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1.
Mil Med ; 184(5-6): e298-e302, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30371879

RESUMO

INTRODUCTION: Low distal aortic flow via partial aortic occlusion (AO) may mitigate ischemia induced by resuscitative endovascular balloon occlusion of the aorta (REBOA). We compared endocrine effects of a novel simulated partial AO strategy, endovascular variable aortic control (EVAC), with simulated REBOA in a swine model. MATERIALS AND METHODS: Aortic flow in 20 swine was routed from the supraceliac aorta through an automated extracorporeal circuit. Following liver injury-induced hemorrhagic shock, animals were randomized to control (unregulated distal flow), simulated REBOA (no flow, complete AO), or simulated EVAC (distal flow of 100-300 mL/min after 20 minutes of complete AO). After 90 minutes, damage control surgery, resuscitation, and full flow restoration ensued. Critical care was continued for 4.5 hours or until death. RESULTS: Serum angiotensin II concentration was higher in the simulated EVAC (4,769 ± 624 pg/mL) than the simulated REBOA group (2649 ± 429) (p = 0.01) at 180 minutes. There was no detectable difference in serum renin [simulated REBOA: 231.3 (227.9-261.4) pg/mL; simulated EVAC: 294.1 (231.2-390.7) pg/mL; p = 0.27], aldosterone [simulated EVAC: 629 (454-1098), simulated REBOA: 777 (575-1079) pg/mL, p = 0.53], or cortisol (simulated EVAC: 141 ± 12, simulated REBOA: 127 ± 9 ng/mL, p = 0.34) concentrations between groups. CONCLUSIONS: Simulated EVAC was associated with higher serum angiotensin II, which may have contributed to previously reported cardiovascular benefits. Future studies should evaluate the renal effects of EVAC and the concomitant therapeutic use of angiotensin II.


Assuntos
Aorta/cirurgia , Oclusão com Balão/efeitos adversos , Sistema Endócrino/enzimologia , Aldosterona/análise , Aldosterona/sangue , Angiotensina II/análise , Angiotensina II/sangue , Animais , Aorta/enzimologia , Oclusão com Balão/métodos , Modelos Animais de Doenças , Sistema Endócrino/irrigação sanguínea , Hidrocortisona/análise , Hidrocortisona/sangue , Renina/análise , Renina/sangue , Estatísticas não Paramétricas , Suínos
2.
J Appl Toxicol ; 37(8): 902-912, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28186326

RESUMO

The study of vascular modulation has received a great deal of attention in recent years as knowledge has increased around the role of angiogenesis within disease contexts such as cancer. Despite rapidly expanding insights into the molecular processes involved and the concomitant generation of a number of anticancer vascular modulating chemotherapeutics, techniques used in the measurement of structural vascular change have advanced more modestly, particularly with regard to the preclinical quantification of off-target vascular regression within systemic, notably endocrine, blood vessels. Such changes translate into a number of major clinical side effects and there remains a need for improved preclinical screening and analysis. Here we present the generation of a novel structural biomarker, which can be incorporated into a number of contemporary image analysis platforms and used to compare tumour versus systemic host tissue vascularity. By contrasting the measurements obtained, the preclinical efficacy of vascular modulating chemotherapies can be evaluated in light of the predicted therapeutic window. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Inibidores da Angiogênese/farmacologia , Sistema Endócrino/irrigação sanguínea , Processamento de Imagem Assistida por Computador , Neoplasias Pulmonares/irrigação sanguínea , Microvasos/efeitos dos fármacos , Neovascularização Patológica/patologia , Animais , Feminino , Neoplasias Pulmonares/patologia , Camundongos Endogâmicos C57BL , Camundongos Nus , Microvasos/patologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Nat Rev Endocrinol ; 10(9): 530-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25048037

