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2.
Turk J Med Sci ; 51(1): 231-237, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33155789

RESUMO

Background/aim: Aldosterone is a mineralocorticoid that secreted from adrenal glands and a known factor to increase magnesium excretion by direct and indirect effects on renal tubular cells. Although the frequency of hypomagnesemia was found to be approximately 5% in adult studies, there is no study in the literature investigating the frequency of hypomagnesemia in children by using fludrocortisone, which has a mineralocorticoid activity. Materials and methods: A multi-center retrospective study was conducted, including children who were under fludrocortisone treatment for primary adrenal insufficiency and applied to participant pediatric endocrinology outpatient clinics. Results: Forty-three patients (58.1% male, 41.9% prepubertal) included in the study, whose median age was 9.18 (0.61-19) years, and the most common diagnosis among the patients was a salt-wasting form of congenital adrenal hyperplasia (67.4%). Mean serum magnesium level was 2.05 (±0.13) mg/dL, and hypomagnesemia was not observed in any of the patients treated with fludrocortisone. None of the patients had increased urinary excretion of magnesium. Conclusion: Unlike the studies performed in adults, we could not find any evidence of magnesium wasting effect of fludrocortisone treatment with normal or even high doses in children and adolescents.


Assuntos
Hiperplasia Suprarrenal Congênita , Fludrocortisona , Deficiência de Magnésio , Magnésio , Hiperplasia Suprarrenal Congênita/sangue , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Criança , Monitoramento de Medicamentos/métodos , Feminino , Fludrocortisona/administração & dosagem , Fludrocortisona/efeitos adversos , Humanos , Transporte de Íons/efeitos dos fármacos , Magnésio/sangue , Magnésio/urina , Deficiência de Magnésio/diagnóstico , Deficiência de Magnésio/etiologia , Deficiência de Magnésio/prevenção & controle , Masculino , Mineralocorticoides/administração & dosagem , Mineralocorticoides/efeitos adversos , Eliminação Renal/efeitos dos fármacos , Estudos Retrospectivos , Medição de Risco , Resultado do Tratamento
3.
Artigo em Alemão | MEDLINE | ID: mdl-32557492

RESUMO

OBJECTIVE: Since 2016 the only approved drug for the treatment of primary hypoadrenocorticism (Addisons disease) in dogs in Germany is desoxycorticosterone pivalate (DOCP), namely Zycortal®. The initial dose recommended by the manufacturer is 2.2 mg/kg. Our own experience and select publications raise the suspicion that a distinctly lower initial dose would be sufficient. Mainly cost reduction motivates for dose reduction and with it comes a higher owner motivation and compliance. It was the objective of our retrospective study to show that an initial dose of 1.5 mg/kg DOCP is sufficient for controlling canine hypoadrenocorticism. MATERIAL AND METHODS: Dogs with primary hypoadrenocorticism were included if the initial starting dose was 1.5 mg/kg DOCP subcutaneously. The first, second and the last known dose of DOCP were documented. Electrolyte concentrations at the time of diagnosis as well as 10-14 days after the first injection, on the day of the second injection as well as at the last known injection were recorded. A dog was considered medically well-regulated when clinically healthy, sodium and potassium concentrations within the reference ranges, and when the responsible veterinarian did not recommended a dose alteration. RESULTS: All 13 included dogs were clinically healthy after the first or second injection. One dog received 1.6 mg/kg DOCP as last documented dose, all other dogs received ≤ 1.5 mg/kg (median: 1.3, range: 0.4-1.6) DOCP. Eleven dogs were injected once monthly, 2 dogs received injections every 60 days. The dogs were followed at least 7 months (median: 20 months, range: 7-26 months). CONCLUSION AND CLINICAL RELEVANCE: We were able to show that a starting dose of 1.5 mg/kg DOCP (Zycortal®) is sufficient for controlling primary hypoadrenocorticism in dogs. Adjustments of the dose are needed in some dogs. Regular measurement of electrolyte concentrations 10 days after treatment initiation and at the monthly DOCP injection is required for a correct disease management with DOCP.


Assuntos
Doença de Addison , Desoxicorticosterona/análogos & derivados , Doenças do Cão/tratamento farmacológico , Mineralocorticoides , Doença de Addison/tratamento farmacológico , Doença de Addison/veterinária , Animais , Desoxicorticosterona/administração & dosagem , Desoxicorticosterona/uso terapêutico , Cães , Mineralocorticoides/administração & dosagem , Mineralocorticoides/uso terapêutico , Potássio/sangue , Estudos Retrospectivos , Sódio/sangue
4.
J Clin Endocrinol Metab ; 105(8)2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32424397

RESUMO

CONTEXT: Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. OBJECTIVE: Multicenter survey on current clinical approaches in managing AI during pregnancy. DESIGN: Retrospective anonymized data collection from 19 international centers from 2013 to 2019. SETTING AND PATIENTS: 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). RESULTS: Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. CONCLUSIONS: This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.


