The ultrastructure of the peritoneal membrane in chronically dialysed rats with spontaneous peritonitis: preliminary observations

In this paper we describe ultrastructure of the peritoneal membrane from single peritoneal biopsies collected from chronically dialysed rats with spontaneous peritonitis. The results were compared with those obtained in chronically dialysed animals without peritonitis. In rats with peritonitis, peritoneum was much thicker than in peritonitis-free animals. The increased thickness of the peritoneum during peritonitis was due to infiltration of the submesothelial tissue with oedematous fluid and to the presence of huge amount of cells in the stroma. The connective tissue cells were accumulated just underneath the peritoneal surface. In deeper parts of the interstitium, infiltrating acute inflammatory cells were present (lymphocytes, polymorphonuclear cells: neutrophils and eosinophils). Inversely, the increased thickness of the peritoneum in peritonitis-free animals was mainly due to enhanced amounts of collagen. Additionally, in rats with peritonitis, the surface was often denuded of mesothelial cells. The damaged mesothelial cells that detached from the peritoneal surface were also found. In conclusion, the morphological changes observed in rats with peritonitis are similar to those reported in humans, thus the model of peritonitis in dialysed rats can be used for the study of peritoneal remodeling during peritoneal dialysis complicated by peritonitis.     

双歧杆菌对裸鼠腹腔巨噬细胞NO形成的调节作用

给裸小鼠腹腔注射青春型双歧杆菌,每天一次,连续５天,以Ｇｒｉｅｓ试剂测定了裸鼠腹腔巨噬细胞分泌ＮＯ的含量。结果表明：双歧杆菌注射组其腹腔巨噬细胞产生ＮＯ的量显著高于对照组,具有显著的统计学意义（Ｐ＜００１）。提示青春型双歧杆菌可激活巨噬细胞,使之产生一定量的ＮＯ,ＮＯ在介导双歧杆菌的多种生理功能方面起重要作用     

Paragonimiasis in the Abdominal Cavity and Subcutaneous Tissue: Report of 3 Cases

Paragonimiasis is a parasitic disease caused by the lung fluke, Paragonimus spp. Lung flukes may be found in various organs, such as the brain, peritoneum, subcutaneous tissues, and retroperitoneum, other than the lungs. Abdominal paragonimiasis raises a considerable diagnostic challenge to clinicians, because it is uncommon and may be confused with other abdominopelvic inflammatory diseases, particularly peritoneal tuberculosis, and peritoneal carcinomatosis. Also, subcutaneous paragonimiasis does not easily bring up clinical suspicion, due to its rarity. We herein report 2 cases of abdominal paragonimiasis and 1 case of subcutaneous paragonimiasis in Korea.     

Role of macrophages in the host response to Lewis lung peritoneal carcinomatosis

Lewis lung (3LL) peritoneal carcinomatosis elicits a complex host response in the peritoneal compartment. The response was delayed, showing few inflammatory cells through day 6 after lethal challenge with 3LL cells. Responses began in about half the mice on day 7 and had appeared in all mice by day 11. On day 7, some mice still showed no detectable 3LL growth in the peritoneal lavage fluid, and no differences in the peritoneal cell populations as compared with the control group. Other tumor-bearing mice, however, had evidence of 3LL cells and hemorrhagic ascites in the peritoneal compartment, with increased numbers of peritoneal macrophages (PM) and polymorphonuclear neutrophils (PMN). By day 11, all tumor-bearing mice had 3LL growth and hemorrhagic ascites. On days 7–11, there was a major influx of macrophages with a later influx of PMN between days 11 and 14. Two distinct PM populations were detected on day 7 in mice that showed detectable 3LL peritoneal carcinomatosis: resident PM, which did not express the Mac-2 antigen, and recruited PM, which were Mac-2⁺. At least some resident PM remained in the peritoneal compartment through day 14. Analysis of the kinetics of the cytotoxic capabilities of PM from tumor-bearing mice showed that by day 7 macrophages were able to kill the B16 melanoma tumor target, but not the 3LL target. The PM, however, were able to be activated further to kill the 3LL target by treatment in vitro with lipopolysaccharide and interferon . No inhibition of PM tumoricidal activity could detected in the peritoneal wash of tumor-bearing mice. A lack of activation of PM from 3LL tumor-bearing mice may be involved in progression of peritoneal carcinomatosis.     

