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2.
Pediatr Blood Cancer ; 67(8): e28319, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32543116

RESUMO

OBJECTIVE: To review the treatment and revaccination of neuroblastoma-associated opsoclonus-myoclonus-ataxia syndrome (OMAS) patients at Memorial Sloan Kettering Cancer Center (MSK). PROCEDURE: Institutional Review Board approval was obtained for this retrospective study of patients with neuroblastoma-associated OMAS followed at MSK from 2000 to 2016. RESULTS: Fourteen patients (nine female) were 9-21 (median 17) months old at diagnosis of neuroblastoma and OMAS syndrome. They had stage 1 (n = 12), stage 2B, or intermediate-risk stage 4. Tumor histology was favorable in 11 patients, unfavorable in two, and unknown in one patient. No patient had amplified MYCN. All patients underwent tumor resection at diagnosis. Anti-neuroblastoma treatment was limited to chemotherapy in one patient. Overall survival is 100% at 3-16 (median 10) years. For OMAS, 13 patients received intravenous immune globulin (IVIg), adrenocorticotropic hormone (ACTH), and rituximab, and one received ACTH and IVIg. Seven patients experienced OMAS relapse. For these relapses, five patients received low-dose cyclophosphamide and two received rituximab. The mean total OMAS treatment was 20-96 (median 48) months. Seven patients started rituximab ≤3 months from diagnosis and did not relapse. The other six experienced OMAS relapse. To date, six patients have been revaccinated at a minimum of 2 years after completion of OMAS therapy without OMAS recurrence. CONCLUSIONS: Patients with neuroblastoma-associated OMAS had excellent overall survival. Early initiation of rituximab, IVIg, and ACTH may reduce risks of OMAS relapse. Revaccination can be resumed without exacerbation of OMAS. Further investigation with a larger cohort of patients is needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neuroblastoma , Síndrome de Opsoclonia-Mioclonia , Hormônio Adrenocorticotrópico/administração & dosagem , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Imunoglobulinas Intravenosas/administração & dosagem , Lactente , Masculino , Estadiamento de Neoplasias , Neuroblastoma/diagnóstico , Neuroblastoma/mortalidade , Neuroblastoma/terapia , Síndrome de Opsoclonia-Mioclonia/diagnóstico , Síndrome de Opsoclonia-Mioclonia/mortalidade , Síndrome de Opsoclonia-Mioclonia/terapia , Estudos Retrospectivos , Rituximab/administração & dosagem , Taxa de Sobrevida
3.
Poult Sci ; 99(2): 1156-1162, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32036967

RESUMO

There is limited information on the effects of stress and/or physiological manipulation on plasma concentrations of corticosterone (CORT) in turkeys. Under basal conditions, there was evidence for episodic release of CORT in turkeys. The present studies determine the effects of handling, herding, herding, the administration of Escherichia coli endotoxin, and challenge with turkey adrenocorticotropic hormone (ACTH) on plasma concentrations of CORT in market-weight male turkeys. Plasma concentrations of CORT were increased after challenge with turkey ACTH, handling together with saline injection or herding (moving birds from one pen to another). There were no effects on plasma concentrations of CORT of the following putative stressors: handling per se, endotoxin challenge, or of placing in an inverted position on simulated shackles.


Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Corticosterona/sangue , Endotoxinas/efeitos adversos , Perus/fisiologia , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Endotoxinas/administração & dosagem , Masculino , Perus/sangue
4.
Horm Res Paediatr ; 92(3): 162-168, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31851964

