Osteoprotective properties of RNA-containing drug osteochondrin S on the model of insufficiency of sex hormones in rats / Propiedades osteoprotectoras del fármaco que contiene ARN de osteocondrina S sobre un modelo de insuficiencia de hormonas sexuales en ratas

SUMMARY: The aim of the study was to evaluate the osteoprotective properties of RNA-containing drug Osteochondrin S on rats with experimental model of osteoporosis. Osteochondrin S contains yeast RNA and RNA of connective tissue of cattle. In order to model osteoporosis in rats bilateral ovariectomy was used. Rats were divided into 3 groups: 1 - ovariectomized rats receiving Osteochondrin S; 2 - ovariectomized rats receiving saline; 3 - sham-ovariectomized rats. Rats in group 1 received Osteochondrin S, Group 2 - physiological saline three times a week for 12 weeks. Based on morphological data and on the results of densitometry, Osteochondrin S prevents a decrease in bone density, i.e. exhibits osteoprotective properties. Under the condition of lack of sex hormones in rats Osteochondrin S reduces reactive oxygen species in blood plasma and limits the degree of decrease in antioxidant capacity of blood plasma.

RESUMEN: El objetivo de este estudio fue evaluar las propiedades osteoprotectoras del fármaco que contiene ARN Osteocondrina S en ratas, como modelo experimental de osteoporosis. La Osteocondrina S contiene ARN de levadura y ARN de tejido conectivo de bovinos. Para modelar la osteoporosis en ratas se utilizó ovariectomía bilateral. Las ratas se dividieron en 3 grupos: grupo 1, ratas ovariectomizadas que recibieron Osteocondrin S; grupo 2, ratas ovariectomizadas recibieron solución salina; grupo 3 - ratas ovariectomizadas simuladas. Las ratas del grupo 1 recibieron Osteocondrina S, el grupo 2 solución de suero fisiológico tres veces por semana durante 12 semanas. En base a los datos morfológicos y los resultados de la densitometría, Osteocondrina S evita una disminución de la densidad ósea, es decir, exhibe propiedades osteoprotectoras. Ante la falta de hormonas sexuales en ratas, Osteocondrina S reduce las especies reactivas de oxígeno en el plasma sanguíneo y limita el grado de disminución de la capacidad antioxidante del plasma sanguíneo.

Deficiency of sex hormones does not affect 17-ß-estradiol-induced coronary vasodilation in the isolated rat heart

The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9−12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 μM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.

Effect of castration on renal glycosaminoglycans and their urinary excretion in male and female rats with chronic renal failure

Glycosaminoglycans (GAGs) participate in a variety of processes in the kidney, and evidence suggests that gender-related hormones participate in renal function. The aim of this study was to analyze the relationship of GAGs, gender, and proteinuria in male and female rats with chronic renal failure (CRF). GAGs were analyzed in total kidney tissue and 24-h urine of castrated (c), male (M), and female (F) Wistar control (C) rats (CM, CMc, CF, CFc) and after 30 days of CRF induced by 5/6 nephrectomy (CRFM, CRFMc, CRFF, CRFFc). Total GAG quantification and composition were determined using agarose and polyacrylamide gel electrophoresis, respectively. Renal GAGs were higher in CF compared to CM. CRFM presented an increase in renal GAGs, heparan sulfate (HS), and proteinuria, while castration reduced these parameters. However, CRFF and CRFFc groups showed a decrease in renal GAGs concomitant with an increase in proteinuria. Our results suggest that, in CRFM, sex hormones quantitatively alter GAGs, mainly HS, and possibly the glomerular filtration barrier, leading to proteinuria. The lack of this response in CRFMc, where HS did not increase, corroborates this theory. This pattern was not observed in females. Further studies of CRF are needed to clarify gender-dependent differences in HS synthesis.

