RESUMO
PURPOSE: Vitamin D deficiency is related to metabolic disturbances. Indeed, a poor vitamin D status has been usually detected in patients with cardiovascular disease (CVD). However, the relationship between vitamin D and CVD risk factors in young adults remains controversial at present. This study aimed to examine the association between circulating 25-hydroxivitamin D (25(OH)D) and CVD risk factors in young adults. METHODS: The present cross-sectional study included a cohort of 177 young adults aged 18-25 years old (65% women). 25(OH)D serum concentrations were assessed using a competitive chemiluminescence immunoassay. Fasting CVD risk factors (i.e., body composition, blood pressure, glucose metabolism, lipid profile, liver, and inflammatory markers) were determined by routine methods. A panel of 63 oxylipins and endocannabinoids (eCBs) was also analyzed by targeted metabolomics. RESULTS: Circulating 25(OH)D concentrations were inversely associated with a wide range of CVD risk factors including anthropometrical (all P ≤ 0.005), body composition (all P ≤ 0.038), glucose metabolism (all P ≤ 0.029), lipid profile (all P < 0.035), liver (all P ≤ 0.011), and pro-inflammatory biomarkers (all P ≤ 0.030). No associations of serum 25(OH)D concentrations were found with pro-inflammatory markers (all P ≥ 0.104), omega-6 and omega-3 oxylipins, nor eCBs concentrations or their analogs (all P ≥ 0.05). CONCLUSION: The present findings support the idea that 25(OH)D could be a useful predictor of CVD risk in young individuals.
Assuntos
Doenças Cardiovasculares , Deficiência de Vitamina D , Vitamina D , Humanos , Feminino , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/epidemiologia , Masculino , Adulto Jovem , Estudos Transversais , Adulto , Vitamina D/sangue , Vitamina D/análogos & derivados , Adolescente , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/complicações , Fatores de Risco , Biomarcadores/sangue , Fatores de Risco de Doenças CardíacasRESUMO
The negative effect of increasing atmospheric nitrogen (N) pollution on grassland biodiversity is now incontrovertible. However, the recent introduction of cleaner technologies in the UK has led to reductions in the emissions of nitrogen oxides, with concomitant decreases in N deposition. The degree to which grassland biodiversity can be expected to 'bounce back' in response to these improvements in air quality is uncertain, with a suggestion that long-term chronic N addition may lead to an alternative low biodiversity state. Here we present evidence from the 160-year-old Park Grass Experiment at Rothamsted Research, UK, that shows a positive response of biodiversity to reducing N addition from either atmospheric pollution or fertilizers. The proportion of legumes, species richness and diversity increased across the experiment between 1991 and 2012 as both wet and dry N deposition declined. Plots that stopped receiving inorganic N fertilizer in 1989 recovered much of the diversity that had been lost, especially if limed. There was no evidence that chronic N addition has resulted in an alternative low biodiversity state on the Park Grass plots, except where there has been extreme acidification, although it is likely that the recovery of plant communities has been facilitated by the twice-yearly mowing and removal of biomass. This may also explain why a comparable response of plant communities to reduced N inputs has yet to be observed in the wider landscape.
Assuntos
Poluição do Ar/efeitos adversos , Biodiversidade , Recuperação e Remediação Ambiental , Pradaria , Nitrogênio/efeitos adversos , Poaceae/classificação , Poaceae/efeitos dos fármacos , Poluição do Ar/análise , Atmosfera/química , Biomassa , Fabaceae/efeitos dos fármacos , Fabaceae/metabolismo , Fertilizantes/efeitos adversos , Fertilizantes/análise , Concentração de Íons de Hidrogênio , Nitrogênio/análise , Parques Recreativos , Poaceae/metabolismo , Reino UnidoRESUMO
Cancer cell invasion takes place at the cancer-host interface and is a prerequisite for distant metastasis. The relationships between current biological and clinical concepts such as cell migration modes, tumour budding and epithelial-mesenchymal transition (EMT) remains unclear in several aspects, especially for the 'real' situation in human cancer. We developed a novel method that provides exact three-dimensional (3D) information on both microscopic morphology and gene expression, over a virtually unlimited spatial range, by reconstruction from serial immunostained tissue slices. Quantitative 3D assessment of tumour budding at the cancer-host interface in human pancreatic, colorectal, lung and breast adenocarcinoma suggests collective cell migration as the mechanism of cancer cell invasion, while single cancer cell migration seems to be virtually absent. Budding tumour cells display a shift towards spindle-like as well as a rounded morphology. This is associated with decreased E-cadherin staining intensity and a shift from membranous to cytoplasmic staining, as well as increased nuclear ZEB1 expression.
Assuntos
Adenocarcinoma/patologia , Transição Epitelial-Mesenquimal , Invasividade Neoplásica/patologia , Biomarcadores Tumorais/análise , Humanos , Imageamento Tridimensional , Imuno-HistoquímicaRESUMO
Signal transducer and activator of transcription 3 (STAT3) is altered in several epithelial cancers and represents a potential therapeutic target. Here, STAT3 expression, activity and cellular functions were examined in two main histotypes of esophageal carcinomas. In situ, immunohistochemistry for STAT3 and STAT3-Tyr705 phosphorylation (P-STAT3) in esophageal squamous cell carcinomas (ESCC, n=49) and Barrett's adenocarcinomas (BAC, n=61) revealed similar STAT3 expression in ESCCs and BACs (P=0.109), but preferentially activated P-STAT3 in ESCCs (P=0.013). In vitro, strong STAT3 activation was seen by epidermal growth factor (EGF) stimulation in OE21 (ESCC) cells, whereas OE33 (BAC) cells showed constitutive weak STAT3 activation. STAT3 knockdown significantly reduced cell proliferation of OE21 (P=0.0148) and OE33 (P=0.0243) cells. Importantly, STAT3 knockdown reduced cell migration of OE33 cells by 2.5-fold in two types of migration assays (P=0.073, P=0.015), but not in OE21 cells (P=0.1079, P=0.386). Investigation of transcriptome analysis of STAT3 knockdown revealed a reduced STAT3 level associated with significant downregulation of cell cycle genes in both OE21 (P<0.0001) and OE33 (P=0.01) cells. In contrast, genes promoting cell migration (CTHRC1) were markedly upregulated in OE21 cells, whereas a gene linked to tight-junction stabilization and restricted cell motility (SHROOM2) was downregulated in OE21 but upregulated in OE33 cells. This study shows frequent, but distinct, patterns of STAT3 expression and activation in ESCCs and BACs. STAT3 knockdown reduces cell proliferation in ESCC and BAC cells, inhibits migration of BAC cells and may support cell migration of ESCC cells. Thereby, novel STAT3-regulated genes involved in ESCC and BAC cell proliferation and cell migration were identified. Thus, STAT3 may be further exploited as a potential novel therapeutic target, however, by careful distinction between the two histotypes of esophageal cancers.
Assuntos
Adenocarcinoma/metabolismo , Esôfago de Barrett/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/biossíntese , Adenocarcinoma/genética , Adenocarcinoma/patologia , Esôfago de Barrett/genética , Esôfago de Barrett/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Ciclo Celular/genética , Processos de Crescimento Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação para Baixo , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago , Técnicas de Silenciamento de Genes , Humanos , Fosforilação , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Regulação para CimaAssuntos
Neoplasias da Orelha/complicações , Neoplasias da Orelha/cirurgia , Perda Auditiva/etiologia , Hemangioma/complicações , Hemangioma/cirurgia , Doenças do Labirinto/complicações , Doenças do Labirinto/cirurgia , Diagnóstico Diferencial , Neoplasias da Orelha/diagnóstico , Perda Auditiva/diagnóstico , Perda Auditiva/prevenção & controle , Hemangioma/diagnóstico , Humanos , Doenças do Labirinto/diagnóstico , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
iThemba Laboratory for Accelerator Based Science (iThemba LABS) is a multi-disciplinary accelerator facility. One of its main activities is the operation of a separated-sector cyclotron with a K-value of 200, which provides beams of various ion species. These beams are used for fundamental nuclear physics research in the intermediate energy region, radioisotope production, and medical physics applications. Due to the requirements of nuclear physics for new ion species and higher energies, the decision was made to install a copy of the so-called Grenoble test source (GTS) at iThemba LABS. In this paper, we will report on the experimental setup and the first results obtained with the GTS2 at iThemba LABS.
