Different tissue reaction of oesophagus and diaphragm after mesh hiatoplasty. Results of an animal study

<p>Abstract</p> <p>Background</p> <p>Laparoscopic mesh-reinforcement of the hiatal region in the treatment of gastroesophageal reflux disease (GERD) and paraesophageal hernia (PEH) reduces the risk of recurrence. However, there are still controversies about the technique of mesh placement, shape, structure and material. We therefore compared tissue integration and scar formation after implantation of two different polypropylene-meshes in a rabbit model.</p> <p>Methods</p> <p>A total of 20 female chinchilla rabbits were included in this study. Two different meshes (Polypropylene PP, Polyglecaprone 25 Composite PP-PG) were implanted on the abdominal diaphragm around the oesophagus. After 3 months the implanted meshes were excised en-bloc. Histological and morphological analyses were carried out accordingly proliferation rate, apoptosis and collagen type I/III ratio.</p> <p>Results</p> <p>Regarding proliferation rate of oesophagus PP (9.31 ± 3.4%) and PP-PG (13.26 ± 2.54%) differ in a significant (p = 0.0097) way. In the diaphragm we found a significant (p = 0.00066) difference between PP (9.43 ± 1.45%) and PP-PG (18.73 ± 5.92%) respectively. Comparing oesophagus and diaphragm we could prove a significant difference within PP-PG-group (p = 0.0195). Within PP-group the difference reached no statistical significance (p = 0.88). We found analogous results regarding apoptosis.</p> <p>Furthermore, there is a significant (p = 0.00013) difference of collagen type I/III ratio in PP-PG (12.28 ± 0.8) compared to PP (8.44 ± 1,63) in case of oesophageal tissue. Concerning diaphragm we found a significant difference (p = 0.000099) between PP-PG (8.85 ± 0.81) and PP (6.32 ± 1.07) as well.</p> <p>Conclusion</p> <p>The histologic and morphologic characteristics after prosthetic enforcement of the hiatus in this animal model show a more distinct tissue integration using PP-PG compared to PP. Additionally, different wound healing and remodelling capability influence tissue integration of the mesh in diaphragm and oesophagus.</p

Gentamicin supplemented polyvinylidenfluoride mesh materials enhance tissue integration due to a transcriptionally reduced MMP-2 protein expression

<p>Abstract</p> <p>Background</p> <p>A beneficial effect of gentamicin supplemented mesh material on tissue integration is known. To further elucidate the interaction of collagen and MMP-2 in chronic foreign body reaction and to determine the significance of the MMP-2-specific regulatory element (RE-1) that is known to mediate 80% of the MMP-2 promoter activity, the spatial and temporal transcriptional regulation of the MMP-2 gene was analyzed at the cellular level.</p> <p>Methods</p> <p>A PVDF mesh material was surface modified by plasma-induced graft polymerization of acrylic acid (PVDF+PAAc). Three different gentamicin concentrations were bound to the provided active sites of the grafted mesh surfaces (2, 5 and 8 μg/mg). 75 male transgenic MMP-2/LacZ mice harbouring the LacZ reporter gene under control of MMP-2 regulatory sequence -1241/+423, excluding the RE-1 were randomized to five groups. Bilateral of the abdominal midline one of the five different meshes was implanted subcutaneously in each animal. MMP-2 gene transcription (anti-ß-galactosidase staining) and MMP-2 protein expression (anti-MMP-2 staining) were analyzed semiquantitatively by immunohistochemistry 7, 21 and 90 days after mesh implantation. The collagen type I/III ratio was analyzed by cross polarization microscopy to determine the quality of mesh integration.</p> <p>Results</p> <p>The perifilamentary ß-galactosidase expression as well as the collagen type I/III ratio increased up to the 90^thday for all mesh modifications, whereas no significant changes could be observed for MMP-2 protein expression between days 21 and 90. Both the 5 and 8 μg/mg gentamicin group showed significantly reduced levels of ß-galactosidase expression and MMP-2 positive stained cells when compared to the PVDF group on day 7, 21 and 90 respectively (5 μg/mg: p < 0.05 each; 8 μg/mg: p < 0.05 each). Though the type I/III collagen ratio increased over time for all mesh modifications significant differences to the PVDF mesh were only detected for the 8 μg/mg group at all 3 time points (p < 0.05 each).</p> <p>Conclusions</p> <p>Our current data indicate that lack of RE-1 is correlated with increased mesh induced MMP-2-gene expression for coated as well as for non-coated mesh materials. Gentamicin coating reduced MMP-2 transcription and protein expression. For the 8 μg/mg group this effect is associated with an increased type I/III collagen ratio. These findings suggest that gentamicin is beneficial for tissue integration after mesh implantation, which possibly is mediated via RE-1.</p

Hernia fibroblasts lack β-estradiol induced alterations of collagen gene expression

BACKGROUND: Estrogens are reported to increase type I and type III collagen deposition and to regulate Metalloproteinase 2 (MMP-2) expression. These proteins are reported to be dysregulated in incisional hernia formation resulting in a significantly decreased type I to III ratio. We aimed to evaluate the β-estradiol mediated regulation of type I and type III collagen genes as well as MMP-2 gene expression in fibroblasts derived from patients with or without history of recurrent incisional hernia disease. We compared primary fibroblast cultures from male/female subjects without/without incisional hernia disease. RESULTS: Incisional hernia fibroblasts (IHFs) revealed a decreased type I/III collagen mRNA ratio. Whereas fibroblasts from healthy female donors responded to β-estradiol, type I and type III gene transcription is not affected in fibroblasts from males or affected females. Furthermore β-estradiol had no influence on the impaired type I to III collagen ratio in fibroblasts from recurrent hernia patients. CONCLUSION: Our results suggest that β-estradiol does not restore the imbaired balance of type I/III collagen in incisional hernia fibroblasts. Furthermore, the individual was identified as an independent factor for the β-estradiol induced alterations of collagen gene expression. The observation of gender specific β-estradiol-dependent changes of collagen gene expression in vitro is of significance for future studies of cellular response

Association and Haplotype Analyses of Positional Candidate Genes in Five Genomic Regions Linked to Scrotal Hernia in Commercial Pig Lines

Scrotal hernia in pigs is a complex trait likely affected by genetic and environmental factors. A large-scale association analysis of positional and functional candidate genes was conducted in four previously identified genomic regions linked to hernia susceptibility on Sus scrofa chromosomes 2 and 12, as well as the fifth region around 67 cM on chromosome 2, respectively. In total, 151 out of 416 SNPs discovered were genotyped successfully. Using a family-based analysis we found that four regions surrounding ELF5, KIF18A, COL23A1 on chromosome 2, and NPTX1 on chromosome 12, respectively, may contain the genetic variants important for the development of the scrotal hernia in pigs. These findings were replicated in another case-control dataset. The SNPs around the ELF5 region were in high linkage disequilibrium with each other, and a haplotype containing SNPs from ELF5 and CAT was highly significantly associated with hernia development. Extensive re-sequencing work focused on the KIF18A gene did not detect any further SNPs with extensive association signals. These genes may be involved in the estrogen receptor signaling pathway (KIF18A and NPTX1), the epithelial-mesenchymal transition (ELF5) and the collagen metabolism pathway (COL23A1), which are associated with the important molecular characteristics of hernia pathophysiology. Further investigation on the molecular mechanisms of these genes may provide more molecular clues on hernia development in pigs

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe