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1.
Respir Physiol Neurobiol ; 298: 103845, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35041989

RESUMO

BACKGROUND: Prolonged apnea is characterized by hypoxia/hypercapnia. Hypoxia can be associated with hormonal dysfunction. We raised the question as to whether steroid hormonal and gonadotropin levels could be influenced by short-term hypoxia/hypercapnia in a model of dry apnea in trained apnea divers. METHODS: Adrenal, sex steroid and pituitary hormones were measured in ten trained voluntary apnea divers before, immediately after, 0.5 h and 4 h after a maximal breath-hold. Apnea was carried out under dry conditions. RESULTS: Corticosterone, progesterone, cortisol, 17-OH-progesterone, dehydroepiandrosterone and androstenedione showed a significant continuous increase with a maximum at 0.5 h after apnea, followed by a decrease back to or below baseline at 4 h after apnea. Testosterone, estradiol, cortisone and dihydrotestosterone showed a decrease 4 h after apnea. Dehydroepiandrosteronesulfate, luteinizing hormone (LH) and follicle stimulating hormone (FSH) showed no significant changes. CONCLUSION: Even a single apnea resulted in two different patterns of hormone response to apnea, with increased adrenal and reduced sex steroid levels, while LH/FSH showed no clear kinetic reaction. Apnea divers might be a suitable clinical model for hypoxic disease.


Assuntos
Corticosteroides/metabolismo , Apneia/metabolismo , Mergulho , Hormônios Esteroides Gonadais/metabolismo , Gonadotropinas Hipofisárias/metabolismo , Hipercapnia/metabolismo , Hipóxia/metabolismo , Adulto , Feminino , Humanos , Masculino , Progesterona , Testosterona
2.
J Cancer Res Clin Oncol ; 147(6): 1733-1743, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33760944

RESUMO

BACKGROUND: In recent years, a variety of innovative therapeutics for castration-resistant prostate cancer have been developed, including novel anti-androgenic drugs, such as abiraterone or VPC-13566. Therapeutic monitoring of these pharmaceuticals is performed either by measuring PSA levels in serum or by imaging. PET using PSMA ligands labeled with Fluor-18 or Gallium-68 is the most sensitive and specific imaging modality for detection of metastases in advanced prostate cancer. To date, it remains unclear how PSMA expression is modulated by anti-hormonal treatment and how it correlates with PSA secretion. METHODS: We analyzed modulation of PSMA-mRNA and protein expression, 68Ga-PSMA uptake and regulation of PSA secretion by abiraterone or VPC-13566 in LNCaP cells in vitro. RESULTS: We found that abiraterone and VPC-13566 upregulate PSMA protein and mRNA expression but block PSA secretion in LNCaP cells. Both anti-androgens also enhanced 68Ga-PSMA uptake normalized by the number of cells, whereas abiraterone and VPC-13566 reduced 68Ga-PSMA uptake in total LNCaP monolayers treated due to cell death. CONCLUSION: Our data indicate that PSA secretion and PSMA expression are differentially regulated upon anti-androgen treatment. This finding might be important for the interpretation of 68Ga-PSMA PET images in monitoring therapies with abiraterone and VPC-13566 in prostate cancer patients, but needs to be validated in vivo.


Assuntos
Adenocarcinoma/metabolismo , Antagonistas de Androgênios/farmacologia , Antígenos de Superfície/genética , Ácido Edético/análogos & derivados , Glutamato Carboxipeptidase II/genética , Oligopeptídeos/farmacocinética , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/metabolismo , Adenocarcinoma/diagnóstico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Antagonistas de Androgênios/uso terapêutico , Androstenos/farmacologia , Androstenos/uso terapêutico , Antígenos de Superfície/metabolismo , Linhagem Celular Tumoral , Ácido Edético/farmacocinética , Isótopos de Gálio , Radioisótopos de Gálio , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glutamato Carboxipeptidase II/metabolismo , Humanos , Masculino , Células PC-3 , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Antígeno Prostático Específico/efeitos dos fármacos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Via Secretória/efeitos dos fármacos
3.
J Cardiovasc Magn Reson ; 20(1): 40, 2018 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-29909774

