The efficacy of a novel compound, (E)-1-(4′-bromo-4-biphenylyl)-1-(4-chlorophenyl)-3-dimethylaminoprop-1-ene againstTrypanosoma cruzi in mice

Summary The biological properties of a novel compound 353C with high activity againstTrypanosoma cruzi, are described. The compound was about 10 times and 20 times more effective than either benznidazole or nifurtimox respectively, in producing radical cure in mice. 353C had a long half-life and showed anti-trypanosomal properties when given to mice at weekly intervals.     

Effects of thyroidectomy and thyroxine replacement on the responsiveness of the anterior pituitaries from male rats to thyrotropin-releasing hormone in vitro

Summary Thyroidectomy decreased prolactin concentrations in the anterior pituitary (AP) and serum of the male rat. The amount of basal and thyrotropin-releasing hormone (TRH)-stimulated release of prolactin by AP in vitro was lower in thyroidectomized (Tx) rats than in sham Tx rats. These results suggest that the inhibitory effects of thyroidectomy on pituitary and serum prolactin in male rats are mediated in part by the reduction of the production and spontaneous release of prolactin and the responsiveness of prolactin to TRH.     

Reciprocal changes in serum free thyroxine fraction and thyrotropin level after administration of thiocyanate to rats

Summary The administration of thiocyanate to rats caused a significant increase of serum free thyroxine fraction, which coincided with the significant decrease of TSH level. The other components (AFT₄, T₄, T₃) in serum at this time were decreased or unchanged. The finding suggests the role of free thyroxine fraction in feed-back regulation of TSH secretion.Acknowledgment. We thank Dr A. Parlow and the NIAMDD, Rat Pituitary Hormone Distribution Program, for material for rat TSH immunoassay; Dr J. Nauman (Inst. Postgrad. Med., Warsaw, Poland) for T₃ antibody, and to Ing. J. Sadlo, Mrs M. t'astná and Miss R Fajkoová for technical assistance.     

Roles for interleukin-2 (IL-2) and IL-4 in the generation of allocytotoxic T cells in the primary and secondary responses in vitro

Roles for interleukin-2(IL-2) and IL-4 in the generation of murine allocytotoxine T lymphocytes (allo-CTL) in the primary and secondary responses were studied in vitro. The generation of allo-CTL in the primary response was inhibited by anti-IL-2 monoclonal antibody (mAb), but was not inhibited by anti-IL-4 mAb. On the other hand, the generation of allo-CTL in the secondary response was partially inhibited by either anti-IL-2 or anti-IL-4 mAb, and it was almost completely inhibited by the combination of two mAbs. CD8⁺ cell-depleted splenocytes produced IL-2, but not IL-4, in response to alloantigens in the primary response, and these cells produced both IL-2 and IL-4 in the secondary response. Both exogenous IL-2 and IL-4 induced functionally active allo-CTL in the primary response from CD4⁺ cell-depleted splenocytes when these cells were stimulated with T cell-depleted allogeneic cells. These results suggest that the allo-CTL induction in the primary response is IL:-2-dependent and secondary allo-CTL induction is both IL-2 and IL-4-dependent, because unprimed CD4⁺ T cells produce IL-2, but not IL-4, whereas primed cells produce both IL-2 and IL-4 in response to alloantigens.     

A dialysis rate method for the measurement of free iodothyronine and steroid hormones in blood

From the dialysis rate of a small amount of tracer hormone from a serum sample through a semipermeable membrane towards an identical serum sample, the free hormone fraction can be calculated. This method is free from a number of artefacts that may occur in equilibrium dialysis.     

Roles for interleukin-2 (IL-2) and IL-4 in the generation of allocytotoxic T cells in the primary and secondary responses in vitro.

Roles for interleukin-2 (IL-2) and IL-4 in the generation of murine allocytotoxine T lymphocytes (allo-CTL) in the primary and secondary responses were studied in vitro. The generation of allo-CTL in the primary response was inhibited by anti-IL-2 monoclonal antibody (mAb), but was not inhibited by anti-IL-4 mAb. On the other hand, the generation of allo-CTL in the secondary response was partially inhibited by either anti-IL-2 or anti-IL-4 mAb, and it was almost completely inhibited by the combination of two mAbs. CD8+ cell-depleted splenocytes produced IL-2, but not IL-4, in response to alloantigens in the primary response, and these cells produced both IL-2 and IL-4 in the secondary response. Both exogenous IL-2 and IL-4 induced functionally active allo-CTL in the primary response from CD4+ cell-depleted splenocytes when these cells were stimulated with T cell-depleted allogeneic cells. These results suggest that the allo-CTL induction in the primary response is IL:-2-dependent and secondary allo-CTL induction is both IL-2 and IL-4-dependent, because unprimed CD4+ T cells produce IL-2, but not IL-4, whereas primed cells produce both IL-2 and IL-4 in response to alloantigens.     

Distribution of 4-methoxy-3-indolylmethyl-glucosinolate (4-methoxy-glucobrassicin) in Brassicaceae

Summary 4-methoxy-3-indolylmethyl-glucosinolate was detectable by HPLC-methods in a representative profile of members of the brassicaceae. In many species it proved to be the main glucosinolate present in young seedlings.     

Variation in the specific activity of intestinal DNA in Alytes obstetricians larvae (Amphibia, Anura) treated with thyroxine]

Treatment by thyroxine modified the specific activity of intestianl DNA in premetamorphic Alytes tadpoles. The activity decreased up to the 3rd day, and showed afterwards a peak which culminates on the 9th day. These results have been discussed in comparison with previous radioautographic observations.     

Annual cycle of plasma testosterone and thyroxine in the European badger (Meles meles L.)]

In the male European Badger there are important variations in the plasma testosterone and thyroxine levels during the annual cycle. During the summer, plasma testosterone concentrations are low while plasma thyroxine rises to a very high level. In winter, when the thyroid activity is minimal, testicular activity increases. From February to May, the plasma testosterone remains at a high level, and then, after a sudden fall, a second peak occurs in June at which time the concentration of thyroxine is low.     

Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles

Summary 2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator drugs.Deceased, May 31, 1978.     

Respective roles of circulating T4 and T3 in control of TSH secretion in severely iodide-deficient rats

Summary After a 6-month iodide deficiency, Wistar male rats were submitted to a normal iodine diet (20 and 50 g of¹²⁷I daily). Plasma T₃, T₄ and TSH were determined by RIA from 0 to 140 days of iodide refeeding. A highly significant correlation was found between plasma TSH and T₄ concentrations, but not between plasma TSH and T₃ levels. These data suggest that an increase in plasma T₃ alone, up to the normal value, is not able to inhibit TSH secretion. It is only when a certain plasma T₄ concentration is also reached, resulting in further T₃ formation through deiodination, that TSH secretion is inhibited.Dedicated to the memory of Prof. C. Simon.This work was supported by grants from the CNRS (Equipe de Recherche Associée no 234) and from the INSERM (A.T.P. 49.77.8).Acknowledgments. The authors wish to thank Mrs M. Chartier for valuable technical assistance. They are indebted to the rat pituitary distribution programme of NIAMDD, NIH, Bethesda, for their gift of rat TSH reagents.     

Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles.

2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator durgs.