RESUMEN
BACKGROUND: Adolescent malnutrition is a significant public health challenge in low-income and middle-income countries (LMICs), with long-term consequences for health and development. Community-based interventions have the potential to address multiple forms of malnutrition and improve the health outcomes of adolescents. However, there is a limited understanding of the content, implementation and effectiveness of these interventions. This scoping review aims to synthesise evidence on community-based interventions targeting multiple forms of malnutrition among adolescents in LMICs and describe their effects on nutrition and health. METHODS AND ANALYSIS: A comprehensive search strategy will be implemented in multiple databases including MEDLINE (through PubMed), Embase, CENTRAL (through Cochrane Library) and grey literature, covering the period from 1 January 2000 to 14 July 2023. We will follow the Participants, Concept and Context model to design the search strategy. The inclusion criteria encompass randomised controlled trials and quasi-experimental studies focusing on adolescents aged 10-19 years. Various types of interventions, such as micronutrient supplementation, nutrition education, feeding interventions, physical activity and community environment interventions, will be considered. Two reviewers will perform data extraction independently, and, where relevant, risk of bias assessment will be conducted using standard Cochrane risk-of-bias tools. We will follow the PRISMA Extension for Scoping Reviews checklist while reporting results. ETHICS AND DISSEMINATION: The scope of this scoping review is restricted to publicly accessible databases that do not require prior ethical approval for access. The findings of this review will be shared through publications in peer-reviewed journals, and presentations at international and regional conferences and stakeholder meetings in LMICs. SCOPING REVIEW REGISTRATION: The final protocol was registered prospectively with the Open Science Framework on 19 July 2023 (https://osf.io/t2d78).
Asunto(s)
Países en Desarrollo , Desnutrición , Humanos , Adolescente , Desnutrición/prevención & control , Desnutrición/epidemiología , Desnutrición/terapia , Proyectos de Investigación , Servicios de Salud Comunitaria/organización & administración , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: Following SARS-CoV-2 infection, a relevant proportion of patients suffer from persistent or recurring sequela, even after initially mild primary illness. Many patients experience exhaustion and fatigue, rendering them incapable of working. Long COVID exerts a substantial burden on society and the healthcare system: at least 65 million people are currently affected worldwide. The underlying pathobiology is a complex derangement in several organ systems. To date, causal pharmaceutical therapies remain elusive. Waiting lists for specialist care are long. Rapidly scalable digital interventions offering support for the frequent subgroup of patients with mild to moderate impairment from Long COVID are urgently needed. The MiLoCoDaS study compares three intensities of a potentially rapidly scalable digital intervention aiming to accelerate recovery. The overall objective is to figure out if there is a difference in the effect sizes between these modalities. METHODS: The online intervention uses a learning platform (LMS, TYPO3 framework) comprising 12 sessions of medical, psychological, physiotherapeutic, and nutritional content. The three modalities differ as follows: patient information only (sham intervention, control), information plus interactive digital workbook including practical exercises (digital intervention), and the digital workbook augmented by once-weekly online seminars and discussion groups (person and peer-contact). Eligible patients are 18-67 years old satisfying Long COVID diagnostic criteria. Patients are recruited through primary care physicians and randomly allocated. The primary endpoint is the number of sick leave days during the 6-month observation period; secondary endpoints are patient-reported symptoms, quality of life, and work ability. The study size provides a power of 80% at a type I error of < 0.05 to show an effect size of Cohen = 0.3 between the augmented and the sham intervention (N = 152 per arm, total accounting for attrition N = 600). DISCUSSION: If one of the two interventions is superior to providing information alone, MiLoCoDaS would provide the starting point for a rapidly scalable digital intervention for the frequent and currently underserved patient group with mild to moderate impairment from Long COVID. Several caveats pertain to the heterogeneity of Long COVID manifestation and duration prior to inclusion. It is conceivable that the possible effect of the intervention may differ across subgroups. Therefore, a priori defined secondary analysis will be conducted. TRIAL REGISTRATION: German Clinical Trials Register (DRKS) DRKS00028964. Registered on 24 August 2022.
