Numerical simulations of delamination in fibre reinforced plastic shell structures using XFEM

[no abstract

Lymphangiogenesis in renal diseases

Lymphatic vessels (LVs) are thin walled structures that transport lymph from tissues to lymph nodes. By this function they are complementary to the cardiovascular system in the maintenance of body fluid homeostasis. They play a pivotal role in many (patho)-physiological processes, such as inflammation, immune surveillance and tolerance, fat abortion and metabolism, and general tissue homeostasis, and are involved in disease conditions as diverse as hypertension, atherosclerosis, transplant rejection and survival, and tumor metastasis. Although our understanding has been improved substantially, the biology of LVs is still in its infancy. During recent years many details have emerged as to how LVs function in diseased states, mostly in cancer related conditions. However, the functional significance of the lymphatic network in individual organ health and disease is still poorly understood. Data obtained in kidney transplantation, albeit few, support the important role of LV in intra-organ pathophysiology. Lymphangiogenesis, the outgrowth of preexisting and genesis of new LVs, is an important component of the tissue response to microenvironmental changes, and can have huge impact on disease progression and tissue homeostasis. In the present thesis, we have provided more insight into the mechanistical role of lymphatic vessels (LVs) and lymphangiogenesis in the pathophysiology of renal diseases. To this end, we evaluated whether lymphangiogenesis occurs in renal disease conditions, and if so, whether lymphangiogenesis associates with the degree of renal damage. Even more important, we studied whether targeting lymphangiogenesis can pose a beneficial therapeutic effect in experimental models of kidney injury

Istraživanje patoloških promjena kod celulitisa uzrokovanog bakterijom Erysipelothrix rhusiopathiae u pokusno zaraženih tovnih pilića.

Avian cellulitis is a serious problem for the commercial broiler industry. Although various agents were isolated from cellulitis lesions, the ability of Erysipelothrix rhusiopathiae in reproduction of cellulitis is not known. Therefore, the objective of this study was to evaluate the ability of these bacteria for induction of avian cellulitis. The study involved two experimental groups, each consisting of twenty randomly selected 15-day-old, mixed sex, healthy, commercially grown broiler chickens of the same strain. A single scratch was induced with a 1.5-inch 18-gauge needle, creating a lesion 2 cm in length on the right dorsolateral surface of the body parallel to the vertebrae. In Group 1, 1ml of 10² bacterial suspension - isolated from a turkey cock with erysipelas - was inoculated into the scratches. Birds in Group 2 received 1ml of the sterile phosphate-buffered saline as negative controls. At 48-hr post inoculation the birds were killed and pathologic and bacteriologic examinations were carried out. Birds in Group1 showed weakness, depression and mild diarrhoea. In this group, 65% of birds showed swelling of the skin with necrosis, infiltration of heterophils and fibrinous exudates, which was characteristic of cellulitis. The remaining 35% of birds were dead within 24-hrs post inoculation, with signs of mild cellulitis. Erysipelothrix rhusiopathiae was recovered from skin and some other internal organs from birds in Group 1. Birds in Group 2 were normal. Results of the present study revealed that E. rhusiopathiae can be considered as a causative agent of avian cellulitis, with public health hazards.Celulitis peradi ozbiljan je problem u proizvodnji tovnih pilića. Iako su različiti agensi izdvojeni iz celulitičnih lezija, sposobnost Erysipelothrix rhusiopathiae u izazivanju celulitisa nije poznata. Stoga je cilj ovog istraživanja bio istražiti ulogu ove bakterije u nastanku celulitisa peradi. Korištene su dvije pokusne skupine, od kojih je svaka bila sastavljena od nasumce odabranih dvadeset komercijalno uzgajanih, zdravih, petnaestodnevnih tovnih pilića, mješovita spolnog sastava i istog soja. Na desnoj dorzolateralnoj strani tijela peralelno s kralježnicom, iglom je načinjena ogrebotina duga 2 cm. Pilićima jedne skupine u tu je ogrebotinu inokuliran 1 ml suspenzije s 102 bakterijskih stanica uzročnika izdvojenog iz purana s vrbancem. Pilići druge skupine primili su 1 ml sterilne puferirane otopine fosfatne soli kao negativnu kontrolu. Pilići su bili žrtvovani 48 sati nakon inokulacije, a potom su načinjena patološka i bakteriološka istraživanja. U 65% pilića iz prve skupine uočeno je otečenje kože s nekrozama, infiltracija heterofila i fibrinozni eksudat, što je osebujno za celulitis. Preostalih 35% pilića je uginulo unutar 24 sata nakon inokulacije sa znakovima blagog celulitisa. Erysipelothrix rhusiopathiae bio je ustanovljen u koži i nekim unutarnjim organima pilića iz prve skupine. Pilići iz druge skupine bili su zdravi. Rezultati ovog istraživanja pokazuju da se E. rhusiopathiae može smatrati uzročnikom celulitisa peradi i predstavlja opasnost za javno zdravstvo

Proteinuria converts hepatic heparan sulfate to an effective proprotein convertase subtilisin kexin type 9 enzyme binding partner:a historical appraisal of its origins and conceptual evolution