Assuntos
Insuficiência Adrenal/tratamento farmacológico , Terapia de Reposição Hormonal/métodos , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/etiologia , Adulto , Cesárea/estatística & dados numéricos , Relação Dose-Resposta a Droga , Feminino , Fludrocortisona/administração & dosagem , Fludrocortisona/efeitos adversos , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Humanos , Hidrocortisona/administração & dosagem , Hidrocortisona/efeitos adversos , Mineralocorticoides/administração & dosagem , Mineralocorticoides/efeitos adversos , Gravidez , Complicações na Gravidez/etiologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
5.
Indian Pediatr ; 57(2): 159-164, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-32060243

RESUMO

Treatment of congenital adrenal hyperplasia (CAH) requires lifelong replacement of glucocorticoids with regular follow up to manage associated morbidities. The current review focuses on follow-up and management of infants diagnosed with classical CAH pertinent to Indian context. Early initiation of oral hydrocortisone in divided doses is recommended after diagnosis in newborn period, infancy and childhood. Fludrocortisone is recommended for all infants with classical CAH. All infants should be monitored as per protocol for disease and treatment related complications. The role of prenatal steroids to pregnant women with previous history of CAH affected infant for prevention of virilization of female fetus is controversial.


Assuntos
Hiperplasia Suprarrenal Congênita/terapia , Administração Oral , Hiperplasia Suprarrenal Congênita/fisiopatologia , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Humanos , Índia , Lactente , Masculino , Mineralocorticoides/administração & dosagem , Mineralocorticoides/uso terapêutico , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Esteroides/administração & dosagem , Esteroides/efeitos adversos , Esteroides/uso terapêutico
6.
J Clin Endocrinol Metab ; 105(1)2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31613957

RESUMO

CONTEXT: No consensus exists for optimization of mineralocorticoid therapy in patients with primary adrenal insufficiency. OBJECTIVE: To explore the relationship between mineralocorticoid (MC) replacement dose, plasma renin concentration (PRC), and clinically important variables to determine which are most helpful in guiding MC dose titration in primary adrenal insufficiency. DESIGN: Observational, retrospective, longitudinal analysis. PATIENTS: A total of 280 patients (with 984 clinical visits and plasma renin measurements) with primary adrenal insufficiency were recruited from local databases and the international congenital adrenal hyperplasia (CAH) registry (www.i-cah.org). Thirty-seven patients were excluded from the final analysis due to incomplete assessment. Data from 204 patients with salt-wasting CAH (149 adults and 55 children) and 39 adult patients with Addison disease (AD) were analysed. MAIN OUTCOME MEASURES: PRC, electrolytes, blood pressure (BP), and anthropometric parameters were used to predict their utility in optimizing MC replacement dose. RESULTS: PRC was low, normal, or high in 19%, 36%, and 44% of patients, respectively, with wide variability in MC dose and PRC. Univariate analysis demonstrated a direct positive relationship between MC dose and PRC in adults and children. There was no relationship between MC dose and BP in adults, while BP increased with increasing MC dose in children. Using multiple regression modeling, sodium was the only measurement that predicted PRC in adults. Longitudinally, the change in MC dose was able to predict potassium, but not BP or PRC. CONCLUSIONS: The relationship between MC dose and PRC is complex and this may reflect variability in sampling with respect to posture, timing of last MC dose, adherence, and concomitant medications. Our data suggest that MC titration should not primarily be based only on PRC normalization, but also on clinical parameters such as BP and electrolyte concentration.