Assuntos
Cardiologia/educação , Competência Clínica , Currículo , Especialização , Humanos , Sociedades MédicasAssuntos
Antimaláricos/química , Antimaláricos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Artemisia/química , Cumarínicos/química , Cumarínicos/farmacologia , Plantas Medicinais/química , Rubiaceae/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , África Austral , Animais , Divisão Celular/efeitos dos fármacos , América Central , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Ensaios de Seleção de Medicamentos Antitumorais , Plasmodium falciparum/efeitos dos fármacos , Células Tumorais CultivadasRESUMO
The analgesic potency of butorphanol 25 microg/kg bodyweight (BW) and levomethadone 100 microg/kg BW, administered together with detomidine 10 microg/kg BW, was measured in twelve Warmblood horses in a randomized, blinded cross-over study. Detomidine with saline 10 ml 0.9% was used as placebo. The nociceptive threshold was determined using a constant current and a pneumatic pressure model for somatic pair Detomidine alone and in combination with butorphanol or levomethadone caused a significant temporary increase (P < 0.05) of the nociceptive threshold with a maximum effect within 15 min and a return to baseline levels within 90 min. Butorphanol and levomethadone increased the nociceptive threshold and prolonged the duration of anti-nociception significantly from 15 to 75 min (P < 0.05) after drug administration compared with detomidine alone to both test methods. No significant difference between butorphanol and levomethadone was registered. It is concluded that the addition of butorphanol or levomethadone to detomidine increases the nociceptive threshold to somatic pain and prolongs the analgesic effect of detomidine in the horse.
Assuntos
Analgésicos Opioides , Butorfanol , Cavalos/fisiologia , Hipnóticos e Sedativos , Imidazóis , Metadona , Animais , Estudos Cross-Over , Feminino , Masculino , Medição da Dor/veterináriaRESUMO
The stem bark of Exostema mexicanum (Rubiaceae) is used in Latin American folk medicine as a quinine substitute for malaria treatment. Bioassay-guided fractionation of lipophilic and hydrophilic extracts from the stem bark and branches yielded two previously undescribed 4-phenylcoumarins: 4',8-dihydroxy-5,7-dimethoxy-4-phenylcoumarin (exomexin A) and 3',4'-dihydroxy-5,7,8-trimethoxy-4-phenylcoumarin (exomexin B). Together with five known derivatives the in vitro activities against a chloroquine-sensitive strain (poW) and a chloroquine-resistant strain (Dd2) of Plasmodium falciparum have been evaluated. The most lipophilic compound, 4',5,7,8-tetramethoxy-4-phenylcoumarin (O-methylexostemin) revealed the strongest antiplasmodial activity (IC50 values: 3.6 microg/ml [poW], 1.6 microg/ml [Dd2]).
