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[PMID]:28521880
[Au] Autor:Werumeus Buning J; Touw DJ; Brummelman P; Dullaart RPF; van den Berg G; van der Klauw MM; Kamp J; Wolffenbuttel BHR; van Beek AP
[Ad] Endereço:Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
[Ti] Título:Pharmacokinetics of oral hydrocortisone - Results and implications from a randomized controlled trial.
[So] Source:Metabolism;71:7-16, 2017 Jun.
[Is] ISSN:1532-8600
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:CONTEXT AND OBJECTIVE: This study aimed at comparing pharmacokinetics of two different doses of hydrocortisone (HC) in patients with secondary adrenal insufficiency (SAI). DESIGN, SETTING AND PATIENTS: Forty-six patients with SAI participated in this randomized double-blind crossover study. INTERVENTION: Patients received two different doses of HC (0.2-0.3mg HC/kg body weight/day and 0.4-0.6mg HC/kg body weight/day). MAIN OUTCOME MEASURES: One- and two-compartment population models for plasma free cortisol, plasma total cortisol and salivary cortisol were parameterized. The individual pharmacokinetic parameters clearance (CL), volume of distribution (V ), elimination half-life (t ), maximum concentration (C ), and area under the curve (AUC) were calculated. RESULTS: The one-compartment models gave a better description of the data compared to the two-compartment models. Weight-adjusted dosing reduced variability in cortisol exposure with comparable AUCs between weight groups. However, there was large inter-individual variation in CL and V of plasma free cortisol, plasma total cortisol and salivary cortisol. As a consequence, AUC varied more than 10 fold. Cortisol exposure was increased with the higher dose, but this was dose proportional only for free cortisol concentrations and not for total cortisol. CONCLUSIONS: Cortisol concentrations after a doubling of the dose were only dose proportional for free cortisol. HC pharmacokinetics can differ up to 10-fold inter-individually and individual adjustment of treatment doses may be necessary. Doubling of the HC dose in fast metabolizers (patients that showed relative low AUC and thus high clearance compared to other patients), does not result in significantly enhanced exposure during large parts of the day and these patients may need other management strategies.
[Mh] Termos MeSH primário: Insuficiência Adrenal/metabolismo
Hidrocortisona/farmacocinética
[Mh] Termos MeSH secundário: Adulto
Idoso
Área Sob a Curva
Estudos Cross-Over
Relação Dose-Resposta a Droga
Método Duplo-Cego
Feminino
Meia-Vida
Terapia de Reposição Hormonal
Seres Humanos
Hidrocortisona/sangue
Hidrocortisona/metabolismo
Masculino
Meia-Idade
Saliva/metabolismo
Albumina Sérica/análise
Transcortina/análise
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Serum Albumin); 9010-38-2 (Transcortin); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170520
[St] Status:MEDLINE


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[PMID]:28411181
[Au] Autor:Lewis JG; Elder PA
[Ad] Endereço:Steroid & Immunobiochemistry Laboratory, Canterbury Health Laboratories, Christchurch, New Zealand. Electronic address: john.lewis@cdhb.health.nz.
[Ti] Título:Monoclonal antibodies to the reactive centre loop (RCL) of human corticosteroid-binding globulin (CBG) can protect against proteolytic cleavage.