RESUMO

Systemic administration of antiangiogenic drugs that target components of the vascular endothelial growth factor A (VEGF-A; VEGF) signal transduction pathway has become a viable therapeutic option for patients with various types of cancer. Nevertheless, these drugs can drive alterations in healthy vasculatures, which in turn are associated with adverse effects in healthy tissues. VEGF is crucial for vascular homeostasis and the maintenance of vascular integrity and architecture in endocrine organs. Given these critical physiological functions, systemic delivery of drugs that target VEGF signalling can block VEGF-mediated vascular functions in endocrine organs, such as the thyroid gland, and lead to endocrine dysfunction, including hypothyroidism, adrenal insufficiency and altered insulin sensitivity. This Review discusses emerging evidence from preclinical and clinical studies that contributes to understanding the mechanisms that underlie the vascular changes and subsequent modulations of endocrine function that are induced by targeted inhibition of VEGF signalling. Understanding these mechanisms is crucial for the design of antiangiogenic drugs with minimal associated adverse effects that will enable effective treatment of patients with cancer.


Assuntos
Neoplasias/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/fisiologia , Indutores da Angiogênese/farmacologia , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Animais , Sistema Endócrino/irrigação sanguínea , Inibidores Enzimáticos/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Humanos , Hipotireoidismo/induzido quimicamente , Terapia de Alvo Molecular , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
4.
Med Tr Prom Ekol ; (3): 11-5, 2013.
Artigo em Russo | MEDLINE | ID: mdl-23785822

RESUMO

The article presents results of the evaluation the changes in the relationships between immune and endocrine systems in reproductive-age women, working under exposure to chemical factors from activated carbon production. A significant increase of some chemical elements and compounds was found in blood that was associated with changes in the endocrine and immune status, as well as the presence of features in correlation parameters of these systems in reproductive-age women, working under exposure to chemical factors.


Assuntos
Poluentes Atmosféricos , Indústria Química , Doenças Profissionais/sangue , Exposição Ocupacional/efeitos adversos , Adolescente , Adulto , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/sangue , Poluentes Atmosféricos/imunologia , Análise Química do Sangue , Carbono/sangue , Carbono/envenenamento , Sistema Endócrino/irrigação sanguínea , Sistema Endócrino/efeitos dos fármacos , Feminino , Humanos , Sistema Imunitário/irrigação sanguínea , Sistema Imunitário/efeitos dos fármacos , Pessoa de Meia-Idade , Doenças Profissionais/imunologia , Federação Russa , Recursos Humanos , Adulto Jovem
5.
J Mol Endocrinol ; 47(2): R59-66, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21622530

RESUMO

Hormones are dynamically collected by fenestrated capillaries to generate pulses, which are then decoded by target tissues to mount a biological response. To generate hormone pulses, endocrine systems have evolved mechanisms to tightly regulate blood perfusion and oxygenation, coordinate endocrine cell responses to secretory stimuli, and regulate hormone uptake from the perivascular space into the bloodstream. Based on recent findings, we review here the mechanisms that exist in endocrine systems to regulate blood flow, and facilitate coordinated cell activity and output under both normal physiological and pathological conditions in the pituitary gland and pancreas.


Assuntos
Células Endócrinas/metabolismo , Sistema Endócrino/irrigação sanguínea , Sistema Endócrino/metabolismo , Animais , Sistema Endócrino/citologia , Humanos , Pâncreas/irrigação sanguínea , Pâncreas/citologia , Pâncreas/metabolismo , Hipófise/irrigação sanguínea , Hipófise/citologia , Hipófise/metabolismo
6.
Eur J Neurosci ; 32(12): 2087-95, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21143663

RESUMO

The pulsatile release of hormone is obligatory for the control of a range of important body homeostatic functions. To generate these pulses, endocrine organs have developed finely regulated mechanisms to modulate blood flow both to meet the metabolic demand associated with intense endocrine cell activity and to ensure the temporally precise uptake of secreted hormone into the bloodstream. With a particular focus on the pituitary gland as a model system, we review here the importance of the interplay between blood flow regulation and oxygen tensions in the functioning of endocrine systems, and the known regulatory signals involved in the modification of flow patterns under both normal physiological and pathological conditions.


