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1.
Sci Rep ; 9(1): 11276, 2019 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-31375732

RESUMO

Gravitational stress in general and microgravity (µg) in particular are regarded as major stress factors responsible for immune system dysfunction in space. To assess the effects of alternating µg and hypergravity (hyper-g) on immune cells, the attachment of peripheral blood mononuclear cells (PBMCs) to adhesion molecules under flow conditions and the antigen-induced immune activation in whole blood were investigated in parabolic flight (PF). In contrast to hyper-g (1.8 g) and control conditions (1 g), flow and rolling speed of PBMCs were moderately accelerated during µg-periods which were accompanied by a clear reduction in rolling rate. Whole blood analyses revealed a "primed" state of monocytes after PF with potentiated antigen-induced pro-inflammatory cytokine responses. At the same time, concentrations of anti-inflammatory cytokines were increased and monocytes displayed a surface molecule pattern that indicated immunosuppression. The results suggest an immunologic counterbalance to avoid disproportionate immune responses. Understanding the interrelation of immune system impairing and enhancing effects under different gravitational conditions may support the design of countermeasures to mitigate immune deficiencies in space.


Assuntos
Hipergravidade/efeitos adversos , Leucócitos Mononucleares/imunologia , Voo Espacial , Simulação de Ausência de Peso/efeitos adversos , Adesão Celular/imunologia , Moléculas de Adesão Celular/imunologia , Moléculas de Adesão Celular/metabolismo , Células Cultivadas , Citocinas/imunologia , Citocinas/metabolismo , Feminino , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Cultura Primária de Células
2.
Biol Sex Differ ; 10(1): 20, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992051

RESUMO

BACKGROUND: Antarctica challenges human explorers by its extreme environment. The effects of these unique conditions on the human physiology need to be understood to best mitigate health problems in Antarctic expedition crews. Moreover, Antarctica is an adequate Earth-bound analogue for long-term space missions. To date, its effects on human physiology have been studied mainly in male cohorts though more female expeditioners and applicants in astronaut training programs are selected. Therefore, the identification of sex differences in stress and immune reactions are becoming an even more essential aim to provide a more individualized risk management. METHODS: Ten female and 16 male subjects participated in three 1-year expeditions to the German Antarctic Research Station Neumayer III. Blood, saliva, and urine samples were taken 1-2 months prior to departure, subsequently every month during their expedition, and 3-4 months after return from Antarctica. Analyses included cortisol, catecholamine and endocannabinoid measurements; psychological evaluation; differential blood count; and recall antigen- and mitogen-stimulated cytokine profiles. RESULTS: Cortisol showed significantly higher concentrations in females than males during winter whereas no enhanced psychological stress was detected in both sexes. Catecholamine excretion was higher in males than females but never showed significant increases compared to baseline. Endocannabinoids and N-acylethanolamides increased significantly in both sexes and stayed consistently elevated during the confinement. Cytokine profiles after in vitro stimulation revealed no sex differences but resulted in significant time-dependent changes. Hemoglobin and hematocrit were significantly higher in males than females, and hemoglobin increased significantly in both sexes compared to baseline. Platelet counts were significantly higher in females than males. Leukocytes and granulocyte concentrations increased during confinement with a dip for both sexes in winter whereas lymphocytes were significantly elevated in both sexes during the confinement. CONCLUSIONS: The extreme environment of Antarctica seems to trigger some distinct stress and immune responses but-with the exception of cortisol and blood cell counts-without any major relevant sex-specific differences. Stated sex differences were shown to be independent of enhanced psychological stress and seem to be related to the environmental conditions. However, sources and consequences of these sex differences have to be further elucidated.


Assuntos
Ambientes Extremos , Caracteres Sexuais , Estresse Psicológico , Adulto , Regiões Antárticas , Antígenos de Fungos/imunologia , Catecolaminas/urina , Citocinas/imunologia , Endocanabinoides/sangue , Feminino , Testes Hematológicos , Humanos , Hidrocortisona/metabolismo , Masculino , Pessoa de Meia-Idade , Mitógenos de Phytolacca americana/imunologia , Estresse Psicológico/sangue , Estresse Psicológico/imunologia , Estresse Psicológico/metabolismo , Estresse Psicológico/urina , Adulto Jovem
3.
Sci Rep ; 8(1): 1754, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29379043