Assuntos
Antimaláricos/farmacologia , Cumarínicos/farmacologia , Magnoliopsida/química , Plasmodium falciparum/efeitos dos fármacos , Rubiaceae/química , Animais , Cumarínicos/química , Cumarínicos/isolamento & purificação , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura MolecularRESUMO
OBJECTIVES: Many antineoplastic drugs were found to have carcinogenic, mutagenic and teratogenic potential. The aim of this study was to carry out cytogenetic and internal dose monitoring of hospital pharmacy personnel regularly involved in the preparation of cytostatic agents, in order to test possible cytostatics-induced genotoxic effects due to occupational exposure under routine working conditions, and in cases of accidental contamination. METHODS: Platinum in whole blood and anthracyclines in plasma were measured to assess internal exposure to cytostatics. The level of cytogenetic damage was determined in peripheral blood lymphocytes with the micronucleus test and the sister chromatid exchange assay. Five series of monitoring were performed over a period of 2 years. RESULTS: No significant differences in the mean frequencies of sister chromatid exchanges (SCE) and micronuclei (MN) were found between occupationally exposed probands and controls (9.9 +/- 1.4 vs 10.1 +/- 1.2 SCEs/cell and 21.2 +/- 7.2 vs 23.3 +/- 7.5 MN/2000 binucleated (BN) cells, n = 16). Significant elevations of SCE or MN were detected in seven out of 12 cases of accidental contamination at the workplace, whereas no increase in platinum in blood and anthracyclines in plasma was observed in these probands. Two cases of non-reported contamination were identified by measurement of epirubicin in plasma. Smoking was found to increase the SCE significantly. No correlation between individual SCE scores and MN scores was observed. CONCLUSIONS: Our findings support a transient increase in SCE or MN after relevant exposure to cytostatic drugs in cases of accidental contamination. The lack of significant differences in SCE and MN between hospital pharmacy personnel and unexposed controls, points to high standards of safety at the corresponding workplaces.
Assuntos
Antineoplásicos/efeitos adversos , Micronúcleos com Defeito Cromossômico/efeitos dos fármacos , Exposição Ocupacional/efeitos adversos , Serviço de Farmácia Hospitalar , Troca de Cromátide Irmã/efeitos dos fármacos , Adulto , Antraciclinas/sangue , Estudos de Casos e Controles , Análise Citogenética , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Micronúcleos com Defeito Cromossômico/genética , Pessoa de Meia-Idade , Platina/sangue , Troca de Cromátide Irmã/genética , Recursos HumanosRESUMO
Unobserved differences in individual's susceptibility to death are an important aspect in the analysis of contemporary mortality patterns. However, observed mortality rates at adult ages, which are usually well described by a Gompertz curve, are often perceived inconsistent with frailty models of mortality. The authors therefore propose a modified DeMoivre hazard function that is suitable for the application of frailty models to adult and old ages. The proposed hazard increases faster than exponential, and when combined with unobserved frailty it can capture a broad range of patterns encountered in the analysis of adult mortality. The authors' application to Bulgaria during 1992-93 suggests that the stronger selection process in the male population, caused by an overall higher level of mortality, may constitute a primary mechanism leading to the convergence of male and female mortality at higher ages. Hence, the convergence between male and female mortality is not necessarily caused by differential process of aging across sexes, but is merely a consequence of the different levels of mortality at adult ages.
Assuntos
Adulto , Idoso , Modelos Teóricos , Mortalidade , Fatores Sexuais , Fatores Etários , Bulgária , Demografia , Países Desenvolvidos , Europa (Continente) , Europa Oriental , População , Características da População , Dinâmica Populacional , PesquisaRESUMO
The anaesthetic effect of carbon dioxide (CO2) was investigated under predetermined exposure times in rats, mice and guinea pigs with admixture of 20% of oxygen (O2), and with 20% of ambient air in rats. In rats first symptoms (median) were detectable between 7 and 9.5 s, the induction time (median) varied between 16 and 20.5 s and the surgical tolerance (median) was 40 s (after 60 s of exposure) and 53.5 s (after 120 s of exposure) to 80% CO2/20% O2. When O2 was replaced by ambient air, a surgical tolerance of 53.5 s (after 60 s of exposure) and 77 s (after 120 s of exposure) was measured. In mice the induction time to 80% CO2/20% O2 was 10 s and the surgical tolerance 19.5 s (after 120 s of exposure). Guinea pigs showed an induction period of 20 s and a surgical tolerance of 50 s (after 30 s of exposure) to 80% CO2/O2. Recovery was short and smooth in all species. This method of general anaesthesia seems to be suitable for short and painful interventions, mainly in rats, but also in guinea pigs.
