RESUMO
The mechanism of immunodepression after brain injury is not yet clear. Here we demonstrate rapid systemic release of the immunoinhibitory cytokine interleukin-10, monocytic deactivation and a high incidence of infection in patients with 'sympathetic storm' due to acute accidental or iatrogenic brain trauma. In vitro studies showed that within minutes catecholamines trigger the secretion of interleukin-10 from unstimulated monocytes through a beta-adrenoreceptor-mediated, cAMP/protein kinase A-dependent pathway. We found that in a rat model of acute brain injury, the beta-receptor antagonist propranolol prevented the increase of interleukin-10 plasma levels. Rapid monocytic interleukin-10 release after sympathetic activation may represent a common pathway for immunodepression induced by stress and injury.
Assuntos
Lesões Encefálicas/sangue , Tolerância Imunológica , Interleucina-10/sangue , Sistema Nervoso Simpático/fisiopatologia , Antagonistas Adrenérgicos beta/farmacologia , Adulto , Idoso , Animais , Encéfalo/cirurgia , Lesões Encefálicas/complicações , Lesões Encefálicas/fisiopatologia , Neoplasias Encefálicas/sangue , Neoplasias Encefálicas/cirurgia , Tronco Encefálico/fisiopatologia , Catecolaminas/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Nervoso/sangue , Neoplasias de Tecido Nervoso/cirurgia , Propranolol/farmacologia , Ratos , Ratos Sprague-Dawley , Sistema Nervoso Simpático/efeitos dos fármacos , Simpatolíticos/farmacologia , Simpatomiméticos/farmacologiaRESUMO
Layers of alumina were deposited on to bundled carbon fibers in an atomic layer deposition (ALD) process via sequential exposure to vapors of aluminium chloride and water, respectively. Scanning electron microscopic (SEM) images of the coated fibers revealed that each individual fiber within a bundle was coated evenly and separately, fibers are not bridged by the coating. SEM and transmission electron microscopic (TEM) images indicate that the coating was uniform and conformal with good adhesion to the fiber surface. Average deposition rate, measured from SEM images, was 0.06 nm per cycle at 500 °C. SEM also revealed that at deposition temperatures of 500 °C few of the fibers were damaged. At temperatures of 300 °C, no damaged fibers were observed, the average deposition rate decreased down to 0.033 nm per cycle. Oxidation resistance of the alumina-coated fibers was characterized by thermogravimetric analysis (TGA). The alumina coating improved oxidation resistance of the carbon fiber significantly. Oxidation onset temperature was 600 °C for fibers coated with a 45 nm thick alumina. Uncoated fibers, on the other hand, started to oxidize at temperatures as low as 250 °C.
RESUMO
Severe immunodysregulation on lymphocyte level has been described in patients with glioblastoma and is likely involved into its unfavorable prognosis. Although the major importance of monocytic cells for immunoregulation is well established, only very limited data exist regarding the monocyte status in glioblastoma patients. Here we demonstrate a markedly diminished monocytic HLA-DR expression and ex vivo cytokine secretion capacity (TNF-alpha, IL-1beta, IL-10) as signs for monocyte deactivation in glioblastoma patients but not in patients with astrocytoma. As known in immunocompromised patients from other reasons, monocyte deactivation indicate global immunodepression associated with an enhanced risk of infectious complications. Interestingly, tumor resection resulted in partial recovery from the monocytic deactivation. This suggests that the glioblastoma itself contributed to this phenomenon. However, IL-10 and the active forms of transforming growth factor-beta2 and -beta1, which are produced by glioblastoma cells and known to inhibit monocyte function, were not detectable in plasma in our patients. Moreover, low levels of the adrenocorticotropic hormone and cortisol excluded hypothalamo-pituitary-adrenal axis involvement. So, further investigations are necessary to clarify the mechanism. The demonstrated severe glioblastoma-associated monocytic deactivation may contribute to its unfavorable prognosis. Therefore, monocytes may represent target cells for new adjuvant immunotherapies in glioblastoma.
Assuntos
Neoplasias Encefálicas/imunologia , Citocinas/metabolismo , Glioblastoma/imunologia , Antígenos HLA-DR/metabolismo , Monócitos/metabolismo , Hormônio Adrenocorticotrópico/sangue , Adulto , Idoso , Endotoxinas/farmacologia , Feminino , Antígenos HLA-DR/biossíntese , Humanos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Sistema Hipófise-Suprarrenal/imunologia , Sistema Hipófise-Suprarrenal/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Rectal suppositories, which are dispensed according prescription in small numbers up to N = 30, do not satisfy the demands in respect of content uniformity, if we consider the last N/10 poured ones. This by sedimentation caused problem is to be solved in increasing the amount of substances by N/10, so that you will get a safety-amount of 15% totally.
Assuntos
Supositórios/análise , Química Farmacêutica , Difusão , Composição de Medicamentos , Cinética , Cloreto de Sódio/análise , Teofilina/administração & dosagemRESUMO
To elucidate the role of cytokines in brain repair processes and in local inflammation after neurosurgical procedures, cerebrospinal fluid (CSF) samples from 8 patients with intra-axial tumours and 8 patients with extra-axial tumours were analysed for interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1 ra), IL-6, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha at the beginning and after surgery. Levels of IL-6 and IL-8 increased dramatically in all patients just hours after surgery and fell during subsequent days. IL-1 beta was found only in low amounts in the CSF of both patient groups. Other cytokines demonstrated different courses. In patients with intra-axial tumours IL-1 ra peaked two to four hours after surgery with a subsequent decrease. In patients with extra-axial tumours there was a continuous low-level IL-1 ra release into the CSF without a peak. TNF-alpha was not present in detectable levels in the CSF after surgery for extra-axial tumours but was found to peak two to four hours after surgery for intra-axial tumours. IL-10 was detected in the CSF of both patient groups, but a higher peak was seen after surgery for extra-axial tumours. These results suggest different requirements for the cytokine response and an involvement of different cell types in cytokine release. However, the analysis of the CSF from both patient groups showed no differences in cell counts and populations, with a mild pleocytosis being present in both patient groups after surgery. Therefore, we conclude that after surgery for extra-axial tumours cytokines were predominately produced by non-immune cells stimulated through hypoxia or mechanical irritation. After surgery for intra-axial tumours with a significant brain injury immune cells-activated by necrotic material-seen to be involved in the process of cytokine synthesis. In these cases an additional IL-1ra and TNF-alpha peak was found and these cytokines may be markers for cerebral injury.