7 research outputs found
Therapeutic success and efficacy of nonviral liposomal cDNA gene transfer to the skin in vivo is dose dependent
It is well documented that responses to growth factor treatment typically display bell-shaped dose responses that can significantly affect efficacy. Here we tested the hypothesis that nonviral liposomal gene delivery also displays this characteristic. We chose two different growth factors, keratinocyte growth factor (KGF) and insulin-like growth factor-I (IGF-I) CMV-driven transfecting constructs at three different concentrations and assessed efficacy on several physiological parameters that are descriptive of wound healing progress in a burn-wound healing model. Rats were given a 60% TBSA scald burn and randomly divided into one of seven groups to receive weekly subcutaneous injections of liposomes containing the cDNA for KGF (0.2 microg, 2.2 microg, or 22.2 microg), or liposomes containing the cDNA for IGF-I (0.2 microg, 2.2 microg, or 22.2 microg) at various concentrations, but constant liposome:DNA ratios and a LacZ gene (0.2 microg) CMV-driven construct for beta-galactosidase as vehicle and marker gene. Transfection was confirmed by histology for beta-galactosidase. Physiological efficacy was evaluated by measuring the wound healing parameters that define dermal and epidermal regeneration. Transfection products were found in the cytoplasm of rapidly dividing cells of the granulation tissue. Different doses of the nonviral cDNA gene transfer coding for KGF or IGF-I resulted in different outcomes for dermal and epidermal regeneration. There was a dose-dependent response to both growth factor gene transfers that was not dissimilar from that typically displayed by treatment with growth factor proteins. Both concentrations below and above the optimal concentration of DNA:liposomal preparations did not yield the results observed at the optimal concentration
Lesões dermatolĂłgicas em pacientes infectados pelo vĂrus linfotrĂłpico humano de cĂ©lulas T do tipo 1 (HTLV-1) Dermatologic lesions in patients infected with the human T-cell lymphotropic vĂrus type 1 (HTLV-1)
O vĂrus linfotrĂłpico humano de cĂ©lulas T do tipo 1 (HTLV-1) Ă© o primeiro retrovĂrus isolado do ser humano. Descreveu-se, em pouco tempo, o seu papel etiolĂłgico em algumas doenças, com destaque para a leucemia/linfoma de cĂ©lulas T do adulto (ATLL), a mielopatia associada ao HTLV-1/paraparesia espástica tropical (HAM/TSP) e a uveĂte associada ao HTLV-1 (HAU). Na dĂ©cada de 90, o HTLV-1 foi associado a eczema grave da infância, conhecido como dermatite infecciosa (DI). Desde entĂŁo, diversos outros tipos de lesões cutâneas tĂŞm sido observados em pacientes infectados pelo HTLV-1, em especial, nos doentes de HAM/TSP ou de ATLL. PorĂ©m, mesmo portadores assintomáticos do vĂrus apresentam doenças dermatolĂłgicas. Excetuando-se a dermatite infecciosa, nĂŁo há lesĂŁo da pele especĂfica da infecção pelo HTLV-1. Aqui, os autores apresentam as principais lesões dermatolĂłgicas descritas em pacientes infectados pelo HTLV-1, destacando o valor epidemiolĂłgico e clĂnico desses achados.<br>Human T-cell Lymphotropic vĂrus type I (HTLV-1) was the first human retrovĂrus described. Some time after its discovery a group of diseases were related to this vĂrus, such as, adult T-cell leukemia lymphoma (ATLL), HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and HTLV-1 associated uveitis (HAU). In the nineties, HTLV-1 was associated to a severe eczema of children, called infective dermatitis (ID). Since then, several other skin manifestations have been observed in HTLV-1-infected individuals, particularly in patients with ATLL or HAM/TSP. However, according to some reports, dermatologic lesions are also common in asymptomatic HTLV-1 carriers. Besides ID, all other skin lesions reported are nonspecific. The aim of this review is to outline the dermatologic manifestations reported in HTLV-1 infected patients, emphasizing the clinical and epidemiological value of these findings