Assuntos
Insuficiência Adrenal/sangue , Insuficiência Adrenal/tratamento farmacológico , Mineralocorticoides/administração & dosagem , Renina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Terapia de Reposição Hormonal/métodos , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mineralocorticoides/farmacologia , Renina/efeitos dos fármacos , Estudos Retrospectivos , Adulto Jovem
7.
Clin J Sport Med ; 29(6): e73-e75, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31688185

RESUMO

Patients with primary adrenal insufficiency (PAI) require increased doses of glucocorticoids and mineralocorticoids during stressors, such as surgery, trauma, and sepsis. Although current guidelines exist for dose adjustments in these situations, there is no accepted dosing regimen for patients with PAI participating in intensive endurance exercise. Given the extensive physiologic stress of events, such as marathons, triathlons, and similar events, it is likely that a "stress-dose" of adrenal replacement therapy will not only prevent adrenal crisis, but also improve performance. A 50-year-old male endurance athlete with known PAI reported severe fatigue, nausea, and malaise after competing in prior marathons and intensive endurance exercise. After supplementing with glucocorticoids and mineralocorticoids before competition, he experienced decreased symptoms and improved performance. To better care for these patients, further studies should be conducted to provide safe and effective glucocorticoid and mineralocorticoid dose adjustments before intensive endurance exercise.


Assuntos
Doença de Addison/tratamento farmacológico , Dexametasona/administração & dosagem , Exercício Físico/fisiologia , Fludrocortisona/administração & dosagem , Glucocorticoides/administração & dosagem , Terapia de Reposição Hormonal , Mineralocorticoides/administração & dosagem , Resistência Física/efeitos dos fármacos , Comportamento Competitivo/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Fisiológico
8.
J Vet Intern Med ; 33(3): 1266-1271, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30865322

RESUMO

BACKGROUND: Lowering the dose of desoxycorticosterone pivalate (DOCP) for the treatment of dogs with primary hypoadrenocorticism (PH) decreases costs and could lead to increased owner motivation to treat their affected dogs. OBJECTIVE: To evaluate the efficacy of a low-dose DOCP treatment protocol in dogs with PH. ANIMALS: Prospective study, 17 client-owned dogs with naturally occurring PH (12 newly diagnosed, 5 previously treated with fludrocortisone acetate [FC]). METHODS: Dogs with newly diagnosed PH were started on 1.5 mg/kg DOCP SC; dogs previously treated with FC were started on 1.0-1.8 mg/kg DOCP SC. Reevaluations took place at regular intervals for a minimum of 3 months and included clinical examination and determination of serum sodium and potassium concentrations. The DOCP dosage was adjusted to obtain an injection interval of 28-30 days and to keep serum electrolyte concentrations within the reference interval. RESULTS: Median (range) follow-up was 16.2 months (4.5-32.3 months). The starting dosage was sufficient in all but 2 dogs and had to be significantly decreased after 2-3 months to a median dosage (range) of 1.1 mg/kg (0.7-1.8). Dogs 3 years of age or younger needed significantly higher dosages compared to older dogs. None of them, however, needed the 2.2 mg/kg DOCP dosage, recommended by the manufacturer. CONCLUSIONS AND CLINICAL IMPORTANCE: A starting dosage of 1.5 mg/kg DOCP is effective in controlling clinical signs and serum electrolyte concentrations in the majority of dogs with PH. An additional dose reduction often is needed to maintain an injection interval of 28-30 days. Young and growing animals seem to need higher dosages.


Assuntos
Doença de Addison/veterinária , Desoxicorticosterona/análogos & derivados , Doenças do Cão/tratamento farmacológico , Mineralocorticoides/administração & dosagem , Doença de Addison/tratamento farmacológico , Doença de Addison/economia , Fatores Etários , Animais , Desoxicorticosterona/administração & dosagem , Desoxicorticosterona/economia , Desoxicorticosterona/uso terapêutico , Doenças do Cão/economia , Cães , Feminino , Masculino , Mineralocorticoides/economia , Mineralocorticoides/uso terapêutico , Potássio/sangue , Estudos Prospectivos , Sódio/sangue
9.
J Clin Endocrinol Metab ; 104(6): 2031-2040, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30608542

RESUMO

CONTEXT: Little is known of cardiovascular disease (CVD) in autoimmune Addison disease (AAD). Inadequate glucocorticoid replacement might potentially increase CVD risk. OBJECTIVE: To examine CVD in AAD in subgroups of ischemic heart disease (IHD) and cerebrovascular disease (CeVD) and investigate the effects of glucocorticoid and mineralocorticoid dosing. DESIGN, SETTING, AND PATIENTS: In this cohort-control study, we used Swedish health registries from 1964 to 2013 to identify 1500 subjects with AAD and 13,758 matched controls. Incident CVD was analyzed from 2006 to 2013. Adjusted hazard ratios (aHRs) were calculated using Cox proportional hazard models. Glucocorticoid and mineralocorticoid doses were stratified to examine dose-related risks. RESULTS: During 8807 person-years (PY), 94 events of first CVD (10.7/1000 PY) in patients with AAD occurred compared with 563 events during 80,163 PY (7.0/1000 PY) in controls. IHD was significantly more common in women (aHR, 2.15; 95% CI, 1.49 to 3.10) but not men (aHR, 1.16; 95% CI, 0.75 to 1.78) with AAD compared with controls. No increase in CeVD risk was detected (aHR, 0.88; 95% CI, 0.56 to 1.37, women; aHR, 0.88; 95% CI 0.53 to 1.50, men). CVD was associated with greater glucocorticoid and mineralocorticoid replacement doses in women but not men. CONCLUSION: The risk of IHD but not CeVD is increased in AAD, especially in women. The risk of CVD independently correlated with greater glucocorticoid and mineralocorticoid replacement doses in women. Our data suggest that close monitoring and early treatment of risk factors for CVD, among women in particular, might be warranted.


