[The activating action of mercaptobenzimidazole derivatives on peritoneal macrophages].

PubMed

Ratnikov, V I; Ratnikova, L I

1991-01-01

It was established that derivatives of mercaptobenzimidazole (bemitil, methoxybemitil, 5-ethoxy-2-ethylmercaptobenzimidazole hydrochloride) in a dose of 25 mg/kg stimulate the mouse peritoneal macrophages by increasing their phagocytic activity and phagocytosis index. Among the studied agents 5-ethoxy-2-ethylmercaptobenzimidazole hydrochloride possesses the greatest effect. The increase of phagocytosis processes was shown to be accompanied with a growth of the number of macrophages reducing nitroblue tetrazolium in diphormazan and with an enhancement of secretion of lysosomal enzymes.

Immunopharmacological properties of noopept.

PubMed

Kovalenko, L P; Shipaeva, E V; Alekseeva, S V; Pronin, A V; Durnev, A D; Gudasheva, T A; Ostrovskaja, R U; Seredenin, S B

2007-07-01

Noopept, a peptide analog of piracetam, enhanced phagocytic activity of mouse peritoneal macrophages, stimulated humoral and cellular immune response to various antigens, and markedly increased spontaneous proliferative activity of splenocytes. In animals with secondary immune deficiency caused by cyclophosphamide, noopept exhibited immunocorrector properties.

The influences of a novel anti-adhesion device, thermally cross-linked gelatin film on peritoneal dissemination of tumor cells: The in vitro and in vivo experiments using murine carcinomatous peritonitis models.

PubMed

Miyamoto, Hiroe; Tsujimoto, Hiroyuki; Horii, Tsunehito; Ozamoto, Yuki; Ueda, Joe; Takagi, Toshitaka; Saitoh, Naoto; Hagiwara, Akeo

2017-10-10

To create anti-adhesive materials to be more effective and safer, we developed a thermally cross-linked gelatin film that showed superior anti-adhesive effects with excellent peritoneal regeneration. However, it may act as a convenient scaffold for tumor cell growth, thereby accelerating peritoneal dissemination when used in surgery for abdominal tumors. In this study, we tried to clarify this issue using mouse carcinomatous peritonitis models. First, we examined the in vitro tumor cell growth of mouse B16 melanoma or Colon26 cells on the gelatin film or the conventional hyarulonate/carboxymethylcellulose film. Tumor cell growth on each film was significantly lower than that of the control (no film). Next, we conducted the following in vivo experiments: After the parietal peritoneum was partially removed and covered with each film or without any film, mice were inoculated intraperitoneally with B16 melanoma or Colon26/Nluc cells expressing NanoLuc luciferase gene. At 7 days after the operation, we measured the weight of B16 melanoma tumors or the NanoLuc activity of Colon26/Nluc cells using in vivo imaging at the injured sites. There were no significant differences in the weight of the tumors and the NanoLuc activity among the three groups. We also observed the survival time of mice receiving the same operation and treatments. There was no significant difference in the survival time among the three groups. These results suggest that the gelatin film will likely not accelerate peritoneal dissemination as a convenient scaffold for tumor cell growth when used in surgery for abdominal tumors. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2017. © 2017 Wiley Periodicals, Inc.

Therapeutic Effects of S-Petasin on Disease Models of Asthma and Peritonitis

PubMed Central

Lee, Kyoung-Pil; Kang, Saeromi; Noh, Min-Soo; Park, Soo-Jin; Kim, Jung-Min; Chung, Hae Young; Je, Nam Kyung; Lee, Young-Geun; Choi, Young-Whan; Im, Dong-Soon

2015-01-01

To explore the anti-allergic and anti-inflammatory effects of extracts of Petasites genus, we studied the effects of s-petasin, a major sesquiterpene from Petasites formosanus (a butterbur species) on asthma and peritonitis models. In an ovalbumin-induced mouse asthma model, s-petasin significantly inhibited the accumulations of eosinophils, macrophages, and lymphocytes in bronchoalveolar fluids. S-petasin inhibited the antigen-induced degranulation of β-hexosamidase but did not inhibit intracellular Ca2+ increase in RBL-2H3 mast cells. S-petasin inhibited the LPS induction of iNOS at the RNA and protein levels in mouse peritoneal macrophages. Furthermore, s-petasin inhibited the production of NO (the product of iNOS) in a concentration-dependent manner in the macrophages. Furthermore, in an LPS-induced mouse model of peritonitis, s-petasin significantly inhibited the accumulation of polymorpho nuclear and mononuclear leukocytes in peritoneal cavity. This study shows that s-petasin in Petasites genus has therapeutic effects on allergic and inflammatory diseases, such as, asthma and peritonitis through degranulation inhibition in mast cells, suppression of iNOS induction and production of NO in macrophages, and suppression of inflammatory cell accumulation. PMID:25593643

Fimbrial phase variation and systemic E. coli infection studied in the mouse peritonitis model.

PubMed

Nowicki, B; Vuopio-Varkila, J; Viljanen, P; Korhonen, T K; Mäkelä, P H

1986-08-01

Mouse peritonitis induced by intraperitoneal injection of a virulent (LD50 4 x 10(5) E. coli 018:K1:H7 strain isolated from neonatal meningitis was studied. These bacteria are capable of producing both type 1 and S fimbriae, binding to mannose or sialic acid containing glycoconjugates, respectively; the production of both fimbrial types is subject to phase variation. A broth culture of the bacteria was fractionated into subpopulations containing either type 1 or S fimbriae or neither (nonfimbriated cells), and each fraction, grown in broth to logarithmic growth phase, was used to infect groups of mice. The type 1 fraction was associated with decreased virulence as the fraction was eliminated rapidly without causing a progressive infection even at 10(6) bacteria/mouse, whereas both S and nonfimbriated cells started rapid multiplication in the peritoneal cavity and spread to the blood. In nonfibriated cells, however, S fimbriae production was induced at the same time so that at 1 h after injection, 60-70% of the bacteria in the peritoneal cavity and in the blood of the mice had S fimbriae. The injected S-fimbriated fraction remained completely S-fimbriated. Rapid induction of S fimbriae also took place in vitro when the nonfimbriated bacteria were grown in mouse serum or peritoneal fluid. Anti-S serum protected the mice from a lethal dose of S-fimbriated bacteria.

Decrease of peritoneal inflammatory CD4(+), CD8(+), CD19(+) lymphocytes and apoptosis of eosinophils in a murine Taenia crassiceps infection.

PubMed

Zepeda, Nadia; Solano, Sandra; Copitin, Natalia; Fernández, Ana María; Hernández, Lilián; Tato, Patricia; Molinari, José L

2010-10-01

After an intraperitoneal infection of mice with Taenia crassiceps metacestodes, peritoneal inflammatory cells labeled with fluoresceinated MoAb anti-mouse were analyzed by flow cytometry. Apoptosis was studied by annexin A/PI, TUNEL assays, DNA laddering, caspase-3 activity, and electron microscopy. An important continuous decrease of CD4+, CD8+ and CD19+ lymphocytes, and an increase of eosinophils and macrophages throughout the observation time were found. Apoptosis of eosinophils was quantified during the observation period with a peak at 6 days post-infection (67.27%). In an additional experiment at 12 days post-infection using TUNEL staining, a high level of apoptosis of eosinophil (92.3%) and a significant decrease of CD4+, CD8+, and CD19+ lymphocytes were confirmed. Caspase-3 activity in peritoneal fluid, peritoneal cells' DNA fragmentation, and apoptosis of eosinophils and monocytes were found. The dramatic decrease of peritoneal inflammatory T and B cells and the high level of apoptosis of inflammatory eosinophils induced in mice by infection with T. crassiceps cysticerci may be important factors of the immunosuppression observed in cysticercosis.

Anti-Inflammatory Effects of Hyptis albida Chloroform Extract on Lipopolysaccharide-Stimulated Peritoneal Macrophages

PubMed Central

Sánchez Miranda, Elizabeth; Pérez Ramos, Julia; Fresán Orozco, Cristina; Zavala Sánchez, Miguel Angel; Pérez Gutiérrez, Salud

2013-01-01

We examined the effects of a chloroform extract of Hyptis albida (CHA) on inflammatory responses in mouse lipopolysaccharide (LPS) induced peritoneal macrophages. Our findings indicate that CHA inhibits LPS-induced production of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). During the process, levels of cyclooxygenase-2 (COX-2), nitric oxide synthase (iNOS), and nitric oxide (NO) increased in the mouse peritoneal macrophages; however, the extract suppressed them significantly. These results provide novel insights into the anti-inflammatory actions of CHA and support its potential use in the treatment of inflammatory diseases. PMID:23970974

Annual Progress Report - Fiscal Year 1982

DTIC Science & Technology

1982-10-01

activity . A published method developed in our laboratory for determining tne antibacterial activity of mouse peritoneal phagocytes in vivo (1) has been...EDITOR’S NOTE This FY 1982 Annual Progress report is a general review of research activities of the U. S. Army Medical Research Institute of Infectious...years earlier. Passive immunization, active immunization using killed or living attenuated whole agent, or immunization with sub-unit antigens achieved

Production of lymphocyte-activating factors by mouse macrophages during aging and under the effect of short peptides.

PubMed

Gumen, A V; Kozinets, I A; Shanin, S N; Malinin, V V; Rybakina, E G

2006-09-01

Age-specific characteristics of production of lymphocyte-activating factor by mouse peritoneal macrophages and modulation of this production by short synthetic peptides (Vilon, Epithalon, and Cortagen) were studied. The production of lymphocyte-activating factors by macrophages stimulated with lipopolysaccharides in vitro was lower in old animals. The opposite modulating effects of short peptides on the production of lymphocyte-activating factors by resident and lipopolysaccharide-stimulated macrophages in young and old mice were demonstrated for the first time. This is a possible mechanism of immune system dysfunction during aging, which opens new vistas for its correction with short synthetic peptides.

Antigiardial activity of Ocimum basilicum essential oil.

PubMed

de Almeida, Igor; Alviano, Daniela Sales; Vieira, Danielle Pereira; Alves, Péricles Barreto; Blank, Arie Fitzgerald; Lopes, Angela Hampshire C S; Alviano, Celuta Sales; Rosa, Maria do Socorro S

2007-07-01

In this study, we investigated the effects of Ocimum basilicum essential oil on Giardia lamblia and on the modulation of the interaction of these parasites by peritoneal mouse macrophage. The essential oil (2 mg/ml) and its purified substances demonstrated antigiardial activity. Linalool (300 microg/ml), however, was able to kill 100% parasites after 1 h of incubation, which demonstrates its high antigiardial potential. Pretreatment of peritoneal mouse macrophages with 2 mg/ml essential oil dilution reduced in 79% the association index between these macrophages and G. lamblia, with a concomitant increase by 153% on nitric oxide production by the G. lamblia-ingested macrophages. The protein profiles and proteolitic activity of these parasite trophozoites, previously treated or not with 2 mg/ml essential oil or with the purified fractions, were also determined. After 1 and 2 h of incubation, proteins of lysates and culture supernatants revealed significant differences in bands patterns when compared to controls. Besides, the proteolitic activity, mainly of cysteine proteases, was clearly inhibited by the essential oil (2 mg/ml) and the purified linalool (300 microg/ml). These results suggest that, with G. lamblia, the essential oil from O. basilicum and its purified compounds, specially linalool, have a potent antimicrobial activity.

A defect in the inflammation-primed macrophage-activation cascade in osteopetrotic rats.

PubMed

Yamamoto, N; Lindsay, D D; Naraparaju, V R; Ireland, R A; Popoff, S N

1994-05-15

Macrophages were activated by administration of lysophosphatidylcholine (lyso-Pc) or dodecylglycerol (DDG) to wild-type rats but not in osteopetrotic (op) mutant rats. In vitro treatment of wild-type rat peritoneal cells with lyso-Pc or DDG efficiently activated macrophages whereas treatment of op mutant rat peritoneal cells with lyso-Pc or DDG did not activate macrophages. The inflammation-primed macrophage activation cascade in rats requires participation of B lymphocytes and vitamin D binding protein (DBP). Lyso-Pc-inducible beta-galactosidase of wild-type rat B lymphocytes can convert DBP to the macrophage-activating factor (MAF), whereas B lymphocytes of the op mutant rats were shown to be deficient in lyso-Pc-inducible beta-galactosidase. DBP is conserved among mammalian species. Treatment of human DBP (Gc1 protein) with commercial glycosidases yields an extremely high titrated MAF as assayed on mouse and rat macrophages. Because the enzymatically generated MAF (GcMAF) bypasses the role of lymphocytes in macrophage activation, the op mutant rat macrophages were efficiently activated by administration of a small quantity (100 pg/rat) of GcMAF. Likewise, in vitro treatment of op rat peritoneal cells with as little as 40 pg GcMAF/ml activated macrophages.

In Vitro Anti-inflammatory Effects of the Phenylbutyric Acid Metabolite Phenylacetyl Glutamine.

PubMed

Hazekawa, Mai; Ono, Kazuhiko; Nishinakagawa, Takuya; Kawakubo-Yasukochi, Tomoyo; Nakashima, Manabu

2018-06-01

Sodium 4-phenylbutyrate (PBA), which exerts a wide range of anti-inflammatory effects, is rapidly cleared from the body (approximately 98%) by urinary excretion by 24 h after oral treatment in humans. PBA was almost entirely excreted to urine as phenylacetyl glutamine (PAGln). However, no data describe the potential anti-inflammatory effects of PAGln. The purpose of this study was to evaluate the anti-inflammatory effects of PAGln on mouse spleen cells and peritoneal cavity cells, and explore the potential mechanism underlying this effect. PAGln was added to mouse spleen cell cultures stimulated by concanavalin A, or mouse peritoneal cavity cell cultures stimulated by lipopolysaccharide. After 72 h of culture, levels of inflammatory cytokines in culture supernatants were measured using a sandwich enzyme-linked immunosorbent assay system, and levels of inflammatory proteins were assessed by Western blotting. PAGln significantly inhibited inflammatory cytokine (interferon-γ, interleukin-6, and tumor necrosis factor-α) production, decrease of cell number in the spleen cell, and suppressed the expression of inflammatory proteins (nuclear factor κB, and inducible nitric oxide synthase). These results suggest that PAGln possesses anti-inflammatory activity via inhibition of T cell activation and Toll-like receptor 4 signaling. This study of the anti-inflammatory mechanism of PAGln provides useful information about its potential for therapeutic applications.

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation.

PubMed

Kwak, Su-Bin; Koppula, Sushruta; In, Eun-Jung; Sun, Xiao; Kim, Young-Kyu; Kim, Myong-Ki; Lee, Kwang-Ho; Kang, Tae-Bong

2018-01-01

Artemisia princeps var. orientalis (Asteraceae, A. princeps ) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1 β regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo . The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1 β levels, significantly ( p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis.

Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

PubMed Central

Kwak, Su-Bin; Koppula, Sushruta; In, Eun-Jung; Sun, Xiao; Kim, Young-Kyu

2018-01-01

Artemisia princeps var. orientalis (Asteraceae, A. princeps) is a well-known traditional medicinal herb used for treating various inflammatory disorders in Korea, Japan, China, and other Asian countries. In the present study, we investigated the effects of A. princeps extract (APO) on interleukin- (IL-) 1β regulation and inflammasome activation in bone marrow-derived macrophages (BMDMs) and monosodium urate- (MSU-) induced peritonitis mouse model in vivo. The APO treatment to BMDMs primed with lipopolysaccharide (LPS) attenuated the NLRP3 and AIM2 inflammasome activation induced by danger signals, such as ATP, nigericin, silica crystals, and poly (dA:dT), respectively. Mechanistic study revealed that APO suppressed the ASC oligomerization and speck formation, which are required for inflammasome activation. APO treatment also reduced the ASC phosphorylation induced by the combination of LPS and a tyrosine phosphatase inhibitor. In vivo evaluation revealed that intraperitoneal administration of APO reduced IL-1β levels, significantly (p < 0.05) and dose dependently, in the MSU-induced peritonitis mouse model. In conclusion, our study is the first to report that the extract of A. princeps inhibits inflammasome activation through the modulation of ASC phosphorylation. Therefore, APO might be developed as therapeutic potential in the treatment of inflammasome-mediated inflammatory disorders, such as gouty arthritis. PMID:29686531

Infectivity of five different types of macrophages by Leishmania infantum.

PubMed

Maia, C; Rolão, N; Nunes, M; Gonçalves, L; Campino, L

2007-08-01

Leishmania are intracellular parasites that multiply as the amastigote form in the macrophages of their vertebrate hosts. Since vaccines against leishmaniases are still under development, the control of these diseases relies on prompt diagnosis and chemotherapy in infected humans as well as in dogs, which are the main reservoir of Leishmania infantum, in Mediterranean countries. To establish the macrophage type to be used as an in vitro model for antileishmanial chemotherapeutic studies, we analysed the susceptibility of human peripheral blood derived macrophages, macrophages derived from mouse bone marrow, mouse peritoneal macrophages and macrophages differentiated from cell lines U-937 and DH82 to infection by two L. infantum strains, one obtained from a human leishmanial infection and other from a canine infection. Both strains displayed comparable behaviour in their capacity of infecting the different macrophage types. Human peripheral blood macrophages and DH82 cells were less infectable by both strains. U-937, mouse peritoneal macrophages and mouse bone marrow derived macrophages are the most active cells to phagocytose the parasites. However, U-937 cell line appears to be the most useful as Leishmania infection model providing an unlimited source of homogeneous host cells with reproducibility of the results, is less time consuming, less expensive and tolerate high doses of first line drugs for human and canine visceral leishmaniasis treatment.

Regulation of LPS-induced mRNA expression of pro-inflammatory cytokines via alteration of NF-κB activity in mouse peritoneal macrophages exposed to fluoride.

PubMed

Tian, Yuhu; Huo, Meijun; Li, Guangsheng; Li, Yanyan; Wang, Jundong

2016-10-01

F toxicity to immune system, especially to macrophage, has been studied a lot recently. Nuclear factor-kappa B (NF-κB), as a transcription factor, plays a central role in immune and inflammatory responses via the regulation of downstream gene expression. Recent studies indicated that fluoride effect on inflammatory cytokine secretion, however, the molecular mechanism was less understood. In our study, peritoneal macrophages (PMs) were divided several groups and were administrated sodium fluoride (NaF, 50, 100, 200, 400, 800 μM) and/or lipopolysaccharide (LPS, 30 ng/mg). The mRNA expression of p65, inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) in macrophages exposed to fluoride was determined by quantitative real-time RT-PCR respectively. The translocation of NF-κB from cytoplasm to nucleus, which in a way reflects NF-κB activity, was demonstrated by Immunofluorescence and ELISA. Our results showed that fluoride had a dose-dependent effect on NF-κB activity, which coincided with LPS-induced mRNA expression of its downstream genes, iNOS and IL-1β. Fluoride alone causes no effect on gene expression. However, the mRNA expression of TNF-α showed non-NF-κB-dependent manner. Therefore, we come to the conclusion that fluoride can regulate LPS-induced mRNA expression of iNOS and IL-1β via NF-κB pathway in mouse peritoneal macrophages. Copyright © 2016 Elsevier Ltd. All rights reserved.

Therapeutic Cell-Cycle-Decoy Efficacy of a Telomerase-Dependent Adenovirus in an Orthotopic Model of Chemotherapy-Resistant Human Stomach Carcinomatosis Peritonitis Visualized With FUCCI Imaging.

PubMed

Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-11-01

We have established an orthotopic nude-mouse model of gastric cancer carcinomatosis peritonitis, a recalcitrant disease in human patients. Human MKN45 poorly-differentiated human gastric cancer cells developed carcinomatosis peritonitis upon orthotopic transplantation in nude mice. The MKN45 cells expressed the fluorescent ubiquitination-based cell cycle indicator (FUCCI) that color codes the phases of the cell cycle. The intra-peritoneal tumors and ascites contained mostly quiescent G 1 /G o cancer cells visualized as red by FUCCI imaging. Cisplatinum (CDDP) treatment did not reduce bloody ascites, and larger tumors formed in the peritoneal cavity after CDDP treatment in an early-stage carcinomatosis peritonitis orthotopic mouse model. Paclitaxel-treated mice had reduced ascites, but also had large tumor masses in the peritonium after treatment with cancer cells mostly in G 0 /G 1 , visualized by FUCCI red. In contrast, OBP-301 telomerase-dependent adenovirus-treated mice had no ascites and only small tumor nodules consisting of cancer cells mostly in S/G 2 phases in the early-stage carcinomatosis peritonitis model, visualized by FUCCI green. Furthermore, OBP-301 significantly reduced the size of tumors (P < 0.01) and ascites even in a late-stage carcinomatosis peritonitis model. These results suggest that quiescent peritoneally-disseminated gastric cancer cells are resistant to conventional chemotherapy, but OBP-301 significantly reduced the weight of the tumors and increased survival, suggesting clinical potential. J. Cell. Biochem. 118: 3635-3642, 2017. © 2016 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Identification of Protein Targets of 12/15-Lipoxygenase-Derived Lipid Electrophiles in Mouse Peritoneal Macrophages Using Omega-Alkynyl Fatty Acid.

PubMed

Isobe, Yosuke; Kawashima, Yusuke; Ishihara, Tomoaki; Watanabe, Kenji; Ohara, Osamu; Arita, Makoto

2018-04-20

The 12/15-lipoxygenase (12/15-LOX) enzyme introduces peroxyl groups, in a position-specific manner, into polyunsaturated fatty acids to form various kinds of bioactive lipid metabolites, including lipid-derived electrophiles (LDE). The resident peritoneal macrophage is the site of highest 12/15-LOX expression in the mouse. However, the role of the enzyme in the regulation of resident macrophages is not fully understood. Here, we describe a chemoproteomic method to identify the targets of enzymatically generated LDE. By treating mouse peritoneal macrophages with omega-alkynyl arachidonic acid (aAA), we identified a series of proteins adducted by LDE generated through a 12/15-LOX catalyzed reaction. Pathway analysis revealed a dramatic enrichment of proteins involved in energy metabolism and found that glycolytic flux and mitochondrial respiration were significantly affected by the expression of 12/15-LOX. Our findings thus highlight the utility of chemoproteomics using aAA for identifying intracellular targets of enzymatically generated LDE.

CD44 deficiency enhanced Streptococcus equi ssp. zooepidemicus dissemination and inflammation response in a mouse model.

PubMed

Fu, Qiang; Xiao, Pingping; Chen, Yaosheng; Wei, Zigong; Liu, Xiaohong

2017-12-01

Streptococcus equi ssp. zooepidemicus (S. zooepidemicus) is responsible for peritonitis, septicemia, meningitis, arthritis and several other serious diseases in various species. Recent studies have demonstrated that CD44 is implicated in the process of host defense against pathogenic microorganisms. In the present study, the role of CD44 in the host response to S. zooepidemicus infection was investigated in a mouse model. Upon intraperitoneal infection with S. zooepidemicus, the expression of CD44 on the peritoneal exudate cells from wild-type (WT) mice was increased. CD44 deficiency accelerated mortality, which was accompanied by increased peritoneal bacterial growth and dissemination to distant body sites. CD44 knock-out (KO) mice showed enhanced early inflammatory cell recruitment into the peritoneal fluid on S. zooepidemicus infection. In line with this, the expression of proinflammatory cytokines, chemokines in peritoneal exudate cells and peritoneal macrophages of CD44 KO mice were increased compared with those of WT mice. In addition, CD44 deficiency was associated with reduced expression of A20, a negative regulator in TLR signaling. Overall, the present study suggests that CD44 plays a protective role in antibacterial defense against S. zooepidemicus in mice. Copyright © 2017. Published by Elsevier Ltd.

HUMAN ALVEOLAR AND PERITONEAL MACROPHAGES MEDIATE FUNGISTASIS INDEPENDENTLY OF L-ARGININE OXIDATION TO NITRITE OR NITRATE

EPA Science Inventory

Human alveolar macrophages (HAM) from 28 normal volunteers were found to inhibit replication of Cryptoccous neoformans. onditions under which fungistasis occurred were different than those required for mouse peritoneal macrophage-mediated fungi stasis. nhibition of fungal replica...

Evaluation of the efficacy of Hylotelephium purpureum gel in the treatment of experimental periodontitis

PubMed Central

Wang, Xiaofeng; Wang, Wei; Li, Wei; Niu, Zhiduo; Wang, Qing; Zhang, Dianwen; Li, Hui; Wang, Jincheng

2018-01-01

Local drug delivery systems have been proposed for the treatment of periodontitis, and Hylotelephium purpureum may be a suitable agent for use in such a system. The present study aimed to formulate a Hylotelephium purpureum gel (HPG) and evaluate the anti-inflammatory activity and antinociceptive effects of Hylotelephium purpureum and to assess the duration of action and efficacy of HPG in the treatment of experimental periodontitis in a KM mouse model. First, an acute toxicity study was performed, and secondly, xylene-induced mouse-ear edema, acetic acid-induced mouse peritoneal capillary permeability and carrageenan-induced hind-paw edema tests were used to investigate the anti-inflammatory activity of the gel. The acetic acid-induced writhing response and hot-plate tests were used to evaluate the antinociceptive activity. The therapeutic effects of HPG in experimental periodontitis were evaluated and minimum inhibitory concentration of the gel was determined. The results showed that intragastrically administration of 80 ml/kg of HPG produced no toxic effects. There were statistically significant changes in gingival indexes and sulcus bleeding indexes in the high-dose HPG-treated group. The serum levels of superoxide dismutase and glutathione peroxidase were significantly heightened, while the level of malondialdehyde was decreased. HPG exhibited 32.7% inhibition of edema, and altered the peritoneal capillary permeability in mice. The gel had relatively good bacteriostatic and bactericidal effects. It also exhibited antinociceptive activity, as demonstrated by the acetic acid-induced writhing response test and hot-plate test. In summary, the present study demonstrates that HPG is effective in the treatment of experimental periodontitis. PMID:29541459

Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer

PubMed Central

Sato, Kazuhide; Hanaoka, Hirofumi; Watanabe, Rira; Nakajima, Takahito; Choyke, Peter L.; Kobayashi, Hisataka

2014-01-01

Near infrared photoimmunotherapy (NIR-PIT) is a new cancer treatment that combines the specificity of intravenously injected antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. Herein, we evaluate the efficacy of NIR-PIT in a mouse model of disseminated peritoneal ovarian cancer. In vitro and in vivo experiments were conducted with a HER2-expressing, luciferase expressing, ovarian cancer cell line (SKOV-luc). An antibody-photosensitizer conjugate (APC) consisting of trastuzumab and a phthalocyanine dye, IRDye-700DX, was synthesized (tra-IR700) and cells or tumors were exposed to near infrared (NIR) light. In vitro PIT cytotoxicity was assessed with dead staining and luciferase activity in freely growing cells and in a 3D spheroid model. In vivo NIR-PIT was performed in mice with tumors implanted in the peritoneum and in the flank and these assessed by tumor volume and/or bioluminescence. In vitro NIR-PIT-induced cytotoxicity was light dose dependent. Repeated light exposures induced complete tumor cell killing in the 3D spheroid model. In vivo the anti-tumor effects of NIR-PIT were confirmed by significant reductions in both tumor volume and luciferase activity in the flank model (NIR-PIT vs control in tumor volume changes at day 10; p=0.0001, NIR-PIT vs control in luciferase activity at day 4; p=0.0237), and the peritoneal model (NIR-PIT vs control in luciferase activity at day 7; p=0.0037). NIR-PIT provided effective cell killing in this HER2 positive model of disseminated peritoneal ovarian cancer. Thus, NIR-PIT is a promising new therapy for the treatment of disseminated peritoneal tumors. PMID:25416790

Treatment of dextran sodium sulfate-induced experimental colitis by adoptive transfer of peritoneal cells

PubMed Central

Liu, Ting; Ren, Jun; Wang, Wei; Wei, Xia-wei; Shen, Guo-bo; Liu, Yan-tong; Luo, Min; Xu, Guang-chao; Shao, Bin; Deng, Sen-yi; He, Zhi-yao; Liang, Xiao; Liu, Yu; Wen, Yan-Zhu; Xiang, Rong; Yang, Li; Deng, Hong-xin; Wei, Yu-quan

2015-01-01

The adoptive transfer of the natural regulatory B cells and macrophages should be a useful treatment for inflammation and autoimmune disease. However, it is usually difficult to isolate these cells from the tissues and expand them. Here, we investigated the feasibility of adoptively transferring peritoneal cells (PCs) as a treatment for DSS-induced colitis. We found that peritoneal cavity can provide an easily accessible site for harvesting enough number of PCs, namely, two-dose PCs for the treatment from a mouse in one operation. Adoptive therapy of these cells from healthy mice or those with disease is effectively in reducing the disease activity score. The natural B cells and macrophages of the infused PCs can selectively migrate to lesion sites and regulate the expression of Stat3, NF−κB, Smad3 and Smad7. Additionally, PCs exert dual activity of IL-10 and TGF-β secreted spontaneously by both peritoneal B cells and macrophages, which in turn enhance the induction of regulatory B cells and Macrophages in microenvironment of inflammation. Moreover, PCs can re-establish immunological tolerance in the OVA-immunized mice. Thus, our findings provide a new strategy for colitis therapy and could be of importance in additional exploration of other inflammation and autoimmune diseases therapy. PMID:26565726

Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression.

PubMed

Blich, Miry; Golan, Amnon; Arvatz, Gil; Sebbag, Anat; Shafat, Itay; Sabo, Edmond; Cohen-Kaplan, Victoria; Petcherski, Sirouch; Avniel-Polak, Shani; Eitan, Amnon; Hammerman, Haim; Aronson, Doron; Axelman, Elena; Ilan, Neta; Nussbaum, Gabriel; Vlodavsky, Israel

2013-02-01

Factors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages. Highly purified heparanase was added to mouse peritoneal macrophages and macrophage-like J774 cells, and the levels of tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 were evaluated by ELISA. Gene expression was determined by RT-PCR. Cells collected from Toll-like receptor-2 and Toll-like receptor-4 knockout mice were evaluated similarly. Heparanase levels in the plasma of patients with acute myocardial infarction, stable angina, and healthy subjects were determined by ELISA. Immunohistochemistry was applied to detect the expression of heparanase in control specimens and specimens of patients with stable angina or acute myocardial infarction. Addition or overexpression of heparanase variants resulted in marked increase in tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 levels. Mouse peritoneal macrophages harvested from Toll-like receptor-2 or Toll-like receptor-4 knockout mice were not activated by heparanase. Plasma heparanase level was higher in patients with acute myocardial infarction, compared with patients with stable angina and healthy subjects. Pathologic coronary specimens obtained from vulnerable plaques showed increased heparanase staining compared with specimens of stable plaque and controls. Heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression toward vulnerability.

Profiling of Candida albicans Gene Expression During Intra-abdominal Candidiasis Identifies Biologic Processes Involved in Pathogenesis

PubMed Central

Cheng, Shaoji; Clancy, Cornelius J.; Xu, Wenjie; Schneider, Frank; Hao, Binghua; Mitchell, Aaron P.; Nguyen, M. Hong

2013-01-01

Background. The pathogenesis of intra-abdominal candidiasis is poorly understood. Methods. Mice were intraperitoneally infected with Candida albicans (1 × 106 colony-forming units) and sterile stool. nanoString assays were used to quantitate messenger RNA for 145 C. albicans genes within the peritoneal cavity at 48 hours. Results. Within 6 hours after infection, mice developed peritonitis, characterized by high yeast burdens, neutrophil influx, and a pH of 7.9 within peritoneal fluid. Organ invasion by hyphae and early abscess formation were evident 6 and 24 hours after infection, respectively; abscesses resolved by day 14. nanoString assays revealed adhesion and responses to alkaline pH, osmolarity, and stress as biologic processes activated in the peritoneal cavity. Disruption of the highly-expressed gene RIM101, which encodes an alkaline-regulated transcription factor, did not impact cellular morphology but reduced both C. albicans burden during early peritonitis and C. albicans persistence within abscesses. RIM101 influenced expression of 49 genes during intra-abdominal candidiasis, including previously unidentified Rim101 targets. Overexpression of the RIM101-dependent gene SAP5, which encodes a secreted protease, restored the ability of a rim101 mutant to persist within abscesses. Conclusions. A mouse model of intra-abdominal candidiasis is valuable for studying pathogenesis and C. albicans gene expression. RIM101 contributes to persistence within intra-abdominal abscesses, at least in part through activation of SAP5. PMID:24006479

22-Oxacalcitriol Prevents Progression of Peritoneal Fibrosis in a Mouse Model

PubMed Central

Hirose, Misaki; Nishino, Tomoya; Obata, Yoko; Nakazawa, Masayuki; Nakazawa, Yuka; Furusu, Akira; Abe, Katsushige; Miyazaki, Masanobu; Koji, Takehiko; Kohno, Shigeru

2013-01-01

♦ Objective: Vitamin D plays an important role in calcium homeostasis and is used to treat secondary hyperparathyroidism among dialysis patients. The biologic activity of vitamin D and its analogs is mediated by vitamin D receptor (VDR), which is distributed widely throughout the body. Recent papers have revealed that low vitamin D levels are correlated with severe fibrosis in chronic diseases, including cystic fibrosis and hepatitis. The aim of the present study was to evaluate the protective effects of vitamin D against the progression of peritoneal fibrosis. ♦ Methods: Peritoneal fibrosis was induced by injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. An analog of vitamin D, 22-oxacalcitriol (OCT), was administered subcutaneously daily from initiation of the CG injections. The peritoneal tissue was excised at 3 weeks. Changes in morphology were assessed by hematoxylin and eosin staining. Expression of VDR, alpha smooth muscle actin (as a marker of myofibroblasts), type III collagen, transforming growth factor β(TGF-β), phosphorylated Smad2/3, F4/80 (as a marker of macrophages), and monocyte chemoattractant protein-1 (MCP-1) was examined by immunohistochemistry. Southwestern histochemistry was used to detect activated nuclear factor κB (NF-κB). ♦ Results: In the CG-injected mice, immunohistochemical analysis revealed expression of VDR in mesothelial cells, myofibroblasts, and macrophages in the thickened submesothelial zone. Treatment with OCT significantly prevented peritoneal fibrosis and reduced the accumulation of type III collagen in CG-treated mice. Among the markers of fibrosis, the numbers of myofibroblasts, cells positive for TGF-β, and cells positive for phosphorylated Smad2/3 were significantly decreased in the OCT-treated group compared with the vehicle-treated group. Furthermore, OCT suppressed inflammatory mediators of fibrosis, as shown by the reduced numbers of activated NF-κB cells, macrophages, and MCP-1-expressing cells. ♦ Conclusions: Our results indicate that OCT attenuates peritoneal fibrosis, an effect accompanied by reduced numbers of myofibroblasts, infiltrating macrophages, and TGF-β-positive cells, suggesting that vitamin D has potential as a novel therapeutic agent for preventing peritoneal sclerosis. PMID:23032084

High efficiency capillary column-gas chromatography mass spectrometry: analysis of the lipoxygenase pathway in eukaryot cells.

PubMed

Rabinovitch-Chable, H; Durand, J; Aldigier, J C; Chebroux, P; Gualde, N; Beneytout, J L; Rigaud, M

1984-01-01

Lipoxygenases are ubiquitous enzymes able to oxygenate polyunsaturated fatty acids. This metabolic pathway leads to hydroperoxides, hydroxyepoxyene compounds and leukotrienes. Using high performance gas chromatography prior to mass spectrometry, we studied the activity of the lipoxygenases from mouse peritoneal macrophages. Further studies on mechanism of biosynthesis of hydroxyepoxyene compounds were successfully carried out using 18O2 labelled precursors.

Pleiotrophin triggers inflammation and increased peritoneal permeability leading to peritoneal fibrosis.

PubMed

Yokoi, Hideki; Kasahara, Masato; Mori, Kiyoshi; Ogawa, Yoshihisa; Kuwabara, Takashige; Imamaki, Hirotaka; Kawanishi, Tomoko; Koga, Kenichi; Ishii, Akira; Kato, Yukiko; Mori, Keita P; Toda, Naohiro; Ohno, Shoko; Muramatsu, Hisako; Muramatsu, Takashi; Sugawara, Akira; Mukoyama, Masashi; Nakao, Kazuwa

2012-01-01

Long-term peritoneal dialysis induces peritoneal fibrosis with submesothelial fibrotic tissue. Although angiogenesis and inflammatory mediators are involved in peritoneal fibrosis, precise molecular mechanisms are undefined. To study this, we used microarray analysis and compared gene expression profiles of the peritoneum in control and chlorhexidine gluconate (CG)-induced peritoneal fibrosis mice. One of the 43 highly upregulated genes was pleiotrophin, a midkine family member, the expression of which was also upregulated by the solution used to treat mice by peritoneal dialysis. This growth factor was found in fibroblasts and mesothelial cells within the underlying submesothelial compact zones of mice, and in human peritoneal biopsy samples and peritoneal dialysate effluent. Recombinant pleiotrophin stimulated mitogenesis and migration of mouse mesothelial cells in culture. We found that in wild-type mice, CG treatment increased peritoneal permeability (measured by equilibration), increased mRNA expression of TGF-β1, connective tissue growth factor and fibronectin, TNF-α and IL-1β expression, and resulted in infiltration of CD3-positive T cells, and caused a high number of Ki-67-positive proliferating cells. All of these parameters were decreased in peritoneal tissues of CG-treated pleiotrophin-knockout mice. Thus, an upregulation of pleiotrophin appears to play a role in fibrosis and inflammation during peritoneal injury.

Integrated Molecular Profiling of Human Gastric Cancer Identifies DDR2 as a Potential Regulator of Peritoneal Dissemination.

PubMed

Kurashige, Junji; Hasegawa, Takanori; Niida, Atsushi; Sugimachi, Keishi; Deng, Niantao; Mima, Kosuke; Uchi, Ryutaro; Sawada, Genta; Takahashi, Yusuke; Eguchi, Hidetoshi; Inomata, Masashi; Kitano, Seigo; Fukagawa, Takeo; Sasako, Mitsuru; Sasaki, Hiroki; Sasaki, Shin; Mori, Masaki; Yanagihara, Kazuyoshi; Baba, Hideo; Miyano, Satoru; Tan, Patrick; Mimori, Koshi

2016-03-03

Peritoneal dissemination is the most frequent, incurable metastasis occurring in patients with advanced gastric cancer (GC). However, molecular mechanisms driving peritoneal dissemination still remain poorly understood. Here, we aimed to provide novel insights into the molecular mechanisms that drive the peritoneal dissemination of GC. We performed combined expression analysis with in vivo-selected metastatic cell lines and samples from 200 GC patients to identify driver genes of peritoneal dissemination. The driver-gene functions associated with GC dissemination were examined using a mouse xenograft model. We identified a peritoneal dissemination-associated expression signature, whose profile correlated with those of genes related to development, focal adhesion, and the extracellular matrix. Among the genes comprising the expression signature, we identified that discoidin-domain receptor 2 (DDR2) as a potential regulator of peritoneal dissemination. The DDR2 was upregulated by the loss of DNA methylation and that DDR2 knockdown reduced peritoneal metastasis in a xenograft model. Dasatinib, an inhibitor of the DDR2 signaling pathway, effectively suppressed peritoneal dissemination. DDR2 was identified as a driver gene for GC dissemination from the combined expression signature and can potentially serve as a novel therapeutic target for inhibiting GC peritoneal dissemination.

Endotoxin contamination of Agaricus blazei Murrill extract enhances murine immunologic responses and inhibits the growth of sarcoma 180 implants in vivo.