RESUMO

INTRODUCTION: Patients with suspected adrenal insufficiency undergo screening with a serum morning cortisol level and confirmatory testing with an adrenocorticotropic hormone (ACTH) stimulation test. However, much of the data collected to determine appropriate values for morning cortisol levels are derived from adult populations and may not accurately represent pediatric physiology. The purpose of this study was to evaluate the mean morning cortisol level in the pediatric population based on pubertal status and sex in order to better understand such influences on laboratory evaluation of adrenal insufficiency. METHODS: A retrospective chart review was conducted using electronic medical records of patients seen at Children's Mercy Kansas City from 11/01/2007 to 11/01/2017. Patients between 2 and 18 years of age who had pubertal staging assessed by a pediatric endocrinologist and confirmed adrenal sufficiency by high-dose ACTH stimulation testing were included. Two-sample Wilcoxon rank sum (Mann-Whitney) tests or t tests were used to compare morning cortisol levels between females and males - both independent of Tanner stage and by Tanner stage. Multivariable regression models were used to evaluate associations among covariates on two outcomes: morning cortisol levels and peak cortisol values with ACTH stimulation. RESULTS: Morning cortisol levels were greater in females than males independent of Tanner staging (p = 0.0054) and also in Tanner stage 1 (p = 0.0042). No differences in mean morning cortisol levels between Tanner stage 2-5 females and males were found (p = 0.4652). Morning cortisol levels were not significantly different between Tanner 1 patients and Tanner 2-5 patients independent of sex (p = 0.0575). Sex was predictive of serum morning cortisol levels (p = 0.015), and morning cortisol levels were predictive of peak cortisol levels during ACTH stimulation testing (p < 0.001). CONCLUSIONS: These data suggest that different normative cortisol values may need to be established for pediatric females and males, and by pubertal status. Larger prospective studies are needed to evaluate the role of sex and pubertal status in identifying adrenal insufficiency in the -pediatric population.


Assuntos
Hidrocortisona/sangue , Puberdade/fisiologia , Fatores Sexuais , Adolescente , Insuficiência Adrenal/sangue , Hormônio Adrenocorticotrópico/administração & dosagem , Índice de Massa Corporal , Criança , Pré-Escolar , Ritmo Circadiano , Feminino , Humanos , Masculino , Valores de Referência , Estudos Retrospectivos
5.
J Toxicol Sci ; 44(9): 601-610, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474741

RESUMO

To verify simultaneous measurement of blood levels of adrenal steroids as a tool to evaluate drug effects on adrenal steroidogenesis, dose- and time-dependent changes in blood levels of corticosterone and its precursors (pregnenolone, progesterone and deoxycorticosterone), as well as their relationship with the pathological changes in the adrenal gland, were examined in rats dosed with ketoconazole (KET). Also examined were whether effects on adrenal steroidogenesis that were not obvious in the blood steroid levels after sole administration of KET could be revealed by post-administration of ACTH, and the correlation between the blood and adrenal steroid levels. Male rats were dosed with 15, 50, or 150 mg/kg of KET for 1 or 7 days with or without ACTH, and the blood and adrenal concentrations of the steroids were measured. KET increased the blood deoxycorticosterone level even at a dose level and time point at which histopathological changes were not obvious. KET-induced changes in blood levels of other steroids were revealed by ACTH, and the blood and adrenal levels were generally correlated especially after ACTH post-administration. Thus, blood levels of adrenal steroids, including precursors, can be a sensitive and early marker of drug effects on the adrenal steroidogenesis that reflect adrenal levels of steroids. The usefulness of the multiple steroid measurement as a method for mechanism investigation of drug effects on the adrenal gland can be further enhanced by ACTH.


Assuntos
Glândulas Suprarrenais/efeitos dos fármacos , Glândulas Suprarrenais/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Desoxicorticosterona/sangue , Desoxicorticosterona/metabolismo , Cetoconazol/toxicidade , Pregnenolona/sangue , Pregnenolona/metabolismo , Progesterona/sangue , Progesterona/metabolismo , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Cromatografia Líquida , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Fatores de Tempo
6.
Pharmacol Biochem Behav ; 186: 172767, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31491434