Assuntos
Doença de Addison/complicações , Transtornos Cerebrovasculares/epidemiologia , Glucocorticoides/administração & dosagem , Mineralocorticoides/administração & dosagem , Isquemia Miocárdica/epidemiologia , Doença de Addison/tratamento farmacológico , Adulto , Idoso , Estudos de Casos e Controles , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/prevenção & controle , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Terapia de Reposição Hormonal/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/prevenção & controle , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Fatores Sexuais , Suécia/epidemiologia
10.
J Pediatr Endocrinol Metab ; 31(8): 937-942, 2018 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-29982238

RESUMO

BACKGROUND: Deficiency of 17α-hydroxylase (17OHD) is a rare form of adrenal hyperplasia. Diagnosis is generally delayed, impairing appropriate treatment. CASE PRESENTATION: Here, we report the clinical, molecular, hormonal, and treatment data of three unrelated 17OHD patients, aged 14-16 years with hypergonadotrophic hypogonadism; uncontrolled hypertension; primary adrenal insufficiency; and high progesterone, low to normal potassium, and low dehydroepiandrosterone, androstenedione, and testosterone levels. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) at baseline and after an adrenocorticotropic hormone test showed low cortisol and cortisone and high deoxycorticosterone (DOC) and corticosterone levels; both DOC/21-deoxycortisol and costicosterone/cortisol ratios were very high. Patient 2 had 46,XX karyotype and patients 1 and 3, had 46,XY. A molecular analysis showed that two of the patients were homozygous for p.W406R mutation and the other patient was compound heterozygous for p.W406R and p.P428L. Hypertension was controlled only after the administration of both prednisone and mineralocorticoid antagonist. CONCLUSIONS: Hypertension in young women must lead to diagnostic suspicion, even in the pre-pubertal period. The basal level of progesterone is an indicator of 17OHD. Mineral and glucocorticoid ratios obtained from LC-MS/MS can reinforce the diagnosis. Hypertension can be controlled using glucocorticoid replacement therapy and mineralocorticoid antagonist.


Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperplasia Suprarrenal Congênita/patologia , Esteroide 17-alfa-Hidroxilase/metabolismo , Adolescente , Hiperplasia Suprarrenal Congênita/sangue , Hormônio Adrenocorticotrópico/administração & dosagem , Adulto , Brasil , Criança , Feminino , Humanos , Mineralocorticoides/administração & dosagem , Progesterona/administração & dosagem , Prognóstico , Adulto Jovem
12.
J Clin Endocrinol Metab ; 103(5): 1767-1778, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29554355

RESUMO

CONTEXT: Management of congenital adrenal hyperplasia (CAH) involves suppression of the hypothalamic-pituitary-adrenal axis using supraphysiological doses of exogenous glucocorticoids. This can pose a challenge, with Cushing syndrome a frequent complication of adequate suppression. Bilateral adrenalectomy, with subsequent replacement of glucocorticoids and mineralocorticoids at physiological doses, has been proposed as an alternative therapeutic strategy. OBJECTIVE: To review the outcomes after bilateral adrenalectomy for CAH. DATA SOURCES: A systematic search of PubMed/MEDLINE and Web of Science, identifying relevant reports published up to 10 January 2018. STUDY SELECTION: Case reports or case series were included if they reported individual patient data from patients with CAH who had undergone bilateral adrenalectomy. DATA EXTRACTION: Information regarding the following was extracted: first author, country, sex, age at adrenalectomy, year of adrenalectomy, diagnosis, molecular abnormality, pre- and postoperative biochemistry, pre- and postoperative medications, pre- and postoperative body mass index, indication for adrenalectomy, surgical technique, gross and microscopic adrenal characteristics, follow-up duration, and short- and long-term postoperative outcomes. DATA SYNTHESIS: We identified 48 cases of bilateral adrenalectomy for CAH, with patients aged from 4 months to 56 years at surgery. The most common indication for surgery was the inability to control hyperandrogenism/virilization and/or Cushing syndrome (n = 30; 62%). Most patients (n = 34; 71%) reported symptomatic improvement postoperatively, with some cases of short-term (n = 5; 10%) and long-term (n = 13; 27%) adverse outcomes. CONCLUSIONS: Bilateral adrenalectomy for CAH appears to be a reasonable therapeutic option for carefully selected patients who have had unsatisfactory outcomes with conventional medical management.