Assuntos
Anestesia por Inalação/veterinária , Bem-Estar do Animal , Dióxido de Carbono/farmacologia , Cobaias/fisiologia , Camundongos/fisiologia , Ratos/fisiologia , Anestesia por Inalação/métodos , Animais , Dióxido de Carbono/administração & dosagem , Feminino , Masculino , Oxigênio/administração & dosagem , Oxigênio/farmacologiaRESUMO
A 5-year-old guinea pig was presented to the University of Berne Small Animal Radiology Department for an ultrasound examination of the abdomen to confirm a suspected diagnosis of Cushing's syndrome. The patient had bilateral alopecia, was apathic and obese. Ultrasonographically, a tumor of the left adrenal gland, obstruction of the left ureter by an ureterolith, as well as hydronephrosis of the left kidney were detected. During surgery to relieve the ureteral obstruction the adrenal gland tumor was removed. The guinea pig died post-operatively due to blood loss. The left adrenal gland tumor was found histopathologically to be an adenoma and the right adrenal gland also had multiple small adenomas, but grossly appeared normal. The ureterolith was analyzed and found by x-ray diffraction to consist of calcium carbonate.
Assuntos
Adenoma/veterinária , Neoplasias das Glândulas Suprarrenais/veterinária , Cobaias , Doenças dos Roedores/diagnóstico por imagem , Cálculos Ureterais/veterinária , Adenoma/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Alopecia/diagnóstico por imagem , Alopecia/veterinária , Animais , Carbonato de Cálcio/análise , Síndrome de Cushing/diagnóstico por imagem , Síndrome de Cushing/veterinária , Hidronefrose/diagnóstico por imagem , Hidronefrose/veterinária , Masculino , Obesidade/diagnóstico por imagem , Obesidade/veterinária , Hemorragia Pós-Operatória/veterinária , Ultrassonografia , Cálculos Ureterais/química , Cálculos Ureterais/diagnóstico por imagem , Difração de Raios XRESUMO
General anaesthesia with 80% CO2/20% O2 and 5% halothane in O2 (mask induction) was compared for castration of 3-4 week-old piglets. One group was castrated without anaesthesia. Of the noncastrated control groups one had CO2- and one halothane anaesthesia, one breathed room air through the induction system, and one was held in castration position. The behaviour to induction and castration was assessed, and the cortisol-, ACTH- and beta-endorphin plasma concentrations were determined to quantify the stress elicited by anaesthesia, castration and handling. Violent struggling and vocalization were elicited by CO2 and positioning into the mask induction system while breathing room air; halothane induction was quiet. CO2 induced profound surgical anaesthesia; whereas under halothane anaesthesia some animals exhibited still a slight reaction to castration. Recovery was fast, smooth and quite. Permanent violent struggling and vocalization were elicited by castration without anaesthesia. Plasma cortisol was not a sensitive tool to judge castration stress. The high ACTH and beta-endorphin plasma concentrations elicited by CO2 anaesthesia confirm our clinical experience. General anaesthesia is fast and safely induced with CO2 in piglets and castration can be performed without any reaction, but with CO2 anaesthesia the stress is not reduced.
