The effect of surgery on the levels of matrix metalloproteinases in patients with inguinal hernia.

Matrix metalloproteinases (MMPs) are associated with the alteration of extracellular matrix. The purpose of this study was to investigate how the levels of matrix metalloproteinases and their inhibitors - TIMPs are influenced by the presence of inguinal hernia as well as by its surgical treatment. The studied group consisted of 25 patients with inguinal hernia and 21 healthy controls for comparison. Two blood samples - before and after the treatment were collected from patients. Serum concentrations of MMPs and TIMPs were analysed by multiplex immunoassays. There was a difference in circulating levels of MMPs in patients before the surgery compared to healthy controls - the concentrations of MMP-2 and MMP-9 were significantly lower (p=0.026, p=0.018, respectively). After the surgery, the levels of MMPs, especially MMP-2 (p<0.0001), were significantly decreased in patients compared to the preoperative values, apart from MMP-9. On the contrary, MMP-9 showed significant increase after the surgery (p<0.0001). Circulation levels of TIMP-2 in patients were significantly decreased in comparison with controls (p=0.004), whereas levels of TIMP-1 were similar to controls. Both tested metalloproteinase inhibitors showed a significant decrease in detected levels (TIMP-1 p=0.0004; TIMP-2 p<0.0001) after the procedure compared to the preoperative values. The levels of MMPs, especially MMP-2 and MMP-9, and their inhibitors TIMP-1 and TIMP-2 are involved by the presence of inguinal hernia as well as are influenced by the surgery.

Altered metalloproteinase-9 expression as least common denominator between varicocele, inguinal hernia, and chronic venous disorders.

BACKGROUND: Varicocele, inguinal hernia, and clinical manifestations related to chronic venous disorders are often associated, and collagen metabolism together with metalloproteinases (MMPs) alterations may be implicated. The aim of this study was to analyze the relationship between these factors. METHODS: We evaluated tissue and plasma samples from patients with varicocele, inguinal hernia, and great saphenous vein reflux, who underwent surgical treatment for their conditions. We then analyzed and correlated these findings with MMP levels. RESULTS: Significantly higher levels of MMP-1, -2, -12, and -13 were found in patients with inguinal hernia. MMP-9 levels were higher in patients with at least two of the conditions indicated. CONCLUSION: MMP-9 seems to be the common thread in various clinical conditions and is related to a more general and progressive disorder of collagen metabolism.

Assessment of insertion/deletion polymorphism of the angiotensin-converting enzyme gene in abdominal aortic aneurysm and inguinal hernia.

The aim of the paper is to determine whether the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism is associated with abdominal aortic aneurysm (AAA) and inguinal hernia. A case-control study was conducted in 264 subjects: 65 patients with AAA, 91 patients with inguinal hernia, 19 patients with both AAA and hernia, and 89 controls were investigated for the ACE I/D polymorphism. Genotype analysis was performed using a polymerase chain reaction technique. Significant differences in the genotype between the patient groups and controls were identified (aneurysm versus control, P = 0.011; aneurysm plus hernia versus control, P = 0.022; hernia versus control, P = 0.001), whereas no differences were found within patient groups. Patients with AAA and/or hernia had an increased prevalence of I/D heterozygosity, which persisted even after adjusting for differences in confounding clinical variables (aneurysm versus control, OR 0.3, 95% CI 0.2-0.8, P = 0.005; aneurysm plus hernia versus control, OR 0.3, 95% CI 0.1-0.9, P = 0.040; hernia versus control, OR 0.4, 95% CI 0.2-0.7, P = 0.004). In conclusion, an association between the heterozygote ACE I/D state and the presence of AAA and/or hernia was identified. The role of the ACE I/D polymorphism in aneurysm and hernia needs further investigation.

¿Existe alteración de los mecanismos de degradación del colágeno de la matriz extracelular manifestada en la expresión de MMP2 y TIMP2 en pacientes con hernia inguinal primaria? / meDoes alteration of extracellular matrix collagen degradation chanisms manifested in the expression of MMP2 and TIMP2 in patients with primary inguinal hernia exists?

