Inhibitory properties of aromatic thiosemicarbazones on mushroom tyrosinase: Synthesis, kinetic studies, molecular docking and effectiveness in melanogenesis inhibition.

The group of 19 thiosemicarbazones (TSCs) were synthesized and its inhibitory activity toward mushroom tyrosinase and ability to inhibition of melanogenesis in B16 cells were investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. The obtained results allowed to make the structure-activity relationship (SAR) analysis. Kinetic studies revealed that TSCs 1, 2, 11 and 18 have better inhibitory properties than kojic acid, a reference compound, with the best inhibitory constant (Ki) value of 0.38 µM for TSC 2. According to SAR analysis, the smaller and less branched molecules exhibit higher affinity to the enzyme. Melanin production in B16 cells was inhibited by all investigated compounds at micromolar level. Most of compounds studied in this work can be considered as potent inhibitors of tyrosinase and melanogenesis. They may have broad application in food preservatives and cosmetics. Combined results of molecular docking and SAR analysis can be helpful in designing novel tyrosinase inhibitors of desired properties.

CD55, CD59, factor H and factor H-like 1 gene expression analysis in tumors of the ovary and corpus uteri origin.

The expression level of complement regulators in ovarian and corpus uteri tumors was not fully established so far. In current manuscript we performed gene expression analysis by the real-time PCR approach to investigate both membrane bound - CD55 and CD59 and fluid phase - factor H and factor H-like 1 complement regulators. We found increased CD55 expression in corpus uteri tumors when compared to control tissues, whereas in ovarian cancer CD55 expression was lower than in control sections. Additionally we found CD59 expression to be more prominent in ovarian cancer than in corpus uteri tumor samples. We observed also the strong positive correlation between the level of expression of the whole group of regulators, which was particularly significant between the expression of factor H and factor H- like 1. In conclusion we present novel results which implicates different role of particular complement inhibitors in the regulation of the complement system in two cancer types examined. Strong positive correlation between examined proteins implicates similar pattern of the regulation which should be taken into consideration with regards to the possible immunotherapy applied as adjuvant therapeutic approach in these two indications. The inhibition of complement regulation may serve as a strategy to potentiate the efficacy of such treatment.

The hypothalamic centres involved in the control of production and release of prolactin in sheep.

Lesions made in the anterior medial basal hypothalamus (MBH) in pregnant or lactating ewes caused lack of development of the mammary gland and depressed milk yield, a decrease in plasma prolactin concentration and structural changes in the prolactin cells as manifested by a lack of the expected degranulation (lack of the hormone release) or by atrophic changes and diminished cell granulation (or granule synthesis). Lesions made in the caudal MBH during pregnancy advanced development of the mammary gland, induced a rapid increase in the plasma prolactin concentration and caused extensive degranulation of prolactin cells. These results indicate that at least two functional systems controlling the secretion and production of prolactin exist in the hypothalamus of sheep: an anterior system which is stimulatory and a caudal which is inhibitory.

Cyclic activity of the pituitary prolactin cells and plasma prolactin levels in the oestrous cycle of the ewe.

The relative proportions of prolactin cells, somatotrophs and gonadotrophs were determined in the adenohypophyses of 28 Merino ewes on selected days during the oestrous cycle. Plasma prolactin levels were measured in 16 of the animals at 3-hr intervals during the 24 hr before autopsy. From Days 1 to 5 of the cycle (Day 0=day of ovulation), plasma prolactin levels were 20-40 ng/ml and the prolactin cells were filled with granules. Plasma levels increased to 168 ng/ml between Days 6 and 9, and marked degranulation of the prolactin cells occurred. The greatest degranulation was found on Days 16 and 0, and was associated with a prolactin surge to a concentration of 610 ng/ml. The rise in plasma prolactin and intensive degranulation of prolactin cells at the time of ovulation and formation of the CL suggest that prolactin is important at this stage of the oestrous cycle.

The role of catecholamines in stimulating the release of pituitary ovulating hormone(s) in sheep.

Noradrenaline (NA) or dopamine (DA) were infused into the 3rd cerebral ventricle of the ewes in the stage of late anestrus and the release of LH and the induction of ovulation (IO) were followed. After the infusion of NA the release of LH and IO in the ewes with so-called "activated" ovaries was observed, while no reaction was found in the ewes with the "inactive" ovaries. The infusion of DA was without any effect either in the ewes with "activated" or with "inactive" ovaries.

The effect and site of action of indoleamines on the hypothalamic centers involved in the control of LH release and ovulation in sheep.

Serotonin or melatonin was infused into the 3rd cerebral ventricle (3rd V) or into the medial basal hypothalamus (MBH) of both intact ewes and ewes with lesions of the anterior hypothalamic area (AHA). Prolongation of the estrous cycle and delay of ovulation were obtained after infusions of melatonin or serotonin in both the intact and lesioned ewes. Statistically, serotonin proved to be more effective in this respect than melatonin in the intact ewes. The infusions also blocked the prevulatory peak of LH. Furthermore, the infusion of serotonin blocked estrous behavior, while that of melatonin did not affect this function. The effect of indoleamine infusions in the lesioned ewes, in which the inhibitory action of the AHA over the transmission of gonadotrophic releasing hormones (G-RH) had been eliminated, seems to indicate that the inhibitory action of indoleamines on the release of these neurohormones is being displayed at the level of the MBH.