[So] Source:J Steroid Biochem Mol Biol;171:247-253, 2017 Jul.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Corticosteroid-binding globulin (CBG) binds most of the cortisol in circulation and is a non-functional member of the family of serine protease inhibitors (serpins) with an exposed elastase sensitive reactive centre loop (RCL). The RCL can be cleaved by human neutrophil elastase, released from activated neutrophils, and can also be cleaved at nearby site(s) by elastase released by Pseudomonas aeruginosa, and at two further sites, also within the RCL, by bovine chymotrypsin. Cleavage of the RCL results in a conformational change accompanied by a marked decrease in affinity for cortisol and hence its release at the site of proteolysis. These cleavages are irreversible and the similar half-lives of cleaved and intact CBG could mean that there may be some advantage in slowing the rate of CBG cleavage in acute inflammation thereby increasing the proportion of intact CBG in circulation. Here we show, for the first time, that pre-incubation of tethered human CBG with two monoclonal antibodies to the RCL of CBG protects against cleavage by all three enzymes. Furthermore, in plasma, pre-incubation with both RCL monoclonal antibodies delays neutrophil elastase cleavage of the RCL and one of these RCL monoclonal antibodies also delays bovine chymotrypsin cleavage of the RCL. These findings may provide a basis and rationale for the concept of the use of RCL antibodies as therapeutic agents to effectively increase the proportion of intact CBG in circulation which may be of benefit in acute inflammation.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Anticorpos Monoclonais/farmacologia
Elastase de Leucócito/metabolismo
Transcortina/antagonistas & inibidores
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/química
Anti-Inflamatórios não Esteroides/metabolismo
Anticorpos Monoclonais/química
Anticorpos Monoclonais/metabolismo
Especificidade de Anticorpos
Proteínas de Bactérias/metabolismo
Bovinos
Quimotripsina/metabolismo
Temperatura Baixa/efeitos adversos
Ensaio de Imunoadsorção Enzimática
Epitopos
Seres Humanos
Hidrocortisona/metabolismo
Proteínas Imobilizadas/antagonistas & inibidores
Proteínas Imobilizadas/química
Proteínas Imobilizadas/metabolismo
Cinética
Fragmentos de Peptídeos/antagonistas & inibidores
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/metabolismo
Domínios e Motivos de Interação entre Proteínas
Redobramento de Proteína
Proteólise/efeitos dos fármacos
Pseudomonas aeruginosa/enzimologia
Serina Endopeptidases/metabolismo
Transcortina/química
Transcortina/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antibodies, Monoclonal); 0 (Bacterial Proteins); 0 (Epitopes); 0 (Immobilized Proteins); 0 (Peptide Fragments); 0 (SERPINA6 protein, human); 9010-38-2 (Transcortin); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.1 (Chymotrypsin); EC 3.4.21.37 (Leukocyte Elastase); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170718
[Lr] Data última revisão:
170718
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170416
[St] Status:MEDLINE


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[PMID]:28041990
[Au] Autor:Basaraba CN; Westhoff CL; Pike MC; Nandakumar R; Cremers S
[Ad] Endereço:Department of Obstetrics and Gynecology and Epidemiology, Columbia University Medical Center, New York, NY, USA.
[Ti] Título:Estimating systemic exposure to levonorgestrel from an oral contraceptive.
[So] Source:Contraception;95(4):398-404, 2017 Apr.
[Is] ISSN:1879-0518
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-h steady-state area under the curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-h steady-state AUC of a particular OC. STUDY DESIGN: We conducted a 13-sample, 24-h pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30-mcg ethinyl estradiol and 150-mcg levonorgestrel (LNG) in 17 normal-weight healthy White women and a single-dose 9-sample study of the same OC after a 1-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes. RESULTS: The 13-sample steady-state 24-h LNG AUC was highly correlated with the steady-state 24-h trough value [r=0.95; 95% confidence interval (0.85, 0.98)] and with the steady-state 6-, 8-, 12- and 16-h values (0.92≤r≤0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-h AUC value [r=0.70; 95% CI (0.27, 0.90) and 0.77; 95% CI (0.40, 0.92), respectively]. CONCLUSIONS: Single time-point concentrations at steady state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects. IMPLICATIONS: A single time-point LNG concentration at steady state is an excellent proxy for complete and resource-intensive steady-state AUC measurement. The trough level after two single doses is a fair proxy for steady-state AUC. These results provide practical tools to facilitate large studies to investigate the relationship between systemic LNG exposure and side effects in a real-life setting.