Assuntos
Hiperplasia Suprarrenal Congênita/cirurgia , Adrenalectomia/métodos , Adolescente , Hiperplasia Suprarrenal Congênita/complicações , Adrenalectomia/mortalidade , Adulto , Criança , Pré-Escolar , Síndrome de Cushing/etiologia , Feminino , Fertilidade , Glucocorticoides/administração & dosagem , Terapia de Reposição Hormonal , Humanos , Hiperandrogenismo/etiologia , Lactente , MEDLINE , Masculino , Pessoa de Meia-Idade , Mineralocorticoides/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Gravidez , Resultado do Tratamento , Virilismo/etiologia
13.
J Vet Intern Med ; 31(6): 1649-1657, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28892205

RESUMO

BACKGROUND: Clinicians alter dosing for desoxycorticosterone pivalate (DOCP) to mitigate costs, but this practice has not been critically evaluated in a prospective clinical trial. HYPOTHESIS/OBJECTIVES: The duration of action of DOCP is longer than 30 days in dogs with primary hypoadrenocorticism (PH). ANIMALS: A total of 53 client-owned dogs with PH. Twenty-four dogs with newly diagnosed PH (Group 1) and 29 dogs with treated PH (Group 2). METHODS: Prospective, multicenter, clinical trial. For phase I, DOCP was administered and plasma sodium and potassium concentrations were measured until the dog developed hyponatremia or hyperkalemia at a planned evaluation, or displayed clinical signs with plasma electrolyte concentrations outside of the reference interval independent of a planned evaluation, thus defining DOCP duration of action. Plasma electrolyte concentrations then were assessed at the end of the individualized dosing interval (IDI; i.e., DOCP duration of action minus 7 days, phase II and at least 3 months after concluding phase II, phase III). RESULTS: The duration of action of DOCP in dogs in phase I with naïve PH (n = 24) ranged from 32 to 94 days (median, 62 days; 95% confidence interval [CI], 57, 65) and previously treated PH (n = 29) from 41 to 124 days (median, 67 days; CI, 56, 72). Overall, the final DOCP dosing interval for all dogs that completed phase II (n = 36) ranged from 38 days to 90 days (median, 58 days; CI, 53, 61). No dog that completed phase III (n = 15) required reduction in the IDI. The DOCP duration of action, independent of group, was not significantly associated with several baseline variables. The median drug cost reduction using IDI was approximately 57.5% per year. CONCLUSION AND CLINICAL IMPORTANCE: The duration of action of DOCP in dogs with PH is >30 days, and plasma sodium and potassium concentrations can be maintained with an IDI >30 days long term.


Assuntos
Doença de Addison/veterinária , Desoxicorticosterona/análogos & derivados , Doenças do Cão/tratamento farmacológico , Mineralocorticoides/farmacologia , Doença de Addison/tratamento farmacológico , Animais , Desoxicorticosterona/administração & dosagem , Desoxicorticosterona/farmacologia , Cães , Eletrólitos/sangue , Feminino , Masculino , Mineralocorticoides/administração & dosagem , Potássio/sangue , Estudos Prospectivos , Sódio/sangue
14.
Methods Mol Biol ; 1614: 155-163, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28500602

RESUMO

Dysfunction of the renin-angiotensin-aldosterone system (RAAS) has been implicated in the etiologies of many cardiovascular diseases, including aortic aneurysm. In particular, the infusion of angiotensin II (Ang II) in the apolipoprotein E-deficient mice (apoE-/-) and low density lipoprotein receptor knockout mice (LDLR-/-) to induce aortic aneurysm has been extensively used in the field. In contrast, whether aldosterone (Aldo), an essential component of RAAS and a downstream effector of Ang II, is involved in aortic aneurysm is largely unknown. Here, we describe a new animal model for induction of aortic aneurysm in mice in which administration of deoxycorticosterone acetate (DOCA) and high salt or aldosterone and high salt, but not DOCA or high salt alone, to C57BL/6 male mice can potently induce aortic aneurysm formation and rupture in an age-dependent manner. This new aortic aneurysm mouse model is different from Ang II infusion mouse model and exhibits several unique features that mimic human aortic aneurysm.


