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Hypothalamic melanortin receptor (MCR) activation inhibits appetite. Neuropeptide Y (NPY) and Agouti Related Protein (AgRP) are coexpressed in some hypothalamic neurons and stimulate feeding, NPY via inhibition of MCR-expressing neurons, and AgRP via MCR4 antagonism. Mutation yellow at the mouse agouti locus (А у ) evokes MCR blockage and stimulates appetite in nulliparous females. The role of MCRs in food intake regulation during pregnancy and lactation is unclear. In this study we measured hypothalamic AgRP and NPY mRNA levels in virgin and mated C57Bl a/a (control) and А у /a females on days 7, 13, 18 of pregnancy, 10, 21 of lactation, and after offspring separation, AgRP immunoreactivity in virgin and lactating females, and correlated gene expression with food intake (FI). Virgin А у /a compared to a/a females had higher FI and lower AgRP expression. Pregnant А у /a and a/a mice showed different patterns of food intake and neuropeptide expressions. NPY mRNA levels increased during pregnancy only in a/a mice, while AgRP mRNA levels increased in both genotypes being lower in А у /a then in a/a mice. In lactating А у /a and a/a mice, AgRP expression and NPY mRNA level were similar. AgRP expression was higher in lactating then in virgin А у /a mice. The results obtained demonstrate that in nonbreeding female mice, MCR blockage is associated with AgRP expression inhibition which vanishes in lactation. In lactation, hyperphagia is independent of MCR blockage. In pregnancy, food intake regulation involves MCR signaling and activation of NPY and AgRP expression.Key words: А у mice; food intake; pregnancy; lactation; melanocortin receptors; NPY; AgRP.Активация меланокортиновых рецепторов (МКР) в гипоталамусе подавляет аппетит. Белок, родственный агути (AgRP), и нейропеп-тид Y (NPY) коэкспрессируются в нейронах гипоталамуса и повы-шают аппетит: NPY -через свои рецепторы на МКР-нейронах, AgRP связывается с МКР и вызывает их инактивацию. У неразмно-жающихся мышей генетическая блокада МКР (мутация yellow в локусе агути А у ) повышает потребление пищи. Остается невыяс-ненной роль МКР в регуляции аппетита в период беремен ности и лактации, когда потребление пищи значительно возрастает. В этой работе у мышей линии C57Bl/6J a/a (контроль) и А у /a генотипов изучали экспрессию AgRP (меланокортиновая регуля-ция) и NPY (немелано кортиновая регуляция) в гипоталамусе в период беременности (7, 13, 18-й дни) и лактации (10-й и 21-й дни) и сопоставили ее с потреблением пищи. У виргинных А у /a (блокада МКР) самок по сравнению с a/a самками потребление пищи было повышено, уровень мРНК и иммунореактивность AgRP понижены. Динамика возрастания потребления пищи по ходу беременности различа лась у А у /a и a/a мышей. Уровень мРНК NPY возрастал только у a/a самок, а уровень мРНК AgRP -у самок обоих генотипов, но у А у /a был ниже, чем у контрольных. После родов потребление пищи, уровни мРНК нейропептидов и иммунореактивность AgRP в гипоталамусе не различались у А у /a и a/a самок, экспрессия AgRP у лактирующих А у /a самок была выше, чем у...
Aim. To evaluate the pharmacoeconomic analysis of three antihypertensive drugs routinely used to optimize blood pressure in young adults.Methods. 250 patients were recruited to the study and subdivided into three groups: Group 1 patients (n = 131) received monotherapy with angiotensin-converting enzyme inhibitor, ramipril; Group 2 and 3 patients (n = 119) received combination therapy with perindopril + amlodipine and ramipril + amlodipine.Results. The group of patients receiving ramipril had the average daily dose of 10 mg, patients taking egipres received 5/10 mg daily, and patients receiving prestans took 5/5 mg daily. Thus, the cost of treatment with ramipril at the dose optimally reducing blood pressure remained the same, while the cost of treatment with prestans decreased up to 37400.00 RUB, and egipres up to 45218.00 RUB. 4.76% of patients who received these antihypertensive medicines experienced side effects, namely cough, dizziness, a sharp decrease in blood pressure, allergic dermatitis, nausea. The least rate of side effects occurred in patients who received perindopril, whereas the highest was recorded in the group of patients receiving ramipril (3.5% vs. 6.5%, respectively).Conclusion. No significant differences found in the antihypertensive effects between three groups of drugs (ramipril, prestans, egipres). All three medicines included in this study effectively reduced blood pressure. However, prestans was associated with the least rate of side effects. Most side effects were short-term and of mild to moderate severity.
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