[Mh] Termos MeSH primário: Área Sob a Curva
Anticoncepcionais Femininos/farmacocinética
Etinilestradiol/farmacocinética
Levanogestrel/farmacocinética
Globulina de Ligação a Hormônio Sexual/metabolismo
Transcortina/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Adulto
Estrogênios
Feminino
Seres Humanos
Progestinas
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contraceptive Agents, Female); 0 (Estrogens); 0 (Progestins); 0 (Sex Hormone-Binding Globulin); 423D2T571U (Ethinyl Estradiol); 5W7SIA7YZW (Levonorgestrel); 9010-38-2 (Transcortin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170103
[St] Status:MEDLINE


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[PMID]:28007663
[Au] Autor:Li Y; Sun Y; Krause JS; Li M; Liu X; Zhu W; Yao Y; Wu Y; Li D
[Ad] Endereço:Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life Sciences, Hebei Normal University, Shijiazhuang 050024, China.
[Ti] Título:Dynamic interactions between corticosterone, corticosteroid binding globulin and testosterone in response to capture stress in male breeding Eurasian tree sparrows.
[So] Source:Comp Biochem Physiol A Mol Integr Physiol;205:41-47, 2017 Mar.
[Is] ISSN:1531-4332
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In birds, corticosterone (CORT), testosterone (T), and corticosteroid binding globulin (CBG) are involved in modulating the trade-off between reproduction and survival. In response to acute stress, increased total plasma CORT is a ubiquitous phenomenon while T levels can decrease, or remain unchanged. Since CORT and T bind competitively with CBG in birds, the underlying regulatory mechanisms and consequences of their dynamic interactions remain largely unknown. Here, we studied the dynamic changes of total CORT, T, and CBG, and estimated free and bound CORT and T in response to capture stress in male Eurasian tree sparrows (Passer montanus) across the nest building, egg-laying, and nestling stages. We predicted that free, bound and total hormone concentrations would increase for CORT and decrease for T in response to acute stress, and the relative magnitude of these changes would vary with life history stage. We found that baseline and stressed-induced CORT values did not vary across breeding sub-stages. However, total and bound CORT increased with stress while free remained unchanged. Baseline levels of total, free and bound T were highest during the nest building and it was the only stage in which all measures of T were affected by stress. Regardless of breeding stage or restraint stress, we did not detect a significant correlation between CORT and T. CBG was found to be mostly unoccupied by steroid hormones under stress and stress-free conditions and this likely provided an adequate buffer for changes in free levels of CORT and T during unpredictable environmental perturbations.
[Mh] Termos MeSH primário: Proteínas Aviárias/sangue
Corticosterona/sangue
Pardais/sangue
Pardais/fisiologia
Testosterona/sangue
Transcortina/metabolismo
[Mh] Termos MeSH secundário: Animais
Cruzamento
China
Masculino
Estresse Fisiológico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Avian Proteins); 3XMK78S47O (Testosterone); 9010-38-2 (Transcortin); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161224
[St] Status:MEDLINE


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[PMID]:27887960
[Au] Autor:Nenke MA; Lewis JG; Rankin W; Shaw D; Torpy DJ
[Ad] Endereço:Endocrine and Metabolic Unit, Royal Adelaide Hospital, Adelaide, SA 5000, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5000, Australia. Electronic address: Marni.Nenke@health.sa.gov.au.
[Ti] Título:Corticosteroid-binding globulin cleavage may be pathogen-dependent in bloodstream infection.
[So] Source:Clin Chim Acta;464:176-181, 2017 Jan.