RESUMO

The pathology of sepsis is typically characterized by an infection and excessive initial inflammation including a cytokine storm, followed by a state of immune suppression or paralysis. This classical view of a two peak kinetic immune response is currently controversially discussed. This study was a sub-study of the randomized clinical Trial SISPCT registered with www.clinicaltrials.gov (NCT00832039, Registration date: 29/01/2009). Blood samples from 76 patients with severe sepsis and septic shock were incubated for 48 h at 37 °C in vitro with bacterial or fungal recall-antigens or specific mitogen antigens within 24 hours of sepsis onset. Recall-antigen stimulation led to a severe dampening of normal cytokine release. This immunologic anergy was similarly observed after mitogen stimulation. Moreover, patients under hydrocortisone therapy or with lowered arterial oxygen tension had further reductions in cytokine levels upon B- and T-cell mitogen stimulation. This investigation reveals an early onset of immunoparalysis during sepsis. This immune incompetence in mounting an adequate response to further infections includes previously sensitized pathogens, as seen with recall-antigens. Also, the immune-suppressive role of hydrocortisone and low PaO2 is highlighted. Aside from early broad-spectrum antimicrobial therapy, our findings reinforce the need for maximal immunological support and protection against further infections at the onset of sepsis.


Assuntos
Antígenos/imunologia , Mitógenos/imunologia , Choque Séptico/imunologia , Antibacterianos/uso terapêutico , Citocinas/imunologia , Feminino , Humanos , Hidrocortisona/uso terapêutico , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Sepse/tratamento farmacológico , Sepse/imunologia , Choque Séptico/tratamento farmacológico
4.
Sci Rep ; 8(1): 1762, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29379127

RESUMO

Adenosine plays a role in the energy supply of cells and provokes differential, hormone-like functions in circulating cells and various tissues. Its release is importantly regulated by oxygen tension. This renders adenosine and its kinetics interesting to investigate in humans subjected to low oxygen conditions. Especially for space exploration scenarios, hypoxic conditions - together with reduced gravity - represent two foreseen living conditions when planning manned long-duration space missions or planetary habitats. The PlanHab study investigated microgravity through inactivity in bed rest and normobaric hypoxia to examine their independent or combined effect on adenosine and its kinetics. Healthy male subjects (n = 14) completed three 21-day interventions: hypoxic bed rest (HBR); hypoxic ambulatory confinement (HAMB); normoxic bed rest (NBR). The interventions were separated by 4 months. Our hypothesis of a hypoxia-triggered increase in adenosine was confirmed in HAMB but unexpectedly also in NBR. However, the highest adenosine levels were noted following HBR. Furthermore, the percentage of hemolysis was elevated in HBR whereas endothelial integrity markers stayed low in all three interventions. In summary, these data suggest that neocytolysis accounts for these effects while we could reduce evidence for microcirculatory changes.


Assuntos
Adenosina/metabolismo , Hipóxia/metabolismo , Adulto , Repouso em Cama/métodos , Humanos , Cinética , Masculino , Microcirculação/fisiologia , Ausência de Peso
5.
Stress ; 20(2): 131-139, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28166699

RESUMO

Immobilization and hypoxemia are conditions often seen in patients suffering from severe heart insufficiency or primary pulmonary diseases (e.g. fibrosis, emphysema). In future planned long-duration and exploration class space missions (including habitats on the moon and Mars), healthy individuals will encounter such a combination of reduced physical activity and oxygen tension by way of technical reasons and the reduced gravitational forces. These overall unconventional extraterrestrial conditions can result in yet unknown consequences for the regulation of stress-permissive, psycho-neuroendocrine responses, which warrant appropriate measures in order to mitigate foreseeable risks. The Planetary Habitat Simulation Study (PlanHab) investigated these two space-related conditions: bed rest as model of reduced gravity and normobaric hypoxia, with the aim of examining their influence on psycho-neuroendocrine responses. We hypothesized that both conditions independently increase measures of psychological stress and enhance neuroendocrine markers of stress, and that these effects would be exacerbated by combined treatment. The cross-over study composed of three interventions (NBR, normobaric normoxic horizontal bed rest; HBR, normobaric hypoxic horizontal bed rest; HAMB, normobaric hypoxic ambulatory confinement) with 14 male subjects during three sequential campaigns separated by 4 months. The psychological state was determined through three questionnaires and principal neuroendocrine responses were evaluated by measuring cortisol in saliva, catecholamine in urine, and endocannabinoids in blood. The results revealed no effects after 3 weeks of normobaric hypoxia on psycho-neuroendocrine responses. Conversely, bed rest induced neuroendocrine alterations that were not influenced by hypoxia.


