RESUMEN

Este livro foi construído com o objetivo de analisar, discutir e divulgar a atualidade das ações que contemplam a interprofissionalidade, os avanços e desafios em construção no âmbito do Programa de Educação pelo Trabalho para a Saúde PET-Saúde/Interprofissionalidade ­ 2018/2021, desenvolvido na Universidade Federal de São Paulo nos campus Baixada Santista e Diadema e na Faculdade de Ciências Médicas de Santos (FCMS/UNILUS). O desafio proposto no livro é discutir o referencial que ampara a interprofissionalidade, sua importância nas abordagens humanizadoras em saúde e as experiências com diferentes grupos populacionais na formação universitária diferenciada. O livro abrange ações dos grupos PET amparadas em discussões que acontecem com diferentes temáticas atuais como a interprofissionalidade na atuação com população que frequenta a Atenção Básica, a Saúde da Família, população em situação de rua, população com necessidades especiais no âmbito da reabilitação, população gestante e população que se utiliza das práticas integrativas. Os capítulos do livro abordam as experiências vivas destes grupos PET/Saúde inseridos em diferentes municípios. Trata-se de realidades territoriais diferentes, mas com condições comuns no que se refere à desigualdade social, às necessidades de serviços nos quais os profissionais desenvolvem a escuta e o cuidado em saúde e necessitam de estruturas adequada para a gestão em saúde. Neste contexto, a atuação dos grupos PET/Saúde Interprofissionalidade emerge como um grande desafio ao propor um olhar diferenciado para as relações entre profissionais no caminho da construção de uma atuação que, além de se pautar na humanização e integralidade das ações, seja amparada na decisão de atuação que surge de uma construção comum, ou seja, "inter" profissionais e entre profissionais. Um compartilhar de conhecimentos que tem potencial de transformar ações em saúde. Os capítulos do livro emergem de um diálogo interprofissional entre docentes tutoras (es), preceptoras(es) do PET/Saúde Interprofissionalidade e estudantes.

Asunto(s)

RESUMEN

O Programa de Educação pelo Trabalho para Saúde (PET-Saúde) é uma política indutora que fomenta o aprendizado por vivências problematizadoras nos locais de trabalho em saúde com foco na interprofissionalidade. O objetivo do presente trabalho foi relatar a experiência do PET-Saúde Interprofissionalidade durante a pandemia de Covid-19, na perspectiva docente. Desenvolver o PET-Saúde com estudantes, preceptores, equipes dos serviços e usuários demandou (re)descobrir possibilidades das tecnologias de informação e comunicação e o aprendizado da produção de "novas presenças" sem desistir da ação coletiva, participativa e composta pelos diferentes saberes. Apreendeu-se o desenvolvimento de competências como escuta qualificada para resolução de conflitos, comunicação interprofissional e liderança colaborativa. Este PET-Saúde mostrou-se um disparador na formação em saúde, conectando universidade, rede de saúde e comunidade; e contribuindo para o desenvolvimento de competências colaborativas e um espaço de acolhimento para as situações vivenciadas.(AU)

El Programa de Educación por el Trabajo para Salud (PET-Saúde) es una política inductora que fomenta el aprendizaje por vivencias problematizadoras en los locales de trabajo en salud con enfoque en la Interprofesionalidad. El objetivo fue relatar la experiencia del PET-Saúde Interprofesionalidad durante la pandemia de Covid-19, desde la perspectiva docente. Desarrollar el PET-Saúde con estudiantes, preceptores, equipos de los servicios y usuarios demandó (re)descubrir posibilidades de las tecnologías de información y comunicación, aprendiendo a producir "nuevas presencias", sin desistir de la acción colectiva, participativa, compuesta por los diferentes saberes. Se aprendió a desarrollar competencias tales como escuchar de forma calificada para la resolución de conflictos, la comunicación interprofesional y el liderazgo colaborativo. Este PET-Saúde se mostró un gatillo en la formación en salud, conectando universidad, red de salud y comunidad, contribuyendo al desarrollo de competencias colaborativas y un espacio de acogida para las situaciones vividas.(AU)