Possible role of leptin, and tumor necrosis factor-alpha in hypoandrogenicity in patients with early rheumatoid arthritis

Hypoandrogenicity is common in men with rheumatoid arthritis who have lower levels of sex hormones such as testosterone and dehydroepiandrosterone sulphate. The fat tissue hormone leptin is stimulated by tumor necrosis factor alpha [TNF-alpha], and was found to be associated with hypoandrogenicity. To study the inter-relation between serum levels of TNF-alpha, leptin and androgens in early diagnosed RA. Serum levels of TNF-alpha, leptin, testosterone, and [DHEAS] hormones were measured by ELISA and compared in 40 men with early RA and 30 healthy volunteers. The mean serum leptin and TNF-alpha were significantly elevated in patients with RA compared to control group, and both of them were positively correlated with the disease activity score [DAS28]. Sex hormones [testosterone and DHEAS] were significantly decreased in male patients with RA compared to control group, and they were negatively correlated with serum TNF-alpha, leptin. Our data suggest that TNF-alpha, and leptin may be involved in hypoandrogenicity in patients with RA and that strategies aimed at interfering with leptin axis could represent innovative therapeutic tool for hypoandrogenicity in RA

Parâmetros mecânicos, físicos e químicos na avaliação de mandíbulas de ratos deficientes em esteróides sexuais / Mechanical, physical and chemical parameters in evaluation of mandibles of rats deficient in sex steroids

O aumento da expectativa de vida vem elevando a ocorrência das alterações degenerativas comuns à terceira idade, como a osteoporose. Essa doença sistêmica também frequente no hipogonadismo, afeta o metabolismo ósseo comprometendo inclusive a mandíbula. O objetivo deste estudo foi avaliar de que forma a deficiência de esteróides sexuais, induzida por orquiectomia ou ovariectomia, influencia o processo de remodelação óssea da mandíbula de ratos por períodos experimentais crônicos. Ratos Wistar, com 3 meses, foram divididos em três grupos experimentais: controles (C), castrados (ORQ; OVX) e castrados com tratamento hormonal (ORQ + PT - propionato de testosterona, 0,4 mg/100g PC/dia; OVX + BE - benzoato de estradiol, 0,7 ug/100g PC/dia). As fêmeas foram previamente avaliadas por citologia vaginal e somente as que apresentaram o ciclo estral regular foram utilizadas. A massa corporal foi verificada semanalmente e ao final dos períodos experimentais (90, 120 e 150 dias) os animais foram sacrificados. O sangue foi coletado e o soro armazenado para posterior análise. As mandíbulas, fêmures e colunas foram excisados, medidos e preparados para análises da densidade mineral óssea e das propriedades físicas e biomecânicas. Observamos que com a castração, machos apresentaram baixo ganho de massa corporal (90d: 12%, 120d: 24% e 150d: 13% a menos que C, p<0,05), ao contrário das fêmeas (90d: 38% e 120d: 41% a mais que C, p<0,05). As medidas de todos os ossos foram menores tanto em machos como em fêmeas (♂ - 90d: vértebra 11.8%, fêmur 4.4%, côndilo MD 9.4%, côndilo VL 16.6%; 120d: vértebra 13.6%, fêmur 4%, côndilo mandibular MD 9%, côndilo mandibular VL 22.2%; 150d: vértebra 16.8%, fêmur 6%, côndilo mandibular MD 21.6%, côndilo mandibular VL 29.1% e ♀ - 90d: vértebra 7.7, fêmur 5.6%, côndilo mandibular MD 29.1%, côndilo mandibular VL 11.8%; 120d: vértebra 15.9%, fêmur 6.1%, côndilo mandibular MD 33.6%, côndilo mandibular VL 14.8%; 150d: vértebra 21.6%, fêmur 5.42%...