RESUMO

Approximately one third of patients with depression remain treatment resistant with existing antidepressants, suggesting that the currently-available antidepressants cannot induce appropriate responses in the brains of all patients. Long-term exposure to adrenocorticotrophic hormone (ACTH) has been proposed as a model that mimics at least some aspects of clinical treatment-resistant depression in rodents. The purpose of this study was to explore potential causes of antidepressant treatment resistance using the chronic ACTH-treated mouse model. We subjected ACTH-treated mice to a rodent model of electroconvulsive therapy, i.e., electroconvulsive seizure (ECS), which induces various molecular and cellular changes, including in gene expression and adult neurogenesis in the hippocampus. First, behavioral effect of repeated ECS in the forced swim test (FST) was examined. In our experimental setting, ACTH-treated mice showed resistance to the antidepressant-like effect of ECS in the FST. We then examined which cellular and molecular changes induced by ECS were attenuated by ACTH administration. Chronic ACTH treatment suppressed the increase of gene expression such as of Bdnf, Npy, and Drd1 induced by ECS in the hippocampus. In contrast, there was no difference in ECS-induced promotion of the early neurogenetic process in the hippocampus between ACTH-treated and control mice. Our results suggest the possibility that impaired neuromodulation and monoamine signaling in the hippocampus are among the factors contributing to antidepressant treatment resistance.


Assuntos
Hormônio Adrenocorticotrópico/administração & dosagem , Eletroconvulsoterapia , Hormônio Adrenocorticotrópico/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/genética , Masculino , Camundongos , Modelos Biológicos , Neurogênese , Neuropeptídeo Y/genética , RNA Mensageiro/metabolismo , Receptores de Dopamina D1/genética
7.
Transplant Proc ; 51(6): 1831-1837, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399168

RESUMO

This retrospective study examined the effect of adrenocorticotropic hormone therapy on remission of recurrent focal segmental glomerulosclerosis (FSGS) in patients with history of kidney transplant (KT) treated at 2 transplant centers. Patients with biopsy-confirmed FSGS following KT who received Acthar Gel (Mallinckrodt ARD, Bedminster, New Jersey, United States) treatment for ≥1 month were eligible. A total of 14 patients with idiopathic FSGS were included. Acthar Gel treatment resulted in complete remission of FSGS in 3 patients and partial remission in 2 patients for a total treatment response rate of 36% (5/14) of patients. Among patients showing complete or partial remission, Acthar Gel treatment duration ranged from 6 months to 2 years and 60% (3/5 patients) had serum creatinine ≤ 2 mg/dL at the start of Acthar Gel treatment. Patient outcomes suggest Acthar Gel may be an effective and tolerable treatment for recurrent FSGS in patients with history of KT. Early initiation of Acthar Gel treatment and therapy duration of at least 6 months may be needed for optimal response to Acthar Gel in patients with history of KT and recurrent FSGS.


Assuntos
Hormônio Adrenocorticotrópico/administração & dosagem , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Hormônios/administração & dosagem , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Adulto , Biópsia , Creatinina/sangue , Feminino , Géis , Glomerulosclerose Segmentar e Focal/sangue , Glomerulosclerose Segmentar e Focal/etiologia , Humanos , Quimioterapia de Indução , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
8.
J Vet Intern Med ; 33(5): 2235-2238, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31448839

RESUMO

A 11-year-old male neutered Shih Tzu was referred to a tertiary facility with a history of weight loss, decreased appetite, polydipsia, and lethargy. The dog had a 10-year history of nonspecific allergic dermatitis and was being treated with 16 mg/kg of ketoconazole q12h for Malassezia dermatitis. Vague gastrointestinal signs, hypocholesterolemia, and lack of a stress leukogram increased suspicion for hypoadrenocorticism (HA). An adrenocorticotropic hormone (ACTH) stimulation test identified hypocortisolemia on pre- and post-ACTH samples and ketoconazole was discontinued. After a short course of corticosteroid treatment, an ACTH stimulation test was repeated and pre-ACTH cortisol concentration was within the reference range, and the post-ACTH cortisol concentration was mildly increased. The temporal association between return of adequate adrenocortical cortisol production and discontinuation of ketoconazole led to the conclusion that the dog had developed iatrogenic HA secondary to ketoconazole treatment.