The Program 'Education through Work for Health' (PET-Health) is a nudging policy that provides learning through problematizing experiences in health workplaces, with a focus on interprofessionality. The aim was to report the experience of PET-Health Interprofessionality during the Covid-19 pandemic, from the teachers' perspective. The development of PET-Health with students, tutors, teams from the health system and users demanded, (re) discovering possibilities of information and communication technologies, learning to produce "new presences", without giving up the collective, participatory action, composed by different knowledge. There was learning of development of skills such as qualified listening for conflict resolution, interprofessional communication and collaborative leadership. This PET-Health proved to be a triggering event towards health education, connecting university, health network and community, and contributed to the development of collaborative skills and constituted a welcoming space for the situations experienced.(AU)

Asunto(s)

RESUMEN

OBJECTIVE: To assess the relationships between serum dehydroepiandrosterone sulfate (DHEA-S) levels and heart rate variability (HRV) among different age groups. SUBJECTS AND METHODS: Forty-five healthy men were divided into 3 groups: young age (YA; 20-39 yrs; n = 15), middle age (MA; 40-59 yrs; n = 15) and old age (OA; ≥ 60 yrs; n = 15). Hemodynamic parameters, linear analyses of HRV and concentrations of cortisol and DHEA-S were measured at rest. RESULTS: The OA group presented a higher resting heart rate (84.3 ± 4.6 bpm) than the YA group (72.0 ± 4.4 bpm; p < 0.05). The YA group showed an attenuated variance of HRV (2235.1 ± 417.9 ms2) compared to the MA (1014.3 ± 265.2 ms2; p < 0.05) and OA (896.3 ± 274.1 ms2; p < 0.05) groups, respectively. The parasympathetic modulation of HRV was lower in both the MA (244.2 ± 58.0 ms2) and OA (172.8 ± 37.9 ms2) groups in comparison with the YA group (996.0 ± 255.4 ms2; p < 0.05), while serum DHEA-S levels were significantly lower in both the MA (91.2 ± 19.6 mg/dL) and OA (54.2 ± 17.7 mg/dL) groups compared to the YA group (240.0 ± 50.8 mg/dL; p < 0.05). A positive correlation between lower serum concentrations of DHEA-S and attenuated variance of HRV (r = 0.47, p = 0.031), as well as lower serum concentrations of DHEA-S and decreased parasympathetic modulation of HRV (r = 0.54, p = 0.010), were found. CONCLUSION: The present study demonstrated that the decline of plasma DHEA-S is associated with reduced cardiac autonomic modulation during the aging process.

Asunto(s)

RESUMEN

ABSTRACT Objective: To assess the relationships between serum dehydroepiandrosterone sulfate (DHEA-S) levels and heart rate variability (HRV) among different age groups. Subjects and methods: Forty-five healthy men were divided into 3 groups: young age (YA; 20-39 yrs; n = 15), middle age (MA; 40-59 yrs; n = 15) and old age (OA; ≥ 60 yrs; n = 15). Hemodynamic parameters, linear analyses of HRV and concentrations of cortisol and DHEA-S were measured at rest. Results: The OA group presented a higher resting heart rate (84.3 ± 4.6 bpm) than the YA group (72.0 ± 4.4 bpm; p < 0.05). The YA group showed an attenuated variance of HRV (2235.1 ± 417.9 ms2) compared to the MA (1014.3 ± 265.2 ms2; p < 0.05) and OA (896.3 ± 274.1 ms2; p < 0.05) groups, respectively. The parasympathetic modulation of HRV was lower in both the MA (244.2 ± 58.0 ms2) and OA (172.8 ± 37.9 ms2) groups in comparison with the YA group (996.0 ± 255.4 ms2; p < 0.05), while serum DHEA-S levels were significantly lower in both the MA (91.2 ± 19.6 mg/dL) and OA (54.2 ± 17.7 mg/dL) groups compared to the YA group (240.0 ± 50.8 mg/dL; p < 0.05). A positive correlation between lower serum concentrations of DHEA-S and attenuated variance of HRV (r = 0.47, p = 0.031), as well as lower serum concentrations of DHEA-S and decreased parasympathetic modulation of HRV (r = 0.54, p = 0.010), were found. Conclusion: The present study demonstrated that the decline of plasma DHEA-S is associated with reduced cardiac autonomic modulation during the aging process.