[Is] ISSN:1873-3492
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The process of enzymatic cleavage of high- to low-affinity corticosteroid-binding globulin (haCBG to laCBG) by neutrophil elastase leads to local tissue release of cortisol. Recently Pseudomonas aeruginosa was shown to instigate CBG cleavage with release of free cortisol in vitro. Hence, CBG cleavage with release of anti-inflammatory cortisol in infection may be pathogen-dependent. Our objective was to determine whether haCBG and laCBG levels are altered in infected patients compared with controls, and whether these alterations were particular to causative bacteria. DESIGN: An observational, cross-sectional study at a public pathology institution and tertiary hospital in Adelaide, South Australia. METHODS: 100 positive blood culture samples and 100 healthy control samples were analysed for serum total CBG, haCBG, laCBG, total and free cortisol, leukocyte and neutrophil count, C-reactive protein and Pitt severity score. RESULTS: Patients with infection had lower serum total CBG, haCBG and laCBG, all P<0.0001, than healthy controls. This was true in patients with and without a systemic inflammatory response and in those with culture-positive and culture-negative infections. Pseudomonas aeruginosa infection was associated with the lowest total and laCBG levels of the pathogen groups despite having the lowest inflammatory markers. CONCLUSIONS: There was evidence of CBG cleavage in early infection both in patients with and without systemic inflammation and regardless of culture status. Pseudomonas infection appeared to enhance cleavage. This observation, along with cleavage in severe neutropenia suggests mechanisms other than neutrophil elastase may be involved in CBG cleavage and local tissue cortisol release in infection.
[Mh] Termos MeSH primário: Bacteriemia/metabolismo
Proteólise
Infecções por Pseudomonas/metabolismo
Pseudomonas aeruginosa/fisiologia
Transcortina/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Bacteriemia/sangue
Proteína C-Reativa/metabolismo
Feminino
Seres Humanos
Hidrocortisona/sangue
Masculino
Meia-Idade
Neutrófilos/citologia
Infecções por Pseudomonas/sangue
Infecções por Pseudomonas/imunologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9007-41-4 (C-Reactive Protein); 9010-38-2 (Transcortin); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170208
[Lr] Data última revisão:
170208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161127
[St] Status:MEDLINE


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[PMID]:27561227
[Au] Autor:Edwards PD; Palme R; Boonstra R
[Ad] Endereço:Centre for the Neurobiology of Stress, Department of Biological Sciences, University of Toronto Scarborough, Toronto, Ontario M1C 1A4, Canada. Electronic address: phoebe.edwards@mail.utoronto.ca.
[Ti] Título:Seasonal programming, not competition or testosterone, drives stress-axis changes in a partially-semelparous mammal.
[So] Source:Horm Behav;85:96-101, 2016 Sep.
[Is] ISSN:1095-6867
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Animals must make tradeoffs between reproduction and longevity. This is particularly pronounced in male arctic ground squirrels (Urocitellus parryii), that compete aggressively for territories and mates during a three-week breeding season. Breeding males have high rates of severe wounding, high mortality rates, and high free cortisol levels, along with downstream consequences of chronic stress (weight loss, reduced immune function) that appear to contribute to their early death. The elevated cortisol levels are thought to be a result of the intense intrasexual competition. An alternative hypothesis, however, is that the hormonal change is a seasonal adaptation facilitating the tradeoff of immediate competitive advantage at the expense of long-term survival. We tested a two-part hypothesis: first, that elevated free cortisol during the breeding period is a seasonal change that will still occur in the absence of actual competition, and second, that testosterone maintains this increase. We measured plasma cortisol, corticosteroid-binding globulin, and fecal glucocorticoid metabolites in three groups: wild male ground squirrels, captive males prevented from fighting, and captive castrated males. There were no differences amongst these three groups in free and total plasma cortisol, fecal glucocorticoids, or downstream measures of chronic stress. This suggests that high free cortisol and its effects on breeding males are not a consequence of contest competition during the breeding season, but rather a generalized seasonal change. We found no evidence that testosterone plays a role in maintaining elevated free cortisol in arctic ground squirrel males.
