Increased expression of epimorphin in a peritoneal fibrosis mouse model

Background: Long-term peritoneal dialysis results in functional and histopathological alterations of the peritoneal membrane, leading to peritoneal fibrosis (PF). The mechanism of PF has not been fully elucidated, and at present there is no effective therapy for PF. Epimorphin is a mesenchymal protein that not only regulates morphogenesis in organ development but is implicated in tissue repair. However, the role of epimorphin in PF has not yet been clarified. Methods: PF was induced in C57/Bl6 mice by intraperitoneal injection of chlorhexidine gluconate (CG-injected mice) three times a week for 3 weeks. The parietal peritoneum was subsequently dissected and assessed by Masson’s trichrome staining, and epimorphin expression was analysed by immunohistochemistry and real-time reverse transcription polymerase chain reaction (RT-PCR). Furthermore, epimorphin-positive regions were analysed by multiple immunofluorescence staining using fibrosis-associated markers. In addition, normal rat fibroblast cells (NRK-49F) were treated with transforming growth factor-β (TGF-β) in the presence or absence of epimorphin. The expression of fibrosis-associated markers was assessed by real-time RT-PCR. Results: In CG-injected mice, Masson’s trichrome staining showed marked thickening of the submesothelial compact zone. Weak epimorphin expression was observed in the narrow submesothelial compact zone beneath the mesothelial cells in control mice; however, epimorphin expression was stronger in the submesothelial compact zone in CG-injected mice. Epimorphin expression was observed mainly in α-smooth muscle actin (α-SMA)-positive myofibroblasts. Epimorphin suppressed the TGF-β-induced upregulation of α-SMA and platelet-derived growth factor receptor-β in cultured cells. Conclusions: Our results suggest that epimorphin may be a therapeutic target for fibrotic diseases of the peritoneum.

Identification of novel pulmonary vein nodes as generators of ectopic arrhythmic foci for atrial fibrillation: An immuno-histochemical proof

Introduction: The atrial muscle sleeve (AMS) of the pulmonary vein is the most common source of the arrhythmogenic triggers in atrial fibrillation (AF). Anatomical substrate generating these ectopic currents is still elusive. The present study was designed to study the AMS of pulmonary veins with an emphasis on the structural basis which might govern AF initiation and perpetuation. Materials and Methods: The study was conducted on longitudinal tissue section of pulmonary vein, taken from 15 human cadaveric non-diseased hearts. Tissue was studied histologically using H&E and Gomori trichrome stain. The pacemaker channels were identified by immunohistochemistry using monoclonal HCN4 and HCN1 antibodies. Results: The AMS was identified in each pulmonary vein, located between the tunica adventitia and tunica media. A node like arrangement of myocytes was seen within the AMS in 30% of veins. It had a compact zone limited by a fibrous capsule and contained much smaller, paler and interconnected myocytes. Outside the capsule there was a zone of dispersed, singly placed myocytes separating the compact zone from the working myocytes of the AMS. HCN4 and HCN1 antibodies were expressed on the cell membrane of nodal myocytes, while the working myocytes demonstrated none to minimal staining. Conclusion: Pulmonary veins nodes are similar to the specialized cardiac conductive tissue in, histological arrangement of compact and transitional zones, cellular characteristics, and the presence of pacemaker channels. They might be the anatomical basis of ectopic arrhythmogenic foci. To our knowledge these nodes are being described for the first time in human.

Mechanisms of Peritoneal Fibrosis: Focus on Immune Cells–Peritoneal Stroma Interactions

Peritoneal fibrosis is characterized by abnormal production of extracellular matrix proteins leading to progressive thickening of the submesothelial compact zone of the peritoneal membrane. This process may be caused by a number of insults including pathological conditions linked to clinical practice, such as peritoneal dialysis, abdominal surgery, hemoperitoneum, and infectious peritonitis. All these events may cause acute/chronic inflammation and injury to the peritoneal membrane, which undergoes progressive fibrosis, angiogenesis, and vasculopathy. Among the cellular processes implicated in these peritoneal alterations is the generation of myofibroblasts from mesothelial cells and other cellular sources that are central in the induction of fibrosis and in the subsequent functional deterioration of the peritoneal membrane. Myofibroblast generation and activity is actually integrated in a complex network of extracellular signals generated by the various cellular types, including leukocytes, stably residing or recirculating along the peritoneal membrane. Here, the main extracellular factors and the cellular players are described with emphasis on the cross-talk between immune system and cells of the peritoneal stroma. The understanding of cellular and molecular mechanisms underlying fibrosis of the peritoneal membrane has both a basic and a translational relevance, since it may be useful for setup of therapies aimed at counteracting the deterioration as well as restoring the homeostasis of the peritoneal membrane.

