Fibroblasts from the transversalis fascia of young patients with direct inguinal hernias show constitutive MMP-2 overexpression.

OBJECTIVE: To determine the expression pattern of certain metalloproteinases (MMPs) known to be involved in the degradation of the extracellular matrix in cultured fibroblasts from the transversalis fascia (TF) of patients with inguinal hernia. SUMMARY BACKGROUND DATA: Inguinal hernia is a common pathology, the cause of which remains unknown. It is, however, clear that the TF is one of the anatomical structures that may impede the formation of hernias, and particularly the direct type of hernia. In previous studies the authors found enhanced MMP-2 expression in TF specimens in vivo. The persistence of increased expression in cultured fibroblasts might support the idea of a genetic defect as the cause for this pathology. METHODS: Fibroblasts from the TF of patients with direct and indirect inguinal hernia were cultured and compared with those obtained from control TF in terms of MMP (MMP-2 and MMP-9) expression. RESULTS: Significant active MMP-2 expression was shown by TF fibroblasts from young patients with direct hernias. These findings were confirmed by immunosorbent assay, immunoblotting, and zymography of the fibroblast culture media. No MMP-9 expression was detected. CONCLUSION: These results indicate that MMP-2 may be involved in the TF matrix degradative process in patients with direct hernia. The persistence of changes in MMP-2 levels in the cell cultures appears to suggest a genetic defect or irreversible change as the origin of this pathology rather than environmental factors, which may later participate in the development of the hernial process.

Cytokine levels after open and laparoscopic cholecystectomy.

A prospective study of serum cytokine levels was performed in patients randomly assigned to undergo either laparoscopic cholecystectomy (LC) or open cholecystectomy (OC). The kinetics of serum interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and cortisol were studied in both groups of patients. Cytokine and cortisol levels were measured in serum samples from patients who underwent either LC (n = 14) or OC (n = 14) using enzyme-linked immunosorbent assay and radioimmunoassay, respectively. Serum samples were obtained 24 h before surgery and 24 h and 7 days after surgery. IL-6 levels differed significantly (p < 0.05) between the LC and OC groups. IL-1 beta, IL-10, TNF-alpha and cortisol levels showed no significant differences (p > 0.05). Kinetic studies of IL-6, IL-1 beta and TNF-alpha levels revealed them to behave similarly, 24 h after surgery the levels of these cytokines were higher than those 24 h before surgery. These levels normalized by 7 days after surgery. Cytokine concentrations were always higher in the OC group than in the LC group. IL-1 beta and IL-10 levels were the most stable in both groups, though cortisol levels were also fairly stable.

Atherogenic effects of cyclosporine in an experimental model of arterial autograft.

One of the effects attributed to CsA is a possible acceleration of atherogenic processes, which contributes to the failure of transplanted organs. This study was undertaken to evaluate the effect of CsA and two vehicles, cremophor and ethanol, in an experimental model of arterial autograft in the rat. Female Sprague-Dawley rats were distributed into 3 study groups: Group 1 (control) had an arterial autograft in the common iliac artery without pretreatment; group 2 (CsA-cremophor) animals were pretreated with a daily dose of CsA (5 mg/kg, Sandimmun) for 4 days before the autograft was made; and group 3 (CsA-ethanol + Tween) animals were pretreated for 4 days before implantation of the autograft with CsA in a vehicle of ethanol + Tween at the same dose as used in group 2 (5 mg/kg). The study periods were 7, 14, 21, 30, and 50 postoperative days. Studies were made by optical microscopy, transmission electron microscopy, scanning electron microscopy, and autoradiography. Evaluation of the results showed that in the control group the postoperative repair process lead to formation of an intimal neolayer throughout the entire surgical zone, with scant participation of white cells. Group 2 (CsA-cremophor) had a marked increase in luminal thrombogenicity, important adhesion and infiltration of white cells, loss of smooth muscle cells in the medial layer, and atherogenic degeneration of the medial layer. The generation of the neointimal layer is delayed by 2 weeks with respect to the control group. However, once the neointimal begins to form, its thickness increases rapidly, reaching values similar to those seen in the control group at 50 days. The myointima also shows atherogenic characteristics, such as monocyte-macrophage infiltration and dystrophic calcification. In group 3 (CsA-ethanol+Tween, that is, CsA in a nonoleaginous vehicle), the effects were similar to those seen in group 2 (CsA-cremophor), with a reduction in the presence of lipid-laden cells in the medial layer. Based on these observations, we conclude that CsA per se induced atherogenic changes in the repair process of the arterial lesion that were independent of the vehicle of administration. CsA delayed, but did not inhibit, formation of a myointima and the myointima formed exhibited atherogenic characteristics. The most important effects were noted in the medial layer, which experienced intense degeneration.