Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Pediatr Diabetes ; 21(8): 1556-1565, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32985057

RESUMO

BACKGROUND: The spectrum of skin disorders in children with type 1 diabetes (T1D) and their impact on affected persons are still incompletely understood. This study assessed the prevalence of skin diseases, cutaneous complications associated with T1D treatment and skin-related quality of life (QoL) in young T1D persons. METHODS: Participation in this interdisciplinary, single-center, cross-sectional, observational study was offered to all persons with T1D ≤20 years. Participants were characterized by a detailed medical history, routine laboratory workup, thorough clinical examinations and an established QoL questionnaire. RESULTS: Three hundred and sixty-nine persons were recruited (55% male; age 12.3 ± 4.4 years; HbA1c 7.4 ± 1.0%; mean ± SD). Continuous subcutaneous insulin infusion (CSII) was used by 72.4%, multiple daily injections (MDI) by 27.6% and continuous glucose monitoring (CGM) by 76%. Skin affections occurred in 91.8% of the study population. Device-associated lesions were most prevalent, including lipohypertrophy in 42.2% of MDI and 46.8% of CGM users and contact eczema associated with CSII or CGM in 14.2% and 18.3%, respectively. Diabetes-associated skin disorders and skin infections were rare or absent. Skin-related QoL impairment was low or absent in 95% of patients. CONCLUSIONS: Skin diseases have a high prevalence and a broad spectrum in young persons with T1D. Eczematous reactions to CSII and CGM devices represent the most frequent skin complications. This highlights the need for regular skin checkups as an integral part of pediatric diabetes consultations and interdisciplinary cooperation for classification and treatment options.


Assuntos
Automonitorização da Glicemia/efeitos adversos , Diabetes Mellitus Tipo 1/complicações , Sistemas de Infusão de Insulina/efeitos adversos , Qualidade de Vida , Dermatopatias/etiologia , Adolescente , Glicemia/metabolismo , Automonitorização da Glicemia/instrumentação , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Feminino , Alemanha/epidemiologia , Humanos , Incidência , Lactente , Masculino , Dermatopatias/epidemiologia , Adulto Jovem
3.
Nat Immunol ; 18(6): 622-632, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28459433

RESUMO

The high risk of neonatal death from sepsis is thought to result from impaired responses by innate immune cells; however, the clinical observation of hyperinflammatory courses of neonatal sepsis contradicts this concept. Using transcriptomic, epigenetic and immunological approaches, we demonstrated that high amounts of the perinatal alarmins S100A8 and S100A9 specifically altered MyD88-dependent proinflammatory gene programs. S100 programming prevented hyperinflammatory responses without impairing pathogen defense. TRIF-adaptor-dependent regulatory genes remained unaffected by perinatal S100 programming and responded strongly to lipopolysaccharide, but were barely expressed. Steady-state expression of TRIF-dependent genes increased only gradually during the first year of life in human neonates, shifting immune regulation toward the adult phenotype. Disruption of this critical sequence of transient alarmin programming and subsequent reprogramming of regulatory pathways increased the risk of hyperinflammation and sepsis. Collectively these data suggest that neonates are characterized by a selective, transient microbial unresponsiveness that prevents harmful hyperinflammation in the delicate neonate while allowing for sufficient immunological protection.


Assuntos
Calgranulina A/imunologia , Calgranulina B/imunologia , Imunidade Inata/imunologia , Monócitos/imunologia , Sepse Neonatal/imunologia , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/imunologia , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Animais Recém-Nascidos , Calgranulina A/efeitos dos fármacos , Calgranulina B/efeitos dos fármacos , Epigênese Genética , Sangue Fetal , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunidade Inata/efeitos dos fármacos , Immunoblotting , Recém-Nascido , Inflamação , Lipopolissacarídeos/farmacologia , Camundongos , Camundongos Knockout , Monócitos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/imunologia , Sepse Neonatal/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptor 4 Toll-Like/imunologia
4.
FASEB J ; 31(3): 1153-1164, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27993995