Asunto(s)
COVID-19 , Humanos , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , SARS-CoV-2 , Síndrome Post Agudo de COVID-19 , Calidad de Vida , Ausencia por Enfermedad , Evaluación de Capacidad de Trabajo , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: During the first waves of the COVID-19 pandemic, many cultural and sporting events were held without spectators or had to be cancelled. Therefore, several containment strategies to provide requirements for safe events were developed and tested. Nonetheless, every second (50.7%) is afraid of becoming infected on an event. We therefore investigated which hygiene and containment measures are perceived to be important from the visitor's point of view and thus might increase subjective sense of safety. METHODS: This online study was carried out in November 2020. A total of 1,004 persons, who regularly attended events before the pandemic, took part in the study. The importance of different hygiene and containment measures was evaluated using a 5-point Likert-scale (1 "unimportant" to 5 "extremely important"). Potential statistical differences in socio-demographical aspects (age, gender, net disposable income for leisure activities) and attendance on events were tested with analyses of variance. RESULTS: Participants perceived the use of disinfectant (M = 4.10) as the most important element of containment strategies, followed by transparent information on the hygiene strategy (M = 4.00), reduced occupancy (M = 3.98), and optimized ventilation (M = 3.97). Body temperature measurement at the entrance (M = 3.27), a negative SARS-CoV-2 test (M = 3.11), completion of a health questionnaire (M = 3.05), and abandoning breaks and catering (M = 2.98) were considered as less important. Analyses of group differences in socio-demographical aspects found abandoning breaks and catering to be more important to men than to women. This strategy is also more important to people aged 66 and above than to younger age groups (e.g., age 20-40). For women, the use of disinfectant is considerably more important. No other significant differences exist. CONCLUSION: Combining relevant measures appears to be important to provide a safe containment strategy. Measures aimed at positively influencing people's sense of safety do not fully correspond to researched knowledge of effectiveness. There are also target group-specific differences in the rating of measures, which should be considered while preparing containment strategies. To describe the dynamic development of changes in subjective rating of containment strategies, continuing research is needed.
Asunto(s)
COVID-19 , Desinfectantes , COVID-19/epidemiología , COVID-19/prevención & control , Femenino , Alemania/epidemiología , Humanos , Masculino , Pandemias/prevención & control , SARS-CoV-2RESUMEN
Opioids in skin function during stress response, regeneration, ageing and, particularly in regulating sensation. In chronic pruritus, topical treatment with Naltrexone changes µ-opioid receptor (µ-OR) localization to relieve itch. The molecular mechanisms behind the effects of Naltrexone on µ-OR function in reduction of itching behavior has not been studied. There is an immediate need to understand the endogenous complexity of µ-OR dynamics in normal and pathological skin conditions. Here we evaluate real-time behavior of µ-OR-Endomorphine complexes in the presence of agonist and antagonists. The µ-OR ligand Endomorphine-1 (EM) was conjugated to the fluorescent dye Tetramethylrhodamine (TAMRA) to investigate the effects of agonist and antagonists in N/TERT-1 keratinocytes. The cellular localization of the EM-TAMRA was followed through time resolved confocal microscopy and population analysis was performed by flow cytometry. The in vitro analyses demonstrate fast internalization and trafficking of the endogenous EM-TAMRA-µ-OR interactions in a qualitative manner. Competition with Endomorphine-1, Naltrexone and CTOP show both canonical and non-canonical effects in basal and differentiated keratinocytes. Acute and chronic treatment with Naltrexone and Endomorphine-1 increases EM-TAMRA binding to skin cells. Although Naltrexone is clinically effective in relieving itch, the mechanisms behind re-distribution of µ-ORs during clinical treatments are not known. Our study has given insight into cellular mechanisms of µ-OR ligand-receptor interactions after opioid agonist and antagonist treatments in vitro. These findings potentially offer opportunities in using novel treatment strategies for skin and peripheral sensory disorders.
Asunto(s)
Colorantes Fluorescentes/metabolismo , Queratinocitos/metabolismo , Receptores Opioides mu/metabolismo , Células Cultivadas , Humanos , Ligandos , Espectrometría de FluorescenciaRESUMEN
What has the opioid receptor system, known for beneficial as well as disastrous effects in the central nervous system, to do with skin? The question is appropriate considering the fact that the nervous system and the skin both derive from the ectoderm. As part of the skin neuroendocrine system, the opioid receptor system exemplifies the closeness between the nervous system and the skin. Overexpression of the δ-opioid receptor in keratinocytes yields dysregulation of involucrin, loricrin, and filaggrin, proteins essential to the integrity of the skin barrier. The µ-opioid receptor ligand ß-endorphin, produced in the pituitary gland and a variety of skin cells, promotes wound healing via regulation of cytokeratin 16 and TGF-ß type II receptor expression in keratinocytes. These and other published results discussed in this viewpoint are evidence for the fundamental role of the skin opioid receptor system in skin homeostasis, regeneration and ageing. While considerable progress in understanding the opioid receptors' function on the cellular level has been made, there is a need to link these results to physiological observations for the development of local skin therapies.