Assuntos
Repouso em Cama/psicologia , Canabinoides/sangue , Hidrocortisona/análise , Hipóxia/fisiopatologia , Hipóxia/psicologia , Adulto , Estudos Cross-Over , Humanos , Masculino , Saliva/química , Adulto Jovem
6.
Brain Behav Immun ; 50: 52-57, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26116982

RESUMO

BACKGROUND: Spaceflight is associated with immune dysregulation which is considered as risk factor for the performance of exploration-class missions. Among the consequences of confinement and other environmental factors of living in hostile environments, the role of different oxygen concentrations is of importance as either low (e.g. as considered for lunar or Martian habitats) or high (e.g. during extravehicular activities) can trigger immune dysfunction. The aim of this study was to investigate the impact of increased oxygen availability--generated through hyperbaricity--on innate immune functions in the course of a 14 days NEEMO mission. METHODS: 6 male subjects were included into a 14 days undersea deployment at the Aquarius station (Key Largo, FL, USA). The underwater habitat is located at an operating depth of 47 ft. The 2.5 times higher atmospheric pressure in the habitat leads to hyperoxia. The collection of biological samples occurred 6 days before (L-6), at day 7 (MD7) and 11/13 (MD11/13) during the mission, and 90 days thereafter (R). Blood analyses included differential blood cell count, ex vivo innate immune activation status and inhibitory competences of granulocytes. RESULTS: The absolute leukocyte count showed an increase during deployment as well as the granulocyte and monocyte count. Lymphocyte count was decreased on MD7. The assessments of native adhesion molecules on granulocytes (CD11b, CD62L) indicated a highly significant cellular activation (L-6 vs. MD7/MD13) during mission. In contrast, granulocytes were more sensitive towards anti-inflammatory stimuli (adenosine) on MD13. CONCLUSION: Living in the NEEMO habitat for 14 days induced significant immune alterations as seen by an activation of adhesion molecules and vice versa higher sensitivity towards inhibition. This investigation under hyperbaric hyperoxia is important especially for Astronauts' immune competence during extravehicular activities when exposed to similar conditions.


Assuntos
Hiperóxia/imunologia , Imunidade Inata , Inflamação/imunologia , Citocinas/imunologia , Humanos , Hiperóxia/sangue , Inflamação/metabolismo , Cadeias beta de Integrinas/imunologia , Cadeias beta de Integrinas/metabolismo , Leucócitos/imunologia , Masculino , Monócitos/imunologia , Voo Espacial , Estados Unidos , United States National Aeronautics and Space Administration
7.
J Appl Physiol (1985) ; 118(9): 1122-7, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25678697

RESUMO

The innate immune system as one key element of immunity and a prerequisite for an adequate host defense is of emerging interest in space research to ensure crew health and thus mission success. In ground-based studies, spaceflight-associated specifics such as confinement caused altered immune functions paralleled by changes in stress hormone levels. In this study, six men were confined for 105 days to a space module of ~500 m(3) mimicking conditions of a long-term space mission. Psychic stress was surveyed by different questionnaires. Blood, saliva, and urine samples were taken before, during, and after confinement to determine quantitative and qualitative immune responses by analyzing enumerative assays and quantifying microbicide and phagocytic functions. Additionally, expression and shedding of L-selectin (CD62L) on granulocytes and different plasma cytokine levels were measured. Cortisol and catecholamine levels were analyzed in saliva and urine. Psychic stress or an activation of the psychoneuroendocrine system could not be testified. White blood cell counts were not significantly altered, but innate immune functions showed increased cytotoxic and reduced microbicide capabilities. Furthermore, a significantly enhanced shedding of CD62L might be a hint at increased migratory capabilities. However, this was observed in the absence of any acute inflammatory state, and no rise in plasma cytokine levels was detected. In summary, confinement for 105 days caused changes in innate immune functions. Whether these changes result from an alert immune state in preparation for further immune challenges or from a normal adaptive process during confinement remains to be clarified in future research.


Assuntos
Astronautas/psicologia , Sistemas Neurossecretores/imunologia , Sistemas Neurossecretores/fisiologia , Neutrófilos/imunologia , Neutrófilos/fisiologia , Adaptação Psicológica/fisiologia , Catecolaminas/sangue , Citocinas/sangue , Humanos , Hidrocortisona/sangue , Imunidade Inata/imunologia , Imunidade Inata/fisiologia , Inflamação/sangue , Inflamação/imunologia , Inflamação/psicologia , Selectina L/sangue , Selectina L/imunologia , Contagem de Leucócitos/métodos , Masculino , Voo Espacial/métodos , Estresse Psicológico/imunologia , Estresse Psicológico/psicologia
8.
Brain Behav Immun ; 40: 203-10, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24704568

RESUMO

During interplanetary exploration, chronic stress caused by long term isolation and confinement in the spacecraft is one of the major concerns of physical and psychological health of space travelers. And for human on Earth, more and more people live in an isolated condition, which has become a common social problem in modern western society. Collective evidences have indicated prolonged chronic stress could bring big influence to human immune function, which may lead to a variety of health problems. However, to what extent long-term isolation can affect the immune system still remains largely unknow. A simulated 520-d Mars mission provided an extraordinary chance to study the effect of prolonged isolation. Six healthy males participated in this mission and their active neuroendocrine and immune conditions were studied with saliva and blood samples from all participants on chosen time points during the isolation period. As a typical neuroendocrine parameter, stress hormone cortisol was measured in the morning saliva samples. Immune phenotype changes were monitored through peripheral leukocyte phenotype analysis. Using an ex vivo viral infection simulation assay we assessed the immune response changes characterized by the ability to produce representative endogenous pro-inflammatory cytokines. The results of this study revealed elevated cortisol levels, increased lymphocyte amount and heightened immune responses, suggesting that prolonged isolation acting as chronic stressors are able to trigger leukocyte phenotype changes and poorly controlled immune responses.


Assuntos
Leucócitos/imunologia , Voo Espacial , Estresse Psicológico/imunologia , Adulto , Contagem de Células , Citocinas/imunologia , Humanos , Hidrocortisona/imunologia , Linfócitos/imunologia , Masculino , Fenótipo , Saliva , Simulação de Ambiente Espacial
9.
J Appl Physiol (1985) ; 115(2): 235-42, 2013 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23681910

RESUMO

Head-down-tilt bed rest (HDTBR) is a popular model, simulating alterations of gravitation during space missions. The aim of this study was to obtain a better insight into the complexly orchestrated regulations of HDTBR-induced immunological responses, hypothesizing that artificial gravity can mitigate these HDTBR-related physiological effects. This crossover-designed 5 days of HDTBR study included three protocols with no, or daily 30 min of centrifugation or 6 × 5 min of centrifugation. Twelve healthy, male participants donated blood pre-HDTBR, post-HDTBR, and twice during HDTBR. Cellular immune changes were assessed either by enumerative and immune cell phenotyping assays or by functional testing of responses to either recall antigens or receptor-dependent activation by chemotactic agents N-formyl-methionyl-leucyl-phenylalanine (fMLP) and with TNF-α. The expression of the adhesion molecule L-selectin (CD62L) on the surface of granulocytes and its shedding into plasma samples were measured. In parallel, other humoral factor, such as interleukin-6 and interleukin-8, parameters of endothelial damage (glycocalyx) were determined. Hematocrit and hemoglobin were significantly increased during HDTBR. Although immune functional tests did not indicate a change in the immune performance, the expression of CD62L on resting granulocytes was significantly shed by 50% during HDTBR. Although the latter is normally associated to an activation of inflammatory innate immune responses and during interaction of granulocytes with the endothelium, CD62L shedding was, however, not related either to a systemic inflammatory alteration or to shedding of the endothelial glycocalyx during bed rest. This suggests a noninflammatory or "mechanical" shedding related to fluid shifts during head-down intervention and not to an acute inflammatory process.


Assuntos
Decúbito Inclinado com Rebaixamento da Cabeça/fisiologia , Inflamação/metabolismo , Inflamação/fisiopatologia , Selectina L/imunologia , Selectina L/metabolismo , Adulto , Repouso em Cama/métodos , Estudos Cross-Over , Endotélio/imunologia , Endotélio/metabolismo , Endotélio/fisiologia , Glicocálix/imunologia , Glicocálix/metabolismo , Granulócitos/imunologia , Granulócitos/metabolismo , Granulócitos/fisiologia , Homeostase/imunologia , Homeostase/fisiologia , Humanos , Imunidade Celular/imunologia , Imunidade Inata/imunologia , Inflamação/imunologia , Interleucina-6/imunologia , Interleucina-6/metabolismo , Interleucina-8/imunologia , Interleucina-8/metabolismo , Masculino , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismo
10.
Clin Exp Immunol ; 172(2): 290-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23574325

