Problemas bioéticos en la investigación de nuevas vacunas: ¿obedecen a razones de salud pública? / Bioethical problems in researching new vaccines: Do they respond to public health reasons?

Los problemas éticos de las investigaciones sobre vacunas han crecido en las últimas décadas en frecuencia y magnitud debido a la posición dominante de la industria farmacéutica en el desarrollo de esos estudios. Las tradicionales cuestiones de seguridad y eficacia se han visto agravadas por el conflicto de intereses introducido por la competencia comercial en un mercado a escala global de miles de millones de dólares. La integridad profesional de los investigadores, la responsabilidad moral de los patrocinadores, y la regulación y control por parte de los Estados nacionales, se muestra cuestionada en varios ejemplos. Los resultados de estos cambios son las amenazas a la protección de los derechos de las personas incluidas en estas investigaciones y el discutible progreso que resulta para la salud pública.

The ethical problems in vaccine research have grown in frequency and magnitude in last decades, due to the dominant place of the pharmaceutical industry in the development of such studies. Traditional issues of security and efficacy have been aggravated by the conflicts of interests introduced by commercial competition in a global market worth billions of dollars. We present here a few examples in which the professional integrity of researchers, the moral responsibility of sponsors, and the public regulation and control by national States are put into question. The consequences of these changes represent serious threats to the rights of people included in these studies as well as disputable progress for public health.

Psychological stress alters the ultrastructure and increases IL-1β and TNF-α in mandibular condylar cartilage

Psychological factors can be correlated with temporomandibular disorders (TMDs), but the mechanisms are unknown. In the present study, we examined the microstructural changes and expression of proinflammatory cytokines in mandibular condylar cartilage of the temporomandibular joint (TMJ) in a psychological stress animal model. Male Sprague-Dawley rats (8 weeks old, 210 ± 10 g) were randomly divided into 3 groups: psychological stress (PS, N = 48), foot shock (FS, N = 24), and control (N = 48). After inducing psychological stress using a communication box with the FS rats for 1, 3, or 5 weeks, PS rats were sacrificed and compared to their matched control littermates, which received no stress and were killed at the same times as the PS rats. Body and adrenal gland weight were measured and corticosterone and adrenocorticotropic hormone levels were determined by radioimmunoassay. After hematoxylin-eosin staining for histological observation, the ultrastructure of the TMJ was examined by scanning electron microscopy. Transcription and protein levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were evaluated by ELISA and semi-quantitative RT-PCR. The PS group showed a significantly higher adrenal gland weight after 3 weeks of stress and higher hormone levels at weeks 1, 3, and 5. Histopathological changes and thinning cartilage were apparent at weeks 3 and 5. In the PS group, TNF-α increased at 1, 3, and 5 weeks and IL-1β increased significantly after 1 and 3 weeks of stress, and then decreased to normal levels by 5 weeks. Psychological stress increased plasma hormone levels and RT-PCR indicated increased IL-1β and TNF-α expression in the TMJ in a time-dependent manner. These results suggest that cytokine up-regulation was accompanied by stress-induced cartilage degeneration in the mandibular condyle. The proinflammatory cytokines play a potential role in initiating the cartilage destruction that eventually leads to the TMDs.

Wound-healing and benzodiazepines: does sleep play a role in this relationship?

Patients who have suffered burns frequently experience psychological consequences, among which anxiety disorders are prominent. Benzodiazepines are commonly administered to treat these symptoms. The effects of benzodiazepines on healing may not be direct but rather are modulated by alterations of the sleep architecture. This hypothesis is supported by studies that demonstrate the effects of benzodiazepines on the immune system and the inflammatory profile under both normal sleep conditions and during sleep deprivation, particularly rapid eye movement sleep deprivation.

Reference range for T lymphocytes populations in blood donors from two different regions in Brazil

This study defined the normal variation range for different subsets of T-lymphocyte cells count in two different Brazilian regions. We analysed the T-lymphocytes subpopulations (CD3+, CD4+, CD8+) in blood donors of two Brazilian cities, located in North (Belem, capital state of Para, indian background) and Northeast (Salvador, capital state od Bahia, African background) regions of Brazil. Results were compared according to gender, stress level (sleep time lower than 8 hours/day), smoking, and alcohol intake. Lymphocytes subpopulations were measured by flow cytometry. Five hundred twenty-six blood donors from two Brazilians cities participated in the study: 450 samples from Bahia and 76 samples from Pará. Most (60 percent) were men, 59 percent reported alcohol intake, 12 percent were smokers, and 80 percent slept at least 8 h/day. Donors from Bahia presented with significantly higher counts for all parameters, compared with Para. Women had higher lymphocytes levels, in both states, but only CD4+ cells count was significantly higher than men's values. Smokers had higher CD4+ counts, but sleep time had effect on lymphocytes levels only for Para's donors (higher CD3+ and CD4+ counts). That state had also, a higher proportion of donors reporting sleep time <8 h/day. The values for CD3, CD4 and CD8+ cells count were significantly higher in blood donors from Bahia than among those from Pará. Female gender, alcohol intake, stress level, and smoking were associated with higher lymphocyte counts. The use of a single reference range for normal lymphocytes count is not appropriate for a country with such diversity, like Brazil is.

Neuroimunomodulação: sobre o diálogo entre os sistemas nervoso e imune / Neuroimmunomodulation: the cross-talk between nervous and immune systems

OBJETIVO: Trabalhos de pesquisa provenientes do campo da neuroimunomodulação vêm tornando explícitas as intrincadas relações existentes entre o sistema nervoso central e o sistema imune. Uma revisão bibliográfica foi realizada com o objetivo de descrever as bases de estudo da neuroimunomodulação. MODELOS EXPERIMENTAIS: Sabe-se, hoje, que estados emocionais como ansiedade e depressão são capazes de modificar a atividade do sistema imune como também o fazem o estresse e fármacos com ação no sistema nervoso central. COMPORTAMENTO DOENTIO: Os comportamentos apresentados por um organismo doente devem ser encarados como decorrência de estratégias homeostáticas de cada indivíduo. POSSÍVEIS MECANISMOS DE SINALIZAÇÃO DO SISTEMA IMUNE PARA O SISTEMA NERVOSO CENTRAL: Grande destaque tem sido atribuído para a participação do eixo hipotálamo-pituitária-adrenal, do sistema nervoso autônomo simpático e das citocinas nas sinalizações entre o sistema nervoso central e o sistema imune. CONCLUSÃO: O presente artigo pretende mostrar a relevância dos fenômenos de neuroimunomodulação; ele faz uma análise crítica das influências do sistema nervoso central sobre o sistema imune e vice-versa.

OBJECTIVE: Several papers arriving from the neuroimmunomodulation field are showing the relevant relationships between the nervous and the immune systems. A review of studies was carried out to describe the bases of the studies on neuroimmunomodulation. EXPERIMENTAL MODELS: It is clear nowadays that emotional states such as anxiety and depression change immune system activity, an affect also observed after both stress and use of nervous system acting drugs. SICK BEHAVIOR: The behavior displayed by sick organisms might be thought as being a consequence of homeostatic strategies. POSSIBLE MECHANISM OF THE ACTION BY MEANS OF IMMUNE SYSTEM TO NERVOUS SYSTEM: A very big emphasis is being given to Hipothalamus-pituitary-adrenal axis, simpathetic nervous system and cytokines participation on nervous system and immune system relationships. CONCLUSION: The present revision intend to show some essential studies in the neuroimmunomodulation field; it makes a critical analysis of the mutual relationships between nervous system and immune system.