Action of low-frequency ultrasound on the peritoneum, peritoneal exudate cells and the course of experimental peritonitis

The authors studied the action of low-frequency ultrasound on rat and guinea-pig peritoneal exudate cells during aseptic peritonitis, on the intact peritoneum of these animals, and on experimental peritonitis in guinea-pigs. It was shown that ultrasound "hammers in" India ink solutions and antibacterial drugs into the peritoneum and in combination with antibiotics, it increases the guinea-pig survival rate in peritonitis. Ultrasound was not found to produce a direct bactericidal effect in vivo. Exposure of peritoneal exudate to ultrasound (1 s/cm2) demonstrated an increase in chemotaxis of neutrophil leukocytes to autologic serum and appreciable phagocytic activity. A longer exposure (up to 3-5 s/cm2 or 6-8 s/cm2) resulted in the partial damage to the peritoneum. Leukocytes, mesotheliocytes and subperitoneal striated muscles were found to be especially sensitive to ultrasound.     

Rat adipose tissue-derived stem cells attenuate peritoneal injuries in rat zymosan-induced peritonitis accompanied by complement activation

Background aimsIn patients receiving peritoneal dialysis, fungal or yeast peritonitis has a poor prognosis. In rat peritoneum with mechanical scraping, severe peritonitis can be induced by zymosan, a component of yeast (Zy/scraping peritonitis). Administration of rat adipose tissue-derived stromal cells (ASCs) potentially can improve several tissue injuries. The present study investigated whether rat ASCs could improve peritoneal inflammation in Zy/scraping peritonitis.MethodsRat ASCs were injected intraperitoneally on a daily basis in rats with Zy/scraping peritonitis.ResultsPeritoneal inflammation accompanied by accumulation of inflammatory cells and complement deposition was suppressed by day 5 after injection of rat ASCs. The peritoneal mesothelial layer in Zy/scraping peritonitis with rat ASC treatment was restored compared with the peritoneal mesothelial layer without rat ASC treatment. Injected rat ASCs co-existed with mesothelial cells in the sub-peritoneal layer. In vitro assays showed increased cellular proliferation of rat mesothelial cells combined with rat ASCs by co-culture assays, confirming that fluid factors from rat ASCs might play some role in facilitating the recovery of rat mesothelial cells. Hepatocyte growth factor was released from rat ASCs, and administration of recombinant hepatocyte growth factor increased rat mesothelial cell proliferation.ConclusionsBecause the peritoneal mesothelium shows strong expression of membrane complement regulators such as Crry, CD55 and CD59, restoration of the mesothelial cell layer by rat ASCs might prevent deposition of complement activation products and ameliorate peritoneal injuries. This study suggests the therapeutic possibilities of intraperitoneal rat ASC injection to suppress peritoneal inflammation by restoring the mesothelial layer and decreasing complement activation in fungal or yeast peritonitis.     

Membrane complement regulators protect against fibrin exudation increases in a severe peritoneal inflammation model in rats