Asunto(s)
Receptores Opioides/metabolismo , Piel/metabolismo , Animales , Proteínas Filagrina , Homeostasis , Humanos , Regeneración , Envejecimiento de la PielRESUMEN
Neogobius melanostomus (round goby) are a benthic dwelling invasive species of fish in the Great Lakes. This study was done to determine if a tone that mimics the frequency (175 Hz) of mating call of a male round goby would have an effect on male and female response. A testing tank and a simulated trap in front of a speaker at each end were used. Each fish was then placed individually into the small holding box that was in the center of the tank. A video camera was then turned on to record fish movement once the door was opened. Next, the artificial sound was turned on for 1 min (175, 300, 500 Hz, and no sound); 175 Hz mimics the conspecific mating call. This process was done for each frequency for each fish. The individual fish was then allowed to roam for 5 min. The video camera recorded fish location and behavior. From the videos, a continuous measure was collected according to when the fish crossed the center line. The hypothesis, if (N. melanostomus) hears different frequencies of sound projected from a certain location in a fish tank habitat, then the females will be attracted and spend more time on the sound-emitting side of the tank, which mimics the frequency of mating call of a male round goby (175 Hz, 13 pulse), was supported; females spent more time on the sound-emitting side of the tank and males avoided the sound-emitting side of the tank, analysis of variance p < 0.012.
Asunto(s)
Conducta Animal/fisiología , Conservación de los Recursos Naturales , Especies Introducidas , Perciformes/fisiología , Localización de Sonidos , Vocalización Animal , Acústica , Animales , Femenino , Masculino , Factores SexualesRESUMEN
Water samples from ten German Baltic estuaries were collected in 2012 in order to study the presence of the herbicide glyphosate, its primary metabolite AMPA and their potential transport to the marine environment. For the analyses an LC-MS/MS based analytical method after derivatization with FMOC-Cl was optimized and validated for marine water samples. All investigated estuarine stations were contaminated with AMPA and nine of them also with glyphosate. Concentration ranges observed were 28 to 1690ng/L and 45 to 4156ng/L for glyphosate and AMPA, respectively with strong spatial and temporal fluctuations. Both contaminants were found at inbound sampling sites in the stream Muehlenfliess and concentrations decreased along the salinity gradient to the estuaries of the Baltic Sea. The data obtained in this study clearly depict the transport of glyphosate and AMPA to the Baltic Sea. Hence, detailed fate and risk assessment for both contaminants in marine environments are required.
Asunto(s)
Glicina/análogos & derivados , Organofosfonatos/análisis , Contaminantes Químicos del Agua/análisis , Países Bálticos , Cromatografía Liquida/métodos , Estuarios , Fluorenos/química , Glicina/análisis , Herbicidas/análisis , Isoxazoles , Océanos y Mares , Organofosfonatos/metabolismo , Espectrometría de Masas en Tándem/métodos , Tetrazoles , GlifosatoRESUMEN
Neuropeptides and their receptors are present in human skin, and their importance for cutaneous homeostasis and during wound healing is increasingly appreciated. However, there is currently a lack of understanding of the molecular mechanisms by which their signaling modulates keratinocyte function. Here, we show that δ-opioid receptor (DOPr) activation inhibits proliferation of human keratinocytes, resulting in decreased epidermal thickness in an organotypic skin model. DOPr signaling markedly delayed induction of keratin intermediate filament (KRT10) during in vitro differentiation and abolished its induction in the organotypic skin model. This was accompanied by deregulation of involucrin (IVL), loricrin, and filaggrin. Analysis of the transcription factor POU2F3, which is involved in regulation of KRT10, IVL, and profilaggrin expression, revealed a DOPr-mediated extracellular signal-regulated kinase (ERK)-dependent downregulation of this factor. We propose that DOPr signaling specifically activates the ERK 1/2 mitogen-activated protein kinase pathway to regulate keratinocyte functions. Complementing our earlier studies in DOPr-deficient mice, these data suggest that DOPr activation in human keratinocytes profoundly influences epidermal morphogenesis and homeostasis.