Effect of Self-Foot Reflexology massage on Depression, Stress Responses and Immune Functions of Middle Aged Women / 간호학회지

PURPOSE: This study was aimed to identify the effects of a self-foot reflexology massage on depression, stress responses and functions of the immune system of middle-aged women. METHOD: This study was a one group pretest-posttest experimental design and the data was collected from August 1st, 2004 to May 31st, 2005. The subjects consisted of 46 middle-aged women (40 - 64 years) who were recruited from the Community Health Center in Busan city. Subjects were not treated for 4 weeks, subsequently they were trained in self foot reflexology massage for 2 weeks, and then they did their own daily for 6weeks (2 days at the research center, 5 days at home).The outcome variables were measured 4 times, at baseline, pre training, after training, and after the intervention. The collected data was analyzed using repeated measure ANOVA by the SPSS/WIN program. RESULT: There was a statistically significant difference in depression, perceived stress, systolic blood pressure, natural-killer cells and Ig G. However, there was not a statistically significant difference in dyastolic blood pressure, pulse or serum cortisol. CONCLUSION: These results suggest that a self-foot reflexology massage could be utilized as an effective nursing intervention to reduce depression and stress responses, and to strengthen immune systems in middle-aged women.

Attenuation of the effect of progesterone and 4'-chlordiazepam on stress-induced immune responses by bicuculline.

The present study investigates the effect of progesterone, a pregnane precursor of neurosteroids, and 4'-chlordiazepam (4'-CD), a specific ligand for mitochondrial diazepam binding inhibitor receptor (MDR) involved in neurosteroidogenesis, on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses. RS produced a significant reduction in anti-sheep red blood cells (SRBC) antibody titre, a measure of humoral immune response, and % leucocyte migration inhibition (LMI) and foot-pad thickness test, measures of cell-mediated immune responses. These effects of RS on immune responses were effectively blocked by pretreating the animals with progesterone (10 mg/kg, sc) or 4'-CD (0.5 mg/kg, sc) administered just before subjecting the animal to RS. The effect of both progesterone and 4'-CD on RS-induced immune modulation was significantly attenuated by bicuculline (2 mg/kg, ip) but not by flumazenil (10 mg/kg, ip). Unlike its effect on RS-induced immune responsiveness, progesterone (5, 10 mg/kg, sc) when administered to non-stressed animals produced a significant suppression of both humoral and cell-mediated immune responses which was not reversed by bicuculline. However, 4'-CD failed to modulate immune response in naive non-stressed animals. These results suggest that progesterone and 4'-CD affect stress-induced immune responses by modulating GABA-ergic mechanism. However, GABA-A receptor system does not appear to be involved in progesterone-induced immunosuppression in nonstressed animals.

Presentación de cinco casos de linfocitopenia CD4+ idiopática / Report of five cases of idiopathic CD4+ lymphocytopenia

Introducción: el objetivo de este trabajo es llamar la atención sobre una inmunodeficiencia recientemente descripta y ofrecer una propuesta de estudio y tratamiento. Material y métodos: período de estudio: enero de 1998 a agosto de 2000. Presentamos 5 pacientes de entre 23 y 86 años de edad (media 51,2 años), todos de sexo femenino, que fueron estudiadas por presentar infecciones a repetición (micóticas, virales y bacterianas). Se les realizó determinación de VIH por ELISA, pruebas cutáneas para antígenos habitualmente reconocidos por el organismo, medición de linfocitos CD4+ y CD8+ por partículas magnéticas. Proteinograma electroforético, dosaje de inmunoglobulinas plasmáticas por inmunodifusión radial. Se efectuó tratamiento con timomodulina 60 mg por día. Conclusiones: al momento del diagnóstico se observó: pruebas cutáneas hipoérgicas, VIH negativo y disminución de linfocitos CD4+. Posterior al tratamiento con timomodulina, se observó buena respuesta clínica, mejoría de las pruebas cutáneas y elevación de los linfocitos CD4+ en todas las pacientes

Aspectos imunologicos da atividade fisica / Imunologic aspects of physical activity

E sabido que atividades fisicas ou psicologicas estressantes causam uma alteracao na resposta imunologica. Tais conclusoes levaram a suspeita de que tecnicas de relaxamento e combate ao estresse pudessem melhorar as defesas imunologicas. A atividade e numero dos linfocitos...

