma in vivo suggest potential applications of the benzothiophenes in the medical management of prostatic neoplasia.