¿La Respuesta Psicofisiológica de Estrés-Relajación es la Misma en todas las Pacientes Sobrevivientes de Cáncer? / Is the Psychophysiological Stress-Relaxation Response the Same in all Cancer Survivors?

Resumen Un sobreviviente de cáncer padece continuamente manifestaciones autonómicas debidas a la enfermedad, su tratamiento oncológico, y el estrés psicológico con que se enfrenta continuamente. Una de las medidas psicofisiológicas utilizada para la valoración del estrés es la disminución de la temperatura periférica. En contraparte, los procedimientos psicológicos de relajación para el manejo de estrés buscan incrementar la temperatura. Sin embargo, se desconoce si esta respuesta es igual en todas pacientes. El objetivo de esta investigación fue examinar los cambios de temperatura durante un protocolo de estrés psicosocial y relajación en pacientes sobrevivientes de cáncer de mama. Adicionalmente, se evaluó el autorreporte de dolor y su interferencia con el funcionamiento psicosocial. Los resultados mostraron variaciones de temperatura periférica en las pacientes; sin embargo, no todas las pacientes presentaron el mismo patrón de temperatura, encontrando 3 subgrupos de pacientes, cuyas trayectorias lineales de temperatura permitieron generar un pronóstico afectivo para el manejo de estrés. Por autorreporte, no se encontraron diferencias psicosociales entre los subgrupos, aunque sí se encontró una asociación inversa entre la interferencia del sueño y la temperatura periférica. Se concluye que la temperatura periférica permite distinguir a las pacientes que se les dificulta el manejo del estrés psicosocial de aquellas que se benefician de los procedimientos psicológicos de relajación.

Abstract A cancer survivor continually suffers from autonomic manifestations due to the disease, their cancer treatment, and the psychological stress they continually face. One of the psychophysiological measures used to assess stress is the decrease in peripheral temperature. In contrast, psychological relaxation procedures for stress management seek to increase temperature. However, it is unknown if this response is the same in all patients. This research examined breast cancer survivors' temperature changes during psychosocial stress and relaxation protocol. Additionally, self-reported pain and its interference with psychosocial functioning were evaluated. The results showed peripheral temperature variations in the patients; however, not all patients presented with the same temperature pattern, finding three subgroups of patients whose linear temperature trajectories allowed generating an affective prognosis for stress management. By self-report, no psychosocial differences were found between the subgroups, although an inverse association between sleep interference and peripheral temperature was found. It is concluded that peripheral temperature distinguishes patients who find it challenging to manage psychosocial stress from those who benefit from psychological relaxation procedures.

Efectos psicofisiológicos de la respiración diafragmática y la estimulación térmica sobre la actividad autonómica del estrés agudo / Psychophysiological effects of diaphragmatic breathing and thermal stimulation on the autonomic activity of acute stress

Resumen Estudios recientes han evaluado los efectos psicofisiológicos del estrés agudo, la respiración diafragmática (RD) y la estimulación térmica cutánea. El paradigma Trier Social Stress Test (TSST) se ha utilizado como prueba de laboratorio para inducir estrés; sin embargo, no cuenta con una fase de reversiva activa de los efectos que induce. La presente investigación tuvo dos objetivos: 1) evaluar el efecto de la RD sobre la actividad autonómica simpática y la respuesta inflamatoria después del TSST para revertir sus efectos cardiovasculares; y 2) explorar el efecto de la estimulación térmica para inhibir la actividad autonómica durante y después del TSST. Se utilizó un diseño cuasi-experimental de medidas repetidas para cada objetivo. Participaron 22 estudiantes universitarios, normotensos y clínicamente sanos divididos en dos subgrupos de 11 participantes cada uno. Se aplicaron medidas psicométricas de distrés psicológico (PHQ-4, PC-PTSD), se registró su presión arterial, su tasa cardiaca, su temperatura nasal y en el dedo de la mano izquierda, así como una muestra salival de interleucina 6 (citoquina asociada a procesos inflamatorios sensible a la alteración física y afectiva del organismo). Aunque se igualaron las características sociodemográficas, debido al horario de registro de la presión arteiral en cada grupo y el periodo escolar de cada participante, las muestras no fueron comparables entre sí por lo que los datos se analizaron por separado para cada objetivo: al primer grupo se le administró el protocolo de TSST y después se les instruyó un ejercicio de RD; mientras que el segundo grupo sostuvo con las manos una compresa térmica a una temperatura aproximada de 41°C durante y después del TSST. Los resultados sugirieron que la RD disminuyó la actividad autonómica, pero no la inflamatoria; mientras que el grupo con estimulación térmica inhibió la actividad autonómica durante y después del TSST. Estos hallazgos se discuten en el contexto de la Teoría Polivagal como estrategias psicológicas para disminuir e inhibir los efectos psicofisiológicos del estrés agudo.