PubMed

Kobayashi, Hitoshi; Masumoto, Junya

2010-01-01

Agaricus blazei Murrill, a native mushroom of Brazil, has been reported to be an immunoreactant with anti-tumor effect. There are many reports on the anti-tumor effect of Agaricus blazei Murrill; however, the precise mechanism of its effect is not fully understood. In this study, we tried to confirm the anti-tumor effect of Agaricus blazei Murrill against Sarcoma 180 cells in a mouse model and found that an inhibitory effect on tumor growth was induced by peritoneal injection of a freeze-dried, hot water extract of Agaricus blazei Murrill (FAG). We noted that there were differences among each sample in terms of anti-tumor activity. We hypothesized that this was because some contaminants of FAG were affecting the anti-tumor activity. We evaluated cytokine secretion from mouse peritoneal cells incubated with FAG. While high interleukin-6 and tumor necrosis factor-α secretions were observed in response to crude FAG, they were dramatically decreased by the removal of endotoxin from the FAG using an endotoxin-specific polymyxin B-conjugated affinity column. The reductions were synergistically recovered by adding an amount of lipopolysaccharide equivalent to the amount of contaminated endotoxin. Thus, these data suggest that the contaminated endotoxin of Agaricus blazei Murrill may act as an immunomodulator of anti-tumor activity.

Anti-carcinogenic activity of 6-methylsulfinylhexyl isothiocyanate-, an active anti-proliferative principal of wasabi (Eutrema wasabi Maxim.).

PubMed

Fuke, Y; Haga, Y; Ono, H; Nomura, T; Ryoyama, K

1997-11-01

Synthetic 4-methylsulfinylhexyl isothiocyanate (MITC)(a potent inducer of phase 2 detoxification enzymes from broccoli) and 6-MITC(a potent anti-proliferative principal from wasabi) slightly inhibited the induction of mouse skin tumor in a two-stage process of carcinogenesis (initiator, 9,10-dimethyl-1,2-benzanthracene; promotor,12-o-tetradecanoylphorbol-13-acetate), but the effect was not significant. Both compounds, however, significantly inhibited the mutation of skin resulting from topical applications of the carcinogens. When a murine hepatoma cell line, Hepa 1c1c7, was treated with 2-,4-,6- and 8-MITCs, they augmented the induction of its quinone reductase, one of the phase 2 detoxification enzymes in a concentration dependent manner, and the 4- and 6-MITCs were much more potent on the reduction of the enzyme than the 2- and 8-MITCs. All 2-, 4-, 6- and 8-MITCs suppressed the growth of murine tumor cells, their suppressive activities being proportional to the length of their methyl residue. They were also cytotoxic to mouse peritoneal exudate macrophages which were not proliferating in vitro, indicating that the cellular targets of isothiocyanate may not be dependent upon the cell cycle. In addition, all the 2-, 4-, 6- and 8-MITCs inhibited the production of nitric oxide (a potent radical carcinogen) by peritoneal macrophages.

Benzenediamine analog FC-99 inhibits TLR2 and TLR4 signaling in peritoneal macrophage in vitro.

PubMed

Yang, Liu; Dou, Huan; Song, Yuxian; Hou, Yayi

2016-01-01

Inflammatory bowel disease (IBD) is an inflammatory disorder, characterized by abnormally increased expression of Toll-like receptors TLR2 and TLR4 in the colon and increased pro-inflammatory cytokine production by macrophages. In the present study, we explored the effect of FC-99, a novel benzenediamine analog, on dextran sulfate sodium (DSS)-induced mouse colitis and investigated its potential mechanism. The results revealed that FC-99 improved the colon morphology and the clinical parameters in DSS-induced mouse colitis. FC-99 inhibited the increase of DSS-induced T helper cells (Th) 1 and Th17 and enhanced the number of regulatory T cells (Treg) in mesenteric lymph nodes (MLN), but had no effect on Th2 cells. FC-99 also suppressed the DSS-induced secretion of interleukin (IL)-1β, IL-6, and the tumor necrosis factor (TNF)-α in the colon and hindered the infiltration of macrophages into colon lamina propria. Flow cytometric analysis also confirmed that FC-99 reduced CD11b(+)F4/80(+) colon macrophages, and down-regulated TNF-α level in situ. Moreover, FC-99 inhibited concentration-dependently the expression of TNF-α and IL-6 in vitro from mouse peritoneal macrophages, which were induced by TLR ligands: PamCSK4 and peptidoglycan (PGN, TLR2 ligand) as well as LPS (TLR4 ligand). Of note, FC-99 also suppressed the activation of TLR2 and TLR4 signaling pathways and the downstream nuclear factor-κB (NF-κB) in the DSS-induced mouse colitis. FC-99 improved the condition of DSS-induced mouse colitis by inhibiting the activation of TLR2 and TLR4 signaling pathways in macrophage. These results suggest that FC-99 may be developed as a new therapeutic drug for IBD. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of various immunosuppressive agents on mouse peritoneal macrophages and on the in vitro phagocytosis of Escherichia coli O4:K3:H5 and degradation of 125I-labelled HSA-antibody complexes by these cells.

PubMed Central

Gadeberg, O V; Rhodes, J M; Larsen, S O

1975-01-01

Large doses of hydrocortisone, cyclophosphamide, and methotrexate injected subcutaneously, and whole-body irradiation (500 rads) caused a reduction in the number of peritoneal cells (PE cells) obtained after intraperitoneal injection of the treated mice with proteose-peptone. The same dose of cyclophosphamide and irradiation induced morphological changes in PE macrophages. There were more giant cells in the peritoneal exudates from treated mice as compared to control mice. 'Pharmacological' and larger doses of hydrocortisone, methotrexate and azathioprine or anti-lymphocyte globulin had no effect on the in vitro phagocytic capacity of proteose-peptone-stimulated mouse PE macrophages. This also applied to doses of up to 50 mg/kg of cyclophosphamide. In contrast, whole-body irradiation (500 rad) and 100 mg/kg of cyclophosphamide decreased the phagocytic capacity of mouse macrophages in vitro and reduced the ability of PE cells to degrade 125I-labelled HSA-antibody complexes in vitro. The greatest effect was noted 4-5 days after whole-body irradiation or four to five subcutaneous injections of cyclophosphamide. Images Figure 1 Figure 2 PMID:1090520

Mouse IgA inhibits cell growth by stimulating tumor necrosis factor-alpha production and apoptosis of macrophage cell lines.

PubMed

Reljic, Rajko; Crawford, Carol; Challacombe, Stephen; Ivanyi, Juraj

2004-04-01

Potent Fcalpha-mediated actions of IgA have previously been shown for myeloid cells from man, but much less is known in relation to murine cells. Here, we report that mouse monoclonal IgA, irrespective of their antigenic specificity, inhibit the proliferation of mouse macrophage cell lines. The anti-proliferative activity was manifested by both monomeric and polymeric mouse IgA, but not by mouse monoclonal IgG and IgM. Growth of J774 cells was significantly inhibited during the 4-8 days of logarithmic growth, followed by a subsequent recovery of cell numbers prior to the stationary phase. We demonstrated that IgA binds to J774 cells, stimulates tumor necrosis factor (TNF)-alpha production and induces apoptosis which is not dependent on NO or FAS/CD95. We also demonstrated that IgA, in synergy with IFN-gamma, induced TNF-alpha production and apoptosis of thioglycollate-elicited mouse peritoneal macrophages. Thus, the in vitro actions of IgA described may also play a regulatory role for mouse macrophages in vivo.

[Effects of interferon-gamma on cytotoxicity of murine activated macrophages against murine glioma cells].

PubMed

Ohyama, K; Kikuchi, H; Oda, Y; Moritake, K; Yamasaki, T

1993-06-01

We studied the effects of mouse IFN-gamma on the cytotoxic activity of murine activated macrophages (M phi) against mouse VM-Glioma cells (H-2b). Activated M phi were obtained from peritoneal exudate cells of mice from four strains, C57BL/6 (H-2b), C3H/He(H-2k), DBA/2 (H-2d), and BALB/c (H-2d), following intraperitoneal injection of (1) LPS 200 micrograms, (2) BCG 200 micrograms, (3) C. parvum 200 micrograms, or (4) MDP 350 micrograms 7 days prior to 20-hr 51Cr release-assay. Of the various combination of mouse strains and activating agents tested, that of activated M phi of the C3H/He mouse with induction by LPS had the most tumoricidal effect against the glioma cells, which was not MHC restricted. Although LPS-activated M phi underwent marked loss of cytotoxicity following initiation of in vitro culture, this 24 hr pretreatment with IFN-gamma inhibited this reduction in tumoricidal effects in a dose-dependent fashion. On the other hand, 24 hr pretreatment of target cells with IFN-gamma did not increase their susceptibility to lysis by activated M phi. These findings suggest that IFN-gamma augments the in vitro tumoricidal activation of M phi; This effect appears to be unrelated to any influence of IFN-gamma on target sensitivity to lysis by macrophages.

Polysaccharide peptides from COV-1 strain of Coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse.

PubMed

Chan, Siu-Lung; Yeung, John H K

2006-04-18

Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been widely used as an adjunct to cancer chemotherapy and as an immuno-stimulator in China. In this study, the anti-nociceptive effects of PSP were investigated in two different pain models in the mouse. In the acetic acid-induced writhing model, initial studies showed that PSP decreased the number of acetic acid-induced writhing by 92.9%, which, by definition, would constitute an analgesic effect. However, further studies showed that PSP itself induced a dose-dependent writhing response. Studies on inflammatory mediator release showed that PSP increased the release of prostaglandin E2, tumor necrosis factor-alpha, interleukin-1beta, and histamine in mouse peritoneal macrophages and mast cells both in vitro and in vivo. The role of inflammatory mediator release in PSP-induced writhing was confirmed when diclofenac and dexamethasone decreased the number of writhing responses by 54% and 58.5%, respectively. Diphenhydramine totally inhibited the PSP-induced writhing. In the hot-plate test, PSP dose-dependently shortened the hind paw withdrawal latency, indicative of a hyperalgesic effect. The hyperalgesic effect was reduced by pretreatment with the anti-inflammatory drugs. In conclusion, the PSP-induced hyperalgesia was related to activation of peritoneal resident cells and an increase in the release of inflammatory mediators.

Use of the short-term inflammatory response in the mouse peritoneal cavity to assess the biological activity of leached vitreous fibers.

PubMed Central

Donaldson, K; Addison, J; Miller, B G; Cullen, R T; Davis, J M

1994-01-01

We used a special-purpose glass microfiber sample, Johns-Manville Code 100/475, to study the effects of various acid and alkali treatments on biological activity as assessed by inflammation in the mouse peritoneal cavity, the leaching of Si, and the phase contrast optical microscopy (PCOM) fiber number. We used mild and medium treatments with oxalic acid and Tris buffer and harsh treatment with concentrated HCl and NaOH. Mild oxalic acid and Tris treatment for 2 weeks had no effect on any of the end-points, but prolonging the mild oxalic acid treatment time to 2 months reduced the biological activity and the fiber number. Medium oxalic acid treatment reduced the biological activity and the fiber number and caused a loss of Si. Medium Tris alkali treatment reduced the PCOM-countable fibers and the biological activity but did not cause a substantial loss of Si. Harsh treatment with strong HCl did not affect the fiber number or cause leaching but the biological activity was reduced; strong NaOH reduced the fiber number and biological activity, and caused marked leaching of Si. The medium oxalic acid conditions (pH 1.4) were more acid than those found in lung cells but produced the same effects (reduction in fiber number and biological activity) as the more physiological mild treatment (pH 4.0), when prolonged. This study suggests that medium oxalic acid treatment can be used as a short-term assay to compare loss of Si, reduction in fiber number, and change in biological activity of vitreous fibers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882922

Factors involved in the cytotoxicity of kaolinite towards macrophages in vitro.

PubMed Central

Davies, R

1983-01-01

The cytotoxicity of a high purity Cornish kaolinite toward mouse peritoneal macrophages in vitro was examined. The material was cytotoxic towards these cells, the activity could be decreased substantially by pretreating the dust with poly(2-vinylpyridine N-oxide). Pretreatment of the dusts with poly(acrylic acid) had a small effect on cytotoxicity, but combinations of the polymer treatments virtually abolished the material's biological activity towards macrophages. These studies indicated that the cytotoxicity of kaolinite is not due to its flakelike morphology. Images FIGURE 1. PMID:6641658

Adjuvant Effect of Killed Propionibacterium acnes on Mouse Peritoneal B-1 Lymphocytes and Their Early Phagocyte Differentiation

PubMed Central

Mussalem, Juliana Sekeres; Squaiella-Baptistão, Carla Cristina; Teixeira, Daniela; Yendo, Tatiana Mina; Thies, Felipe Garutti; Popi, Ana Flavia; Mariano, Mario; Longo-Maugéri, Ieda

2012-01-01

B-1 lymphocytes are the predominant cells in mouse peritoneal cavity. They express macrophage and lymphocyte markers and are divided into B-1a, B-1b and B-1c subtypes. The role of B-1 cells is not completely clear, but they are responsible for natural IgM production and seem to play a regulatory role. An enriched B-1b cell population can be obtained from non-adherent peritoneal cell cultures, and we have previously demonstrated that these cells undergo differentiation to acquire a mononuclear phagocyte phenotype upon attachment to the substrate in vitro. Nevertheless, the B-1 cell response to antigens or adjuvants has been poorly investigated. Because killed Propionibacterium acnes exhibits immunomodulatory effects on both macrophages and B-2 lymphocytes, we analyzed whether a killed bacterial suspension or its soluble polysaccharide (PS) could modulate the absolute number of peritoneal B-1 cells in BALB/c mice, the activation status of these cells and their ability to differentiate into phagocytes in vitro. In vivo, P. acnes treatment elevated the absolute number of all B-1 subsets, whereas PS only increased B-1c. Moreover, the bacterium increased the number of B-1b cells that were positive for MHC II, TLR2, TLR4, TLR9, IL-4, IL-5 and IL-12, in addition to up-regulating TLR9, CD80 and CD86 expression. PS increased B-1b cell expression of TLR4, TLR9, CD40 and CD86, as well as IL-10 and IL-12 synthesis. Both of the treatments decreased the absolute number of B-1b cells in vitro, suggesting their early differentiation into B-1 cell-derived phagocytes (B-1CDP). We also observed a higher phagocytic activity from the phagocytes that were derived from B-1b cells after P. acnes and PS treatment. The adjuvant effect that P. acnes has on B-1 cells, mainly the B-1b subtype, reinforces the importance of B-1 cells in the innate and adaptive immune responses. PMID:22448280

Adjuvant effect of killed Propionibacterium acnes on mouse peritoneal B-1 lymphocytes and their early phagocyte differentiation.

PubMed

Mussalem, Juliana Sekeres; Squaiella-Baptistão, Carla Cristina; Teixeira, Daniela; Yendo, Tatiana Mina; Thies, Felipe Garutti; Popi, Ana Flavia; Mariano, Mario; Longo-Maugéri, Ieda

2012-01-01

B-1 lymphocytes are the predominant cells in mouse peritoneal cavity. They express macrophage and lymphocyte markers and are divided into B-1a, B-1b and B-1c subtypes. The role of B-1 cells is not completely clear, but they are responsible for natural IgM production and seem to play a regulatory role. An enriched B-1b cell population can be obtained from non-adherent peritoneal cell cultures, and we have previously demonstrated that these cells undergo differentiation to acquire a mononuclear phagocyte phenotype upon attachment to the substrate in vitro. Nevertheless, the B-1 cell response to antigens or adjuvants has been poorly investigated. Because killed Propionibacterium acnes exhibits immunomodulatory effects on both macrophages and B-2 lymphocytes, we analyzed whether a killed bacterial suspension or its soluble polysaccharide (PS) could modulate the absolute number of peritoneal B-1 cells in BALB/c mice, the activation status of these cells and their ability to differentiate into phagocytes in vitro. In vivo, P. acnes treatment elevated the absolute number of all B-1 subsets, whereas PS only increased B-1c. Moreover, the bacterium increased the number of B-1b cells that were positive for MHC II, TLR2, TLR4, TLR9, IL-4, IL-5 and IL-12, in addition to up-regulating TLR9, CD80 and CD86 expression. PS increased B-1b cell expression of TLR4, TLR9, CD40 and CD86, as well as IL-10 and IL-12 synthesis. Both of the treatments decreased the absolute number of B-1b cells in vitro, suggesting their early differentiation into B-1 cell-derived phagocytes (B-1CDP). We also observed a higher phagocytic activity from the phagocytes that were derived from B-1b cells after P. acnes and PS treatment. The adjuvant effect that P. acnes has on B-1 cells, mainly the B-1b subtype, reinforces the importance of B-1 cells in the innate and adaptive immune responses.

Immunotherapy of BALB/c mice bearing Ehrlich ascites tumor with vitamin D-binding protein-derived macrophage activating factor.

PubMed

Yamamoto, N; Naraparaju, V R

1997-06-01

Vitamin D3-binding protein (DBP; human DBP is known as Gc protein) is the precursor of macrophage activating factor (MAF). Treatment of mouse DBP with immobilized beta-galactosidase or treatment of human Gc protein with immobilized beta-galactosidase and sialidase generated a remarkably potent MAF, termed DBPMAF or GcMAF, respectively. The domain of Gc protein responsible for macrophage activation was cloned and enzymatically converted to the cloned MAF, designated CdMAF. In Ehrlich ascites tumor-bearing mice, tumor-specific serum alpha-N-acetylgalactosaminidase (NaGalase) activity increased linearly with time as the transplanted tumor cells grew in the peritoneal cavity. Therapeutic effects of DBPMAF, GcMAF, and CdMAF on mice bearing Ehrlich ascites tumor were assessed by survival time, the total tumor cell count in the peritoneal cavity, and serum NaGalase activity. Mice that received a single administration of DBPMAF or GcMAF (100 pg/mouse) on the same day after transplantation of tumor (1 x 10(5) cells) showed a mean survival time of 35 +/- 4 days, whereas tumor-bearing controls had a mean survival time of 16 +/- 2 days. When mice received the second DBPMAF or GcMAF administration at day 4, they survived more than 50 days. Mice that received two DBPMAF administrations, at days 4 and 8 after transplantation of 1 x 10(5) tumor cells, survived up to 32 +/- 4 days. At day 4 posttransplantation, the total tumor cell count in the peritoneal cavity was approximately 5 x 10(5) cells. Mice that received two DBPMAF administrations, at days 0 and 4 after transplantation of 5 x 10(5) tumor cells, also survived up to 32 +/- 4 days, while control mice that received the 5 x 10(5) ascites tumor cells only survived for 14 +/- 2 days. Four DBPMAF, GcMAF, or CdMAF administrations to mice transplanted with 5 x 10(5) Ehrlich ascites tumor cells with 4-day intervals showed an extended survival of at least 90 days and an insignificantly low serum NaGalase level between days 30 and 90.

Antitumor effect of nuclear factor-κB decoy transfer by mannose-modified bubble lipoplex into macrophages in mouse malignant ascites

PubMed Central

Kono, Yusuke; Kawakami, Shigeru; Higuchi, Yuriko; Maruyama, Kazuo; Yamashita, Fumiyoshi; Hashida, Mitsuru

2014-01-01

Patients with malignant ascites (MAs) display several symptoms, such as dyspnea, nausea, pain, and abdominal tenderness, resulting in a significant reduction in their quality of life. Tumor-associated macrophages (TAMs) play a crucial role in MA progression. Because TAMs have a tumor-promoting M2 phenotype, conversion of the M2 phenotypic function of TAMs would be promising for MA treatment. Nuclear factor-κB (NF-κB) is a master regulator of macrophage polarization. Here, we developed targeted transfer of a NF-κB decoy into TAMs by ultrasound (US)-responsive, mannose-modified liposome/NF-κB decoy complexes (Man-PEG bubble lipoplexes) in a mouse peritoneal dissemination model of Ehrlich ascites carcinoma. In addition, we investigated the effects of NF-κB decoy transfection into TAMs on MA progression and mouse survival rates. Intraperitoneal injection of Man-PEG bubble lipoplexes and US exposure transferred the NF-κB decoy into TAMs effectively. When the NF-κB decoy was delivered into TAMs by this method in the mouse peritoneal dissemination model, mRNA expression of the Th2 cytokine interleukin (IL)-10 in TAMs was decreased significantly. In contrast, mRNA levels of Th1 cytokines (IL-12, tumor necrosis factor-α, and IL-6) were increased significantly. Moreover, the expression level of vascular endothelial growth factor in ascites was suppressed significantly, and peritoneal angiogenesis showed a reduction. Furthermore, NF-κB decoy transfer into TAMs significantly decreased the ascitic volume and number of Ehrlich ascites carcinoma cells in ascites, and prolonged mouse survival. In conclusion, we transferred a NF-κB decoy efficiently by Man-PEG bubble lipoplexes with US exposure into TAMs, which may be a novel approach for MA treatment. PMID:24850474

Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fang, Qilu; Diabetes Center and Department of Endocrinology, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang; Wang, Jingying

High glucose-induced inflammatory response in diabetic complications plays an important role in disease occurrence and development. With inflammatory cytokines and signaling pathways as important mediators, targeting inflammation may be a new avenue for treating diabetic complications. Chalcones are a class of natural products with various pharmacological activities. Previously, we identified L2H17 as a chalcone with good anti-inflammatory activity, inhibiting LPS-induced inflammatory response in macrophages. In this study, we examined L2H17's effect on hyperglycemia-induced inflammation both in mouse peritoneal macrophages and a streptozotocin-induced T1D mouse model. Our results indicate that L2H17 exhibits a strong inhibitory effect on the expression of pro-inflammatorymore » cytokines, cell adhesion molecules, chemokines and macrophage adhesion via modulation of the MAPK/NF-κB pathway. Furthermore, in vivo oral administration of L2H17 resulted in a significant decrease in the expression of pro-inflammatory cytokines and cell adhesion molecules, contributing to a reduction of key markers for renal and cardiac dysfunction and improvements in fibrosis and pathological changes in both renal and cardiac tissues of diabetic mice. These findings provide the evidence supporting targeting MAPK/NF-κB pathway may be effective therapeutic strategy for diabetic complications, and suggest that L2H17 may be a promising anti-inflammatory agent with potential as a therapeutic agent in the treatment of renal and cardiac diabetic complications. - Highlights: • Chalcones are a class of natural products with various pharmacological activities. • We identified L2H17 a chalcone with good anti-inflammatory activity. • L2H17 improved histological abnormalities both in diabetic heart and kidney. • L2H17 reduced inflammatory responses in HG-stimulated mouse peritoneal macrophages. • MAPKs/NF-κB pathway may be a promising therapeutic target for diabetic complications.« less

Addition of Alanyl-Glutamine to Dialysis Fluid Restores Peritoneal Cellular Stress Responses – A First-In-Man Trial

PubMed Central

Boehm, Michael; Herzog, Rebecca; Gruber, Katharina; Lichtenauer, Anton Michael; Kuster, Lilian; Csaicsich, Dagmar; Gleiss, Andreas; Alper, Seth L.; Aufricht, Christoph; Vychytil, Andreas

2016-01-01

Background Peritonitis and ultrafiltration failure remain serious complications of chronic peritoneal dialysis (PD). Dysfunctional cellular stress responses aggravate peritoneal injury associated with PD fluid exposure, potentially due to peritoneal glutamine depletion. In this randomized cross-over phase I/II trial we investigated cytoprotective effects of alanyl-glutamine (AlaGln) addition to glucose-based PDF. Methods In a prospective randomized cross-over design, 20 stable PD outpatients underwent paired peritoneal equilibration tests 4 weeks apart, using conventional acidic, single chamber 3.86% glucose PD fluid, with and without 8 mM supplemental AlaGln. Heat-shock protein 72 expression was assessed in peritoneal effluent cells as surrogate parameter of cellular stress responses, complemented by metabolomics and functional immunocompetence assays. Results AlaGln restored peritoneal glutamine levels and increased the primary outcome heat-shock protein expression (effect 1.51-fold, CI 1.07–2.14; p = 0.022), without changes in peritoneal ultrafiltration, small solute transport, or biomarkers reflecting cell mass and inflammation. Further effects were glutamine-like metabolomic changes and increased ex-vivo LPS-stimulated cytokine release from healthy donor peripheral blood monocytes. In patients with a history of peritonitis (5 of 20), AlaGln supplementation decreased dialysate interleukin-8 levels. Supplemented PD fluid also attenuated inflammation and enhanced stimulated cytokine release in a mouse model of PD-associated peritonitis. Conclusion We conclude that AlaGln-supplemented, glucose-based PD fluid can restore peritoneal cellular stress responses with attenuation of sterile inflammation, and may improve peritoneal host-defense in the setting of PD. PMID:27768727

Medicinal foodstuffs. XIV. On the bioactive constituents of moroheiya. (2): New fatty acids, corchorifatty acids A, B, C, D, E, and F, from the leaves of Corchorus olitorius L. (Tiliaceae): structures and inhibitory effect on NO production in mouse peritoneal macrophages.

PubMed

Yoshikawa, M; Murakami, T; Shimada, H; Yoshizumi, S; Saka, M; Yamahara, J; Matsuda, H

1998-06-01

Following the characterization of the glycosidic constituents in a medical foodstuff "moroheiya," the leaves of Corchorus olitorius L., four higher fatty acids with a trienone function, corchorifatty acids, A, B, C, and D, an undecanoic acid, corchorifatty acid E, and a trihydroxyfatty acid, corchorifatty acid F, were isolated from the less polar fraction of "moroheiya". The structures and optical purity of corchorifatty acids were determined on the basis of chemical and physicochemical evidence. Corchorifatty acids A, B, and C showed an inhibitory effect on lipopolysaccharide-induced NO production in cultured mouse peritoneal macrophages.

Development of a mouse-feline chimeric antibody against feline tumor necrosis factor-alpha.

PubMed

Doki, Tomoyoshi; Takano, Tomomi; Hohdatsu, Tsutomu

2016-10-01

Feline infectious peritonitis (FIP) is a fatal inflammatory disease caused by FIP virus infection. Feline tumor necrosis factor (fTNF)-alpha is closely involved in the aggravation of FIP pathology. We previously described the preparation of neutralizing mouse anti-fTNF-alpha monoclonal antibody (mAb 2-4) and clarified its role in the clinical condition of cats with FIP using in vitro systems. However, administration of mouse mAb 2-4 to cat may lead to a production of feline anti-mouse antibodies. In the present study, we prepared a mouse-feline chimeric mAb (chimeric mAb 2-4) by fusing the variable region of mouse mAb 2-4 to the constant region of feline antibody. The chimeric mAb 2-4 was confirmed to have fTNF-alpha neutralization activity. Purified mouse mAb 2-4 and chimeric mAb 2-4 were repeatedly administered to cats, and the changes in the ability to induce feline anti-mouse antibody response were investigated. In the serum of cats treated with mouse mAb 2-4, feline anti-mouse antibody production was induced, and the fTNF-alpha neutralization effect of mouse mAb 2-4 was reduced. In contrast, in cats treated with chimeric mAb 2-4, the feline anti-mouse antibody response was decreased compared to that of mouse mAb 2-4-treated cats.

Uptake of acetaldehyde-modified (ethylated) low-density lipoproteins by mouse peritoneal macrophages.

PubMed

Wehr, Hanna; Mirkiewicz, Ewa; Rodo, Maria; Bednarska-Makaruk, Malgorzata

2002-04-01

The uptake of acetaldehyde-modified (ethylated) low-density lipoproteins (LDLs) by murine peritoneal macrophages is described and compared with the uptake of acetylated LDLs. The fluorescent marker DiI was used. No competition between ethylated and acetylated LDLs was observed. Ethylated LDL uptake was not inhibited by polyinosinic acid or fucoidin. Our conclusion is that uptake of ethylated and acetylated LDLs can be done by two different receptors.

The antibacterial activity of syringopicroside, its metabolites and natural analogues from Syringae Folium.

PubMed

Zhou, Zhengyuan; Han, Na; Liu, Zhihui; Song, Zehai; Wu, Peng; Shao, Jingxuan; Zhang, Jia Ming; Yin, Jun

2016-04-01

In the present study, the in vitro antibacterial activity of an effective fraction (ESF) from Syringae Folium (SF) on Methicillin-resistant Staphylococcus aureus (MRSA) was evaluated and then its in vivo activity was evaluated by using the MRSA-infected mouse peritonitis model. The ESF showed a significant in vitro and in vivo activity on decreasing the Minimum Inhibitory Concentrations (MICs) and increasing the survival rate of mouse from 42.8% to 100%. Six iridoid glucosides (IGs) of ESF were characterized by UPLC-TOF-MS method and also isolated by column chromatography. Most of them showed in vitro anti MRSA activity. Syringopicroside (Sy), the major compound of IGs, was found to increase the survival rate from 42.8% to 92.8% of the MRSA-infected mouse, which revealed Sy is also the main active components of ESF. In order to know why the effect of oral administration of SF is better than its injections in clinic and the metabolites of Sy, seven metabolites of Sy were isolated from rat urine and identified on the basis of NMR and MS spectra. Most of metabolites possessed stronger in vitro anti-MRSA activity than that of Sy, which furtherly proved the clinical result. Copyright © 2016 Elsevier B.V. All rights reserved.

Thalidomide Prevents the Progression of Peritoneal Fibrosis in Mice

PubMed Central

Arai, Hideyuki; Furusu, Akira; Nishino, Tomoya; Obata, Yoko; Nakazawa, Yuka; Nakazawa, Masayuki; Hirose, Misaki; Abe, Katsushige; Koji, Takehiko; Kohno, Shigeru

2011-01-01

Thalidomide is clinically recognized as a therapeutic agent for multiple myeloma and has been known to exert anti-angiogenic actions. Recent studies have suggested the involvement of angiogenesis in the progression of peritoneal fibrosis. The present study investigated the effects of thalidomide on the development of peritoneal fibrosis induced by injection of chlorhexidine gluconate (CG) into the mouse peritoneal cavity every other day for 3 weeks. Thalidomide was given orally every day. Peritoneal tissues were dissected out 21 days after CG injection. Expression of CD31 (as a marker of endothelial cells), proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), α-smooth muscle actin (as a marker of myofibroblasts), type III collagen and transforming growth factor (TGF)-β was examined using immunohistochemistry. CG group showed thickening of the submesothelial zone and increased numbers of vessels and myofibroblasts. Large numbers of VEGF-, PCNA-, and TGF-β-positive cells were observed in the submesothelial area. Thalidomide treatment significantly ameliorated submesothelial thickening and angiogenesis, and decreased numbers of PCNA- and VEGF-expressing cells, myofibroblasts, and TGF-β-positive cells. Moreover, thalidomide attenuated peritoneal permeability for creatinine, compared to the CG group. Our results indicate the potential utility of thalidomide for preventing peritoneal fibrosis. PMID:21614166

Effects of interleukins on connective tissue type mast cells co-cultured with fibroblasts.

PubMed Central

Levi-Schaffer, F; Segal, V; Shalit, M

1991-01-01

We investigated the effects of interleukin-2 (IL-2), interleukin-3 (IL-3) and interleukin-4 (IL-4) on mouse and rat peritoneal mast cells (MC) co-cultured with 3T3 fibroblasts (MC/3T3). The continuous presence of these cytokines for 7-9 days in the culture media was neither toxic nor caused proliferation of MC, as determined by the stability of MC numbers in culture. Long-term incubation of mouse MC/3T3 with IL-2 (100 U/ml), IL-3 (50 U/ml), IL-4 (50 U/ml) or a mixture of IL-3 and IL-4 (25 U/ml) induced an increase in basal histamine release of 79.3 +/- 19.0%, 41.0 +/- 17.3%, 25.2 +/- 10.4% and 30.2 +/- 3.2%, respectively, over control cells incubated with medium alone. When rat MC/3T3 were incubated for 7 days with the various interleukins an enhancement in histamine release similar to that observed with mouse MC/3T3 was found. Preincubation (1 hr) of rat MC/3T3 with interleukins prior to immunological activation with anti-IgE antibodies enhanced histamine release. The highest effect was observed with IL-3 + IL-4 (60.4 +/- 10.8% increase) followed by IL-2 (51.5 +/- 4.5%), IL-4 (28.6 +/- 10.3%) and IL-3 (13.2 +/- 4.2%). This study demonstrates that when mouse and rat peritoneal MC are cultured with fibroblasts in the presence of interleukins they do not proliferate, suggesting that they preserve their connective tissue type MC phenotype. Moreover, interleukins display a pro-inflammatory effect on these cells by enhancing both basal and anti-IgE-mediated histamine release. PMID:2016117

Asbestos body formation and iron accumulation in mouse peritoneal granulomas after the introduction of crocidolite asbestos fibers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koerten, H.K.; Hazekamp, J.; Kroon, M.

This report describes the cell biology of the development of asbestos bodies after a single intraperitoneal injection of a suspension of crocidolite asbestos fibers into the mouse peritoneal cavity. The majority of the infected fibers were found in aggregates of peritoneal macrophages, exudate cells, and fibrous tissue. These aggregates developed into granulomas containing not only numerous asbestos fibers, but also cells of various types, including macrophages, multinucleated giant cells, fibroblasts, plasma cells, granulocytes, and mast cells. Cytoplasmic ferritin was abundantly present in macrophages and giant cells. In addition, iron-rich inclusion bodies were detected. The results of this study show thatmore » asbestos body formation can occur outside the pleural cavity. Asbestos body formation occurred in the granulomas after periods of 1 month and longer. On the basis of morphologic criteria, various types of asbestos body were distinguished. X-ray microanalysis showed that variations in the density of the coat could attributed to the presence of chemical elements in various concentrations. Evidence is presented that asbestos body formation is an extracellular phenomenon.« less

Assessment of intensive care unit‐acquired weakness in young and old mice: An E. coli septic peritonitis model

PubMed Central

Hoogland, Inge C.M.; Wieske, Luuk; Weber, Nina C.; Verhamme, Camiel; Schultz, Marcus J.; van Schaik, Ivo N.; Horn, Janneke

2015-01-01

ABSTRACT Introduction: There are few reports of in vivo muscle strength measurements in animal models of ICU‐acquired weakness (ICU‐AW). In this study we investigated whether the Escherichia coli (E. coli) septic peritonitis mouse model may serve as an ICU‐AW model using in vivo strength measurements and myosin/actin assays, and whether development of ICU‐AW is age‐dependent in this model. Methods: Young and old mice were injected intraperitoneally with E. coli and treated with ceftriaxone. Forelimb grip strength was measured at multiple time points, and the myosin/actin ratio in muscle was determined. Results: E. coli administration was not associated with grip strength decrease, neither in young nor in old mice. In old mice, the myosin/actin ratio was lower in E. coli mice at t = 48 h and higher at t = 72 h compared with controls. Conclusions: This E. coli septic peritonitis mouse model did not induce decreased grip strength. In its current form, it seems unsuitable as a model for ICU‐AW. Muscle Nerve 53: 127–133, 2016 PMID:26015329

Metamorphosis of mesothelial cells with active horizontal motility in tissue culture.

PubMed

Nagai, Hirotaka; Chew, Shan Hwu; Okazaki, Yasumasa; Funahashi, Satomi; Namba, Takashi; Kato, Takuya; Enomoto, Atsushi; Jiang, Li; Akatsuka, Shinya; Toyokuni, Shinya

2013-01-01

Mesothelial cells, which have diverse roles in physiology and pathology, constitute the mesothelium along with connective tissue and the basement membrane; the mesothelium serves to shield the somatic cavities. After mesothelial injury, mesothelial cells undergo tissue recovery. However, the mechanism of mesothelial regeneration remains poorly understood. In this study, we used confocal time-lapse microscopy to demonstrate that transformed mesothelial cells (MeT5A) and mouse peritoneal mesothelial cells can randomly migrate between cells in cell culture and in ex vivo tissue culture, respectively. Moreover, peritoneal mesothelial cells changed their morphology from a flattened shape to a cuboidal one prior to the migration. Conversely, MDCKII epithelial cells forming tight cell-cell contacts with one another do not alter the arrangement of adjacent cells during movement. Our evidence complements the current hypotheses of mesothelial regeneration and suggests that certain types of differentiated mesothelial cells undergo morphological changes before initiating migration to repair injured sites.

Structural definition of a potent macrophage activating factor derived from vitamin D3-binding protein with adjuvant activity for antibody production.

PubMed

Yamamoto, N

1996-10-01

Incubation of human vitamin D3-binding protein (Gc protein), with a mixture of immobilized beta-galactosidase and sialidase, efficiently generated a potent macrophage activating factor, a protein with N-acetylgalactosamine as the remaining sugar. Stepwise incubation of Gc protein with immobilized beta-galactosidase and sialidase, and isolation of the intermediates with immobilized lectins, revealed that either sequence of hydrolysis of Gc glycoprotein by these glycosidases yields the macrophage-activating factor, implying that Gc protein carries a trisaccharide composed of N-acetylgalactosamine and dibranched galactose and sialic acid termini. A 3 hr incubation of mouse peritoneal macrophages with picomolar amounts of the enzymatically generated macrophage-activating factor (GcMAF) resulted in a greatly enhanced phagocytic activity. Administration of a minute amount (10-50 pg/mouse) of GcMAF resulted in a seven- to nine-fold enhanced phagocytic activity of macrophages. Injection of sheep red blood cells (SRBC) along with GcMAF into mice produced a large number of anti-SRBC antibody secreting splenic cells in 2-4 days.

Selective Blocking of TNF Receptor 1 Attenuates Peritoneal Dialysis Fluid Induced Inflammation of the Peritoneum in Mice.

PubMed

Kälble, Florian; Damaske, Janine; Heide, Danijela; Arnold, Iris; Richter, Fabian; Maier, Olaf; Eisel, Ulrich; Scheurich, Peter; Pfizenmaier, Klaus; Zeier, Martin; Schwenger, Vedat; Ranzinger, Julia

2016-01-01

Chronic inflammatory conditions during peritoneal dialysis (PD)-treatment lead to the impairment of peritoneal tissue integrity. The resulting structural and functional reorganization of the peritoneal membrane diminishes ultrafiltration rate and thereby enhances mortality by limiting dialysis effectiveness over time. Tumour necrosis factor (TNF) and its receptors TNFR1 and TNFR2 are key players during inflammatory processes. To date, the role of TNFR1 in peritoneal tissue damage during PD-treatment is completely undefined. In this study, we used an acute PD-mouse model to investigate the role of TNFR1 on structural and morphological changes of the peritoneal membrane. TNFR1-mediated TNF signalling in transgenic mice expressing human TNFR1 was specifically blocked by applying a monoclonal antibody (H398) highly selective for human TNFR1 prior to PD-treatment. Cancer antigen-125 (CA125) plasma concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were applied to determine TNFR2 protein concentrations. Histological staining of peritoneal tissue sections was performed to assess granulocytes within the peritoneal membrane as well as the content of hyaluronic acid and collagen. We show for the first time that the number of granulocytes within the peritoneal membrane is significantly reduced in mice pre-treated with H398. Moreover, we demonstrate that blocking of TNFR1 not only influences CA125 values but also hyaluronic acid and collagen contents of the peritoneal tissue in these mice. These results strongly suggest that TNFR1 inhibition attenuates peritoneal damage caused by peritoneal dialysis fluid (PDF) and therefore may represent a new therapeutic approach in the treatment of PD-related side effects.

Molecular target of decursins in the inhibition of lipid droplet accumulation in macrophages.