[Mh] Termos MeSH primário: Comportamento Competitivo/fisiologia
Reprodução/fisiologia
Sciuridae
Estações do Ano
Estresse Psicológico/metabolismo
Estresse Psicológico/fisiopatologia
Testosterona/sangue
[Mh] Termos MeSH secundário: Adaptação Fisiológica/fisiologia
Agressão/fisiologia
Animais
Feminino
Hidrocortisona/metabolismo
Masculino
Sciuridae/metabolismo
Sciuridae/psicologia
Comportamento Social
Transcortina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
3XMK78S47O (Testosterone); 9010-38-2 (Transcortin); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160827
[St] Status:MEDLINE


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[PMID]:27418032
[Au] Autor:Hill LA; Bodnar TS; Weinberg J; Hammond GL
[Ad] Endereço:Department of Cellular and Physiological SciencesUniversity of British Columbia, Vancouver, British Columbia, Canada Department of Obstetrics and GynaecologyUniversity of British Columbia, Vancouver, British Columbia, Canada.
[Ti] Título:Corticosteroid-binding globulin is a biomarker of inflammation onset and severity in female rats.
[So] Source:J Endocrinol;230(2):215-25, 2016 Aug.
[Is] ISSN:1479-6805
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Plasma corticosteroid-binding globulin (CBG) plays a critical role in regulating glucocorticoid bioavailability and is an acute phase 'negative' protein during inflammation. In an adjuvant-induced arthritis model, plasma CBG levels decrease in rats that develop severe inflammation, and we have now determined when and how these reductions in CBG occur. After administering complete Freund's adjuvant or saline intra-dermally at the tail base, blood samples were taken periodically for 16days. In adjuvant-treated rats, decreases in plasma CBG levels matched the severity of inflammation, and decreases were observed 4days before any clinical signs of inflammation. Decreases in CBG levels coincided with an ~5kDa reduction in its apparent size, consistent with proteolytic cleavage, and cleaved CBG lacked steroid-binding activity. At the termination of the experimental period, hepatic Cbg mRNA levels were decreased in rats with severe inflammation. While plasma TNF-α increased in all adjuvant-treated rats, increases in Il-4, IL-6, IL-10, IL-13 and IFN-γ were only observed in rats with cleaved CBG. Rats with cleaved CBG also exhibited increased spleen weights, and strong negative correlations were observed among CBG, IL-6 and spleen weights, respectively. However, there were no differences in hepatic Cbg mRNA levels in relation to the apparent proteolysis of CBG, suggesting that CBG cleavage occurs before changes in hepatic Cbg expression. Our results indicate that the levels and integrity of plasma CBG are biomarkers of the onset and severity of inflammation. Dynamic changes in the levels and function of CBG likely modulate the tissue availability of corticosterone during inflammation.
[Mh] Termos MeSH primário: Inflamação/sangue
Transcortina/metabolismo
[Mh] Termos MeSH secundário: Animais
Biomarcadores/sangue
Peso Corporal
Citocinas/sangue
Feminino
Fígado/metabolismo
Proteólise
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 9010-38-2 (Transcortin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170801
[Lr] Data última revisão:
170801
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160716
[St] Status:MEDLINE
[do] DOI:10.1530/JOE-16-0047


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[PMID]:27411675
[Au] Autor:Henley D; Lightman S; Carrell R
[Ad] Endereço:Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA, Australia; Faculty of Medicine, Dentistry and Health Sciences, School of Medicine and Pharmacology, University of Western Australia, Crawley, WA, Australia.
[Ti] Título:Cortisol and CBG - Getting cortisol to the right place at the right time.
[So] Source:Pharmacol Ther;166:128-35, 2016 Oct.
