Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031154 (peritonitis)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peritoneal membrane fibrosis, ranging from mild inflammation to severe sclerosing peritonitis, is one of the complications of peritoneal dialysis (PD). In parallel with fibrosis, the peritoneum shows a progressive increase of capillaries and vasculopathy, involved in increased small solute transport across the membrane and ultrafiltration failure. Glucose and glucose degradation products from PD solutions are responsible of stimulating transforming growth factor-beta (TGF-beta) and vascular endothelial growth factor (VEGF) production by mesothelial cells (MCs). TGF-beta is a potent pro-fibrotic factor and inducer of epithelial-to-mesenchymal transition (EMT) of the MC. Local production of VEGF by transitional MC appears to play a central role in the processes leading to peritoneal angiogenesis. This review addresses the mechanism involved in peritoneal structural alteration by dialysis and points to the EMT of MC as the initiating mechanism of peritoneal injury. Information from multiple origins about TGF-beta and VEGF is integrated into EMT process in a comprehensive manner. Regulation and new targets for inhibition of EMT or its deleterious effects are discussed.
 ...
PMID:Epithelial-to-mesenchymal transition of the mesothelial cell--its role in the response of the peritoneum to dialysis. 1682 54

Dialysate concentrations of inflammatory mediators and growth factors, such as vascular endothelial growth factor (VEGF), are increased during acute peritonitis in peritoneal dialysis patients; however, it can be difficult to determine whether these high concentrations are caused by either increased peritoneal permeability or enhanced local production within peritoneal tissues. VEGF and total protein kinetics were first compared in a rabbit model during an 8-h dwell of dialysis solution containing 2.5% dextrose with (peritonitis) and without (control) the addition of 1-2 x 10(5) colony forming units (cfus) of Escherichia coli (series 1 experiments). Series 2 experiments determined whether intraperitoneal administration of indomethacin (75 microg/mL) altered the kinetics of VEGF and its local production during peritonitis. Series 1 experiments showed that peritonitis resulted in increased peritoneal permeability to total protein, enhanced appearance of VEGF in the dialysate, and increased tissue VEGF mRNA expression in the cecum and abdominal muscle tissues. Series 2 experiments showed that intraperitoneal administration of indomethacin during peritonitis blocked the increase in peritoneal permeability to total protein but had no effect on the appearance rate of VEGF in the dialysate. Intraperitoneal indomethacin decreased tissue VEGF mRNA expression in the cecum but not in the diaphragm or abdominal muscle tissues. It is concluded that the enhanced appearance of VEGF in peritoneal dialysate during peritonitis is largely from increased local production within peritoneal tissues. These observations also demonstrate that enhanced local production of VEGF is not sufficient to increase peritoneal permeability to total protein during peritonitis.
 ...
PMID:Enhanced local production of vascular endothelial growth factor is not sufficient to increase peritoneal permeability to protein during acute peritonitis. 1765 33

Studies using animal models of peritoneal dialysis (PD) have commonly induced acute peritonitis by intraperitoneal (IP) administration of lipopolysaccharide (LPS). We compared the effects of peritonitis induced by IP administration of either LPS or zymosan on inflammatory parameters [dialysate leukocyte counts and dialysate concentrations of prostaglandin E2 (PGE2) and vascular endothelial growth factor (VEGF)] and peritoneal transport of fluid, small solutes (glucose), and macromolecules (total protein) in a mouse model of PD. Eighteen hours after induction of peritonitis, mice were studied by injecting 2 mL of 4.25% dextrose-containing PD solution into the peritoneal cavity for a 2-hour dwell. Concentrations of glucose, total protein, PGE2, and VEGF were determined in the dialysate effluent. Acute peritonitis induced by IP administration of LPS induced changes in peritoneal transport similar to those observed during clinical PD, but without a significant increase in the dialysate leukocyte count. In contrast, acute peritonitis induced by IP administration of zymosan induced a large increase in dialysate leukocyte count, more substantial changes in peritoneal transport, and increases in dialysate PGE2 and VEGF concentrations. We conclude that acute peritonitis induced by IP administration of zymosan in the mouse may be a more relevant model for clinical PD, because it produces substantial changes in peritoneal transport and leukocyte migration into the peritoneal cavity.
 ...
PMID:Acute peritonitis in a C57BL/6 mouse model of peritoneal dialysis. 1788 6