Assuntos
Insuficiência Adrenal/veterinária , Doenças do Cão/induzido quimicamente , Doença Iatrogênica/veterinária , Cetoconazol/efeitos adversos , Insuficiência Adrenal/induzido quimicamente , Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico/administração & dosagem , Hormônio Adrenocorticotrópico/farmacologia , Animais , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Dermatomicoses/tratamento farmacológico , Dermatomicoses/veterinária , Doenças do Cão/diagnóstico , Cães , Hidrocortisona/sangue , Cetoconazol/administração & dosagem , Cetoconazol/uso terapêutico , Malassezia , Masculino
9.
Clin Dermatol ; 37(3): 240-254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31178106

RESUMO

Sarcoidosis is a chronic multisystemic, inflammatory disease with specific granulomatous cutaneous lesions. The cutaneous form may be considered a "great imitator," due to its extensive clinical morphology that occurs in upwards of 20% to 35% of patients. Cutaneous lesions may have a variety of presentations including papules, plaques, nodules, infiltrative scars, annular, angiolupoid, psoriasiform, hypopigmented, atrophic, ulcerative lesions, scarring and nonscarring alopecia, erythroderma, and ichthyosiform lesions. The dermatopathology is generally the same for all of the clinical presentations; however, variations in the cutaneous findings cause confusion in following a clinical course, therapeutic approach, or prognosis.


Assuntos
Sarcoidose , Dermatopatias , Pele/patologia , Corticosteroides/administração & dosagem , Hormônio Adrenocorticotrópico/administração & dosagem , Idade de Início , Antimaláricos/uso terapêutico , Fatores Biológicos/uso terapêutico , Diagnóstico Diferencial , Feminino , Humanos , Infliximab/uso terapêutico , Injeções , Masculino , Mercaptopurina/análogos & derivados , Mercaptopurina/uso terapêutico , Metotrexato/uso terapêutico , Prognóstico , Rituximab/administração & dosagem , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Sarcoidose/etiologia , Sarcoidose/patologia , Dermatopatias/diagnóstico , Dermatopatias/etiologia , Dermatopatias/patologia , Talidomida/uso terapêutico
10.
J Vet Intern Med ; 33(4): 1766-1774, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31111575

RESUMO

BACKGROUND: The hypothalamic-pituitary-adrenal axis regulates the response to sepsis-associated stress. Relative adrenal insufficiency or adrenocorticotropic hormone (ACTH):cortisol imbalance, defined as a poor cortisol response to administration of ACTH, is common and associated with death in hospitalized foals. However, information on other adrenal steroid response to ACTH stimulation in sick foals is minimal. OBJECTIVE: To investigate the response of multiple adrenocortical steroids to administration of ACTH in foals. ANIMALS: Hospitalized (n = 34) and healthy (n = 13) foals. METHODS: In this prospective study, hospitalized foals were categorized into 2 groups using cluster analysis based on adrenal steroids response to ACTH stimulation: Cluster 1 (n = 11) and Cluster 2 (n = 23). After baseline blood sample collection, foals received 10 µg of ACTH with additional samples collected at 30 and 90 minutes after ACTH. Steroid and ACTH concentrations were determined by immunoassays. The area under the curve (AUC) and Delta0-30 were calculated for each hormone. RESULTS: The AUC for cortisol, aldosterone, androstenedione, pregnenolone, 17α-OH-progesterone, and progesterone were higher in critically ill (Cluster 1) compared to healthy foals (P < .01). Delta0-30 for cortisol and 17α-OH-progesterone was lower in Cluster 1 (24%, 26.7%) and Cluster 2 (16%, 11.2%) compared to healthy foals (125%, 71%), respectively (P < .05). Foals that died had increased AUC for endogenous ACTH (269 versus 76.4 pg/mL/h, P < .05) accompanied by a low AUC for cortisol (5.5 versus 15.5 µg/dL/h, P < .05), suggesting adrenocortical dysfunction. CONCLUSION AND CLINICAL IMPORTANCE: The 17α-OH-progesterone response to administration of ACTH was a good predictor of disease severity and death in hospitalized foals.