Existe evidencia de asociación de alteraciones de la matriz colágena en sujetos con hernia inguinal (HI). El objetivo de este estudio fue determinar la existencia de alteraciones en la expresión de MMP2 y TIMP2 en sujetos con HI primaria. Estudio de casos y controles, realizado en los Servicios de Cirugía y de Urgencias del Hospital Regional de Temuco entre 2009-2010. Se incluyeron pacientes con HI primaria mayores de 15 años, sin restricción de género (casos), e Individuos sin hernias, mayores de 15 años, intervenidos por apendicitis aguda (controles). Se excluyeron portadores de condiciones predisponentes al desarrollo de hernias de pared abdominal. La variable resultado fue determinación de MMP2 y TIMP2 mediante inmunohitoquímica (IHQ). Otras variables de interés estudiadas fueron: hábito tabáquico, antecedente familiar de hernia, historia de estreñimiento, peso, estatura e índice de masa corporal (IMC). Se utilizó estadística descriptiva; analítica y modelos de regresión logística. Se estudiaron 21 casos y 20 controles. El 73 por ciento correspondió a hombres. La edad promedio fue 55,3+/-18,9 y 38,9+/-16,9 para casos y controles respectivamente. No se observaron diferencias estadísticamente significativas en las variables sexo, estatura, peso, IMC y hábito tabáquico entre casos y controles. Se verificaron diferencias significativas en las variables, antecedente familiar de hernia e historia de estreñimiento (más frecuentes en casos). La tinción IHQ de MMP2, fue mayor en los casos (53,4 por ciento vs. 40,0 por ciento; p=0,5068), y la de TIMP2, fue mayor en los controles (35,0 por ciento vs. 23,8 por ciento; p=0, 7333). El análisis multivariado descartó confundentes. Con la metodología utilizada no se verificó asociación entre alteración de los mecanismos de degradación del colágeno, manifestados en la expresión de MMP2 y TIMP2, con el desarrollo de HI primaria.

There is some evidence of association b collagen matrix alterations in patients with inguinal hernia (IH). The aim of this study was to determine the existence of alterations in the expression of MMP2 and TIMP2 in patients with primary IH. Case-control study conducted in the Department of Surgery and Emergency of Temuco Regional Hospital in 2009-2010 periods. We included subjects with primary IH over 15 years, without gender restriction (cases) and subjects without hernias, aged 15, underwent surgery for acute appendicitis (controls). Patients with conditions predisposing to the development of abdominal wall hernias were excluded. End point was determination of MMP2 and TIMP2 by Immunohistochemistry (IHC). Other studied variables were: smoking, family history of hernia, history of constipation, weight, height and body mass index (BMI). Descriptive statistics, analytical and logistic regression models were used. 21 cases and 20 controls were studied. 73 percent were men. The average age was 55.3+/-18.9 and 38.9+/-16.9 for cases and controls respectively. There were no statistically significant differences in the variables sex, height, weight, BMI and smoking between cases and controls. Significant difference was found in the variables, family history of hernia and history of constipation (more common in cases). IHC staining of MMP2 was higher in cases (53.4 percent vs. 40.0 percent, p=0.5068) and IHC of TIMP2 was higher in controls (35.0 percent vs. 23.8 percent, p=0.7333). Multivariate analysis discarded confounders. With the methodology used has not been tested association between alteration of mechanisms of collagen degradation, manifested in MMP2 and TIMP2 expression with primary IH development.

Roles of matrix metalloproteinases in the etiology of inguinal hernia.

INTRODUCTION: The fascia transversalis is accepted as one of the anatomical structures that can prevent hernia formation. Degradation of collagen within the fascia transversalis is one of the known reasons for the development of inguinal hernia. In the present study, we investigated the roles of matrix metalloproteinases (MMPs), specifically MMP-1, MMP-2, and MMP-9 in the etiology of inguinal hernia. MATERIALS AND METHODS: This prospective study included 60 inguinal hernia patients: 30 patients had indirect inguinal hernia and 30 patients had direct inguinal hernia. An additional 30 patients operated for reasons other than hernia in the inguinal canal were included as a control group. All patients underwent operations at Istanbul Training and Research Hospital between 1 June 2009 and 1 December 2009. Tissue specimens were taken from the fascia transversalis from patient and control groups during the operation, and MMP-1, MMP-2, MMP-9 values were investigated using immunohistochemical methods. RESULTS: Significantly higher values of MMP-1, MMP-2, MMP-9, were found in inguinal hernia cases than in the control group (P = 0.0001, P = 0.007, P = 0.021, respectively). CONCLUSION: Increased MMP-1, MMP-2, MMP-9 values play a role in the etiology of inguinal hernia. Since weakening may also occur in other tissues in addition to the floor of inguinal canal in inguinal hernia patients, the association of arterial aneurisms and connective tissue diseases should also be investigated in these patients.