Peritonitis and the rare sequela of encapsulating peritoneal sclerosis (EPS) are serious problems in patients on peritoneal dialysis therapy. Chronic and persistent peritoneal injuries may be a risk factor of EPS. We previously reported that a chronic, proliferative peritonitis developed when zymosan was administered intraperitoneally following scraping injury of rat peritoneum (Mizuno M, Ito Y, Hepburn N, Mizuno T, Noda Y, Yuzawa Y, Harris CL, Morgan BP, Matsuo S. J Immunol 183: 1403-1412, 2009). Peritoneal membrane complement regulators (CRegs), especially Crry and CD59, protected from injury by inhibiting local complement activation, suggesting that CRegs play important roles in maintaining homeostasis in rat peritoneum. Here, we investigated roles of complement in the development of EPS by neutralizing CReg function with monoclonal antibodies (MAbs). Proliferative peritonitis was induced by scraping the peritoneum, followed by daily intraperitoneal administration of zymosan. When either Crry or CD59 alone was neutralized by MAb, the tissue injuries were not significantly changed compared with rats without neutralizing MAb. When both Crry and CD59 were neutralized in this model, severe fibrin exudation was observed on the peritoneal surface on day 5, accompanied by inflammatory cell infiltration, resembling the early stages of development of EPS. Dense peritoneal deposition of C3 fragments and membrane attack complex were observed, along with the fibrin exudates. Intravenous administration of cobra venom factor, which profoundly activates complement, further enhanced these pathological changes. Our results show that complement activation in injured peritoneum drives peritoneal inflammation, and that enhancement of complement activation by inhibiting CReg and/or enhancing systemic activation contributes to the initiation of EPS; therefore, anti-complement agents might be of therapeutic value in humans for the treatment of EPS.     

Synthesis and biological evaluation of sulfonyl acrylonitriles as novel inhibitors to peritoneal carcinomatosis

The vast majority of cancer patients die from metastasis, the process by which cancer cells spread to secondary tissues through body fluids. Peritoneal carcinomatosis is a type of metastasis in which cancer cells gain access to the intra-abdominal cavity and then implant in the peritoneum, the thin tissue that lines the abdominal wall and internal organs. Unfortunately, peritoneal carcinomatosis can occur following surgical resection of intra-abdominal malignancies. We previously reported proapoptotic activity of (2E)-3-[[4-(1,1-dimethylethyl)phenyl]sulfonyl]-2-propenenitrile (BAY 11-7085, 1) on colon and pancreatic cancer cells during adhesion and demonstrated that this compound could significantly inhibit peritoneal carcinomatosis in mice.(1,2) In order to determine the chemical basis of the anti-metastatic properties of BAY 11-7085, a series of analogs were synthesized and evaluated for their ability to induce apoptosis in pancreatic and ovarian cancer cells during adhesion to mesothelial cells, which line the surface of the peritoneum. The co-culture assay results were validated using a murine peritoneal carcinomatosis model. These analogs may greatly benefit patients undergoing surgical resections of colorectal, pancreatic, and ovarian cancers depending on their tolerability.     

Stimulus-dependent requirement for granulocyte-macrophage colony-stimulating factor in inflammation

Data from several inflammation/autoimmunity models indicate that GM-CSF can be a key inflammatory mediator. Convenient models in readily accessible tissues are needed to enable the GM-CSF-dependent cellular responses to be elaborated. In this study, we show that, in contrast to the response to the commonly used i.p. irritant, thioglycolate medium, an Ag-specific methylated BSA-induced peritonitis in GM-CSF(-/-) mice was severely compromised. The reduced response in the latter peritonitis model was characterized by fewer neutrophils and macrophages, as well as by deficiencies in the properties of the remaining macrophages, namely size and granularity, phagocytosis, allogeneic T cell triggering, and proinflammatory cytokine production. B1 lymphocytes were more evident in the GM-CSF(-/-) Ag-specific exudates, indicating perhaps that GM-CSF can act on a common macrophage-B1 lymphocyte precursor in the inflamed peritoneum. We propose that these findings contribute to our understanding of how GM-CSF acts as a proinflammatory cytokine in many chronic inflammatory/autoimmune diseases. Of general significance, the findings also indicate that the nature of the stimulus is quite critical in determining whether a particular inflammatory mediator, such as GM-CSF, plays a role in an ensuing inflammatory reaction.     