Asunto(s)

RESUMEN

Grapes are fruits that grow in clusters and can be crimson, black, dark blue, yellow, green, orange, and pink. Cadmium is a non-essential metal toxic to living organisms and the environment. Recently, health professionals, food scientists, and consumers have paid much attention to grapes for their health-promoting effects. To the best of our knowledge, there are no reviews describing the ability of grapes to mitigate the toxic effects induced by cadmium exposure in different tissues and/or organs. Herein, the aim of this review is to present the effects of grapes following cadmium exposure on the number of papers published in the scientific literature. The results showed that grapes are able to mitigate the harmful activities induced by exposure to cadmium in several tissues and organs. The main actions are closely related to tissue regeneration as a result of the reestablishment of morphology and antioxidant activity. However, further studies are welcomed in order to elucidate new biological pathways regarding the outcomes promoted by grapes in this context, specially related to inflammation, tissue regeneration and cellular death.

Asunto(s)

RESUMEN

BACKGROUND: Alterations in the structure of resistance vessels contribute to elevated systemic vascular resistance in hypertension and are linked to sympathetic hyperactivity and related lesions in target organs. OBJECTIVE: To assess the effects of exercise training on hemodynamic and autonomic parameters, as well as splenic arteriolar damages in male Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). METHODS: Normotensive sedentary (WKYS) and trained (WKYT) rats, and hypertensive sedentary (SHRS) and trained (SHRT) rats were included in this study. After 9 weeks of experimental protocol (swimming training or sedentary control), arterial pressure (AP) and heart rate (HR) were recorded in freely moving rats. We assessed the autonomic control of the heart by sympathetic and vagal autonomic blockade. Morphometric analyses of arterioles were performed in spleen tissues. The statistical significance level was set at p < 0.05. RESULTS: Resting bradycardia was observed in both trained groups (WKYT: 328.0 ± 7.3 bpm; SHRT: 337.0 ± 5.2 bpm) compared with their respective sedentary groups (WKYS: 353.2 ± 8.5 bpm; SHRS: 412.1 ± 10.4 bpm; p < 0.001). Exercise training attenuated mean AP only in SHRT (125.9 ± 6.2 mmHg) vs. SHRS (182.5 ± 4.2 mmHg, p < 0.001). The WKYT showed a higher vagal effect (∆HR: 79.0 ± 2.3 bpm) compared with WKYS (∆HR: 67.4 ± 1.7 bpm; p < 0.05). Chronic exercise decreased sympathetic effects on SHRT (∆HR: -62.8 ± 2.8 bpm) in comparison with SHRS (∆HR: -99.8 ± 9.2 bpm; p = 0.005). The wall thickness of splenic arterioles in SHR was reduced by training (332.1 ± 16.0 µm2 in SHRT vs. 502.7 ± 36.3 µm2 in SHRS; p < 0.05). CONCLUSIONS: Exercise training attenuates sympathetic activity and AP in SHR, which may be contributing to the morphological improvement of the splenic arterioles.

Asunto(s)

RESUMEN

Abstract Background: Alterations in the structure of resistance vessels contribute to elevated systemic vascular resistance in hypertension and are linked to sympathetic hyperactivity and related lesions in target organs. Objective: To assess the effects of exercise training on hemodynamic and autonomic parameters, as well as splenic arteriolar damages in male Wistar Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Methods: Normotensive sedentary (WKYS) and trained (WKYT) rats, and hypertensive sedentary (SHRS) and trained (SHRT) rats were included in this study. After 9 weeks of experimental protocol (swimming training or sedentary control), arterial pressure (AP) and heart rate (HR) were recorded in freely moving rats. We assessed the autonomic control of the heart by sympathetic and vagal autonomic blockade. Morphometric analyses of arterioles were performed in spleen tissues. The statistical significance level was set at p < 0.05. Results: Resting bradycardia was observed in both trained groups (WKYT: 328.0 ± 7.3 bpm; SHRT: 337.0 ± 5.2 bpm) compared with their respective sedentary groups (WKYS: 353.2 ± 8.5 bpm; SHRS: 412.1 ± 10.4 bpm; p < 0.001). Exercise training attenuated mean AP only in SHRT (125.9 ± 6.2 mmHg) vs. SHRS (182.5 ± 4.2 mmHg, p < 0.001). The WKYT showed a higher vagal effect (∆HR: 79.0 ± 2.3 bpm) compared with WKYS (∆HR: 67.4 ± 1.7 bpm; p < 0.05). Chronic exercise decreased sympathetic effects on SHRT (∆HR: -62.8 ± 2.8 bpm) in comparison with SHRS (∆HR: -99.8 ± 9.2 bpm; p = 0.005). The wall thickness of splenic arterioles in SHR was reduced by training (332.1 ± 16.0 µm2 in SHRT vs. 502.7 ± 36.3 µm2 in SHRS; p < 0.05). Conclusions: Exercise training attenuates sympathetic activity and AP in SHR, which may be contributing to the morphological improvement of the splenic arterioles.