RESUMO

The human immune system is orchestrated in a complex manner and protects the host against invading organisms and controls adequate immune responses to different antigen challenges in an endo-, auto- and paracrine-regulated fashion. The variety and intensity of immune responses are known to be dependent on stress-sensitive neural, humoral and metabolic pathways. The delayed-type hypersensitivity (DTH) skin test was a validated and standardized measure applied in clinical studies to monitor the integral function of cellular immune responses in vivo. The DTH skin test was, however, phased out in 2002. To obtain insight into the mechanisms of stress-sensitive immune reactions, we have developed an alternative in-vitro assay which allows the evaluation of antigen-dependent cellular immune responses triggered by T lymphocytes. The change in the concentration of proinflammatory cytokines in supernatant of the blood-antigen mixture is of particular interest to mirror the degree and adequacy of cellular immune responses. In this study we report that the proinflammatory cytokines interleukin (IL)-2, interferon (IFN)-γ and tumour necrosis factor (TNF)-α show a time-dependent increase upon ex-vivo bacterial, viral and fungal antigen stimulations. Furthermore, evidence is provided that this assay is sensitive to mirror stress hormone-mediated immune modulation in humans as shown either after hydrocortisone injection or after acute stress exposure during free fall in parabolic flight. This in-vitro test appears to be a suitable assay to sensitively mirror stress hormone-dependent inhibition of cellular immune responses in the human. Because of its standardization and relatively simple technical handling, it may also serve as an appropriate research tool in the field of psychoneuroendocrinology in clinical as in field studies.


Assuntos
Bioensaio/métodos , Monitorização Imunológica/métodos , Estresse Fisiológico/imunologia , Corticosteroides , Adulto , Bactérias/imunologia , Fungos/imunologia , Humanos , Hidrocortisona/análise , Imunidade Celular , Interferon gama/análise , Interleucina-2/análise , Masculino , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/análise , Vírus/imunologia
11.
Eur J Appl Physiol ; 113(8): 2057-65, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23579361

RESUMO

This study aimed to investigate psychological stress and endocrine responses during 5 days of head-down tilt bed rest (HDTBR) with or without the impact of artificial gravity (AG). Participants were assigned to one of three bed-rest-protocols either with (i) no centrifugation, (ii) continuous 30 min (AG1) or (iii) discontinuous 6 × 5 min (AG2) centrifugation periods at 1G in the center of mass periods. Centrifugations were performed daily in one session. Questionnaires for assessing psychological stress and the corresponding biological sample collection were performed before, during and after HDTBR or centrifugation. Overall, questionnaires showed no significant changes of anxiety or emotional stress during HDTBR. In the AG1-group, salivary cortisol levels were significantly higher after centrifugation irrespective of the progress of the HDTBR and day of intervention. The AG2-group showed higher cortisol concentrations after centrifugation only on the first days of head-down tilt but no more on day 5 of HDTBR. During bed rest, urine epinephrine excretion increased in all groups, but showed the highest day concentrations in the AG1-group, which were also significantly higher when compared with AG2. These results indicate that 5 days of HDT alone is not a major stressor and accordingly resulted only in moderate changes of neuroendocrine responses over time. However, daily centrifugation for a continuous duration of 30 min induced a significant neuroendocrine response, which was not subject to a habituation as compared with daily but intermittent centrifugation for 6 × 5 min. Discontinuous centrifugation is better tolerated and associated with lower adrenocortical stress responses during HDTBR.


Assuntos
Ansiedade/etiologia , Repouso em Cama/efeitos adversos , Gravidade Alterada/efeitos adversos , Decúbito Inclinado com Rebaixamento da Cabeça/efeitos adversos , Estresse Psicológico/etiologia , Adulto , Ansiedade/metabolismo , Estudos de Casos e Controles , Epinefrina/urina , Humanos , Hidrocortisona/análise , Masculino , Saliva/química , Estresse Psicológico/metabolismo , Fatores de Tempo
12.
Infection ; 41(3): 687-90, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23536310