[Is] ISSN:1879-016X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cortisol is transported in the blood by corticosteroid-binding globulin (CBG), a non-inhibitory member of the serpin family of serine protease inhibitors. Recent structural advances reveal how CBG acts as a releasing-agent as well as a carrier of cortisol. Taken together, the structures of the various forms of CBG and of the closely related thyroxine binding-globulin, show how the inherent conformational mechanism of the serpins has been adapted to modulate hormone release to the tissues by changes in binding affinities. A deduction from this, of the temperature dependence of hormone binding, is remarkably borne out with CBG, with a doubling in plasma free cortisol as the body temperature rises to 39°C. Another insight, against a dogma in the corticosteroid field, is that the proteolytic cleavage of CBG in inflammation results in a partial and not a complete loss of cortisol binding. This becomes of medical importance in conjunction with recent evidence of a pool of the circulating cleaved-form of CBG. It is now evident that tissue levels of free cortisol are buffered by two responsive plasma pools, intact CBG with a high binding-affinity and, particularly in inflammation and sepsis, a further pool of cleaved-CBG with a ten-fold lower affinity. The new molecular understandings, as well as providing insights into the differential release of circulating hormones, also open prospects for therapeutic interventions and draw attention to the potential of CBG and TBG as vehicles for the targeted delivery of drugs.
[Mh] Termos MeSH primário: Hidrocortisona/metabolismo
Transcortina/metabolismo
[Mh] Termos MeSH secundário: Temperatura Corporal
Sistemas de Liberação de Medicamentos/métodos
Liberação Controlada de Fármacos
Febre/fisiopatologia
Seres Humanos
Hidrocortisona/sangue
Inflamação/fisiopatologia
Ligação Proteica/fisiologia
Estrutura Quaternária de Proteína/fisiologia
Tiroxina/metabolismo
Globulina de Ligação a Tiroxina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Thyroxine-Binding Globulin); 9010-38-2 (Transcortin); Q51BO43MG4 (Thyroxine); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170731
[Lr] Data última revisão:
170731
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160715
[St] Status:MEDLINE


  9 / 1605 MEDLINE  
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[PMID]:27374762
[Au] Autor:Tilgar V; Mägi M; Lind M; Lodjak J; Moks K; Mänd R
[Ad] Endereço:Department of Zoology, Institute of Ecology and Earth Sciences, University of Tartu, Vanemuise 46, Tartu 51014, Estonia. Electronic address: vallo.tilgar@ut.ee.
[Ti] Título:Acute embryonic exposure to corticosterone alters physiology, behaviour and growth in nestlings of a wild passerine.
[So] Source:Horm Behav;84:111-20, 2016 Aug.
[Is] ISSN:1095-6867
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Maternally-derived glucocorticoids can modify the normal development of young animals. To date, little is known about maternal effects that are mediated by acute embryonic exposure to glucocorticoids. In birds, elevated maternal transmission of corticosterone (CORT) to egg albumen is mainly dependent on acute stress. In this study, we increased CORT levels in the egg albumen of a wild passerine, the great tit (Parus major), breeding in favourable deciduous and less suitable coniferous habitat. Subsequently we measured the somatic growth, baseline and acute glucocorticoid responses, immunity and behaviour of prenatally manipulated offspring with respect to control siblings. We found that prenatally CORT-exposed nestlings had lower baseline CORT levels, a more rapid decline in CORT during recovery from a standardized stressor, and a reduced heterophil/lymphocyte ratio compared with controls. Although stress-induced total CORT levels remained unchanged, free CORT levels were significantly lower and the levels of corticosteroid binding globulins (CBG) significantly higher in experimental offspring. Prenatally CORT-exposed offspring begged longer after hatching than controls. Stress-induced behavioural activity of fledglings did not differ between treatments, while its association with baseline CORT levels was significant in the control group only. The body mass and tarsus length of fledglings was positively affected by manipulation in unfavourable coniferous habitat only. We conclude that maternal effects related to elevated levels of albumen CORT modify diverse aspects of offspring phenotype and potentially increase offspring performance in resource poor environments. Moreover, our results indicate that maternal glucocorticoids may suppress the effect of hormones on behavioural responses.
