Search

In the wound bed of chronic venous leg ulcers, an imbalance of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) may cause excessive proteolysis and impair wound granulation. Soluble mediators in the wound environment may be responsible for this imbalance. The in vitro effect of wound fluid from venous leg ulcers on dermal fibroblast production of MMP-1, MMP-3 and TIMP-1 was compared with the effect of acute wound fluid from two different sources: fluid from post-mastectomy axillary drains and fluid from skin graft donor sites. Significantly higher MMP-1 and MMP-3 levels were induced by chronic venous leg ulcer wound fluid compared with both types of acute wound fluid (P < 0.005). Chronic venous ulcer wound fluid reduced TIMP-1 protein levels significantly more than acute graft fluid (P < 0.05). Venous ulcer wound fluid significantly increased MMP-1 and MMP-3 production in dermal fibroblasts and reduced TIMP-1 production, confirming that mediators in the leg ulcer microenvironment can potentially induce excessive proteolysis in the ulcer dermis by altering the balance between MMPs and TIMPs. Inflammatory mediators including interleukin-1beta and tumour necrosis factor-alpha can induce these MMPs. Further work is required to confirm the factors responsible for the induction of a high MMP and low TIMP profile in fibroblasts by venous ulcer wound fluid.

Unlabelled: Coagulation factors (F)VIIa, FXa and thrombin are implicated in cellular responses in vascular, mesenchymal and inflammatory cells. Fibroblasts are the most abundant cells in connective tissue, and damage to blood vessels places coagulation factors in contact with these and other cell types., Objectives: To investigate cellular responses of primary dermal fibroblasts to FVIIa, FXa and thrombin by following changes in expression of candidate proteins: monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8), interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), and to determine the expression of receptors implicated in signaling by these coagulation factors., Methods: Steady-state mRNA levels were quantified by RNase protection assay, and protein secretion by ELISA. PAR gene expression was assessed by ribonuclease protection assay and conventional and quantitative reverse-transcription-polymerase chain reaction., Results: FVIIa did not induce the candidate genes. In contrast, FXa and thrombin induced MCP-1 mRNA and protein secretion strongly, IL-8 moderately, and IL-6 weakly. Neither FXa nor thrombin induced VEGF mRNA or protein secretion, although FXa induced VEGF protein secretion in lung fibroblasts. Comparison of the presence of candidate receptors in the two fibroblast subtypes demonstrated higher levels of PAR-1 and PAR-3 in lung fibroblasts relative to their dermal counterparts and the additional expression of PAR-2., Conclusions: FXa and thrombin induce expression of MCP-1, IL-8 and IL-6, and distribution and expression of PARs on dermal fibroblasts is reduced relative to their lung counterparts. Tissue origin may influence the cellular response of fibroblasts to coagulation proteases.

Tyrosine aminotransferase (TyrAT) is one of several gluconeogenic enzymes which appear postnatally in humans and rodents in response to increased glucocorticoid and glucagon levels and decreased insulin. Primary cultured fetal rat hepatocytes older than day 15 of gestation (>E15) transcribe the TyrAT gene in response to the synergistic effect of dexamethasone and N6,2'-O-dibutyryl-adenosine 3',5'-monophosphate (Bt2cAMP), whereas less mature hepatocytes (E15 hepatocytes, and not

During a survey period of 9 months, diabetic patients attending an outpatient clinic were asked routinely by the nursing staff to produce their home urine/glucose monitoring charts and diet charts. If they could not do so, the importance of bringing these charts was explained and they were instructed to bring their charts at subsequent visits. In addition, the individual responses of 109 consecutive patients were monitored as index cases. The physicians of these 109 patients were asked to grade each patient according to their estimate of the patient's compliance. This subjective rating was correlated with the actual performance of the patients in bringing charts. During the survey the overall number of patients attending the clinic who brought urine/blood charts increased from 31% to 59%. The corresponding figures for diet charts were 6% and 21%. Before intervention, the group rated "high compliance" was more likely than the "low compliance" rated group to bring urine/glucose charts. However, after adjustment for this baseline difference the subsequent performances of the high and low rated groups were comparable. These two groups of patients also performed similarly with respect to diet charts. It is concluded that patients judged subjectively to have poor compliance were able to modify their behaviour similarly to those assessed as having good compliance.