10 research outputs found
A case of 17-beta-hydroxysteroid dehydrogenase deficiency type 3 in adult endocrinologist practice
17β-Hydroxysteroid dehydrogenase 3 deficiency (17HSD3) is a rare autosomal recessive cause of 46, XY disorders of sex development resulting from HSD17B3 gene mutations, in which conversion of androstenedione to testosterone is impared. The clinical signs of 17HSD3 deficiency depend on the residual activity of the enzyme. The diagnosis of 17HSD3 deficiency is based on reduced testosterone/androstenedione ratio (T/AD < 0.8). Patients are usually assigned at birth and raise as female. If the diagnosis is made before puberty, gonadectomy is recommended, taking into account the risk of masculinization during the puberty and estrogen therapy initiation in this period. If the diagnosis of 17HSD3 deficiency is established during puberty, when virilization manifests, the therapeutic strategy is based on the results of comprehensive psychological testing and gender identity of a patient. In patients with more pronounced masculinization or diagnosis established shortly after birth, who are assigned at birth and raise as male, testosterone therapy is used to achieve a male phenotype. The 17HSD3 deficiency and virilization often result in a change of gender identity during puberty. The article presents a clinical case of 17-βhydroxysteroid dehydrogenase type 3 deficiency with late diagnosis due to parental will. The diagnostic approaches and management of the disease are also described
Diastereoselective Synthesis of C60/Steroid Conjugates
The design and synthesis of fullerene–steroid hybrids by using Prato’s protocol has afforded new fullerene derivatives endowed with epiandrosterone, an important naturally occurring steroid hormone. Since the formation of the pyrrolidine ring resulting from the 1,3-dipolar cyloaddition reaction takes place with generation of a new stereogenic center on the C2 of the five-membered ring, the reaction proceeds with formation of a diastereomeric mixture [compounds 6 and 7 in 70:30 ratio, 8 and 9 in 26:74 ratio (HPLC)] in which the formation of the major diasteroisomers 6 and 9 is consistent with an electrophilic attack of [60]fullerene on the Re face of the azomethine ylide directed by the steroidic unit. The chiroptical properties of these conjugates reveal typical Cotton effects in CD spectra that have been used to assign the absolute configuration of the new fulleropyrrolidines. The electrochemical study of the new compounds reveals the presence of four quasi-reversible reduction waves which are cathodically shifted in comparison with the parent C60, thus ascertaining the proposed structures.Financial support by the Ministerio de Ciencia e Innovación (MINECO) of Spain (CTQ2011-24652, CTQ2011-27253, PIB2010JP-00196, and CSD2007-00010 projects) and CAM (Madrisolar-2) is acknowledged; A.R. thanks UCM for financial support; M.S. is indebted to Programa del Grupo Santander 2012
Clinical case of factitious hypoglycemia
Hypoglycemic syndrome (HGS) is a significant decrease glucose in blood, manifested by neurological symptoms, and stopped by the introduction of glucose. Among the many causes of HGS the special place is taken by the factitious hypoglycemia, as one of the variants of Munchausen syndrome. Hypoglycemia in such cases is achieved by the intentional introduction of hypoglycemic drugs. The most commonly used medications are sulfonylurea derivatives, which are affordable, inexpensive and legal. The close collaboration of clinicians with the laboratory service plays a key role in the diagnosis of factitious hypoglycemia. Since the results of biochemical and hormonal analyzes in patients with hypoglycemia due to reception of oral hypoglycemic medications and pancreatogenous HGS are identical, the only way to differentiate these conditions is by detection of insulin secretagogue substances in the blood (or urine).The determination of oral hypoglycemic medications in cases of suspicion of artificial reception is not implemented in Russia. Factitious hypoglycemia in most cases is the diagnosis of exclusion, and its confirmation if often based on detection of medications among the personal effects of patient. This is a significant difficulty given the ethical standards. However, since 2018 we conduct in our Centre the determination of 7 oral hypoglycemic medications (glibenclamide, gliquidone, gliclazide, glimepiride, glipizide, nateglinide and repaglinide) in patient’s blood using the liquid chromatography–tandem mass spectrometry (LC-MS). This article presents a clinical case of a patient without diabetes mellitus taking glibenclamide and detection of this drug using highly selective LC-MS
Fat tissue and adrenal function: mechanisms of mutual influence
The mechanisms of mutual influence of fat tissue and the hypothalamo-pituitary-adrenal (HPA) axis include the regulation of the metabolism of adipocytes by adrenal cortex hormones, on the one part, and the effect of adipocytes and adipocytokines on secretion, metabolism and action of steroid hormones in target cells - on the other part.Glucocorticoids contribute to the differentiation of preadipocytes into mature adipocytes; brown fat tissue transforms into white under the effect of GC. Mineralocorticoids are also involved in the process of adipocyte differentiation, regulate adipokine expression, and induce oxidative stress in fat tissue. There is evidence that suggest that circulating dehydroepiandrosterone sulfate (DHEAS), obesity, insulin sensitivity are associated with the presence of cardiovascular diseases.Orexigenic neuropeptides and inflammatory mediators, which trigger the synthesis of corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nuclei, are considered as possible mechanisms of (HPA) axis activation in obesity. Expression of 1ip-hydroxysteroid dehydrogenase type 1 (11P-HSD1) in fat tissue and the formation of cortisol from cortisone at the tissue level can be considered as one of the factors involved in development of insulin resistance. The autocrine and paracrine regulatory effect of these hormones on adipocyte function is the consequence of aldosterone production and aromatization of androgens by fat tissue