The increase in the life expectancy has been raising the occurrence of common degenerative alterations in aging population, as osteoporosis. This systemic disease is also frequent in hypogonadism and affects the bone metabolism, included mandibular bone. The aim of this study was to evaluate how sex steroid deficiency, induced by orchiectomy (ORX) or ovariectomy (OVX), influences on mandible bone remodeling of rats, in groups of chronic experimental periods. Wistar rats, 3 mouths, had been divided in three groups: controls (C), castrated (ORX; OVX) and castrated with hormonal treatment (ORX+TP - testosterone propionate, 0,4 mg/100g BW/day; OVX+EB - estradiol benzoate, 0.7 ug/100g BW/day). Females were previously evaluated by vaginal cytology and only rats with regular estrous cycle were used. The corporal mass was weekly verified and after experimental periods (90, 120 and 150 days), the animals were sacrificed. The blood was collected and serum stored for posterior analysis. Mandibles, femurs and columns were excised, measured and prepared to analyses of bone mineral density and physical and biomechanical properties. After castration, males presented low gain in body mass (90d: 12%, 120d: 24% and 150d: 13% lower than C, p<0,05), in contrast of females (90d: 38% and 120d: 41% upper than C, p<0,05). The measures of all bones were lower in males and in females (♂ - 90d: vertebrae 11.8%, femur 4.4%, mandibular condyle MD 9.4%, mandibular condyle VL 16.6%; 120d: vertebrae 13.6%, femur 4%, mandibular condyle MD 9%, mandibular condyle VL 22.2%; 150d: vertebrae 16.8%, femur 6%, mandibular condyle MD 21.6%, mandibular condyle VL 29.1% and ♀ - 90d: vertebrae 7.7%, femur 5.6%, mandibular condyle MD29.1%, mandibular condyle VL11.8%; 120d: vertebrae 15.9%, femur 6.1%, mandibular condyle MD 33.6%, mandibular condyle VL 14.8% and 150d: vertebrae 21.6%, femur 5.42%, mandibular condyle MD 29.1%, mandibular condyle VL 15.1% lower than C, p<0,05), in all experimental periods...

[Effect of sexual hormone elimination on the changes of craniofacial dimensions in rats]

It is well - known that sex hormones regulate bone metabolism. Sex steroids increase osteoblasts activities and affect growth, remodeling and bone homeostasis. The aim of this study was to examine the effects of sex hormones deficiency on craniofacial growth in rats. Fifty, thirty-day-old Wistar rats comprised the sample in this experimental study. 25 male rats were divided into 2 groups: Experimental group, ORX, [n=15] and control group, sham-operation, [n=10] and 25 female rats were divided in the same way: Experimental group, OVX, [n=15] and control group, sham-operation, [n=10]. Body length and weight were registered monthly. The rats were sacrificed 6 months after the surgery. Direct millimetric measurements of the skeletodental variables and the tibial length were obtained by using electronic caliper. Serum testosterone, progesterone and estradiol levels were measured by ELISA. One Way ANOVA, Tukey and Student t tests were used to analyze the data. Serum testosterone level significantly decreased in the ORX group as compared with the male sham-operated group. In the ORX group, body length and weight, coronoid height, mandibular length, mandibular arch length, midfacial width, midfacial length, midfacial height, calvarial width, maxillary arch width, premaxillary length, nasal bone height, facial width, basisphenoid bone length and tibia bone length were significantly smaller than in the male control group. Structures showing cartilaginous growth were influenced more than structures showing sutural growth. Estradiol level did not change in OVX group, but despite the significant decrease in progesterone level, no significant differences except weight were found between the OVX group and female control group. In conclusion, it is strongly suggested that the suppression of sex hormones secretion in the growth phase might inhibit craniofacial growth and results in poor craniofaeial development and developing malocclusion

Gigantism associated with slipped capital femoral epiphysis.

The etiology of slipped capital femoral epiphysis (SCFE) is unknown, though hormonal as well as mechanical factors have been implicated. We report a case of gigantism who presented with SCFE. This case provides an insight into the genesis of SCFE, which in this case was related to growth hormone excess and sex-hormone deficiency.