RESUMO

The high susceptibility of newborn infants to sepsis is ascribed to an immaturity of the neonatal immune system, but the molecular mechanisms remain unclear. Newborn monocytes massively release the alarmins S100A8/S100A9. In adults, these are major regulators of immunosuppressive myeloid-derived suppressor cells (MDSCs). We investigated whether S100A8/S100A9 cause an expansion of monocytic MDSCs (Mo-MDSCs) in neonates, thereby contributing to an immunocompromised state. Mo-MDSCs have been assigned to CD14+/human leukocyte antigen (HLA)-DR-/low/CD33+ monocytes in humans and to CD11b+/Gr-1int/Ly6G-/Ly6Chi cells in mice. We found monocytes with these phenotypes significantly expanded in their respective newborns. Functionally, however, they did not prove immunosuppressive but rather responded inflammatorily to microbial stimulation. Their expansion did not correlate with high S100A8/S100A9 levels in cord blood. Murine studies revealed an excessive expansion of CD11b+/Gr-1int/Ly6G-/Ly6Chi monocytes in S100A9-/- neonates compared to wild-type neonates. This strong baseline expansion was associated with hyperinflammatory responses during endotoxemia and fatal septic courses. Treating S100A9-/- neonates directly after birth with S100A8/S100A9 alarmins prevented excessive expansion of this inflammatory monocyte population and death from septic shock. Our data suggest that a specific population of inflammatory monocytes promotes fatal courses of sepsis in neonates if its expansion is not regulated by S100A8/S100A9 alarmins.-Heinemann, A. S., Pirr, S., Fehlhaber, B., Mellinger, L., Burgmann, J., Busse, M., Ginzel, M., Friesenhagen, J., von Köckritz-Blickwede, M., Ulas, T., von Kaisenberg, C. S., Roth, J., Vogl, T., Viemann, D. In neonates S100A8/S100A9 alarmins prevent the expansion of a specific inflammatory monocyte population promoting septic shock.


Assuntos
Alarminas/sangue , Calgranulina A/sangue , Calgranulina B/sangue , Monócitos/imunologia , Sepse Neonatal/sangue , Animais , Calgranulina A/uso terapêutico , Calgranulina B/uso terapêutico , Células Cultivadas , Feminino , Humanos , Recém-Nascido , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sepse Neonatal/prevenção & controle , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/genética , Lectina 3 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo
5.
Cell Rep ; 9(6): 2112-23, 2014 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-25497086

RESUMO

Hyporesponsiveness by phagocytes is a well-known phenomenon in sepsis that is frequently induced by low-dose endotoxin stimulation of Toll-like receptor 4 (TLR4) but can also be found under sterile inflammatory conditions. We now demonstrate that the endogenous alarmins MRP8 and MRP14 induce phagocyte hyporesponsiveness via chromatin modifications in a TLR4-dependent manner that results in enhanced survival to septic shock in mice. During sterile inflammation, polytrauma and burn trauma patients initially present with high serum concentrations of myeloid-related proteins (MRPs). Human neonatal phagocytes are primed for hyporesponsiveness by increased peripartal MRP concentrations, which was confirmed in murine neonatal endotoxinemia in wild-type and MRP14(-/-) mice. Our data therefore indicate that alarmin-triggered phagocyte tolerance represents a regulatory mechanism for the susceptibility of neonates during systemic infections and sterile inflammation.


Assuntos
Calgranulina A/metabolismo , Calgranulina B/metabolismo , Tolerância Imunológica , Fagócitos/metabolismo , Adulto , Idoso , Animais , Queimaduras/imunologia , Queimaduras/metabolismo , Calgranulina A/sangue , Calgranulina A/genética , Calgranulina B/sangue , Calgranulina B/genética , Linhagem Celular , Células Cultivadas , Montagem e Desmontagem da Cromatina , Feminino , Humanos , Inflamação/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Fagócitos/imunologia , Choque Séptico/imunologia , Choque Séptico/metabolismo , Estresse Fisiológico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...