Efficacy of adalimumab therapy in experimental rat sclerosing encapsulated peritonitis model

Aim To investigate the efficacy of adalimumab treatment in an experimental rat sclerosing encapsulated peritonitis (SEP) model. Methods The study involved 40 Wistar albino rats divided into four groups: chlorhexidine (CH) group, control group, CH + adalimumab group, and CH + resting group. The control group received normal saline intraperitoneally (i.p.). Other groups received 0.1% CH gluconate, 15% ethanol, and normal saline mixture i.p. for three weeks in order to induce SEP. CH + adalimumab group received 5 mg/kg adalimumab i.p. at the beginning of week 4 and week 6, while CH + resting group was followed-up for three weeks without applying any procedure after the onset of SEP. Rats in groups CH and control group were sacrificed on day 21, and rats in group CH + adalimumab and CH + resting were sacrificed on day 42. All groups were evaluated for peritoneal thickness, inflammation, vascularization, and fibrosis. Results CH + adalimumab group showed a significant decrease in peritoneal thickness, fibrosis score, and vascular score compared with CH group and CH + resting group. Conclusion Adalimumab can prevent SEP development

Efficacy of novel albendazole salt formulations against secondary cystic echinococcosis in experimentally infected mice

8 páginas, 5 figuras, 1 tablaIn this study, we evaluated the efficacy, expressed as a mean weight decrease of the whole echinococcal cyst mass, of novel benzimidazole salt formulations in a murine Echinococcus granulosus infection model. BALB/c mice were intraperitoneally infected with protoscoleces of E. granulosus (genotype G1). At 9 months post-infection, treatment with albendazole (ABZ), ricobendazole (RBZ) salt formulations, and RBZ enantiomer salts (R)-(+)-RBZ-Na and (S)-(−)-RBZ-Na formulations were initiated. Drugs were orally applied by gavage at 10 mg kg−1 body weight per day during 30 days. Experimental treatments with benzimidazole sodium salts resulted in a significant reduction of the weight of cysts compared to conventional ABZ treatment, except for the (S)-(−)-RBZ-Na enantiomer formulation. Scanning electron microscopy and histological inspection revealed that treatments impacted not only the structural integrity of the parasite tissue in the germinal layer, but also induced alterations in the laminated layer. Overall, these results demonstrate the improved efficacy of benzimidazole salt formulations compared to conventional ABZ treatment in experimental murine cystic echinococcosis.The research leading to these results received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under the project HERACLES (http://www.heracles-fp7.eu/), grant agreement no. 602051. The funder of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report.Peer reviewe

EDC/NHS cross-linked collagen foams as scaffolds for artificial corneal stroma.

International audienceIn this study, a highly porous collagen-based biodegradable scaffold was developed as an alternative to synthetic, non-degradable corneal implants. The developed method involved lyophilization and subsequent stabilization through N-ethyl-N'-[3-dimethylaminopropyl] carbodiimide/N-hydroxy succinimide (EDC/NHS) cross-linking to yield longer lasting, porous scaffolds with a thickness similar to that of native cornea (500 microm). For collagen-based scaffolds, cross-linking is essential; however, it has direct effects on physical characteristics crucial for optimum cell behavior. Hence, the effect of cross-linking was studied by examining the influence of cross-linking on pore size distribution, bulk porosity and average pore size. After seeding the foam with human corneal keratocytes, cell proliferation, cell penetration into the scaffold and ECM production within the scaffold were studied. After a month of culture microscopical and immunohistochemical examinations showed that the foam structure did not undergo any significant loss of integrity, and the human corneal keratocytes populated the scaffold with cells migrating both longitudinally and laterally, and secreted some of the main constituents of the corneal ECM, namely collagen types I, V and VI. The foams had a layer of lower porosity (skin layer) both at the top and the bottom. Foams had an optimal porosity (93.6%), average pore size (67.7 microm), and chemistry for cell attachment and proliferation. They also had a sufficiently rapid degradation rate (73.6+/-1.1% in 4 weeks) and could be produced at a thickness close to that of the natural corneal stroma. Cells were seeded at the top surface of the foams and their numbers there was higher than the rest, basically due to the presence of the skin layer. This is considered to be an advantage when epithelial cells need to be seeded for the construction of hemi or full thickness cornea.In this study, a highly porous collagen-based biodegradable scaffold was developed as an alternative to synthetic, non-degradable corneal implants. The developed method involved lyophilization and subsequent stabilization through N-ethyl-N'-[3-dimethylaminopropyl] carbodiimide/N-hydroxy succinimide (EDC/NHS) cross-linking to yield longer lasting, porous scaffolds with a thickness similar to that of native cornea (500 microm). For collagen-based scaffolds, cross-linking is essential; however, it has direct effects on physical characteristics crucial for optimum cell behavior. Hence, the effect of cross-linking was studied by examining the influence of cross-linking on pore size distribution, bulk porosity and average pore size. After seeding the foam with human corneal keratocytes, cell proliferation, cell penetration into the scaffold and ECM production within the scaffold were studied. After a month of culture microscopical and immunohistochemical examinations showed that the foam structure did not undergo any significant loss of integrity, and the human corneal keratocytes populated the scaffold with cells migrating both longitudinally and laterally, and secreted some of the main constituents of the corneal ECM, namely collagen types I, V and VI. The foams had a layer of lower porosity (skin layer) both at the top and the bottom. Foams had an optimal porosity (93.6%), average pore size (67.7 microm), and chemistry for cell attachment and proliferation. They also had a sufficiently rapid degradation rate (73.6+/-1.1% in 4 weeks) and could be produced at a thickness close to that of the natural corneal stroma. Cells were seeded at the top surface of the foams and their numbers there was higher than the rest, basically due to the presence of the skin layer. This is considered to be an advantage when epithelial cells need to be seeded for the construction of hemi or full thickness cornea