RESUMO

PURPOSE: To test a new assay based on an ex vivo cytokine release from whole blood for the monitoring of immune changes in human immunodeficiency virus (HIV)-infected patients. METHODS: A pilot study of outpatients with HIV infection (n = 9) at a large academic hospital who were divided into three groups: HIV-infected patients on highly active antiretroviral therapy (HAART) with a CD4(+) cell count >350/µL (group I) or a CD4(+) cell count <350/µL (group II) and HIV-infected HAART-naïve subjects with a CD4(+) cell count >350/µL (group III). All groups were compared with healthy volunteers (n = 3). The ex vivo cytokine release assay was performed in a three-step process: (1) blood collection, (2) whole-blood ex vivo incubation over 48 h without or with a standard set of well-defined recall antigens as comparable to those used formerly in the skin delayed-type hypersensitivity (DTH) test, (3) cytokine determination from the assay supernatant. RESULTS: Under stimulated conditions, untreated HIV-infected patients with a CD4(+) count >350/µL had similar interleukin-2 (IL-2) levels in the supernatant of the whole-blood incubation to HIV-infected patients on HAART with a low CD4(+) count. Both groups revealed lower IL-2 levels in the supernatant than HIV-infected patients on HAART and with a CD4(+) count >350/µL or healthy volunteers. The determination of interferon-γ and tumour necrosis factor-α in the supernatant showed a similar arrangement of cytokines between groups. CONCLUSIONS: Our results suggest that this cytokine release assay could be a suitable tool to mirror the immunological responsiveness of patients with HIV infection in a gradual manner; further studies are required in order to assess its value in HAART monitoring.


Assuntos
Citocinas/análise , Monitoramento de Medicamentos/métodos , Infecções por HIV/diagnóstico , Infecções por HIV/imunologia , Testes Imunológicos/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Citocinas/metabolismo , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade
13.
Br J Anaesth ; 110(6): 1001-9, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23399557

RESUMO

BACKGROUND: Propofol is increasingly used in paediatric anaesthesia, but can be challenging to titrate accurately in this group. Mid-latency auditory-evoked potentials (MLAEPs) can be used to help titrate propofol. However, the effects of propofol on MLAEP in children are unclear. Therefore, we investigated the relationship between propofol and MLAEP in children undergoing anaesthesia. METHODS: Fourteen healthy children aged 4-16 yr received anaesthesia for elective surgery. Before surgery, propofol was administered in three concentrations (3, 6, 9 µg ml(-1)) through a target-controlled infusion pump using Kataria and colleagues' model. MLAEPs were recorded 5 min after having reached each target propofol concentration at each respective concentration. Additionally, venous propofol blood concentrations were assayed at each measuring time point. RESULTS: Propofol increased all four MLAEP peak latencies (peaks Na, Pa, Nb, P1) in a dose-dependent manner. In addition, the differences in amplitudes were significantly smaller with increasing propofol target concentrations. The measured propofol plasma concentrations correlated positively with the latencies of the peaks Na, Pa, and Nb. CONCLUSIONS: Propofol affects MLAEP latencies and amplitudes in children in a dose-dependent manner. MLAEP measurement might therefore be a useful tool for monitoring depth of propofol anaesthesia in children.


Assuntos
Anestésicos Intravenosos/farmacologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Propofol/farmacologia , Tempo de Reação/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Propofol/sangue
14.
Cryo Letters ; 33(2): 151-60, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22576119

RESUMO

In experimental and clinical studies, expression of surface adhesion molecules such as ß2-integrine (CD11b) and L-selectin (CD62L) on polymorphonuclear leukocyte (PMNL) are investigated to assess certain crucial innate immune functions. Because the expression of CD11b and CD62L on PMNL can alter they cannot be quantified reliably when the time between blood draw and measurements is prolonged. Goals of this study were to test effects of cryopreservation on the expression of CD11b and CD62L on human PMNLs either under native conditions as well as after stimulation-dependant adhesion molecules´ expression pattern. CD11b and CD62L expression on PMNL can be cryopreserved with 10% of PEG-solution for at least one month at -60 degree C. This was observed in native, unstimulated as well as in stimulated cell-preparations. CD11b is very stable in contrast to CD62L expression which appears to be more susceptible to alteration due to freezing-thawing. However, the relative stimulus-dependant changes of activation can still be reflected.


Assuntos
Antígeno CD11b/imunologia , Criopreservação , Crioprotetores/metabolismo , Selectina L/imunologia , Neutrófilos/imunologia , Polietilenoglicóis/metabolismo , Antígeno CD11b/genética , Regulação da Expressão Gênica , Humanos , Selectina L/genética , Neutrófilos/metabolismo
15.
Eur J Appl Physiol ; 112(7): 2777-81, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22101870