IL-17A as a Potential Therapeutic Target for Patients on Peritoneal Dialysis

Chronic kidney disease (CKD) is a health problem reaching epidemic proportions. There is no cure for CKD, and patients may progress to end-stage renal disease (ESRD). Peritoneal dialysis (PD) is a current replacement therapy option for ESRD patients until renal transplantation can be achieved. One important problem in long-term PD patients is peritoneal membrane failure. The mechanisms involved in peritoneal damage include activation of the inflammatory and immune responses, associated with submesothelial immune infiltrates, angiogenesis, loss of the mesothelial layer due to cell death and mesothelial to mesenchymal transition, and collagen accumulation in the submesothelial compact zone. These processes lead to fibrosis and loss of peritoneal membrane function. Peritoneal inflammation and membrane failure are strongly associated with additional problems in PD patients, mainly with a very high risk of cardiovascular disease. Among the inflammatory mediators involved in peritoneal damage, cytokine IL-17A has recently been proposed as a potential therapeutic target for chronic inflammatory diseases, including CKD. Although IL-17A is the hallmark cytokine of Th17 immune cells, many other cells can also produce or secrete IL-17A. In the peritoneum of PD patients, IL-17A-secreting cells comprise Th17 cells, γδ T cells, mast cells, and neutrophils. Experimental studies demonstrated that IL-17A blockade ameliorated peritoneal damage caused by exposure to PD fluids. This article provides a comprehensive review of recent advances on the role of IL-17A in peritoneal membrane injury during PD and other PD-associated complications.

The 21 May 1960 Mw 8.1 Concepción Earthquake: A Deep Megathrust Foreshock That Started the 1960 Central-South Chilean Seismic Sequence

One of the most notable seismic sequences in modern times was recorded in May 1960 along the southern Chilean subduction zone. The sequence started on 21 May with the Mw 8.1 Concepción earthquake; 33 hr later the Mw 9.5 Valdivia megathrust earthquake occurred, the largest ever recorded in the instrumental period. These events changed the geomorphology of the coast along more than 1000 km, generated extensive structural damage in the main cities of central-south Chile, and triggered a Trans-Pacific tsunami. Observed land-level changes due to both earthquakes were reported in 1970. These observations were ascribed to both events but have been used to study only the general source properties of the 22 May Valdivia mainshock. Here, we separate these data to constrain for the first time the slip distribution of the 21 May Concepción earthquake, applying a Bayesian approach that considers uncertainties in the data. Our results show that the Mw 8.1 Concepción earthquake ruptured a deep segment of the megathrust, concentrated in a compact zone below the Arauco peninsula between depths of 20 and 50 km. Tsunami generation from this deep source agrees well with the tsunami arrival times and small amplitudes recorded by tide gauges along the Chilean coast. Our study highlights the importance of the 21 May 1960 Concepción earthquake in the context of large historical Chilean earthquakes.

A study of a quasilinear model of the particles of a suspension that are aggregated and settled in an inhomogeneous field

The mathematical model of the sedimentation process of suspension particles is usually a quasilinear hyperbolic system of partial differential equations, supplemented by initial and boundary conditions. In this work, we study a complex model that takes into account the aggregation of particles and the inhomogeneity of the field of external mass forces. The case of homogeneous initial conditions is considered, when all the parameters of the arising motion depend on only one spatial Cartesian coordinate x and on time t. In contrast to the known formulations for quasilinear systems of equations (for example, as in gas dynamics), the solutions of which contain discontinuities, in the studied formulation the basic system of equations occurs only on one side of the discontinuity line in the plane of variables (t; x). On the opposite side of the discontinuity surface, the equations have a different form in general. We will restrict ourselves to considering the case when there is no motion in a compact zone occupied by settled particles, i.e. all velocities are equal to zero and the volumetric contents of all phases do not change over time. The problem of erythrocyte sedimentation in the field of centrifugal forces in a centrifuge, with its uniform rotation with angular velocity ω = const is considered. We have studied the conditions for the existence of various types of solutions. One of the main problems is the evolution (stability) problem of the emerging discontinuities. The solution of this problem is related to the analysis of the relationships for the characteristic velocities and the velocity of the discontinuity surface. The answer depends on the number of characteristics that come to the jump, and the number of additional conditions set on the interface. The discontinuity at the lower boundary of the area occupied by pure plasma is always stable. But for the surface separating the zones of settled and of moving particles, the condition of evolution may be violated. In this case, it is necessary to adjust the original mathematical model.