Circulating matrix metalloproteinases and their inhibitors in inguinal hernia and abdominal aortic aneurysm.

AIM: There is evidence supporting the role of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in aortic and abdominal wall connective tissue degeneration, resulting in aneurysm and hernia formation. Furthermore, clinical association studies have demonstrated increased prevalence of abdominal wall hernias in patients with aortic aneurysms. Our objective was to estimate the levels of MMPs and TIMPs in the blood of patients with aortic aneurysm and inguinal hernia, in order to investigate whether there is potential pathogenic linkage of impaired collagen metabolism. METHODS: Plasma concentrations of MMP-9, MMP-2, TIMP-1 and TIMP-2 were quantified using ELISA in 33 male patients with abdominal aortic aneurysm and 91 male patients with inguinal hernia. They were consecutive patients undergoing repair during the study period. The same substances were measured in 35 healthy male controls. RESULTS: MMP-9 and MMP-2 concentrations were lower in the plasma of patients with inguinal hernia and abdominal aortic aneurysm than controls, with hernia patients having the lowest circulating levels. The levels of TIMP-2 were significantly elevated in patients with inguinal hernia and significantly reduced in patients with aortic aneurysm, whereas opposite correlations were found for circulating TIMP-1. CONCLUSION: Different patterns of circulating MMP and TIMP levels were found in patients with aneurysm and hernia compared with controls. Underlying pathogenic processes implicating MMPs and TIMPs in connective tissue metabolism are expressed by differing plasma levels in the two disease states. Further research including combined plasma and tissue analyses is required to further investigate potential common pathogenesis of these diseases.

Sarco(endo)plasmic reticulum and plasmalemmal Ca(2+)-ATPase activities in cremaster muscles and sacs differ according to the associated inguinal pathology.

Sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) and plasmalemmal Ca(2+)-ATPase (PMCA) activities in cremaster muscles and sacs, which have been subjected to different autonomic tonuses, were determined and compared. Samples of cremaster muscles and sacs associated with male or female inguinal hernia, hydrocele or undescended testis were obtained from children during operations and activities of SERCA and PMCA were determined. While highest SERCA and PMCA activities were encountered among cremaster muscles and sacs associated with undescended testis, least activities were encountered among structures associated with hydrocele. The alterations in SERCA and PMCA activities in cremaster muscles associated with undescended testis appear to reflect the attempts at maintaining the levels of cytosolic calcium. Despite similar total calcium contents, lower SERCA and PMCA activities were found in sacs associated with hydrocele compared to those associated with undescended testis suggest a difference among the levels of cytosolic calcium.

Comparison of the plasma and hernia sac tissue copper levels in direct and indirect inguinal hernia patients.

Although the inguinal hernia is among the most commonly encountered and well-described health problems all over the world, the etiology is still controversial. The aim of this study was to compare the plasma and hernia sac tissue copper levels in direct and indirect inguinal hernia patients. Plasma and hernia sac tissue copper levels obtained from patients operated under spinal anesthesia with primary direct (group I, n = 55, 45 male, mean age = 45.68 yr) and indirect (group II, n = 55, 40 male, mean age = 38.57 yr) hernias were detected by atomic absorption spectrophotometer. Significantly lower plasma and hernia sac tissue copper levels were detected in group I in comparison to group II (p < 0.001). Both plasma and hernia sac tissue copper levels were significantly lower in males when we compare the patients according to their sex characteristics, including both direct and indirect hernia groups (p < 0.05 and p < 0.01, respectively). Age was not a significant factor. The plasma and hernia sac tissue copper levels were significantly lower in direct hernia patients in comparison to indirect hernia patients. Copper is a cofactor of lysyl oxidase, an important enzyme in collagen tissue metabolism, so there might be a defect in the collagen synthesis of direct hernia patients because of the decreased activity of the lysyl oxidase. Further investigations are necessary to clarify this concept.

Role of TIMP-2 in fascia transversalis on development of inguinal hernias.