RESUMO

The effects of physical exercise stress on the endocannabinoid system in humans are almost unexplored. In this prospective study, we investigated in a crossover design and under field conditions at different altitudes the effects of physical exercise on the endocannabinoid system (ECS) in 12 trained healthy volunteers. For determination of alterations on the ECS three different protocols were analyzed: Protocol A (physical exercise at lower altitude) involved strenuous hiking below 2,100 m, whereas Protocol B (physical exercise by active ascent to high altitude) involved hiking up to 3,196 m, an accommodation at the cottage and a descent the next day. Protocol C (passive ascent) included a helicopter ascent to 3,196 m, an overnight stay at this altitude and a flight back to the base camp the following day. The cumulative hiked altitude in Protocol A and B was comparable (~1,650 m). The blood EC concentrations of anandamide increased significantly in Protocol A/B from baseline (T0) 0.12 ± 0.01/0.16 ± 0.02 (mean ± SEM) to 0.27 ± 0.02/0.42 ± 0.02 after exercise (T1) (p < 0.05). Anandamide levels in Protocol C remained stable at 0.20 ± 0.02. We conclude that the ECS is activated upon strenuous exercise whereas the combination with hypoxic stress further increases its activity. The reduced partial pressure of oxygen at high altitude alone did not affect this system. In summary, physical exercise activates the endocannabinoid system, whereas the combination with high altitude enhances this activation. This discloses new perspectives to adaptation mechanisms to physical exercise.


Assuntos
Altitude , Ácidos Araquidônicos/sangue , Moduladores de Receptores de Canabinoides/sangue , Endocanabinoides , Exercício Físico/fisiologia , Resistência Física/fisiologia , Esforço Físico/fisiologia , Alcamidas Poli-Insaturadas/sangue , Adaptação Fisiológica/fisiologia , Humanos , Masculino , Adulto Jovem
16.
Br J Anaesth ; 107(5): 726-34, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21862495

RESUMO

BACKGROUND: Detection of mid-latency auditory evoked potentials (MLAEPs) is a technology to monitor central nervous structures. As seen in adults and children, general anaesthesia influences the MLAEP latencies. MLAEP detection seems to be a promising tool to assess different levels of anaesthesia depth in adults and children. METHODS: MLAEPs were recorded in 10 infants (2 months-3 yr), 12 schoolchildren (6-14 yr), and 10 elderly (75-89 yr) under general anaesthesia with increasing concentrations of sevoflurane at steady state. In addition, MLAEPs were detected before and after the application of sufentanil. RESULTS: At all different ages, MLAEP latencies increased significantly with higher volume percentages of sevoflurane. These results were also detectable when MAC values of sevoflurane were compared with MLAEP peaks. An age-dependent effect could be displayed as elderly people need lower absolute sevoflurane concentrations to achieve the same MLAEP peak increase. Overall, the application of sufentanil under steady-state sevoflurane application at 1 MAC did not importantly affect the MLAEP latencies. CONCLUSIONS: MLAEP latencies increase at the influence of sevoflurane in a dose-dependent manner and in relation to age. These results imply that MLAEP detection is a reasonable tool for monitoring hypnotic effects at all ages. Further studies are required to standardize MLAEP alterations related to effects of medication used for general anaesthesia at all different ages.


Assuntos
Anestésicos Inalatórios/farmacologia , Potenciais Evocados Auditivos/efeitos dos fármacos , Éteres Metílicos/farmacologia , Adolescente , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Anestesia Geral/métodos , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Masculino , Tempo de Reação/efeitos dos fármacos , Sevoflurano , Vigília
17.
Eur J Clin Invest ; 39(8): 723-8, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19473213

RESUMO

BACKGROUND: Previously performed in vitro studies suggested that gravitational stress may alter functions of immune cells. This study investigated the in vivo effects of parabolic flight manoeuvres as a short-term model of micro- and hypergravity on the cytotoxic and microbicidal polymorphonuclear leucocyte (PMN) functions as the key element of innate immunity. MATERIAL AND METHODS: Twenty-one healthy male volunteers underwent 30 subsequent parabolic flight manoeuvres. Each manoeuvre produced 22-s periods of nearly weightlessness close to <<0g>>, with each parabola starting with a pull-up and ending with a pull-out (hypergravity) at 1.8 g for about 20 s each. Blood samples were drawn 24 h prior to take off (T0), after 25-30 parabolas (T1), and 24 h (T2) and 48 h (T3) after flight for determination of (i) leucocyte number and subpopulations, (ii) PMNs' capabilities to produce hydrogen peroxide (H(2)O(2)) and to adhere and phagocytose particles and (iii) plasma cytokines known to prime PMN functions [interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha), granulocyte-colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF)]. RESULTS: Parabolic flight induced an increase in leucocyte number with a significant elevation of the PMN fraction. The spontaneous H(2)O(2) production by PMNs did not change; however, the capability of PMNs to produce H(2)O(2) in response to soluble stimuli [N-formyl-methionyl-leucyl-phenylalanine (fMLP), fMLP and TNF-alpha, calcium ionophore (A23187), phorbol myristate acetate (PMA)] was increased. Adhesive and phagocytic properties of PMNs were not altered. Regarding priming cytokines, IL-8 and G-CSF were significantly elevated. CONCLUSIONS: Our data indicate that parabolic flight induces priming of the cytotoxic capabilities of PMNs without affecting microbicidal functions.