Osteoporose e os distúrbios endócrinos da tireóide e das gônadas / Osteoporosis and the endocrine disturbances of thyroid and gonads

Apesar da dedicação incessante dos pesquisadores no estudo da osteoporose, muito ainda necessita ser elucidado. A deficiência dos esteróides sexuais, principalmente a de estrógeno, é considerada a principal causa de osteoporose, embora existam inúmeros outros fatores envolvidos. O hipertireoidismo, por exemplo, é considerado um dos fatores de risco para indução ou agravamento da osteoporose e tem despertado o interesse para o estudo dos efeitos de T3 e T4 sobre o metabolismo ósseo. Embora o hipotireoidismo e a afuncionalidade das gônadas seja uma associação freqüente na mulher, a hipofunção da tireóide não é considerada fator de risco para a osteoporose da menopausa. Assim, o estudo da inter-relação entre os distúrbios endócrinos, tão comuns na idade avançada, e a osteoporose é fundamental, pois deste conhecimento poderão advir meios de controle e tratamento adequados, bem como a definição da real natureza do distúrbio ósseo. O objetivo desta revisão é apresentar e discutir alguns aspectos da osteoporose e sua inter-relação com os distúrbios endócrinos da tireóide e das gônadas.

Anomalías de la esteroidogénesis suprarrenal en niños chilenos con micropene / Abnormalities in adrenal steroidogenesis in chilean boys with micropenis

Background: Mutations in type II 3ß hydroxysteroid Dehydrogenase (3ßHSD) are found in male children with severe undervirilized genitalia. Mild undervirilization (isolated micropenis or with distal hypospadia) can be associated with a partial deficit in 3ßHSD activity. Aim: To assess the frequency of abnormal adrenal response to ACTH, suggesting a deficit in adrenal enzymatic activity, in children with mild undervirilization. Patients and methods : We studied 26 male children with micropenis, aged one to eight years. Children with evidences of puberal development or in treatment with drugs that affect steroidal metabolism were excluded from the study. Serum levels of androstenedione (A), dehydroepiandrosterone (DHEA), progesterone (P), 17 hydroxyprogesterone (17 P) and the ratios DHEA/A, P/17 P, 17 P/DHEA were measured after an adrenal stimulation with 0.25 mg/m2 intramuscular ACTH. Results: Two children had DHEA y DHEA/A values suggesting a defective 3ßHSD activity. Other two children had high levels of 17 P, suggesting a deficiency of cytochrome p450c21. A CYP 21 gene mutation was found in one of the later children. Conclusions: A low proportion of children with micropenis have a deficient 3ßHSD activity

El dilema de la andropausia y el reemplazo hormonal en el hombre mayor / The dilemma of andropause and hormone replacement in the aged man

Los niveles de testosterona plasmática disminuyen con el correr de los años, calculándose que en un 20-30 por ciento de los hombres mayores de 60 años tiene valores por debajo de lo normal. Este estado de déficit ha sido denominado PADAM (déficit parcial de andrógenos en hombres de edad, por sus siglas en inglés). Los andrógenos en el adulto actúan sobre varias estructuras, como el hueso, el músculo, la hematopoyesis y la función sexual. La terapia de reemplazo hormonal puede realizarse con medicación oral o inyectable, debiendo valorarse los riesgos potenciales, especialmente sobre la próstata, lo que requiere un estricto monitoreo

Aspectos neuro-psicológicos do climatérios / Neuropsychological symptoms in menopause

É destacado o papel dos neuropeptídios, neurotransmissores cerebrais e dos hormônios sexuais na neuromodulaçäo dos sintomas psicológicos do climatério. É também enfatizada a influência sócio-cultural e a vivência pessoal e profissional sobre esses sintomas

Female sex hormones in hepatosplenic bilharziasis

The effect of hepatosplenic bilharziasis on female sex hormones has been investigated in twenty women. The patients were segregated into two equal groups according to the presence or absence of ascites. The result were compared with ten healthy women. The study revealed that in early non ascitic stage there was concomitant rise in estradiol and prolactin level with reduction in the gonadotropins level and testosterone and insignificant changes in progosterone. After developing ascites all hormones including progesterone were much lowered with infertility