小鼠腹膜透析模型的构建及腹膜转运关键蛋白的表达

目的构建小鼠腹膜透析模型,以腹膜平衡试验（PET）曲线描述其转运特征,并观察腹膜转运关键蛋白在小鼠腹膜的表达。方法以C57BL/6小鼠为动物模型,通过PET建立透析模型,分别进行生化测定描绘PET曲线,以及蛋白印迹进行关键蛋白的检测。结果C57BL/6小鼠的PET曲线图形与人类接近。AQP-1、eNOS、Cav-1在小鼠腹膜均有稳定的表达。结论该模型结果可靠,代表性强,适合推广。     

Use of high throughput genomic tools for the study of endothelial cell biology

The endothelium is an active, dynamic and heterogeneous organ. It lines the vessels in every organ system and regulates diverse and important biological functions. Over the past several years researchers have gained enormous insights into endothelial cell function in physiological processes such as coagulation and vascular reactivity, and pathophysiological disease states such as inflammation and atherosclerosis. Despite our expanding knowledge of endothelial cell biology, the molecular mechanisms underlying these functions remain largely unknown. The newly developed high throughput genomic tools and accompanying analytical methods provide powerful approaches for identifying new endothelial cell genes and characterizing their role in health and disease. Here, we review some of the recent genomics and proteomic advances that are providing new methodologies for endothelial cell and vascular biology research.     

Oxidative stress and antioxidant strategies in dermatology

Oxidative stress results from a prooxidant-antioxidant imbalance, leading to cellular damage. It is mediated by free radicals, such as reactive oxygen species or reactive nitrogen species, that are generated during physiological aerobic metabolism and pathological inflammatory processes. Skin serves as a protective organ that plays an important role in defending both external and internal toxic stimuli and maintaining homeostasis. It is becoming increasingly evident that oxidative stress is involved in numerous skin diseases and that antioxidative strategies can serve as effective and easy methods for improving these conditions. Herein, we review dysregulated antioxidant systems and antioxidative therapeutic strategies in dermatology.     

Intérêt de la TEP/TDM dans le diagnostic de la carcinose péritonéale : à propos d’une observation

PET/CT is a significant examination recognized in the detection of tumors and their metastases. Through a rare case of peritoneal carcinomatosis complicating an endometrial carcinoma, the authors discuss utility of FDG-PET/CT in the diagnosis and follow-up of this disease.     

A critical role for sphingosine kinase in anaphylatoxin-induced neutropenia, peritonitis, and cytokine production in vivo

The aim of our study was to investigate the roles played by sphingosine kinase (SPHK) in the anaphylatoxin C5a-triggered responses in vivo. Our data show that i.v. administration of C5a triggers a rapid neutropenic response, but pretreating mice with the SPHK inhibitor, N,N-dimethylsphingosine (DMS), 10 min before the C5a i.v. administration substantially inhibited the C5a-triggered neutropenia. Similarly the i.v. administration of C5a caused a rapid increase in the serum levels of TNF-alpha and IL-6, and this increase in cytokine levels was blocked by DMS. We then induced acute peritonitis with C5a. The C5a i.p. injection triggered a fast recruitment of neutrophils, later followed by monocytes, into the peritoneal cavity. Vascular permeability was also observed: when we i.v. injected Evans blue before C5a i.p. injection, we could observe a continued influx of the dye into the peritoneum. In mice pretreated with DMS, there was a significant reduction on the C5a-triggered neutrophil and monocyte infiltration, as well as a marked reduction on the Evans blue influx. Our data also show that the i.p. administration of C5a caused a rapid increase in TNF-alpha and IL-6 levels in the peritoneal cavity, and this increase in cytokine levels was substantially inhibited in mice pretreated with the SPHK inhibitor. Taken together, these observations suggest a potential role for SPHK in the C5a-triggered inflammatory responses in vivo.     

Slit-Robo细胞信号转导通路研究进展

Slit-Robo细胞信号转导通路调控多种多样的生理功能,不同的下游信号转导途径可产生不同的生理功能.其中最广为人知的功能是介导双侧对称生物体胚胎神经系统发育时的轴突排斥现象.近年来,作为一种在生物体内广泛表达的细胞信号转导通路,Slit-Robo的功能库已大大扩展,与神经发育、血管生成、器官及组织发育以及干细胞的增殖...     