PubMed

Ohshiro, Taichi; Namatame, Ichiji; Lee, Eun Woo; Kawagishi, Hirokazu; Tomoda, Hiroshi

2006-05-01

During screening for inhibitors of lipid droplet accumulation in mouse peritoneal macrophages, two coumarins identified as decursin and decursinol angelate were isolated from the roots of Angelicae gigantis. The cellular molecular target of these inhibitors in macrophages was studied. Decursin and decursinol angelate inhibited cholesteryl ester (CE) synthesis with IC50 values of 9.7 and 10.1 microM, respectively, whereas they enhanced triacylglycerol (TG) synthesis. Lysosomal metabolism of cholesterol to CE was inhibited by the compounds, indicating that the site of inhibition is one of the steps between the exiting of cholesterol from the lysosomes and CE synthesis in the endoplasmic reticulum. Therefore, acyl-CoA:cholesterol acyltransferase (ACAT) activity in the microsomal fractions prepared from mouse macrophages was studied, and the results showed inhibition of this activity by decursin and decursinol angelate with IC50 values of 43 and 22 microM, respectively. Thus, it was concluded that the compounds inhibit macrophage ACAT activity to decrease CE synthesis, leading to a reduction of lipid droplets in macrophages.

Serratia marcescens Induces Apoptotic Cell Death in Host Immune Cells via a Lipopolysaccharide- and Flagella-dependent Mechanism*

PubMed Central

Ishii, Kenichi; Adachi, Tatsuo; Imamura, Katsutoshi; Takano, Shinya; Usui, Kimihito; Suzuki, Kazushi; Hamamoto, Hiroshi; Watanabe, Takeshi; Sekimizu, Kazuhisa

2012-01-01

Injection of Serratia marcescens into the blood (hemolymph) of the silkworm, Bombyx mori, induced the activation of c-Jun NH2-terminal kinase (JNK), followed by caspase activation and apoptosis of blood cells (hemocytes). This process impaired the innate immune response in which pathogen cell wall components, such as glucan, stimulate hemocytes, leading to the activation of insect cytokine paralytic peptide. S. marcescens induced apoptotic cell death of silkworm hemocytes and mouse peritoneal macrophages in vitro. We searched for S. marcescens transposon mutants with attenuated ability to induce apoptosis of silkworm hemocytes. Among the genes identified, disruption mutants of wecA (a gene involved in lipopolysaccharide O-antigen synthesis), and flhD and fliR (essential genes in flagella synthesis) showed reduced motility and impaired induction of mouse macrophage cell death. These findings suggest that S. marcescens induces apoptosis of host immune cells via lipopolysaccharide- and flagella-dependent motility, leading to the suppression of host innate immunity. PMID:22859304

Baicalin inhibits biofilm formation, attenuates the quorum sensing-controlled virulence and enhances Pseudomonas aeruginosa clearance in a mouse peritoneal implant infection model

PubMed Central

Wang, Ke; Cai, Shuangqi; Liu, Tangjuan; Cheng, Xiaojing; Lei, Danqing; Chen, Yanling; Li, Yanan; Kong, Jinliang; Chen, Yiqiang

2017-01-01

The quorum sensing (QS) circuit plays a role in the precise regulation of genes controlling virulence factors and biofilm formation in Pseudomonas aeruginosa. QS-controlled biofilm formation by Pseudomonas aeruginosa in clinical settings has remained controversial due to emerging drug resistance; therefore, screening diverse compounds for anti-biofilm or anti-QS activities is important. This study demonstrates the ability of sub-minimum inhibitory concentrations (sub-MICs) of baicalin, an active natural compound extracted from the traditional Chinese medicinal Scutellaria baicalensis, to inhibit the formation of Pseudomonas aeruginosa biofilms and enhance the bactericidal effects of various conventional antibiotics in vitro. In addition, baicalin exerted dose-dependent inhibitory effects on virulence phenotypes (LasA protease, LasB elastase, pyocyanin, rhamnolipid, motilities and exotoxin A) regulated by QS in Pseudomonas aeruginosa. Moreover, the expression levels of QS-regulatory genes, including lasI, lasR, rhlI, rhlR, pqsR and pqsA, were repressed after sub-MIC baicalin treatment, resulting in significant decreases in the QS signaling molecules 3-oxo-C12-HSL and C4-HSL, confirming the ability of baicalin-mediated QS inhibition to alter gene and protein expression. In vivo experiments indicated that baicalin treatment reduces Pseudomonas aeruginosa pathogenicity in Caenorhabditis elegans. Greater worm survival in the baicalin-treated group manifested as an increase in the LT50 from 24 to 96 h. In a mouse peritoneal implant infection model, baicalin treatment enhanced the clearance of Pseudomonas aeruginosa from the implants of mice infected with Pseudomonas aeruginosa compared with the control group. Moreover, the combination of baicalin and antibiotics significantly reduced the numbers of colony-forming units in the implants to a significantly greater degree than antibiotic treatment alone. Pathological and histological analyses revealed mitigation of the inflammatory response and reduced cell infiltration in the peritoneal tissue surrounding the implants after baicalin treatment. Measurement of the cytokine levels in the peritoneal lavage fluid of mice in the baicalin treatment group revealed a decrease in IL-4, an increase in interferon γ (IFN-γ), and a reversed IFN-γ/IL-4 ratio compared with the control group, indicating that baicalin treatment activated the Th1-induced immune response to expedite bacterial load clearance. Based on these results, baicalin might be a potent QS inhibitor and anti-biofilm agent for combating Pseudomonas aeruginosa biofilm-related infections. PMID:28453568

Cytoprotective function of heme oxygenase 1 induced by a nitrated cyclic nucleotide formed during murine salmonellosis.

PubMed

Zaki, Mohammad Hasan; Fujii, Shigemoto; Okamoto, Tatsuya; Islam, Sabrina; Khan, Shahzada; Ahmed, Khandaker Ahtesham; Sawa, Tomohiro; Akaike, Takaaki

2009-03-15

Signaling mechanisms of NO-mediated host defense are yet to be elucidated. In this study, we report a unique signal pathway for cytoprotection during Salmonella infection that involves heme oxygenase 1 (HO-1) induced by a nitrated cyclic nucleotide, 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP). Wild-type C57BL/6 mice and C57BL/6 mice lacking inducible NO synthase (iNOS) were infected with Salmonella enterica serovar Typhimurium LT2. HO-1 was markedly up-regulated during the infection, the level being significantly higher in wild-type mice than in iNOS-deficient mice. HO-1 up-regulation was associated with 8-nitro-cGMP formation detected immunohistochemically in Salmonella-infected mouse liver and peritoneal macrophages. 8-Nitro-cGMP either exogenously added or formed endogenously induced HO-1 in cultured macrophages infected with Salmonella. HO-1 inhibition by polyethylene glycol-conjugated zinc-protoporphyrin IX impaired intracellular killing of bacteria in mouse liver and in both RAW 264 cells and peritoneal macrophages. Infection-associated apoptosis was also markedly increased in polyethylene glycol-conjugated zinc-protoporphyrin IX-treated mouse liver cells and cultured macrophages. This effect of HO-1 inhibition was further confirmed by using HO-1 short interfering RNA in peritoneal macrophages. Our results suggest that HO-1 induced by NO-mediated 8-nitro-cGMP formation contributes, via its potent cytoprotective function, to host defense during murine salmonellosis.

Antitumor activity of the Korean mistletoe lectin is attributed to activation of macrophages and NK cells.

PubMed

Yoon, Taek Joon; Yoo, Yung Choon; Kang, Tae Bong; Song, Seong Kyu; Lee, Kyung Bok; Her, Erk; Song, Kyung Sik; Kim, Jong Bae

2003-10-01

Inhibitory effect of the lectins (KML-C) isolated from Korean mistletoe (KM; Viscum album coloratum) on tumor metastases produced by murine tumor cells (B16-BL6 melanoma, colon 26-M3.1 carcinoma and L5178Y-ML25 lymphoma cells) was investigated in syngeneic mice. An intravenous (i.v.) administration of KML-C (20-50 ng/mouse) 2 days before tumor inoculation significantly inhibited lung metastases of both B16-BL6 and colon 26-M3.1 cells. The prophylactic effect of 50 ng/mouse of KML-C on lung metastasis was almost the same with that of 100 microg/mouse of KM. Treatment with KML-C 1 day after tumor inoculation induced a significant inhibition of not only the experimental lung metastasis induced by B16-BL6 and colon 26-M3.1 cells but also the liver and spleen metastasis of L5178Y-ML25 cells. Furthermore, multiple administration of KML-C given at 3 day-intervals after tumor inoculation led to a significant reduction of lung metastasis and suppression of the growth of B16-BL6 melanoma cells in a spontaneous metastasis model. In an assay for natural killer (NK) cell activity, i.v. administration of KML-C (50 ng/mouse) significantly augmented NK cytotoxicity against Yac-1 tumor cells 2 days after KML-C treatment. In addition, treatment with KML-C (50 ng/mouse) induced tumoricidal activity of peritoneal macrophages against B16-BL6 and 3LL cells. These results suggest that KML-C has an immunomodulating activity to enhance the host defense system against tumors, and that its prophylactic and therapeutic effect on tumor metastasis is associated with the activation of NK cells and macrophages.

Relationship of IgG, C3 and transferrin with opsonising and bacteriostatic activity of peritoneal fluid from CAPD patients and the incidence of peritonitis.

PubMed

McGregor, S J; Brock, J H; Briggs, J D; Junor, B J

1987-01-01

IgG, C3 and transferrin in peritoneal dialysis effluent of patients undergoing continuous ambulatory peritoneal dialysis (CAPD) were 1%-2% of those in serum. In contrast, the values in normal peritoneal fluid were not significantly different from those in serum. The three proteins correlated with each other in peritoneal dialysis effluent, but were independent of the amount in the corresponding patients' sera. There was also an overall inverse correlation between total protein in peritoneal dialysis effluent and time on CAPD during the first 6 months of treatment but not thereafter, which suggests that changes in membrane permeability occur during the early months. In peritoneal dialysis effluent, but not in normal peritoneal fluid, there was a correlation between opsonising capacity and IgG or C3 concentrations. An inverse correlation between opsonic activity of peritoneal dialysis effluent and frequency of peritonitis was also found. Peritoneal dialysis effluent permitted significantly faster multiplication of Staphylococcus epidermidis than sera or normal peritoneal fluid, and the growth rate correlated inversely with the transferrin levels in peritoneal dialysis effluent. Overall IgG, C3 and transferrin in peritoneal dialysis effluent are inadequate for optimal opsonising and bacteriostatic activity, and the peritoneal cavities of CAPD patients are therefore immunocompromised sites.

Experimental characterization of recurrent ovarian immature teratoma cells after optimal surgery.

PubMed

Tanaka, Tetsuji; Toujima, Saori; Utsunomiya, Tomoko; Yukawa, Kazunori; Umesaki, Naohiko

2008-07-01

Minimal optimal surgery without chemotherapy is often performed for patients with ovarian immature teratoma, which frequently occurs in young women who hope for future pregnancies. If tumors recur after the operation, anticancer drug chemotherapy is often administered, although few studies have highlighted differences between the recurrent and the primary tumor cells. Therefore, we have established experimental animal models of recurrent ovarian immature teratoma cells after optimal surgery and characterized the anticancer drug sensitivity and antigenicity of the recurrent tumors. Surgically-excised tumor cells of a grade II ovarian immature teratoma were cultured in vitro and transplanted into nude mice to establish stable cell lines. Differential drug sensitivity and antigenicity of the tumor cells were compared between the primary and the nude mouse tumors. Nude mouse tumor cells showed a normal 46XX karyotype. Cultured primary cells showed a remarkably high sensitivity to paclitaxel, docetaxel, adriamycin and pirarubicin, compared to peritoneal cancer cells obtained from a patient with ovarian adenocarcinomatous peritonitis. The drug sensitivity of teratoma cells to 5-fluorouracil, bleomycin or peplomycin was also significantly higher. However, there was no significant difference in sensitivity to platinum drugs between the primary teratoma and the peritoneal adenocarcinoma cells. As for nude mouse tumor cells, sensitivity to 12 anticancer drugs was significantly lower than that of the primary tumor cells, while there was little difference in sensitivity to carboplatin or peplomycin between the primary and nude mouse tumor cells. Flow cytometry showed that the expression of smooth muscle actin (SMA) significantly decreased in nude mouse tumor cells when compared to cultured primary cells. In conclusion, ovarian immature teratomas with normal karyotypes have a malignant potential to recur after minimal surgery. During nude mouse transplantation, SMA-overexpressing cells appeared to be selectively excluded and nude mouse tumor cells were less sensitive to the majority of anticancer drugs than the primary tumor cells. These results indicate that after optimal surgery for ovarian immature teratoma, recurrent cells can be more resistant to anticancer drugs than the primary tumors. Therefore, it is likely that adjuvant chemotherapy lowers the risk of ovarian immature teratomas recurring after optimal surgery. BEP and PBV regimens are frequently given to teratoma patients. However, paclitaxel/carboplatin or docetaxel/carboplatin, which are the most effective chemotherapy treatments for epithelial ovarian cancer patients, are considered to be an alternative regimen, especially in the prevention of reproductive toxicity.

A Pathogenetic Role for Endothelin-1 in Peritoneal Dialysis-Associated Fibrosis

PubMed Central

Busnadiego, Oscar; Loureiro-Álvarez, Jesús; Sandoval, Pilar; Lagares, David; Dotor, Javier; Pérez-Lozano, María Luisa; López-Armada, María J.; Lamas, Santiago; López-Cabrera, Manuel

2015-01-01

In patients undergoing peritoneal dialysis (PD), chronic exposure to nonphysiologic PD fluids elicits low-grade peritoneal inflammation, leading to fibrosis and angiogenesis. Phenotype conversion of mesothelial cells into myofibroblasts, the so-called mesothelial-to-mesenchymal transition (MMT), significantly contributes to the peritoneal dysfunction related to PD. A number of factors have been described to induce MMT in vitro and in vivo, of which TGF-β1 is probably the most important. The vasoconstrictor peptide endothelin-1 (ET-1) is a transcriptional target of TGF-β1 and mediates excessive scarring and fibrosis in several tissues. This work studied the contribution of ET-1 to the development of peritoneal damage and failure in a mouse model of PD. ET-1 and its receptors were expressed in the peritoneal membrane and upregulated on PD fluid exposure. Administration of an ET receptor antagonist, either bosentan or macitentan, markedly attenuated PD-induced MMT, fibrosis, angiogenesis, and peritoneal functional decline. Adenovirus-mediated overexpression of ET-1 induced MMT in human mesothelial cells in vitro and promoted the early cellular events associated with peritoneal dysfunction in vivo. Notably, TGF-β1–blocking peptides prevented these actions of ET-1. Furthermore, a positive reciprocal relationship was observed between ET-1 expression and TGF-β1 expression in human mesothelial cells. These results strongly support a role for an ET-1/TGF-β1 axis as an inducer of MMT and subsequent peritoneal damage and fibrosis, and they highlight ET-1 as a potential therapeutic target in the treatment of PD-associated dysfunction. PMID:25012164

Granulocyte colony-stimulating factor enhances protection by anti-K1 capsular IgM antibody in murine Escherichia coli sepsis.

PubMed

Hustinx, W; Benaissa-Trouw, B; Van Kessel, K; Kuenen, J; Tavares, L; Kraaijeveld, K; Verhoef, J; Hoepelman, A

1997-12-01

Combined prophylactic treatment with recombinant murine granulocyte colony-stimulating factor (G-CSF) and a suboptimal dose of anti-K1 capsular IgM monoclonal antibody (MAb) significantly enhanced survival in an experimental mouse Escherichia coli O7:K1 peritonitis model compared with untreated animals (67% vs. 11% survival; P < 0.001) and with either treatment alone (67 vs. 29% and 27% survival, respectively; P < 0.01), which suggests synergism between these agents. Enhanced survival by combined treatment was associated with increased neutrophil counts in blood and peritoneal lavage fluid, lower systemic and higher levels of local tumour necrosis factor (TNF) and lower bacterial counts in blood cultures. Mouse neutrophils treated with G-CSF but not infected with E. coli showed enhanced phagocytic and respiratory burst capacity, down-regulation of L-selectin receptors and enhanced expression of Fc RII-III receptors but not of complement receptors.

[The effect of polyamines on lysosome fusion with phagosomes in mouse peritoneal macrophages].

PubMed

Mozhenok, T P; Bulychev, A G; Braun, A D

1990-01-01

The influence of polyamines on the phagosome-lysosome fusion in murine peritoneal macrophages and on polymerization of G-actin from the rabbit muscle in vitro has been studied. Both natural polyamines (spermin, spermidin, putrescin) and synthetic phenyl derivates of polyamines (3,3'-diaminobensidin, 1,5-naphtalin diamine, 4,4'-diaminodiphenilmetan, dancylcadaverin) were used. Unlike the phenyl derivates of polyamines and putrescin, spermin and spermidin stimulate the phagosome-lysosome fusion to induce G-actin polymerization. Possible mechanisms of action of the above polyamines are discussed.

Intra-Peritoneal Hyperthermia Combining α-Galactosylceramide in the Treatment of Ovarian Cancer

PubMed Central

Hsu, Yun-Ting; Huang, Jung-Tang; Wu, T. -C; Hung, Chien-Fu; Yang, Yuh-Cheng; Chang, Chih-Long

2013-01-01

The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8+/IFN-γ+ tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer. PMID:23935988

Interaction between harmane, a class of β-carboline alkaloids, and the CA1 serotonergic system in modulation of memory acquisition.

PubMed

Nasehi, Mohammad; Ghadimi, Fatemeh; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2017-09-01

This study set to assess the involvement of dorsal hippocampus (CA1) serotonergic system on harmane induced memory acquisition deficit. We used one trial step-down inhibitory avoidancetask to evaluate memory retention and then, open field test to evaluate locomotor activity in adult male NMRI mice. The results showed that pre-training intra-peritoneal (i.p.) administration of harmane (12mg/kg) induced impairment of memory acquisition. Pre-training intra-CA1 administration of 5-HT1B/1D receptor agonist (CP94253; 0.5 and 5ng/mouse) and 5-HT2A/2B/2C receptor agonist (α-methyl 5-HT; 50ng/mouse) impaired memory acquisition. Furthermore, intra-CA1 administration of 5-HT1B/1D receptor antagonist (GR127935; 0.5ng/mouse) and 5-HT2 receptor antagonist (cinancerine; 5ng/mouse) improved memory acquisition. In addition, pre-training intra-CA1 injection of sub-threshold dose of CP94253 (0.05ng/mouse) and α-methyl 5-HT (5ng/mouse) potentiated impairment of memory acquisition induced by harmane (12mg/kg, i.p.). On the other hand, pre-training intra-CA1 infusion of sub-threshold dose of GR127935 (0.05ng/mouse) and cinancerine (0.5ng/mouse) with the administration of harmane (12mg/kg, i.p.) weakened impairment of memory acquisition. Moreover, all above doses of drugs did not change locomotor activity. The present findings suggest that there is an interaction between harmane and the CA1 serotonergic system in modulation of memory acquisition. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information

PubMed Central

Horejs, Christine-Maria; St-Pierre, Jean-Philippe; Ojala, Juha R. M.; Steele, Joseph A. M.; da Silva, Patricia Barros; Rynne-Vidal, Angela; Maynard, Stephanie A.; Hansel, Catherine S.; Rodríguez-Fernández, Clara; Mazo, Manuel M.; You, Amanda Y. F.; Wang, Alex J.; von Erlach, Thomas; Tryggvason, Karl; López-Cabrera, Manuel; Stevens, Molly M.

2017-01-01

Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis. Importantly, our data demonstrate that the membrane inhibits MMP2 expression. Changes in the expression of epithelial-to-mesenchymal transition (EMT)-related molecules further point towards a contribution of the modulation of EMT. Biomaterial-based presentation of regulatory basement membrane signals directly addresses limitations of current therapeutic approaches by enabling a localized and specific method to counteract MMP2 release applicable to a broad range of therapeutic targets. PMID:28593951

Preventing tissue fibrosis by local biomaterials interfacing of specific cryptic extracellular matrix information

NASA Astrophysics Data System (ADS)

Horejs, Christine-Maria; St-Pierre, Jean-Philippe; Ojala, Juha R. M.; Steele, Joseph A. M.; da Silva, Patricia Barros; Rynne-Vidal, Angela; Maynard, Stephanie A.; Hansel, Catherine S.; Rodríguez-Fernández, Clara; Mazo, Manuel M.; You, Amanda Y. F.; Wang, Alex J.; von Erlach, Thomas; Tryggvason, Karl; López-Cabrera, Manuel; Stevens, Molly M.

2017-06-01

Matrix metalloproteinases (MMPs) contribute to the breakdown of tissue structures such as the basement membrane, promoting tissue fibrosis. Here we developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of MMP2 in this context. We demonstrate that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogates the release of active MMP2 in response to transforming growth factor β1 and rescues tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis. Importantly, our data demonstrate that the membrane inhibits MMP2 expression. Changes in the expression of epithelial-to-mesenchymal transition (EMT)-related molecules further point towards a contribution of the modulation of EMT. Biomaterial-based presentation of regulatory basement membrane signals directly addresses limitations of current therapeutic approaches by enabling a localized and specific method to counteract MMP2 release applicable to a broad range of therapeutic targets.

Dissecting the Mechanisms of Linezolid Resistance in a Drosophila melanogaster Infection Model of Staphylococcus aureus

PubMed Central

Diaz, Lorena; Kontoyiannis, Dimitrios P.; Panesso, Diana; Albert, Nathaniel D.; Singh, Kavindra V.; Tran, Truc T.; Munita, Jose M.; Murray, Barbara E.; Arias, Cesar A.

2013-01-01

Background. Mini-host models are simple experimental systems to study host-pathogen interactions. We adapted a Drosophila melanogaster infection model to evaluate the in vivo effect of different mechanisms of linezolid (LNZ) resistance in Staphylococcus aureus. Methods. Fly survival was evaluated after infection with LNZ-resistant S. aureus strains NRS119 (which has mutations in 23S ribosomal RNA [rRNA]), CM-05 and 004-737X (which carry cfr), LNZ-susceptible derivatives of CM-05 and 004-737X (which lack cfr), and ATCC 29213 (an LNZ-susceptible control). Flies were then fed food mixed with LNZ (concentration, 15–500 µg/mL). Results were compared to those in mouse peritonitis, using LNZ via oral gavage at 80 and 120 mg/kg every 12 hours. Results. LNZ at 500 µg/mL in fly food protected against all strains, while concentrations of 15–250 µg/mL failed to protect against NRS119 (survival, 1.6%–20%). An in vivo effect of cfr was only detected at concentrations of 30 and 15 µg/mL. In the mouse peritonitis model, LNZ (at doses that mimic human pharmacokinetics) protected mice from challenge with the cfr+ 004-737X strain but was ineffective against the NRS119 strain, which carried 23S rRNA mutations. Conclusions. The fly model offers promising advantages to dissect the in vivo effect of LNZ resistance in S. aureus, and findings from this model appear to be concordant with those from the mouse peritonitis model. PMID:23547139

Effects of Omega-3-Rich Harp Seal Oil on the Production of Pro-Inflammatory Cytokines in Mouse Peritoneal Macrophages.

PubMed

Choi, Myungwon; Ju, Jaehyun; Suh, Jae Soo; Park, Kun-Young; Kim, Kwang Hyuk

2015-06-01

Omega-3, a polyunsaturated fatty acid, is an essential fatty acid necessary for human health, and it protects against cardiovascular disease, inflammation, autoimmune diseases, and cancer. In the present study, we investigated the effects of omega-3-rich harp seal oil (HSO) on the production of nitric oxide (NO) and cytokines, such as tumor necrosis factor (TNF)-α, interleukin-(IL)-1β, IL-6, and IL-12/IL-23 (p40) in peritoneal macrophages of mice. The culture supernatants of murine macrophages exposed to lipopolysaccharide (LPS), HSO, or HSO+LPS were harvested to assay IL-1β, TNF-α, IL-6, and IL-12/IL-23 (p40) cytokines and NO. TNF-α, IL-1 β, and IL-12/IL-23 (p40) levels, except IL-6, were lower in the culture supernatants of mouse peritoneal macrophages exposed to LPS plus HSO than those of the groups exposed to LPS alone. These observations demonstrate that omega-3-rich harp seal oil downregulates the production of the pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-12/IL-23 (p40). These results suggest that HSO could be potentially used as a preventive agent or as an adjunct in anti-inflammatory therapy, if more research results were accumulated.

Protective activity of Lentinan in experimental tuberculosis.

PubMed

Markova, Nadya; Kussovski, Vesselin; Drandarska, Ivanka; Nikolaeva, Sascha; Georgieva, Neli; Radoucheva, Tatyana

2003-10-01

Protective effects of Lentinan (Ajinomoto, Japan) against Mycobacterium tuberculosis infection were studied by in vitro and in vivo mouse models. The effectiveness of Lentinan administrated intraperitoneally (i.p.) before infection at a dose of 1 mg/kg three times at 2-day intervals was monitored in vivo by several parameters (body temperature; spleen weight; CFU counts of M. tuberculosis in spleen, liver and lung; and histomorphological observations). Peritoneal macrophages obtained from animals treated with Lentinan were greatly stimulated, as assayed by establishing their number, acid phosphatase activity, H2O2 production and killing ability against M. tuberculosis in vitro. The in vivo model demonstrated that administration of Lentinan before infection can mobilize host defense potential and reduce mycobacterial infection.

Vascular endothelial growth factor receptor-3 is a novel target to improve net ultrafiltration in methylglyoxal-induced peritoneal injury.

PubMed

Terabayashi, Takeshi; Ito, Yasuhiko; Mizuno, Masashi; Suzuki, Yasuhiro; Kinashi, Hiroshi; Sakata, Fumiko; Tomita, Takako; Iguchi, Daiki; Tawada, Mitsuhiro; Nishio, Ryosuke; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Takei, Yoshifumi

2015-09-01

Appropriate fluid balance is important for good clinical outcomes and survival in patients on peritoneal dialysis. We recently reported that lymphangiogenesis associated with fibrosis developed in the peritoneal cavity via the transforming growth factor-β1-vascular endothelial growth factor-C (VEGF-C) pathway. We investigated whether VEGF receptor-3 (VEGFR-3), the receptor for VEGF-C and -D, might be a new target to improve net ultrafiltration by using adenovirus-expressing soluble VEGFR-3 (Adeno-sVEGFR-3) in rodent models of peritoneal injury induced by methylglyoxal (MGO). We demonstrated that lymphangiogenesis developed in these MGO models, especially in the diaphragm, indicating that lymphangiogenesis is a common feature in the peritoneal cavity with inflammation and fibrosis. In MGO models, VEGF-D was significantly increased in the diaphragm; however, VEGF-C was not significantly upregulated. Adeno-sVEGFR-3, which was detected on day 50 after administration via tail vein injections, successfully suppressed lymphangiogenesis in the diaphragm and parietal peritoneum in mouse MGO models without significant effects on fibrosis, inflammation, or neoangiogenesis. Drained volume in the peritoneal equilibration test using a 7.5% icodextrin peritoneal dialysis solution (the 7.5% icodextrin peritoneal equilibration test) was improved by Adeno-sVEGFR-3 on day 22 (P<0.05) and day 50 after reduction of inflammation (P<0.01), indicating that the 7.5% icodextrin peritoneal equilibration test identifies changes in lymphangiogenesis. The solute transport rate was not affected by suppression of lymphangiogenesis. In human peritoneal dialysis patients, the dialysate to plasma ratio of creatinine positively correlated with the dialysate VEGF-D concentration (P<0.001). VEGF-D mRNA was significantly higher in the peritoneal membranes of patients with ultrafiltration failure, indicating that VEGF-D is involved in the development of lymphangiogenesis in peritoneal dialysis patients. These results indicate that VEGFR-3 is a new target to improve net ultrafiltration by suppressing lymphatic absorption and that the 7.5% icodextrin peritoneal equilibration test is useful for estimation of lymphatic absorption.

Immune-Regulatory Molecule CD69 Controls Peritoneal Fibrosis

PubMed Central

Liappas, Georgios; González-Mateo, Guadalupe Tirma; Sánchez-Díaz, Raquel; Lazcano, Juan José; Lasarte, Sandra; Matesanz-Marín, Adela; Zur, Rafal; Ferrantelli, Evelina; Ramírez, Laura García; Aguilera, Abelardo; Fernández-Ruiz, Elena; Beelen, Robert H.J.; Selgas, Rafael; Sánchez-Madrid, Francisco

2016-01-01

Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69−/− mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody–mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69−/− mice. Finally, IL-17 blockade in cd69−/− mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69−/− and Rag2−/−γc−/− mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69−/− mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation. PMID:27151919

MTOR Suppresses Environmental Particle-Induced Inflammatory Response in Macrophages.

PubMed

Li, Zhouyang; Wu, Yinfang; Chen, Hai-Pin; Zhu, Chen; Dong, Lingling; Wang, Yong; Liu, Huiwen; Xu, Xuchen; Zhou, Jiesen; Wu, Yanping; Li, Wen; Ying, Songmin; Shen, Huahao; Chen, Zhi-Hua

2018-04-15

Increasing toxicological and epidemiological studies have demonstrated that ambient particulate matter (PM) could cause adverse health effects including inflammation in the lung. Alveolar macrophages represent a major type of innate immune responses to foreign substances. However, the detailed mechanisms of inflammatory responses induced by PM exposure in macrophages are still unclear. We observed that coarse PM treatment rapidly activated mechanistic target of rapamycin (MTOR) in mouse alveolar macrophages in vivo, and in cultured mouse bone marrow-derived macrophages, mouse peritoneal macrophages, and RAW264.7 cells. Pharmacological inhibition or genetic knockdown of MTOR in bone marrow-derived macrophages leads to an amplified cytokine production upon PM exposure, and mice with specific knockdown of MTOR or ras homolog enriched in brain in myeloid cells exhibit significantly aggregated airway inflammation. Mechanistically, PM activated MTOR through modulation of ERK, AKT serine/threonine kinase 1, and tuberous sclerosis complex signals, whereas MTOR deficiency further enhanced the PM-induced necroptosis and activation of subsequent NF κ light-chain-enhancer of activated B cells (NFKB) signaling. Inhibition of necroptosis or NFKB pathways significantly ameliorated PM-induced inflammatory response in MTOR-deficient macrophages. The present study thus demonstrates that MTOR serves as an early adaptive signal that suppresses the PM-induced necroptosis, NFKB activation, and inflammatory response in lung macrophages, and suggests that activation of MTOR or inhibition of necroptosis in macrophages may represent novel therapeutic strategies for PM-related airway disorders. Copyright © 2018 by The American Association of Immunologists, Inc.

Degalactosylated/desialylated human serum containing GcMAF induces macrophage phagocytic activity and in vivo antitumor activity.

PubMed

Kuchiike, Daisuke; Uto, Yoshihiro; Mukai, Hirotaka; Ishiyama, Noriko; Abe, Chiaki; Tanaka, Daichi; Kawai, Tomohito; Kubo, Kentaro; Mette, Martin; Inui, Toshio; Endo, Yoshio; Hori, Hitoshi

2013-07-01

The group-specific component protein-derived macrophage-activating factor (GcMAF) has various biological activities, such as macrophage activation and antitumor activity. Clinical trials of GcMAF have been carried out for metastatic breast cancer, prostate cancer, and metastatic colorectal cancer. In this study, despite the complicated purification process of GcMAF, we used enzymatically-treated human serum containing GcMAF with a considerable macrophage-stimulating activity and antitumor activity. We detected GcMAF in degalactosylated/desialylated human serum by western blotting using an anti-human Gc globulin antibody, and Helix pomatia agglutinin lectin. We also found that GcMAF-containing human serum significantly enhanced the phagocytic activity of mouse peritoneal macrophages and extended the survival time of mice bearing Ehrlich ascites tumors. We demonstrated that GcMAF-containing human serum can be used as a potential macrophage activator for cancer immunotherapy.

Bactericidal Activity of Ceragenin CSA-13 in Cell Culture and in an Animal Model of Peritoneal Infection.

PubMed

Bucki, Robert; Niemirowicz, Katarzyna; Wnorowska, Urszula; Byfield, Fitzroy J; Piktel, Ewelina; Wątek, Marzena; Janmey, Paul A; Savage, Paul B

2015-10-01

Ceragenins constitute a novel family of cationic antibiotics characterized by a broad spectrum of antimicrobial activities, which have mostly been assessed in vitro. Using a polarized human lung epithelial cell culture system, we evaluated the antibacterial activities of the ceragenin CSA-13 against two strains of Pseudomonas aeruginosa (PAO1 and Xen5). Additionally, the biodistribution and bactericidal activity of a CSA-13-IRDye 800CW derivate were assessed using an animal model of peritoneal infection after PAO1 challenge. In cell culture, CSA-13 bactericidal activities against PAO1 and Xen5 were higher than the activities of the human cathelicidin peptide LL-37. Increased CSA-13 activity was observed in polarized human lung epithelial cell cultures subjected to butyric acid treatment, which is known to increase endogenous LL-37 production. Eight hours after intravenous or intraperitoneal injection, the greatest CSA-13-IRDye 800CW accumulation was observed in mouse liver and kidneys. CSA-13-IRDye 800CW administration resulted in decreased bacterial outgrowth from abdominal fluid collected from animals subjected to intraperitoneal PAO1 infection. These observations indicate that CSA-13 may synergistically interact with antibacterial factors that are naturally present at mucosal surfaces and it maintains its antibacterial activity in the infected abdominal cavity. Cationic lipids such as CSA-13 represent excellent candidates for the development of new antibacterial compounds. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

TNFRp55 deficiency promotes the development of ectopic endometriotic-like lesions in mice.

PubMed

Vallcaneras, Sandra; Ghersa, Federica; Bastón, Juan; Delsouc, María Belén; Meresman, Gabriela; Casais, Marilina

2017-09-01

Endometriosis is an inflammatory disease depending on estradiol, with TNF-α being one of the most representative cytokines involved in its pathogenesis. TNF-α acts through its bond to the TNFRp55 and TNFRp75 membrane receptors. The aim of this study was to analyze the effect of the TNFRp55 deficiency on the development of ectopic endometriotic-like lesions. Endometriosis was induced surgically in mice of the C57BL/6 strain, wild type (WT) and TNFRp55-/- (KO). After four weeks, the peritoneal fluid was collected and the lesions were counted, measured with a caliper, removed, weighed, fixed or kept at -80°C. We evaluated the cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry and apoptosis by TUNEL technique in the ectopic lesions. MMP-2 and MMP-9 activities (factors involved in invasiveness) were measured by zymography in the peritoneal fluid; estradiol and progesterone levels were measured by radioimmunoassay in the lesions and in the peritoneal fluid. We found that in KO animals the mean number of lesions established per mouse, the lesion volume, weight and cell proliferation increased and apoptosis decreased. In addition, the activity of MMP-2 and the estradiol level increased, whereas the progesterone level was not significantly modified. In conclusion, the deficiency of TNFRp55 promoted the establishment and development of endometriosis through an increase in the lesion size and high levels of estradiol which correlate with an increase in the MMP-2 activity. This is evidence of the possible association of the deregulation of the TNFRp55 expression and the survival of the endometriotic tissue in ectopic sites. © 2017 Society for Endocrinology.

Significance of SYT8 For the Detection, Prediction, and Treatment of Peritoneal Metastasis From Gastric Cancer.

PubMed

Kanda, Mitsuro; Shimizu, Dai; Tanaka, Haruyoshi; Tanaka, Chie; Kobayashi, Daisuke; Hayashi, Masamichi; Iwata, Naoki; Niwa, Yukiko; Yamada, Suguru; Fujii, Tsutomu; Sugimoto, Hiroyuki; Murotani, Kenta; Fujiwara, Michitaka; Kodera, Yasuhiro

2018-03-01

To develop novel diagnostic and therapeutic targets specific for peritoneal metastasis of gastric cancer (GC). Advanced GC frequently recurs because of undetected micrometastases even after curative resection. Peritoneal metastasis has been the most frequent recurrent pattern after gastrectomy and is incurable. We conducted a recurrence pattern-specific transcriptome analysis in an independent cohort of 16 patients with stage III GC who underwent curative gastrectomy and adjuvant S-1 for screening candidate molecules specific for peritoneal metastasis of GC. Next, another 340 patients were allocated to discovery and validation sets (1:2) to evaluate the diagnostic and predictive value of the candidate molecule. The results of quantitative reverse-transcription PCR and immunohistochemical analysis were correlated with clinical characteristics and survival. The effects of siRNA-mediated knockdown on phenotype and fluorouracil sensitivity of GC cells were evaluated in vitro, and the therapeutic effects of siRNAs were evaluated using a mouse xenograft model. Synaptotagmin VIII (SYT8) was identified as a candidate biomarker specific to peritoneal metastasis. In the discovery set, the optimal cut-off of SYT8 expression was established as 0.005. Expression levels of SYT8 mRNA in GC tissues were elevated in the validation set comprising patients with peritoneal recurrence or metastasis. SYT8 levels above the cut-off value were significantly and specifically associated with peritoneal metastasis, and served as an independent prognostic marker for peritoneal recurrence-free survival of patients with stage II/III GC. The survival difference between patients with SYT8 levels above and below the cut-off was associated with patients who received adjuvant chemotherapy. Inhibition of SYT8 expression by GC cells correlated with decreased invasion, migration, and fluorouracil resistance. Intraperitoneal administration of SYT8-siRNA inhibited the growth of peritoneal nodules and prolonged survival of mice engrafted with GC cells. SYT8 represents a promising target for the detection, prediction, and treatment of peritoneal metastasis of GC.

Interplay between Endometriosis and Pregnancy in a Mouse Model.

PubMed

Bilotas, Mariela Andrea; Olivares, Carla Noemí; Ricci, Analía Gabriela; Baston, Juan Ignacio; Bengochea, Tatiana Soledad; Meresman, Gabriela Fabiana; Barañao, Rosa Inés

2015-01-01

To evaluate the effect of endometriosis on fertility and the levels of the IL-2 and IFN-γ in the peritoneal fluid in a mouse model; to evaluate the effect of pregnancy on endometriotic lesion growth, apoptosis and cell proliferation. Two month old C57BL/6 female mice underwent either a surgical procedure to induce endometriosis or a sham surgery. Four weeks after surgery mice were mated and sacrificed at day 18 of pregnancy. Number of implantation sites, fetuses and fetal weight were recorded. Endometriotic lesions were counted, measured, excised and fixed. Apoptosis and cell proliferation were evaluated in lesions by TUNEL and immunohistochemistry for PCNA respectively. Levels of IL-2 and IFN-γ were assessed by ELISA in the peritoneal fluid. Pregnancy rate (i.e. pregnant mice/N) decreased in mice with endometriosis. However there were no significant differences in resorption rate, litter size and pup weight between groups. IFN-γ augmented in endometriosis mice independently of pregnancy outcome. Additionally IFN-γ increased in pregnant endometriosis mice compared to pregnant sham animals. While IFN-γ increased in non pregnant versus pregnant mice in the sham group, IL-2 was increased in non pregnant mice in the endometriosis group. The size of endometriotic lesions increased in pregnant mice while apoptosis increased in the stroma and cell proliferation decreased in the epithelium of these lesions. Additionally, leukocyte infiltration, necrosis and decidualization were increased in the same lesions. Pregnancy rate is reduced in this mouse model of endometriosis. Levels of IL-2 are increased in the peritoneal fluid of mice with endometriosis suggesting a role of this cytokine in infertility related to this disease. The size of endometriotic lesions is increased in pregnant mice; however pregnancy has a beneficial effect on lesions by decreasing cell proliferation and by increasing apoptosis, decidualization and necrosis.

Isolation of two triterpenoids and a biflavanone with anti-Inflammatory activity from Schinus molle fruits.