Abstract Recent studies have evaluated the psychophysiological effects of acute stress, diaphragmatic breathing (DB) and cutaneous thermal stimulation. The Trier Social Stress Test (TSST) paradigm has been used as a laboratory test to induce stress; however, it does not have an active reversal phase of the effects it induces. The present investigation had two objectives: 1) to evaluate the effect of DB on autonomic activity and inflammatory response after TSST; and 2) explore the effect of thermal stimulation to inhibit autonomic activity during and after TSST. A quasi-experimental design of repeated measures was used for each objective. Twenty-two university students, normotensive and clinically healthy participated. Psychometric measures of psychological distress (PHQ-4, PC-PTSD) were applied, their blood pressure, heart rate, nasal temperature and on the finger of the left hand were recorded, as well as a salivary sample of interleukin 6 (inflammatory sensitive cytokine to the physical and affective alteration of the organism). They were divided into two sub-groups of 11 participants each. The first group he was administered the TSST protocol and then they were instructed an DB exercise; while the second group held with their hands a thermal compress at a temperature of about 41 ° C during and after the TSST. The results suggested that DR decreased autonomic activity, but not inflammatory activity; while the group with thermal stimulation inhibited the autonomic activity during and after the TSST. These findings are discussed in the context of the Polivagal Theory as psychological strategies to diminish and inhibit the psychophysiological effects of acute stress.

La escucha de música antes del TSST regula los niveles de cortisol en saliva independiente de la preferencia musical en estudiantes universitarios / Listening to music before TSST modulates salivary cortisol levels in a nondependent way of music preference in college students

El presente estudio evaluó si la escucha de música preferida por los participantes o la música relajante elegida por los investigadores previa al protocolo de estrés social modificado TSST (Trier Social Stress Test) afectaba el desempeño de las actividades realizadas durante el propio test, modulaba la respuesta de estrés que este induce, y en conjunto con el estresor, afectaba el desempeño en una tarea de atención en setenta y seis estudiantes universitarios asignados a uno de seis grupos: música relajante del investigador, música preferida por el participante y silencio, con o sin TSST Los resultados mostraron que la escucha de ambos tipos de música provocó una pendiente ascendente menos pronunciada en los niveles de cortisol en saliva luego del TSST, comparada con la que presentaron quienes no escucharon música, mientras que el aumento en la ansiedad-estado evaluada con el IDARE (Inventario de Ansiedad Rasgo-Estado) fue semejante en todos los grupos. No se encontraron diferencias debidas a la música en el desempeño de las tareas evaluadas. Se discute que la modulación de la escucha de música, independiente de la preferencia musical, tiene un efecto sobre la respuesta fisiológica de estrés posiblemente por la inducción de reacciones emocionales que esta provoca.

The present study examines the effects of listening to music selected by participants or relaxing music chosen by researchers before modified TSST (Trier Social Stress Test) on: 1) TSST tasks, 2) TSST-induced stress responses, and 3) one attention task with both music and TSST before it. Seventy six college students were randomly assigned to one of six groups: listening to relaxing music chosen by researchers, previously selected music by students, or silence, any of them with or without TSST Results showed that both relaxing or selected-by-participant music slowed salivary cortisol increase levels after TSST, whereas STAI (State-Trait Anxiety Inventory) increases were not significantly different. Listening to music has no significant effects on either TSST or attention tasks. Effects of listening to music on salivary cortisol levels due to possible emotional responses irrespective of music preference were discussed.