Assuntos
Aneurisma Aórtico/induzido quimicamente , Modelos Animais de Doenças , Camundongos , Aldosterona , Animais , Determinação da Pressão Arterial , Acetato de Desoxicorticosterona , Infusões Parenterais , Masculino , Camundongos Endogâmicos C57BL , Mineralocorticoides/administração & dosagem , Mineralocorticoides/toxicidade , Cloreto de Sódio
15.
FASEB J ; 31(1): 60-71, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27650398

RESUMO

Hypertension is a key risk factor for heart failure, with the latter characterized by diaphragm muscle weakness that is mediated in part by increased oxidative stress. In the present study, we used a deoxycorticosterone acetate (DOCA)-salt mouse model to determine whether hypertension could independently induce diaphragm dysfunction and further investigated the effects of high-intensity interval training (HIIT). Sham-treated (n = 11), DOCA-salt-treated (n = 11), and DOCA-salt+HIIT-treated (n = 15) mice were studied over 4 wk. Diaphragm contractile function, protein expression, enzyme activity, and fiber cross-sectional area and type were subsequently determined. Elevated blood pressure confirmed hypertension in DOCA-salt mice independent of HIIT (P < 0.05). Diaphragm forces were impaired by ∼15-20% in DOCA-salt vs. sham-treated mice (P < 0.05), but this effect was prevented after HIIT. Myosin heavy chain (MyHC) protein expression tended to decrease (∼30%; P = 0.06) in DOCA-salt vs. sham- and DOCA-salt+HIIT mice, whereas oxidative stress increased (P < 0.05). Enzyme activity of NADPH oxidase was higher, but superoxide dismutase was lower, with MyHC oxidation elevated by ∼50%. HIIT further prevented direct oxidant-mediated diaphragm contractile dysfunction (P < 0.05) after a 30 min exposure to H2O-2 (1 mM). Our data suggest that hypertension induces diaphragm contractile dysfunction via an oxidant-mediated mechanism that is prevented by HIIT.-Bowen, T. S., Eisenkolb, S., Drobner, J., Fischer, T., Werner, S., Linke, A., Mangner, N., Schuler, G., Adams, V. High-intensity interval training prevents oxidant-mediated diaphragm muscle weakness in hypertensive mice.


Assuntos
Diafragma/patologia , Treinamento Intervalado de Alta Intensidade , Debilidade Muscular/prevenção & controle , Oxidantes/metabolismo , Condicionamento Físico Animal/fisiologia , Animais , Fenômenos Fisiológicos Cardiovasculares , Desoxicorticosterona/administração & dosagem , Desoxicorticosterona/farmacologia , Hipertensão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mineralocorticoides/administração & dosagem , Mineralocorticoides/farmacologia , Mitocôndrias/fisiologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Debilidade Muscular/metabolismo , Estresse Oxidativo
16.
Neurobiol Learn Mem ; 136: 139-146, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27725248

RESUMO

OBJECTIVES: Stress hormones such as cortisol are known to influence a wide range of cognitive functions, including hippocampal based spatial memory. In the brain, cortisol acts via two different receptors: the glucocorticoid (GR) and the mineralocorticoid receptor (MR). As the MR has a high density in the hippocampus, we examined the effects of pharmacological MR stimulation on spatial memory. METHODS: Eighty healthy participants (40 women, 40 men, mean age=23.9years±SD=3.3) completed the virtual Morris Water Maze (vMWM) task to test spatial encoding and spatial memory retrieval after receiving 0.4mg fludrocortisone, a MR agonist, or placebo. RESULTS: There was no effect of MR stimulation on spatial encoding during the vMWM task. However, participants who received fludrocortisone exhibited improved spatial memory retrieval performance. There was neither a main effect of sex nor a sex-by-treatment interaction. CONCLUSION: In young healthy participants, MR stimulation improved hippocampal based spatial memory retrieval in a virtual Morris Water Maze task. Our study not only confirms the importance of MR function in spatial memory, but suggests beneficial effects of acute MR stimulation on spatial memory retrieval in humans.