PubMed

Yueqin, Zeng; Recio, M Carmen; Máñez, Salvador; Giner, Rosa M; Cerdá-Nicolás, M; Ríos, José-Luis

2003-10-01

Three compounds with anti-inflammatory activity were isolated from Schinus molle fruits. Two of the compounds were identified as 3- epi-isomasticadienolalic acid ( 1), isomasticadienonalic acid ( 2) and chamaejasmin ( 3). Triterpenes 1 and 2, and biflavanone 3 were tested on two models of mice paw inflammation: one of acute inflammation, induced by subcutaneous injection of either phospholipase A (2) (PLA (2)) or carrageenan in the paws of mice, and one of chronic inflammation in the form of eczema, provoked by repeated administration of TPA to the ears of mice. On the PLA (2)-induced mouse paw oedema, only 2 was active (30 mg/kg, 66 % inhibition at 60 min), whereas all compounds reduced the chronic model of inflammation (48 to 26 % of swelling reduction), but only triterpenes reduced the leukocyte infiltration, measured as tissue peroxidase activity. In the case of the carrageenan-induced mouse paw oedema, only 3 led to a reduction of the swelling 3 h after challenge (50 mg/kg, 46 % oedema inhibition). In addition, 3 inhibited the LTB (4) production in rat peritoneal polymorphonuclear leukocytes with an IC (50) value of 29.8 microM, while triterpenes showed toxicity against cells at 100 microM.

Mangiferin ameliorates colitis by inhibiting IRAK1 phosphorylation in NF-κB and MAPK pathways.

PubMed

Jeong, Jin-Ju; Jang, Se-Eun; Hyam, Supriya R; Han, Myung Joo; Kim, Dong-Hyun

2014-10-05

Mangiferin, a main constituent of the root of Anemarrhena asphodeloides and the leaves of Mangifera indica, inhibits NF-κB activation in macrophages. Therefore, we investigated effect of mangiferin on 2,3,4-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice and its anti-inflammatory mechanism in lipolysaccharide (LPS)- or peptidoglycan-stimulated mouse peritoneal macrophages. Mangiferin inhibited phosphorylation of nuclear factor-kappaB (NF-κB), interleukin-1 receptor-associated kinase 1 (IRAK1), and mitogen-activated protein kinases (MAPK) in peptidoglycan- or LPS-stimulated peritoneal macrophages. Mangiferin in the presence of SN50 inhibited LPS-stimulated NF-κB activation more potently than mangiferin alone. Mangiferin inhibited interaction of fluorescent p-IRAK1 antibody to LPS-stimulated peritoneal macrophages, but increased binding of fluorescent IRAK1 antibody. Mangiferin did not influence interaction of fluorescent LPS to toll-like receptor-4 on the macrophages. Molecular peak of mangiferin bound to IRAK1 was detected in the macrophages by mass analysis. Mangiferin (10 μM) inhibited LPS-stimulated expression of TNF-α, IL-1β and IL-6 by 81.0%, 89.5% and 88.3%, respectively, whereas it increased IL-10 expression by 131.8% compared to LPS-nontreated group. Mangiferin furthermore inhibited colon shortening, macroscopic score, and colonic myeloperoxidase activity in TNBS-induced colitic mice. Mangiferin inhibited TNBS-induced IRAK1 phosphorylation and NF-κB activation. Mangiferin suppressed TNBS-induced up-regulation of cyclooxygenase-2 and inducible NO synthase. Furthermore, mangiferin (20mg/kg) significantly inhibited TNF-α by 78%, IL-1β by 82%, and IL-6 expressions by 88% (P<0.05), but induced IL-10 expression to 79% of the normal control group (P<0.05). Based on these findings, mangiferin may ameliorate inflammatory diseases such as colitis by regulating NF-κB and MAPK signaling pathways through the inhibition of IRAK1 phosphorylation. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhanced hydrogen peroxide release from macrophages stimulated with streptococcal preparation OK-432.

PubMed Central

Saito, H; Tomioka, H

1979-01-01

Wheat germ lectin was found to be a potent triggering agent for hydrogen peroxide release from mouse peritoneal macrophages. Macrophages stimulated by intraperitoneal injection of OK-432, a lyophilized attenuated streptococcal preparation, were highly responsive to wheat germ lectin. PMID:546795

On sample size of the kruskal-wallis test with application to a mouse peritoneal cavity study.

PubMed

Fan, Chunpeng; Zhang, Donghui; Zhang, Cun-Hui

2011-03-01

As the nonparametric generalization of the one-way analysis of variance model, the Kruskal-Wallis test applies when the goal is to test the difference between multiple samples and the underlying population distributions are nonnormal or unknown. Although the Kruskal-Wallis test has been widely used for data analysis, power and sample size methods for this test have been investigated to a much lesser extent. This article proposes new power and sample size calculation methods for the Kruskal-Wallis test based on the pilot study in either a completely nonparametric model or a semiparametric location model. No assumption is made on the shape of the underlying population distributions. Simulation results show that, in terms of sample size calculation for the Kruskal-Wallis test, the proposed methods are more reliable and preferable to some more traditional methods. A mouse peritoneal cavity study is used to demonstrate the application of the methods. © 2010, The International Biometric Society.

Silver enhances antibiotic activity against gram-negative bacteria.

PubMed

Morones-Ramirez, J Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

2013-06-19

A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

Sustained release of antibiotic complexed by multivalent ion: in vitro and in vivo study for the treatment of peritonitis.

PubMed

Na, Seung Yeon; Oh, Se Heang; Kim, Tae Ho; Yoon, Jin A; Lee, In Soo; Lee, Jin Ho

2014-12-10

The main aims of this study are (i) the development of an antibiotic complexed with multivalent ion, which can allow sustained release of the antibiotic without any additional matrix or difficult process and (ii) the feasibility study of the ion-complexed antibiotic as a therapeutic technique for peritonitis treatment. An ion-complexed antibiotic is prepared by simple mixing of two aqueous solutions containing an ionized (water-soluble) drug (tetracycline) and a multivalent counter ionic compound. The ion-complexed antibiotic shows a continuous release of the antibiotic up to 21 days, and thus prolonged anti-bacterial effect by gradual ionic exchange between the multivalent ions in the complex and same-charged monovalent ions in surrounding medium. From the in vivo animal study using a cecum perforated peritonitis mouse model, the ion-complexed antibiotic group shows sufficient anti-bacterial effect and thus effectively treat the peritonitis because of the extermination of the contaminated enteric bacteria in the peritoneum during wound healing of injury cecum (by the sustained release of antibiotic from the ion complex). These results suggest that the ion-complexed antibiotic system may be promising for the effective treatment of the peritonitis caused by frequent gastrointestinal defect in clinical fields. Copyright © 2014 Elsevier B.V. All rights reserved.

Additive effect of harmane and muscimol for memory consolidation impairment in inhibitory avoidance task.

PubMed

Nasehi, Mohammad; Morteza-Zadeh, Parastoo; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2016-12-17

In the current study, we examined the effect of bilateral intra-dorsal hippocampal (intra-CA1) microinjections of GABA A receptor agents on amnesia induced by a β-carboline alkaloid, harmane in mice. We used a single-trial step-down passive avoidance task to assess memory retention and then, open-field test to assess locomotor activity. The results indicated that post-training intra-CA1 injections of bicuculline - a GABA A receptor antagonist - had no significant effect, while muscimol (0.01 and 0.1μg/mouse) - a GABA A receptor agonist - impaired memory consolidation. Post-training intra-peritoneal (i.p.) infusion of harmane (3 and 5mg/kg) decreased memory consolidation. Furthermore, post-training intra-CA1 administration of sub-threshold dose of bicuculline (0.001μg/mouse) restored, whereas muscimol (0.001μg/mouse) potentiated impairment of memory consolidation induced by harmane. The isobologram analysis revealed that there is an additive effect between harmane and muscimol on impairment of memory consolidation. Moreover, all above doses of drugs did not alter locomotor activity. These findings suggest that GABA A receptors of the CA1 area, at least partly, play a role in modulating the effect of harmane on memory consolidation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

PubMed

Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

2017-01-01

The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

LPS receptor CD14 participates in release of TNF-alpha in RAW 264.7 and peritoneal cells but not in kupffer cells.

PubMed

Lichtman, S N; Wang, J; Lemasters, J J

1998-07-01

Lipopolysaccharide (LPS) is a bacterial polymer that stimulates macrophages to release tumor necrosis factor-alpha (TNF-alpha). In macrophages (RAW 264.7 and peritoneal cells), LPS binds to the CD14 surface receptor as the first step toward signaling. Liver macrophages, Kupffer cells, are the most numerous fixed-tissue macrophage in the body. The presence of CD14 on Kupffer cells and its role in LPS stimulation of TNF-alpha were examined. TNF-alpha release by Kupffer cells after LPS stimulation was the same in the presence and absence of serum. RAW 264.7 and peritoneal cells, which utilize the CD14 receptor, released significantly less TNF-alpha after LPS stimulation in the absence of serum because of the absence of LPS-binding protein. Phosphatidylinositol-phospholipase C treatment, which cleaves the CD14 receptor, decreased LPS-stimulated TNF-alpha release by RAW 264.7 cells but not by Kupffer cells. Deacylated LPS (dLPS) competes with LPS at the CD14 receptor when incubated in a ratio of 100:1 (dLPS/LPS). Such competition blocked LPS-stimulated TNF-alpha release from RAW 264.7 cells but not from Kupffer cells. Western and fluorescence-activated cell sorter analysis directly demonstrated the presence of CD14 on RAW 264.7 cells and murine peritoneal cells but showed only minimal amounts of CD14 in murine Kupffer cells. LPS stimulation did not increase the amount of CD14 detectable on mouse Kupffer cells. CD14 expression is very low in Kupffer cells, and LPS-stimulated TNF-alpha release is independent of CD14 in these cells.

Inhibiting core fucosylation attenuates glucose-induced peritoneal fibrosis in rats.

PubMed

Li, Longkai; Shen, Nan; Wang, Nan; Wang, Weidong; Tang, Qingzhu; Du, Xiangning; Carrero, Juan Jesus; Wang, Keping; Deng, Yiyao; Li, Zhitong; Lin, Hongli; Wu, Taihua

2018-06-01

Ultrafiltration failure is a major complication of long-term peritoneal dialysis, resulting in dialysis failure. Peritoneal fibrosis induced by continuous exposure to high glucose dialysate is the major contributor of ultrafiltration failure, for which there is no effective treatment. Overactivation of several signaling pathways, including transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) pathways, contribute to the development of peritoneal fibrosis. Therefore, simultaneously blocking multiple signaling pathways might be a potential novel method of treating peritoneal fibrosis. Previously, we showed that core fucosylation, an important posttranslational modification of the TGF-β1 receptors, can regulate the activation of TGF-β1 signaling in renal interstitial fibrosis. However, it remains unclear whether core fucosylation affects the progression of peritoneal fibrosis. Herein, we show that core fucosylation was enriched in the peritoneal membrane of rats accompanied by peritoneal fibrosis induced by a high glucose dialysate. Blocking core fucosylation dramatically attenuated peritoneal fibrosis in the rat model achieved by simultaneously inactivating the TGF-β1 and PDGF signaling pathways. Next the protective effects of blocking core fucosylation and imatinib (a selective PDGF receptor inhibitor) on peritoneal fibrosis were compared and found to exhibit a greater inhibitory effect over imatinib alone, suggesting that blocking activation of multiple signaling pathways may have superior inhibitory effects on the development of peritoneal fibrosis. Thus, core fucosylation is essential for the development of peritoneal fibrosis by regulating the activation of multiple signaling pathways. This may be a potential novel target for drug development to treat peritoneal fibrosis. Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

In vitro cytotoxicity and quantitative silica analysis of diatomaceous earth products.

PubMed

Bye, E; Davies, R; Griffiths, D M; Gylseth, B; Moncrieff, C B

1984-05-01

Mouse peritoneal macrophages were used to evaluate the relative cytotoxicity of a series of diatomaceous earth products in vitro. The amorphous and crystalline silica content of the products was determined by a combination of infrared spectroscopy and x ray powder diffraction techniques. The cytotoxicities of the high cristobalite content flux calcined materials were similar to that of the standard cristobalite ; both the natural and straight calcined materials had significantly greater activities than the flux calcined materials. Thus within the limitations of the macrophage cytotoxicity test the hypothesis that crystalline content is the only determinant of fibrogenicity of diatomaceous earth is not supported.

In vitro cytotoxicity and quantitative silica analysis of diatomaceous earth products.

PubMed Central

Bye, E; Davies, R; Griffiths, D M; Gylseth, B; Moncrieff, C B

1984-01-01

Mouse peritoneal macrophages were used to evaluate the relative cytotoxicity of a series of diatomaceous earth products in vitro. The amorphous and crystalline silica content of the products was determined by a combination of infrared spectroscopy and x ray powder diffraction techniques. The cytotoxicities of the high cristobalite content flux calcined materials were similar to that of the standard cristobalite ; both the natural and straight calcined materials had significantly greater activities than the flux calcined materials. Thus within the limitations of the macrophage cytotoxicity test the hypothesis that crystalline content is the only determinant of fibrogenicity of diatomaceous earth is not supported. Images PMID:6326795

Metabolism of polyunsaturated fatty acids by mouse peritoneal macrophages: the lipoxygenase metabolic pathway.

PubMed

Rabinovitch, H; Durand, J; Gualde, N; Rigaud, M

1981-12-01

When resident macrophages from mice are incubated with exogenous polyunsaturated fatty acids, they produce lipoxygenic metabolites. To delineate this metabolic chart we used high pressure liquid chromatography and gas chromatography prior to mass spectrometry-computer system. The lipoxygenic activity of these cells leads to many compounds. Among them we describe the monohydroxylated metabolites and vicinal hydroxyepoxyenes. In the mechanism of formation of the latter unstable cyclic precursors might occur as intermediates between hydroperoxides and them. Dihydroxy compounds could arise from hydrolysis of unstable epoxide precursor which could be the second substrate of the glutathione transferase system and could lead to thioaminolipids.

Connective tissue growth factor acts as a therapeutic agent and predictor for peritoneal carcinomatosis of colorectal cancer.

PubMed

Lin, Been-Ren; Chang, Cheng-Chi; Chen, Robert Jeen-Chen; Jeng, Yung-Ming; Liang, Jin-Tung; Lee, Po-Huang; Chang, King-Jen; Kuo, Min-Liang

2011-05-15

Here, we aimed to investigate the role of connective tissue growth factor (CTGF) in peritoneal carcinomatosis (PC) associated with colorectal cancer (CRC) and to characterize the underlying mechanism of CTGF mediating adhesion. A cohort of 136 CRC patient specimens was analyzed in this study. CRC cell lines were used for in vitro adhesion assay and in vivo peritoneal dissemination experiment. Recombinant CTGF protein treatment, transfection of CTGF expression plasmids, and knockdown of CTGF expression in CRC cells were utilized to evaluate the integrin α5, which served as a target of CTGF in inhibiting peritoneal seeding. The analysis of CRC tissues revealed an inverse correlation between CTGF expression and prevalence of PC. Lower CTGF level in CRC patients was associated with higher peritoneal recurrence rate after surgery. Inducing CTGF expression in cancer cells resulted in decreased incidence of PC and increased rate of mice survival. The mice received intraperitoneal injection of recombinant CTGF protein simultaneously with cancer cells or following tumor formation; in both cases, peritoneal tumor dissemination was found to be effectively inhibited in the mouse model. Functional assay revealed that CTGF significantly decreased the CRC cell adhesion ability, and integrin α5 was confirmed by reverse transcriptase PCR and functional blocking assay as a downstream effector in the CTGF-mediated inhibition of CRC cell adhesion. CTGF acts as a molecular predictor of PC and could be a potential therapeutic target for the chemoprevention and treatment of PC in CRC patients. ©2011 AACR.

Peritoneal sarcomatosis: site of origin for the establishment of an in vitro and in vivo cell line model to study therapeutic resistance in dedifferentiated liposarcoma.

PubMed

Mersch, Sabrina; Riemer, Jasmin C; Schlünder, Philipp M; Ghadimi, Markus P; Ashmawy, Hany; Möhlendick, Birte; Topp, Stefan A; Arent, Tanja; Kröpil, Patric; Stoecklein, Nikolas H; Gabbert, Helmut E; Knoefel, Wolfram T; Krieg, Andreas

2016-02-01

Approximately 50-70 % of patients with retroperitoneal or intraabdominal sarcoma develop a relapse after surgical therapy, including peritoneal sarcomatosis, an extremely rare site of metastatic disease which is associated with an extremely poor prognosis. Accordingly, the establishment of a permanent cell line derived from peritoneal sarcomatosis might provide a helpful tool to understand the biological behavior and to develop new therapeutic strategies. Thus, we established and characterized a liposarcoma cell line (Lipo-DUE1) from a peritoneal sarcomatosis that was permanently cultured without showing any morphological changes. Lipo-DUE1 cells exhibited a spindle-shaped morphology and positive staining for S100. Tumorigenicity was demonstrated in vitro by invasion and migration assays and in vivo by using a subcutaneous xenograft mouse model. In addition, aCGH analysis revealed concordant copy number variations on chromosome 12q in the primary tumor, peritoneal sarcomatosis, and Lipo-DUE1 cells that are commonly observed in liposarcoma. Chemotherapeutic sensitivity assays revealed a pronounced drug-resistant phenotype of Lipo-DUE1 cells to conventionally used chemotherapeutic agents. In conclusion, we describe for the first time the establishment and characterization of a liposarcoma cell line derived from a peritoneal sarcomatosis. Hence, in the future, the newly established cell line Lipo-DUE1 might serve as a useful in vitro and in vivo model to investigate the biological behavior of liposarcoma and to assess novel targeted therapies.

Jungle Honey Enhances Immune Function and Antitumor Activity

PubMed Central

Fukuda, Miki; Kobayashi, Kengo; Hirono, Yuriko; Miyagawa, Mayuko; Ishida, Takahiro; Ejiogu, Emenike C.; Sawai, Masaharu; Pinkerton, Kent E.; Takeuchi, Minoru

2011-01-01

Jungle honey (JH) is collected from timber and blossom by wild honey bees that live in the tropical forest of Nigeria. JH is used as a traditional medicine for colds, skin inflammation and burn wounds as well as general health care. However, the effects of JH on immune functions are not clearly known. Therefore, we investigated the effects of JH on immune functions and antitumor activity in mice. Female C57BL/6 mice were injected with JH (1 mg/mouse/day, seven times intra-peritoneal). After seven injections, peritoneal cells (PC) were obtained. Antitumor activity was assessed by growth of Lewis Lung Carcinoma/2 (LL/2) cells. PC numbers were increased in JH-injected mice compared to control mice. In Dot Plot analysis by FACS, a new cell population appeared in JH-injected mice. The percent of Gr-1 surface antigen and the intensity of Gr-1 antigen expression of PC were increased in JH-injected mice. The new cell population was neutrophils. JH possessed chemotactic activity for neutrophils. Tumor incidence and weight were decreased in JH-injected mice. The ratio of reactive oxygen species (ROS) producing cells was increased in JH-injected mice. The effective component in JH was fractionized by gel filtration using HPLC and had an approximate molecular weight (MW) of 261. These results suggest that neutrophils induced by JH possess potent antitumor activity mediated by ROS and the effective immune component of JH is substrate of MW 261. PMID:19141489

Stimulation of IFN-γ production by garlic lectin in mouse spleen cells: involvement of IL-12 via activation of p38 MAPK and ERK in macrophages.

PubMed

Dong, Qing; Sugiura, Tsutomu; Toyohira, Yumiko; Yoshida, Yasuhiro; Yanagihara, Nobuyuki; Karasaki, Yuji

2011-02-15

Several lectins, present in beans and edible plant products, have immuno-potentiating and anti-tumor activities. We here report the effects of garlic lectin purified from garlic bulbs on the production of cytokines such as interleukin-12 (IL-12) and interferon-γ (IFN-γ) in the mouse. Garlic lectin induced IFN-γ production in spleen cells in a bell-shaped time (24-60 h)- and concentration (0.25-2.0 mg/ml)-dependent manner. The maximal enhancement was observed at 36 h with 0.5 mg/ml of garlic lectin. The stimulatory effect of garlic lectin on IFN-γ production was completely inhibited by both actinomycin D and cycloheximide, an inhibitor of ribosomal protein synthesis and DNA-dependent RNA polymerase, respectively, and was associated with an increase in IFN-γ mRNA level. Garlic lectin also induced IL-12 production in mouse peritoneal macrophages in a concentration (0.25-1.0 mg/ml)- and bell-shaped time (3-24 h)-dependent manner. The lectin increased the phosphorylation of extracellular signal-regulated kinases (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) in macrophages. Furthermore, specific pharmacological inhibitors of ERK kinase (U0126) and p38 MAPK (SB203580) also suppressed the production of IL-12 induced by garlic lectin. The present findings suggest that garlic lectin induces IL-12 production via activation of p38 MAPK and ERK in mouse macrophages, which, in turn, stimulates IFN-γ production through an increase in IFN-γ mRNA in the spleen cells. Copyright © 2010 Elsevier GmbH. All rights reserved.

DICHLOROACETONITRILE INDUCES OXIDATIVE STRESS AS A MEDIATOR OF APOPTOSIS OR NECROSIS IN MOUSE PERITONEAL MACROPHAGES (MPM). (R825955)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Bacillus anthracis Edema Toxin Inhibits Staphylococcus aureus Enterotoxin B Effects in Vitro: A Potential Protein Therapeutic?

DTIC Science & Technology

2005-10-01

5). Inherent characteristics of edema toxin and other procaryotic adenylate cyclases from Bordetella pertussis, Pseudomonas aeruginosa, and Yersinia...by mouse peritoneal macrophages: the role of cellular cyclic AMP. Immunology 64:719–724. 12. Krakauer, T. 1999. Induction of CC chemokines in human

Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis.

PubMed

Hull, M L; Prentice, A; Wang, D Y; Butt, R P; Phillips, S C; Smith, S K; Charnock-Jones, D S

2005-02-01

Women with endometriosis have elevated levels of cyclooxygenase-2 (COX-2) in peritoneal macrophages and endometriotic tissue. Inhibition of COX-2 has been shown to reduce inflammation, angiogenesis and cellular proliferation. It may also downregulate aromatase activity in ectopic endometrial lesions. Ectopic endometrial establishment and growth are therefore likely to be suppressed in the presence of COX-2 inhibitors. We hypothesized that COX-2 inhibition would reduce the size and number of ectopic human endometrial lesions in a nude mouse model of endometriosis. The selective COX-2 inhibitor, nimesulide, was administered to estrogen-supplemented nude mice implanted with human endometrial tissue. Ten days after implantation, the number and size of ectopic endometrial lesions were evaluated and compared with lesions from a control group. Immunohistochemical assessment of vascular development and macrophage and myofibroblast infiltration in control and treated lesions was performed. There was no difference in the number or size of ectopic endometrial lesions in control and nimesulide-treated nude mice. Nimesulide did not induce a visually identifiable difference in blood vessel development or macrophage or myofibroblast infiltration in nude mouse explants. The hypothesized biological properties of COX-2 inhibition did not influence lesion number or size in the nude mouse model of endometriosis.

Peritoneal retention of liposomes: Effects of lipid composition, PEG coating and liposome charge.

PubMed

Dadashzadeh, S; Mirahmadi, N; Babaei, M H; Vali, A M

2010-12-01

In the treatment of peritoneal carcinomatosis, systemic chemotherapy is not quite effective due to the poor penetration of cytotoxic agents into the peritoneal cavity, whereas intraperitoneal administration of chemotherapeutic agents is generally accompanied by quick absorption of the free drug from the peritoneum. Local delivery of drugs with controlled-release delivery systems like liposomes could provide sustained, elevated drug levels and reduce local and systemic toxicity. In order to achieve an ameliorated liposomal formulation that results in higher peritoneal levels of the drug and retention, vesicles composed of different phospholipid compositions (distearoyl [DSPC]; dipalmitoyl [DPPC]; or dimiristoylphosphatidylcholine [DMPC]) and various charges (neutral; negative, containing distearoylphosphatidylglycerol [DSPG]; or positive, containing dioleyloxy trimethylammonium propane [DOTAP]) were prepared at two sizes of 100 and 1000nm. The effect of surface hydrophilicity was also investigated by incorporating PEG into the DSPC-containing neutral and charged liposomes. Liposomes were labeled with (99m)Tc and injected into mouse peritoneum. Mice were then sacrificed at eight different time points, and the percentage of injected radiolabel in the peritoneal cavity and the tissue distribution in terms of the percent of the injected dose/gram of tissue (%ID/g) were obtained. The ratio of the peritoneal AUC to the free label ranged from a minimum of 4.95 for DMPC/CHOL (cholesterol) 100nm vesicles to a maximum of 24.99 for DSPC/CHOL/DOTAP 1000nm (DOTAP 1000) vesicles. These last positively charged vesicles had the greatest peritoneal level; moreover, their level remained constant at approximately 25% of the injected dose from 2 to 48h. Among the conventional (i.e., without PEG) 100nm liposomes, the positively charged vesicles again showed the greatest retention. Incorporation of PEG at this size into the lipid structures augmented the peritoneal level, particularly for negatively charged liposomes. The positively charged PEGylated vesicles (DOTAP/PEG 100) had the second-greatest peritoneal level after DOTAP 1000; however, their peritoneal-to-blood AUC ratio was low (3.05). Overall, among the different liposomal formulations, the positively charged conventional liposomes (100 and 1000nm) provided greater peritoneal levels and retention. DOTAP/PEG100 may also be a more efficient formulation because this formulation can provide a high level of anticancer drug into the peritoneal cavity and also can passively target the primary tumor. Copyright © 2010 Elsevier B.V. All rights reserved.

[Can dexpanthenol prevent peritoneal adhesion formation? An experimental study].

PubMed

Akdeniz, Yusuf; Tarhan, Omer Ridvan; Barut, Ibrahim

2007-04-01

Peritoneum has an intrinsic fibrinolytic activity that breaks the peritoneal adhesions. Ischemic peritoneal injuries interfere with this fibrinolytic activity. Local application of dexpanthenol, the alcohol form of pantothenic acid (vitamin B5) accelerates wound healing by increasing mitosis. We hypothesized that dexpanthenol would decrease peritoneal adhesions. In rats, antimesenteric border of cecum was abraded with gauze. No medication was given to the control group (n=15). Dexpanthenol was administered intraperitoneally (IP) (n=15, 25 mg/kg, before abdominal closure) or intravenously (IV) (n=15, 25 mg/kg, for 9 days after operation) in the experiment groups. On postoperative day 10, adhesions were graded; activities and concentrations of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), tPA/PAI-1 complex and hydroxyproline contents were determined in peritoneum. Adhesion formation was decreased in IP dexpanthenol group compared with control group (p=0.034). tPA concentration and activity and tPA/PAI-1 complex levels were increased in the treated groups compared to controls. PAI-1 levels were similar among the three groups. Peritoneal hydroxyproline levels were lower in animals receiving IV dexpanthenol compared with control animals and in addition, they remained unchanged in IP dexpanthenol treated group (p=0.009, p=0.84, respectively). Our results suggest that dexpanthenol administration through IP may reduce peritoneal adhesion formation probably by altering peritoneal fibrinolytic activity.

IL-12 Expressing oncolytic herpes simplex virus promotes anti-tumor activity and immunologic control of metastatic ovarian cancer in mice.

PubMed

Thomas, Eric D; Meza-Perez, Selene; Bevis, Kerri S; Randall, Troy D; Gillespie, G Yancey; Langford, Catherine; Alvarez, Ronald D

2016-10-27

Despite advances in surgical aggressiveness and conventional chemotherapy, ovarian cancer remains the most lethal cause of gynecologic cancer mortality; consequently there is a need for new therapeutic agents and innovative treatment paradigms for the treatment of ovarian cancer. Several studies have demonstrated that ovarian cancer is an immunogenic disease and immunotherapy represents a promising and novel approach that has not been completely evaluated in ovarian cancer. Our objective was to evaluate the anti-tumor activity of an oncolytic herpes simplex virus "armed" with murine interleukin-12 and its ability to elicit tumor-specific immune responses. We evaluated the ability of interleukin-12-expressing and control oncolytic herpes simplex virus to kill murine and human ovarian cancer cell lines in vitro. We also administered interleukin-12-expressing oncolytic herpes simplex virus to the peritoneal cavity of mice that had developed spontaneous, metastatic ovarian cancer and determined overall survival and tumor burden at 95 days. We used flow cytometry to quantify the tumor antigen-specific CD8 + T cell response in the omentum and peritoneal cavity. All ovarian cancer cell lines demonstrated susceptibility to oncolytic herpes simplex virus in vitro. Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus demonstrated a more robust tumor antigen-specific CD8 + T-cell immune response in the omentum (471.6 cells vs 33.1 cells; p = 0.02) and peritoneal cavity (962.3 cells vs 179.5 cells; p = 0.05). Compared to controls, mice treated with interleukin-12-expressing oncolytic herpes simplex virus were more likely to control ovarian cancer metastases (81.2 % vs 18.2 %; p = 0.008) and had a significantly longer overall survival (p = 0.02). Finally, five of 6 mice treated with interleukin-12-expressing oHSV had no evidence of metastatic tumor when euthanized at 6 months, compared to two of 4 mice treated with sterile phosphate buffer solution. Our pilot study demonstrates that an interleukin-12-expressing oncolytic herpes simplex virus effectively kills both murine and human ovarian cancer cell lines and promotes tumor antigen-specific CD8 + T-cell responses in the peritoneal cavity and omentum, leading to reduced peritoneal metastasis and improved survival in a mouse model.

Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells

PubMed Central

2013-01-01

Background Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear. Results We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release of IL-1β, IL-6, IL-8, and Vascular Endothelial Growth Factor (VEGF). Transcription and release of these proteins are inhibited in vitro using Anakinra, an IL-1 receptor antagonist that reduces these cytokines in a human peritoneal MM mouse xenograft model. Conclusions These novel data show that asbestos-induced priming and activation of the NLRP3 inflammasome triggers an autocrine feedback loop modulated via the IL-1 receptor in mesothelial cell type targeted in pleural infection, fibrosis, and carcinogenesis. PMID:23937860

A neurokinin 1 receptor antagonist decreases postoperative peritoneal adhesion formation and increases peritoneal fibrinolytic activity.

PubMed

Reed, Karen L; Fruin, A Brent; Gower, Adam C; Stucchi, Arthur F; Leeman, Susan E; Becker, James M

2004-06-15

Fibrous adhesions remain a major sequela of abdominal surgery. The proinflammatory peptide substance P (SP), known to participate in inflammatory events, may play a key role in adhesion formation. This hypothesis was tested by using an antagonist, CJ-12,255 (Pfizer), that blocks the binding of SP to the neurokinin 1 receptor (NK-1R). Adhesion formation was surgically induced in the peritoneum of rats receiving daily doses of the NK-1R antagonist (NK-1RA; 5.0 or 10.0 mg/kg per day) or saline. On postoperative day 7, both the low and high doses of NK-1RA significantly (P < 0.05) reduced adhesion formation by 45% and 53%, respectively, compared with controls. Subsequently, the effect of NK-1RA administration on peritoneal fibrinolytic activity was investigated to determine a potential mechanism for SP action in the peritoneum. Samples were collected from nonoperated controls and from animals 24 h postsurgery that were administered either NK-1RA or saline. Fibrinolytic activity in peritoneal fluid was assayed by zymography, and expression of tissue plasminogen activator (tPA) and plasminogen activator inhibitor 1, both regulators of fibrinolytic activity, was assessed in peritoneal tissue and fluid by RT-PCR and bioassay, respectively. NK-1RA administration led to a marked (P < 0.05) increase in tPA mRNA levels in peritoneal tissue compared with nonoperated and saline-administered animals. Likewise, NK-1RA administration significantly (P < 0.05) increased tPA in the peritoneal fluid. These data suggest that activation of the NK-1R promotes peritoneal adhesion formation by limiting fibrinolytic activity in the postoperative peritoneum, thus enabling fibrinous adhesions to persist.

MIF-driven activation of macrophages induces killing of intracellular Trypanosoma cruzi dependent on endogenous production of tumor necrosis factor, nitric oxide and reactive oxygen species.

PubMed

Cutrullis, Romina A; Petray, Patricia B; Corral, Ricardo S

2017-02-01

The proinflammatory cytokine macrophage migration inhibitory factor (MIF) is a key player in innate immunity. MIF has been considered critical for controlling acute infection by the protozoan Trypanosoma cruzi, but the underlying mechanisms are poorly understood. Our study aimed to analyze whether MIF could favor microbicidal activity of the macrophage, a site where T. cruzi grows and the initial effector cell against this parasite. Using murine macrophages infected in vitro, we examined the effect of MIF on their parasiticidal ability and attempted to identify inflammatory agents involved in MIF-induced protection. Our findings show that MIF is readily secreted from peritoneal macrophages upon T. cruzi infection. MIF activates both primary and J774 phagocytes boosting the endogenous production of tumor necrosis factor-alpha via mitogen-activated protein kinase p38 signaling, as well as the release of nitric oxide and reactive oxygen species, leading to enhanced pathogen elimination. MIF can also potentiate the effect of interferon-gamma on T. cruzi killing by J774 and mouse peritoneal macrophages, rendering these cells more competent in reducing intracellular parasite burden. The present results unveil a novel innate immune pathway that contributes to host defense and broaden our understanding of the regulation of inflammatory mediators implicated in early parasite containment that is decisive for resistance to T. cruzi infection. Copyright © 2016 Elsevier GmbH. All rights reserved.

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis.

PubMed

Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie

2015-12-01

♦ As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 - 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 - 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 - 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 - 0.94) and 0.39 (95% CI 0.20 - 0.75), respectively. ♦ Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. Copyright © 2015 International Society for Peritoneal Dialysis.

Multiple bidirectional alterations of phenotype and changes in proliferative potential during the in vitro and in vivo passage of clonal mast cell populations derived from mouse peritoneal mast cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanakura, Y.; Thompson, H.; Nakano, T.

1988-09-01

Mouse peritoneal mast cells (PMC) express a connective tissue-type mast cell (CTMC) phenotype, including reactivity with the heparin-binding fluorescent dye berberine sulfate and incorporation of (35S) sulfate predominantly into heparin proteoglycans. When PMC purified to greater than 99% purity were cultured in methylcellulose with IL-3 and IL-4, approximately 25% of the PMC formed colonies, all of which contained both berberine sulfate-positive and berberine sulfate-negative mast cells. When these mast cells were transferred to suspension culture, they generated populations that were 100% berberine sulfate-negative, a characteristic similar to that of mucosal mast cells (MMC), and that synthesized predominantly chondroitin sulfate (35S)more » proteoglycans. When ''MMC-like'' cultured mast cells derived from WBB6F1-+/+ PMC were injected into the peritoneal cavities of mast cell-deficient WBB6F1-W/Wv mice, the adoptively transferred mast cell population became 100% berberine sulfate-positive. In methylcellulose culture, these ''second generation PMC'' formed clonal colonies containing both berberine sulfate-positive and berberine sulfate-negative cells, but exhibited significantly less proliferative ability than did normal +/+ PMC. Thus, clonal mast cell populations initially derived from single PMC exhibited multiple and bidirectional alterations between CTMC-like and MMC-like phenotypes. However, this process was associated with a progressive diminution of the mast cells' proliferative ability.« less

Co-treatment with a C1B5 peptide of protein kinase Cγ and a low dose of gemcitabine strongly attenuated pancreatic cancer growth in mice through T cell activation.

PubMed

Ishiguro, Susumu; Kawabata, Atsushi; Zulbaran-Rojas, Alejandro; Monson, Kelsey; Uppalapati, Deepthi; Ohta, Naomi; Inui, Makoto; Pappas, Charalampos G; Tzakos, Andreas G; Tamura, Masaaki

2018-01-01

Although gemcitabine is an effective chemotherapeutic for pancreatic cancer, severe side effects often accompany its use. Since we have discovered that locally administered C1B domain peptides effectively control tumor growth without any side effects, the efficacy of co-treatment with this peptide and a low dose of gemcitabine on the growth of pancreatic cancer was examined. Two- and three-dimensional cell culture studies clarified that a co-treatment with C1B5 peptide and gemcitabine significantly attenuated growth of PAN02 mouse and PANC-1 human pancreatic cancer cells in 2D and 3D cultures. Although treatment with the low dose of gemcitabine alone (76%) or the C1B5 peptide alone (39%) inhibited tumor growth moderately, a co-treatment with C1B5 peptide and a low dose of gemcitabine markedly inhibited the growth of PAN02 autografts in the mouse peritoneal cavity (94% inhibition) without any noticeable adverse effect. The number of peritoneal cavity-infiltrating neutrophils and granzyme B + lymphocytes was significantly higher in the co-treatment group than in the control group. A significant increase of granzyme B mRNA expression was also detected in human T cells by the co-treatment. Taken together, the current study suggests that C1B5 peptide offers a remarkably effective combination treatment strategy to reduce side effects associated with gemcitabine, without losing its tumoricidal effect. Copyright © 2017 Elsevier Inc. All rights reserved.

MAPK/p38 regulation of cytoskeleton rearrangement accelerates induction of macrophage activation by TLR4, but not TLR3.

PubMed

Bian, Hongjun; Li, Feifei; Wang, Wenwen; Zhao, Qi; Gao, Shanshan; Ma, Jincai; Li, Xiao; Ren, Wanhua; Qin, Chengyong; Qi, Jianni

2017-11-01

Toll-like receptor 3 (TLR3) and TLR4 utilize adaptor proteins to activate mitogen‑activated protein kinase (MAPK), resulting in the acute but transient inflammatory response aimed at the clearance of pathogens. In the present study, it was demonstrated that macrophage activation by lipopolysaccharide (LPS) or poly(I:C), leading to changes in cell morphology, differed significantly between the mouse macrophage cell line RAW264.7 and mouse primary peritoneal macrophages. Moreover, the expression of α- and β-tubulin was markedly decreased following LPS stimulation. By contrast, α- and β-tubulin expression were only mildly increased following poly(I:C) treatment. However, the expression of β-actin and GAPDH was not significantly affected. Furthermore, it was verified that vincristine pretreatment abrogated the cytoskeleton rearrangement and decreased the synthesis and secretion of proinflammatory cytokines and migration of macrophages caused by LPS. Finally, it was observed that the MAPK/p38 signaling pathway regulating cytoskeleton rearrangement may participate in LPS‑induced macrophage cytokine production and migration. Overall, the findings of the present study indicated that MAPK/p38 regulation of the cytoskeleton, particularly tubulin proteins, plays an important role in LPS-induced inflammatory responses via alleviating the synthesis and secretion of proinflammatory cytokines and inhibiting the migration of macrophages.

Differential activation of peritoneal cells by subcutaneous treatment of rats with cryptococcal antigens.

PubMed

Baronetti, José L; Chiapello, Laura S; Garro, Ana P; Masih, Diana T

2009-08-01

Previous studies in our laboratory have shown that the subcutaneous pretreatment of rats with heat-killed cells (HKC) of Cryptococcus neoformans emulsified in complete Freund adjuvant (CFA) promotes protective immunity against an intraperitoneal challenge with C. neoformans. In contrast, subcutaneous treatment with the capsular polysaccharide (PSC) emulsified in CFA exacerbates the cryptococcal infection. The purpose of this study was to analyze the mechanisms involved in these phenomena. Adherent peritoneal cells from rats treated with HKC-CFA showed upregulated ED2, CD80, and CD86 expression; an increase in the level of production of anticryptococcal metabolites; and the enhanced production of interleukin-12 (IL-12) in comparison with the findings for cells from rats treated with CFA-phosphate-buffered saline (PBS). Adherent peritoneal cells from rats treated with PSC-CFA, however, also presented upregulated ED2, CD80, and CD86 expression compared to the level of expression for peritoneal cells from controls, but these cells showed an increase in arginase activity and decreased levels of production of IL-12 and tumor necrosis factor (TNF) compared with the activity and levels of production by peritoneal cells from CFA-PBS-treated rats. In addition, treatment with HKC-CFA resulted in a rise in the phagocytic and anticryptococcal activities of adherent peritoneal cells compared to those for control rats. However, adherent peritoneal cells from rats treated with PSC-CFA presented a reduction in anticryptococcal activity in comparison with that for cells from animals treated with CFA-PBS. These results show the differential activation between adherent peritoneal cells from HKC-CFA- and PSC-CFA-treated rats, with this differential activation at the primary site of infection possibly being responsible, at least in part, for the phenomena of protection and exacerbation observed in our model.