Assuntos
Oxigênio/sangue , Adeno-Hipófise/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Animais , Sistema Endócrino/irrigação sanguínea , Sistema Endócrino/metabolismo , Humanos , Consumo de Oxigênio , Pressão Parcial , Adeno-Hipófise/citologia , Hormônios Adeno-Hipofisários/metabolismo
8.
Ann N Y Acad Sci ; 1014: 50-7, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15153419

RESUMO

Angiogenesis is the focus of therapeutic efforts to promote new vessel development in damaged tissues. Conversely, inhibiting endothelial cell growth and survival is a strategy to treat various proliferative diseases. Much evidence indicates that VEGF is a key mediator of angiogenesis. Recently, a novel angiogenic mitogen with tissue-specific expression and target selectivity was characterized. Human endocrine gland derived vascular endothelial growth factor (EG-VEGF) is selectively expressed in steroidogenic glands and promotes growth of endocrine gland endothelium. The identification of tissue-selective angiogenic factors raises the possibility that other secreted molecules in this class exist. The potential advantage of tissue-specific angiogenic therapeutics may be the reduction of systemic side effects. Additionally, these peptides or their receptors may be attractive targets for inhibition in several disorders.


Assuntos
Sistema Endócrino/irrigação sanguínea , Neovascularização Fisiológica/fisiologia , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/genética , Fator de Crescimento do Endotélio Vascular Derivado de Glândula Endócrina/metabolismo , Sistema Endócrino/citologia , Células Endoteliais/citologia , Células Endoteliais/fisiologia , Humanos
9.
Microsc Res Tech ; 60(1): 98-106, 2003 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-12500266

RESUMO

Formation of new blood vessels occurs in many physiological states (during development of the embryo, cycling changes of the female reproductive tract), as well as in pathological processes (such as diabetic retinopathy and wound healing). Angiogenesis has been shown to be related to tumor formation, prognosis, and response to treatment in many tumor types. Intratumoral microvessels can be related to tumor behavior or hormone secretion in different endocrine tumors. For example, invasive prolactinomas are more vascular than noninvasive adenomas; a surgical approach is more successful in macroprolactinomas with lower microvessel density. A higher number of microvessels have been found in papillary thyroid carcinomas during recurrences. A correlation between microvessel count and prognosis in papillary and medullary thyroid carcinomas has been suggested. Several stimulating and inhibiting factors involved in the regulation of angiogenesis have been identified. Among them, vascular endothelial growth factor (VEGF) has been shown to be critically involved in angiogenesis and also in the neovascularization of solid tumors. Dopamine agonists (already in clinical use for prolactinomas) have potent inhibitory actions on VEGF signaling, and thus may be a new tool in antiangiogenic therapy. Secretion of VEGF in the great majority of human pituitary adenomas is inhibited by dexamethasone. This suggests that glucocorticoids can be considered in the treatment of certain pituitary tumors. The cyclic nature of angiogenesis in the female reproductive tract indicates that stimulation or inhibition of paracrine angiogenic factors may lead to new approaches for being able to influence reproductive endocrine disorders. Experimental and clinical aspects of interactions between angiogenic factors and tumor growth of the endocrine system are also discussed.


Assuntos
Sistema Endócrino , Neovascularização Patológica/fisiopatologia , Neovascularização Fisiológica/fisiologia , Inibidores da Angiogênese/uso terapêutico , Animais , Sistema Endócrino/irrigação sanguínea , Sistema Endócrino/patologia , Sistema Endócrino/fisiologia , Sistema Endócrino/fisiopatologia , Fatores de Crescimento Endotelial/antagonistas & inibidores , Fatores de Crescimento Endotelial/metabolismo , Feminino , Humanos , Camundongos , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/fisiopatologia
10.
J Comp Neurol ; 449(4): 390-404, 2002 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-12115674

