Tri-n-butyltin-induced change in cellular level of glutathione in rat thymocytes: a flow cytometric study

Since some of organotins, accumulated in edible mollusks of aquatic environments, exert a variety of toxic actions on experimental animals, it causes concern for the health of humans. We examined the effects of tri-n-butyltin chloride (TBT) and other organotins (triethyltin chloride, trimethyltin chloride, triphenyltin chloride and tetrabutyltin) on cellular content of glutathione (GSH) in rat thymocytes using a flow cytometer to further characterize the toxicity of TBT. When the cells were incubated with TBT at concentrations of 3 nM or more for 15 min, the cellular content of GSH dose-dependently decreased. However, it completely or partly recovered until 180 min even in the continued presence of TBT. This recovery was temperature-sensitive, suggesting an involvement of metabolic process. The efficacy of TBT to decrease the cellular content of GSH was greater than those of other organotins. Results suggest that TBT and some organotins at environmentally relevant (nanomolar) concentrations significantly reduce the cellular content of GSH, suggesting that they increase the vulnerability to some biological and chemical insults.     

Changing behavior of estrogen and progesterone receptors with metastasis or recurrence of breast cancer

Changes in level of estrogen receptor (ER) and progesterone receptor (PgR) and their affecting factors were studied with metastasis or recurrence of breast cancer. Since 1983, from 177 patients, 443 specimens were obtained and 244 simultaneous and 122 sequential pairs were compared. The consistency rate was 81% for both ER and PgR with simultaneous comparison,and 69% for ER and 71% for PgR with sequential comparison, mainly due to positive-to-negative change, and less than 10% of negative-to-positive change. Positive-to-negative change was prominent with intervening endocrine treatment, and it was significant (p=0.015) for ER by multiple regression analysis of age, interval of sampling and from prior surgery, intervening chemotherapy, endocrine therapy and human epidermal growth factor receptor 2 (HER 2). Based on recent data of ER and PgR, feasible treatment seems to be planned, because about 30% of them are different from that of primary lesion.     

Efferent connections of the anterior hypothalamic nucleus: a biocytin study in the cat

The efferent connections of the anterior hypothalamic nucleus (AH) were examined using biocytin as anterograde tracer in the cat. The results provide several new findings in addition to confirming earlier observations. In the hypothalamus, the AH projections terminated mainly in the medial regions which are related to the defensive, reproductive and feeding behaviors, and autonomic functions. Moreover, we found dense patches of the AH terminals in the medial preoptic area and ventromedial hypothalamic nucleus, which suggests the existence of modular connections between sub-regions of each nucleus. In addition, the AH projected to regions which may be related to the emotional and autonomic responses, i.e., such regions in the amygdala, midline thalamus, septum, subthalamus, and midbrain. The data suggest that the AH may play an important role in the autonomic functions and behaviors between animals, and thus may play a key role in the defensive behavior elicited in the medial preoptic area and ventromedial hypothalamic nucleus.     

Flow cytometric estimation of cytotoxic activity of rhodexin A isolated from Rhodea japonica in human leukemia K562 cells

We have examined the cytotoxic effect of rhodexin A isolated from the extract of Rhodea japonica on human leukemia K562 cells using a flow cytometer and compared it with that of ouabain. Rhodexin A at 30 nM started to attenuate growth without affecting viability and further increases in the concentration of rhodexin A (100 nM or more) completely inhibited growth with decreasing viability. Rhodexin A at 30-100 nM increased the G(2)M population, but decreased the G(0)G(1) population, suggesting cell cycle arrest in the G(2)M phase. Rhodexin A at 100 nM increased the number of cells with hypodiploid DNA, indicating that rhodexin A induced apoptosis. The potency of rhodexin A to inhibit growth was greater than that of ouabain. The results indicate that rhodexin A exerts a potent inhibitory action on the growth of human leukemia K562 cells by inducing cell cycle arrest and apoptosis. Rhodexin A may also be a candidate for cancer treatment because there have been clinical reports of tumor regression in patients taking cardiac glycosides.     

Exposure of rat thymocytes to hydrogen peroxide increases annexin V binding to membranes: inhibitory actions of deferoxamine and quercetin

N(G)-(Nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase, induces catalepsy in mice. The objective of the present work was to investigate if serotonergic drugs are able to modulate this effect. Results showed that the cataleptogenic effect of L-NOARG (40 mg/kg) in male albino-Swiss mice was enhanced by pre-treatment with (+)-N-tert-butyl-3-(4-[2-methoxyphenyl]piperazin-1-yl)-2-phenylpro panamide ((+)-WAY-100135, 5 or 10 mg/kg), a 5-HT1A-selective receptor antagonist, and by ketanserin (5 or 10 mg/kg), a 5-HT2A receptor and alpha1-adrenoceptor antagonist. Prazosin (3 or 5 mg/kg), an alpha1-adrenoceptor antagonist, and endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3yl)-2,3-dihydro-3,3-dimet hyl-indole-1-carboxamide HCl (BRL-46470A, 0.05 or 0.5 mg/kg), a 5-HT3 receptor antagonist, did not interfere with L-NOARG-induced catalepsy. Ritanserin (3 or 10 mg/kg), a 5-HT2A and 5-HT2C receptor antagonist, tended to enhance the effect of L-NOARG. These results confirm that interference with the formation of nitric oxide induces catalepsy in mice, and suggest that this effect is modulated by 5-HT1A and 5-HT2A receptors.