Evaluation of the levels of metalloproteinsase-2 in patients with abdominal aneurysm and abdominal hernias.

UNLABELLED: Abdominal aortic aneurysms and abdominal hernias become an important health problems of our times. Abdominal aortic aneurysm and its rupture is one of the most dangerous fact in vascular surgery. There are some theories pointing to a multifactoral genesis of these kinds of diseases, all of them assume the attenuation of abdominal fascia and abdominal aortic wall. The density and continuity of these structures depend on collagen and elastic fibers structure. Reducing the strength of the fibers may be due to changes in the extracellular matrix (ECM) by the proteolytic enzymes-matrix metalloproteinases (MMPs) that degrade extracellular matrix proteins. These enzymes play an important role in the development of many disease: malignant tumors (colon, breast, lung, pancreas), cardiovascular disease (myocardial infarction, ischemia-reperfusion injury), connective tissue diseases (Ehler-Danlos Syndrome, Marfan's Syndrome), complications of diabetes (retinopathy, nephropathy). One of the most important is matrix metalloproteinase-2 (MMP-2). The aim of the study was an estimation of the MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia, and in patients with only abdominal aortic aneurysm. MATERIAL AND METHODS: The study involved 88 patients aged 42 to 89 years, including 75 men and 13 women. Patients were divided into two groups: patients with abdominal aortic aneurysm and primary abdominal hernia (45 persons, representing 51.1% of all group) and patients with only abdominal aortic aneurysm (43 persons, representing 48,9% of all group). RESULTS: It was a statistically significant increase in MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia compared to patients with only abdominal aortic aneurysm. It was a statistically significant increase in the prevalence of POCHP in patients with only abdominal aortic aneurysm compared to patients with abdominal aortic aneurysm and primary abdominal hernia. CONCLUSIONS: Statistically significant higher MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia seems shows that this enzyme plays a role in the pathogenesis of primary abdominal hernias. The observed distribution of MMP-2 blood levels in patients with abdominal aortic aneurysm and primary abdominal hernia may raise the conclusion that this enzyme determines the presence of multi-organ failure of the connective tissue--the patients with only abdominal aortic aneurysm had significantly lower MMP-2 blood levels.

Epigenetic effect of cadmium on global de novo DNA hypomethylation in the cadmium-induced ventral body wall defect (VBWD) in the chick model.

Administration of the heavy metal cadmium (Cd) induces ventral body wall defects (VBWD) in the chick embryo. In this model, the expression of most genes involved in body wall formation is altered 4h-posttreatment. However, the mechanism by which Cd results in the initiation of altered gene expression remains unclear. Epigenetic mechanisms can change genome function under exogenous influences. Moreover, Cd is one of the environmental factors that can affect epigenomic programming. De novo DNA methylation is essential for normal embryogenesis and is regulated by the DNA methyltransferases (DNMT)3A and DNMT3B. The objective of this study was to investigate the hypothesis that gene expression levels of DNMT3A/3B were altered, resulting in global DNA methylation changes during the critical period of embryogenesis in the Cd chick model. After 60-h incubation, chick embryos (n = 48) were harvested at 1, 4, and 8 h after treatment with saline or Cd, and divided into controls and Cd groups. Quantitative reverse transcription PCR was performed to evaluate the gene expression levels of DNMT3A/3B in the chick embryos and was statistically analyzed using Student's t-test. Immunohistochemistry was performed using a monoclonal antibody against 5-methylcytidine (5'MeC), which labels methyl-rich regions within the nucleus. DNMT3A/3B gene expression levels at 4 h were significantly downregulated in the Cd group compared with controls (p < 0.005/p < 0.00001, respectively). Immunoreactivity of 5'MeC was markedly diminished in the Cd group at 4 h. Our findings demonstrates for the first time that Cd impacts on the expression levels of DNMT3A/3B, which may underlie the pathogenesis of VBWD in the Cd chick model.

MMPs/TIMPs and inflammatory signalling de-regulation in human incisional hernia tissues.