Asunto(s)
Epidermis/fisiología , Quinasas MAP Reguladas por Señal Extracelular/fisiología , Homeostasis/fisiología , Factores de Transcripción de Octámeros/antagonistas & inhibidores , Receptores Opioides delta/fisiología , Calcio/metabolismo , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Proteínas Filagrina , Humanos , Queratinocitos/citología , Factores de Transcripción de Octámeros/fisiologíaRESUMEN
Chronic venous leg ulcers are common and cause considerable burden of disease for affected patients with significant costs for health care systems worldwide. The complex pathophysiology of chronic venous leg ulcers is still not entirely understood. In addition, reliable pathogenic and/or prognostic parameters are not known. Published data suggest that patients with chronic venous leg ulcers reveal congenital or acquired thrombophilia. We examined the serum Lipoprotein (a) [Lp(a)] level, a proatherogenic and prothrombotic risk factor, in patients with chronic venous leg ulcers (n=210, stratified into patients with postthrombotic syndrome or without) and in a healthy control group (n=341). Forty-two percent of all patients, compared with 20% of healthy controls, revealed significantly increased Lp(a) serum concentrations above 0.3 g/L. Furthermore, 49% without postthrombotic syndrome but only 35% with postthrombotic syndrome showed increased Lp(a) levels. The increase of Lp(a) level was significantly different between all three groups (p<0.001). There was no correlation of Lp(a) levels and CRP values in all groups. Based on these data, it is conceivable that Lp(a) plasma level is a novel pathogenic parameter for chronic venous leg ulcers. Elevated concentrations may contribute to the pathogenesis through induction of thrombogenic microcirculatory dysregulations, impaired extravascular fibrinolysis, or other mechanisms like proinflammatory effects.
Asunto(s)
Lipoproteína(a)/sangre , Síndrome Postrombótico/complicaciones , Úlcera Varicosa/sangre , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Úlcera Varicosa/complicacionesRESUMEN
The cyclin-dependent kinase inhibitor 2A (CDKN2A) gene on chromosome 9p21 encodes p16 (INK4A), the inhibitor of the CDK4/retinoblastoma (Rb) cell proliferation pathway, as well as p14 (ARF), which controls p53-dependent pathways. Inactivation of p16 has previously been associated with the prognostically unfavourable primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL, LT). In this work, we analysed 22 tumors [nine primary cutaneous follicle centre lymphomas (PCFCL), seven primary cutaneous marginal zone lymphomas (PCMZL) and six PCLBCL, LT] not only for alterations of the p16 gene but also for p14, p53 and Rb by fluorescence in situ hybridization (FISH) and immunohistochemistry. In most PCLBCL, LT (4/6) alterations of CDKN2A (two biallelic deletions, one monoallelic deletion and one trisomy 9) and in addition the highest frequency of deletions of p53 (3/6) and Rb (3/6) were detected. p16 was not expressed but very high levels of phosphorylated Rb, indicating a functional effect of genomic CDKN2A alterations on the protein level in PCLBCL, LT. Regarding the p14/p53 axis, PCLBCL, LT showed a variable expression. Neither PCFCL nor PCMZL showed alterations of CDKN2A and also deletions of p53 or Rb were extremely rare in these subtypes. Exclusively in PCMZL, p53 protein was consistently lacking. In conclusion, only PCLBCL, LT is characterized by a high frequency of aberrations of the CDKN2A network components in both important tumor suppressor pathways regulated by the CDKN2A gene. Moreover, PCLBCL, LT appears to be distinguishable from PCMZL not only by its level of p53 expression but also by its stage of Rb phosphorylation. The latter may also apply to a subgroup of PCFCL.