Applicability of Capillary Gas-Liquid Chromatography for Determination of Parabens in Pharmaceutical Analysis
The traditional gas-liquid chromatography (GLC) method using packed columns is still used in pharmaceutical analysis for determination of parabens, despite the fact that this technique has a number of serious drawbacks.The aim of the study was to develop a more effective capillary GLC method for determination of parabens in active pharmaceutical ingredients and finished pharmaceutical products.Materials and methods: the study was performed using Agilent 6890N and Agilent 7890B systems with flame-ionisation detectors. The systems were equipped with Agilent 7683B and Agilent G4513A autosamplers, respectively. The following columns were used in the study: ZB-1 15 m х 0.32 mm х 0.25 pm, DB-1 30 m х 0.32 mm х 3.0 pm, Cp-Sil 5-CB 30 m х 0.32 mm х 3.0 pm.Results: the authors developed a method for methylparaben and propylparaben determination using capillary column GLC. The chromatographic parameters (chromatographic system performance, reproducibility of peak areas, peak asymmetry) were determined for both capillary and packed column GLC. The authors outlined the prospects for simultaneous determination of several compounds using the proposed method: a four-component mixture containing methyl-, ethyl-, propyl-, and butylparaben was separated in 9 minutes. The authors used Loma Lux Psoriasis to perform partial validation of the test method. They determined the linearity range and the limit of quantitation for methylparaben and propylparaben, and verified accuracy and intermediate precision of the test method.Conclusions: the results of the study allowed for selection of optimal chromatographic conditions for rapid and high-precision determination of methylparaben and propylparaben in medicinal products. The developed method is recommended for control of the content of these compounds in medicinal products
Возможность применения капиллярной газожидкостной хроматографии в фармацевтическом анализе при определении парабенов
The traditional gas-liquid chromatography (GLC) method using packed columns is still used in pharmaceutical analysis for determination of parabens, despite the fact that this technique has a number of serious drawbacks.The aim of the study was to develop a more effective capillary GLC method for determination of parabens in active pharmaceutical ingredients and finished pharmaceutical products.Materials and methods: the study was performed using Agilent 6890N and Agilent 7890B systems with flame-ionisation detectors. The systems were equipped with Agilent 7683B and Agilent G4513A autosamplers, respectively. The following columns were used in the study: ZB-1 15 m х 0.32 mm х 0.25 pm, DB-1 30 m х 0.32 mm х 3.0 pm, Cp-Sil 5-CB 30 m х 0.32 mm х 3.0 pm.Results: the authors developed a method for methylparaben and propylparaben determination using capillary column GLC. The chromatographic parameters (chromatographic system performance, reproducibility of peak areas, peak asymmetry) were determined for both capillary and packed column GLC. The authors outlined the prospects for simultaneous determination of several compounds using the proposed method: a four-component mixture containing methyl-, ethyl-, propyl-, and butylparaben was separated in 9 minutes. The authors used Loma Lux Psoriasis to perform partial validation of the test method. They determined the linearity range and the limit of quantitation for methylparaben and propylparaben, and verified accuracy and intermediate precision of the test method.Conclusions: the results of the study allowed for selection of optimal chromatographic conditions for rapid and high-precision determination of methylparaben and propylparaben in medicinal products. The developed method is recommended for control of the content of these compounds in medicinal products.В практике фармацевтического анализа для определения парабенов применяется имеющий ряд серьезных недостатков метод классической газожидкостной хроматографии (ГЖХ) с использованием насадочных колонок.Цель работы: разработать методику более эффективного определения парабенов в фармацевтических субстанциях и лекарственных средствах методом капиллярной ГЖХ.Материалы и методы: исследования проводились на газовых хроматографах Agilent 6890N и Agilent 7890B с пламенно-ионизационным детектором, оснащенных автосамплерами Agilent 7683B и Agilent G4513A соответственно. В работе использованы хроматографические колонки ZB-1 15 м х 0,32 мм х 0,25 мкм, DB-1 30 м х 0,32 мм х 3,0 мкм, CP-Sil 5-CB 30 м х 0,32 мм х 3,0 мкм.Результаты: разработана методика определения метилпарабена и пропилпарабена с использованием метода газожидкостной хроматографии с капиллярной колонкой. Определены параметры (эффективность хроматографической системы, воспроизводимость площадей пиков, асимметрия пиков) хроматографического определения парабенов методом капиллярной ГЖХ и методом ГЖХ с насадочной колонкой. Обозначены перспективы единовременного определения нескольких соединений с помощью предложенной методики: за 9 минут была разделена четырехкомпонентная смесь метил-, этил-, пропил- и бутилпарабена. Проведена частичная валидация методики на примере лекарственного средства «Лома Люкс Псориасис». Установлен диапазон линейности методики, предел количественного определения метилпарабена и пропилпарабена, подтверждены правильность и прецизионность (сходимость и внутрилабораторная воспроизводимость).Выводы: проведенные испытания позволили выбрать оптимальные хроматографические условия для быстрого и прецизионного определения метилпарабена и пропилпарабена в лекарственных средствах. Разработанную методику рекомендовано использовать для контроля содержания данных соединений в средствах медицинского применения