BACKGROUND: Incisional hernia is a common and important complication of laparotomies. Epidemiological studies allude to an underlying biological cause, at least in a subset of population. Interest has mainly focused on abnormal collagen metabolism. However, the role played by other determinants of extracellular matrix (ECM) composition is unknown. To date, there are few laboratory studies investigating the importance of biological factors contributing to incisional hernia development. We performed a descriptive tissue-based analysis to elucidate the possible relevance of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in association with local cytokine induction in human incisional hernia tissues. The expression profiles of MMPs, TIMPs and pro-inflammatory cytokine signalling were investigated in aponeurosis and skeletal muscle specimens taken intraoperatively from incisional hernia (n= 10) and control (n= 10) patients. Semiquantitative RT-PCR, zymography and immunoblotting analyses were done. Incisional hernia samples displayed alterations in the microstructure and loss of ECM, as assessed by histological analyses. Moreover, incisional hernia tissues showed increased MMP/TIMP ratios and de-regulated inflammatory signalling (tumor necrosis factor [TNFA] and interleukin [IL]-6 tended to increase, whereas aponeurosis TNFA receptors decreased). The changes were tissue-specific and were detectable at the mRNA and/or protein level. Statistical analyses showed several associations between individual MMPs, TIMPs, interstitial collagens and inflammatory markers. The increment of MMPs in the absence of a counterbalance by TIMPs, together with an ongoing de-regulated inflammatory signalling, may contribute in inducing a functional defect of the ECM network by post-translational mechanisms, which may trigger abdominal wall tissue loss and eventual rupture. The notable TIMP3 protein down-regulation in incisional hernia fascia may be of pathophysiological significance. We conclude that this study may help to pinpoint novel hypotheses of pathogenesis that can lead to a better understanding of the disease and ultimately to improvement in current therapeutic approaches.

Degradation of collagen by metalloproteinase 2 in patients with abdominal hernias.

BACKGROUND: The groin hernia is a significant social and economic problem of our times. The pathogenesis of the disease is not clear. The metalloproteinases (MMP) are the group of proteolytic enzymes responsible for the degradation of extracellular matrix proteins and the basic membrane of blood vessels. THE AIMS OF OUR STUDY WERE: (1) to estimate the MMP-2 levels in the blood and tissues of patients with a groin hernia; (2) to answer the question of whether changes in MMP-2 activity correlate with the occurrence of inguinal hernias. METHOD: The study was performed on a group of 90 male patients suffering from inguinal hernias, aged 28-70 years (mean: 49 years). The control group was made up of 10 healthy (free from hernia) males, aged 30-68 years (mean: 46 years). RESULTS: We noticed increased levels of MMP-2 in patients with all types of hernia and across all age groups. The MMP-2 mean serum levels were statistically higher in patients with a groin hernia when compared to the control group. The highest blood levels of MMP-2 were observed in young men with a direct hernia. CONCLUSIONS: This study confirmed the important role of MMP-2 in the pathogenesis of inguinal hernia. The increased activity may lead to dysfunctions in collagen fiber, which is responsible for forming fascial structures, and as a result weaken their durability.

O uso de telas Parietex® e Surgisis® na correção de defeitos produzidos na parede abdominal de coelhos / The repair of abdominal defects in rabbits with Parietex® and Surgisis® meshes abdominal wall

RACIONAL: Na cirurgia geral, as correções das hérnias da parede abdominal ocupam lugar de destaque e, cada vez mais, as indicações e usos de telas têm aumentado devido aos melhores resultados. OBJETIVO: Comparar as correções de orifícios produzidos em parede abdominal com telas Parietex® e Surgisis® em contato direto com as vísceras abdominais. MÉTODO: Para os experimentos foram utilizadas 16 coelhas adultas jovens e produção de defeitos triangulares de 2 cm de base por 2,5 cm de altura, comprometendo os planos músculo-aponeurótico-peritoniais da parede abdominal, nos flancos, simétricos à linha média que foram corrigidos com telas retangulares de 3 cm de base por 3,5 cm de altura. No lado direito usou-se tela Parietex® (poliéster/colágeno-polietilenoglicol-glicerol) e no lado esquerdo tela Surgisis® (submucosa intestinal suína). Na avaliação utilizaram-se parâmetros clínico-cirúrgicos, histológicos e imunoistoquímicos. Oito coelhas foram submetidas a eutanásia em 30 dias e as 8 restantes, em 60. Comparou-se a eficiência das duas telas. RESULTADOS: As duas telas provocaram erosões de pele e não ocorreu nenhum caso de hérnia incisional. As aderências ocorreram em todas as telas no primeiro mês e em menor grau e intensidade, no segundo mês; a retração delas foi de 1/3 do tamanho original; a Parietex® provocou menor processo inflamatório; não houve diferença significante de deposição de entre as duas telas; a deposição do colágeno tipo III foi mais intensa no segundo mês em ambas; na remodelação do colágeno a produção da enzima MMP8 foi maior na tela Parietex® no primeiro mês e a enzima MMP13 aumentou no segundo mês em ambas as telas, porém com significância apenas na Parietex®. CONCLUSÃO: As duas telas foram eficientes na correção de hérnias incisionais e com resultados semelhantes, sendo que a Parietex® apresentou menor processo inflamatório, maior quantidade de metaloproteinases MMP8 e MMP13 em relação à Surgisis®.