RESUMO

BACKGROUND: Prolonged breath holding results in hypoxemia and hypercapnia. Compensatory mechanisms help maintain adequate oxygen supply to hypoxia sensitive organs, but burden the cardiovascular system. The aim was to investigate human compensatory mechanisms and their effects on the cardiovascular system with regard to cardiac function and morphology, blood flow redistribution, serum biomarkers of the adrenergic system and myocardial injury markers following prolonged apnoea. METHODS: Seventeen elite apnoea divers performed maximal breath-hold during cardiovascular magnetic resonance imaging (CMR). Two breath-hold sessions were performed to assess (1) cardiac function, myocardial tissue properties and (2) blood flow. In between CMR sessions, a head MRI was performed for the assessment of signs of silent brain ischemia. Urine and blood samples were analysed prior to and up to 4 h after the first breath-hold. RESULTS: Mean breath-hold time was 297 ± 52 s. Left ventricular (LV) end-systolic, end-diastolic, and stroke volume increased significantly (p < 0.05). Peripheral oxygen saturation, LV ejection fraction, LV fractional shortening, and heart rate decreased significantly (p < 0.05). Blood distribution was diverted to cerebral regions with no significant changes in the descending aorta. Catecholamine levels, high-sensitivity cardiac troponin, and NT-pro-BNP levels increased significantly, but did not reach pathological levels. CONCLUSION: Compensatory effects of prolonged apnoea substantially burden the cardiovascular system. CMR tissue characterisation did not reveal acute myocardial injury, indicating that the resulting cardiovascular stress does not exceed compensatory physiological limits in healthy subjects. However, these compensatory mechanisms could overly tax those limits in subjects with pre-existing cardiac disease. For divers interested in competetive apnoea diving, a comprehensive medical exam with a special focus on the cardiovascular system may be warranted. TRIAL REGISTRATION: This prospective single-centre study was approved by the institutional ethics committee review board. It was retrospectively registered under ClinicalTrials.gov (Trial registration: NCT02280226 . Registered 29 October 2014).


Assuntos
Apneia/diagnóstico por imagem , Suspensão da Respiração , Sistema Cardiovascular/diagnóstico por imagem , Mergulho , Imagem Cinética por Ressonância Magnética , Adaptação Fisiológica , Adulto , Apneia/sangue , Apneia/fisiopatologia , Biomarcadores/sangue , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Mergulho/efeitos adversos , Epinefrina/sangue , Feminino , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Norepinefrina/sangue , Fragmentos de Peptídeos/sangue , Valor Preditivo dos Testes , Fluxo Sanguíneo Regional , Fatores de Risco , Fatores de Tempo , Troponina/sangue , Função Ventricular Esquerda , Adulto Jovem
4.
Med Klin Intensivmed Notfmed ; 113(5): 418-425, 2018 06.
Artigo em Alemão | MEDLINE | ID: mdl-28589296

RESUMO

BACKGROUND: The emergency department (ED) is increasingly becoming the primary care unit of patients who are no longer able to meet the necessary minimum requirements for a healthy life. In the emergency medical care of these patients, fixation errors and stereotyped thinking can distract from serious illnesses, which can be tended by emergency medicine. This group of patients, with their multifactorial problems, represents a special challenge for the staff of the ED. The aim of this study is to improve the quality of the care for a special patient group. MATERIALS AND METHODS: A monocentric retrospective observation study was conducted at the University Hospital Bonn (UKB). On the basis of case studies, the emergency medical care of this special patient group was examined in the ED. RESULTS: Over the period of 7 years (2009 to 2016), 17 patients in a state of total neglect could be examined. The endpoints identified, during the emergency care, are the therapy of life-threatening diseases, laboratory pathologies, introduction of infectious protective measures, initiation of diagnostic measures, measures to be initiated within different departments (operating room, intensive care unit) and outcome. CONCLUSION: Patients in a state of total neglect require interdisciplinary primary care at a hospital with extended care structures. The apparent primary impression of these patients must not lead to a fixation error. Due to the often not obtainable history of the patient's and the complex appearance of these patients, the evaluation should be carried out according to a defined algorithm in the emergency room.


Assuntos
Serviços Médicos de Emergência , Serviço Hospitalar de Emergência , Atenção Primária à Saúde , Isolamento Social , Populações Vulneráveis , Emergências , Humanos , Estudos Retrospectivos
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