Microglial cells and peritoneal macrophages release activin A upon stimulation with Toll-like receptor agonists.

PubMed

Ebert, Sandra; Zeretzke, Moritz; Nau, Roland; Michel, Uwe

2007-02-21

Activin A levels are elevated in the cerebrospinal fluid (CSF) of patients with meningitis and in the sera of patients with sepsis. The source(s) of the elevated concentrations of activin A in CSF and serum have not yet been discovered. Here we demonstrate that primary mouse microglial cells and peritoneal macrophages release activin A after treatment with agonists of Toll-like receptor (TLR) 2, 4, and 9. These findings provide further evidence for a role of activin in the innate immune response and suggest that microglial cells and macrophages are a source of elevated activin A concentrations observed in the CSF during bacterial meningitis and in the systemic circulation during sepsis.

Interplay between Endometriosis and Pregnancy in a Mouse Model

PubMed Central

Bilotas, Mariela Andrea; Olivares, Carla Noemí; Ricci, Analía Gabriela; Baston, Juan Ignacio; Bengochea, Tatiana Soledad; Meresman, Gabriela Fabiana; Barañao, Rosa Inés

2015-01-01

Objectives To evaluate the effect of endometriosis on fertility and the levels of the IL-2 and IFN-γ in the peritoneal fluid in a mouse model; to evaluate the effect of pregnancy on endometriotic lesion growth, apoptosis and cell proliferation. Study Design Two month old C57BL/6 female mice underwent either a surgical procedure to induce endometriosis or a sham surgery. Four weeks after surgery mice were mated and sacrificed at day 18 of pregnancy. Number of implantation sites, fetuses and fetal weight were recorded. Endometriotic lesions were counted, measured, excised and fixed. Apoptosis and cell proliferation were evaluated in lesions by TUNEL and immunohistochemistry for PCNA respectively. Levels of IL-2 and IFN-γ were assessed by ELISA in the peritoneal fluid. Results Pregnancy rate (i.e. pregnant mice/N) decreased in mice with endometriosis. However there were no significant differences in resorption rate, litter size and pup weight between groups. IFN-γ augmented in endometriosis mice independently of pregnancy outcome. Additionally IFN-γ increased in pregnant endometriosis mice compared to pregnant sham animals. While IFN-γ increased in non pregnant versus pregnant mice in the sham group, IL-2 was increased in non pregnant mice in the endometriosis group. The size of endometriotic lesions increased in pregnant mice while apoptosis increased in the stroma and cell proliferation decreased in the epithelium of these lesions. Additionally, leukocyte infiltration, necrosis and decidualization were increased in the same lesions. Conclusions Pregnancy rate is reduced in this mouse model of endometriosis. Levels of IL-2 are increased in the peritoneal fluid of mice with endometriosis suggesting a role of this cytokine in infertility related to this disease. The size of endometriotic lesions is increased in pregnant mice; however pregnancy has a beneficial effect on lesions by decreasing cell proliferation and by increasing apoptosis, decidualization and necrosis. PMID:25915402

Low level laser therapy reduces acute lung inflammation in a model of pulmonary and extrapulmonary LPS-induced ARDS.

PubMed

Oliveira, Manoel Carneiro; Greiffo, Flávia Regina; Rigonato-Oliveira, Nicole Cristine; Custódio, Ricardo Wesley Alberca; Silva, Vanessa Roza; Damaceno-Rodrigues, Nilsa Regina; Almeida, Francine Maria; Albertini, Regiane; Lopes-Martins, Rodrigo Álvaro B; de Oliveira, Luis Vicente Franco; de Carvalho, Paulo de Tarso Camillo; Ligeiro de Oliveira, Ana Paula; Leal, Ernesto César P; Vieira, Rodolfo P

2014-05-05

The present study aimed to investigate the effects low level laser therapy (LLLT) in a LPS-induced pulmonary and extrapulmonary acute respiratory distress syndrome (ARDS) in BALB/c mice. Laser (830nm laser, 9J/cm(2), 35mW, 80s per point, 3 points per application) was applied in direct contact with skin, 1h after LPS administration. Mice were distributed in control (n=6; PBS), ARDS IT (n=7; LPS orotracheally 10μg/mouse), ARDS IP (n=7; LPS intra-peritoneally 100μg/mouse), ARDS IT+Laser (n=9; LPS intra-tracheally 10μg/mouse), ARDS IP+Laser (n=9; LPS intra-peritoneally 100μg/mouse). Twenty-four hours after last LPS administration, mice were studied for pulmonary inflammation by total and differential cell count in bronchoalveolar lavage (BAL), cytokines (IL-1beta, IL-6, KC and TNF-alpha) levels in BAL fluid and also by quantitative analysis of neutrophils number in the lung parenchyma. LLLT significantly reduced pulmonary and extrapulmonary inflammation in LPS-induced ARDS, as demonstrated by reduced number of total cells (p<0.001) and neutrophils (p<0.001) in BAL, reduced levels of IL-1beta, IL-6, KC and TNF-alpha in BAL fluid and in serum (p<0.001), as well as the number of neutrophils in lung parenchyma (p<0.001). LLLT is effective to reduce pulmonary inflammation in both pulmonary and extrapulmonary model of LPS-induced ARDS. Copyright © 2014 Elsevier B.V. All rights reserved.

Screening of In Vivo Activated Genes in Enterococcus faecalis during Insect and Mouse Infections and Growth in Urine

PubMed Central

Hanin, Aurelie; Sava, Irina; Bao, YinYin; Huebner, Johannes; Hartke, Axel; Auffray, Yanick; Sauvageot, Nicolas

2010-01-01

Enterococcus faecalis is part of the commensal microbiota of humans and its main habitat is the gastrointestinal tract. Although harmless in healthy individuals, E. faecalis has emerged as a major cause of nosocomial infections. In order to better understand the transformation of a harmless commensal into a life-threatening pathogen, we developed a Recombination-based In Vivo Expression Technology for E. faecalis. Two R-IVET systems with different levels of sensitivity have been constructed in a E. faecalis V583 derivative strain and tested in the insect model Galleria mellonella, during growth in urine, in a mouse bacteremia and in a mouse peritonitis model. Our combined results led to the identification of 81 in vivo activated genes. Among them, the ef_3196/7 operon was shown to be strongly induced in the insect host model. Deletion of this operonic structure demonstrated that this two-component system was essential to the E. faecalis pathogenic potential in Galleria. Gene ef_0377, induced in insect and mammalian models, has also been further analyzed and it has been demonstrated that this ankyrin-encoding gene was also involved in E. faecalis virulence. Thus these R-IVET screenings led to the identification of new E. faecalis factors implied in in vivo persistence and pathogenic potential of this opportunistic pathogen. PMID:20686694

Serum 25-Hydroxyvitamin D Level Could Predict the Risk for Peritoneal Dialysis-Associated Peritonitis

PubMed Central

Pi, Hai-Chen; Ren, Ye-Ping; Wang, Qin; Xu, Rong; Dong, Jie

2015-01-01

♦ Background: As an immune system regulator, vitamin D is commonly deficient among patients on peritoneal dialysis (PD), which may contribute to their impaired immune function and increased risk for PD-related peritonitis. In this study, we aimed to investigate whether vitamin D deficiency could predict the risk of peritonitis in a prospective cohort of patients on PD. ♦ Methods: We collected 346 prevalent and incident PD patients from 2 hospitals. Baseline demographic data and clinical characteristics were recorded. Serum 25-hydroxyvitamin D (25[OH]D) was measured at baseline and prior to peritonitis. The mean doses of oral active vitamin D used during the study period were also recorded. The outcome was the occurrence of peritonitis. ♦ Results: The mean age of patients and duration of PD were 58.95 ± 13.67 years and 28.45 (15.04 – 53.37) months, respectively. Baseline 25(OH)D level was 16.15 (12.13 – 21.16) nmol/L, which was closely associated with diabetic status, longer PD duration, malnutrition, and inflammation. Baseline serum 25(OH)D predicted the occurrence of peritonitis independently of active vitamin D supplementation with a hazard ratio (HR) of 0.94 (95% confidence interval [CI] 0.90 – 0.98) after adjusting for recognized confounders (age, gender, dialysis duration, diabetes, albumin, residual renal function, and history of peritonitis). Compared to the low tertile, middle and high 25(OH)D level tertiles were associated with a decreased risk for peritonitis with HRs of 0.54 (95% CI 0.31 – 0.94) and 0.39 (95% CI 0.20 – 0.75), respectively. ♦ Conclusions: Vitamin D deficiency evaluated by serum 25(OH)D rather than active vitamin D supplementation is closely associated with a higher risk of peritonitis. PMID:26224791

Therapeutic Efficacy of Alpha-RIT Using a (213)Bi-Anti-hCD138 Antibody in a Mouse Model of Ovarian Peritoneal Carcinomatosis.

PubMed

Derrien, Aurélie; Gouard, Sébastien; Maurel, Catherine; Gaugler, Marie-Hélène; Bruchertseifer, Frank; Morgenstern, Alfred; Faivre-Chauvet, Alain; Classe, Jean-Marc; Chérel, Michel

2015-01-01

Ovarian peritoneal carcinomatosis is a pathology for which effective cures are currently lacking. New research protocols seek to eradicate residual micrometastases following cytoreductive surgery by using hyperthermic intraperitoneal chemotherapy (HIPEC) or radioimmunotherapy (RIT). This study aims to first develop alpha-RIT using an anti-CD138 mAb radiolabeled with an alpha-emitter, bismuth-213 ((213)Bi-B-B4) and HIPEC in a nude mouse model and second to compare and combine these techniques. A murine model of postoperative ovarian peritoneal carcinomatosis was established. A pilot group of six mice received an intraperitoneal injection of luciferase-tagged SHIN-3 cells and bioluminescence was measured every day. Cytoreductive surgery was performed at day 14 (n = 4) and 29 (n = 2). Because the residual bioluminescence signal measured after surgery was equivalent to that obtained 3 days after the graft, HIPEC or alpha-RIT treatments were applied 3 days after the graft. Ten mice were treated by HIPEC with cisplatine (37.5 mg/mL), 11 with 7.4 MBq of (213)Bi-B-B4, seven with 11.1 MBq of (213)Bi-B-B4, and 10 mice were treated with the combined therapy (HIPEC + 7.4 MBq of (213)Bi-B-B4). Eleven mice received no treatment. Bioluminescence imaging and survival were assessed. Alpha-RIT 7.4 MBq and 11.1 MBq significantly improved survival (p = 0.0303 and p = 0.0070, respectively), whereas HIPEC and HIPEC + alpha-RIT treatments did not significantly ameliorate survival as compared to the control group. Survival was significantly increased by alpha-RIT treatment in mice with peritoneal carcinomatosis of ovarian origin; however, HIPEC alone or in combination with alpha-RIT had no significant effect.

Daily peritoneal administration of sodium pyrophosphate in a dialysis solution prevents the development of vascular calcification in a mouse model of uraemia.

PubMed

Riser, Bruce L; Barreto, Fellype Carvalho; Rezg, Raja; Valaitis, Paul W; Cook, Chyung S; White, Jeffrey A; Gass, Jerome H; Maizel, Julien; Louvet, Loic; Drueke, Tilman B; Holmes, Clifford J; Massy, Ziad A

2011-10-01

The high rate of cardiovascular mortality in patients with end-stage renal disease (ESRD) is a significant barrier to improved life expectancy. Unique in this population is the marked development and aggressive worsening of vascular calcification (VC). Pyrophosphate (PPi), an endogenous molecule, appears to naturally inhibit soft tissue calcification, but may be depressed in chronic kidney disease (CKD) and ESRD. Although once thought to be a promising therapeutic, PPi's very short half-life in circulation curtailed earlier studies. We tested the possibility that a slow, continuous entry of PPi into the circulation and prevention of VC might be achieved by daily peritoneal dialysis (PD). Pharmacokinetic studies were first carried out in rats with renal impairment resulting from a 5/6 nephrectomy. Efficacy studies were then performed in the apolipoprotein E gene knockout mouse model overlaid with CKD. PPi was delivered by means of a permanent peritoneal catheter in a solution simulating PD, but without the timed removal of spent dialysate. von Kossa's staining followed by semiquantitative morphological image processing, with separation of inside (intimal) and outside (presumed medial) lesions, was used to determine aortic root calcification. In comparison to an intravenous bolus, delivery of PPi in a PD solution resulted in a slower, extended delivery over >4 h. Next, the efficacy studies showed that a 6-day/week PD-simulated administration of PPi resulted in a dose-dependent inhibition of aortic calcification in both intimal and medial lesions. A dose-response effect on total aortic calcification was also documented, with a full inhibition seen at the highest dose. A limited peritoneal catheter-related inflammation was observed, as expected, and included the placebo-treated control groups. This inflammatory response could have masked a lower level PPi-specific adverse effect, but none was observed. Our findings suggest potential for PPi, administered during PD, to prevent the development of VC and to potentially extend the life of ESRD patients.

Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation.

PubMed

Mohamad, Saharuddin B; Nagasawa, Hideko; Uto, Yoshihiro; Hori, Hitoshi

2002-05-01

Alpha-N-acetyl galactosaminidase (alpha-NaGalase) has been reported to accumulate in serum of cancer patients and be responsible for deglycosylation of Gc protein, which is a precursor of GcMAF-mediated macrophage activation cascade, finally leading to immunosuppression in advanced cancer patients. We studied the biochemical characterization of alpha-NaGalase from several human tumor cell lines. We also examined its effect on the potency of GcMAF to activate mouse peritoneal macrophage to produce superoxide in GcMAF-mediated macrophage activation cascade. The specific activity of alpha-NaGalases from human colon tumor cell line HCT116, human hepatoma cell line HepG2, and normal human liver cells (Chang liver cell line) were evaluated using two types of substrates; GalNAc-alpha-PNP (exo-type substrate) and Gal-beta-GalNAc-alpha-PNP (endo-type substrate). Tumor-derived alpha-NaGalase having higher activity than normal alpha-NaGalase, had higher substrate specificity to the exo-type substrate than to the endo-type substrate, and still maintained its activity at pH 7. GcMAF enhance superoxide production in mouse macrophage, and pre-treatment of GcMAF with tumor cell lysate reduce the activity. We conclude that tumor-derived alpha-NaGalase is different in biochemical characterization compared to normal alpha-NaGalase from normal Chang liver cells. In addition, tumor cell-derived alpha-NaGalase decreases the potency of GcMAF on macrophage activation.

The PPARβ/δ agonist GW501516 attenuates peritonitis in peritoneal fibrosis via inhibition of TAK1-NFκB pathway in rats.

PubMed

Su, Xuesong; Zhou, Guangyu; Wang, Yanqiu; Yang, Xu; Li, Li; Yu, Rui; Li, Detian

2014-06-01

Peritoneal fibrosis is a common consequence of long-term peritoneal dialysis (PD), and peritonitis is a factor in its onset. Agonist-bound peroxisome proliferator-activated receptors (PPARs) function as key regulators of energy metabolism and inflammation. Here, we examined the effects of PPARβ/δ agonist GW501516 on peritonitis in a rat peritoneal fibrosis model. Peritoneal fibrosis secondary to inflammation was induced into uremic rats by daily injection of Dianeal 4.25% PD solutions along with six doses of lipopolysaccharide before commencement of GW501516 treatment. Normal non-uremic rats served as control, and all rats were fed with a control diet or a GW501516-containing diet. Compared to control group, exposure to PD fluids caused peritoneal fibrosis that was accompanied by increased mRNA levels of monocyte chemoattractant protein-1, tumor necrotic factor-α, and interleukin-6 in the uremic rats, and these effects were prevented by GW501516 treatment. Moreover, GW501516 was found to attenuate glucose-stimulated inflammation in cultured rat peritoneal mesothelial cells via inhibition of transforming growth factor-β-activated kinase 1 (TAK1), and nuclear factor kappa B (NFκB) signaling pathway (TAK1-NFκB pathway), a main inflammation regulatory pathway. In conclusion, inhibition of TAK1-NFκB pathway with GW501516 may represent a novel therapeutic approach to ameliorate peritonitis-induced peritoneal fibrosis for patients on PD.

Immunoenhancement of Edible Fungal Polysaccharides (Lentinan, Tremellan, and Pachymaran) on Cyclophosphamide-Induced Immunosuppression in Mouse Model

PubMed Central

Zhang, Qian; Cong, Renhuai; Hu, Minghua; Yang, Xiangliang

2017-01-01

Fungal polysaccharides display a variety of important biological activities, including anti-inflammatory, antitumor, and immune-stimulating activities. The aim of present study was to investigate the immunomodulatory effect of fungal polysaccharides on cyclophosphamide-induced immunosuppression in mice. Mice were pretreated orally with lentinan, tremellan, pachymaran, or a mixture of the three, respectively. The results showed that pretreatments with polysaccharides significantly increased the thymus index in cyclophosphamide-induced immunosuppression mice. The level of the cytokine IL-10 in sera of cyclophosphamide-induced mice was decreased after pretreatments of polysaccharides. Flow cytometry results showed that pretreatments with polysaccharides enhanced the phagocytosis of peritoneal macrophages in mice. The increased levels of serum antibody IgG and IgM were observed in the groups pretreated with polysaccharides. Our work demonstrated that the treatment of polysaccharides elicited strong immune activity and a protective effect against cyclophosphamide-induced immunosuppression. PMID:29358974

Assessment of the cytotoxicity of a mineral trioxide aggregate-based sealer with respect to macrophage activity.

PubMed

Braga, Julia Mourão; Oliveira, Ricardo Reis; de Castro Martins, Renata; Vieira, Leda Quercia; Sobrinho, Antonio Paulino Ribeiro

2015-10-01

To assess the influence of co-culture with mineral trioxide aggregate (MTA) and MTA Fillapex (FLPX) on the viability, adherence, and phagocytosis activity of peritoneal macrophages from two mouse strains. Cellular viability, adherence, and phagocytosis of Saccharomyces boulardii were assayed in the presence of capillaries containing MTA and MTA Fillapex. The data were analyzed using parametric (Student's t) and non-parametric (Mann-Whitney) tests. FLPX was severely cytotoxic and decreased cell viability, adherence, and phagocytic activity of both macrophage subtypes. Cells that were treated with MTA Fillapex remained viable (>80%) for only 4 h after stimulation. Macrophages from C57BL/6 mice presented higher adherence and higher phagocytic activity compared with macrophages from BALB/c mice. Comparison of MTA and FLPX effects upon macrophages indicates that FLPX may impair macrophage activity and viability, while MTA seems to increase phagocytic activity. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species.

PubMed

Shen, Fengge; Tang, Xudong; Cheng, Wei; Wang, Yang; Wang, Chao; Shi, Xiaochen; An, Yanan; Zhang, Qiaoli; Liu, Mingyuan; Liu, Bo; Yu, Lu

2016-01-18

The successful treatment of bacterial infections is the achievement of a synergy between the host's immune defences and antibiotics. Here, we examined whether fosfomycin (FOM) could improve the bactericidal effect of phagocytes, and investigated the potential mechanisms. FOM enhanced the phagocytosis and extra- or intracellular killing of S. aureus by phagocytes. And FOM enhanced the extracellular killing of S. aureus in macrophage (MФ) and in neutrophils mediated by extracellular traps (ETs). ET production was related to NADPH oxidase-dependent reactive oxygen species (ROS). Additionally, FOM increased the intracellular killing of S. aureus in phagocytes, which was mediated by ROS through the oxidative burst process. Our results also showed that FOM alone induced S. aureus producing hydroxyl radicals in order to kill the bacterial cells in vitro. In a mouse peritonitis model, FOM treatment increased the bactericidal extra- and intracellular activity in vivo, and FOM strengthened ROS and ET production from peritoneal lavage fluid ex vivo. An IVIS imaging system assay further verified the observed in vivo bactericidal effect of the FOM treatment. This work may provide a deeper understanding of the role of the host's immune defences and antibiotic interactions in microbial infections.

Fosfomycin enhances phagocyte-mediated killing of Staphylococcus aureus by extracellular traps and reactive oxygen species

PubMed Central

Shen, Fengge; Tang, Xudong; Cheng, Wei; Wang, Yang; Wang, Chao; Shi, Xiaochen; An, Yanan; Zhang, Qiaoli; Liu, Mingyuan; Liu, Bo; Yu, Lu

2016-01-01

The successful treatment of bacterial infections is the achievement of a synergy between the host’s immune defences and antibiotics. Here, we examined whether fosfomycin (FOM) could improve the bactericidal effect of phagocytes, and investigated the potential mechanisms. FOM enhanced the phagocytosis and extra- or intracellular killing of S. aureus by phagocytes. And FOM enhanced the extracellular killing of S. aureus in macrophage (MФ) and in neutrophils mediated by extracellular traps (ETs). ET production was related to NADPH oxidase-dependent reactive oxygen species (ROS). Additionally, FOM increased the intracellular killing of S. aureus in phagocytes, which was mediated by ROS through the oxidative burst process. Our results also showed that FOM alone induced S. aureus producing hydroxyl radicals in order to kill the bacterial cells in vitro. In a mouse peritonitis model, FOM treatment increased the bactericidal extra- and intracellular activity in vivo, and FOM strengthened ROS and ET production from peritoneal lavage fluid ex vivo. An IVIS imaging system assay further verified the observed in vivo bactericidal effect of the FOM treatment. This work may provide a deeper understanding of the role of the host’s immune defences and antibiotic interactions in microbial infections. PMID:26778774

Lysozyme activates Enterococcus faecium to induce necrotic cell death in macrophages.

PubMed

Gröbner, Sabine; Fritz, Evelyn; Schoch, Friederike; Schaller, Martin; Berger, Alexander C; Bitzer, Michael; Autenrieth, Ingo B

2010-10-01

Enterococci are commensal organisms in the alimentary tract. However, they can cause a variety of life-threatening infections, especially in nosocomial settings. We hypothesized that induction of cell death might enable these facultative pathogenic bacteria to evade the innate immune response and to cause infections of their host. We demonstrate that E. faecium when exposed to lysozyme induces cell death in macrophages in vitro and in vivo. Flow cytometric analyses of J774A.1 macrophages infected with E. faecium revealed loss of cell membrane integrity indicated by uptake of propidium iodide and decrease of the inner mitochondrial transmembrane potential DeltaPsi(m). Inhibition of caspases, treatment of macrophages with cytochalasin D, or rifampicin did not prevent cells from dying, suggesting cell death mechanisms that are independent of caspase activation, bacterial uptake, and intracellular bacterial replication. Characteristics of necrotic cell death were demonstrated by both lack of procaspase 3 activation and cell shrinkage, electron microscopy, and release of lactate dehydrogenase. Pretreatment of E. faecium with lysozyme and subsequently with broad spectrum protease considerably reduced cell death, suggesting that a bacterial surface protein is causative for cell death induction. Moreover, in a mouse peritonitis model we demonstrated that E. faecium induces cell death of peritoneal macrophages in vivo. Altogether, our results show that enterococci, under specific conditions such as exposure to lysozyme, induce necrotic cell death in macrophages, which might contribute to disseminated infections by these facultative pathogenic bacteria.

Plasminogen activator inhibitor-1 is an independent prognostic factor of ovarian cancer and IMD-4482, a novel plasminogen activator inhibitor-1 inhibitor, inhibits ovarian cancer peritoneal dissemination.

PubMed

Nakatsuka, Erika; Sawada, Kenjiro; Nakamura, Koji; Yoshimura, Akihito; Kinose, Yasuto; Kodama, Michiko; Hashimoto, Kae; Mabuchi, Seiji; Makino, Hiroshi; Morii, Eiichi; Yamaguchi, Yoichi; Yanase, Takeshi; Itai, Akiko; Morishige, Ken-Ichirou; Kimura, Tadashi

2017-10-27

In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous adenocarcinoma, PAI-1 expression was an independent prognostic factor. The effect of a novel PAI-1 inhibitor, IMD-4482, on ovarian cancer cell lines was assessed and its therapeutic potential was examined using a xenograft mouse model of ovarian cancer. IMD-4482 inhibited in vitro cell adhesion to vitronectin in PAI-1-positive ovarian cancer cells, followed by the inhibition of extracellular signal-regulated kinase and focal adhesion kinase phosphorylation through dissociation of the PAI-urokinase receptor complex from integrin αVβ3. IMD-4482 caused G0/G1 cell arrest and inhibited the proliferation of PAI-1-positive ovarian cancer cells. In the xenograft model, IMD-4482 significantly inhibited peritoneal dissemination with the reduction of PAI-1 expression and the inhibition of focal adhesion kinase phosphorylation. Collectively, the functional inhibition of PAI-1 significantly inhibited ovarian cancer progression, and targeting PAI-1 may be a potential therapeutic strategy in ovarian cancer.

Plasminogen activator inhibitor-1 is an independent prognostic factor of ovarian cancer and IMD-4482, a novel plasminogen activator inhibitor-1 inhibitor, inhibits ovarian cancer peritoneal dissemination

PubMed Central

Nakatsuka, Erika; Sawada, Kenjiro; Nakamura, Koji; Yoshimura, Akihito; Kinose, Yasuto; Kodama, Michiko; Hashimoto, Kae; Mabuchi, Seiji; Makino, Hiroshi; Morii, Eiichi; Yamaguchi, Yoichi; Yanase, Takeshi; Itai, Akiko; Morishige, Ken-ichirou; Kimura, Tadashi

2017-01-01

In the present study, the therapeutic potential of targeting plasminogen activator inhibitor-1 (PAI-1) in ovarian cancer was tested. Tissues samples from 154 cases of ovarian carcinoma were immunostained with anti-PAI-1 antibody, and the prognostic value was analyzed. Among the samples, 67% (104/154) showed strong PAI-1 expression; this was significantly associated with poor prognosis (progression-free survival: 20 vs. 31 months, P = 0.0033). In particular, among patients with stage II-IV serous adenocarcinoma, PAI-1 expression was an independent prognostic factor. The effect of a novel PAI-1 inhibitor, IMD-4482, on ovarian cancer cell lines was assessed and its therapeutic potential was examined using a xenograft mouse model of ovarian cancer. IMD-4482 inhibited in vitro cell adhesion to vitronectin in PAI-1-positive ovarian cancer cells, followed by the inhibition of extracellular signal-regulated kinase and focal adhesion kinase phosphorylation through dissociation of the PAI-urokinase receptor complex from integrin αVβ3. IMD-4482 caused G0/G1 cell arrest and inhibited the proliferation of PAI-1-positive ovarian cancer cells. In the xenograft model, IMD-4482 significantly inhibited peritoneal dissemination with the reduction of PAI-1 expression and the inhibition of focal adhesion kinase phosphorylation. Collectively, the functional inhibition of PAI-1 significantly inhibited ovarian cancer progression, and targeting PAI-1 may be a potential therapeutic strategy in ovarian cancer. PMID:29163796

Neutrophilia, gelatinase release and microvascular leakage induced by human mast cell tryptase in a mouse model: Lack of a role of protease-activated receptor 2 (PAR2).

PubMed

Khedr, M E M S; Abdelmotelb, A M; Pender, S L F; Zhou, X; Walls, A F

2018-05-01

Tryptase, the most abundant protease of the human mast cell, has been implicated as a key mediator of allergic inflammation that acts through activation of PAR2. To investigate the contribution of PAR2 in the pro-inflammatory actions mediated by tryptase in a mice model. We have injected recombinant human βII-tryptase into the peritoneum of PAR2-deficient and wild-type C57BL/6 mice. After 6, 12 and 24 hours, mice were killed, peritoneal lavage performed and inflammatory changes investigated. Tryptase stimulated an increase in neutrophil numbers in the peritoneum, but responses did not differ between PAR2-deficient and wild-type mice. Heat inactivation of tryptase or pre-incubation with a selective tryptase inhibitor reduced neutrophilia, but neutrophil accumulation was not elicited with a peptide agonist of PAR2 (SLIGRL-NH 2 ). Zymography indicated that tryptase stimulated the release of matrix metalloproteinases (MMP) 2 and 9 in the peritoneum of both mouse strains. Studies involving immunomagnetic isolation of neutrophils suggested that neutrophils represent the major cellular source of tryptase-induced MMP2 and MMP9. At 24 hours after tryptase injection, there was increased microvascular leakage as indicated by high levels of albumin in peritoneal lavage fluid, and this appeared to be partially abolished by heat-inactivating tryptase or addition of a protease inhibitor. There was no corresponding increase in levels of histamine or total protein. The extent of tryptase-induced microvascular leakage or gelatinase release into the peritoneum did not differ between PAR2-deficient and wild-type mice. Our findings indicate that tryptase is a potent stimulus for neutrophil accumulation, MMP release and microvascular leakage. Although these actions required an intact catalytic site, the primary mechanism of tryptase in vivo would appear to involve processes independent of PAR2. © 2018 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Expression of the Homeobox Gene HOXA9 in Ovarian Cancer Induces Peritoneal Macrophages to Acquire an M2 Tumor-Promoting Phenotype

PubMed Central

Ko, Song Yi; Ladanyi, Andras; Lengyel, Ernst; Naora, Honami

2015-01-01

Tumor-associated macrophages (TAMs) exhibit an M2 macrophage phenotype that suppresses anti-tumor immune responses and often correlates with poor outcomes in patients with cancer. Patients with ovarian cancer frequently present with peritoneal carcinomatosis, but the mechanisms that induce naïve peritoneal macrophages into TAMs are poorly understood. In this study, we found an increased abundance of TAMs in mouse i.p. xenograft models of ovarian cancer that expressed HOXA9, a homeobox gene that is associated with poor prognosis in patients with ovarian cancer. HOXA9 expression in ovarian cancer cells stimulated chemotaxis of peritoneal macrophages and induced macrophages to acquire TAM-like features. These features included induction of the M2 markers, CD163 and CD206, and the immunosuppressive cytokines, IL-10 and chemokine ligand 17, and down-regulation of the immunostimulatory cytokine, IL-12. HOXA9-mediated induction of TAMs was primarily due to the combinatorial effects of HOXA9-induced, tumor-derived transforming growth factor-β2 and chemokine ligand 2 levels. High HOXA9 expression in clinical specimens of ovarian cancer was strongly associated with increased abundance of TAMs and intratumoral T-regulatory cells and decreased abundance of CD8+ tumor-infiltrating lymphocytes. Levels of immunosuppressive cytokines were also elevated in ascites fluid of patients with tumors that highly expressed HOXA9. HOXA9 may, therefore, stimulate ovarian cancer progression by promoting an immunosuppressive microenvironment via paracrine effects on peritoneal macrophages. PMID:24332016

A Novel Pharmacologic Activity of Ketorolac for Therapeutic Benefit in Ovarian Cancer Patients.

PubMed

Guo, Yuna; Kenney, S Ray; Cook, Linda; Adams, Sarah F; Rutledge, Teresa; Romero, Elsa; Oprea, Tudor I; Sklar, Larry A; Bedrick, Edward; Wiggins, Charles L; Kang, Huining; Lomo, Lesley; Muller, Carolyn Y; Wandinger-Ness, Angela; Hudson, Laurie G

2015-11-15

We previously identified the R-enantiomer of ketorolac as an inhibitor of the Rho-family GTPases Rac1 and Cdc42. Rac1 and Cdc42 regulate cancer-relevant functions, including cytoskeleton remodeling necessary for tumor cell adhesion and migration. This study investigated whether administration of racemic (R,S) ketorolac after ovarian cancer surgery leads to peritoneal distribution of R-ketorolac, target GTPase inhibition in cells retrieved from the peritoneal cavity, and measureable impact on patient outcomes. Eligible patients had suspected advanced-stage ovarian, fallopian tube or primary peritoneal cancer. Secondary eligibility was met when ovarian cancer was confirmed and optimally debulked, an intraperitoneal port was placed, and there were no contraindications for ketorolac administration. R- and S-ketorolac were measured in serum and peritoneal fluid, and GTPase activity was measured in peritoneal cells. A retrospective study correlated perioperative ketorolac and ovarian cancer-specific survival in ovarian cancer cases. Elevated expression and activity of Rac1 and Cdc42 was detected in ovarian cancer patient tissues, confirming target relevance. Ketorolac in peritoneal fluids was enriched in the R-enantiomer and peritoneal cell GTPase activity was inhibited after ketorolac administration when R-ketorolac was at peak levels. After adjusting for age, AJCC stage, completion of chemotherapy, and neoadjuvant therapy, women given perioperative ketorolac had a lower hazard of death (HR, 0.30; 95% confidence interval, 0.11-0.88). Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, potentially contributing to the observed survival benefit in women who received ketorolac. ©2015 American Association for Cancer Research.

A novel pharmacologic activity of ketorolac for therapeutic benefit in ovarian cancer patients

PubMed Central

Guo, Yuna; Kenney, S. Ray; Cook, Linda; Adams, Sarah F.; Rutledge, Teresa; Romero, Elsa; Oprea, Tudor I.; Sklar, Larry A.; Bedrick, Edward; Wiggins, Charles L.; Kang, Huining; Lomo, Lesley; Muller, Carolyn Y.; Wandinger-Ness, Angela; Hudson, Laurie G.

2015-01-01

PURPOSE We previously identified the R-enantiomer of ketorolac as an inhibitor of the Rho-family GTPases Rac1 and Cdc42. Rac1 and Cdc42 regulate cancer-relevant functions including cytoskeleton remodeling necessary for tumor cell adhesion and migration. This study investigated whether administration of racemic (R,S) ketorolac after ovarian cancer surgery leads to peritoneal distribution of R-ketorolac, target GTPase inhibition in cells retrieved from the peritoneal cavity, and measureable impact on patient outcomes. EXPERIMENTAL DESIGN Eligible patients had suspected advanced stage ovarian, fallopian tube or primary peritoneal cancer. Secondary eligibility was met when ovarian cancer was confirmed and optimally debulked, an intraperitoneal port was placed, and there were no contraindications for ketorolac administration. R- and S-ketorolac were measured in serum and peritoneal fluid, and GTPase activity was measured in peritoneal cells. A retrospective study correlated peri-operative ketorolac and ovarian cancer-specific survival in ovarian cancer cases. RESULTS Elevated expression and activity of Rac1 and Cdc42 was detected in ovarian cancer patient tissues, confirming target relevance. Ketorolac in peritoneal fluids was enriched in the R-enantiomer and peritoneal cell GTPase activity was inhibited after ketorolac administration when R-ketorolac was at peak levels. After adjusting for age, AJCC stage, completion of chemotherapy, and neo-adjuvant therapy, women given peri-operative ketorolac had a lower hazard of death (Hazard Ratio=0.30 [95%CI 0.11–0.88]). CONCLUSION Ketorolac has a novel pharmacologic activity conferred by the R-enantiomer and R-ketorolac achieves sufficient levels in the peritoneal cavity to inhibit Rac1 and Cdc42, potentially contributing to the observed survival benefit in women who received ketorolac. PMID:26071482

Garlic compounds modulate macrophage and T-lymphocyte functions.

PubMed

Lau, B H; Yamasaki, T; Gridley, D S

1991-06-01

Organosulfur compounds of garlic have been shown to inhibit growth of animal tumors and to modulate the activity of diverse chemical carcinogens. There is also evidence that garlic may modulate antitumor immunity. In this study, we determined the effects of an aqueous garlic extract and a protein fraction isolated from the extract on the chemiluminescent oxidative burst of the murine J774 macrophage cell line and thioglycollate-elicited peritoneal macrophages obtained from BALB/c mice. T-lymphocyte activity was determined using mouse splenocytes incubated with phytohemagglutinin, labeled with [3H]-thymidine and assayed for lymphoproliferation. Significant dose-related augmentation of oxidative burst was observed with garlic extract and the protein fraction. The protein fraction also enhanced the T-lymphocyte blastogenesis. The data suggest that garlic compounds may serve as biological response modifiers by augmenting macrophage and T-lymphocyte functions.

Rosiglitazone, a Peroxisome Proliferator-Activated Receptor (PPAR)-γ Agonist, Attenuates Inflammation Via NF-κB Inhibition in Lipopolysaccharide-Induced Peritonitis.

PubMed

Zhang, Yun-Fang; Zou, Xun-Liang; Wu, Jun; Yu, Xue-Qing; Yang, Xiao

2015-12-01

We assessed the anti-inflammatory effect of peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, in a lipopolysaccharide (LPS)-induced peritonitis rat model. LPS was intraperitoneally injected into rats to establish peritonitis model. Male Sprague-Dawley (SD) rats were assigned to normal saline (the solvent of LPS), LPS, rosiglitazone plus LPS, and rosiglitazone alone. A simple peritoneal equilibrium test was performed with 20 ml 4.25 % peritoneal dialysis fluid. We measured the leukocyte count in dialysate and ultrafiltration volume. Peritoneal membrane histochemical staining was performed, and peritoneal thickness was assessed. CD40 and intercellular adhesion molecule-1 messenger RNA (ICAM-1 mRNA) levels in rat visceral peritoneum were detected by reverse transcription (RT)-PCR. IL-6 in rat peritoneal dialysis effluent was measured using enzyme-linked immunosorbent assay. The phosphorylation of NF-κB-p65 and IκBα was analyzed by Western blot. LPS administration resulted in increased peritoneal thickness and decreased ultrafiltration volume. Rosiglitazone pretreatment significantly decreased peritoneal thickness. In addition to CD40 and ICAM-1 mRNA expression, the IL-6, p-p65, and p-IκBα protein expressions were enhanced in LPS-administered animals. Rosiglitazone pretreatment significantly decreased ICAM-1 mRNA upregulation, secretion of IL-6 protein, and phosphorylation of NF-κB-p65 and IκBα without decreasing CD40 mRNA expression. Rosiglitazone has a protective effect in peritonitis, simultaneously decreasing NF-κB phosphorylation, suggesting that NF-κB signaling pathway mediated peritoneal inflammation induced by LPS. PPAR-γ might be considered a potential therapeutic target against peritonitis.

Thalidomide suppresses sclerosing encapsulating peritonitis in a rat experimental model.

PubMed

Mondello, Stefania; Mazzon, Emanuela; Di Paola, Rosanna; Crisafulli, Concetta; Mondello, Paolo; Buemi, Michele; Aloisi, Carmelo; Cuzzocrea, Salvatore

2009-09-01

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.

Combination therapy of 15-epi-lipoxin A4 with antibiotics protects mice from Escherichia coli-induced sepsis*.

PubMed

Ueda, Tomomi; Fukunaga, Koichi; Seki, Hiroyuki; Miyata, Jun; Arita, Makoto; Miyasho, Taku; Obata, Toru; Asano, Koichiro; Betsuyaku, Tomoko; Takeda, Junzo

2014-04-01

Inflammation occurs along with infection during sepsis. 15-Epi-lipoxin A4 has protective and resolving effects in experimental models of infection. In this study, we examined the effects of 15-epi-lipoxin A4 combined with antibiotics on Escherichia coli-induced peritonitis. Prospective experimental study. University research laboratory. Male C57BL/6 mice. Mice were injected with E. coli to induce peritonitis and were given either 15-epi-lipoxin A4 (1 μg/mouse) or placebo (saline) with antibiotics (ceftazidime). The effects of 15-epi-lipoxin A4 on peritoneal cell populations, bacterial burden, and cytokine production were assessed. Survival rates were observed for up to 7 days. In addition, we examined the effects of 15-epi-lipoxin A4 on peritoneal macrophages stimulated with lipopolysaccharide, CpG DNA, or live E. coli. Treatment with 15-epi-lipoxin A4 significantly reduced the number of neutrophils in the peritoneum, inhibited production of cytokines and chemokines, and decreased bacterial load in the serum. Combined treatment of 15-epi-lipoxin A4 with antibiotics significantly improved survival in E. coli-infected mice. 15-Epi-lipoxin A4 also attenuated the production of interleukin-6 and tumor necrosis factor-α by lipopolysaccharide- or CpG DNA-stimulated peritoneal macrophages. Furthermore, 15-epi-lipoxin A4 combined with antibiotics synergistically reduced the production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages stimulated with live E. coli. 15-Epi-lipoxin A4 combined with antibiotics attenuated systemic inflammation, inhibited bacteria dissemination, and improved survival in E. coli-infected mice. The reduced production of interleukin-6 and tumor necrosis factor-α by peritoneal macrophages suggested that 15-epi-lipoxin A4 blocked the initial proinflammatory response. Taken together, these data suggested that 15-epi-lipoxin A4 combined with antibiotics was beneficial in regulating the proinflammatory response in sepsis without exacerbating infection.

Inhibition of IRAK-4 activity for rescuing endotoxin LPS-induced septic mortality in mice by lonicerae flos extract.

PubMed

Park, Sun Hong; Roh, Eunmiri; Kim, Hyun Soo; Baek, Seung-Il; Choi, Nam Song; Kim, Narae; Hwang, Bang Yeon; Han, Sang-Bae; Kim, Youngsoo

2013-12-13

Lonicerae flos extract (HS-23) is a clinical candidate currently undergoing Phase I trial in lipopolysaccharide (LPS)-injected healthy human volunteers, but its molecular basis remains to be defined. Here, we investigated protective effects of HS-23 or its major constituents on Escherichia coli LPS-induced septic mortality in mice. Intravenous treatment with HS-23 rescued LPS-intoxicated C57BL/6J mice under septic conditions, and decreased the levels of cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and high-mobility group box-1 (HMGB-1) in the blood. Chlorogenic acid (CGA) and its isomers were assigned as major constituents of HS-23 in the protection against endotoxemia. As a molecular mechanism, HS-23 or CGA isomers inhibited endotoxin LPS-induced autophosphorylation of the IL-1 receptor-associated kinase 4 (IRAK-4) in mouse peritoneal macrophages as well as the kinase activity of IRAK-4 in cell-free reactions. HS-23 consequently suppressed downstream pathways critical for LPS-induced activation of nuclear factor (NF)-κB or activating protein 1 (AP-1) in the peritoneal macrophages. HS-23 also inhibited various toll-like receptor agonists-induced nitric oxide (NO) production, and down-regulated LPS-induced expression of NF-κB/AP-1-target inflammatory genes in the cells. Taken together, HS-23 or CGA isomers exhibited anti-inflammatory therapy against LPS-induced septic mortality in mice, at least in part, mediated through the inhibition of IRAK-4. Copyright © 2013 Elsevier Inc. All rights reserved.

Histone deacetylase 7 promotes Toll-like receptor 4-dependent proinflammatory gene expression in macrophages.

PubMed

Shakespear, Melanie R; Hohenhaus, Daniel M; Kelly, Greg M; Kamal, Nabilah A; Gupta, Praveer; Labzin, Larisa I; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A; Reid, Robert C; Irvine, Katharine M; Fairlie, David P; Sweet, Matthew J

2013-08-30

Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target.

Histone Deacetylase 7 Promotes Toll-like Receptor 4-dependent Proinflammatory Gene Expression in Macrophages*

PubMed Central

Shakespear, Melanie R.; Hohenhaus, Daniel M.; Kelly, Greg M.; Kamal, Nabilah A.; Gupta, Praveer; Labzin, Larisa I.; Schroder, Kate; Garceau, Valerie; Barbero, Sheila; Iyer, Abishek; Hume, David A.; Reid, Robert C.; Irvine, Katharine M.; Fairlie, David P.; Sweet, Matthew J.

2013-01-01

Broad-spectrum inhibitors of histone deacetylases (HDACs) constrain Toll-like receptor (TLR)-inducible production of key proinflammatory mediators. Here we investigated HDAC-dependent inflammatory responses in mouse macrophages. Of the classical Hdacs, Hdac7 was expressed at elevated levels in inflammatory macrophages (thioglycollate-elicited peritoneal macrophages) as compared with bone marrow-derived macrophages and the RAW264 cell line. Overexpression of a specific, alternatively spliced isoform of Hdac7 lacking the N-terminal 22 amino acids (Hdac7-u), but not the Refseq Hdac7 (Hdac7-s), promoted LPS-inducible expression of Hdac-dependent genes (Edn1, Il-12p40, and Il-6) in RAW264 cells. A novel class IIa-selective HDAC inhibitor reduced recombinant human HDAC7 enzyme activity as well as TLR-induced production of inflammatory mediators in thioglycollate-elicited peritoneal macrophages. Both LPS and Hdac7-u up-regulated the activity of the Edn1 promoter in an HDAC-dependent fashion in RAW264 cells. A hypoxia-inducible factor (HIF) 1 binding site in this promoter was required for HDAC-dependent TLR-inducible promoter activity and for Hdac7- and HIF-1α-mediated trans-activation. Coimmunoprecipitation assays showed that both Hdac7-u and Hdac7-s interacted with HIF-1α, whereas only Hdac7-s interacted with the transcriptional repressor CtBP1. Thus, Hdac7-u positively regulates HIF-1α-dependent TLR signaling in macrophages, whereas an interaction with CtBP1 likely prevents Hdac7-s from exerting this effect. Hdac7 may represent a potential inflammatory disease target. PMID:23853092

Norcantharidin Facilitates LPS-Mediated Immune Responses by Up-Regulation of AKT/NF-κB Signaling in Macrophages

PubMed Central

Li, Ruimei; Tan, Binghe; Han, Honghui; Liu, Mingyao; Qian, Min; Du, Bing

2012-01-01

Norcantharidin (NCTD), a demethylated analog of cantharidin, is a common used clinical drug to inhibit proliferation and metastasis of cancer cells. But the role of NCTD in modulating immune responses remains unknown. Here, we investigated the function and mechanism of NCTD in regulation of TLR4 associated immune response in macrophages. We evaluated the influence of NCTD on host defense against invaded pathogens by acute peritonitis mouse model, ELISA, Q-PCR, nitrite quantification, phagocytosis assay and gelatin zymography assay. Our data showed that the survival and the serum concentrations of IL-6 and TNF-α were all enhanced by NCTD significantly in peritonitis mouse model. Accordingly, LPS-induced cytokine, nitric oxide and MMP-9 production as well as the phagocytosis of bacteria were all up-regulated by NCTD in a dose dependent manner in both RAW264.7 cells and bone marrow-derived macrophages (BMMs). Then we further analyzed TLR4 associated signaling pathway by Western blot, Immunofluorescence and EMSA in the presence or absence of LPS. The phosphorylation of AKT and p65 at serine 536 but not serine 468 was enhanced obviously by NCTD in a dose dependent manner, whereas the degradation of IκBα was little effected. Consequently, the nuclear translocation and DNA binding ability of NF-κB was also increased by NCTD obviously in RAW264.7 cells. Our results demonstrated that NCTD could facilitate LPS-mediated immune response through promoting the phosphorylation of AKT/p65 and transcriptional activity of NF-κB, thus reprofiling the traditional anti-tumor drug NCTD as a novel immune regulator in promoting host defense against bacterial infection. PMID:22984593

Activated T-cell Therapy, Low-Dose Aldesleukin, and Sargramostim in Treating Patients With Ovarian, Fallopian Tube, or Primary Peritoneal Cancer That is Stage III-IV, Refractory, or Recurrent

ClinicalTrials.gov

2016-02-15

Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Serous Tumor; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Effects of Opsonization and Gamma Interferon on Growth of Brucella Melitensis 16M in Mouse Peritoneal Macrophages In Vitro

DTIC Science & Technology

2000-01-01

bacterial CFU (Fig. 3). Macrophages cultured without brucel - lae or cultured with brucellae but without IFN-7 made ɘ.3 nmol of nitrite/200 JJLI well...receptors used for the uptake of nonopsonized brucel - lae are unknown. Synergy between the receptor for the Fc domain of immunoglobulin G (FcR) and

Anti-tumor effect of Coriolus versicolor methanol extract against mouse B16 melanoma cells: in vitro and in vivo study.

PubMed

Harhaji, Lj; Mijatović, S; Maksimović-Ivanić, D; Stojanović, I; Momcilović, M; Maksimović, V; Tufegdzić, S; Marjanović, Z; Mostarica-Stojković, M; Vucinić, Z; Stosić-Grujicić, S

2008-05-01

Numerous studies have shown immunostimulatory and anti-tumor effects of water and standardized aqueous ethanol extracts derived from the medicinal mushroom, Coriolus versicolor, but the biological activity of methanol extracts has not been examined so far. In the present study we investigated the anti-tumor effect of C. versicolor methanol extract (which contains terpenoids and polyphenols) on B16 mouse melanoma cells both in vitro and in vivo. In vitro treatment of the cells with the methanol extract (25-1600 microg/ml) reduced melanoma cell viability in a dose-dependent manner. Furthermore, in the presence of the methanol extract (200 microg/ml, concentration IC(50)) the proliferation of B16 cells was arrested in the G(0)/G(1) phase of the cell cycle, followed by both apoptotic and secondary necrotic cell death. In vivo methanol extract treatment (i.p. 50 mg/kg, for 14 days) inhibited tumor growth in C57BL/6 mice inoculated with syngeneic B16 tumor cells. Moreover, peritoneal macrophages collected 21 days after tumor implantation from methanol extract-treated animals exerted stronger tumoristatic activity ex vivo than macrophages from control melanoma-bearing mice. Taken together, our results demonstrate that C. versicolor methanol extract exerts pronounced anti-melanoma activity, both directly through antiproliferative and cytotoxic effects on tumor cells and indirectly through promotion of macrophage anti-tumor activity.

Extracts of Crinum latifolium inhibit the cell viability of mouse lymphoma cell line EL4 and induce activation of anti-tumour activity of macrophages in vitro.

PubMed

Nguyen, Hoang-Yen T; Vo, Bach-Hue T; Nguyen, Lac-Thuy H; Bernad, Jose; Alaeddine, Mohamad; Coste, Agnes; Reybier, Karine; Pipy, Bernard; Nepveu, Françoise

2013-08-26

Crinum latifolium L. (CL) leaf extracts have been traditionally used in Vietnam and are now used all over the world for the treatment of prostate cancer. However, the precise cellular mechanisms of the action of CL extracts remain unclear. To examine the effects of CL samples on the anti-tumour activity of peritoneal murine macrophages. The properties of three extracts (aqueous, flavonoid, alkaloid), one fraction (alkaloid), and one pure compound (6-hydroxycrinamidine) obtained from CL, were studied (i) for redox capacities (DPPH and bleaching beta-carotene assays), (ii) on murine peritoneal macrophages (MTT assay) and on lymphoma EL4-luc2 cells (luciferine assay) for cytotoxicity, (iii) on macrophage polarization (production of ROS and gene expression by PCR), and (iv) on the tumoricidal functions of murine peritoneal macrophages (lymphoma cytotoxicity by co-culture with syngeneic macrophages). The total flavonoid extract with a high antioxidant activity (IC50=107.36 mg/L, DPPH assay) showed an inhibitory action on cancer cells. Alkaloid extracts inhibited the proliferation of lymphoma cells either by directly acting on tumour cells or by activating of the tumoricidal functions of syngeneic macrophages. The aqueous extract induced mRNA expression of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin 6 (IL-6) indicating differentiation of macrophages into pro-inflammatory M1 polarized macrophages. The total flavonoid, alkaloid extracts and an alkaloid fraction induced the expression of the formyl peptide receptor (FPR) on the surface of the polarized macrophages that could lead to the activation of macrophages towards the M1 phenotype. Aqueous and flavonoid extracts enhanced NADPH quinine oxido-reductase 1 (NQO1) mRNA expression in polarized macrophages which could play an important role in cancer chemoprevention. All the samples studied were non-toxic to normal living cells and the pure alkaloid tested, 6-hydroxycrinamidine, was not active in any of the models investigated. Our results indicate that CL extracts and alkaloid fraction (but not pure 6-hydroxycrinamidine) inhibit the proliferation of lymphoma cells in multiple pathways. Our results are in accordance with traditional usage and encourage further studies and in vivo assays. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis.

PubMed

Combet, S; Miyata, T; Moulin, P; Pouthier, D; Goffin, E; Devuyst, O

2000-04-01

Long-term peritoneal dialysis (PD) is associated with alterations in peritoneal permeability and loss of ultrafiltration. These changes originate from increased peritoneal surface area, but the morphologic and molecular mechanisms involved remain unknown. The hypothesis that modifications of activity and/or expression of nitric oxide synthase (NOS) isozymes might play a role in these modifications, via enhanced local production of nitric oxide, was tested in this study. NOS activities were measured by the L-citrulline assay in peritoneal biopsies from seven control subjects, eight uremic patients immediately before the onset of PD, and 13 uremic patients on short-term (<18 mo, n = 6) or long-term(>18 mo, n = 7) PD. Peritoneal NOS activity is increased fivefold in long-term PD patients compared with control subjects. In uremic patients, NOS activity is positively correlated with the duration of PD. Increased NOS activity is mediated solely by Ca(2+)-dependent NOS and, as shown by immunoblotting, an upregulation of endothelial NOS. The biologic relevance of increased NOS in long-term PD was demonstrated by enhanced nitrotyrosine immunoreactivity and a significant increase in vascular density and endothelial area in the peritoneum. Immunoblotting and immunostaining studies demonstrated an upregulation of vascular endothelial growth factor (VEGF) mostly along the endothelium lining peritoneal blood vessels in long-term PD patients. In the latter, VEGF colocalized with the advanced glycation end product pentosidine deposits. These data provide a morphologic (angiogenesis and increased endothelial area) and molecular (enhanced NOS activity and endothelial NOS upregulation) basis for explaining the permeability changes observed in long-term PD. They also support the implication of local advanced glycation end product deposits and liberation of VEGF in that process.

Houttuynia cordata Thunb. volatile oil exhibited anti-inflammatory effects in vivo and inhibited nitric oxide and tumor necrosis factor-α production in LPS-stimulated mouse peritoneal macrophages in vitro.

PubMed

Li, Weifeng; Fan, Ting; Zhang, Yanmin; Fan, Te; Zhou, Ping; Niu, Xiaofeng; He, Langchong

2013-11-01

Houttuynia cordata Thunb. (HC) is a medicinal herb that generally used in traditional Chinese medicine for treating allergic inflammation. The present study investigated the inhibitory effect of the volatile oil from HC Thunb. on animal models of inflammation and the production of inflammatory mediators in vivo and in vitro. In vivo, xylene-induced mouse ear edema, formaldehyde-induced paw edema and carrageenan-induced mice paw edema were significantly decreased by HC volatile oil. HC volatile oil showed pronounced inhibition of prostaglandin (PG) E2 and malondialdehyde production in the edematous exudates. In vitro exposure of mouse resident peritoneal macrophages to 1, 10, 100 and 1000 µg/mL of HC volatile oil significantly suppressed lipopolysaccharide (LPS)-stimulated production of NO and tumor necrosis factor-α (TNF-α) in a dose-dependent manner. Exposure to HC volatile oil had no effect on cell viability and systemic toxicity. Furthermore, HC volatile oil inhibited the production of NO and TNF-α by down-regulating LPS-stimulated iNOS and TNF-α mRNA expression. Western blot analysis showed that HC volatile oil attenuated LPS-stimulated synthesis of iNOS and TNF-α protein in the macrophages, in parallel. These findings add a novel aspect to the biological profile of HC and clarify its anti-inflammatory mechanism. Copyright © 2012 John Wiley & Sons, Ltd.

Conjugation of tetanus toxoid with Salmonella typhimurium PTCC 1735 O-specific polysaccharide and its effects on production of opsonizing antibodies in a mouse model.

PubMed

Jazani, Nima Hosseini; Worobec, Elizabeth; Shahabi, Shahram; Nejad, Ghorban Behzadian

2005-04-01

Serious enteric and extra-intestinal infections with Salmonella typhimurium are very common in many human populations. Phagocytosis is the main defense mechanism against this bacterium; however, the unique structure of S. typhimurium lipopolysaccharide (LPS) makes it resistant to opsonization by complement components. In the present study, the S. typhimurium LPS O-chain was purified and conjugated with tetanus toxoid and the effects of the conjugated vaccine (O-specific polysaccharide tetanus toxoid (O-SP-TT)) on induction of specific antibodies were investigated in a mouse model. In vitro assays measuring phagocytosis in the presence of opsonizing antibodies were performed. Three subcutaneous injections of the O-SP-TT conjugate conferred protection against the intraperitoneal challenge with S. typhimurium and the LD50 was greater for immunized animals than for controls. The mean number of ingested S. typhimirium / mouse peritoneal cell in the presence of sera obtained from immunized mice with purified O-chain, O-SP-TT conjugate, heat-killed bacteria, and negative control were 6.96, 14.24, 15.96, and 6.67, respectively. In summary, we developed an O-SP-TT conjugate that induced opsonizing antibodies that increased phagocytosis, as determined by in vitro assays. In addition, chemiluminescence results, an indicator of oxidative burst, indicated that peritoneal cells respond better to live S. typhimurium cells in the presence of sera obtained from O-SP-TT conjugate immunized mice.

Antioxidant status in experimental peritonitis: effects of alpha tocopherol and taurolin.

PubMed

Konukoglu, D; Iynem, H; Ziylan, E

1999-03-01

The role of oxidative stress and antioxidant defences in inflammation-induced organ injury is not clearly understood. We determined the effects of Escherichia coli (E. coli) peritonitis in rats on peritoneum lipid peroxidation and antioxidant defences. Tissue malondialdehyde (MDA) levels were measured to determine the free radical-induced lipid peroxidation in peritonitis. Tissue glutathione (GSH) levels, and activities of GSH-peroxidase, GSH-reductase and superoxide dismutase were examined to show antioxidant status. We also examined the effects of alpha-tocopherol (20 mg kg-1 body weight) as antioxidant and taurolin (200 mg kg-1 body weight) as chemotherapeutic agents on the oxidant stress and antioxidant defence. The treatment agents and E. coli were administrated intraperitoneally. Animals were killed at 2 h after the onset symptoms and then the peritoneum were obtained. Untreated rats with peritonitis had significantly higher MDA levels and significantly lower antioxidant activity than that of the control animals. Treatment of alpha-tocopherol and taurolin decreased the antioxidant activity and improved the antioxidant status. Pretreatment with alpha-tocopherol for 3 days prior to the induction of peritonitis (IP) and administration of taurolin at the time of the IP were more effective than treatment with alpha-tocopherol at the time of the IP and pretreatment of taurolin, respectively. These results are consistent with the idea that an oxidant/antioxidant imbalance is involved in animal peritonitis. Uses of alpha-tocopherol and taurolin in peritonitis were effective in decreasing the oxidative stress of tissue during peritonitis. Copyright 1999 The Italian Pharmacological Society.

Activation of the cholinergic anti-inflammatory pathway ameliorates postoperative ileus in mice.

PubMed

The, Frans O; Boeckxstaens, Guy E; Snoek, Susanne A; Cash, Jenna L; Bennink, Roel; Larosa, Gregory J; van den Wijngaard, Rene M; Greaves, David R; de Jonge, Wouter J

2007-10-01

We previously showed that intestinal inflammation is reduced by electrical stimulation of the efferent vagus nerve, which prevents postoperative ileus in mice. We propose that this cholinergic anti-inflammatory pathway is mediated via alpha7 nicotinic acetylcholine receptors expressed on macrophages. The aim of this study was to evaluate pharmacologic activation of the cholinergic anti-inflammatory pathway in a mouse model for postoperative ileus using the alpha7 nicotinic acetylcholine receptor-agonist AR-R17779. Mice were pretreated with vehicle, nicotine, or AR-R17779 20 minutes before a laparotomy (L) or intestinal manipulation (IM). Twenty-four hours thereafter gastric emptying was determined using scintigraphy and intestinal muscle inflammation was quantified. Nuclear factor-kappaB transcriptional activity and cytokine production was assayed in peritoneal macrophages. Twenty-four hours after surgery IM led to a delayed gastric emptying compared with L (gastric retention: L(saline) 14% +/- 4% vs IM(saline) 38% +/- 10%, P = .04). Pretreatment with AR-R17779 prevented delayed gastric emptying (IM(AR-R17779) 15% +/- 4%, P = .03). IM elicited inflammatory cell recruitment (L(saline) 50 +/- 8 vs IM(saline) 434 +/- 71 cells/mm(2), P = .001) which was reduced by AR-R17779 pretreatment (IM(AR-R17779) 231 +/- 32 cells/mm(2), P = .04). An equimolar dose of nicotine was not tolerated. Subdiaphragmal vagotomy did not affect the anti-inflammatory properties of AR-R17779. In peritoneal macrophages, both nicotinic agonists reduced nuclear factor kappaB transcriptional activity and proinflammatory cytokine production, with nicotine being more effective than AR-R17779. AR-R17779 treatment potently prevents postoperative ileus, whereas toxicity limits nicotine administration to ineffective doses. Our data further imply that nicotinic inhibition of macrophage activation may involve other receptors in addition to alpha7 nicotinic acetylcholine receptor.

Heat stable antigen (mouse CD24) supports myeloid cell binding to endothelial and platelet P-selectin.

PubMed

Aigner, S; Ruppert, M; Hubbe, M; Sammar, M; Sthoeger, Z; Butcher, E C; Vestweber, D; Altevogt, P

1995-10-01

P-selectin is a Ca(2+)-dependent lectin that participates in leukocyte adhesion to vascular endothelium and platelets. Myeloid cells and a subset of T lymphocytes express carbohydrate ligands at the cell surface. Previously, we suggested that heat stable antigen (HSA/mouse CD24), an extensively glycosylated cell surface molecule on many mouse cells, is a ligand for P-selectin. Here we show that HSA mediates the binding of monocytic cells and neutrophils to P-selectin. The monocytic cell lines ESb-MP and J774, peritoneal exudate cells, and bone marrow neutrophils could bind to lipopolysaccharide-activated bend3 endothelioma cells under rotation-induced shear forces and this binding was inhibited by mAb to P-selectin and HSA. Blocking was weak at room temperature but more efficient at 4 degrees C when integrin-mediated binding was decreased. Also the adhesion of neutrophils to stimulated platelets expressing P-selectin was blocked by HSA- and P-selectin-specific mAb. Latex beads coated with purified HSA from myeloid cells bound to activated endothelioma cells or platelets, and the binding was similarly blocked by mAb to P-selectin and HSA respectively. The HSA-coated beads were stained with P-selectin-IgG, very weakly with L-selectin-IgG but not with E-selectin-IgG. The staining was dependent on divalent cations and treatment with endoglycosidase F or neuraminidase indicated that sialylated N-linked glycans were recognized. The presence of these glycans was confirmed by biosynthetic labeling studies. Our data suggest that HSA, in addition to the recently identified 160 kDa glycoprotein ligand on mouse neutrophils, belongs to a group of monospecific P-selectin ligands on myeloid cells.

Inhibition of neutrophil and monocyte recruitment by endogenous and exogenous lipocortin 1

PubMed Central

Getting, Stephen J; Flower, Roderick J; Perretti, Mauro

1997-01-01

The role played by endogenous lipocortin 1 in the anti-migratory action exerted by dexamethasone (Dex) on monocyte recruitment in an in vivo model of acute inflammation was investigated by use of several neutralizing polyclonal antibodies raised against lipocortin 1 or a lipocortin 1-derived N-terminus peptide (peptide Ac2-26). The efficacy of peptide Ac2-26 in inhibiting monocyte and polymorphonuclear leucocyte (PMN) recruitment was also tested.Intraperitoneal (i.p.) injection of zymosan A (1 mg) produced a time-dependent cell accumulation into mouse peritoneal cavities which followed a typical profile of acute inflammation: PMN influx was maximal at 4 h post-zymosan (between 15 and 20×106 cells per mouse), and this was followed by an accumulation of monocytes which peaked at the 24 h time-point (between 10 and 15×106 cells per mouse).Dex administration to mice reduced zymosan-induced 4 h PMN infiltration and 24 h monocyte accumulation with similar efficacy: approximately 50% of inhibition of recruitment of both cell types was achieved at the dose of 30 μg per mouse (∼1 mg kg−1, subcutaneously (s.c.)). Maximal inhibitions of 64% and 67% on PMN and monocyte recruitment, respectively, were measured after a dose of 100 μg per mouse (∼3 mg kg−1, s.c.).Dex (30 μg s.c.) inhibited monocyte (53%) and PMN (69%) accumulation in response to zymosan application in mice which had been treated with a non-immune sheep serum (50 μl s.c.). In contrast, the steroid was no longer active in reducing cell accumulation in mice which had been passively immunized against full length human recombinant lipocortin 1 (serum LCS3), or against lipocortin 1 N-terminus peptide.Treatment of mice with vinblastine (1 mg kg−1, intravenously (i.v.)) produced a remarkable leucopenia as assessed 24 h after administration. This was accompanied by a 60% reduction in 4 h-PMN influx, and by a 27% reduction in 24 h-monocyte accumulation, measured after zymosan administration. The inhibitory effect of Dex on monocyte recruitment was not significantly modified in vinblastine-treated mice, with 36% and 57% of inhibition calculated at the dose of 30 μg Dex, and 70% and 60% of inhibition at 100 μg Dex, in vehicle- and vinblastine-treated mice, respectively.Treatment of mice with peptide Ac2-26 dose-dependently attenuated PMN influx at 4 h post-zymosan with a significant effect at 100 μg per mouse (45% of inhibition, n=9, P<0.05) and a maximal effect of 61% inhibition at the highest dose tested of 200 μg s.c. (n=14, P<0.05). No effect of peptide Ac2-26 (200 μg s.c.) was seen on zymosan-induced 24 h monocyte recruitment. In contrast, administration of 200 μg peptide Ac2-26 every 6 h was effective in reducing the number of monocytes harvested from the inflamed peritoneal cavities at 24 h post-zymosan: 9.40±0.58×106 monocytes per mouse (n=13) and 5.74±0.34 monocytes per mouse (n=14) in vehicle- and peptide Ac2-26-treated mice, respectively (P<0.05).Finally, peptide Ac2-26 produced a concentration-dependent inhibition of the rate of phagocytosis of mouse resident peritoneal macrophages as measured by flow cytometry, with a maximal reduction of 34% at the highest concentration tested of 100 μg ml−1 (n=8 experiments performed in duplicate; P<0.05).In conclusion, this study suggests that in vivo monocyte recruitment during acute inflammation is, at least in part, under the negative modulatory control of endogenous lipocortin 1 (as seen after administration of Dex by using the specific antisera) and exogenous lipocortin 1 mimetics (as observed with peptide Ac2-26). In addition to the neutrophil, we can now propose that the monocyte also can be a target for the in vivo anti-inflammatory action of lipocortin 1. PMID:9134220

Inflammatory effects of the toxic cyanobacterium Geitlerinema amphibium.

PubMed

Dogo, Camila Ranzatto; Bruni, Fernanda Miriane; Elias, Fabiana; Rangel, Marisa; Pantoja, Patricia Araujo; Sant'anna, Célia Leite; Lima, Carla; Lopes-Ferreira, Monica; de Carvalho, Luciana Retz

2011-11-01

Toxic cyanobacteria in public water reservoirs may cause severe health issues for livestock and human beings. Geitlerinema amphibium, which is frequently found in São Paulo City's drinking water supplies, showed toxicity in the standard mouse bioassay, while displaying signs of intoxication and post-mortem findings different from those showed by animals intoxicated by known cyanotoxins. We report here the alterations caused by G. amphibium methanolic extract on mouse microcirculatory network, as seen by in vivo intravital microscopy, besides observations on leukocyte migration, cytokine quantitation, and results of toxicological essays. Our data showed that G. amphibium methanolic extract displayed time- and dose-dependent pro-inflammatory activity, and that at lower doses [125 and 250 mg/kg body weight (b.w.)] increased the leukocyte rolling, caused partial venular stasis, as well as induced an increase in leukocyte counts in the peripheral blood and peritoneal washings. At higher doses (500 and 1000 mg/kg b.w.), the extract caused ischemic injury leading to animal death. As confirmed by mass spectrometric studies and polymyxin B test, the G. amphibium methanolic extract did not contain lipopolysaccharides. Copyright © 2011 Elsevier Ltd. All rights reserved.

Fat-associated lymphoid cluster in Cyprinus carpio: Characterisation and its relation with peritoneal haemangiosarcoma.

PubMed

Madera-Sandoval, Ruth L; Reyes-Maldonado, Elba; Dzul-Caamal, Ricardo; Gallegos-Rangel, Esperanza; Domínguez-López, María Lilia; García-Latorre, Ethel; Vega-López, Armando

2015-06-01

FALC cells are natural helper cells producing Th2-type cytokines, which express c-kit, Sca-1, IL7R and CD45 in mouse and human. These cells are involved in allergic responses and contribute to the inflammatory reactions of adipose tissue; however, a lack of information prevails about the presence of these cells in other species. The aim of the study was to identify and characterise FALC cells in the common carp (Cyprinus carpio) using immunohistochemistry and molecular biology techniques as well as to explore their relationships with their microenvironment. Histological description of the FALC was performed using H&E and polyclonal antibodies were used against cell-surface markers such as c-kit, Sca-1 and CD45. Furthermore, gene expression of c-kit, Sca-1 and IL7R was assessed. C. carpio FALC cells express the same surface markers reported in FALC of the mouse at both the pre- and post-transcriptional level. By exposure to the soluble fraction of helminths, FALC cells produce abundant Th2 cytokines (IL-5, IL-6 and IL-13) but do not synthesise IL-1α. Additionally, FALC cells probably participate in vascular remodelling of the intestine vessels, inducing tumours because a malignant haemangiosarcoma in the peritoneal cavity was found. In this tumour, abundant FALC with their characteristic cell-surface markers were detected. The findings of this study suggest the involvement of some proto-oncogenes such as c-kit and Sca-1, and the deregulation of Src kinases modulated by CD45 present in C. carpio FALC with the ontogeny of peritoneal haemangiosarcoma in this fish species. Copyright © 2015 Elsevier Ltd. All rights reserved.

Increased 13-hydroxyoctadecadienoic acid content in lipopolysaccharide stimulated macrophages.

PubMed

Schade, U F; Burmeister, I; Engel, R

1987-09-15

Endotoxin-stimulated mouse peritoneal macrophages were found to contain 13-hydroxyoctadecadienoic acid, which was released upon alkaline hydrolysis of the cells. Compared to untreated cells, incubation with LPS increased the content of 13-hydroxyoctadecadienoic acid in macrophage hydrolysates to about 8-fold. Analysis of the material on chiralphase HPLC revealed that it consisted prevalently of 13(S)-hydroxyoctadecadienoic acid. This indicates its enzymatic origine.

Photoimmunotherapy of Gastric Cancer Peritoneal Carcinomatosis in a Mouse Model

PubMed Central

Sato, Kazuhide; Choyke, Peter L.; Kobayashi, Hisataka

2014-01-01

Photoimmunotherapy (PIT) is a new cancer treatment that combines the specificity of antibodies for targeting tumors with the toxicity induced by photosensitizers after exposure to near infrared (NIR) light. We performed PIT in a model of disseminated gastric cancer peritoneal carcinomatosis and monitored efficacy with in vivo GFP fluorescence imaging. In vitro and in vivo experiments were conducted with a HER2-expressing, GFP-expressing, gastric cancer cell line (N87-GFP). A conjugate comprised of a photosensitizer, IR-700, conjugated to trastuzumab (tra-IR700), followed by NIR light was used for PIT. In vitro PIT was evaluated by measuring cytotoxicity with dead staining and a decrease in GFP fluorescence. In vivo PIT was evaluated in a disseminated peritoneal carcinomatosis model and a flank xenograft using tumor volume measurements and GFP fluorescence intensity. In vivo anti-tumor effects of PIT were confirmed by significant reductions in tumor volume (at day 15, p<0.0001 vs. control) and GFP fluorescence intensity (flank model: at day 3, PIT treated vs. control p<0.01 and peritoneal disseminated model: at day 3 PIT treated vs. control, p<0.05). Cytotoxic effects in vitro were shown to be dependent on the light dose and caused necrotic cell rupture leading to GFP release and a decrease in fluorescence intensity in vitro. Thus, loss of GFP fluorescence served as a useful biomarker of cell necrosis after PIT. PMID:25401794

Lactobacillus johnsonii HY7042 ameliorates Gardnerella vaginalis-induced vaginosis by killing Gardnerella vaginalis and inhibiting NF-κB activation.

PubMed

Joo, Hyun-Min; Hyun, Yang-Jin; Myoung, Kil-Sun; Ahn, Young-Tae; Lee, Jung-Hee; Huh, Chul-Sung; Han, Myung Joo; Kim, Dong-Hyun

2011-11-01

Hydrogen peroxide-producing lactic acid bacteria (LAB) were isolated from women's vaginas and their anti-inflammatory effects against Gardnerella vaginalis-induced vaginosis were examined in β-estradiol-immunosuppressed mice. Oral and intravaginal treatment with five LABs significantly decreased viable G. vaginalis numbers in vaginal cavities and myeloperoxidase activity in mouse vaginal tissues. Of the LABs examined, Lactobacillus johnsonii HY7042 (LJ) most potently inhibited G. vaginalis-induced vaginosis. This LAB also inhibited the expressions of IL-1β, IL-6, TNF-α, COX-2, and iNOS, and the activation of NF-κB in vaginal tissues, but increased IL-10 expression. Orally administered LJ (0.2×10(8) CFU/mouse) also inhibited the expression of TNF-α by 91.7% in β-estradiol-immunosuppressed mice intraperitoneally injected with LPS. However, it increased IL-10 expression by 63.3% in these mice. Furthermore, LJ inhibited the expressions of the pro-inflammatory cytokines, TNF-α and IL-1β, and the activation of NF-κB in lipopolysaccharide-stimulated peritoneal macrophages. LJ also killed G. vaginalis attached with and without HeLa cells. These findings suggest that LJ inhibits bacterial vaginosis by inhibiting the expressions of COX-2, iNOS, IL-1β, and TNF-α by regulating NF-κB activation and by killing G. vaginalis, and that LJ could ameliorate bacterial vaginosis. Copyright © 2011 Elsevier B.V. All rights reserved.

Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production.

PubMed

Uto, Yoshihiro; Kawai, Tomohito; Sasaki, Toshihide; Hamada, Ken; Yamada, Hisatsugu; Kuchiike, Daisuke; Kubo, Kentaro; Inui, Toshio; Mette, Martin; Tokunaga, Ken; Hayakawa, Akio; Go, Akiteru; Oosaki, Tomohiro

2015-08-01

Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Citral and eugenol modulate DNA damage and pro-inflammatory mediator genes in murine peritoneal macrophages.

PubMed

Porto, Marilia de Paula; da Silva, Glenda Nicioli; Luperini, Bruno Cesar Ottoboni; Bachiega, Tatiana Fernanda; de Castro Marcondes, João Paulo; Sforcin, José Maurício; Salvadori, Daisy Maria Fávero

2014-11-01

Citral and eugenol have been broadly studied because of their anti-inflammatory, antioxidant and antiparasitic potentials. In this study, the effects of citral (25, 50 and 100 µg/mL) and eugenol (0.31, 0.62, 1.24 and 2.48 µg/mL) on the expression (RT-PCR) of the pro-inflammatory mediator genes NF-κB1, COX-2 and TNF-α were evaluated in mouse peritoneal macrophages with or without activation by a bacterial lipopolysaccharide (LPS). Additionally, the genotoxic potentials of two compounds and their capacities to modulate the DNA damage induced by doxorubicin (DXR) were investigated using the comet assay. The data revealed that neither citral nor eugenol changed COX-2, NF-κB1 or TNF-α expression in resting macrophages. However, in LPS-activated cells, citral induced the hypoexpression of COX-2 (100 µg/mL) and TNF-α (50 and 100 µg/mL). Hypoexpression of TNF-α was also detected after cellular exposure to eugenol at the highest concentration (2.48 µg/mL). Both compounds exhibited genotoxic potential (citral at 50 and 100 µg/mL and eugenol at all concentrations) but also showed chemopreventive effects, in various treatment protocols. Both citral and eugenol might modulate inflammatory processes and DXR-induced DNA damage, but the use of these compounds must be viewed with caution because they are also able to induce primary DNA lesions.

HILIC quantification of oenotheralanosterol A and B from Oenothera biennis and their suppression of IL-6 and TNF-α expression in mouse macrophages.

PubMed

Singh, Rashmi; Trivedi, Priyanka; Bawankule, Dnyaneshwar Umrao; Ahmad, Ateeque; Shanker, Karuna

2012-05-07

Evening primrose (Oenothera biennis L.) is a wild medicinal herb of Central American origin that is now globally widespread. Its traditional uses include treatment of rheumatoid arthritis and premenopausal pain both of which have an inflammatory component. The present study demonstrates the in vitro anti-inflammatory activity of three Oenothera biennis compounds. Oenotheralanosterol A and B (Oen-A & Oen-B) along with gallic acid (GA) were isolated and characterized using column chromatography and NMR. The compounds were tested with LPS stimulated peritoneal mouse macrophages assaying for suppression of IL-6, TNF-α and NO synthesis. An HILIC method for the simultaneous quantitation of GA, Oen-A, and Oen-B in Oenothera biennis plant material was also developed as a means of monitoring quality of plant material. Significant inhibition of TNF-α and IL-6 by GA, Oen-A and Oen-B was observed (p<0.05). Inhibition was concentration dependent and no synergistic or antagonistic effect on pro-inflammatory cytokines was found when used in combination (1:1) (p>0.05). The HILIC analysis method was validated using Oenothera biennis root. The study demonstrates the anti-inflammatory activity of Oenothera biennis root compounds and supports its traditional use in arthritis management. Active anti-inflammatory compounds were identified and quantified by the HILIC method. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cuadrado, Irene; Cidre, Florencia; Herranz, Sandra

Labdane derivatives obtained from the diterpenoid labdanediol suppressed NO and PGE{sub 2} production in LPS-stimulated RAW 264.7 macrophages. However, mechanisms involved in these inhibitory effects are not elucidated. In this study, we investigated the signaling pathways involved in the anti-inflammatory effects of labdanolic acid methyl ester (LAME) in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. This effect involved the inhibition of NOS-2 and COX-2 gene expression, acting at the transcription level. Examination of the effects of the diterpene on NF-κB signaling showedmore » that LAME inhibits the phosphorylation of IκBα and IκBβ, preventing their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signaling was also observed. A further experiment revealed that LAME inhibited the phosphorylation of transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1), an upstream signaling molecule required for IKK and mitogen-activated protein kinases (MAPKs) activation. Inflammatory cytokines such as IL-6, TNF-α and IP-10 were downregulated in the presence of this compound after stimulation with LPS. Additionally, LAME also improved survival in a mouse model of endotoxemia and reduced the circulatory levels of cytokines (IL-6, TNF-α). In conclusion, these results indicate that labdane diterpene LAME significantly attenuates the pro-inflammatory response induced by LPS both in vivo and in vitro. Highlights: ► LAME reduced the production of NO and PGE{sub 2} in LPS-activated macrophages. ► IL-6, TNF-α and IP-10 were also inhibited by LAME. ► Inhibition of TAK-1 activation is the mechanism involved in this process. ► LAME improved survival in a mouse model of endotoxemia. ► LAME reduced the circulatory levels of cytokines (IL-6, TNF-α).« less

Induction of mast cell accumulation by chymase via an enzymatic activity- and intercellular adhesion molecule-1-dependent mechanism.