Psiconeuroimunoendocrinologia / Psychoneuroimmunoendocrinology

Os autores definen Psiconeuroimunoendocrinologia, fazem uma introduçäo sobre o funcionamento do sistema imune e uma ampla revisäo dos trabalhos referentes à relaçäo entre luto, estresse, depressäo e a resposta imune. Concluem que pacientes submetidos a estresse psicológico agudo (natural ou experimental) ou crônico (natural) apresentam um aumento de catecolaminas, ACTH e cortisol, uma diminuiçäo da resposta proliferativa dos linfócitos aos mitógenos PHA, ConA e PWK, e do número de células T auxiliares, T supressoras / citotóxicas e também do número e atividade dos linfócitos B e da atividade das NK, o que explicaria a associaçäo encontrada na prática clínica entre estresse e infecçäo, particularmente as viróticas. Na depressäo clínica ligada ou näo nos quadros que apresentam apenas alguns sintomas depressivos, há uma diminiçäo da resposta proliferativa aos mitógenos PHA, ConA e PWK, do número de linfócitos T auxiliares e do número e da atividade das célula NK, o que explicaria a menor resistência à infecçäo por parte de alguns deprimidos assim como a propensäo ao desenvolvimento, morbidade por câncer

Neuropeptídios e dermatologia / Neuropeptides and dermatology

Os autores apresentam novos conceitos científicos dosneuropeptídeos, que atuam como neurotransmissores, neuro moduladores e neuro hormônios. Sua participaçäo na imunidade cutânea, nos processos de cicatrizaçäo e doenças crônicas da pele, säo evidentes. Os neuropeptídeos agem como mensageiros químicos, interligando o cérebro com os receptores da pele. Existem mais de cinqüenta neuropeptídeos envolvidos na transmissäo de sinais entre as células nervosas e o sistema auto-imune. Säo produzidos na pele neuropeptídeos opióides, que atuariam nas dores e emoçöes, promovendo a integraçäo do sistema neuroimunocutâneo. Uma das propostas do trabalho é uma visäo integrativa da Dermatologia na medicina geral.

Implicações psiconeuroimunológicas do estresse no desencadeamento de doenças / Psychoneuroimmunology of stress implications in unchain diseases

Os autores apresentam as correlações do estresse com a patogênese de várias doenças. Antes, expõem os aspectos fundamentais da Psiconeuroimunologia, para uma compreensão das interconexões no complexo microambiente onde ocorrem as influências do estresse. Concluem que, apesar de todas as implicações do estresse na desestruturação da homeostasia imunológica ainda não estarem completamente definidas, e das limitações metodológicas, há consenso de que fatores estressantes propiciam a vulnerabilidade do organismo a determinadas doenças.

The authors introduce the correlations between stress and the pathogenesis of various diseases. Previously, they expose the fundamental factors of Psychoneuroimmunology for the comprehension of the inter-connections in the complex microenvoironment where the influence of stress occurs. They conclude that despite all the implications of stress on the desestruturation of immunologic homeostasy are not already completely defined and despite metodologic limitations, there are a consensus that stressor factors provide vulnerability to the organism concerned to certain disorders.

Respuesta inmune disminuída por estrés académico intenso: cambios de la proliferación linfocitaria en estudiantes de medicina / Decreased immune response by acute academic stress: changes in lymphocyte proliferation in medical students

Blood samples were obtained from 42 medical students during a period of moderate academic stress, immediately before a final examination and after their summer vacations. T lymphocyte proliferation in response to 5, 10 and 20 mg/ml phytohemagglutinin was measured by the incorporation of 3H-thymidine, and plasma cortisol was measured by RIA. Results: T lymphocyte stimulation index in response to all phytohemagglutinin concentrations was significatively lower in the period before examination than in the other two periods.There were no differences in the index between the period of moderate stress and after summer vacations. Plasma cortisol levels were 15.6 ñ 4.3, 18.6 ñ 5.8 and 16.7 ñ 5.1 mg/dl during the periods of moderate stress, before the examination and after vacations, respectively (p < 0.05 for the difference between examination and the other two periods). Conclusions: There is a decrease in lymphocyte proliferation and an increase in cortisol levels during a period of acute academic stress in medical students, suggesting that, the exposure of healthy subjects to common stress ful stimuli, may affect their immunocompetance