BACKGROUND: In general surgery, the repair of abdominal wall hernias has a prominent place, and the indications and uses of meshes have increased due to better results. AIM: To compare the repair of induced abdominal wall defects with Parietex® and Surgisis® meshes, in direct contact with abdominal viscera (intraperitoneal mesh). METHOD: For the experiments, were used 16 female young adult rabbits. Two full thickness triangular defects of 2 cm base by 2.5 cm high were created, lateral to the linea alba, one at each side. They were repaired with rectangular meshes of 3 cm base by 3.5 cm high, on the right side with Parietex® mesh (polyester/collagen-polyethylenglycol-glycerol), and on the left side with Surgisis® mesh (lyophilized porcine small bowel submucosa). The evaluation included clinical-surgical findings as well as histological and immunohistochemical parameters. Eight rabbits were subjected to euthanasia after 30 days, and the eight after 60 days. RESULTS: Both meshes induced skin erosions, despite the varying levels of mesh undermining evaluated, no incisional hernia occurred. There were peritoneal adhesions to the surface of both types of meshes after 30 days and in a lower extent and intensity after 60 days. Meshes' shrinking correspond to 1/3 of the original size and Parietex® caused less inflammatory process at the histologic evaluation. Deposition of collagen type I presented no significant difference between the meshes, but deposition of collagen type III was more intense after 60 days, in both groups. Regarding collagen's rearrangement, the production of MMP8 was higher on Parietex® after 30 days, and MMP13 enzyme was increased after 60 days, in both meshes (significant only for Parietex®). CONCLUSION: Both meshes were efficient in the correction of abdominal wall defects, and with similar results, but Parietex® presented less inflammatory process and greater amount of matrix-metalloproteinases MMP8 and MMP13 than Surgisis®.

Retraction transaminitis: an inevitable but benign complication of laparoscopic fundoplication.

BACKGROUND: Transient transaminitis has been identified following laparoscopic abdominal surgery. However, the importance of posture, duration of surgery, and mechanical retraction in its etiology remain unclear. METHODS: Liver function was assessed preoperatively then at 8, 24, 48 and 72 h following laparoscopic surgery including the following procedures: Nissen fundoplication (LN: n = 10); cholecystectomy (LC: n = 10); inguinal herniorrhaphy (LH: n = 10); and gastrectomy (LG: n = 5). RESULTS: Aspartate aminotransferase (AST) levels in LN patients exhibited a rapid rise within 8 h, peaking at 48 h before returning toward baseline. In the LN group, AST levels were significantly higher at 8 h and 24 hours compared to all other groups and compared to LG at 48 h and 72 h. At 6-week follow-up all AST levels were normal. No significant differences were seen in other hepatic parameters, and no correlation between AST and duration of operation, gender, or age was identified. CONCLUSIONS: Antireflux surgery is associated with transaminitis related to hepatic retraction, which is independent of patient posture or duration of observation, and it resolves spontaneously with no clinical consequences.

[The repair of abdominal defects in rabbits with Parietex and Surgisis meshes abdominal wall]. / O uso de telas Parietex e Surgisis na correção de defeitos produzidos na parede abdominal de coelhos.

BACKGROUND: In general surgery, the repair of abdominal wall hernias has a prominent place, and the indications and uses of meshes have increased due to better results. AIM: To compare the repair of induced abdominal wall defects with Parietex and Surgisis meshes, in direct contact with abdominal viscera (intraperitoneal mesh). METHOD: For the experiments, were used 16 female young adult rabbits. Two full thickness triangular defects of 2 cm base by 2.5 cm high were created, lateral to the linea alba, one at each side. They were repaired with rectangular meshes of 3 cm base by 3.5 cm high, on the right side with Parietex mesh (polyester/collagen-polyethylenglycol-glycerol), and on the left side with Surgisis mesh (lyophilized porcine small bowel submucosa). The evaluation included clinical-surgical findings as well as histological and immunohistochemical parameters. Eight rabbits were subjected to euthanasia after 30 days, and the eight after 60 days. RESULTS: Both meshes induced skin erosions, despite the varying levels of mesh undermining evaluated, no incisional hernia occurred. There were peritoneal adhesions to the surface of both types of meshes after 30 days and in a lower extent and intensity after 60 days. Meshes' shrinking correspond to 1/3 of the original size and Parietex caused less inflammatory process at the histologic evaluation. Deposition of collagen type I presented no significant difference between the meshes, but deposition of collagen type III was more intense after 60 days, in both groups. Regarding collagen's rearrangement, the production of MMP8 was higher on Parietex after 30 days, and MMP13 enzyme was increased after 60 days, in both meshes (significant only for Parietex). CONCLUSION: Both meshes were efficient in the correction of abdominal wall defects, and with similar results, but Parietex presented less inflammatory process and greater amount of matrix-metalloproteinases MMP8 and MMP13 than Surgisis.