PubMed

Zhang, Huiyun; Wang, Junling; Wang, Ling; Zhan, Mengmeng; Li, Shigang; Fang, Zeman; Xu, Ciyan; Zheng, Yanshan; He, Shaoheng

2018-02-01

Chymase is a unique, abundant secretory product of mast cells and a potent chemoattractant for eosinophils, monocytes and neutrophils, but little is known of its influence on mast cell accumulation. A mouse peritoneal inflammation model, cell migration assay and flowcytometry analysis, were used to investigate the role of chymase in recruiting mast cells. Chymase increased, by up to 5.4-fold, mast cell numbers in mouse peritoneum. Inhibitors of chymase, heat-inactivation of the enzyme, sodium cromoglycate and terfenadine, and pretreatment of mice with anti-intercellular adhesion molecule 1, anti-L-selectin, anti-CD11a and anti-CD18 antibodies dramatically diminished the chymase-induced increase in mast cell accumulation. These findings indicate that this effect of chymase is dependent on its enzymatic activity and activation of adhesion molecules. In addition, chymase provoked a significant increase in 5-HT and eotaxin release (up to 1.8- and 2.2-fold, respectively) in mouse peritoneum. Since 5-HT, eotaxin and RANTES can induce marked mast cell accumulation, these indirect mechanisms may also contribute to chymase-induced mast cell accumulation. Moreover, chymase increased the trans-endothelium migration of mast cells in vitro indicating it also acts as a chemoattractant. The finding that mast cells accumulate in response to chymase implies further that chymase is a major pro-inflammatory mediator of mast cells. This effect of chymase, a major product of mast cell granules, suggests a novel self-amplification mechanism for mast cell accumulation in allergic inflammation. Mast cell stabilizers and inhibitors of chymase may have potential as a treatment of allergic disorders. © 2017 The British Pharmacological Society.

Cellular events in adhesion formation due to thermal trauma.

PubMed

Kaplun, A; Aronson, M; Halperin, B; Griffel, B

1984-01-01

Consequent to thermal traumatization of the intestinal wall of the mouse, histopathological events ensue which lead to peritoneal adhesion formation. In the first 48 h, the main pathological findings are of a necrotic and inflammatory nature, but subsequently fibroplasia is the main feature, as evidenced by the appearance of spindle-shaped cells followed by fibroblasts. Factors essential for and contributing to the formation of adhesions are described.

Mastitis Pathogens with High Virulence in a Mouse Model Produce a Distinct Cytokine Profile In Vivo

PubMed Central

Johnzon, Carl-Fredrik; Artursson, Karin; Söderlund, Robert; Guss, Bengt; Rönnberg, Elin; Pejler, Gunnar

2016-01-01

Mastitis is a serious medical condition of dairy cattle. Here, we evaluated whether the degree of virulence of mastitis pathogens in a mouse model can be linked to the inflammatory response that they provoke. Clinical isolates of Staphylococcus aureus (S. aureus) (strain 556 and 392) and Escherichia coli (E. coli) (676 and 127), and laboratory control strains [8325-4 (S. aureus) and MG1655 (E. coli)], were injected i.p. into mice, followed by the assessment of clinical scores and inflammatory parameters. As judged by clinical scoring, E. coli 127 exhibited the largest degree of virulence among the strains. All bacterial strains induced neutrophil recruitment. However, whereas E. coli 127 induced high peritoneal levels of CXCL1, G-CSF, and CCL2, strikingly lower levels of these were induced by the less virulent bacterial strains. High concentrations of these compounds were also seen in blood samples taken from animals infected with E. coli 127, suggesting systemic inflammation. Moreover, the levels of CXCL1 and G-CSF, both in the peritoneal fluid and in plasma, correlated with clinical score. Together, these findings suggest that highly virulent clinical mastitis isolates produce a distinct cytokine profile that shows a close correlation with the severity of the bacterial infection. PMID:27713743

Peritoneal Tumorigenesis and Inflammation are Ameliorated by Humidified-Warm Carbon Dioxide Insufflation in the Mouse.

PubMed

Carpinteri, Sandra; Sampurno, Shienny; Bernardi, Maria-Pia; Germann, Markus; Malaterre, Jordane; Heriot, Alexander; Chambers, Brenton A; Mutsaers, Steven E; Lynch, Andrew C; Ramsay, Robert G

2015-12-01

Conventional laparoscopic surgery uses CO2 that is dry and cold, which can damage peritoneal surfaces. It is speculated that disseminated cancer cells may adhere to such damaged peritoneum and metastasize. We hypothesized that insufflation using humidified-warm CO2, which has been shown to reduce mesothelial damage, will also ameliorate peritoneal inflammation and tumor cell implantation compared to conventional dry-cold CO2. Laparoscopic insufflation was modeled in mice along with anesthesia and ventilation. Entry and exit ports were introduced to maintain insufflation using dry-cold or humidified-warm CO2 with a constant flow and pressure for 1 h; then 1000 or 1 million fluorescent-tagged murine colorectal cancer cells (CT26) were delivered into the peritoneal cavity. The peritoneum was collected at intervals up to 10 days after the procedure to measure inflammation, mesothelial damage, and tumor burden using fluorescent detection, immunohistochemistry, and scanning electron microscopy. Rapid temperature control was achieved only in the humidified-warm group. Port-site tumors were present in all mice. At 10 days, significantly fewer tumors on the peritoneum were counted in mice insufflated with humidified-warm compared to dry-cold CO2 (p < 0.03). The inflammatory marker COX-2 was significantly increased in the dry-cold compared to the humidified-warm cohort (p < 0.01), while VEGFA expression was suppressed only in the humidified-warm cohort. Significantly less mesothelial damage and tumor cell implantation was evident from 2 h after the procedure in the humidified-warm cohort. Mesothelial cell damage and inflammation are reduced by using humidified-warm CO2 for laparoscopic oncologic surgery and may translate to reduce patients' risk of developing peritoneal metastasis.

Intravenous Glutamine Administration Modulates TNF-α/IL-10 Ratio and Attenuates NFkB Phosphorylation in a Protein Malnutrition Model.

PubMed

Santos, Andressa Cristina Antunes; Correia, Carolina Argondizo; de Oliveira, Dalila Cunha; Nogueira-Pedro, Amanda; Borelli, Primavera; Fock, Ricardo Ambrosio

2016-12-01

Protein malnutrition (PM) is a major public health problem in developing countries, affecting the inflammatory response and increasing susceptibility to opportunistic infections. For this reason, an adequate nutritional intervention can improve the quality of life of patients. Glutamine (GLN) is a nonessential amino acid, but can be considered "conditionally essential" for macrophage function in stress situations, in which it plays a role in the improvement of the inflammatory response. Concerning this issue, in the current study, it was of interest to evaluate some biological aspects of peritoneal cells from a protein malnutrition (PM) mouse model challenged with lipopolysaccharide (LPS) and treated intravenously with GLN. Two-month-old male Balb/c mice were subjected to a low-protein diet (2 % protein) and stimulated intravenously with LPS 1 h prior to the injection of 0.75 mg/kg GLN. Malnourished animals showed a reduced number of total peritoneal cells. Malnourished animals stimulated with LPS or LPS plus GLN did not show differences in peritoneal cell counts; however, the control group showed increased cellularity after LPS stimulus, which was reversed after GLN injection. Further, in the animals from both groups stimulated with LPS, GLN decreased the circulating levels of TNF-α and the levels of TNF-α produced by peritoneal cells; additionally, GLN decreased the IL-10 circulating levels in the malnourished animals stimulated with LPS. In addition, peritoneal cells of the control and malnourished groups stimulated with LPS showed a negative modulation of the NFkB signaling pathway after GLN injection. In conclusion, this study shows that GLN has the capacity to reduce TNF-α synthesis as well as to act as a negative regulator of NFkB phosphorylation, leading to a positive outcome in the control of TNF-α production.

The IL-4/STAT6 signaling axis establishes a conserved microRNA signature in human and mouse macrophages regulating cell survival via miR-342-3p.

PubMed

Czimmerer, Zsolt; Varga, Tamas; Kiss, Mate; Vázquez, Cesaré Ovando; Doan-Xuan, Quang Minh; Rückerl, Dominik; Tattikota, Sudhir Gopal; Yan, Xin; Nagy, Zsuzsanna S; Daniel, Bence; Poliska, Szilard; Horvath, Attila; Nagy, Gergely; Varallyay, Eva; Poy, Matthew N; Allen, Judith E; Bacso, Zsolt; Abreu-Goodger, Cei; Nagy, Laszlo

2016-05-31

IL-4-driven alternative macrophage activation and proliferation are characteristic features of both antihelminthic immune responses and wound healing in contrast to classical macrophage activation, which primarily occurs during inflammatory responses. The signaling pathways defining the genome-wide microRNA expression profile as well as the cellular functions controlled by microRNAs during alternative macrophage activation are largely unknown. Hence, in the current work we examined the regulation and function of IL-4-regulated microRNAs in human and mouse alternative macrophage activation. We utilized microarray-based microRNA profiling to detect the dynamic expression changes during human monocyte-macrophage differentiation and IL-4-mediated alternative macrophage activation. The expression changes and upstream regulatory pathways of selected microRNAs were further investigated in human and mouse in vitro and in vivo models of alternative macrophage activation by integrating small RNA-seq, ChIP-seq, ChIP-quantitative PCR, and gene expression data. MicroRNA-controlled gene networks and corresponding functions were identified using a combination of transcriptomic, bioinformatic, and functional approaches. The IL-4-controlled microRNA expression pattern was identified in models of human and mouse alternative macrophage activation. IL-4-dependent induction of miR-342-3p and repression of miR-99b along with miR-125a-5p occurred in both human and murine macrophages in vitro. In addition, a similar expression pattern was observed in peritoneal macrophages of Brugia malayi nematode-implanted mice in vivo. By using IL4Rα- and STAT6-deficient macrophages, we were able to show that IL-4-dependent regulation of miR-342-3p, miR-99b, and miR-125a-5p is mediated by the IL-4Rα-STAT6 signaling pathway. The combination of gene expression studies and chromatin immunoprecipitation experiments demonstrated that both miR-342-3p and its host gene, EVL, are coregulated directly by STAT6. Finally, we found that miR-342-3p is capable of controlling macrophage survival through targeting an anti-apoptotic gene network including Bcl2l1. Our findings identify a conserved IL-4/STAT6-regulated microRNA signature in alternatively activated human and mouse macrophages. Moreover, our study indicates that miR-342-3p likely plays a pro-apoptotic role in such cells, thereby providing a negative feedback arm to IL-4-dependent macrophage proliferation.

The CD44-initiated pathway of T-cell extravasation uses VLA-4 but not LFA-1 for firm adhesion

PubMed Central

Siegelman, Mark H.; Stanescu, Diana; Estess, Pila

2000-01-01

Leukocytes extravasate from the blood in response to physiologic or pathologic demands by means of complementary ligand interactions between leukocytes and endothelial cells. The multistep model of leukocyte extravasation involves an initial transient interaction (“rolling” adhesion), followed by secondary (firm) adhesion. We recently showed that binding of CD44 on activated T lymphocytes to endothelial hyaluronan (HA) mediates a primary adhesive interaction under shear stress, permitting extravasation at sites of inflammation. The mechanism for subsequent firm adhesion has not been elucidated. Here we demonstrate that the integrin VLA-4 is used in secondary adhesion after CD44-mediated primary adhesion of human and mouse T cells in vitro, and by mouse T cells in an in vivo model. We show that clonal cell lines and polyclonally activated normal T cells roll under physiologic shear forces on hyaluronate and require VCAM-1, but not ICAM-1, as ligand for subsequent firm adhesion. This firm adhesion is also VLA-4 dependent, as shown by antibody inhibition. Moreover, in vivo short-term homing experiments in a model dependent on CD44 and HA demonstrate that superantigen-activated T cells require VLA-4, but not LFA-1, for entry into an inflamed peritoneal site. Thus, extravasation of activated T cells initiated by CD44 binding to HA depends upon VLA-4–mediated firm adhesion, which may explain the frequent association of these adhesion receptors with diverse chronic inflammatory processes. PMID:10712440

[Peritoneal dialysis at a regional hospital in Norway].

PubMed

Paulsen, Dag; Solbakken, Kjell; Valset, Torstein

2011-08-23

In 2006, an expert group appointed by the Norwegian Social and Health Directory recommended that the proportion of patients on peritoneal dialysis should increase from 15 % to about 30 %. We wanted to investigate if treatment in our hospital was in compliance with that recommendation. The patient material consisted of the total number of patients on dialysis and anonymised data collected for patients treated with peritoneal dialysis at Innlandet Hospital Trust, Lillehammer in the period 1.01.2004-31.12.2008. For patients in peritoneal dialysis we assessed patient dynamics, length of hospital stay, incidence of peritonitis, need for assistance and organisation of peritoneal dialysis activity. Dialysis treatment was given to 176 patients, 62 (35 %) of whom were treated by peritoneal dialysis for at least 30 days (mean treatment time 16.2 months). 17 patients were switched from hemodialysis to peritoneal dialysis and nine patients from peritoneal dialysis to hemodialysis. Patients older than 70 years stayed in hospital 6 days longer than those younger than 70 years. 27 (44 %) of the patients acquired peritonitis in the study period and 18 (29 %) patients needed help to exchange the dialysis bag. The proportion of patients treated with peritoneal dialysis in our hospital has reached the recommended level. The reason may be that all eligible patients are offered peritoneal dialysis and that the treatment chain is well organised.

The Mutual Relationship Between Peritonitis and Peritoneal Transport.

PubMed

van Esch, Sadie; van Diepen, Anouk T N; Struijk, Dirk G; Krediet, Raymond T

2016-01-01

♦ Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD. Copyright © 2016 International Society for Peritoneal Dialysis.

Interleukin-33 Increases Antibacterial Defense by Activation of Inducible Nitric Oxide Synthase in Skin

PubMed Central

Jiang, Ziwei; Zhang, Tian; Wang, Yue; Li, Zhiheng; Wu, Yelin; Ji, Shizhao; Xiao, Shichu; Ryffel, Bernhard; Radek, Katherine A.; Xia, Zhaofan; Lai, Yuping

2014-01-01

Interleukin-33 (IL-33) is associated with multiple diseases, including asthma, rheumatoid arthritis, tissue injuries and infections. Although IL-33 has been indicated to be involved in Staphylococcus aureus (S. aureus) wound infection, little is known about how IL-33 is regulated as a mechanism to increase host defense against skin bacterial infections. To explore the underlying intricate mechanism we first evaluated the expression of IL-33 in skin from S. aureus-infected human patients. Compared to normal controls, IL-33 was abundantly increased in skin of S. aureus-infected patients. We next developed a S. aureus cutaneous infection mouse model and found that IL-33 was significantly increased in dermal macrophages of infected mouse skin. The expression of IL-33 by macrophages was induced by staphylococcal peptidoglycan (PGN) and lipoteichoic acid (LTA) via activation of toll-like receptor 2(TLR2) –mitogen-activated protein kinase (MAPK)-AKT-signal transducer and activator of transcription 3(STAT3) signaling pathway as PGN and LTA failed to induce IL-33 in Tlr2-deficient peritoneal macrophages, and MAPK,AKT, STAT3 inhibitors significantly decreased PGN- or LTA-induced IL-33. IL-33, in turn, acted on macrophages to induce microbicidal nitric oxygen (NO) release. This induction was dependent on inducible nitric oxide synthase (iNOS) activation, as treatment of macrophages with an inhibitor of iNOS, aminoguanidine, significantly decreased IL-33-induced NO release. Moreover, aminoguanidine significantly blocked the capacity of IL-33 to inhibit the growth of S. aureus, and IL-33 silencing in macrophages significantly increased the survival of S. aureus in macrophages. Furthermore, the administration of IL-33-neutralizing antibody into mouse skin decreased iNOS production but increased the survival of S. aureus in skin. These findings reveal that IL-33 can promote antimicrobial capacity of dermal macrophages, thus enhancing antimicrobial defense against skin bacterial infections. PMID:24586149

Spectrum and mechanisms of inflammasome activation by chitosan.

PubMed

Bueter, Chelsea L; Lee, Chrono K; Wang, Jennifer P; Ostroff, Gary R; Specht, Charles A; Levitz, Stuart M

2014-06-15

Chitosan, the deacetylated derivative of chitin, can be found in the cell wall of some fungi and is used in translational applications. We have shown that highly purified preparations of chitosan, but not chitin, activate the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in primed mouse bone marrow-derived macrophages (BMMΦ), inducing a robust IL-1β response. In this article, we further define specific cell types that are activated and delineate mechanisms of activation. BMMΦ differentiated to promote a classically activated (M1) phenotype released more IL-1β in response to chitosan than intermediate or alternatively activated macrophages (M2). Chitosan, but not chitin, induced a robust IL-1β response in mouse dendritic cells, peritoneal macrophages, and human PBMCs. Three mechanisms for NLRP3 inflammasome activation may contribute: K(+) efflux, reactive oxygen species, and lysosomal destabilization. The contributions of these mechanisms were tested using a K(+) efflux inhibitor, high extracellular potassium, a mitochondrial reactive oxygen species inhibitor, lysosomal acidification inhibitors, and a cathepsin B inhibitor. These studies revealed that each of these pathways participated in optimal NLRP3 inflammasome activation by chitosan. Finally, neither chitosan nor chitin stimulated significant release from unprimed BMMΦ of any of 22 cytokines and chemokines assayed. This study has the following conclusions: 1) chitosan, but not chitin, stimulates IL-1β release from multiple murine and human cell types; 2) multiple nonredundant mechanisms appear to participate in inflammasome activation by chitosan; and 3) chitin and chitosan are relatively weak stimulators of inflammatory mediators from unprimed BMMΦ. These data have implications for understanding the nature of the immune response to microbes and biomaterials that contain chitin and chitosan. Copyright © 2014 by The American Association of Immunologists, Inc.

The Mutual Relationship Between Peritonitis and Peritoneal Transport

PubMed Central

van Esch, Sadie; van Diepen, Anouk T.N.; Struijk, Dirk G.; Krediet, Raymond T.

2016-01-01

♦ Background: Preservation of the peritoneum is required for long-term peritoneal dialysis (PD). We investigated the effect of multiple peritonitis episodes on peritoneal transport. ♦ Methods: Prospectively collected data from 479 incident PD patients treated between 1990 and 2010 were analyzed, using strict inclusion criteria: follow-up of at least 3 years with the availability of a Standard Peritoneal Permeability Analysis (SPA) in the first year after start of PD and within the third year of PD, without peritonitis preceding the first SPA. For the purpose of the study, we only included patients who remained peritonitis-free (n = 28) or who experienced 3 or more peritonitis episodes (n = 16). ♦ Results: At baseline the groups were similar with regard to small solute and fluid transport. However, the frequent peritonitis group had lower peritoneal protein clearances compared to the no peritonitis group, resulting in lower dialysate concentrations of proteins: albumin 196.5 mg/L vs 372.5 mg/L, IgG 36.4 mg/L vs 65.0 mg/L, and α-2-macroglobulin (A2M) 1.9 mg/L vs 3.6 mg/L, p <0.01. No differences in serum concentrations were present. A comparison between the transport slopes over time in both groups showed a positive time trend of mass transfer area coefficient (MTAC) creatinine (p = 0.03) and glucose absorption (p = 0.09) and a negative trend of transcapillary ultrafiltration (p = 0.06), when compared to the no peritonitis group. Frequent peritonitis did not affect free water transport. ♦ Conclusions: Slow initial peritoneal transport rates of serum proteins result in lower dialysate concentrations, and likely a lower opsonic activity, which is a risk factor for peritonitis. Patients with frequent peritonitis show an increase in small solute transport and a concomitant decrease of ultrafiltration. In long-term peritonitis-free PD patients, small solute transport decreased, while ultrafiltration increased. This suggests that frequent peritonitis leads to an increase of the vascular peritoneal surface area without all the structural membrane alterations that may develop after long-term PD. PMID:25395498

RhoA/Rho-kinase triggers epithelial-mesenchymal transition in mesothelial cells and contributes to the pathogenesis of dialysis-related peritoneal fibrosis

PubMed Central

Wang, Qinglian; Yang, Xiaowei; Xu, Ying; Shen, Zhenwei; Cheng, Hongxia; Cheng, Fajuan; Liu, Xiang; Wang, Rong

2018-01-01

Peritoneal fibrosis (PF) with associated peritoneal dysfunction is almost invariably observed in long-term peritoneal dialysis (PD) patients. Advanced glycation end products (AGEs) are pro-oxidant compounds produced in excess during the metabolism of glucose and are present in high levels in standard PD solutions. The GTPase RhoA has been implicated in PF, but its specific role remains poorly understood. Here, we studied the effects of RhoA/Rho-kinase signaling in AGEs-induced epithelial-mesenchymal transition (EMT) in human peritoneal mesothelial cells (HPMCs), and evaluated morphological and molecular changes in a rat model of PD-related PF. Activation of RhoA/Rho-kinase and activating protein-1 (AP-1) was assessed in HPMCs using pull-down and electrophoretic mobility shift assays, respectively, while expression of transforming growth factor-β, fibronectin, α-smooth muscle actin, vimentin, N-cadherin, and E-cadherin expression was assessed using immunohistochemistry and western blot. AGEs exposure activated Rho/Rho-kinase in HPMCs and upregulated EMT-related genes via AP-1. These changes were prevented by the Rho-kinase inhibitors fasudil and Y-27632, and by the AP-1 inhibitor curcumin. Importantly, fasudil normalized histopathological and molecular alterations and preserved peritoneal function in rats. These data support the therapeutic potential of Rho-kinase inhibitors in PD-related PF. PMID:29581852

Impact of Glutathione Peroxidase-1 Deficiency on Macrophage Foam Cell Formation and Proliferation: Implications for Atherogenesis

PubMed Central

Degreif, Adriana; Rossmann, Heidi; Canisius, Antje; Lackner, Karl J.

2013-01-01

Clinical and experimental evidence suggests a protective role for the antioxidant enzyme glutathione peroxidase-1 (GPx-1) in the atherogenic process. GPx-1 deficiency accelerates atherosclerosis and increases lesion cellularity in ApoE−/− mice. However, the distribution of GPx-1 within the atherosclerotic lesion as well as the mechanisms leading to increased macrophage numbers in lesions is still unknown. Accordingly, the aims of the present study were (1) to analyze which cells express GPx-1 within atherosclerotic lesions and (2) to determine whether a lack of GPx-1 affects macrophage foam cell formation and cellular proliferation. Both in situ-hybridization and immunohistochemistry of lesions of the aortic sinus of ApoE−/− mice after 12 weeks on a Western type diet revealed that both macrophages and – even though to a less extent – smooth muscle cells contribute to GPx-1 expression within atherosclerotic lesions. In isolated mouse peritoneal macrophages differentiated for 3 days with macrophage-colony-stimulating factor (MCSF), GPx-1 deficiency increased oxidized low density-lipoprotein (oxLDL) induced foam cell formation and led to increased proliferative activity of peritoneal macrophages. The MCSF- and oxLDL-induced proliferation of peritoneal macrophages from GPx-1−/−ApoE−/− mice was mediated by the p44/42 MAPK (p44/42 mitogen-activated protein kinase), namely ERK1/2 (extracellular-signal regulated kinase 1/2), signaling pathway as demonstrated by ERK1/2 signaling pathways inhibitors, Western blots on cell lysates with primary antibodies against total and phosphorylated ERK1/2, MEK1/2 (mitogen-activated protein kinase kinase 1/2), p90RSK (p90 ribosomal s6 kinase), p38 MAPK and SAPK/JNK (stress-activated protein kinase/c-Jun N-terminal kinase), and immunohistochemistry of mice atherosclerotic lesions with antibodies against phosphorylated ERK1/2, MEK1/2 and p90RSK. Representative effects of GPx-1 deficiency on both macrophage proliferation and MAPK phosphorylation could be abolished by the GPx mimic ebselen. The present study demonstrates that GPx-1 deficiency has a significant impact on macrophage foam cell formation and proliferation via the p44/42 MAPK (ERK1/2) pathway encouraging further studies on new therapeutic strategies against atherosclerosis. PMID:23991041

Pharmacokinetics of single-dose oral ciprofloxacin in patients undergoing chronic ambulatory peritoneal dialysis.

PubMed Central

Shalit, I; Greenwood, R B; Marks, M I; Pederson, J A; Frederick, D L

1986-01-01

The prevention and treatment of peritonitis in patients undergoing peritoneal dialysis is often complicated by several factors, including nephrotoxicity, requirement for hospitalization, parenteral antibiotic therapy, and infection caused by resistant microorganisms. Ciprofloxacin, a new carboxyquinolone derivative, may offer the advantages of oral administration, a broad spectrum of antibacterial activity, and safety for the management of these patients. The pharmacokinetics of ciprofloxacin in serum and peritoneal fluid of eight adult patients undergoing chronic ambulatory peritoneal dialysis (CAPD) were investigated. Each patient ingested a single 750-mg dose of ciprofloxacin, and drug concentrations were measured by high-pressure liquid chromatography in serum and peritoneal fluid for 48 h after the dose. Serum concentrations reached a mean peak of 3.6 micrograms/ml 1 to 2 h after the oral dose. The mean terminal serum half-life was 16.8 h, and the mean peritoneal fluid/serum concentration ratio was 0.64. The mean peak ciprofloxacin concentration in peritoneal fluid was 1.3 micrograms/ml, and the bioactivity of the drug in peritoneal fluid was confirmed. These data indicated that therapeutic concentrations of ciprofloxacin against bacterial pathogens commonly associated with peritonitis in CAPD patients may be achievable in the peritoneal fluid after oral administration to patients undergoing CAPD. In addition, the pharmacokinetic data provide guidelines for further clinical studies of oral ciprofloxacin in CAPD patients. PMID:2944477

Identification of Aminopeptidase N as a Cellular Receptor for Human Coronavirus-229E

DTIC Science & Technology

1992-05-12

hemagglutinating encephalomyelitis virus (HEV), canine coronavirus (CCV), cat FIPV and feline enteric corona virus (FECV), human CVLPs, mouse...While the cat , dog and pig serve as natural hosts for the other coronavirus group 1 viruses , feline infectious peritonitis virus (FIPV), canine...3 2 . Virus Receptors ••••••••.••••••.....•................ 20 3. Viruses Which Cause Common Colds

High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients.

PubMed

Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B Paul; Ito, Yasuhiko

2017-01-01

We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis.

Progesterone production is affected by unfolded protein response (UPR) signaling during the luteal phase in mice.

PubMed

Park, Hyo-Jin; Park, Sun-Ji; Koo, Deog-Bon; Lee, Sang-Rae; Kong, Il-Keun; Ryoo, Jae-Woong; Park, Young-Il; Chang, Kyu-Tae; Lee, Dong-Seok

2014-09-15

We examined whether the three unfolded protein response (UPR) signaling pathways, which are activated in response to endoplasmic reticulum (ER)-stress, are involved in progesterone production in the luteal cells of the corpus luteum (CL) during the mouse estrous cycle. The luteal phase of C57BL/6 female mice (8 weeks old) was divided into two stages: the functional stage (16, 24, and 48 h) and the regression stage (72 and 96 h). Western blotting and reverse transcription (RT)-PCR were performed to analyze UPR protein/gene expression levels in each stage. We investigated whether ER stress affects the progesterone production by using Tm (0.5 μg/g BW) or TUDCA (0.5 μg/g BW) through intra-peritoneal injection. Our results indicate that expressions of Grp78/Bip, p-eIF2α/ATF4, p50ATF6, and p-IRE1/sXBP1 induced by UPR activation were predominantly maintained in functional and early regression stages of the CL. Furthermore, the expression of p-JNK, CHOP, and cleaved caspase3 as ER-stress mediated apoptotic factors increased during the regression stage. Cleaved caspase3 levels increased in the late-regression stage after p-JNK and CHOP expression in the early-regression stage. Additionally, although progesterone secretion and levels of steroidogenic enzymes decreased following intra-peritoneal injection of Tunicamycin, an ER stress inducer, the expression of Grp78/Bip, p50ATF6, and CHOP dramatically increased. These results suggest that the UPR signaling pathways activated in response to ER stress may play important roles in the regulation of the CL function. Furthermore, our findings enhance the understanding of the basic mechanisms affecting the CL life span. Copyright © 2014 Elsevier Inc. All rights reserved.

Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models.

PubMed

Rodrigues, Lindaiane Bezerra; Oliveira Brito Pereira Bezerra Martins, Anita; Cesário, Francisco Rafael Alves Santana; Ferreira E Castro, Fyama; de Albuquerque, Thaís Rodrigues; Martins Fernandes, Maria Neyze; Fernandes da Silva, Bruno Anderson; Quintans Júnior, Lucindo José; da Costa, José Galberto Martins; Melo Coutinho, Henrique Douglas; Barbosa, Roseli; Alencar de Menezes, Irwin Rose

2016-09-25

The genus Ocimum are used in cooking, however, their essential oils are utilized in traditional medicine as aromatherapy. The present study was carried out to investigate the chemical composition and systemic anti-inflammatory activity of the Ocimum basilicum essential oil (EOOB) and its major component estragole, as well as its possible mechanisms of action. The Ocimum basilicum essential oil was obtained by hydrodistillation and analyzed by GC-MS. The anti-inflammatory action was verified using acute and chronic in vivo tests as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was analyzed by the participation of histamine and arachidonic acid pathways. The chemical profile analysis identified fourteen components present in the essential oil, within them: estragole (60.96%). The in vivo test results show that treatment with EOOB (100 and 50 mg/kg) and estragole (60 and 30 mg/kg) significantly reduced paw edema induced by carrageenan and dextran. The smallest doses of EOOB (50 mg/kg) and estragole (30 mg/kg) showed efficacy in the reduction of paw edema induced by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. Theses doses were capable of reducing the chronic inflammatory process. The results observed between the EOOB and estragole demonstrate efficacy in anti-inflammatory activity, however, the essential oil is more efficacious in the acute and chronic anti-inflammatory action. This study confirms the therapeutic potential of this plant and reinforces the validity of its use in popular medicine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Ilexgenin A, a novel pentacyclic triterpenoid extracted from Aquifoliaceae shows reduction of LPS-induced peritonitis in mice.

PubMed

Sun, Weidong; Liu, Chang; Zhang, Yaqi; Qiu, Xia; Zhang, Li; Zhao, Hongxia; Rong, Yi; Sun, Yun

2017-02-15

Ilexgenin A (IA) is a novel pentacyclic triterpenoid, which extracted from leaves of Ilex hainanensis Merr. In the present study, we aim to explore anti-inflammatory activity of IA on LPS-induced peritonitis and its underlying molecular mechanism. The results determined that IA was capable of suppressing peritonitis in mice induced by intraperitoneal (i.p.) injection of lipopolysaccaride (LPS). Furthermore, the results showed that IA dramatically inhibited levels of inflammatory cells infiltration in peritoneal cavity and serum in LPS-induced mice peritonitis model. Besides, IA could dramatically inhibit levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) in peritoneal cavity in LPS-induced mice peritonitis model. In vitro study, the results showed that IA inhibited production of IL-1β, IL-6 and TNF-α at transcriptional and translational levels in RAW 264.7 cells induced by LPS. Furthermore, IA could suppress the LPS-induced activation of Akt and downstream degradation and phosphorylation of kappa B-α (IκB-α). Moreover, IA could significantly inhibit ERK 1/2 phosphorylation in RAW 264.7 cells induced by LPS. These results were concurrent with molecular docking which revealed ERK1/2 inhibition. These results demonstrated that IA might as an anti-inflammatory agent candidate for inflammatory disease therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3

PubMed Central

Deng, Lulu; Li, Qin; Lin, Guixian; Huang, Dan; Zeng, Xuxin; Wang, Xinwei; Li, Ping; Jin, Xiaobao; Zhang, Haifeng; Li, Chunmei; Chen, Lixin; Wang, Liwei; Huang, Shulin; Shao, Hongwei; Xu, Bin; Mao, Jianwen

2016-01-01

P-glycoprotein (P-gp) is encoded by the multidrug resistance (MDR1) gene and is well studied as a multi-drug resistance transporter. Peritoneal adhesion formation following abdominal surgery remains an important clinical problem. Here, we found that P-gp was highly expressed in human adhesion fibroblasts and promoted peritoneal adhesion formation in a rodent model. Knockdown of P-gp expression by intraperitoneal injection of MDR1-targeted siRNA significantly reduced both the peritoneal adhesion development rate and adhesion grades. Additionally, we found that operative injury up-regulated P-gp expression in peritoneal fibroblasts through the TGF-β1/Smad signaling pathway and histone H3 acetylation. The overexpression of P-gp accelerated migration and proliferation of fibroblasts via volume-activated Cl- current and cell volume regulation by enhancing phosphorylation of the chloride channel-3. Therefore, P-gp plays a critical role in postoperative peritoneal adhesion formation and may be a valuable therapeutic target for preventing the formation of peritoneal adhesions. PMID:26877779

Identification of anti-inflammatory constituents in Hypericum perforatum and Hypericum gentianoides extracts using RAW 264.7 mouse macrophages

PubMed Central

Huang, Nan; Rizshsky, Ludmila; Hauck, Cathy; Nikolau, Basil J.; Murphy, Patricia A.; Birt, Diane F.

2011-01-01

Hypericum perforatum (St. John’s wort) is an herb widely used as supplement for mild to moderate depression. Our prior studies revealed synergistic anti-inflammatory activity associated with 4 bioactive compounds in a fraction of H. perforatum ethanol extract. Whether these 4 compounds also contributed to the ethanol extract activity was addressed in the research reported here. Despite the popularity of H. perforatum, other Hypericum species with different phytochemical profiles could have their anti-inflammatory potentials attributed to these or other compounds. In the current study, ethanol extracts of different Hypericum species were compared for their inhibitory effect on LPS-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 mouse macrophages. Among these extracts, those made from H. perforatum and H. gentianoides demonstrated stronger overall efficacy. LC-MS analysis indicated the 4 compounds in H. perforatum extract and pseudohypericin in all active fractions. The 4 compounds accounted for a significant part of the extract’s inhibitory activity on PGE2, NO, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in RAW 264.7 as well as peritoneal macrophages. Pseudohypericin was the most important contributor of the anti-inflammatory potential among the 4 compounds. The lipophilic fractions of H. gentianoides extract, which did not contain the previously identified active constituents, decreased PGE2 and NO potently. These fractions were rich in acylphloroglucinols, including uliginosin A that accounted for a proportion of the anti-inflammatory activity observed with the active fractions. Overall, the current study revealed a different group of major anti-inflammatory constituents in H. gentianoides, while showing that a previously identified 4 compounds combination was important for H. perforatum’s anti-inflammatory potential. PMID:21855951

Inhibition of colony-stimulating-factor-1 signaling in vivo with the orally bioavailable cFMS kinase inhibitor GW2580.

PubMed

Conway, James G; McDonald, Brad; Parham, Janet; Keith, Barry; Rusnak, David W; Shaw, Eva; Jansen, Marilyn; Lin, Peiyuan; Payne, Alan; Crosby, Renae M; Johnson, Jennifer H; Frick, Lloyd; Lin, Min-Hwa Jasmine; Depee, Scott; Tadepalli, Sarva; Votta, Bart; James, Ian; Fuller, Karen; Chambers, Timothy J; Kull, Frederick C; Chamberlain, Stanley D; Hutchins, Jeff T

2005-11-01

Colony-stimulating-factor-1 (CSF-1) signaling through cFMS receptor kinase is increased in several diseases. To help investigate the role of cFMS kinase in disease, we identified GW2580, an orally bioavailable inhibitor of cFMS kinase. GW2580 completely inhibited human cFMS kinase in vitro at 0.06 microM and was inactive against 26 other kinases. GW2580 at 1 microM completely inhibited CSF-1-induced growth of mouse M-NFS-60 myeloid cells and human monocytes and completely inhibited bone degradation in cultures of human osteoclasts, rat calvaria, and rat fetal long bone. In contrast, GW2580 did not affect the growth of mouse NS0 lymphoblastoid cells, human endothelial cells, human fibroblasts, or five human tumor cell lines. GW2580 also did not affect lipopolysaccharide (LPS)-induced TNF, IL-6, and prostaglandin E2 production in freshly isolated human monocytes and mouse macrophages. After oral administration, GW2580 blocked the ability of exogenous CSF-1 to increase LPS-induced IL-6 production in mice, inhibited the growth of CSF-1-dependent M-NFS-60 tumor cells in the peritoneal cavity, and diminished the accumulation of macrophages in the peritoneal cavity after thioglycolate injection. Unexpectedly, GW2580 inhibited LPS-induced TNF production in mice, in contrast to effects on monocytes and macrophages in vitro. In conclusion, GW2580's selective inhibition of monocyte growth and bone degradation is consistent with cFMS kinase inhibition. The ability of GW2580 to chronically inhibit CSF-1 signaling through cFMS kinase in normal and tumor cells in vivo makes GW2580 a useful tool in assessing the role of cFMS kinase in normal and disease processes.

Therapeutically Targeting the Inflammasome Product in a Chimeric Model of Endometriosis-Related Surgical Adhesions.

PubMed

Stocks, Meredith M; Crispens, Marta A; Ding, Tianbing; Mokshagundam, Shilpa; Bruner-Tran, Kaylon L; Osteen, Kevin G

2017-08-01

Development of adhesions commonly occurs in association with surgery for endometriosis. Even in the absence of surgery, women with endometriosis appear to be at an enhanced risk of developing adhesions. In the current study, we utilized a chimeric mouse model of experimental endometriosis in order to examine the role of inflammasome activation in the development of postsurgical adhesions. Mice were randomized to receive peritoneal injections of human endometrial tissue fragments or endometrial tissue conditioned media (CM) from women with or without endometriosis 16 hours after ovariectomy and placement of an estradiol-releasing silastic capsule. A subset of mice receiving CM was also treated with interleukin (IL) 1 receptor antagonist (IL-1ra). Our studies demonstrate that peritoneal injection of endometrial tissue fragments near the time of surgery resulted in extensive adhesive disease regardless of tissue origin. However, adhesion scores were significantly higher in mice receiving CM from tissues acquired from patients with endometriosis compared to control tissue CM ( P = .0001). Cytokine bead array analysis of endometrial CM revealed enhanced expression of IL-1β from patients with endometriosis compared to controls ( P < .01). Finally, the ability of human tissue CM to promote adhesive disease was dramatically reduced in mice cotreated with IL-1ra ( P < .0001). Our data implicate enhanced expression of IL-1β in women with endometriosis as a potential causal factor in their increased susceptibility of developing postsurgical adhesions. Thus, targeting inflammasome activation may be an effective strategy for the prevention of surgical adhesions in patients with endometriosis.

Histamine release, formation of prostaglandin-like activity (SRS-C) and mast cell degranulation by the direct lytic factor (DLF) and phospholipase A of cobra venom.