Las emociones y su relación con el sistema inmune / Emotion and its relation to the immune system

El avance de diversas áreas de la medicina ha permitido a la psiquiatría formular respuestas teóricas con bases científicas en torno a la génesis de algunos procesos fisiopatológicos vinculados anteriormente en observaciones empíricas, con elementos psicológicos. El funcionamiento del sistema inmune se encuentra estrechamente vinculado a los procesos de regulación del sistema nervioso. Se describen tres mecanismos fundamentales involucrados en la comunicación neuroinmune: la modulación neuroendocrina, el envío de señales autonómicas y la acción directa de neuropéptidos. En este trabajo se revisan estudios básicos y clínicos que apoyan el papel de los procesos psicopatológicos y la exposición a estímulos adversos del medio ambiente como los estados de duelo, la depresión, el abandono y el estrés en el desarreglo del sistema inmune

Bacterial translocation and wasting in stressed mice

The effects of strees immunity and on the bacterial translocation from intestine to mesenteric lymph nodes, liver, and spleen were studied in a group of newborn CD1 mice. Animals were separated into three experimental groups. Mice from group I were stressed by intraperitoneal (IP) injections of heatkilled staphylococci for 4 weeks. Mice from group II were IP injected with saline solution only. The remaining mice, group III, were not injected. The clinical condition, presence of bacteria in abdominal organs, mitochondrial activity in splenic cells, lymphocyte proliferative response to Concanavalin-A and in vitro antibody production were evaluated in each mouse. Results showed that prolonged IP stressor challenge causes severe weight loss and immunodeficiency. The splenic lymphocytes from stressed mice exhibited a significant depression of both proliferative response to Concanavalin-A stimulation and anti-erythrocytes antibody synthesis. Instead, cultured in basal conditions, the splenic cells from stressed mice have an increased capacity to reduce the tetrazolium salts. Bacterial dissemination from intestine to mesenteric lymphoid nodes was also confirmed in the same group of mice. In contrast, mice in groups II and III presented no weight loss and immunodeficiency. Results suggest that chronic biological stress induced in newborn mice could facilitate the translocation of Gramnegative bacteria. Probable pathogenic mechanisms are commented upon and a correlation is proposed between the bacterial dissemination and the wasting development

Stress y función inmunológica en humanos (III) / Stress and inmunological function in humans (III)

En una revisión anterior presenté las estrechas interacciones entre el sistema nervioso central y el sistema inmunológico. En esta revisión presentaré los aspectos de esas complejas interacciones desde la perspectiva de la inmunología conductual, explorando las hipótesis sobre el impacto de los stressores psicológicos sobre el SNC, resultando en la modulación por el SNC sobre la respuesta inmunológica. Las dos cuestiones fundamentales a ser exploradas comprenden los mecanismos de las interacciones del eje SNC-endocrino-inmunológico y las implicaciones sobre la salud

Estres, depresión e inmunología / Stress, depression and immunology

Estrés es un concepto científico que se refiere a la respuesta inespecífica del organismo frente a cualquier demanda, en la cual la capacidad de adaptación individual constituye el factor más importante. Los sistemas nervioso, endocrino e inmune están en estrecha interrelación y hoy en día la célula inmune puede considerarse un órgano sensorial ya que es capaz de responder tanto a estímulos físicos como psíquicos. Se revisan las características del sistema inmune, la red neuroinmunoendocrina y los mecanismos de neuro-inmuno-modulación. El estudio de la inmunidad celular en la depresión se ha abordado, in vitro, a través del recuento de células, de la proliferación de linfocitos mediante mitógenos y de la actividad de las células natural killer. En pacientes, in vivo, se ha determinado la respuesta cutánea de hipersensibilidad retardada. Los resultados en general han sido contradictorios ya que existen reparos metodológicos y diversos factores; edad, gravedad del cuadro depresivo, hospitalización, trastornos del sueño, baja de peso, que dificultan las conclusiones definitivas. Las alteraciones en la función noradrenégica o en el eje hipotálamo-hipófisis-adrenal pudieran explicar algunos casos de deterioro de la inmunidad en la depresión