Asunto(s)
Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Genes de Retinoblastoma/genética , Genes p16 , Linfoma de Células B de la Zona Marginal/genética , Linfoma Folicular/genética , Linfoma de Células B Grandes Difuso/genética , Fosforilación/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Cromosomas Humanos Par 13/genética , Cromosomas Humanos Par 13/metabolismo , Cromosomas Humanos Par 17/genética , Cromosomas Humanos Par 17/metabolismo , Cromosomas Humanos Par 9/genética , Cromosomas Humanos Par 9/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Análisis Mutacional de ADN , Femenino , Genes p53 , Humanos , Hibridación Fluorescente in Situ , Linfoma de Células B de la Zona Marginal/metabolismo , Linfoma Folicular/metabolismo , Linfoma de Células B Grandes Difuso/metabolismo , Masculino , Persona de Mediana Edad , Eliminación de Secuencia , Trisomía , Proteína p14ARF Supresora de Tumor/genética , Proteína p14ARF Supresora de Tumor/metabolismo , Adulto JovenRESUMEN
Vaccination protocols that utilize dendritic cells (DCs) to elicit therapeutic immunity against tumors are the subject of intense research. Given that the capacity of DCs to cross-present antigens is physiologically low, there is considerable interest to develop strategies that enhance that pathway. In order to best exploit the enhanced cross-presentation of antigens bound to heat shock protein 70 (HSP70), we analysed melanoma cell preparations for their HSP70 expression. Western blotting revealed strong upregulation of HSP70 after heat-killing in contrast to UV-B irradiation. When the uptake of heat-killed necrotic cells by DCs at various levels of maturation was assessed, 61 +/- 7% of immature DCs (iDCs) internalized fluorescence-labelled necrotic material. Apoptotic material from UV-B-irradiated cells was internalized by only 48 +/- 5% of iDCs. Maturation-inducing cytokines did not affect the uptake when added simultaneously with the tumor cell preparations. Loading DCs with heat-necrotic or apoptotic melanoma cells slightly reduced CD83 expression while leaving CD208 (DC-LAMP) expression unchanged. As determined by IFN-gamma-detecting enzyme-linked-immunospot assays, iDCs loaded with heat-killed melanoma cells activated autologous T cells most effectively when used without any further maturation, whereas DCs loaded with apoptotic material required maturation. In conclusion, HSP70-expressing melanoma cells could be generated by heat-killing. Loading iDCs with heat-killed melanoma cells resulted in a superior priming of autologous T cells in vitro.
Asunto(s)
Células Dendríticas/inmunología , Proteínas HSP70 de Choque Térmico/metabolismo , Activación de Linfocitos , Melanoma/inmunología , Linfocitos T/inmunología , Apoptosis , Línea Celular Tumoral , Calor , Humanos , Melanoma/metabolismo , FagocitosisRESUMEN
The optimal processing for the pathology of sentinel lymph nodes of patients with melanoma is still a matter of debate. We compared two protocols of sentinel lymph node processing, which were consecutively applied. For the first protocol, the sentinel lymph nodes were cut into 1-2 mm thick slices. From each slice, 12 microtome sections were stained (multiple slices protocol). For the second protocol, which is a modification of the recent European Organisation for Research and Treatment of Cancer protocol, the sentinel lymph nodes were bivalved. Five consecutive series of microtome sections, with gaps of 50 microm between them, were prepared from each cut surface (bivalving protocol). H&E and immunohistochemical staining were integral elements of both protocols. A total of 584 sentinel lymph nodes (1.8+/-0.9 per patient) were examined. The percentages of micrometastases (29 versus 27%) and of capsular naevi (13 versus 15%) detected were very similar for both protocols. As shown by multivariate logistic regression, Breslow thickness (P=0.003) and younger age (P=0.01) correlated with nodal metastasis. The type of histological preparation, ulceration and sex were not significant. The multiple slices protocol produced, on average, 4 paraffin blocks and 46 microtome sections per node. The bivalving protocol constantly produced 2 paraffin blocks and 42 microtome sections. For technical processing, the multiple slices protocol required, on average, 38 min per sentinel lymph node, whereas the bivalving protocol required 55 min. Both protocols yielded excellent detection rates with a similar amount of work being required on the part of the pathologist. Compared with the bivalving protocol, the multiple slices protocol was less labor intensive for the technical staff.
Asunto(s)
Melanoma/patología , Microtomía , Biopsia del Ganglio Linfático Centinela/métodos , Neoplasias Cutáneas/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Colorantes , Eosina Amarillenta-(YS) , Femenino , Hematoxilina , Humanos , Inmunohistoquímica , Modelos Logísticos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Adhesión en Parafina , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Coloración y Etiquetado/métodos , Estudios de Tiempo y Movimiento , Carga de Trabajo , Adulto JovenRESUMEN
Blastic plasmacytoid dendritic cell (BPDC) neoplasm, formerly called blastic natural killer cell lymphoma or CD4+/CD56+ hematodermic neoplasm, is a rare tumor entity, now regarded to be derived from the plasmacytoid dendritic cell (PDC) lineage. Because over 90% of patients present with skin lesions usually early in their disease, dermatologists have to be familiar with the specific diagnostic features and the clinical course of this devastating disease. We present a woman with a long standing solitary skin tumor of BPDC neoplasm, who experienced a deleterious clinical course, which is typical for this disease. Phenotypic and karyotypic characteristics distinguishing this tumor from myelomonocytic leukemia with skin involvement are presented.