Cyclooxygenase-2 (COX-2) inhibitor has been reported to suppress tumor progression. However, it is unclear whether this inhibitor can also prevent lymphatic metastasis. To determine the effects of COX-2 inhibitor on lymphatic metastasis, etodolac, a COX-2 inhibitor, was given p.o. to mice bearing orthotopic xenografts or with carcinomatous peritonitis induced with a highly metastatic human diffuse-type gastric carcinoma cell line, OCUM-2MLN. Tumor lymphangiogenesis was significantly decreased in etodolac-treated mice compared with control mice. Consistent with this decrease in lymphangiogenesis, the total weight of metastatic lymph nodes was less in etodolac-treated mice than in control mice. Immunohistochemical analysis revealed that the major source of vascular endothelial growth factor-C (VEGF-C) and VEGF-D was F4/80-positive macrophages in our models. The mRNA levels of VEGF-C in mouse macrophage-like RAW264.7 cells, as well as those in tumor tissues, were suppressed by etodolac. The growth of human dermal lymphatic microvascular endothelial cells was also suppressed by etodolac. Supporting these findings, etodolac also inhibited lymphangiogenesis in a model of chronic aseptic peritonitis, suggesting that COX-2 can enhance lymphangiogenesis in the absence of cancer cells. Our findings suggest that COX-2 inhibitor may be useful for prophylaxis of lymph node metastasis by reducing macrophage-mediated tumor lymphangiogenesis.
 ...
PMID:Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via reduction of lymphangiogenesis. 1797 58

Lymphangiogenesis is induced by various growth factors, including VEGF-C. Although TGF-beta plays crucial roles in angiogenesis, the roles of TGF-beta signaling in lymphangiogenesis are unknown. We show here that TGF-beta transduced signals in human dermal lymphatic microvascular endothelial cells (HDLECs) and inhibited the proliferation, cord formation, and migration toward VEGF-C of HDLECs. Expression of lymphatic endothelial cell (LEC) markers, including LYVE-1 and Prox1 in HDLECs, as well as early lymph vessel development in mouse embryonic stem cells in the presence of VEGF-A and C, were repressed by TGF-beta but were induced by TGF-beta type I receptor (TbetaR-I) inhibitor. Moreover, inhibition of endogenous TGF-beta signaling by TbetaR-I inhibitor accelerated lymphangiogenesis in a mouse model of chronic peritonitis. Lymphangiogenesis was also induced by TbetaR-I inhibitor in the presence of VEGF-C in pancreatic adenocarcinoma xenograft models inoculated in nude mice. These findings suggest that TGF-beta transduces signals in LECs and plays an important role in the regulation of lymphangiogenesis in vivo.
 ...
PMID:Inhibition of endogenous TGF-beta signaling enhances lymphangiogenesis. 1831 May 2

Ultrafiltration failure is the most frequent alteration of peritoneal transport in peritoneal dialysis (PD) patients, and is a frequent cause of technical withdrawal. At the beginning of the therapy, there is a great functional diversity, but alter the third or fourth years the 20% of patients develop progressive ultrafiltration failure and an increase of the small solute transport. In parallel to this functional alteration, the peritoneum of PD patients shows morphological alterations, such as loss or transformation of mesothelial cells, basal membrane reduplication, submesothelial fibrosis, hyalinazing vasculopathy and neoangiogenesis. There are scant comparative studies of morphofunctional correlation. Most of them have been reported on long-term PD patients and showed a progressive increase of fibrosis and vasculopathy with time on PD, specially in patients with ultrafiltration failure and in those with sclerosing peritonitis. The peritoneal vessel number do not always increase with time on PD, and it is associated with advanced ultrafiltration failure. Some short-term studies have demonstrated that the initial lesion related to the high small solute peritoneal transport is the epithelial to mesenchimal transition of the mesothelial cell (the transformation of mesothelial cell into fibroblastic cell). The higher secretion of extracellular matrix and vascular endothelial growth factor by the transformed mesothelial cells should participated on later development of fibrosis and high peritoneal permeability, not always in relation with higher number of peritoneal vessels.
 ...
PMID:[Anatomic-functional correlation of the peritoneal membrane]. 1895 6

Increased submesothelial collagen deposition, loss of mesothelial cells and increased peritoneal vascularization of peritoneal membrane with vasculopathy leads to peritoneal fibrosis in a patient on long-term peritoneal dialysis (PD). This vascular proliferation within the peritoneum is associated with an increased expression of vascular endothelial growth factor (VEGF), which in turn leads to functional loss or deterioration of the peritoneal membrane over time. Vascular endothelial growth factor inhibitors may slow or even prevent vascular proliferation and subsequent loss of membrane function in peritoneal dialysis patient. We have observed the anti-VGEF effects of a tyrosine kinase inhibitor, sunitinib maleate, in a patient who was on this medication for renal cell carcinoma with extensive abdominal metastasis. The patient had also been on PD for 26 months at the time of the study. In this patient, the tyrosine kinase inhibitor helped to stabilize the abdominal metastasis as well as the thickness of the peritoneal membrane. The D/P creatinine ratio also remained stable. These observations suggest that this tyrosine kinase inhibitor may have prevented peritoneal membrane angiogenesis. We also observed that the patient did not have any further episode of peritonitis from gut-derived organisms, suggesting that stabilization of the intestinal metastasis prevented the transmural migration of bacteria from the gut, thereby preventing peritonitis.
 ...
PMID:Prolonged use of the tyrosine kinase inhibitor in a peritoneal dialysis patient with metastatic renal cell carcinoma: possible beneficial effects on peritoneal membrane and peritonitis rates. 1925 67