Resumo Fundamento: Alterações na estrutura dos vasos de resistência contribuem para elevar a resistência vascular sistêmica na hipertensão, estando ligadas à hiperatividade simpática e lesões em órgãos-alvo. Objetivo: Avaliar os efeitos do treinamento físico nos parâmetros hemodinâmicos e autônomos, assim como as lesões arteriolares esplênica em ratos machos Wistar Kyoto (WKY) e espontaneamente hipertensos (SHR). Métodos: Ratos normotensos sedentários (WKYS) e treinados (WKYT), e ratos hipertensos sedentários (SHRS) e treinados (SHRT) foram incluídos neste estudo. Após nove semanas de aplicação do protocolo experimental (treinamento de natação ou controle sedentário), registraram-se a pressão arterial (PA) e a frequência cardíaca (FC) dos ratos em movimento livre. Avaliamos o controle autônomo do coração através de bloqueio autônomo simpático e vagal. Análises morfométricas das arteríolas esplênicas foram realizadas. Adotou-se o nível de significado estatístico de p < 0,05. Resultados: Observou-se bradicardia de repouso nos dois grupos treinados (WKYT: 328,0 ± 7,3 bpm; SHRT: 337,0 ± 5,2 bpm) em comparação aos seus respectivos grupos sedentários (WKYS: 353,2 ± 8,5 bpm; SHRS: 412,1 ± 10,4 bpm; p < 0,001). O treinamento físico atenuou a PA média apenas no grupo SHRT (125,9 ± 6,2 mmHg vs. 182,5 ± 4,2 mmHg no SHRS; p < 0,001). O grupo WKYT mostrou maior efeito vagal (∆FC: 79,0 ± 2,3 bpm) em comparação ao grupo WKYS (∆FC: 67,4 ± 1,7 bpm; p < 0,05). Exercício crônico diminuiu os efeitos simpáticos em SHRT (∆FC: -62.8 ± 2.8 bpm) em comparação a SHRS (∆FC: -99,8 ± 9,2 bpm; p = 0,005). A espessura da parede das arteríolas esplênicas nos SHR foi reduzida pelo treinamento (332,1 ± 16,0 µm2 nos SHRT vs. 502,7 ± 36,3 µm2 nos SHRS; p < 0,05). Conclusões: O treinamento físico atenua a atividade simpática e a PA em SHR, o que pode contribuir para melhorar a morfologia das arteríolas esplênicas.

Asunto(s)

RESUMEN

Abstract Background: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. Objective: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. Methods: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. Results: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). Discussion: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. Conclusion: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats.

Resumo Fundamento: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. Objetivo: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. Métodos: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. Resultados: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). Discussão: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. Conclusão: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

Asunto(s)