Assuntos
Fludrocortisona/farmacologia , Aprendizagem em Labirinto/fisiologia , Mineralocorticoides/farmacologia , Receptores de Mineralocorticoides/agonistas , Memória Espacial/fisiologia , Adolescente , Adulto , Feminino , Fludrocortisona/administração & dosagem , Humanos , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Mineralocorticoides/administração & dosagem , Memória Espacial/efeitos dos fármacos , Adulto Jovem
17.
Horm Behav ; 79: 28-36, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26730722

RESUMO

The controls of thirst and sodium appetite are mediated in part by the hormones aldosterone and angiotensin II (AngII). The present study examined the behavioral and neural mechanisms of altered effort-value in animals treated with systemic mineralocorticoids, intracerebroventricular AngII, or both. First, rats treated with mineralocorticoid and AngII were tested in the progressive ratio operant task. The willingness to work for sodium versus water depended on hormonal treatment. In particular, rats treated with both mineralocorticoid and AngII preferentially worked for access to sodium versus water compared with rats given only one of these hormones. Second, components of the mesolimbic dopamine pathway were examined for modulation by mineralocorticoids and AngII. Based on cFos immunohistochemistry, AngII treatment activated neurons in the ventral tegmental area and nucleus accumbens, with no enhancement by mineralocorticoid pretreatment. In contrast, Western blot analysis revealed that combined hormone treatment increased levels of phospho-tyrosine hydroxylase in the ventral tegmental area. Thus, mineralocorticoid and AngII treatments differentially engaged the mesolimbic pathway based on tyrosine hydroxylase levels versus cFos activation.


Assuntos
Angiotensina II/farmacologia , Sistema Límbico/efeitos dos fármacos , Mineralocorticoides/farmacologia , Motivação/efeitos dos fármacos , Angiotensina II/administração & dosagem , Animais , Dopamina/fisiologia , Infusões Intraventriculares , Sistema Límbico/fisiologia , Masculino , Mineralocorticoides/administração & dosagem , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Ratos , Ratos Sprague-Dawley , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/efeitos dos fármacos , Área Tegmentar Ventral/metabolismo
19.
Arq. ciênc. vet. zool. UNIPAR ; 19(2): 107-111, abr.-jun. 2016. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-833117

RESUMO

This report describes the clinical and laboratorial findings as well as the therapeutic protocol performed in a three-year-old mongrel female intact dog, referred to the Veterinary Hospital of FAMEZ/UFMS. The animal had a previous history of recurrent gastrointestinal signs (such as lethargy, vomiting, loss of appetite, melena and abdominal pain), acute crisis episodes, bradycardia, hypotension, hypothermia and increase of capillary refill time, recognized as addisonian crisis due to primary hypoadrenocorticism. Laboratorial findings included anemia, eosinophilia, neutrophilia, lymphocytosis, sodium-potassium ratio of 14,02 mEq/L and prerenal azotemia. Based on that, it was confirmed the diagnosis of primary hypoadrenocorcitism. Thus, it was recommended supplementation therapy with mineralocorticoid (aldosterone) and glucocorticoid (cortisol) corresponding respectively, fludrocortisone acetate of 0.2 mg per kg of BW, by mouth, once daily and prednisone 0.2 mg per kg of BW, by mouth, twice daily until further recommendations. The prognostic was excellent, since the animal significantly improved body condition, andclinical signs disappeared after therapy which lead the sodium-potassium ratio to 35.11 mEq/L. Thus, the clinician must always suspect of primary hypoadrenocorticism in dogs with intermittent nonspecific signs that get better with support therapy. Presumably, hypoarenocorticism must be under diagnosed in veterinary medicine, reinforcing the need to require specific exams in patients that show this wax and wane feature of clinical signs.


O presente relato descreve os achados clínicos, laboratoriais e conduta terapêutica de um animal da espécie canina, fêmea, com três anos de idade, inteiro, sem raça definida, diagnosticado com hipoadrenocorticismo primário atendido no Hospital Veterinário da FAMEZ/UFMS. O animal apresentou histórico de recidivas de sinais gastrintestinais (letargia, vômitos, perda de apetite, melena e dor abdominal), crise adrenal aguda, bradicardia, hipotensão, hipotermia e aumento do tempo de preenchimento capilar. As alterações laboratoriais compreenderam linfocitose, anemia, eosinofilia, neutrofilia, densidade urinária < 1.030, relação sódio: potássio 14,02 mEq/L e azotemia pré-renal. Baseado nos achados clínicos-laboratoriais confirmou-se o hipoadrenocorticismo primário. Em seguida, foi instituído terapia de suplementação de mineralocorticoide (aldosterona) e glicocorticoide (cortisol), correspondendo respectivamente ao acetato de fludrocortisona na dose de 0,2 mg/kg por via oral uma vez ao dia e prednisona 0,2 mg/kg por via oral duas vezes por dia até novas recomendações. O prognóstico foi excelente para este caso, já que houve melhora significativa do animal, com o desaparecimento dos sinais clínicos e com nova relação sódio: potássio de 35,11 mEq/L. Assim, deve-se sempre suspeitar de hipoadrenocorticismo primário canino em pacientes com o curso de aparecimento e desaparecimento com sinais inespecíficos que melhorem com terapia de suporte. Presume-se que o hipoadrenocorticismo primário em cães seja subdiagnosticado na medicina veterinária, por isso a importância dos clínicos em suspeitar e solicitar exames específicos em pacientes que apresentam esse curso da doença.