Assuntos
Corticosteroides/sangue , Hormônio Adrenocorticotrópico/farmacologia , Doenças dos Cavalos/sangue , Doenças dos Cavalos/tratamento farmacológico , 17-alfa-Hidroxiprogesterona/sangue , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Animais Recém-Nascidos , Área Sob a Curva , Análise por Conglomerados , Estado Terminal , Feminino , Doenças dos Cavalos/mortalidade , Cavalos , Masculino , Prognóstico , Estudos Prospectivos , Sepse/tratamento farmacológico , Sepse/veterinária
11.
J Pediatr Endocrinol Metab ; 32(5): 529-531, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31005951

RESUMO

Diagnosis of adrenal insufficiency (AI) in infants can be difficult. While a low random cortisol can signal AI, often confirmatory tests are required when clinical suspicion is strong but the cortisol levels are equivocal. Several studies have demonstrated that in sick preterm infants, there is relative adrenal insufficiency (RAI) defined as an inadequate cortisol production relative to the degree of stress or illness, a condition which can last for several weeks, while in term infants the adrenal axis is mature at birth (Bagnoli F, Mori A, Fommei C, Coriolani G, Badii S, et al. ACTH and cortisol cord plasma concentrations in preterm and term infants. J Perinatol 2013;33:520-4). Adrenocorticotrophic hormone (ACTH) and corticotrophin releasing hormone (CRH) stimulation tests have been validated in infants in several studies. In light of recent reports of false-negative results of stimulation tests, it is imperative to highlight the pitfalls of these tests. The purpose of this communication is to bring attention to the accuracy of timing of these tests in infants.


Assuntos
Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico/administração & dosagem , Biomarcadores/sangue , Hormônio Liberador da Corticotropina/administração & dosagem , Hormônios/administração & dosagem , Hidrocortisona/sangue , Insuficiência Adrenal/sangue , Humanos , Lactente , Recém-Nascido Prematuro , Prognóstico
12.
Epilepsia ; 60(3): 441-451, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30801699

RESUMO

OBJECTIVE: To compare the efficacy and safety of the ketogenic diet (KD) with standard adrenocorticotropic hormone (ACTH) treatment in infants with West syndrome. METHODS: In this parallel-cohort (PC) randomized controlled trial (RCT), infants were randomly allocated to KD or high-dose ACTH. Those who could not be randomized were followed in a PC. Primary end point was electroclinical remission at day 28. Secondary end points were time to electroclinical remission, relapse after initial response, seizure freedom at last follow-up, adverse effects, and developmental progress. RESULTS: One hundred one infants were included: 32 in the RCT (16 KD; 16 ACTH) and 69 in the PC (37 KD; 32 ACTH). Electroclinical remission at day 28 was similar between KD and ACTH (RCT: 62% vs 69%; PC: 41% vs 38%; combined cohort: 47% vs 48%; KD vs ACTH, respectively). In the combined cohort, time to electroclinical remission was similar between both treatments (14 days for KD, 16 days for ACTH). However, relapse rates were 16% (KD) and 43% (ACTH, P = 0.09), and seizure freedom at last follow-up was 40% (KD) and 27% (ACTH, P = 0.18). Adverse effects needing acute medical intervention occurred more often with ACTH (30% with KD, 94% with ACTH, P < 0.001). Age-appropriate psychomotor development and adaptive behavior were similar. Without prior vigabatrin (VGB) treatment, remission at day 28 was 47% (KD) and 80% (ACTH, P = 0.02); relapse rates were 29% (KD) and 56% (ACTH, P = 0.13). Consequently, seizure freedom at last follow-up was similar. In infants with prior VGB, seizure freedom at last follow-up was 48% (KD) and 21% (ACTH, P = 0.05). SIGNIFICANCE: The study is underpowered; therefore, its results should be interpreted with caution. KD is as effective as ACTH in the long term but is better tolerated. Without prior VGB treatment, ACTH remains the first choice to achieve short-term remission. However, with prior VGB, KD was at least as effective as ACTH in the short term and was associated with lower relapse rates in the long term; therefore, it represents an appropriate second-line treatment after VGB.