The study of friction layer and tribological property of PI–matrix composites

Purpose This paper aims to study the friction layer and tribological property of polyimide (PI)–matrix composites under different friction speeds. Design/methodology/approach Friction tests were conducted under friction speeds ranging from 20-120 km/h and pressure of 0.57 MPa by a pin-on-disk tribometer. Findings The results indicate that the friction coefficient decreases with the increasing of the friction speed. Under different friction speeds, the structure of the friction layer and debris are different, which affects the actual tribological performance of the composites. At low friction speed, the morphology of the friction layer is mainly particulate. The higher level of clenching action between the friction pair leads to a high friction coefficient, and the morphology of the particles in the particulate zone and the wear debris are mostly equiaxial particles. At high friction speed, the morphology of the friction layer is mainly a compact zone. The reduction of the surface roughness leads to a low friction coefficient. The debris collected on the counter surface at high friction speeds are mostly big sheets, and the morphology of the particles in the particulate zone is mostly rod-like. Controlling the conditions of the disk and the pin can reveal the influence of friction speed on the friction layer. The wear mechanisms at different friction speeds are also discussed. Originality/value By controlling the conditions of the disk and the pin to reveal the influence of friction speed on the friction layer, and the evolutions of the friction layer, wear debris were carefully inspected with the aim of demonstrating the relationship between friction speed and wear mechanism of PI–matrix composites.

Recommendations for pathological diagnosis on biopsy samples from peritoneal dialysis patients

Peritoneal dialysis (PD) has been established as an essential renal replacement therapy for patients with end stage renal disease during the past half century. Histological evaluation of the peritoneal membrane has contributed to the pathophysiological understanding of PD-related peritoneal injury such as peritonitis, fibrosis, and encapsulating peritoneal sclerosis (EPS). Hyalinizing peritoneal sclerosis (HPS), also known as simple sclerosis, is observed in almost all of PD patients. HPS is morphologically characterized by fibrosis of the submesothelial interstitium and hyalinizing vascular wall, particularly of the post-capillary venule (PCV). Two histological factors, the thickness of submesothelial compact zone (SMC) and the lumen/vessel ratio (L/V) at the PCV, have been used for the quantitative evaluation of HPS. The measuring system on SMC thickness and L/V ratio is easy and useful for evaluating the severity of HPS. On the other hand, EPS is characterized by unique encapsulation of the intestines by an “encapsulating membrane”. This newly formed membranous structure covers the visceral peritoneum of the intestines, which contains fibrin deposition, angiogenesis, and proliferation of fibroblast-like cells and other inflammatory cells. This review will cover the common understandings of PD-related peritoneal alterations and provide a basic platform for clinical applications and future studies in this field.

EFFECTS OF NUMBER OF CONNECTIONS AND PIPE LENGTH TO THE WATER LOSSES IN MELAKA

One of the major challenges facing our water utilities is the high level of Non-Revenue Water (NRW) in the distribution networks. This paper assessed the performance of current management practices by Syarikat Air Melaka Berhad (SAMB) to deal with NRW. Information and NRW management data (from 2012 to 2013) were gathered and analysed. Statistical methods were used to evaluate the effects of pipe length and number of connections of the distribution network to the leakage level; and to determine the causes of leakage (water loss). In 2014, Melaka’s NRW percentage was 21.4% as compared to the national average of 35.6%, which is the second lowest rate among the states in Malaysia. Results of the study revealed significant positive relationships between average MNF (L/s) with number of connections and pipe length, with the prediction model of average MNF (L/s)=-4.42+1.088*10-2(NC)+1.07*10-4(PL), R2= 73.19%. The results also indicated that in a compact and urbanized city like Melaka, number of connections in the network appears to be most influential to the average MNF (water loss) (shown by a strong positive relationship, r = 0.847) as compared to the less compact zone (such as Perak) where pipe length appears to be more influential.

Importance of Endogenous Atrial and Brain Natriuretic Peptides in Murine Embryonic Vascular and Organ Development

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) bind to the receptor guanylyl cyclase (GC)-A, leading to diuresis, natriuresis, and blood vessel dilation. In addition, ANP and BNP have various angiogenic properties in ischemic tissue. When breeding mice devoid of GC-A, we noted significant skewing of the Mendelian ratio in the offspring, suggesting embryonic lethality due to knockout of GC-A. Consequently, we here investigated the roles of endogenous ANP and BNP in embryonic neovascularization and organ morphogenesis. Embryos resulting from GC-A−/− × GC-A+/− crosses developed hydrops fetalis (HF) beginning at embryonic day (E)14.5. All embryos with HF had the genotype GC-A−/−. At E17.5, 33.3% (12 of 36) of GC-A−/− embryos had HF, and all GC-A−/− embryos with HF were dead. Beginning at E16.0, HF-GC-A−/− embryos demonstrated poorly developed superficial vascular vessels and sc hemorrhage, the fetal side of the placenta appeared ischemic, and vitelline vessels on the yolk sac were poorly developed. Furthermore, HF-GC-A−/− embryos also showed abnormal constriction of umbilical cord vascular vessels, few cardiac trabeculae and a thin compact zone, hepatic hemorrhage, and poor bone development. Electron microscopy of E16.5 HF-GC-A−/− embryos revealed severe vacuolar degeneration in endothelial cells, and the expected 3-layer structure of the smooth muscle wall of the umbilical artery was indistinct. These data demonstrate the importance of the endogenous ANP/BNP-GC-A system not only in the neovascularization of ischemic tissues but also in embryonic vascular development and organ morphogenesis.