RESUMO

Using a sensitive immunohistochemical technique, the localization of neuropeptide Y (NPY) Y1-receptor (Y1R)-like immunoreactivity (LI) was studied in various peripheral tissues of rat. Wild-type (WT) and Y1R-knockout (KO) mice were also analyzed. Y1R-LI was found in small arteries and arterioles in many tissues, with particularly high levels in the thyroid and parathyroid glands. In the thyroid gland, Y1R-LI was seen in blood vessel walls lacking alpha-smooth muscle actin, i.e., perhaps in endothelial cells of capillaries. Larger arteries lacked detectable Y1R-LI. A distinct Y1R-immunoreactive (IR) reticulum was seen in the WT mouse spleen, but not in Y1R-KO mouse or rat. In the gastrointestinal tract, Y1R-positive neurons were observed in the myenteric plexus, and a few enteroendocrine cells were Y1R-IR. Some cells in islets of Langerhans in the pancreas were Y1R-positive, and double immunostaining showed coexistence with somatostatin in D-cells. In the urogenital tract, Y1R-LI was observed in the collecting tubule cells of the renal papillae and in some epithelial cells of the seminal vesicle. Some chromaffin cells of adrenal medulla were positive for Y1R. The problem of the specificity of the Y1R-LI is evaluated using adsorption tests as well as comparisons among rat, WT mouse, and mouse with deleted Y1R. Our findings support many earlier studies based on other methodologies, showing that Y1Rs on smooth muscle cells of blood vessels mediate NPY-induced vasoconstriction in various organs. In addition, Y1Rs in other cells in parenchymal tissues of several organs suggest nonvascular effects of NPY via the Y1R.


Assuntos
Músculo Liso Vascular/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Animais , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/ultraestrutura , Sistema Digestório/irrigação sanguínea , Sistema Digestório/metabolismo , Sistema Digestório/ultraestrutura , Sistema Endócrino/irrigação sanguínea , Sistema Endócrino/metabolismo , Sistema Endócrino/ultraestrutura , Feminino , Gânglios Autônomos/irrigação sanguínea , Gânglios Autônomos/metabolismo , Gânglios Autônomos/ultraestrutura , Sistema Linfático/irrigação sanguínea , Sistema Linfático/metabolismo , Sistema Linfático/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/ultraestrutura , Neurônios/química , Neurônios/ultraestrutura , Especificidade de Órgãos/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de Neuropeptídeo Y/deficiência , Receptores de Neuropeptídeo Y/genética , Receptores de Neuropeptídeo Y/ultraestrutura , Pele/irrigação sanguínea , Pele/metabolismo , Pele/ultraestrutura , Traqueia/irrigação sanguínea , Traqueia/metabolismo , Traqueia/ultraestrutura , Sistema Urogenital/irrigação sanguínea , Sistema Urogenital/metabolismo , Sistema Urogenital/ultraestrutura
11.
Bull Cancer ; 86(2): 148-53, 1999 Feb.
Artigo em Francês | MEDLINE | ID: mdl-10066945

RESUMO

Endocrine tumors are characteristically hypervascularized. This property recalls that of normal endocrine tissues, which possess a dense and specialized capillary network. The cellular and molecular mechanisms of the angiogenesis process associated with endocrine tumorigenesis are poorly known. Most normal endocrine cells constituvely express high levels of angiogenic factors, such as VEGF, which likely play an important role in the development of the characteristic vascular architecture of normal endocrine tissues. Clinical and experimental data suggest that a surexpression of such angiogenic factors is unlikely to be involved in the induction of the angiogenic process associated with endocrine tumorigenesis. In contrast, according to some experimental observations, the loss of endocrine-specific anti-angiogenic factors may be required for the initiation of the angiogenic process and the transition from endocrine hyperplasia to endocrine neoplasia. Such inhibitory factors remain to be identified and characterized. A better understanding of the mechanisms of angiogenesis in endocrine tumors is important for the delineation of novel therapeutic strategies.


Assuntos
Neoplasias das Glândulas Endócrinas/irrigação sanguínea , Neovascularização Patológica/patologia , Animais , Capilares/anatomia & histologia , Divisão Celular , Sistema Endócrino/irrigação sanguínea , Fatores de Crescimento Endotelial/metabolismo , Endotélio Vascular/citologia , Humanos , Linfocinas/metabolismo , Camundongos , Camundongos Transgênicos , Neovascularização Patológica/tratamento farmacológico , Neoplasias Pancreáticas/irrigação sanguínea , Fator de Crescimento Transformador alfa/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular
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