Assuntos
Hormônio Adrenocorticotrópico/uso terapêutico , Dieta Cetogênica , Espasmos Infantis/terapia , Hormônio Adrenocorticotrópico/administração & dosagem , Hormônio Adrenocorticotrópico/efeitos adversos , Pré-Escolar , Dieta Cetogênica/efeitos adversos , Dieta Cetogênica/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Espasmos Infantis/dietoterapia , Espasmos Infantis/tratamento farmacológico , Resultado do Tratamento
13.
Reprod Domest Anim ; 54(1): 46-54, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30120850

RESUMO

The objective of this study was to examine the expression of transforming growth factor beta receptor (TGFBR)1, TGFBR2, TGFBR3, activin receptor (ACVR)1B and ACVR2B in ovaries of cows with cystic ovarian disease (COD). The expression of the selected receptors was determined by immunohistochemistry in sections of ovaries from cows with ACTH-induced and spontaneous COD. Expression of TGFBR1 and TGFBR3 was higher in granulosa cells of cysts from cows with spontaneous COD than in tertiary follicles from the control group. Additionally, TGFBR3 expression was higher in granulosa cells of cysts from cows with ACTH-induced COD than in those from the control group and lower in theca cells of spontaneous and ACTH-induced cysts than in tertiary control follicles. There were no changes in the expression of TGFBR2. ACVR1B expression was higher in granulosa cells of tertiary follicles of cows with spontaneous COD than in the control group, whereas ACVR2B expression was higher in cysts of the spontaneous COD group than in tertiary follicles from the control group. The alterations here detected, together with the altered expression of the ligands previously reported, indicate alterations in the response of the ligands in the target cells, modifying their actions at cellular level.


Assuntos
Receptores de Ativinas/metabolismo , Doenças dos Bovinos/metabolismo , Cistos Ovarianos/veterinária , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Bovinos , Feminino , Células da Granulosa/metabolismo , Imuno-Histoquímica , Cistos Ovarianos/induzido quimicamente , Cistos Ovarianos/metabolismo , Ovário/metabolismo , Células Tecais/metabolismo
14.
Eur J Paediatr Neurol ; 23(1): 136-142, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30293931

RESUMO

West syndrome is a distinct, infantile onset, epileptic encephalopathy, associated with poor neurodevelopmental outcome. The present study was designed as a randomized, open-label, pilot study to evaluate the safety, feasibility, and effectiveness of oral zonisamide therapy in comparison with adrenocorticotropic hormone therapy in infants with West syndrome. Thirty infants with West syndrome were randomized to receive treatment with either synthetic, intramuscular adrenocorticotropic hormone (30-60 IU) or oral zonisamide (4-25 mg/kg/day). The study participants had a long treatment lag and preponderance of male sex (90%). The primary effectiveness outcome measure was the cessation of epileptic spasms at 2 weeks of initiation of therapy and persistent till 6 weeks as per West Delphi consensus statement recommendations. Comparison of efficacies of zonisamide versus adrenocorticotropic hormone was as following: the cessation of epileptic spasms (27% vs. 40%, p = 0.70), resolution of hypsarrhythmia at 14 days (20% vs. 33%, p = 0.68) and resolution of hypsarrhythmia at 6 weeks (36% vs. 71%, p = 0.14). Overall, the study observed a poor efficacy of both adrenocorticotropic hormone and zonisamide therapy, which is probably due to long treatment lag and a high proportion of structural aetiology. However, oral zonisamide appeared to be safe and tolerable in the study.