The adipose organ at a glance

The main parenchymal cells of the adipose organ are adipocytes. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions can both originate from endothelial cells, and co-exist in the multiple fat depots of the adipose organ – a feature that I propose is crucial for this organ’s plasticity. This poster review provides an overview of the adipose organ, describing its anatomy, cytology, physiological function and histopathology in obesity. It also highlights the remarkable plasticity of the adipose organ, explaining theories of adipocyte transdifferentiation during chronic cold exposure, physical exercise or lactation, as well as in obesity. White-to-brown adipocyte transdifferentiation is of particular medical relevance, because animal data indicate that higher amounts of brown adipose tissue are positively associated with resistance to obesity and its co-morbidities, and that ‘browning’ of the adipose organ curbs these disorders.     

Peritoneal carcinomatosis 2011; it's about time for chemosurgery

The aim of this article was to offer a review on the management of peritoneal carcinomatosis (PC) from cancers of different primary origins. Peritoneal surface malignancies have been traditionally regarded as end-stage conditions amenable to merely palliative options, treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 months. The combination of aggressive cytoreductive surgery (CRS), involving peritonectomy procedures and multivisceral resections with hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) to treat microscopic residual disease is a new concept. This method was established with several phase III studies in well selected patients with PC in whom sufficient cytoreduction could be achieved. Despite the need for more high quality phase III studies, there is now a consensus among many surgical teams around the world about the use of this new combination strategy as a standard of care in pseudomyxoma peritonei, peritoneal mesothelioma and colorectal cancer patients. This review summarizes the current status and possible progress in the future.     

Expression and contribution of endogenous IL-13 in an experimental model of sepsis

IL-13 has been shown to exert potent anti-inflammatory properties. In this study, we elucidated the functional role of endogenous IL-13 in a murine model of septic peritonitis induced by cecal ligation and puncture (CLP). Initial studies demonstrated that the level of IL-13 increased in tissues including liver, lung, and kidney, whereas no considerable increase was found in either peritoneal fluid or serum after CLP. Immunohistochemically, IL-13-positive cells were Kupffer cells in liver, alveolar macrophages in lung, and epithelial cells of urinary tubules in kidney. IL-13 blockade with anti-IL-13 Abs significantly decreased the survival rate of mice after CLP from 53% to 14% on day 7 compared with control. To determine the potential mechanisms whereby IL-13 exerted a protective role in this model, the effects of anti-IL-13 Abs on both local and systemic inflammation were investigated. Administration of anti-IL-13 Abs did not alter the leukocyte infiltration and bacterial load in the peritoneum after CLP but dramatically increased the neutrophil influx in tissues after CLP, an effect that was accompanied by significant increases in the serum levels of aspartate transaminase, alanine transaminase, blood urea nitrogen, and creatinine. Tissue injury caused by IL-13 blockade was associated with increases in mRNA and the protein levels of CXC chemokines macrophage inflammatory protein-2 and KC as well as the CC chemokine macrophage inflammatory protein-1alpha and the proinflammatory cytokine TNF-alpha. Collectively, these results suggest that endogenous IL-13 protected mice from CLP-induced lethality by modulating inflammatory responses via suppression of overzealous production of inflammatory cytokines/chemokines in tissues.     

Preclinical Assessment of Adjunctive tPA and DNase for Peritoneal Dialysis Associated Peritonitis

A major complication of peritoneal dialysis is the development of peritonitis, which is associated with reduced technique and patient survival. The inflammatory response elicited by infection results in a fibrin and debris-rich environment within the peritoneal cavity, which may reduce the effectiveness of antimicrobial agents and predispose to recurrence or relapse of infection. Strategies to enhance responses to antimicrobial agents therefore have the potential to improve patient outcomes. This study presents pre-clinical data describing the compatibility of tPA and DNase in combination with antimicrobial agents used for the treatment of PD peritonitis. tPA and DNase were stable in standard dialysate solution and in the presence of antimicrobial agents, and were safe when given intraperitoneally in a mouse model with no evidence of local or systemic toxicity. Adjunctive tPA and DNase may have a role in the management of patients presenting with PD peritonitis.