Biomedical subjects

Dagmar Klein

Publications and source records attributed to Dagmar Klein.

21 records · Page 2Linked to original sources

PubMed2002

Insulin attenuates the systemic inflammatory response to thermal trauma.

BACKGROUND: Insulin has been recently shown to decrease mortality and prevent the incidence of multi-organ failure in critically ill patients. The molecular mechanisms by which insulin improves survival have not been defined. The purpose of the present study was to determine the effect of insulin therapy on the systemic inflammatory response. In vivo we determined the effect of insulin therapy on the inflammatory cascade, which was induced by thermal injury. MATERIALS AND METHODS: Thermally injured rats (30% TBSA) were randomly divided into two groups to receive either saline (n= 28) or insulin (n= 28). Our outcome measures encompassed the effect of insulin on pro- inflammatory cytokines, anti-inflammatory cytokines, and hepatic signal transcription factor mRNA expression. RESULTS: Insulin significantly decreased dose dependently serum pro-inflammatory cytokines IL-1beta at 1, 5, and 7 days, IL-6 at 1 day, MIF at 5 and 7 days, and TNF at 1 and 2 days after injury when compared with controls (p<0.05). Insulin increased anti-inflammatory cytokines IL-2 and IL-4 at 5 and 7 days after trauma, and IL-10 at 2, 5 and 7 days after trauma when compared with controls (p< 0.05). Pro-inflammatory signal transcription factors STAT-5 and C/EBP-beta mRNA were significantly decreased 1 and 2 days posttrauma; insulin increased anti-inflammatory signal transcription factor mRNA expression of SOCS-3 and RANTES 7 days after the injury (p< 0.05). CONCLUSIONS: Our data provide insight that insulin attenuates the inflammatory response by decreasing the pro- inflammatory and increasing the anti-inflammatory cas-cade, thereby restoring systemic homeostasis, which has been shown critical for organ function and survival in critically ill patients.

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PubMedDate not supplied

Interaction of exogenous liposomal insulin-like growth factor-I cDNA gene transfer with growth factors on collagen expression in acute wounds.

Growth factors have been shown to modulate the complex cascade of wound healing, however, interaction between different growth factors during dermal and epidermal regeneration is still not entirely defined. We have recently shown that exogenous liposomal gene transfer of cDNA results in physiologic expression and response in an acute wound. In the present study we determined the interaction between insulin-like growth factor-I (IGF-I), a mesenchymal growth factor, administered as liposomal cDNA, with other dermal and epidermal growth factors on collagen synthesis in an acute wound. Sprague-Dawley rats were given a scald burn to inflict an acute wound and divided into two groups to receive weekly subcutaneous injections of liposomes plus a beta-galactosidase containing plasmid (Lac Z [0.2 microg, vehicle]), or liposomes plus the IGF-I cDNA containing plasmid (2.2 microg) and Lac Z (0.2 microg). Immunological assays, histological and immunohistochemical techniques were used to determine growth factor concentration and different types of collagen (I, III, and IV) after IGF-I cDNA gene transfer. IGF-I cDNA transfer accelerated reepithelization and was associated with increased levels of IGF-I, fibroblast growth factor, keratinocyte growth factor, vascular endothelial cell growth factor, and platelet-derived growth factor protein expression. IGF-I cDNA had no effect on transforming growth factor-beta. IGF-I cDNA significantly increased type IV collagen while it had no effect on types I and III collagen. Exogenously administered IGF-I cDNA increased protein concentrations of keratinocyte growth factor, fibroblast growth factor, platelet-derived growth factor, and type IV collagen. We conclude that liposomal IGF-I gene transfer can accelerate wound healing without causing an increase in types I and III collagen expression.

Animals↗

PubMedDate not supplied

Effect of oxidized regenerated cellulose/collagen matrix on dermal and epidermal healing and growth factors in an acute wound.

Rapid healing of acute wounds, e.g., in burned patients, can be essential for survival. Oxidized regenerated cellulose/collagen (ORC/collagen) has been shown to improve wound healing of chronic wounds. The aim of the present study was to determine the effect of ORC/collagen on dermal and epidermal healing as well as growth factor concentration in acute wounds. Rats received a full-thickness excision wound and were treated with either ORC/collagen plus a hydrocolloid dressing or a hydrocolloid dressing alone. Planimetry, immunological assays, histological and immunohistochemical techniques were used to determine dermal and epidermal regeneration, protein concentration, and growth factor concentration. In addition, dermal vascularization and structure were determined. Wounds treated with ORC/collagen showed a significantly faster reepithelization than those treated with hydrocolloid alone, p < 0.05. This accelerated wound healing rate may be explained by significantly higher levels of platelet-derived growth factor, keratinocyte growth factor, insulin-like growth factor-I, and insulin-like growth factor binding protein-3 in the ORC/collagen group leading to antiapoptotic effects of skin cells, p < 0.05. There were no significant differences in collagen morphology or deposition, neo-angiogenesis, or vascular endothelial growth factor concentration between both treatment groups. We conclude that ORC/collagen matrix accelerates epidermal regeneration and locally increases growth factor concentrations. Increased reepithelization was associated with decreased skin cell apoptosis. Based on our data we hypothesize that the ORC/collagen matrix may also have beneficial effects on acute wounds in a clinical setting.

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