Assuntos
Hormônio Adrenocorticotrópico/administração & dosagem , Anticonvulsivantes/uso terapêutico , Espasmos Infantis/tratamento farmacológico , Zonisamida/administração & dosagem , Administração Oral , Feminino , Humanos , Lactente , Injeções Intramusculares , Masculino , Projetos Piloto , Resultado do Tratamento
15.
J Pediatr Endocrinol Metab ; 32(1): 57-63, 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30530907

RESUMO

Background The diagnosis of adrenal insufficiency (AI) is based on the basal and stimulated levels of serum cortisol in response to the short Synacthen test (SST). In patients with secondary AI (SAI) due to hypothalamic-pituitary-adrenal (HPA) axis defects, the SST has been validated against the insulin tolerance test (ITT), which is the gold standard. However, injection Synacthen is not easily available in some countries, and endocrinologists often use Acton-Prolongatum (intramuscular [IM] long-acting adrenocorticotropic hormone [ACTH]) in place of Synacthen. There are no studies validating the use of IM-ACTH in children with suspected AI. We evaluated the diagnostic value of the IM-ACTH test against the ITT for the diagnosis of SAI in children. Methods All children with suspected growth hormone deficiency (GHD) undergoing a routine ITT were evaluated using the IM-ACTH test within 1 week. Results Forty-eight patients (36 boys/12 girls, age range: 5-14 years) were evaluated using both the ITT and the IM-ACTH test. Twenty-eight patients had a normal cortisol response (≥18 µg/dL, 500 nmol/L) in the ITT and 20 had low values. In patients with a normal cortisol response on the ITT, the peak value obtained after the IM-ACTH test was higher than that on the ITT (28.7 µg/dL [± 8.8] vs. 23.8 µg/dL [± 4.54], respectively; p=0.0012). Compared to the ITT, the sensitivity and specificity of the IM-ACTH test for the diagnosis of SAI at cortisol cut-offs <18 µg/dL (500 nmol/L) and <22 µg/dL (600 nmol/L) were 57.1% and 92.8%, and 100% and 73.5%, respectively. Conclusions A peak cortisol value <18 µg/dL on the IM-ACTH test is highly suggestive of SAI, whereas a value >22 µg/dL rules out SAI.


Assuntos
Testes de Função do Córtex Suprarrenal/métodos , Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico/administração & dosagem , Hormônio Adrenocorticotrópico/sangue , Biomarcadores/sangue , Adolescente , Insuficiência Adrenal/sangue , Criança , Feminino , Seguimentos , Humanos , Hidrocortisona/sangue , Injeções Intramusculares , Insulina/sangue , Resistência à Insulina , Masculino , Valor Preditivo dos Testes
16.
FASEB J ; 33(3): 3264-3278, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30423262

RESUMO

Stress is known to cause corpus luteum (CL) dysfunction, and stress hormones play a critical role in this process. However, the mechanism remains unclear. In this study, weaned sows were injected with synthetic adrenocorticotropic hormone (ACTH) for 7 d; whole-genome bisulfite sequencing (WGBS) and RNA sequencing was used respectively to investigate the systematic association between ACTH administration and DNA methylation in CL and its relationship to gene expression. Results showed that ACTH treatment significantly increased the concentrations of cortisol ( P < 0.05). The genome-wide DNA methylation maps of CL were provided, and the global analysis showed the difference between the 2 groups exists in the chromosomes and feature regions of the genome. A total of 88,559 DMRs were identified and the most DMR-related genes were gathered in terms of metabolic biologic processes, and some DMR-related genes were involved in cellular differentiation. Nine differentially expressed genes were screened out of coexpressed genes and 4 DMR-associated genes that were also differentially expressed ( P < 0.05). In summary, our study firstly provides insight into the regulation of ACTH administration on genomic DNA methylation and gene expression in CL. We revealed a remarkable alteration of DNA methylation in CL caused by ACTH treatment, and identified 4 DMR-related genes that may be involved in the CL function under stress conditions.-Zhao, F., Wu, W., Wei, Q., Shen, M., Li, B., Jiang, Y., Liu, K., Liu, H. Exogenous adrenocorticotropic hormone affects genome-wide DNA methylation and transcriptome of corpus luteum in sows.


