The melatonergic pathway and its interactions in modulating respiratory system disorders.

Melatonin is a key intracellular neuroimmune-endocrine regulator and coordinator of multiple complex and interrelated biological processes. The main functions of melatonin include the regulation of neuroendocrine and antioxidant system activity, blood pressure, rhythms of the sleep-wake cycle, the retardation of ageing processes, as well as reseting and optimizing mitochondria and thereby the cells of the immune system. Melatonin and its agonists have therefore been mooted as a treatment option across a wide array of medical disorders. This article reviews the role of melatonin in the regulation of respiratory system functions under normal and pathological conditions. Melatonin can normalize the structural and functional organization of damaged lung tissues, by a number of mechanisms, including the regulation of signaling molecules, oxidant status, lipid raft function, optimized mitochondrial function and reseting of the immune response over the circadian rhythm. Consequently, melatonin has potential clinical utility for bronchial asthma, chronic obstructive pulmonary disease, lung cancer, lung vascular diseases, as well as pulmonary and viral infections. The integration of melatonin's effects with the alpha 7 nicotinic receptor and the aryl hydrocarbon receptor in the regulation of mitochondrial function are proposed as a wider framework for understanding the role of melatonin across a wide array of diverse pulmonary disorders.

Telocytes in the human sinoatrial node.

The sinoatrial node (SAN) is composed mostly of pacemaker, transitional and Purkinje-like cells. Pacemaker cells, especially in the centre of the SAN, are surrounded by dense fibrous tissue and do not have any contact with transitional cells. We hypothesize that the SAN contains telocytes that have contacts with pacemaker cells and contractile myocardium. Immunohistochemistry using antibodies against HCN4 and antibody combinations against CD34 and HCN4 was carried out on 12 specimens. Confocal laser scanning microscopy (CLSM) with two mixtures of primary antibodies, namely CD34/S100 and vimentin/S100, was performed in three cases. In two cases, CLSM was carried out with CD117 antibody. Specimens for electron microscopy and immunocytochemistry with HCN4 immunogold labelling were taken from another three patients. In our study, we found cells with the immunophenotype of telocytes in the SAN. There were twice as many of these cells in the centre of the SAN as in the periphery (20.3 ± 4.8 versus 10.8 ± 4.4 per high-power field). They had close contact with pacemaker cells and contractile cardiomyocytes and expressed HCN4. The ultrastructural characteristics of these cells are identical to those of telocytes observed earlier in other organs. Our study provides evidence that telocytes are present in the SAN.

Plurihormonal cells of normal anterior pituitary: Facts and conclusions.

INTRODUCTION: plurihormonality of pituitary adenomas is an ability of adenoma cells to produce more than one hormone. After the immunohistochemical analysis had become a routine part of the morphological study, a great number of adenomas appeared to be multihormonal in actual practice. We hypothesize that the same cells of a normal pituitary gland releases several hormones simultaneously. OBJECTIVE: To analyse a possible co-expression of hormones by the cells of the normal anterior pituitary of adult humans in autopsy material. MATERIALS AND METHODS: We studied 10 pituitary glands of 4 women and 6 men with cardiovascular and oncological diseases. Double staining immunohistochemistry using 11 hormone combinations was performed in all the cases. These combinations were: prolactin/thyroid-stimulating hormone (TSH), prolactin/luteinizing hormone (LH), prolactin/follicle-stimulating hormone (FSH), prolactin/adrenocorticotropic hormone (ACTH), growth hormone (GH)/TSH, GH/LH, GH/FSH, GH/ACTH, TSH/LH, TSH/FSH, TSH/ACTH. Laser Confocal Scanning Microscopy with a mixture of primary antibodies was performed in 2 cases. These mixtures were ACTH/prolactin, FSH/prolactin, TSH/prolactin, ACTH/GH, and FSH/GH. RESULTS: We found that the same cells of the normal adenohypophysis can co-express prolactin with ACTH, TSH, FSH, LH; GH with ACTH, TSH, FSH, LH, and TSH with ACTH, FSH, LH. The comparison of the average co-expression coefficients of prolactin, GH and TSH with other hormones showed that the TSH co-expression coefficient was significantly the least (9,5±6,9%; 9,6±7,8%; 1,0±1,3% correspondingly). CONCLUSION: Plurihormonality of normal adenohypophysis is an actually existing phenomenon. Identification of different hormones in pituitary adenomas enables to find new ways to improve both diagnostic process and targeted treatment.

Assessment of the Potential Biological Activity of Low Molecular Weight Metabolites of Freshwater Macrophytes with QSAR.

The paper focuses on the assessment of the spectrum of biological activities (antineoplastic, anti-inflammatory, antifungal, and antibacterial) with PASS (Prediction of Activity Spectra for Substances) for the major components of three macrophytes widespread in the Holarctic species of freshwater, emergent macrophyte with floating leaves, Nuphar lutea (L.) Sm., and two species of submergent macrophyte groups, Ceratophyllum demersum L. and Potamogeton obtusifolius (Mert. et Koch), for the discovery of their ecological and pharmacological potential. The predicted probability of anti-inflammatory or antineoplastic activities above 0.8 was observed for twenty compounds. The same compounds were also characterized by high probability of antifungal and antibacterial activity. Six metabolites, namely, hexanal, pentadecanal, tetradecanoic acid, dibutyl phthalate, hexadecanoic acid, and manool, were a part of the major components of all three studied plants, indicating their high ecological significance and a certain universalism in their use by various species of water plants for the implementation of ecological and biochemical functions. This report underlines the role of identified compounds not only as important components in regulation of biochemical and metabolic pathways and processes in aquatic ecological systems, but also as potential pharmacological agents in the fight against different diseases.