RESUMEN

BACKGROUND:: Isotonic blood volume expansion (BVE) induced alterations of sympathetic and parasympathetic activity in the heart and blood vessels, which can be modulated by serotonergic pathways. OBJECTIVE:: To evaluate the effect of saline or serotonergic agonist (DOI) administration in the hypothalamic paraventricular nucleus (PVN) on cardiovascular responses after BVE. METHODS:: We recorded pulsatile blood pressure through the femoral artery to obtain the mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), heart rate (HR) and the sympathetic-vagal ratio (LF/HF) of Wistar rats before and after they received bilateral microinjections of saline or DOI into the PVN, followed by BVE. RESULTS:: No significant differences were observed in the values of the studied variables in the different treatments from the control group. However, when animals are treated with DOI followed by BVE there is a significant increase in relation to the BE control group in all the studied variables: MBP (114.42±7.85 vs 101.34±9.17); SBP (147.23±14.31 vs 129.39±10.70); DBP (98.01 ±4.91 vs 87.31±8.61); HR (421.02±43.32 vs 356.35±41.99); and LF/HF ratio (2.32±0.80 vs 0.27±0.32). DISCUSSION:: The present study showed that the induction of isotonic BVE did not promote alterations in MAP, HR and LF/HF ratio. On the other hand, the injection of DOI into PVN of the hypothalamus followed by isotonic BVE resulted in a significant increase of all variables. CONCLUSION:: These results suggest that serotonin induced a neuromodulation in the PVN level, which promotes an inhibition of the baroreflex response to BVE. Therefore, the present study suggests the involvement of the serotonergic system in the modulation of vagal reflex response at PVN in the normotensive rats. FUNDAMENTO:: Expansão de volume extracelular (EVEC) promove alterações da atividade simpática e parassimpática no coração e vasos sanguíneos, os quais podem ser moduladas por vias serotoninérgicas. OBJETIVO:: Avaliar o efeito da administração de salina ou agonista serotoninérgico (DOI) nos núcleos paraventriculares hipotalâmico (NPV) sobre respostas cardiovasculares após EVEC. MÉTODOS:: Foram obtidos registros da pressão arterial pulsátil, por meio da artéria femoral, para obtenção dos valores da pressão arterial média (PAM), sistólica (PAS), diastólica (PAD), frequência cardíaca (FC) e razão simpático-vagal (LF/HF) de ratos Wistar antes e após receberem microinjeções bilaterais no NPV de salina ou DOI seguida de EVEC. RESULTADOS:: Não foram observadas diferenças significativas dos valores das variáveis estudadas nos diferentes tratamentos do grupo controle. Entretanto, quando os animais são tratados com DOI seguida de EVEC ocorre aumento significativo em relação ao grupo controle com EVEC em todas as variáveis estudadas: PAM (114,42±7,85 vs 101,34±9,17), PAS (147,23±14,31 vs 129,39±10,70), PAD (98,01 ±4,91 vs 87,31±8,61), FC (421,02±43,32 vs 356,35±41,99) e LF/HF (2,32±0,80 vs 0,27±0,32). DISCUSSÃO:: O presente estudo mostrou que a indução de EVEC isotônica não promoveu alterações na PAM, PAD, PAS, FC e LF/HF. Por outro lado, os animais que receberam microinjeção de DOI no NPV seguida de EVEC apresentaram aumento significativo de todas as variáveis. CONCLUSÃO:: Esses resultados sugerem que a serotonina exerce uma neuromodulação em nivel do NPV, e essa promove uma inibição da resposta barorreflexa frente à EVEC. Assim, o presente trabalho sugere o envolvimento serotoninérgico na neuromodulação no nivel do NPV na resposta reflexa vagal em ratos normotensos.

Asunto(s)

RESUMEN

AIMS: We evaluated whether exercise training ameliorates cardiovascular autonomic dysfunction in obesity-induced by high-fat diet (HFD) in rats. METHODS Wistar male rats were assigned in normal diet, sedentary (ND-S) and trained (ND-T) and HFD, sedentary (HFD-S) and trained (HFD-T). Blood pressure (BP), heart rate (HR), HR variability (HRV), BP variability (BPV), cardiac baroreflex and cardiac autonomic tonus were assessed. HFD-S showed higher bodyweight increase (19.4%) compared to all other groups (HFD-T: 13.2%, ND-S: 14% and ND-T: 12.4%). Relative epididymal, retroperitoneal and visceral fat was also greater in HFD-S compared to all other groups. Resting bradycardia in ND-T (339.5±10.6 bpm) and HFD-T (341.0 ± 9.4 bpm) was more pronounced than ND-S (438.4 ± 6.3 bpm; p<0.05) and HFD-S (448.5 ± 18.7 bpm; p<0.05). The HFD-T group showed lower systolic (125.3 ( 1.9 mmHg), diastolic (88.5 ( 2.0 mmHg) and mean BP (100.3 ± 2.5 mmHg) in comparison with HFD-S (153.8 ( 3.7; 103.5 ( 2.6 and 120.5 ± 3.7 mmHg; p<0.05, respectively). Lower variance of HRV and higher variance of diastolic BPV was observed in HFD-S compared to other groups while sympathetic modulation of HRV and BPV was higher in HFD-S, as well as the LF/HF ratio. HFD-T showed a decrease in sympathetic tonus compared to HFD-S. ND-T and HFD-T showed higher cardiac vagal tonus than respective sedentary groups. Analysis showed an association between visceral fat, sympathetic activity and BP. CONCLUSIONS: HFD induces hypertension and is associated with autonomic imbalance in rats, while exercise training may reverse these harmful changes.(AU)

