RESUMO
Ultraviolet B (UVB) irradiation affects epidermal cells, which respond via a cascade of inflammation markers. After initial in vitro and ex vivo experiments, this study used cutaneous microdialysis to generate a kinetic profile for 16 cytokines and 4 prostanoids in human skin in vivo. Skin areas 9 cm2 were irradiated with UVB (2× minimal erythematous dose) 16 h after catheter placement in the dermis of the volar forearms of healthy volunteers. Dialysates were collected at 4-h intervals up to 64 h and analysed for 5- and 8-iso-PGF2α, 9α,11α-PGF2α and PGE2 by gas chromatography-mass spectrometry (GC/MS). Dialysates were also analysed for interleukin (IL)-1ß, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, Fas ligand (FasL), interferon-γ-inducible protein-10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), RANTES, eotaxin, and granulocyte-macrophage colony-stimulating factor (GM-CSF) using a multiplex-based cytometric-bead-array. In conclusion, 3 peaks with synchronic release of T helper (TH) 1-directed inflammatory cytokines and prostanoids could be detected post-UVB: an early phase (4-12 h), an intermediate phase (16-24 h) and a late phase (32-40 h). A TH2-directed cytokine response was detectable at intermediate and late phases.
Assuntos
Citocinas/metabolismo , Prostaglandinas/metabolismo , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta , Adulto , Células Cultivadas , Feminino , Antebraço , Cromatografia Gasosa-Espectrometria de Massas , Voluntários Saudáveis , Humanos , Masculino , Microdiálise , Pessoa de Meia-Idade , Pele/citologiaRESUMO
Atopic dermatitis (AD) is a multifactorial inflammatory skin disease with release of distinct inflammatory signals. This study investigated the presence of eicosanoids in AD skin and the effect of topical agents with potential to suppress inflammation. Twelve patients with moderate AD received topical treatment on either arm with tacrolimus 0.1% ointment or a lotion containing 12% ω-6 fatty acids (polyunsaturated fatty acids; PUFA) twice daily for 5 consecutive days. Interstitial fluid was collected in vivo via dermal microdialysis from 4 defined skin areas: lesional, non-lesional and topically treated skin (tacrolimus or PUFA). Markers of oxidative stress (F2-isoprostanes; 5- and 8-prostaglandin F2α) and inflammation (9α,11α-prostaglandin F2α; and prostaglandin E2) were determined by gas chromatography-mass spectrometry. All eicosanoid levels were reduced in non-lesional and tacrolimus-treated skin. A significant reduction was observed in total F2-isoprostanes; 9α,11α-prostaglandin F2α; and prostaglandin E2 in non-lesional skin and in 9α,11α-prostaglandin F2α in tacrolimus-treated compared with untreated AD skin. In conclusion, treatment with tacrolimus compared with PUFA appears to suppress eicosanoids more efficiently in AD skin.
Assuntos
Dermatite Atópica/tratamento farmacológico , Eicosanoides/metabolismo , Ácidos Graxos Insaturados/uso terapêutico , Imunossupressores/farmacologia , Microdiálise , Tacrolimo/farmacologia , Administração Tópica , Animais , Biomarcadores/metabolismo , Ácidos Graxos Insaturados/administração & dosagem , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunossupressores/administração & dosagem , Masculino , Estresse Oxidativo , Suínos , Tacrolimo/administração & dosagem , Adulto JovemAssuntos
Antialérgicos/administração & dosagem , Anticorpos Anti-Idiotípicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Imunoglobulina E/sangue , Biomarcadores/sangue , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Esquema de Medicação , Humanos , Masculino , Pessoa de Meia-Idade , Omalizumab , Recidiva , Indução de Remissão , Índice de Gravidade de Doença , Testes Cutâneos , Fatores de Tempo , Resultado do TratamentoAssuntos
Anti-Inflamatórios/farmacologia , Sedimentos Geológicos/química , Microdiálise , Água do Mar/química , Pele/efeitos dos fármacos , Cloreto de Sódio/farmacologia , Administração Cutânea , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Química Farmacêutica , Eritema/tratamento farmacológico , Eritema/etiologia , Humanos , Concentração de Íons de Hidrogênio , Pomadas , Prostaglandinas/metabolismo , Radiodermite/tratamento farmacológico , Radiodermite/etiologia , Água do Mar/efeitos adversos , Pele/metabolismo , Pele/efeitos da radiação , Cloreto de Sódio/administração & dosagem , Cloreto de Sódio/química , Fatores de Tempo , Perda Insensível de Água , Adulto JovemRESUMO
BACKGROUND: The transplantation of keratinocytes suspended in fibrin carrier represents a candidate regimen for chronic ulcer treatment in an outpatient setting. We evaluated the integration and survival of autologous individualized keratinocytes applied within fibrin matrix onto chronic venous leg ulcers in vivo. Parallel in vitro culture was used to validate keratinocyte survival and apoptosis in fibrin compared to collagen matrix carrier. METHODS: Seven patients with chronic venous leg ulcers were transplanted with autologous keratinocytes suspended in fibrin sealant after isolation and expansion from full-skin biopsy. The fibrin carrier was removed in three patients after 7 days, whereas four patients served as control with fibrin remaining. In parallel in vitro cultures, primary keratinocyte movement in fibrin as well as viability in three-dimensional (3D) fibrin versus collagen lattices was examined. RESULTS: Complete ulcer healing was observed in four of seven ulcers after a mean duration of 14.5 weeks. If the fibrin layer was removed, complete wound healing occurred in three of three patients, compared to one of four in the control group. In vitro, keratinocytes formed a monolayer underneath but remained isolated and nonmobile within the fibrin matrix, suggesting reepithelialization along the lower fibrin interphase. Keratinocyte culture in 3D fibrin at clinically used concentration (90 mg/mL) caused high levels of apoptosis, similar to 3D collagen, which was prevented by diluting fibrin concentration to 3 mg/mL. CONCLUSIONS: Transplantation of autologous keratinocytes suspended in fibrin is efficient in the treatment of chronic venous leg ulcers. Due to an antimigratory and survival-compromising effect, the presently used fibrin carrier should be removed after a few days of transplantation.
Assuntos
Queratinócitos/transplante , Úlcera Varicosa/terapia , Idoso , Idoso de 80 Anos ou mais , Apoptose , Sobrevivência Celular , Colágeno , Feminino , Fibrina , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Autólogo , CicatrizaçãoRESUMO
Serotonin plays an essential role in cognition, locomotor activity, and the regulation of sleep, pain, mood, and aggression. Polymorphisms of the HTR1B gene have been implicated in a variety of psychiatric disorders including attention deficit hyperactivity disorder (ADHD) and obsessive-compulsive disorder (OCD). The objectives of this study were to: (i) expand our original investigation of the relationship between the HTR1B receptor gene and attention deficit/hyperactivity and; (ii) to investigate a possible association of obsessive behaviors/perfectionism and the HTR1B gene in a sample of 203 families with an ADHD proband. Six single nucleotide polymorphisms (SNPs) of the HTR1B receptor gene were genotyped using standard methods. Evidence for an association between the HTR1B gene and ADHD as a qualitative diagnosis, or the inattentive and hyperactive-impulsive quantitative traits was not supported by either TDT single marker analysis or haplotype analysis. In addition we did not find evidence to suggest an association between HTR1B and perfectionism in this sample of ADHD families.