Structure-activity relationship for peptídic growth hormone secretagogues.

Growth hormone releasing peptides (GHRPs) could be widely used by cheating athletes because they produce growth hormone (GH) secretion, so may generate an ergogenic effect in the body. Knowledge of the essential amino acids needed in GHRP structure for interaction with the target biological receptor GHSR1a, the absorption through different administration routes, and the maintenance of pharmacological activity of potential biotransformation products may help in the fight against their abuse in sport. Several GHRPs and truncated analogues with the common core Ala-Trp-(D-Phe)-Lys have been studied with a radio-competitive assay for the GHSR1a receptor against the radioactive natural ligand ghrelin. Relevant chemical modifications influencing the activity for positions 1, 2, 3, and 7 based on the structure aa-aa-aa-Ala-Trp-(D-Phe)-Lys have been obtained. To test in vivo the applicability of the activities observed, the receptor assay activity in samples from excretion studies performed after nasal administration of GHRP-1, GHRP-2, GHRP-6, Hexarelin, and Ipamorelin was confirmed. Overall results obtained allow to infer structure-activity information for those GHRPs and to detect GHSR1a binding (intact GHRPs plus active metabolites) in excreted urines. Copyright © 2016 John Wiley & Sons, Ltd.

[Clinical and genetic markers of chronic cerebral ischemia].

OBJECTIVE: To study the effectiveness of common neuropsychological tests for the verification of the diagnosis of cerebral ischemia (CE) and a role of polymorphisms in SERT, ApoE and BDNF genes in its development. MATERIAL AND METHODS: We studied 272 inpatients, aged from 37 to 70 years, with CE of the first stage (58 patients), CE of the second stage (121 patients) and CE of the third stage (93 patients). A set of neuropsychological tests, as well as biochemical and molecular-genetic studies were performed. RESULTS AND CONCLUSION: Reitan test was the most effective test for the diagnosis of cognitive impairment. The results of the Clock Drawing Test and MMSE were correlated with the disease severity but did not distinguish between the first and second stages of CE. Arterial hypertension and stenosing atherosclerosis of brain vessels were significant predictors of CE. SERT gene was a marker of the CE risk in men. The genotype SS was associated with the risk of CE with early age-at-onset. No association of ApoE and BDNF genes with CE was found.

An investigation of the age-dependency of chromosome abnormalities in human populations exposed to low-dose ionising radiation.

Among various cytogenetic changes stable chromosome aberrations (SCHA) seem to be the most significant for ageing and carcinogenesis. Being nonlethal they can persist through cell divisions and accumulate in time. We studied the age response of SCHA (translocations and insertions) in normal and radiation exposed human populations. Two cohorts of people at the age range of 3--72 years were studied: control (43 persons) and exposed to low doses of accidental irradiation due to Chernobyl accident and atomic bomb testing in Semipalatinsk (67 persons). FISH method was used for visualisation of chromosome aberrations. Metaphases from cultured lymphocytes were hybridised with biotinilated whole chromosome specific DNA probes for 1, 4 and 12 chromosomes, and with pancentromeric probe labelled with digoxigenin. The frequency of SCHA in lymphocytes increased as a quadratic function of donor age in both populations studied, being higher in exposed cohort as compared with control one. No age dependence for dicentrics was observed. The frequency of SCHA is a reliable biomarker of ageing in humans. Quadratic model of their age-response gives reasons to suggest that their increase is due to lower level of DNA repair or/and the genomic instability in older people. The exposure of people to low doses of ionising radiation accelerates the age-related increase of SCHA frequency.

[Effect of experimental herpesvirus infection on morphofunctional state of mast cells]. / Vliianie éksperimental'no'i gerpesvirusno'i infektsii na morfofunk tsional'noe sostoianie tuchnykh kletok.

Mast cells are involved in the reaction of the organism to herpesvirus infection, which manifests by changes in their count, morphology, and function. The onset of infection is characterized by primary activation of mast cells, the peak of disease by suppressed function, and convalescence by secondary activation and stabilization of cell morphology and function. Viral infection running in the presence of immunosuppression caused by cyclophosphamide is characterized by deep persistent suppression of the morphology and functions of mast cells at the peak of disease.

[The effect of different infectious agents on the intensification of hematopoiesis during immunosuppression]. / Vliianie razlichnykh infektsionnykh agentov na usilenie krovetvoreniia v usloviiakh immunosupressii.

The action of Staphylococcus aureus, Escherichia coli and Herpes simplex virus on the hemopoiesis of mice with cytostatic myelosuppression was studied. The study revealed that the infection of the animals simultaneously with the action of cyclophosphamide considerably activated the processes leading to the restoration of hemopoiesis due to an increase in the mitotic activity of hemopoietic cells, the accelerated differentiation of hemopoietic precursor cells which could survive the cytostatic action and an increase in the functional activity of the hemopoiesis-producing microenvironment.