Asunto(s)
Células Dendríticas/patología , Leucemia/patología , Linfoma/patología , Neoplasias Primarias Secundarias/patología , Neoplasias Cutáneas/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Artritis Reumatoide/complicaciones , Biomarcadores de Tumor/análisis , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Leucemia/genética , Linfoma/tratamiento farmacológico , Linfoma/genética , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genéticaAsunto(s)
Cadenas Ligeras de Inmunoglobulina/genética , Linfoma de Células B de la Zona Marginal/patología , Proteínas de Fusión Oncogénica , Proteínas Proto-Oncogénicas c-myc/genética , Neoplasias Cutáneas/secundario , Translocación Genética , Aberraciones Cromosómicas , Genes myc , Humanos , Hibridación Fluorescente in Situ , Linfoma de Células B de la Zona Marginal/genética , Masculino , Persona de Mediana Edad , Piel/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patologíaRESUMEN
The title compound, C(6)H(16)N(3) (+)·Br(-), is the bromide of the monoprotonated aza-macrocyclic triamine 1,4,7-triaza-cyclo-nonane (tacn). The threefold axis of the triamine is broken by the protonation of one of the three amine functions. The ammonium proton is bonded in an intra-molecular symmetrically bifurcated hydrogen bond to the two endodentate amine functions. Direct cation-anion contacts are established via N-Hâ¯Br hydrogen bonds between the bromide anions and tacnH(+) cations.
RESUMEN
BACKGROUND: Breath analysis could offer a non-invasive means of drug monitoring if adequate analytical methods and robust correlations between drug concentrations in breath and blood can be established. We therefore applied headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry (HS-SPME-GC-MS) to assess breath and blood concentrations of the intravenous drug propofol in patients under anesthesia or sedation. METHODS: Arterial, central- and peripheral-venous blood and alveolar breath samples were drawn in parallel from 16 mechanically ventilated patients. In addition, six patients undergoing lung resection were investigated. Substances were preconcentrated by means of HS-SPME, separated by GC and identified by MS. RESULTS: Propofol detection limits were 0.006 nmol/L in breath and 72.20 nmol/L in blood, the quantitation limits were 0.009 nmol/L and 75.89 nmol/L (end tidal breath/blood). Intraday precision was 8-11%, recovery 97-103%. Propofol concentrations were 0.04-0.5 nmol/L in breath and 2-120 micromol/L in blood. Only arterial propofol concentrations showed a correlation with concentrations in breath. Impaired ventilation/perfusion ratios in patients under lung resection resulted in changes of correlation coefficients. CONCLUSIONS: Reliable and precise analytical methods such as HS-SPME-GC-MS represent basic requirements if breath analysis is to be set up for non-invasive monitoring of intravenous drugs and control of anesthesia.
Asunto(s)
Cromatografía de Gases y Espectrometría de Masas/métodos , Propofol/análisis , Propofol/sangre , Microextracción en Fase Sólida/métodos , Adulto , Anciano , Anciano de 80 o más Años , Pruebas Respiratorias , Cromatografía Líquida de Alta Presión/métodos , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y EspecificidadRESUMEN
T cell activation via dendritic cells (DC) is an important step in the adaptive immune response, which requires DC maturation, migration to lymph nodes and presentation of antigen to T cells. CD137 receptor expressed on activated T cells is a potent costimulatory molecule. Here, we investigated the functions of CD137 ligand (CD137L) in human monocyte-derived DC during an immune response. Cross-linking of CD137L on DC leads to cell maturation in an autocrine fashion, mostly via release of TNF-alpha. Reverse signaling of CD137L also mediates migration of DC via up-regulation of the CCR7 chemokine receptor, demonstrated by an in vivo MIP-3beta-dependent SCID mouse migration model. Finally, CD137L-activated DC induce differentiation of human T cells into potent Th1 effectors. Cocultivation of autologous T cells and CD137L-activated DC in an antigen-specific reaction leads to T cell proliferation and the release of IL-12p70 and IFN-gamma. These findings deliver new insights into the multiple effects of reverse signaling of CD137L in human DC during the initiation of an adaptive immune response, including the key features of DC maturation, migration and, ultimately, antigen-specific T cell differentiation.