[The effect of 1-p-bromphenyl-5-mercapto-1,2,3,4-tetrazole (Br FMT) on thyroid gland function in rats]. / Vliv 1-p-bromfenyl-5-merkapto-1,2,3,4-tetrazolu (Br FMT) na funkci stítné zlázy potkana.

The effects of the novel potential thyrostatic agent 1-p-bromphenyl-5- mercapto-1,2,3,4-tetrazole (Br-FMT) on the serum levels of thyroxine, thyrotropic hormone (TSH), the content of cyclic adenosine monophosphate (cAMP) in the thyroid gland, the body weight and the weight of the thyroid gland in liver transaminases and the white blood picture in Wistar strain rats were investigated. The effect of Br-FMT was compared with the effect of the well-known thyrostatic agent and goitrogen ethylester of 3-methyl-2-thio-4-imidazoline-1- carboxylic acid, carbimazole (Spofa) and with the control group, which received placebo only. The drugs tested were administered to animals in the dose do 7.5 mumol/animal via a gastric tube for the period of one month. Br-FMT and carbimazole decreased the level of serum thyroxine in a statistically significant manner. The serum level of TSH was evidently decreased after Br-FMT; it was not changed after administration of carbimazole in the given dose. The content of cAMP in the thyroid gland was significantly increased only after carbimazole. The weight of the thyroid gland was not significantly changed in any group under study, though after carbimazole the mean value was higher by a quarter as compared with the control group. The body weight and white blood picture were not significantly changed in all groups under study. ALT and AST values were evidently lower after carbimazole and Br-FMT, most probably due to the hypothyroid state of the animals.(ABSTRACT TRUNCATED AT 250 WORDS)

[Radioprotective effects of DDP]. / Radioprotektivní úcinek DDP.

The authors studied the effect of various DDP applications (sodium salt of dimethyl-dioxopiperazine thiosulfonate) in a dose of 45 mg/kg w. administered 10 min before irradiation, on the survival of female mice C57 and (CBA x C57BL/F1 after a single whole-body exposure to a sublethal dose of gamma rays (LD50/5 = magnitude of 15.495 +/- 0.781 magnitude of Gy and LD50/30 = magnitude of 7.864 +/- 0.018 magnitude of Gy). The depth of DDP protection effect on the haemopoietic stem cells was studied using the method of endogenous spleen colonies (ESC) of haemopoietic tissue. DDP radioprotective effect was also demonstrated after s. c. and i. m. application of this substance 10 min before 6 Gy of gamma radiation; it was shown by a prolongation of the survival time of experimental animals and by an increase in the number of individuals surviving till the 30th day after irradiation. Higher ESC numbers in the animals with DDP protection demonstrate survival of higher number of the haemopoietic stem cells and indicate that DDP is the biological active substance and contributes to the repair of haematopoiesis damaged by radiation and to the survival of irradiated animals.

[5-Substituted 3-mercapto-4H-1,2,4-triazoles as a potential thyrostaticagent]. / 5-Substituované 3-merkapto-4H-1,2,4-triazoly jako potenciální thyreostatika.

Within the framework of the study of the relationships between the structure and thyreostatic activity of cyclic analogues of thiourea, a series of 5-substituted 3-mercapto-4H-1,2,4-triazoles was prepared in order to answer the question of how the presence of another nitrogen atom in position 1 and the presence of the substituent in position 5 would influence thyreostatic activity. The synthesis was based on 1-acylsubstituted thiosemicarbazides which were cyclized to the pertinent 3-mercapto-4H-1,2,4-triazoles. Furthermore, esters of dicarboxylic acids were used, which with thiosemicarbazide in alcoholate yielded the pertinent mercaptotriazoles. Selected 5-substituted 3-mercapto-4H-1,2,4-triazoles were tested on adult male rats of Wistar strain. The effects of the agents under study on the level of serum thyroxine (T4), total body weight, heart weight, thyroid gland weight, and the number of leucocytes were investigated. The results of the tests show that whereas the presence of nitrogen in position 1 influenced the thyreostatic activity of the agents prepared in an insubstantial manner only, the presence of a substituent in position 5 acts, except a methyl or ethyl group, dystherapeutically, and with the increasing volume of the substituent therapeutic activity disappears regardless of the fact whether an aliphatic or aromatic substituent is concerned.

Embryotoxicity of L-prolyl-L-leucyl-glycinamide, cyclo(1-amino-cyclopentanecarbonyl-alanyl) and cyclo(glycyl-leucyl), new potential neuropeptides in chick embryos.

With the use of the method Chick Embryotoxicity Screening Test II (CHEST II), the potential neuropeptides L-prolyl-L-leucyl-glycinamide (MIF), cyclo(1-aminocyclo-pentanecarbonyl-L-alanyl)[cyclo(Acp-Ala)] and cyclo(glycyl-L-leucyl)[Cyclo(Gly-Leu)] were tested in the critical developmental periods of d 1.5 to 4 of chick embryogenesis in order to objectively examine their undesirable interactions with the developing morphogenetic systems of the brain, eye, face, body wall, limbs, trunk and heart. All compounds tested showed positive dose- and stage-response relationships. The body wall defects are the prevailing type of malformations.

Effect of a spirocyclic cyclodipeptide derivate of MIF on passive avoidance behavior and amnesia in rats.

Cyclo (1-amino-1-cyclopentane-carbonyl-L-alanyl)-c(Acp-Ala), a derivative of MIF (prolyl-leucyl-glycinamide) affected passive avoidance behavior of rats when administered at different phases of the step-through type of experimental paradigm. c(Acp-Ala) given s.c. or orally in a 1 mg/kg dose increased avoidance latencies not only when administered before, or immediately after the shock trial but also when given before the pretraining trial, i.e. at the first exposure of animals to the experimental situation without shock treatment. The notion is discussed, that it is the influence of c(Acp-Ala) on processing of information received during the pretraining trial that manifests itself in the facilitation of avoidance response. The drug appears to have a long-term action since it was active when given 20 h before the pretraining trial or the shock trial or the test of retention. c(Acp-Ala) when administered immediately after the shock trial, attenuated amnesia in rats induced by electroconvulsive shock (ECS).

Inhibition of proliferative activity by cyclic dipeptides: spirocyclic derivatives of 1-aminocyclopentane-carboxylic acid.

The antiproliferative activity of spirocyclic cyclodipeptides containing 1-aminocyclopentanecarboxylic acid (Acp) was investigated and compared with Pro-Leu-Gly-NH2 (MIF), cyclo(Gly-Leu) and cyclo (Sar-Sar), a compound with denaturing activity, employing the chick embryonic caudal morphogenetic system. Out of the compounds tested, MIF and cyclo(Acp-Ala) appear to exhibit the least inhibitory activity on growth.