International audienc

Targeting tubulointerstitial remodeling in proteinuric nephropathy in rats

Proteinuria is an important cause of tubulointerstitial damage. Anti-proteinuric interventions are not always successful, and residual proteinuria often leads to renal failure. This indicates the need for additional treatment modalities by targeting the harmful downstream consequences of proteinuria. We previously showed that proteinuria triggers renal lymphangiogenesis before the onset of interstitial inflammation and fibrosis. However, the interrelationship of these interstitial events in proteinuria is not yet clear. To this end, we specifically blocked lymphangiogenesis (anti-VEGFR3 antibody), monocyte/macrophage influx (clodronate liposomes) or lymphocyte and myofibroblast influx (S1P agonist FTY720) separately in a rat model to investigate the role and the possible interaction of each of these phenomena in tubulointerstitial remodeling in proteinuric nephropathy. Proteinuria was induced in 3-month old male Wistar rats by adriamycin injection. After 6 weeks, when proteinuria has developed, rats were treated for another 6 weeks by anti-VEGFR3 antibody, clodronate liposomes or FTY720 up to week 12. In proteinuric rats, lymphangiogenesis, influx of macrophages, T cells and myofibroblasts, and collagen III deposition and interstitial fibrosis significantly increased at week 12 vs week 6. Anti-VEGFR3 antibody prevented lymphangiogenesis in proteinuric rats, however, without significant effects on inflammatory and fibrotic markers or proteinuria. Clodronate liposomes inhibited macrophage influx and partly reduced myofibroblast expression; however, neither significantly prevented the development of lymphangiogenesis, nor fibrotic markers and proteinuria. FTY720 prevented myofibroblast accumulation, T-cell influx and interstitial fibrosis, and partially reduced macrophage number and proteinuria; however, it did not significantly influence lymphangiogenesis and collagen III deposition. This study showed that proteinuria-induced interstitial fibrosis cannot be halted by blocking lymphangiogenesis or the influx of macrophages. On the other hand, FTY720 treatment did prevent T-cell influx, myofibroblast accumulation and interstitial fibrosis, but not renal lymphangiogenesis and proteinuria. We conclude that tubulointerstitial fibrosis and inflammation are separate from lymphangiogenesis, at least under proteinuric conditions

Urinary collagen degradation products as early markers of progressive renal fibrosis

Background: Renal fibrogenesis is associated with increased ECM remodeling and release of collagen fragments in urine in progressive renal disease. We investigated the diagnostic value of urinary collagen degradation products in a proteinuria-driven fibrosis rat model with and without anti-fibrotic S1P-receptor modulator FTY720 treatment. Methods: Proteinuria was induced in male Wistar rats by Adriamycin (ADR) injection (n = 16). Healthy rats served as controls (n = 12). Six weeks post-injection, all underwent renal biopsy, and FTY720-treatment started in ADR-rats (n = 8) and controls (n = 6). Others remained untreated. Rats were sacrificed after 12 weeks. Collagen type I (C1M) and III (C3M) degradation fragments were measured in blood and urine using ELISA. Kidneys were stained for various inflammatory and fibrotic markers. Results: Six weeks post-injection proteinuria increased (versus controls, P <0.001) and although no accumulation of interstitial renal collagen type III (iColl3) was observed at this time, urinary C3M (uC3M) and C1M (uC1M) were significantly increased (both P <0.001). At 12 weeks, uC3M (P <0.001) and uC1M (P <0.01) further increased in ADR-rats versus controls, just as fibronectin, PDGF-beta receptor, hyaluronan (all P <0.01), iColl3, PAS, myofibroblasts, macrophages and T-cells (all P <0.05). FTY720-treatment reduced accumulation of immune cells, alpha-SMA+ myofibroblasts and PAS-score, but not iColl3 and uC3M. Correlation analyses indicated that uC3M and uC1M reflected and predicted tubulointerstitial fibrogenesis. Conclusions: These data displayed urinary collagen breakdown products as sensitive early markers of interstitial fibrosis, preceding histological fibrotic changes, which might replace the invasive renal biopsy procedure to assess fibrosis. Anti-fibrotic FTY720 intervention reduced some fibrotic markers without affecting collagen type III metabolism

Basement Membrane Zone Collagens XV and XVIII/Proteoglycans Mediate Leukocyte Influx in Renal Ischemia/Reperfusion

Collagen type XV and XVIII are proteoglycans found in the basement membrane zones of endothelial and epithelial cells, and known for their cryptic anti-angiogenic domains named restin and endostatin, respectively. Mutations or deletions of these collagens are associated with eye, muscle and microvessel phenotypes. We now describe a novel role for these collagens, namely a supportive role in leukocyte recruitment. We subjected mice deficient in collagen XV or collagen XVIII, and their compound mutant, as well as the wild-type control mice to bilateral renal ischemia/reperfusion, and evaluated renal function, tubular injury, and neutrophil and macrophage influx at different time points after ischemia/reperfusion. Five days after ischemia/reperfusion, the collagen XV, collagen XVIII and the compound mutant mice showed diminished serum urea levels compared to wild-type mice (all