Effect of curcumin on superantigen TSST-1 induced inflammatory cytokines by splenocytes / 中国人兽共患病学报

In the present study ,we aimed to observe the effect of curcumin on TSST-1-induced inflammatory cytokines in splenocytes of mouse and provide evidence for the further study on the effect of curcumin on inflammatory shock .Lactate de-hydrogenase (LDH) release assay was used to determine cytotoxicity of different doses of TSST-1 and curcumin .Inflammatory cytokines were determined by ELISA and flow cytometry .The doses of TSST-1 and curcumin we used in the present study did not cause significant cytotoxicity .TSST-1 induced higher level of IFN-γand IL-2 production but relatively lower level of TNF-α.The production of IL-1β,IL-6 and IL-12 was undetectable .TSST-1 induced Th1 cytokines (IFN-γand IL-2) were not IL-12-dependent which was different from LPS-induced IFN-γ.Curcumin significantly reduced IFN-γand TNF-αproduction at the concentration of 15 umol/L (P0 .05) .It’s suggested that curcumin could significantly inhibit the production of IFN-γand TNF-αby splenocytes induced by TSST-1 ,but could not affect the prolifera-tion of T cells .

Efecto de la exposición a un protocolo de estrés social agudo sobre los niveles sistémicos de cortisol y la ejecución de una tarea de atención sostenida y dividida / Efeito da exposição a um protocolo de estresse social agudo sobre os níveis sistêmicos de cortisol e a execução de uma tarefa de atenção sustentada e dividida / Effects of exposure to an acute social stress protocol on systemic levels of cortisol and on the execution of a sustained and divided attention task

La presente investigación tuvo como objetivo determinar los efectos del estrés social agudo inducido experimentalmente con una versión modificada del TSST (Trier Social Stress Test), en los niveles sistémicos de la hormona cortisol y en la ejecución de una tarea de atención sostenida y dividida, en estudiantes universitarios de ambos sexos. Los resultados mostraron que el protocolo modificado del TSST produjo incrementos en los niveles sistémicos de cortisol en los participantes de sexo masculino, pero no afectó la ejecución en la prueba PASAT (Paced Auditory Serial Addition Task). Se discuten estos resultados a la luz de trabajos previos en los que se observan diferencias por género en los efectos del estrés.

A presente pesquisa teve como objetivo determinar os efeitos do estresse social agudo induzido experimentalmente com uma versão modificada do TSST (Trier Social Stress Test), nos níveis sistêmicos do hormônio cortisol e na execução de uma tarefa de atenção sustentada e dividida, em estudantes universitários de ambos os sexos. Os resultados mostraram que o protocolo modificado do TSST produziu aumento nos níveis sistêmicos de cortisol nos participantes de sexo masculino, mas não afetou a execução na prova PASAT (Paced Auditory Serial Addition Task). Discutem-se esses resultados à luz de trabalhos prévios nos quais se observam diferenças por gênero nos efeitos do estresse.

This research project examined the effects of acute social stress induced experimentally with a modified version of TSST (Trier Social Stress Test) on the systemic levels of the cortisol hormone and on the execution of a sustained and divided attention task, in male and female university students. Results showed that the modified TSST protocol caused increases in the systemic levels of cortisol in male participants, but did not affect the execution of the PASAT (Paced Auditory Serial Addition Task). The results are discussed in the light of previous studies in which gender differences in the effects of stress are observed.

The use of mice as animal model for testing acute toxicity (LD-50) of toxic shock syndrome toxin / Utilização de camundongos como modelo animal para a verificação da toxicidade aguda da toxina-1 da síndrome do choque tóxico

Acute toxicity test (LD-50) using toxic shock syndrome toxin (TSST-1) was tested in BALB/c, C57BL/6 and Swiss mice. Animals (n = 10) were intraperitoneally injected with TSST-1 (0.01-10.0µg/mouse) followed 4h later by potentiating dose of lipopolysaccharide (75.0µg of LPS - E. coli O111:B4) and cumulative mortality was recorded over 72h. Control animals received either TSST-1 or LPS alone. The data were submitted to qui-Square test and acute toxicity test was calculated by probit analysis (confidence limits expressed as µg toxin/kg). BALB/c mice was the most sensitive (20.0µg/kg, 95 percent confidence limits: 9.0-92.0) followed by C57BL/6 (38.5µg/kg, 95 percent confidence limits: 9.11- 401.6). Data from Swiss mice was not conclusive, indicating only low sensitivity. Selection of the animal model and standardization of the experiment are fundamental for the development of serum neutralization tests used for final quality control of vaccine production.

A toxicidade aguda (DL-50) da toxina da síndrome do choque tóxico (TSST-1) foi testada em linhagens de camundongos BALB/c, C57BL/6 e Suíça. Os animais (n=10) inoculados intraperitoneal com doses crescentes de toxina (0,01 - 10,0µg/animal) receberam 4h após 75µg de LPS (E. coli O111: B4). A toxicidade aguda (DL50) foi observada por um período de 72h e os dados submetidos ao teste de qui- quadrado. Os resultados e os limites de confiança foram expressos em µg de toxina/kg. A linhagem BALB/c apresentou maior sensibilidade (20µg/kg - limite de confiança a 95 por cento entre 9,0- 92,0), seguida da C57BL/6 (38,5µg/kg - limite de confiança a 95 por cento entre 9,11 - 401,6). A amplitude dos limites de confiança deve-se à natureza da toxina, ao mecanismo de ação, a via de inoculação e ao animal utilizado. A seleção do modelo animal e a padronização do experimento são fundamentais para o desenvolvimento de testes de soro neutralização para fins de controle de qualidade do processo de produção de vacinas.

Produção de enterotoxinas e da toxina da síndrome do choque tóxico por cepas de Staphylococcus aureus isoladas na mastite bovina / Production of enterotoxins and toxic shock syndrome toxin by Staphylococcus aureus strains isolated from bovine mastitis

A total of 72 strains of Staphylococcus aureus were examined for the production of staphylococcal enterotoxins (SE) A, B, C, D and toxic shock syndrome toxin (TSST-1). The strains were isolated from milk samples from cows with mastitis in dairy herds of São Paulo State, Brazil. Off 72 isolates, 38 (52.8 percent) produced SEA, 38 (52.8 percent) SEB, 32 (44.4 percent) SED, 28 (38.9 percent) SEC and 27 (37.5 percent) TSST-1. From the 72 strains, 66 (91.7 percent) produced, at least, one or more toxin, including TSST-1

Inhibitory Effects of Dexamethasone on Production IL-1alpha and TNF-alpha in Peripheral Blood Mononuclear Cells

PURPOSE: IL-1alpha and TNF-alpha have a seminal role in the intial events of inflammation. An area of intense interest is the assessment of new therapeutic modalities that regulate inflammatory response in acute bacterial infection. We conducted this study to compare the inhibitory effects of dexamethasone on the secretion of proinflammatory cytokines, such as IL-lalpha and TNF-alpha from cord blood mononuclear cells(MC) to those of adult blood MC during stimulation with S. aureus TSST-1 and E. coli LPS. METHODS: MC were isolated by differential centrifugation on Ficoll-Hypaque gradients. Each MC were incubated with TSST-1(2ug/ml) or LPS(0.2ug/ml), with various concentrations of dexamethasone for 72hr. And the other MC were incubated with TSST-1 or LPS, using the same concentration of dexamethasone, which was added 4hr before or simultaneously or 4hr, 24hr, 48hr after the stimulation. Concentration of IL-1alpha and TNF-alpha was measured by ELISA kit. RESULTS: Dexamethasone showed significant inhibitory effects on secretion of IL-1alpha and TNF-alpha. In comparison with both cytokines, secretion of IL-1alpha was suppressed more severely than TNF-alpha. In comparison with each stimulators, inhibition of TSST-1 induced cytokines production was greater than LPS. There was no difference between adult and cord blood MC. When dexamethasone was added to MC 4hr before the stimulation, it had the best inhibitory effects on the production of proinflammatory cytokines. CONCLUSION: Proinflammatory cytokine production in cord and adult blood MC were inhibited by dexamethasone in a dose-dependent manner. Early treatment of dexamethasone is more effective and can be used for modulating or suppressing excessive proinflammatory cytokine production in acute bacterial infection.

Inhibitory Effects of Actinomycin-D and Pentoxifylline on the Production of IL-1alpha and TNF-alpha by Human Cord and Adult Blood Mononuclear Cells

PURPOSE: An area of intense intrest is assessment of new therapeutic modalities that regulate the inflammatory response in acute bacterial infection is proving to be an area of interest these days. So we conducted this study to compare the inhibitory effects of actinomycin-D and pentoxifylline on the production of IL-lalpha and TNF-alpha from cord blood mononuclear cells (MC) to those from adult blood MC stimulated with S. aureus toxic shock syndrome toxin (TSST)-1 and E. coli lipopolysaccharide (LPS). METHODS: Cord and adult blood MC were isolated by differential centrifugation on Ficoll-Hypaque gradients. Each mononuclear cells were incubated with TSST-1 (2 microgram/ml) or LPS (0.2 microgram/ml), simultaneously with various concentrations of actinomycin-D or pentoxifylline added for inhibition. Concentration of interleukin-1alpha (IL-lalpha) and tumor necrosis factor-alpha (TNF-alpha) were measured by means of ELISA. RESULTS: In comparison with each inhibitory drug, actinomycin-D showed more potent inhibitory effects on the production of IL-1alpha and TNF-alpha from adult and cord blood MC stimulated by TSST-1 and LPS, than pentoxifylline (P<0.05). There was no difference between adult and cord blood MC. In comparison with each stimulator, inhibition of TSST-1 induced cytokines production with actinomycin-D was greater than pentoxifylline, in contrast to inhibition of LPS induced cytokines production with pentoxifylline which was greater than actinomycin-D in adult blood MC (P<0.05). CONCLUSION: Proinflammatory cytokine production in cord and adult blood MC were inhibited by each drug in the same manner except, the inhibition of pentoxifylline for LPS in cord blood MC. So it is possible that these drugs can be used to modulate or suppress excessive proinflammatory cytokine production in acute bacterial infection.

Mechanism of Toxic Shock Syndrome Toxin-1 as a Superantigen / 감염

BACKGROUND: Staphylococcus aureus TSST-1 is a microbial superantigen which requires interaction between MHC class II molecules and T-cell receptors. To characterize the mechanism of TSST-1 as a superantigen, we investigated the influence of TSST-1 on the binding of T-cell receptor and MHC II. METHODS: For control, A20 cells and lymphocytes from healthy volunteers were measured by the IL-2 bioassay with or withtout TSST-1, which was then purified and confirmed using immunoblot. mRNA for TNF from PBMC was prepared and RT-PCR for mRNA expression was performed. RESULTS: When stimulated by TSST-1(100pg/ mL), lymphocytes produced 135microgram/ml of IL-2 compared to the control A20 cells which produced 5microgram/ ml of 1L-2. TSST-1 was confirmed to be the strong inducer for mRNA expression by RT-PCR. CONCLUSION: The binding to T-cell receptor was enhanced by TSST-1 as confirmed by the bioassay of IL-2. This data may contribute to the understanding of mechanism of cell-toxin interaction.

Production of Interleukin-1alpha and Tumor Necrosis Factor-alpha by Human Cord and Adult Blood Mononuclear Cells Stimulated by TSST-1 and LPS

PURPOSE: Immature immunological defens mechanism in the neonate may contribute to the high susceptibility to overwhelming sepsis. S. aureus TSST-1 and E. coli LPS known as one of the important pathogens of septic shock or toxic shock induce massive release of various cytokines, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1alpha (IL-1alpha) produced from peripheral blood mononuclear cells (PBMC). In contrast, limited information has been provided so far concerning the capacity of cytokine production from neonatal immune cells. METHODS: This study was conducted to compare the secretion of proinflammatory cytokines, such as IL-l and TNF-alpha from cord blood PBMC to those from adult blood PBMC stimulated by S. aureus TSST-1 and E. coli LPS. RESULTS: 1) IL 1-alpha was secreted in a time-dependent manner from cord & adult blood PBMC stimulated with several cytokine inducers, and LPS stimulated adult & cord blood PBMC secreted IL 1-alpha in a dose-dependent manner. 2) TNF-alpha secretion from cord blood PBMC stimulated with LPS and IFN- significantly decreased in a time dependent manner, but not from adult PBMC. And secretion of TNF- from cord blood PBMC reached the highest level 24 hours after stimulated with LPS or IFN-gamma. The secretion of TNF-alpha from adult blood PBMC showed similar pattern to those from cord blood PBMC, but higher than cord blood PBMC. 3) IL-1alpha & TNF-alpha secretion from cord & adult blood PBMC stimulated with TSST-1 had no significant difference except in TNF- secretion by TSST-1 at 96 hours. 4) The secretion of IL-1alpha from adult PBMC stimulated with LPS showed higher and longer than that from cord blood PBMC. 5) IL-1alpha & TNF-alpha secretion from cord & adult blood PBMC stimulated with IFN-gamma had no significant difference. CONCLUSIONS: In summary, proinflammatory cytokines such as IL-1alpha, TNF-alpha in cord blood PBMC were secreted in a time dependent manner, but the amounts of IL-1alpha and TNF-alpha secretion were lesser than those of adult blood PBMC, especially stimulated by LPS. These results suggest that increased susceptibility to infection in neonatal period may be partially from a functional immaturity of cord blood mononuclear cells.