Assuntos
Hormônio Adrenocorticotrópico/administração & dosagem , Corpo Lúteo/efeitos dos fármacos , Corpo Lúteo/metabolismo , Metilação de DNA/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Hormônio Adrenocorticotrópico/metabolismo , Animais , Epigênese Genética/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Sus scrofa
18.
Clin Lab ; 64(10): 1695-1700, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30336519

RESUMO

BACKGROUND: The adrenocorticotropic hormone (ACTH) stimulation test is a widely used diagnostic tool to assess the adrenal gland function. Beyond that the ACTH test can be used in stress research to induce a biochemical stress response under standardized conditions. To study the impact of the stress response on protein metabolism, time-course plasma amino acid profiling in healthy individuals was performed with high performance liquid chromatography tandem-mass spectrometry (HPLC-MS/MS). METHODS: A set of 39 samples (pre/post 30´ and 60´ IV-ACTH) from 13 healthy individuals (age range 26 - 58, 3 female and 10 male) was investigated. Plasma amino acids were quantified by LC-MS/MS using the AbsoluteIDQ® p180 Kit (Biocrates Life Science, Innsbruck, Austria) including 19 biogenic amino acids, ornithine, and citrulline. RESULTS: Statistically significant decreases were observed for 11 proteinogenic amino acids (alanine, asparagine, isoleucine, leucine, tyrosine, phenylalanine, tryptophan, valine, methionine, aspartate, and threonine). The amino acids alanine, asparagine, and isoleucine showed markedly pronounced relative changes with short-term reduction of median inter-individual plasma concentrations of up to 25%. CONCLUSIONS: Amino acid profiling with LC-MS/MS revealed highly dynamic plasma alterations upon application of exogenous corticotropin as a stress model. Our findings provide novel insights into the biochemical stress response and improve our understanding of short-term metabolic consequences. Further studies should elucidate the impact of corticotropin mediated stress responses on amino acid catabolism.


Assuntos
Hormônio Adrenocorticotrópico/administração & dosagem , Aminoácidos/metabolismo , Metaboloma/efeitos dos fármacos , Metabolômica , Adulto , Aminoácidos/sangue , Cromatografia Líquida , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Fatores de Tempo
20.
J Vet Intern Med ; 32(6): 1886-1890, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30230611

RESUMO

BACKGROUND: Low-dose ACTH stimulation testing would lower cost and may increase sensitivity for identification of partial ACTH deficiency. HYPOTHESIS: (1) The low-dose ACTH stimulation test will provide comparable results to the standard-dose ACTH stimulation test in dogs suspected of hypoadrenocorticism and (2) partial ACTH deficiency exists in dogs and can result in chronic, intermittent gastrointestinal signs. ANIMALS: Thirty-one client-owned dogs suspected of having hypoadrenocorticism. METHODS: Prospective study. Dogs suspected of having hypoadrenocorticism received 1 µg/kg cosyntropin IV for the first ACTH stimulation test; the second test was performed 4 h later and dogs received 5 µg/kg cosyntropin IV. Blood samples were obtained pre-ACTH and 1 hour post-ACTH for each dose (4 measurements total). Samples for endogenous ACTH measurement were obtained at the time of initial blood collection. RESULTS: No significant difference was observed in the basal cortisol concentration before administration of a 1 µg/kg versus before a 5 µg/kg dose of cosyntropin (P = .544). For dogs suspected of having hypoadrenocorticism, the ACTH-stimulated cortisol concentrations in response to both doses of ACTH were equivalent (90% confidence interval [CI], 80.5-97.2%; P = .04). No cases with partial ACTH deficiency were identified conclusively. CONCLUSIONS AND CLINICAL IMPORTANCE: A 1 µg/kg dose of cosyntropin is equivalent to a 5 µg/kg dose of cosyntropin for screening dogs suspected of hypoadrenocorticism. The existence of partial ACTH deficiency was not identified in this small group of dogs.


Assuntos
Insuficiência Adrenal/veterinária , Hormônio Adrenocorticotrópico/farmacologia , Doenças do Cão/diagnóstico , Insuficiência Adrenal/diagnóstico , Hormônio Adrenocorticotrópico/administração & dosagem , Hormônio Adrenocorticotrópico/sangue , Animais , Cosintropina/administração & dosagem , Cosintropina/farmacologia , Cães , Feminino , Hidrocortisona/sangue , Masculino , Estudos Prospectivos , Reprodutibilidade dos Testes
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