[Mh] Termos MeSH primário: Comportamento Animal/efeitos dos fármacos
Corticosterona/farmacologia
Glucocorticoides/farmacologia
Passeriformes/fisiologia
[Mh] Termos MeSH secundário: Animais
Corticosterona/sangue
Ecossistema
Feminino
Fenótipo
Gravidez
Estresse Fisiológico/efeitos dos fármacos
Estresse Psicológico/metabolismo
Transcortina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Glucocorticoids); 9010-38-2 (Transcortin); W980KJ009P (Corticosterone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171003
[Lr] Data última revisão:
171003
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160705
[St] Status:MEDLINE


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[PMID]:27339896
[Au] Autor:Sumer-Bayraktar Z; Grant OC; Venkatakrishnan V; Woods RJ; Packer NH; Thaysen-Andersen M
[Ad] Endereço:From the Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales 2109, Australia and.
[Ti] Título:Asn347 Glycosylation of Corticosteroid-binding Globulin Fine-tunes the Host Immune Response by Modulating Proteolysis by Pseudomonas aeruginosa and Neutrophil Elastase.
[So] Source:J Biol Chem;291(34):17727-42, 2016 08 19.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Corticosteroid-binding globulin (CBG) delivers anti-inflammatory cortisol to inflamed tissues upon elastase-based proteolysis of the exposed reactive center loop (RCL). However, the molecular mechanisms that regulate the RCL proteolysis by co-existing host and bacterial elastases in inflamed/infected tissues remain unknown. We document that RCL-localized Asn(347) glycosylation fine-tunes the RCL cleavage rate by human neutrophil elastase (NE) and Pseudomonas aeruginosa elastase (PAE) by different mechanisms. NE- and PAE-generated fragments of native and exoglycosidase-treated blood-derived CBG of healthy individuals were monitored by gel electrophoresis and LC-MS/MS to determine the cleavage site(s) and Asn(347) glycosylation as a function of digestion time. The site-specific (Val(344)-Thr(345)) and rapid (seconds to minutes) NE-based RCL proteolysis was significantly antagonized by several volume-enhancing Asn(347) glycan features (i.e. occupancy, triantennary GlcNAc branching, and α1,6-fucosylation) and augmented by Asn(347) NeuAc-type sialylation (all p < 0.05). In contrast, the inefficient (minutes to hours) PAE-based RCL cleavage, which occurred equally well at Thr(345)-Leu(346) and Asn(347)-Leu(348), was abolished by the presence of Asn(347) glycosylation but was enhanced by sialoglycans on neighboring CBG N-sites. Molecular dynamics simulations of various Asn(347) glycoforms of uncleaved CBG indicated that multiple Asn(347) glycan features are modulating the RCL digestion efficiencies by NE/PAE. Finally, high concentrations of cortisol showed weak bacteriostatic effects toward virulent P. aeruginosa, which may explain the low RCL potency of the abundantly secreted PAE during host infection. In conclusion, site-specific CBG N-glycosylation regulates the bioavailability of cortisol in inflamed environments by fine-tuning the RCL proteolysis by endogenous and exogenous elastases. This study offers new molecular insight into host- and pathogen-based manipulation of the human immune system.
[Mh] Termos MeSH primário: Proteínas de Bactérias/imunologia
Interações Hospedeiro-Patógeno/imunologia
Hidrocortisona/imunologia
Elastase de Leucócito/imunologia
Proteólise
Pseudomonas aeruginosa/fisiologia
Transcortina/imunologia
[Mh] Termos MeSH secundário: Asparagina/imunologia
Glicosilação
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (SERPINA6 protein, human); 7006-34-0 (Asparagine); 9010-38-2 (Transcortin); EC 3.4.21.37 (Leukocyte Elastase); WI4X0X7BPJ (Hydrocortisone)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160625
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.735258



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