Synthesis and neuroleptic activity of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles.

The synthesis of a series of 3-(1-substituted-4-piperidinyl)-1,2-benzisoxazoles is described. The neuroleptic activity of the series was evaluated by utilizing the climbing mice assay and inhibition of [3H]spiroperidol binding. Structure-activity relationships were studied by variation of the substituent on the benzisoxazole ring with concomitant variation of four different 1-piperidinyl substituents.

Evidence for reopening of the cranial neural tube in mouse embryos treated with cadmium chloride.

Use of the whole-embryo culture technique resulted in experimental evidence that the pathogenesis of exencephaly in mouse embryos after cadmium chloride treatment results from reopening of the cranial neural tube.

Pharmacokinetics of amiodarone, desethylamiodarone and other iodine-containing amiodarone metabolites.

In 23 patients treated with the iodine-containing antiarrhythmic drug amiodarone, the plasma concentrations of amiodarone, desethylamiodarone and iodine have been studied. Besides amiodarone and desethylamiodarone, a pool of iodine-containing substances, NANDAI (non-amiodarone-, non-desethylamiodarone-iodine), was present. At steady state the iodine content of NANDAI amounted to 64% and the iodine content of amiodarone plus desethylamiodarone to 36% of total serum iodine.

Niche width and variation within and between populations in colonizing species (Carex flava group).

Taxa of the Carex flava group in Switzerland show a trend towards increased colonizing ability (r-selection). High colonizing ability is correlated with a large fundamental but a small and discontinuous realized niche. It is argued that r-selected species with wide niches should be monomorphic with generalists rather than polymorphic with specialists since they have small effective population sizes in which high genetic variability cannot be maintained.

Monitoring of organ formation in rat embryos after in vitro exposure to azathioprine, mercaptopurine, methotrexate or cyclosporin A.

Rat embryos in the organ formation phase (days 9.5-11.5 post coitum) were cultivated in pure rat serum in the presence of an Aroclor 1254 pretreated liver microsomal preparation (S9-mix).

DNA-damaging potential of diethylstilbestrol evaluated in the germ cell unscheduled DNA synthesis assay.

Despite the fact that the nonsteroidal estrogen diethylstilbestrol (DES) exerts its toxic effects primarily on the reproductive system, little is known about the possible interference of this compound with germ cell DNA. The measurement of unscheduled DNA synthesis (UDS) in spermatocytes and early spermatids of mice germ cells is a valid indicator for the DNA-damaging potential of a compound. UDS occurrence was thus determined after IP administration of 10, 30, 60 or 180 mg/kg DES to male mice.

[Does HDL-cholesterol determination facilitate the assessment of risk in coronary patients?].

Serum lipids (cholesterol, triglycerides, HDL-cholesterol) were analyzed in 153 patients with proven coronary heart disease (CHD) with the target to characterize the risk potential of HDL-cholesterol. It turns out, that the specificity of HDL-C is low (too many unexpected high values in CHD). Consequently this parameter is of little use in evaluating the individual risk for CHD.

A comparative study of digoxin levels by radioimmunoassay micromethod in capillary and venous blood samples in children.

In a group of 30 digitalized children, we compared the digoxin levels in capillary and venous plasma samples, both of which were obtained simultaneously from each child. We statistically concluded that the venous plasma samples could surely be replaced by capillary plasma samples for measurements of plasma digoxin levels without any significant difference. Additionally, we showed that storing the capillary plasma samples at room temperature for 3 days did not lead to any significant change in digoxin levels.

In vitro exposure of male and female mice gametes to cadmium chloride during the fertilization process, and its effects on pregnancy outcome.

The effect of cadmium chloride (Cd) on gamete fusion in vitro was evaluated, with further observations of the embryonic development and assessment of the pregnancy outcome of the in vitro fertilized mice. Oocytes were recovered from superovulated B6C3F1 females. Of 1210 control oocytes, 53.

Teratogenicity induced in cultured rat embryos by the serum of procarbazine treated rats.

Male rats were injected with single intraperitoneal doses of 50-200 mg/kg of procarbazine hydrochloride (P). Their undiluted serum was then used as the culture medium for 9.5-day-old embryos to evaluate its teratogenic and toxic potential in vitro.

Assessment of the teratogenic potential of acrolein and cyclophosphamide in a rat embryo culture system.

Rat conceptuses were explanted from the uterus on day 10.5 of gestation. The embryos within the yolk-sacs were then transferred to culture bottles containing pure male rat serum either with or without liver microsomes and NADPH.

Biological assessment of chemical DNA damage in germ cells of male rabbits.

DNA damage represents a key step in mutagenesis and carcinogenesis. Excision repair has been described to be the major pathway restoring damaged DNA. Assaying DNA repair may thus illuminate the mechanism of mutagenesis and carcinogenesis and serve as an indicator of the mutagenic and carcinogenic potential of environmental chemicals and drugs.

Assessment of DNA damage in germ cells of male rabbits treated with isoniazid and procarbazine.

The 2 hydrazine derivatives isoniazid (INH) and procarbazine hydrochloride (P) were injected intravenously into rabbits. Radioactive thymidine was injected into both testicles. Rabbits were ejaculated repeatedly, sperms were counted and incorporation of [3H] thymidine into sperm head DNA was determined by liquid scintillation counting.

Unscheduled DNA synthesis in male rabbit germ cells induced by methylmethane sulfonate, cyclophosphamide and adriamycin.

Male rabbit germ cells were labelled by intratesticular injection of [3H]-thymidine (3H-T). In sperms of control animals, radioactivity was first demonstrated between the 40th and 43rd day after labelling, corresponding to preleptotene spermatocytes. In rabbits treated with 22.