Assuntos
Peróxido de Hidrogênio/farmacologia , Neutrófilos/fisiologia , Fagocitose/fisiologia , Câmaras de Exposição Atmosférica , Gravidade Alterada/efeitos adversos , Humanos , Masculino , Neutrófilos/imunologia , Fagocitose/imunologia
18.
Br J Anaesth ; 99(6): 837-44, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17942820

RESUMO

BACKGROUND: Midlatency auditory evoked potentials (MLAEP) are a promising tool for monitoring suppression of sensory processing during anaesthesia and might help to avoid awareness. MLAEP in children are different to those in adults and the exact changes during general anaesthesia are unknown. METHODS: In 49 children of age between 2 and 12 yr, MLAEP were recorded before anaesthesia, during tracheal intubation, at steady-state balanced anaesthesia, and after extubation. RESULTS: MLAEP were recordable in all children in the awake (premedicated) state with latencies but not amplitudes dependent on children's age. MLAEP latencies significantly increased during tracheal intubation and steady-state anaesthesia. Changes in amplitudes were inconsistent. All MLAEP variables returned to near baseline values after extubation. CONCLUSIONS: The results of this study imply that MLAEP can successfully be recorded during anaesthesia in children above the age of 2 yr. Further studies are necessary before MLAEP might be applicable for monitoring purposes in paediatric anaesthesia.


Assuntos
Envelhecimento/fisiologia , Anestesia Geral , Potenciais Evocados Auditivos/fisiologia , Monitorização Intraoperatória/métodos , Anestésicos Inalatórios/farmacologia , Conscientização/efeitos dos fármacos , Conscientização/fisiologia , Criança , Pré-Escolar , Remoção de Dispositivo , Potenciais Evocados Auditivos/efeitos dos fármacos , Feminino , Humanos , Lactente , Intubação Intratraqueal , Modelos Lineares , Masculino , Tempo de Reação
19.
Anaesthesist ; 55(10): 1058-63, 2006 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-16897020

RESUMO

Intraoperative wakefulness is not only limited to adults and can also be found at a similar percentage (0.8%) in paediatric anaesthesia. For prevention of awareness neurophysiologic methods like auditory evoked potentials might be helpful. We report a case of a 2-year-old boy receiving balanced anaesthesia with sevoflurane and alfentanil. Midlatency auditory evoked potentials (MLAEPs) were recorded continuously before, during and after the surgical procedure. During the surgical procedure sevoflurane was withdrawn unintentionally. After a short period of time the boy started coughing and moved his legs, which was interpreted as insufficient analgesia. Several boli of alfentanil did not lead to the expected clinical effect on the depth of anaesthesia. After a recheck of the anaesthetic ventilator the error was determined and delivery of the volatile anaesthetic restored. The postoperative evaluation of the MLAEPs revealed the inadequate suppression of auditory processing during this incident with latencies comparable to the awake state. After reapplication of sevoflurane the MLAEPs were almost completely suppressed demonstrating adequate anesthetic depth. Exemplarily this case suggests that MLAEPs could be used to detect intraoperative awareness also in paediatric anaesthesia. Investigations to prove the validity and reproducibility of MLAEPs in children will be necessary.


Assuntos
Anestesia/efeitos adversos , Conscientização/efeitos dos fármacos , Potenciais Evocados Auditivos/efeitos dos fármacos , Complicações Intraoperatórias/diagnóstico , Monitorização Intraoperatória/métodos , Anestesiologia/instrumentação , Pressão Sanguínea/fisiologia , Pré-Escolar , Eletroencefalografia/efeitos dos fármacos , Falha de Equipamento , Frequência Cardíaca/fisiologia , Humanos , Complicações Intraoperatórias/terapia , Masculino , Erros Médicos , Dor/etiologia , Manejo da Dor
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