Asunto(s)

RESUMEN

Glucocorticoids (GC) represent the main treatment for pemphigus; however, some patients show GC resistance. GC sensitivity was evaluated in 19 pemphigus patients and 41 controls by the number of binding sites [B(max) (fmol/mg protein)] and the affinity of GC receptor [Kd (nM)] to dexamethasone (DEX) as well as by the pattern of cytokine by DEX-mediated inhibition of concanavalin-A (Con-A)-stimulated PBMC proliferation. The Kd (15.7 ± 2.8 vs.8.1 ± 1.3) and Bmax (6.5 ± 0.9 vs. 3.9 ± 0.3) were higher in pemphigus than controls (p = 0.002). Considering the values above the 95th percentile of normal group as a cut-off (K(d) > 24.9 nM and B(max) > 8.1 fmol/mg protein), elevated K(d) and B(max) were observed in 9.8% and 2.4% of controls and 15.8% and 36.8% of patients (p = 0.02). PBMC proliferation was stimulated by Con-A and inhibited by DEX (p < 0.001) in both pemphigus and control groups. IL-6 and TNFα (pg/mL) basal production were higher in patients than controls. There was an increment of these cytokines after Con-A stimulation, and they were inhibited by DEX (p = 0.002) in controls and remained elevated in pemphigus (p < 0.02). Patients and controls showed no difference in basal and stimulated production of IL-8 and IL-10. There is an alteration on GC sensitivity in pemphigus patients and a higher production of proinflammatory cytokines. Therefore, in pemphigus patients, proinflammatory cytokines might be involved in the mechanism of GC resistance and/or in its maintenance.

Asunto(s)

RESUMEN

CONTEXT: Interindividual variation and tissue specificity of glucocorticoid (GC) sensitivity may occur in healthy subjects. OBJECTIVE AND PARTICIPANTS: The objective of this study was to evaluate the GC sensitivity in 40 healthy young subjects (21 women and 19 men; 22-42 yr old). DESIGN: We measured salivary and plasma cortisol levels before and after the administration of 0.25, 0.5, and 1 mg dexamethasone (DEX), given at 2300 h. We also evaluated the pattern of DEX-mediated inhibition of concanavalin A-stimulated peripheral blood mononuclear cell proliferation using different DEX doses, the number of binding sites, and the affinity of the GC receptor (Kd). RESULTS: The increasing DEX doses resulted in a dose-dependent decrease in cortisol levels. The majority of the subjects (70%) suppressed cortisol with DEX doses lower than 0.5 mg, and two did not suppress even with 1 mg DEX. The binding capacity was 4.1 +/- 0.3 fmol/mg protein, and the Kd was 8.1 +/- 1.3 nm. Four individuals presented with elevated Kd. Peripheral blood mononuclear cell proliferation was inhibited by DEX in a dose-dependent pattern. The median IC50 value was 7.1 x 10(-7) mol/liter. We found 77.5% (31 of 40) concordance among all three tests; 29 subjects showed all parameters between the 10th and 90th percentiles (P10-P90), one above P90, and one below P10. These two subjects could be classified as more GC resistant or sensitive, respectively. No concordance between in vivo and in vitro tests in two subjects suggested a tissue-specific sensitivity. CONCLUSIONS: This is the first report that, taking advantage of three bioassays performed on the same subject, demonstrated a considerable interindividual variability and tissue-specific GC sensitivity in a young healthy population.

Asunto(s)