The exact reason for the development of inguinal hernia has not been completely determined. However, it is known that the fascia transversalis (FT) is one of the structures preventing development of hernias. In the etiology of the inguinal hernia, disorders in collagen metabolism have been proposed, and the role of metalloproteinases in remodeling the collagen has recently been of great importance. We could not encounter any study where the role of metalloproteinase inhibitors was evaluated in inguinal hernia. We obtained samples of FT from patients with direct and indirect hernia and used an immunohistochemical method to determine tissue inhibitor of metalloproteinase-2 (TIMP-2) expression. In the study group, samples of FT were taken during the operation from 45 patients, of which 35 were indirect and 10 were direct inguinal hernias. In the control group, samples of FT from various abdominal incisions were also taken from 45 patients with no hernia and operated upon for another pathology. TIMP-2 scores of a direct inguinal hernia were significantly less than those of the control group. However, no difference has been found between the TIMP-2 scores of an indirect inguinal hernia and those of the control group. Decreased TIMP-2 scores in patients with a direct inguinal hernia, compared with both the indirect inguinal hernia group and the control group, explain the reason for the increase in matrix metalloproteinase-2 (MMP-2) that has been proposed in some studies. Therefore, it can be expressed that a decreased activity of TIMP-2 plays a role in inguinal hernia development.

Distribution and morphometry of fiber types in cremaster muscles of boys with inguinal hernia or undescended testis.

In the present study, we determined and compared the distribution and mean diameters of fiber in the cremaster muscles (CM) of boys with either inguinal hernia (IH) or undescended testis (UT). Samples of CM were obtained from 20 patients (10 boys with IH, and 10 boys with UT) of similar age. The CM muscles of two boys each, without inguinal pathology, were sampled during autopsy. Sections were stained for oxidative and glycolytic enzymes, as well as for ATP-ase reactions after acid (pH: 4.6) and alkaline (pH: 10.6) preincubations. Specimens were also analyzed morphometrically using a KONTRON 400 computerized image analysis system. The Mann- Whitney U test was applied to compare the percentages of fiber types and mean diameters of fibers according to the types of the CM of boys with IH or UT. In boys, the CM is mainly composed of type 1 fibers. The CMs of patients with UT reveal alterations of neurogenic origin. Although both type 1 and type 2 fibers reveal alterations, type 2 fibers appear to be affected more profoundly and characterized by significantly decreased mean diameters. Significantly decreased mean diameters of type 2 fibers in CM may support disuse, lack of sensitivity to the hormonal influences, or an alteration in the corticospinal tracts of boys with UT.

Study of biochemical substrate and role of metalloproteinases in fascia transversalis from hernial processes.

The aim of this study was to examine the fascia transversalis (FT) from patients with direct and indirect hernia in an attempt to identify possible differences between each type of hernia. FT samples were obtained from 36 patients presenting inguinal hernia (23 indirect hernia and 13 direct hernia) who underwent surgery. We have analysed the ultrastructure of the fascia surrounding the hernial lesions, the proline and lysine hydroxylation in the tissue, the type I-type III collagen ratio and the presence of metalloproteinases. We have not detected ultrastructural differences in the collagen fibrils from FT in direct and indirect hernias. However, the interfibrillar matrix was more abundant in direct hernias, showing abundant electron-dense particles. No differences in proline hydroxylation were observed between each type of hernia. A small decrease in lysine hydroxylation was detected in patients with direct hernia. Enzyme-linked immunosorbent assays (ELISAs) showed no statistically significant differences in the type I-type III collagen absorbance ratios. Immunohistochemistry revealed no differences in the expression of matrix metalloproteinase-1. FT from patients presenting direct hernia showed a very strong staining vs. metalloproteinase-2 when compared with that observed in indirect hernia.

Abdominal aortic aneurysm, Leriche's syndrome, inguinal herniation, and smoking.

We previously found an increase in serum proteolytic activity in smokers with direct inguinal herniation and a similar imbalance in smokers with abdominal aortic aneurysm (AAA), but not in smokers with Leriche's syndrome (LS). If the protease imbalance in the blood of smokers with AAA or herniation is a causal factor, these conditions should be associated. Therefore, we determined whether this is true using patients with LS as control subjects. The frequency of inguinal herniation was significantly higher in the AAA population (N = 341; 25.8%) than in patients with LS (N = 417; 14.6%). In addition, patients with AAA had more severe herniation (direct, bilateral, recurrent, or earlier onset) and had more pronounced leukocytosis (9,000/cu mm v 8,190/cu mm). These data suggest that increased blood proteolytic activity may play a role in the development of both AAA and adult inguinal herniation but not LS. Men who smoke manifest different systemic effects.