El informe describe los hallazgos clínicos, de laboratorio y manejo terapéutico de un perro, hembra, con tres años de edad, entera, mestizo, con diagnóstico de hipoadrenocorticismo primario atendido en el Hospital Veterinario de la FAMEZ/UFMS. El animal tuvo un historial de signos gastrointestinales recurrentes (letargia, vómitos, pérdida de apetito, melena y dolor abdominal), crisis renal aguda, bradicardia, hipotensión, hipotermia y un aumento del tiempo de llenado capilar. Las alteraciones de laboratorio presentaron linfocitosis, anemia, eosinofilia, neutrofilia, densidad de la orina < 1,030, relación sodio: potasio 14,02 mEq/L y azotemia prerrenal. Con base en los hallazgos clínicos y de laboratorio, se confirmó el hipoadrenocorticismo primario. A continuación, se introdujo terapia con administración de mineralocorticoide (aldosterona) y glucocorticoide (cortisol), que correspondieron respectivamente al acetato de fludrocortisona a una dosis de 0,2mg/kg por vía oral una vez al día y prednisona 0,2 mg/kg por vía oral dos veces al día hasta nuevas recomendaciones. El pronóstico fue excelente para este caso, ya que hubo mejora significativa del animal, desapareciendo los signos clínicos y con una nueva relación sodio: potasio de 35,11 mEq/L. Por lo tanto, siempre se debe sospechar del hipoadrenocorticismo primario canino en pacientes con el curso de aparecimiento y desaparecimiento con signos inespecíficos que mejoran con terapia de soporte. Es posible que el hipoadrenocorticismo primario en perros sea diagnosticado en la medicina veterinaria, así la importancia de los clínicos en sospechar y solicitar exámenes específicos en pacientes que presentan ese curso de la enfermedad.


Assuntos
Animais , Feminino , Cães , Doença de Addison/classificação , Doença de Addison/diagnóstico , Doenças do Sistema Endócrino/classificação , Mineralocorticoides/administração & dosagem
20.
Can Vet J ; 56(11): 1158-60, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26538671

RESUMO

A 6-year-old, castrated male Siamese cat was diagnosed with primary hypoadrenocorticism, confirmed by an adrenocorticotopic hormone (ACTH) stimulation test documenting both hypocortisolism and hypoaldosteronism. The cat was successfully treated using a combination of prednisolone and desoxycorticosterone pivalate (DOCP). This case demonstrates that DOCP can be used successfully as mineralocorticoid supplementation in cats with hypoadrenocorticism and may have a longer therapeutic duration than that in dogs.


Traitement réussi d'un chat atteint d'hypoadrénocorticisme primaire et d'hyponatrémie à l'aide de pivalate de désoxycorticostérone (DOCP). Un diagnostic d'hypoadrénocorticisme primaire a été posé pour un chat Siamois castré âgé de 6 ans et confirmé par un test de stimulation de l'hormone adrénocorticotope (ACTH) qui a documenté l'hypocortisolisme et l'hypoaldostéronisme. Le chat a été traité avec succès à l'aide d'une combinaison de prednisolone et de pivalate de désoxycorticostérone (DOCP). Ce cas démontre que le DOCP peut être utilisé avec succès en tant que supplément de minéralocorticoïdes chez les chats atteints d'hypoadrénocorticisme et peut présenter une durée thérapeutique plus longue que chez les chiens.(Traduit par Isabelle Vallières).


Assuntos
Insuficiência Adrenal/veterinária , Doenças do Gato/tratamento farmacológico , Desoxicorticosterona/análogos & derivados , Hiponatremia/veterinária , Insuficiência Adrenal/tratamento farmacológico , Animais , Gatos , Desoxicorticosterona/administração & dosagem , Desoxicorticosterona/uso terapêutico , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hiponatremia/tratamento farmacológico , Masculino , Mineralocorticoides/administração & dosagem , Mineralocorticoides/uso terapêutico , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico
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