Peritoneal dialysis is an alternative treatment of patients with end-stage renal disease. Sclerosing encapsulating peritonitis is a life-threatening complication of continuous ambulatory peritoneal dialysis. The aim of the present study was to evaluate the effect of thalidomide, which is used for the treatment of various inflammatory and autoimmune diseases, on the development of sclerosing encapsulating peritonitis induced by chlorhexidine gluconate (CG). A peritoneal fibrosis model was established using rats treated intraperitoneally with injections of CG. Thalidomide was administered orally at a dose of 100 mg/kg three times per week. When compared with CG-treated rats, thalidomide (100 mg/kg orally)-treated mice subjected to CG-induced peritoneal fibrosis experienced a significantly lower rate in the extent and severity of histological signs of peritoneal injury. Thalidomide also caused a substantial reduction of 1) the rise in myeloperoxidase activity (mucosa); 2) the expression in the tissue of TNF-alpha, IL-1beta, transforming growth factor-beta, and vascular endothelial growth factor; 3) the increase in staining (immunohistochemistry) for nitrotyrosine and for poly(ADP ribose), as well as 4) the nuclear factor-kappaB activation caused by CG in the peritoneum. Thus, thalidomide treatment reduces the degree of peritoneal fibrosis caused by CG. We propose that this evidence may help clarify the potential therapeutic actions of thalidomide in patients with peritoneal fibrosis.
 ...
PMID:Thalidomide suppresses sclerosing encapsulating peritonitis in a rat experimental model. 1968 75

Lymphatic vessels in the diaphragm are essential for draining peritoneal fluid, but little is known about their pathological changes during inflammation. Here we characterized diaphragmatic lymphatic vessels in a peritonitis model generated by daily i.p. administration of lipopolysaccharide (LPS) in mice. Intraperitoneal LPS increased lymphatic density, branching, sprouts, connections, and network formation in the diaphragm in time- and dose-dependent manners. These changes were reversible on discontinuation of LPS administration. The LPS-induced lymphatic density and remodeling occur mainly through proliferation of lymphatic endothelial cells. CD11b+ macrophages were massively accumulated and closely associated with the lymphatic vessels changed by i.p. LPS. Both RT-PCR assays and experiments with vascular endothelial growth factor-C/D blockade and macrophage-depletion indicated that the CD11b+ macrophage-derived lymphangiogenic factors vascular endothelial growth factor-C/D could be major mediators of LPS-induced lymphangiogenesis and lymphatic remodeling through paracrine activity. Functional assays with India ink and fluorescein isothiocyanate-microspheres indicated that impaired peritoneal fluid drainage in diaphragm of LPS-induced peritonitis mice was due to inflammatory fibrosis and massive attachment of CD11b+ macrophages on the peritoneal side of the diaphragmatic lymphatic vessels. These findings reveal that CD11b+ macrophages play an important role in i.p. LPS-induced aberrant lymphangiogenesis and lymphatic dysfunction in the diaphragm.
 ...
PMID:Role of CD11b+ macrophages in intraperitoneal lipopolysaccharide-induced aberrant lymphangiogenesis and lymphatic function in the diaphragm. 1976 11

We present a case of pseudo-meigs' syndrome caused by a metastatic ovarian tumor of rectal cancer origin, and examine the possible involvement of vascular endothelial growth factor (VEGF) in the pathogenesis of refractory fluid retention. A 42-year-old woman with advanced rectal cancer underwent a laparoscopic anterior resection of the rectum. During systemic chemotherapy treatment, she complained of severe abdominal distension 16 months following the operation. We failed to improve massive ascites by diuretics and repeated abdominocenteses. Without any definite evidence of carcinomatous peritonitis, we chose to extirpate an enlarged ovarian tumor on the presumptive diagnosis of pseudo-meigs' syndrome. Ascites disappeared promptly after resecting the ovarian tumors and the subject resumed systemic chemotherapy. Preoperative high levels of serum VEGF were normalized promptly after the operation. Levels of VEGF expression in metastatic ovarian tumors were as weak as in the primary tumor upon immunohistochemical staining. In contrast, increased VEGF expression was evident in epithelial cells of oviducts. For patients with massive and refractory ascites, we need to keep in mind the disease entity of pseudo-meigs' syndrome, since surgical intervention possibly improves conditions. Furthermore, the hypersecretion of VEGF from oviducts may play a role in the pathogenesis of clinical manifestations of pseudo-meigs' syndrome.
 ...
PMID:VEGF hypersecretion as a plausible mechanism for pseudo-meigs' syndrome in advanced colorectal cancer. 2018 51


<< Previous 1 2 3 4 Next >>