Assuntos
Anestesia por Inalação/veterinária , Dióxido de Carbono , Halotano , Orquiectomia/veterinária , Anestesia por Inalação/instrumentação , Anestesia por Inalação/métodos , Animais , Masculino , SuínosRESUMO
The class III receptor tyrosine kinase FLT3/FLK2 (FLT3; CD135) represents an important molecule involved in early steps of hematopoiesis. Here we compare cell-surface expression of FLT3 on bone marrow (BM) and cord blood (CB) cells using monoclonal antibodies (MoAbs) specific for the extracellular domain of human FLT3. Flow cytometric analysis of MACS-purified BM and CB cells showed that 63% to 82% of BM CD34+ and 88% to 95% of the CB CD34+ cells coexpress FLT3. Clonogenic assays and morphological characterization of FACS-sorted BM CD34+ cells demonstrate that colony-forming unit-granulocyte-macrophage (CFU-GM) and immature myelo-monocytic precursor cells are enriched in the subpopulation staining most brightly with the FLT3 MoAb whereas the majority of the burst-forming units-erythroid (BTU-E) and small cells with lymphoid morphology are found in the FLT3- population. In contrast, statistically indistinguishable proportions of CFU-granulocyte-erythrocyte-megakaryocyte-macrophage (CFU-GEMM) and more primitive cobblestone area forming cells (CAFC) were detected in both fractions, albeit the FLT3+ fraction consistently showed more CAFC activity than the FLT3- fraction. Although in both, BM and CB the majority of CD34+CD117+ (KIT+), CD34+CD90+ (Thy-1+), and CD34+CD109+ cells coexpress FLT3, three-color phenotypic analyses are consistent with the functional findings and suggest that the most primitive cells defined as CD34+CD38-, CD34+CD71low, CD34+HLA-DR-, CD34+CD117low, CD34+CD90+, and CD34+CD109+ express low levels of cell-surface FLT3 and were therefore not enriched to a statistically significant extent with the bright versus negative sorting scheme. Thus, clear segregation of the most primitive progenitors from BM CD34+ cells was confounded by low apparent levels of FLT3 cell-surface expression on these cells, whereas myeloid progenitors unambiguously segregated with the FLT3 brightest cells and erythroid progenitors with the FLT3 dimmest. Additional phenotypic analyses using MoAbs against progenitor/stem cell markers including the mucinlike molecule MGC-24v (CD164), the receptor tyrosine kinases TIE, FMS (CD115), and KIT (CD117) further illustrate the differences in surface antigen expression profiles of BM and CB CD34+ cells. Notably, CD115 is rarely detected on CB CD34+ cells, whereas 20% to 25% of the BM CD34+FLT3+ cells are CD115+. Furthermore, 80% to 95% of the CB CD34+CD117+ but only 60% to 75% of the BM CD34+CD117+ cells coexpress FLT3. Only a negligible amount of CD34+CD19+ are detected in CB, while in BM 20% to 30% of CD34+CD19+ presumed pro/pre-B cells coexpress FLT3. In contrast, the majority of the CD34+CD164+ and CD34+TIE+ subsets in both CB and BM coexpress FLT3. Analysis of unseparated cells showed that FLT3 expression is not restricted to CD34+ subsets. About 65% to 70% of lymphocyte-gated BM CD34-FLT3+ cells are positive for the monocytic marker CD115 whereas 25% to 30% of these cells consist of CD10 expressing B-cell precursors. Finally, CD34- monocytes in BM, CB, and PB express FLT3 whereas granulocytes are FLT3-. Our data show that detectable FLT3 appears first at low levels on the surface of primitive multilineage progenitor cells and disappears during defined stages of B-cell development, but is upregulated and maintained during monocytic maturation.