Effects of Renin-Angiotensin-Aldosterone System Blockade on Chlorhexidine Gluconate-Induced Sclerosing Encapsulated Peritonitis in Rats

Sclerosing encapsulated peritonitis (SEP) is a rare complication of long term peritoneal dialysis. Renin-angiotensin-aldosterone system (RAAS) may play a role in the development of peritoneal fibrosis in CAPD patients. We aimed to evaluate the effect of aliskiren, valsartan, and aliskiren + valsartan therapy on SEP. The study included 30 Wistar albino rats which were divided into five groups: I (Control) SF solution i.p.; II (CG group) chlorhexidine gluconate i.p.; III aliskiren oral plus CG i.p.; IV valsartan oral plus CG i.p.; and V aliskiren oral, valsartan oral and CG i.p. On the twenty-first day, all of the rats were sacrificed. All of the groups were analyzed in terms of peritoneal thickness, degree of inflammation, vasculopathy, neovascularization and fibrosis. Also, the parietal peritoneal tissue samples were evaluated for matrix metalloproteinase 2 (MMP-2) using the ELISA method. Peritoneal thickness and fibrosis scores were lower in the valsartan group compared to the CG group (P 0.05). Tissue MMP-2 levels were significantly higher in the CG group compared other groups (P < 0.05). There were no statistically significant differences between the aliskiren, valsartan and aliskiren + valsartan groups according to the tissue MMP-2 levels. Due to the antifibrotic properties of valsartan, it is thought to be a possible choice to prevent SEP development. We found no positive impact of aliskiren or aliskiren + valsartan combination compared to valsartan alone

EDC/NHS cross-linked collagen foams as scaffolds for artificial corneal stroma

In this study, a highly porous collagen-based biodegradable scaffold was developed as an alternative to synthetic, non-degradable corneal implants. The developed method involved lyophilization and subsequent stabilization through N-ethyl-N'-[3-dimethylaminopropyl] carbodiimide/N-hydroxy succinimide (EDC/NHS) cross-linking to yield longer lasting, porous scaffolds with a thickness similar to that of native cornea (500 pm). For collagen-based scaffolds, cross-linking is essential; however, it has direct effects on physical characteristics crucial for optimum cell behavior. Hence, the effect of cross-linking was studied by examining the influence of cross-linking on pore size distribution, bulk porosity and average pore size. After seeding the foam with human corneal keratocytes, cell proliferation, cell penetration into the scaffold and ECM production within the scaffold were studied. After a month of culture microscopical and immunohistochemical examinations showed that the foam structure did not undergo any significant loss of integrity, and the human corneal keratocytes populated the scaffold with cells migrating both longitudinally and laterally, and secreted some of the main constituents of the corneal ECM, namely collagen types 1, V and VI. The foams had a layer of lower porosity (skin layer) both at the top and the bottom. Foams had an optimal porosity (93.6%), average pore size (67.7 mu m), and chemistry for cell attachment and proliferation. They also had a sufficiently rapid degradation rate (73.6 +/- 1.1% in 4 weeks) and could be produced at a thickness close to that of the natural corneal stroma. Cells were seeded at the top surface of the foams and their numbers there was higher than the rest, basically due to the presence of the skin layer. This is considered to be an advantage when epithelial cells need to be seeded for the construction of hemi or full thickness cornea

Influence of Bone Morphogenic Protein 7 (BMP7) on the Progression of Chronic Kidney Disease

Background-Aims: Chronic kidney disease (CKD) is an important health problem worldwide. TGF (transforming growth factor)-beta and particularly bone morphogenetic protein 7 (BMP7) are held responsible for renal fibrosis. In our study we aimed to evaluate the association between CKD progression and BMP7 levels.Materials and Methods: Our study included 80 patients who are diagnosed with CKD and being followed between January 2008 and December 2010. Progression of CKD was defined as 50% decrease in glomerular filtration rate (GFR), doubling of serum creatinine and initiation of renal replacement therapy. Serum BMP7 levels have been measured initially and at the end of two years follow-up.Results: At the end of the follow-up CKD progression was detected in 18 out of 80 patients (%22.5). Decrease in glomerular filtration rate was found to be correlated with an increase in PTH, phosphorus and a decrease in serum albumin levels. In patients with progressive disease serum BMP7 levels were significantly higher than the ones with stable disease, which were 458±62.3 pg/mL and 360±82.4 pg/mL, respectively.Conclusion: Our results show that the patients with progressive disease have higher BMP7 levels which is a different finding from the previous trials. We speculate that this paradoxal increase may be a compensatory action against the increase in other profibrotic cytokines

Seismic performance of existing RC framed buildings using pushover analysis method

The aim of this study is to present a methodology on the determination of the seismic performance of existing reinforced concrete (RC) structures subjected to earthquake effects. This paper focuses on the assessment of existing RC structures with a nonlinear analysis (pushover analysis) method. The research is presented with the case study of an existing RC structure. The investigations on this RC structure is done with the field surveys, lab studies and numerical analyses. The first stage of the study includes the assessment of the compliance between the architectural and structural design projects of the related structure. Necessary checks have been made whether the projects of the structure are consistent with its existing state. Secondly, on-site mechanical tests were conducted on the structural members, and laboratory tests were performed on the samples collected from the structure. In the last stage, the seismic performance of the structure was determined based on the three-dimensional finite element model prepared for the existing state of the structure. The analysis results are discussed considering the target performance level parameter. The results have shown the importance of designating the appropriate target performance level in the evaluation of the seismic performance of RC structures