Assuntos
Células da Medula Óssea , Sangue Fetal/citologia , Células-Tronco Hematopoéticas/citologia , Proteínas Proto-Oncogênicas/biossíntese , Receptores Proteína Tirosina Quinases/biossíntese , Medula Óssea/metabolismo , Diferenciação Celular , Feminino , Sangue Fetal/metabolismo , Citometria de Fluxo , Células-Tronco Hematopoéticas/metabolismo , Humanos , Imunofenotipagem , Recém-Nascido , Gravidez , Receptores de Superfície Celular , Tirosina Quinase 3 Semelhante a fmsRESUMO
Chronic skin colonization with Staphylococcus aureus is a characteristic feature of atopic eczema, and about 60% of S. aureus strains isolated from the skin of patients with atopic eczema secrete enterotoxins. T-cell stimulation by staphylococcal enterotoxins is restricted to the V beta-chain of the T-cell receptor. Therefore, the expression of different V beta-chains (V beta 3, 5 a,b,c, 6, 8, 12) on peripheral blood T-cells (CD4+) from patients with atopic eczema was measured by flowcytometry before and after stimulation with staphylococcal enterotoxin B. Lymphocytes from healthy donors served as controls. Additionally, the expression of V beta-chains in normal skin and in lesional skin of patients with atopic eczema was determined by immunofluorescence histology. In atopic eczema, higher numbers of CD4+ T-cells expressed V beta 3, V beta 8 and V beta 12 compared to the control group. No correlation between S. aureus enterotoxin B-stimulated V beta-expression and HLA-haplotypes was found. In lesional skin of patients with atopic eczema most of the infiltrating T-cells were V beta 3+, whereas in normal skin only very few T-cell receptor-expressing cells were detected. To evaluate the significance of these T-cell clones for allergic inflammation, T-cells from patients with atopic eczema and normal donors were stimulated with monoclonal antibodies against V beta 3, 5(c) and 8. Afterwards, the proliferative response of lymphocytes as well as IL-5 and IFN gamma synthesis were measured. T-cells from patients with atopic eczema showed a significantly higher proliferation and IL-5 secretion than normal donors after stimulation with monoclonal antibodies against V beta 3 and V beta 8. In contrast, the monoclonal antibodies directed to V beta 5(c) induced a markedly elevated proliferation and IFN gamma production of normal lymphocytes compared to patients with atopic eczema. Our results suggest a preferential expression of certain V beta-subgroups during inflammation in atopic eczema; this may be explained by a selective stimulation of TH2-cells via S. aureus-derived enterotoxins.
Assuntos
Dermatite Atópica/imunologia , Região Variável de Imunoglobulina/análise , Receptores de Antígenos de Linfócitos T alfa-beta/análise , Pele/imunologia , Células Cultivadas , Enterotoxinas/farmacologia , Citometria de Fluxo , Imunofluorescência , Antígenos de Histocompatibilidade Classe II/análise , Humanos , Interferon gama/análise , Interleucina-5/análise , Ativação Linfocitária , Staphylococcus aureus , Subpopulações de Linfócitos TRESUMO
BACKGROUND: The diagnosis of a chronic disease in children challenges parents' emotional coping abilities and cognitive capacities. OBJECTIVE: To study parents' emotional and cognitive reactions to the diagnosis of cystic fibrosis (CF) in their children. METHODS: Postal survey by means of a written questionnaire. PARTICIPANTS: Forty-six parents of 29 children with a median age of 2 months at diagnosis. RESULTS: Most parents initially lacked knowledge of CF (76%) and were provided only oral information (96%). Parental estimates of how much of the information given they had understood and retained were 77% and 76%, respectively, with 15 parents (33%) having understood and remembered less than 50% of what the physicians had told them. The most frequent stressing feelings were fear (83%) and despair (56%). Fifty-four percent of parents had initial shocklike reactions. In this group, a significant decrease in the understanding and recall of information was noted compared with parents who had less-emotional responses. CONCLUSIONS: Parents learning the diagnosis are, in effect, receiving a kind of lecture, which contains more information than they can possibly assimilate. Because of the incompatibility of emotional distress and optimum learning, impairment of early comprehension and retention of information about CF is unavoidable. Repeated interviews with both parents and the provision of written and audiovisual materials should be mandatory.
Assuntos
Comunicação , Fibrose Cística , Rememoração Mental , Pais/psicologia , Estresse Psicológico , Adulto , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-IdadeRESUMO
Interactions between keratinocytes and mononuclear cells via cytokines and adhesion molecules are thought to play a crucial part in inflammatory skin diseases. The cytokine-mediated effects of peripheral blood mononuclear cells (PBMC) from patients with atopic eczema (AE) and healthy individuals on keratinocytes (HaCaT) were investigated in vitro. A new coculture model (Transwell system) which consists of a lower and an upper compartment, which are separated by a polycarbonate-treated membrane, was established. 3[H]thymidine incorporation of keratinocytes and lymphocytes, as well as IL-6, IL-8 and IFN-gamma synthesis, were measured. Keratinocyte proliferation was significantly enhanced in the presence of PBMC from patients with AE. In contrast, PBMC from normal donors did not enhance HaCaT cell proliferation when they were cocultured. Lymphocytes from patients with AE showed a significantly enhanced proliferation after coculture with keratinocytes. However, PBMC from normal donors did not proliferate in the presence of HaCaT cells. Keratinocyte supernatants incubated with PBMC from either atopic or normal volunteers induced a suppression of lymphocyte 3[H]thymidine incorporation. In supernatants from cocultures of PBMC from patients with AE and keratinocytes, significantly enhanced amounts of IL-6 and IL-8, compared with normal donor's lymphocytes and HaCaT cells, were measured. No differences in IFN gamma production were observed. When PBMC were cultured without HaCaT cells, supernatants contained equal levels of IL-6, IL-8 and IFN-gamma in normal donors and in patients with AE. Interestingly, HaCaT cells spontaneously secrete measurable amounts of IL-6, IL-8 and IFN-gamma. Blocking experiments with neutralizing antibodies against these interleukins showed a complete inhibition of keratinocyte proliferation when PBMC from normal donors were used whereas the proliferative potency of PBMC supernatants from patients with AE on keratinocytes remained. Our data indicate that (i) PBMC from patients with AE stimulate keratinocyte proliferation via soluble factor(s) that are different from IL-6, IL-8 and IFN-gamma; (ii) probably, HaCaT cells spontaneously produce lymphocyte/monocyte inhibitory soluble factors and IL-6, IL-8 as well as IFN-gamma; and (iii) secretion and/or activity of keratinocyte-derived inhibitory mediators is regulated via cytokines of PBMC infiltrating inflammatory skin.
Assuntos
Citocinas/metabolismo , Dermatite Atópica/imunologia , Queratinócitos/fisiologia , Leucócitos Mononucleares/fisiologia , Anticorpos Monoclonais/farmacologia , Técnicas de Cultura de Células , Divisão Celular/fisiologia , Linhagem Celular , Técnicas de Cocultura , Humanos , Interferon gama/metabolismo , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Queratinócitos/citologia , Leucócitos Mononucleares/citologia , Timidina/metabolismoRESUMO
Unlike the other former Soviet-block countries, Eastern Germany/the "GDR", had the opportunity to the re-unification with a highly developed western country, the Federal Republic of (West) Germany in 1990. In order to record the following rapid improvements in renal replacement therapy, we performed our own survey in Eastern Germany--excluding Eastern Berlin--by questionnaire, comparing the years 1989/December, and 1994/December. 112 of the 113 dialysis facilities for adult regular dialysis patients replied to our questionnaire (99%). From 1989 to 1994, the number of dialysis centers increased from 53 to 113 (-->213%), reaching 7.9 centres p.m.p. Of these facilities, 29% were hospital centers, 48% were private dialysis units, and 23% were run by nonprofit dialysis organizations. The number of dialysis stations increased from 602 to 1,719 (-->286%), i.e. 120 stations p.m.p. The number of patients in regular dialysis treatment rose from 2,127 to 5,335 (-->251%), that means a prevalence of 373 patients p.m.p. In 1989, 67 new patients (p.m.p.) had been accepted for maintenance treatment (incidence), in contrast to 130 new patients p.m.p. in 1994 (-->194%), now under the conditions of unlimited accessibility to dialysis treatment. Questions referring to this point--the incidence of new patients--were only asked in Thüringen (2.5 mio. inhabitants). Alternative treatment modalities became feasible under the new conditions in Eastern Germany. In contrast to 99% hemodialysis patients in December 1989, at the end of 1994 92.8% of the patients were treated by hemodialysis, 2.0% by hemofiltration, and 5.2% by peritoneal dialysis, predominantly CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)