PubMed

Damerau, B; Lege, L; Oldigs, H D; Vogt, W

1975-01-01

Cobra venom, alone and in combination, on mast cell degranulation, histamine release and formation of prostaglandin-like activity (SRS-C) was studied in perfused guinea-pig lungs and in mast cell-containing rat peritoneal cell suspensions. For comparison, the effect of equivalent doses of whole cobra venom was investigated. 1. Cobra venom caused mast cell degranulation, histamine release and SRS-C formation in both systems. For comparable effects much higher doses had to be used in guine-pig lungs than in rat peritoneal cell suspensions. 2. Phase A showed little degranulation of mast cells in both systems, a limited histamine release in rat peritoneal cell suspensions and none in perfused guinea-pig lungs. It caused a considerable SRS-C formation in both, lung tissue and peritoneal cell suspensions. 3. DLF caused histamine release, SRS-C formation and mast cell degranulation in both systems; in rat peritoneal cell suspensions it acted almost as strong as equivalent doses of cobra venom, in guinea pig lungs it was much less active. 4. In rat peritoneal cell suspensions the effects of DLF and phase A in combination did not exceed the sum of their single effects. In guinea-pig lungs these two substances interacted in a potentiating synergism. It is concluded that DLF is the main cytotoxic principle of cobra venom, whereas ph-ase A alone is not cytotoxic. The difference in the synergism of DLF and ph-ase A between rat peritoneal cells and guinea-pig lungs may be due to two different actions of DLF and species differences as regards sensitivity against these actions.

Calcitriol decreases TGF-β1 and angiotensin II production and protects against chlorhexide digluconate-induced liver peritoneal fibrosis in rats.

PubMed

Lee, Chung-Jen; Subeq, Yi-Maun; Lee, Ru-Ping; Liou, Hung-Hsiang; Hsu, Bang-Gee

2014-01-01

Peritoneal fibrosis is a major complication of peritoneal dialysis that can lead to ultrafiltration failure. This study investigates the protective effects of calcitriol on chlorhexidine digluconate-induced peritoneal fibrosis in rats. Peritoneal fibrosis was induced in Sprague-Dawley rats by daily administration of 0.5mL 0.1% chlorhexidine digluconate in normal saline via peritoneal dialysis for 1week. Rats received daily intravenous injections of calcitriol (low-dose, 10ng/kg; or high-dose, 100ng/kg) for 1week. After 7days, conventional 4.25% Dianeal (30mL) was administered via peritoneal dialysis over 4h. Peritoneal solute transport was calculated from the dialysate concentration relative to its concentration in the initial infused dialysis solution (D4/D0 glucose) for glucose, and the dialysate-to-plasma concentration ratio (D4/P4 urea) at 4h for urea. Rats were then sacrificed and the liver peritoneum was harvested for immunohistochemical analysis via microscopy. After dialysis, the D4/P4 Urea level was reduced; increases were observed in the D4/D0 glucose level and the levels of active transforming growth factor-β1 and angiotensin II in serum and dialysate; the liver peritoneum and muscle peritoneum was markedly thickened, and the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and phosphorylated Smad2/3 (P-Smad2/3)-positive cells in the liver peritoneum was elevated in the peritoneal fibrosis group compared with the vehicle group. Calcitriol decreased the serum and dialysate active transforming growth factor-β1 and angiotensin II level, decreased the thickness of the liver peritoneum and muscle peritoneum, and decreased the expression of α-SMA, fibronectin, collagen, vascular endothelial growth factor, angiotensin II, transforming growth factor-β1, and P-Smad2/3-positive cells in liver peritoneum cells. High-dose calcitriol exhibited better protective effects against peritoneal fibrosis than did the lower dose. Calcitriol protected against chlorhexidine digluconate-induced peritoneal fibrosis in rats by decreasing transforming growth factor-β1 and angiotensin II production. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mouse CD23 regulates monocyte activation through an interaction with the adhesion molecule CD11b/CD18.

PubMed

Lecoanet-Henchoz, S; Plater-Zyberk, C; Graber, P; Gretener, D; Aubry, J P; Conrad, D H; Bonnefoy, J Y

1997-09-01

CD23 is expressed on a variety of hemopoietic cells. Recently, we have reported that blocking CD23 interactions in a murine model of arthritis resulted in a marked improvement of disease severity. Here, we demonstrate that CD11b, the alpha chain of the beta 2 integrin adhesion molecule complex CD11b/CD18 expressed on monocytes interacts with CD23. Using a recombinant fusion protein (ZZ-CD23), murine CD23 was shown to bind to peritoneal macrophages and peripheral blood cells isolated from mice as well as the murine macrophage cell line, RAW. The interactions between mouse ZZ-CD23 and CD11b/CD18-expressing cells were significantly inhibited by anti-CD11b monoclonal antibodies. A functional consequence was then demonstrated by inducing an up-regulation of interleukin-6 (IL-6) production following ZZ-CD23 incubation with monocytes. The addition of Fab fragments generated from the monoclonal antibody CD11b impaired this cytokine production by 50%. Interestingly, a positive autocrine loop was identified as IL-6 was shown to increase CD23 binding to macrophages. These results demonstrate that similar to findings using human cells, murine CD23 binds to the surface adhesion molecule, CD11b, and these interactions regulate biological activities of murine myeloid cells.

Anti-atherogenic properties of date vs. pomegranate polyphenols: the benefits of the combination.

PubMed

Rosenblat, Mira; Volkova, Nina; Borochov-Neori, Hamutal; Judeinstein, Sylvie; Aviram, Michael

2015-05-01

Hydrolysable tannin polyphenols in pomegranate and phenolic acids in date fruit and seeds are potent antioxidants and anti-atherogenic agents, and thus, in the present study we investigated the possible benefits of combining them in vivo in atherosclerotic apolipoprotein E KO (E(0)) mice, compared with the individual fruit. In vitro studies revealed that the date seed extract contains more polyphenols than Amari or Hallawi date extracts, and possesses a most impressive free radical scavenging capacity. Similarly, pomegranate juice (PJ), punicalagin, punicalain, gallic acid, and urolithins A and B are very potent antioxidants. E(0) mice consumed 0.5 μmol gallic acid equivalents (GAE) per mouse per day of PJ, Hallawi extract, date seed extract, or a combination for 3 weeks. Consumption of the combination was the most potent treatment, as it decreased serum cholesterol and triglyceride levels, and increased serum paraoxonase 1 (PON1) activity. Consumption of the combination also significantly reduced mouse peritoneal macrophage (MPM) oxidative stress, MPM cholesterol content, and MPM LDL uptake. Finally, the lipid peroxide content in the aortas of the mice significantly decreased, and the PON lactonase activity of the aortas increased after treatment with the combination. We thus conclude that consumption of pomegranate, together with date fruit and date seeds, has the most beneficial anti-atherogenic effects on E(0) mice serum, macrophages, and aortas, probably due to their unique and varied structures.

Three Novel Triterpenoids from Taraxacum officinale Roots.

PubMed

Kikuchi, Takashi; Tanaka, Ayaka; Uriuda, Mayu; Yamada, Takeshi; Tanaka, Reiko

2016-08-27

Three novel lupane-, bauerane-, and euphane-type triterpenoids (1-3), in addition to seven known triterpenoids (4-10)-18β,19β-epoxy-21β-hydroxylupan-3β-yl acetate (4), 21-oxolup-18-en-3β-yl acetate (5), betulin (6), officinatrione (7), 11α-methoxyolean-12-en-3-one (8), eupha-7,24-dien-3-one (9), and 24-oxoeupha-7,24-dien-3β-yl acetate (10)-were isolated from the roots of Taraxacum officinale. Their structures were elucidated on the basis of spectroscopic analyses using 1D and 2D-NMR spectra and electron ionization mass spectrometry (EIMS). The effects of compounds 1-10 on the production of nitric oxide (NO) in lipopolysaccharide (LPS)-activated mouse peritoneal macrophages were evaluated. Compounds 4, 6, and 10 exhibited similar NO inhibitory activities to N(G)-monomethyl-l-arginine acetate (l-NMMA). These compounds did not exhibit cytotoxicity at an effective concentration. The results of present study suggest that compounds 4, 6, and 10 have potential as anti-inflammatory disease agents.

Regional Control of Tumor Growth

PubMed Central

Zaslavsky, Alexander; Chen, Catherine; Grillo, Jenny; Baek, Kwan-Hyuck; Holmgren, Lars; Yoon, Sam S.; Folkman, Judah; Ryeom, Sandra

2010-01-01

Tumors implanted near the scapulae have been shown to grow four-times faster than the same tumors implanted at the iliac crest. While there were marked differences in the vascularization of tumors from these two different sites, the mechanism controlling regional angiogenesis was not identified. Here we demonstrate site-specific growth of intraperitoneal tumor implants in the mouse abdomen. Our data indicate that the angiogenic response of the host differs significantly between the upper and lower sites in the mouse abdomen and reveals that the expansion of tumor mass is restricted at sites with low angiogenic responses such as the bowel mesentery in the lower abdomen. We show that in this model, this suppression of angiogenesis is due to an expression gradient of thrombospondin-1, a potent endogenous angiogenesis inhibitor. Mice with a targeted deletion of thrombospondin-1 no longer demonstrate regional restriction of tumor growth. The physiological relevance of these findings may be seen in patients with peritoneal carcinomatosis, whereby tumors spread within the peritoneal cavity and show differential growth in the upper and lower abdomen. We hypothesize that the difference in tumor growth in these patients may be due to a gradient of thrombospondin-1 expression in stroma. Finally, our studies suggest that upregulation of thrombospondin-1 in tumor cells is one method to suppress the growth of tumors in the upper abdomen. PMID:20736295

Inhibition of IRAK-4 activity for rescuing endotoxin LPS-induced septic mortality in mice by lonicerae flos extract

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Sun Hong; Roh, Eunmiri; Kim, Hyun Soo

Highlights: •Lonicerae flos extract (HS-23) is a clinical candidate, Phase I for sepsis treatment. •Here, HS-23 or its major constituents rescued LPS-induced septic mortality in mice. •As a mechanism, they directly inhibited IRAK-4-catalyzed kinase activity. •Thus, they suppressed LPS-induced expression of NF-κB/AP-1-target inflammatory genes. -- Abstract: Lonicerae flos extract (HS-23) is a clinical candidate currently undergoing Phase I trial in lipopolysaccharide (LPS)-injected healthy human volunteers, but its molecular basis remains to be defined. Here, we investigated protective effects of HS-23 or its major constituents on Escherichia coli LPS-induced septic mortality in mice. Intravenous treatment with HS-23 rescued LPS-intoxicated C57BL/6J micemore » under septic conditions, and decreased the levels of cytokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and high-mobility group box-1 (HMGB-1) in the blood. Chlorogenic acid (CGA) and its isomers were assigned as major constituents of HS-23 in the protection against endotoxemia. As a molecular mechanism, HS-23 or CGA isomers inhibited endotoxin LPS-induced autophosphorylation of the IL-1 receptor-associated kinase 4 (IRAK-4) in mouse peritoneal macrophages as well as the kinase activity of IRAK-4 in cell-free reactions. HS-23 consequently suppressed downstream pathways critical for LPS-induced activation of nuclear factor (NF)-κB or activating protein 1 (AP-1) in the peritoneal macrophages. HS-23 also inhibited various toll-like receptor agonists-induced nitric oxide (NO) production, and down-regulated LPS-induced expression of NF-κB/AP-1-target inflammatory genes in the cells. Taken together, HS-23 or CGA isomers exhibited anti-inflammatory therapy against LPS-induced septic mortality in mice, at least in part, mediated through the inhibition of IRAK-4.« less

Selective modulation of the prostaglandin F2α pathway markedly impacts on endometriosis progression in a xenograft mouse model.

PubMed

Ahmad, Syed Furquan; Akoum, Ali; Horne, Andrew W

2015-12-01

Selective activation or blockade of the prostaglandin (PG) F2α receptor (FP receptor) affects ectopic endometrial tissue growth and endometriosis development. FP receptor antagonists might represent a promising approach for the treatment of peritoneal endometriosis. Eutopic and ectopic endometrium from women with endometriosis exhibit higher expression of key enzymes involved in the PGF2α biosynthetic pathway. It has also been shown that the PGF2α-FP receptor interaction induces angiogenesis in human endometrial adenocarcinoma. For this study, a mouse model of endometriosis was developed by inoculating human endometrial biopsies into the peritoneal cavity of nude mouse (n = 15). Mice were treated with AL8810 (FP receptor antagonist), Fluprostenol (FP receptor agonist) or PBS. Endometriosis-like lesions were collected and analysed for set of markers for angiogenesis, tissue remodelling, apoptosis, cell proliferation and capillary formation using qPCR and immunohistochemistry. We found that selective inhibition of the FP receptor with a specific antagonist, AL8810, led to a significant decline in the number (P < 0.01) and size of endometriosis-like lesions (P < 0.001), down-regulated the expression of key mediators of tissue remodelling (MMP9, P < 0.05) and angiogenesis (VEGF, P < 0.01) and up-regulated the pro-apoptotic factor (Bax, P < 0.01) as compared with controls. Immunohistochemical analyses further showed a marked decrease in cell proliferation and capillary formation in endometrial implants from AL8810-treated mice, as determined by proliferating cell nuclear antigen (PCNA) and von Willebrand factor (vWF) immunostaining, respectively. Moreover, Fluprostenol, a selective FP receptor agonist, showed the opposite effects. We carried out this study in nude mice, which have low levels of endogenous estrogens which may affect the lesion growth. Caution is required when interpreting these results to women. This study extends the role of PG signalling in endometriosis pathogenesis and points towards the possible relevance of selective FP receptor antagonism as a targeted treatment for endometriosis. Not Applicable. This work was supported by grant MOP-123259 to the late Dr Ali Akoum from the Canadian Institutes for Health Research. The authors have no conflict of interest. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Zinc Chloride and Lead Acetate-Induced Passive Avoidance Memory Retention Deficits Reversed by Nicotine and Bucladesine in Mice.

PubMed

Tabrizian, Kaveh; Yazdani, Abdolmajid; Baheri, Behnam; Payandemehr, Borna; Sanati, Mehdi; Hashemzaei, Mahmoud; Miri, Abdolhossein; Zandkarimi, Majid; Belaran, Maryam; Fanoudi, Sahar; Sharifzadeh, Mohammad

2016-01-01

It is very important to investigate the neurotoxic effects of metals on learning and memory processes. In this study, we tried to investigate the effects and time course properties of oral administration of zinc chloride (25, 50, and 75 mg/kg, for 2 weeks), lead acetate (250, 750, 1,500, and 2,500 ppm for 4, 6 and 8 weeks), and their possible mechanisms on a model of memory function. For this matter, we examined the intra-peritoneal injections of nicotine (0.25, 0.5, 1, and 1.5 mg/kg) and bucladesine (50, 100, 300, and 600 nM/mouse) for 4 days alone and in combination with mentioned metals in the step-through passive avoidance task. Control animals received saline, drinking water, saline, and DMSO (dimethyl sulfoxide)/deionized water (1:9), respectively. At the end of each part of studies, animals were trained for 1 day in step-through task. The avoidance memory retention alterations were evaluated 24 and 48 h later in singular and combinational studies. Zinc chloride (75 mg/kg) oral gavage for 2 weeks decreased latency times compared to control animals. Also, lead acetate (750 ppm oral administrations for 8 weeks) caused significant lead blood levels and induced avoidance memory retention impairments. Four-days intra-peritoneal injection of nicotine (1 mg/kg) increased latency time compared to control animals. Finally, findings of this research showed that treatment with intra-peritoneal injections of nicotine (1 mg/kg) and/or bucladesine (600 nM/mouse) reversed zinc chloride- and lead acetate-induced avoidance memory retention impairments. Taken together, these results showed the probable role of cholinergic system and protein kinase A pathways in zinc chloride- and lead acetate-induced avoidance memory alterations.

Biochemical actions of glucocorticoids on macrophages in culture. Specific inhibition of elastase, collagenase, and plasminogen activator secretion and effects on other metabolic functions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werb, Z.

1978-01-01

The effects of glucocorticoids on biochemical functions of macrophages from man, mouse, rabbit, and guinea pig were examined. Secretion of plasminogen activator by human peripheral blood monocytes was decreased 50% with 1 nM dexamethasone. Differentiation of murine monocytic and granulocytic colonies in agar from bone marrow precursors was decreased 50% at 7 days with 20 nM dexamethasone. Secretion of elastase, collagenase, and plasminogen activator by resident and thioglycollate-elicited mouse peritoneal macrophages was decreased by dexamethasone, cortisol, and triamcinolone acetonide (1 to 1,000 nM), but not by progesterone, estradiol, and dihydrotestosterone (1,000 nM); in contast, secretion of lysozyme was not affectedmore » by glucocorticoids. The inhibition of macrophage secretion by dexamethasone was both time and dose dependent. Inhibition of macrophage secretion increased with increasing glucocorticoid concentration. Half-maximum inhibition of secretion of elastase, collagenase, and plasminogen activator was seen at dexamethasone concentrations (1 to 10 nM) similar to those that half-saturated the specific glucocorticoid receptors. At high concentrations of dexamethasone (100 to 1,000 nM) the secretion of plasminogen activator was inhibited to a greater extent (>95%) than the secretion of elastase (60 to 80%).Progesterone alone had no effect on secretion, but blocked the inhibitory effects of dexamethasone and cortisol. Secretion of collagenase, neutral proteinases, and plasminogen activator by elicited rabbit alveolar macrophages was inhibited with glucocorticoids (0.1 to 100 nM) but not with progesterone or sex steroids. Secretion of a neutral elastinolytic proteinase by guinea pig alveolar macrophages was also inhibited by dexamethasone.« less

[Effects of intrasplenic transplantation of IL-18 gene-modified fetal hepatocytes on mouse immune function

PubMed

Yao, Hang-Ping; Zhang, Li-Huang; Sun, Wen-Ji; Leng, Jian-Hang

2002-04-01

OBJECTIVE: To investigate the effects of IL-18 gene-modified fetal hepatocytes (AdmIL-18/MNL.CL2) intrasplenic transplantation on mouse immune function. METHODS: Forty mice were evenly divided into 4 groups of 10. Each group received an intrasplenic transplantation one of the following: AdmIL-18/BNL.CL2, Ad-LacZ/BNL.CL2 (virus control), BNL.CL2 (cell control) and PBS (blank control). After two weeks, the mice were sacrificed. Serum cytokine levels, Mpsi and splenic cell culture supernatant and liver tissue extracts supernatants were measured using ELISA. Hepatic cytokines mRNA expression were determined by RT-PCR. THe cytotoxicity of peritoneal Mpsi and NK activity of spienocytes were detected by LDH release assay. The proliferation of splenic lymphocytes was determined by MTT assay. RESULTS: The IL-18, IL-2,IFN-gamma, TNF-alpha levels of serum, Mpsi and splenocyte culture supernatant, liver tissue extracts supernatants in mice transplanted with AdmIL-18/BNL.CL2 were higher and the IL-4, IL-10 levels were lower compared to their levels in other 3 groups. The highest IL-18, IL-2, IFN-gamma, TNF-alpha and the lowest IL-4, IL-10 mRNA expressions in the liver were observed in mice transplanted with AdmIL-18/BNL.CL2. The mice transplanted with AdmIL-18/BNL.Cl2 showed significantly increases cytotoxicity of Mpsi, NK activity and splenic cell proliferation compared with the other 3 groups. CONCLUSION: AdmIL-18 can be effectively transfected into mice fetal heptocytes which subsequently IL-18. Intransplenic transplantation of IL-18 gene-modified fetal hepatocytes may augment mouse immune function and provide an useful basis for targeted gene therapy of liver disease.

Mutant matrix metalloproteinase-9 reduces postoperative peritoneal adhesions in rats.

PubMed

Atta, Hussein; El-Rehany, Mahmoud; Roeb, Elke; Abdel-Ghany, Hend; Ramzy, Maggie; Gaber, Shereen

2016-02-01

Postoperative peritoneal adhesions continue to be a major source of morbidity and occasional mortality. Studies have shown that matrix metalloproteinase-9 (MMP-9) levels are decreased postoperatively which may limits matrix degradation and participate in the development of peritoneal adhesions. In this proof-of-principle study, we evaluated the effect of gene therapy with catalytically inactive mutant MMP-9 on postoperative peritoneal adhesions in rats. Adenovirus encoding mutant MMP-9 (Ad-mMMP-9) or saline was instilled in the peritoneal cavity after cecal and parietal peritoneal injury in rats. Expression of mutant MMP-9 transcript was verified by sequencing. Adenovirus E4 gene expression, adhesion scores, MMP-9, tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1) and transforming growth factor-β1 (TGF-β1) expression were evaluated at sacrifice one week after treatment. Both mutant MMP-9 transcripts and adenovirus E4 gene were expressed in Ad-mMMP-9 treated adhesions. Adhesions severity decreased significantly (p = 0.036) in the Ad-mMMP-9-treated compared with saline-treated adhesions. Expression of MMP-9 mRNA and protein were elevated (p = 0.001 and p = 0.029, respectively) in the Ad-mMMP-9-treated adhesions compared with saline-treated adhesions. While tPA levels were increased (p = 0.02) in Ad-mMMP-9 treated adhesions compared with saline-treated adhesions, TGF-β1 and PAI-1 levels were decreased (p = 0.017 and p = 0.042, respectively). No difference in mortality were found between groups (p = 0.64). Mutant MMP-9 gene therapy effectively transduced peritoneal adhesions resulting in reduction of severity of primary peritoneal adhesions. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

High Levels of Soluble C5b-9 Complex in Dialysis Fluid May Predict Poor Prognosis in Peritonitis in Peritoneal Dialysis Patients

PubMed Central

Mizuno, Masashi; Suzuki, Yasuhiro; Higashide, Keiko; Sei, Yumi; Iguchi, Daiki; Sakata, Fumiko; Horie, Masanobu; Maruyama, Shoichi; Matsuo, Seiichi; Morgan, B. Paul; Ito, Yasuhiko

2017-01-01

Background We searched for indicators to predict the prognosis of infectious peritonitis by measuring levels of complement proteins and activation products in peritoneal dialysis (PD) fluid (PDF) of patients at early stages of peritonitis. We retrospectively analyzed the relationship between the levels of sC5b-9, C3 and C4 in PDF and the subsequent clinical prognosis. Methods We measured levels of sC5b-9, C3 and C4 in PDF on days 1, 2 and 5 post-onset of peritonitis in 104 episodes of infectious peritonitis in PD patients from 2008 and retrospectively compared levels with clinical outcomes. Further analysis for the presence of causative microorganisms or to demonstrate bacterial culture negative peritonitis was performed and correlated with change of levels of sC5b-9 in PDF. Results When PD patients with peritonitis were divided into groups that either failed to recover from peritonitis and were finally withdrawn from PD (group 1; n = 25) or recovered (group 2; n = 79), levels of sC5b-9, C3 and C4 in PDF were significantly higher in group 1 patients compared to those in group 2 on day5. Analysis of microorganisms showed significantly higher sC5b-9 levels in PDF of peritonitis cases caused by culture negative peritonitis in group 1 compared with group 2 when we analyzed for individual microorganisms. Of note, on day5, the sC5b-9 levels in PDF were similarly high in peritonitis caused by fungi or other organisms. Conclusion Our results suggested that levels of complement markers in PDF, especially sC5b-9, have potential as surrogate markers to predict prognosis of PD-related peritonitis. PMID:28046064

A new antifungal protein and a chitinase with prominent macrophage-stimulating activity from seeds of Phaseolus vulgaris cv. pinto.

PubMed

Ye, X Y; Ng, T B

2002-01-18

From the seeds of the pinto bean (Phaseolus vulgaris cv. pinto), a chitinase and a novel antifungal protein, both with the ability of markedly augmenting nitrite production by murine peritoneal macrophages, were isolated. The antifungal proteins, designated phasein A and phasein B, exhibited molecular weights of 28 and 32 kDa, respectively. Phaseins A and B were adsorbed on Affi-gel blue gel and CM-Sepharose and were eluted as adjacent peaks from CM-Sepharose. Phasein A demonstrated potent antifungal activity toward Fusarium oxysporum and Physalospora piricola. Phasein B was more potent than phasein A toward P. piricola but less potent than phasein A toward F. oxysporum and Rhizoctonia solani. Both antifungal proteins inhibited the activity of HIV-1 reverse transcriptase and translation in a rabbit reticulocyte lysate system, with phasein B being more potent. Nitrite production by mouse macrophages was greatly boosted in the presence of both phaseins A and B, although the effect of phasein A was more prominent. The bioactivities of phaseins were in general potent compared with those of other antifungal proteins.

Anti-Inflammatory and Antibothropic Properties of Jatropha Elliptica, a Plant from Brazilian Cerrado Biome

PubMed Central

Ferreira-Rodrigues, Sára Cósta; Rodrigues, Cássio Milhomens; Dos Santos, Marcio Galdino; Gautuz, Jean Antonio Abraham; Silva, Magali Glauzer; Cogo, José Carlos; Batista-Silva, Camila; Dos Santos, Cleiton Pita; Groppo, Francisco Carlos; Cogo-Müller, Karina; Oshima-Franco, Yoko

2016-01-01

Purpose: The aim of this study was to evaluate the antibothropic and anti-inflammatory properties of J. elliptica. Methods: Phytochemical screening and thin-layer chromatography (TLC) assays were performed on J. elliptica hydroalcoholic extract (TE) in order to observe its main constituents. The antibothropic activity of TE was evaluated by the in vitro neuromuscular blockade caused by Bothrops jararacussu venom (Bjssu), in a mouse phrenic nerve-diaphragm model (PND). A quantitative histological study was carried out to observe a possible protection of TE against the venom myotoxicity. The anti-inflammatory activity was also evaluated in two models, Bjssu-induced paw edema, and carrageenan-induced neutrophils migration in the peritoneal cavity. Results: TLC analysis revealed several compounds in TE, such as saponins, alkaloids, and phenolic constituents. TE was able to neutralize the blockade and the myotoxicity induced by venom, when it was pre-incubated for 30 min with venom. In addition, it showed anti-inflammatory activity, inducing less neutrophils migration and reducing paw edema. Conclusion: J. elliptica showed both antibothropic and anti-inflammatory properties. PMID:28101464

Bactericidal Activity of Micromolar N-Chlorotaurine: Evidence for Its Antimicrobial Function in the Human Defense System

PubMed Central

Nagl, Markus; Hess, Michael W.; Pfaller, Kristian; Hengster, Paul; Gottardi, Waldemar

2000-01-01

N-Chlorotaurine, the main representative of long-lived oxidants found in the supernatant of stimulated granulocytes, has been investigated systematically with regard to its antibacterial activity at different physiological concentrations for the first time. N-Chlorotaurine (12.5 to 50 μM) demonstrated a bactericidal effect i.e., a 2 to 4 log10 reduction in viable counts, after incubation at 37°C for 6 to 9 h at pH 7.0, which effect was significantly enhanced in an acidic milieu (at pH 5.0), with a 3 to 4 log10 reduction after 2 to 3 h. Moreover, bacteria were attenuated after being incubated in N-chlorotaurine for a sublethal time, as demonstrated with the mouse peritonitis model. The supernatant of stimulated granulocytes exhibited similar activity. Transmission electron microscopy revealed changes in the bacterial cell membrane and cytoplasmic disintegration with both reacting systems, even in the case of a mere attenuation. The results of this study suggest a significant bactericidal function of N-chlorotaurine and other chloramines during inflammation. PMID:10952603

Mast cells express 11β-hydroxysteroid dehydrogenase type 1: a role in restraining mast cell degranulation.

PubMed

Coutinho, Agnes E; Brown, Jeremy K; Yang, Fu; Brownstein, David G; Gray, Mohini; Seckl, Jonathan R; Savill, John S; Chapman, Karen E

2013-01-01

Mast cells are key initiators of allergic, anaphylactic and inflammatory reactions, producing mediators that affect vascular permeability, angiogenesis and fibrosis. Glucocorticoid pharmacotherapy reduces mast cell number, maturation and activation but effects at physiological levels are unknown. Within cells, glucocorticoid concentration is modulated by the 11β-hydroxysteroid dehydrogenases (11β-HSDs). Here we show expression and activity of 11β-HSD1, but not 11β-HSD2, in mouse mast cells with 11β-HSD activity only in the keto-reductase direction, regenerating active glucocorticoids (cortisol, corticosterone) from inert substrates (cortisone, 11-dehydrocorticosterone). Mast cells from 11β-HSD1-deficient mice show ultrastructural evidence of increased activation, including piecemeal degranulation and have a reduced threshold for IgG immune complex-induced mast cell degranulation. Consistent with reduced intracellular glucocorticoid action in mast cells, levels of carboxypeptidase A3 mRNA, a glucocorticoid-inducible mast cell-specific transcript, are lower in peritoneal cells from 11β-HSD1-deficient than control mice. These findings suggest that 11β-HSD1-generated glucocorticoids may tonically restrain mast cell degranulation, potentially influencing allergic, anaphylactic and inflammatory responses.

Effect of heated naringenin on immunomodulatory properties and cellular antioxidant activity.

PubMed

Maatouk, Mouna; Elgueder, Dorra; Mustapha, Nadia; Chaaban, Hind; Bzéouich, Imen Mokdad; Loannou, Irina; Kilani, Soumaya; Ghoul, Mohamed; Ghedira, Kamel; Chekir-Ghedira, Leila

2016-11-01

Naringenin is one of the most popular flavonoids derived from citrus. It has been reported to be an effective anti-inflammatory compound. Citrus fruit may be used raw, cooked, stewed, or boiled. The present study was conducted to investigate the effect of thermal processes on naringenin in its immunomodulatory and cellular antioxidant activities. The effects of flavonoids on B and T cell proliferation were assessed on splenocytes stimulated or not with mitogens. However, their effects on cytotoxic T lymphocyte (CTL) and natural killer (NK) activities were assessed in splenocytes co-incubated with target cells. The amount of nitric oxide production and the lysosomal enzyme activity were evaluated in vitro on mouse peritoneal macrophages. Cellular antioxidant activity in splenocytes and macrophages was determined by measuring the fluorescence of the dichlorofluorescin (DCF). Our findings revealed that naringenin induces B cell proliferation and enhances NK activity. The highest concentration of native naringenin exhibits a significant proliferation of T cells, induces CTL activity, and inhibits cellular oxidation in macrophages. Conversely, it was observed that when heat-processed, naringenin improves the cellular antioxidant activity in splenocytes, increases the cytotoxic activity of NK cells, and suppresses the cytotoxicity of T cells. However, heat treatment maintains the anti-inflammatory potency of naringenin.

Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome Activation.

PubMed

Kim, Young-Kyu; Koppula, Sushruta; Shim, Do-Wan; In, Eun-Jung; Kwak, Su-Bin; Kim, Myong-Ki; Yu, Sang-Hyeun; Lee, Kwang-Ho; Kang, Tae-Bong

2018-01-01

Arctium lappa (A. lappa) , Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1 β secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1 β in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa , which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders.

Inhibitory Effect and Mechanism of Arctium lappa Extract on NLRP3 Inflammasome Activation

PubMed Central

Kim, Young-Kyu; Koppula, Sushruta; Shim, Do-Wan; In, Eun-Jung; Kwak, Su-Bin; Yu, Sang-Hyeun

2018-01-01

Arctium lappa (A. lappa), Compositae, is considered a potential source of nutrition and is used as a traditional medicine in East Asian countries for centuries. Although several studies have shown its biological activities as an anti-inflammatory agent, there have been no reports on A. lappa with regard to regulatory role in inflammasome activation. The purpose of this study was to investigate the inhibitory effects of A. lappa extract (ALE) on NLRP3 inflammasome activation and explore the underlying mechanisms. We found that ALE inhibited IL-1β secretion from NLRP3 inflammasome activated bone marrow derived macrophages but not that secreted by NLRC4 and AIM2 inflammasomes activation. Mechanistic studies revealed that ALE suppressed the ATPase activity of purified NLRP3 and reduced mitochondrial reactive oxygen species (mROS) generated during NLRP3 activation. Therefore, the inhibitory effect of ALE on NLRP3 inflammasome might be attributed to its ability to inhibit the NLRP3 ATPase function and attenuated the mROS during inflammasome activation. In addition, ALE significantly reduced the LPS-induced increase of plasma IL-1β in mouse peritonitis model. These results provide evidence of novel anti-inflammatory mechanisms of A. lappa, which might be used for therapeutic applications in the treatment of NLRP3 inflammasome-associated inflammatory disorders. PMID:29576797

Anti histaminic activity of cissus quadragularis.

PubMed

Begum, V H; Sadique, J

1999-01-01

Anti histaminic activity of cissus quadrangularis stem powder was carried out determining the histamine activity and histamine content in carrageenin induced rat paw swelling model and formalin induced peritonitis respectively. The crude powder at the dose of 100mg/1QQ00 gm exerted reduction to the maximum of 44% in the early hisamine phase swelling. Further it significantly reduced the histamine content in the peritoneal fluid. For comparison standard steroidal drug hydrocortisone and avil were used.

Methanol extract of Ocimum gratissimum protects murine peritoneal macrophages from nicotine toxicity by decreasing free radical generation, lipid and protein damage and enhances antioxidant protection

PubMed Central

Mahapatra, Santanu Kar; Chakraborty, Subhankari Prasad; Das, Subhasis

2009-01-01

In the present study, methanol extract of Ocimum gratissimum Linn (ME-Og) was tested against nicotine-induced murine peritoneal macrophage in vitro. Phytochemical analysis of ME-Og shown high amount of flavonoid and phenolic compound present in it. The cytotoxic effect of ME-Og was studied in murine peritoneal macrophages at different concentrations (0.1 to 100 µg/ml) using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide (MTT) method. To establish the protective role of ME-Og against nicotine toxicity, peritoneal macrophages from mice were treated with nicotine (10 mM), nicotine + ME-Og (1 to 25 µg/ml) for 12 h in culture media. The significantly (p < 0.05) increased super oxide anion generation, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, myeloperoxidase (MPO) activity, lipid peroxidation, protein carbonyls, oxidized glutathione levels were observed in nicotine-treated group as compared to control group; those were significantly (p < 0.05) reduced in ME-Og supplemented groups in concentration dependent manner. More over, significantly (p < 0.05) reduced antioxidant status due to nicotine exposure was effectively ameliorated by ME-Og supplementation in murine peritoneal macrophages. Among the different concentration of ME-Og, maximum protective effect was observed by 25 µg/ml, which does not produce significant cell cytotoxicity in murine peritoneal macrophages. These findings suggest the potential use and beneficial role of O. gratissimum as a modulator of nicotine-induced free radical generation, lipid-protein damage and antioxidant status in important immune cell, peritoneal macrophages. PMID:20716908

Role of the International Society for Peritoneal Dialysis (ISPD) in the future of peritoneal dialysis.

PubMed

Lo, Wai Kei

2009-01-01

The International Society for Peritoneal Dialysis (ISPD) was established in 1984. Throughout the years, the ISPD has been playing a pivotal role in the development of peritoneal dialysis (PD) through organizing congresses, publishing the Peritoneal Dialysis International formation of treatment and training guidelines, and supporting international studies. In recent years, it has enhanced its educational programs through organizing PD courses in developing countries, online education videos and a function 'Questions about PD' on its website. Several regional chapters - Asian, North American and Latin American - have been formed to target the special needs of different regions. To move forward, apart from enhancing the current activities, good use of cyber technology for out-reaching and educational purposes, and collaboration with other international or national societies particularly in the area of national policy making are envisaged.

Citral alleviates an accelerated and severe lupus nephritis model by inhibiting the activation signal of NLRP3 inflammasome and enhancing Nrf2 activation.

PubMed

Ka, Shuk-Man; Lin, Jung-Chen; Lin, Tsai-Jung; Liu, Feng-Cheng; Chao, Louis Kuoping; Ho, Chen-Lung; Yeh, Li-Tzu; Sytwu, Huey-Kang; Hua, Kuo-Feng; Chen, Ann

2015-11-19

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. NLRP3 inflammasome activation, reactive oxygen species (ROS) and mononuclear leukocyte infiltration in the kidney have been shown to provoke the acceleration and deterioration of LN, such as accelerated and severe LN (ASLN). Development of a novel therapeutic remedy based on these molecular events to prevent the progression of the disease is clinically warranted. Citral (3,7-dimethyl-2,6-octadienal), a major active compound in a Chinese herbal medicine Litsea cubeba, was used to test its renoprotective effects in a lipopolysaccharide (LPS)-induced mouse ASLN model by examining NLRP3 inflammasome activation, ROS and COX-2 production as well as Nrf2 activation. The analysis of mechanisms of action of Citral also involved its effects on IL-1β secretion and signaling pathways of NLRP3 inflammasome in LPS-primed peritoneal macrophages or J774A macrophages. Attenuated proteinuria, renal function impairment, and renal histopathology, the latter including intrinsic cell proliferation, cellular crescents, neutrophil influx, fibrinoid necrosis in the glomerulus, and peri-glomerular infiltration of mononuclear leukocytes as well as glomerulonephritis activity score were observed in Citral-treated ASLN mice. In addition, Citral inhibited NLRP3 inflammasome activation and levels of ROS, NAD(P)H oxidase subunit p47(phox), or COX-2, and it enhanced the activation of nuclear factor E2-related factor 2 (Nrf2). In LPS-primed macrophages, Citral reduced ATP-induced IL-1β secretion and caspase-1 activation, but did not affect LPS-induced NLRP3 protein expression. Our data show that Citral alleviates the mouse ASLN model by inhibition of the activation signal, but not the priming signal, of NLRP3 inflammasome and enhanced activation of Nrf2 antioxidant signaling.

Intra-peritoneal chronic loculation in peritoneal dialysis patients - a new medical management approach.

PubMed

Mitoiu, Dan; David, Cristiana; Peride, Ileana; Niculae, Andrei; Mureşan, Alin; Ciocâlteu, Alexandru; Geavlete, Bogdan Florin; Checheriţă, Ionel Alexandru

2014-01-01

Peritoneal dialysis (PD) limitation as renal replacement therapy is mostly due to peritonitis and complications. Formation and persistence of intra-abdominal loculations is often under-diagnosed. Encapsulated peritoneal sclerosis (EPS) is a life-threatening complication, but malnutrition, recurrent peritonitis and early membrane failure are insidious enemies that need to be emphasized. It is important to highlight the persistence of intra-abdominal fluid collection after clinical resolution of peritonitis in PD patients and to indicate a new medical management approach for an early diagnosis. During five years, we selected PD peritonitis cases followed by a six months interval free of infections. Ninety-seven subjects were followed at six months and one year after the first peritonitis. Tomography had been performed to patients presenting a positive inflammatory state without a specific infectious cause. Subjects presenting documented localized fluid collection (31 cases) were divided into: drug-treated group and those undergoing laparoscopy by a new surgery technique (seven patients); a comparison regarding the clinical state and biohumoral parameters was assessed in both groups. The prevalence of intra-abdominal loculation following an apparent resolved peritonitis was high (31.9%). The cases undergoing laparoscopy presented a better evolution - improved clinical status (p=0.001), higher hemoglobin values (p=0.06), significant lower doses of erythropoietin requirement (p=0.03), improved dialysis adequacy (p=0.005) and inflammatory state. In cases with confirmed fluid encapsulated loculation, an active attitude (screening imaging protocol and laparoscopic exploration) appears to be mandatory, decreasing the risk of EPS, a serious complication which pathology and treatment are incompletely understood.

Chemotactic activity from rabbit peritoneal neutrophils. Lack of identity with N-acetyl-DL-phenylalanine beta-napthyl esterase.

PubMed

Tsung, P K; Showell, H J; Kegeles, S W; Becker, E L

1976-08-12

The chemotactic and N-acetyl-DL-phenylalanine beta-naphthyl esterase activities of rabbit peritoneal neutrophils are separable from each other by both DEAE cellulose and Sephadex G-100 column chromatography. Partially purified esterase obtained from DEAE-cellulose chromatography had molecular weight of 70 000. However, the partially purified fraction contained chemotactic activities with major activity in molecular weight of 28000 and minor activities in the molecular weights of 45000, 21900, 14500 and 10500. Esterase activity is inhibited by 10(-7) M p-nitrophenylethyl-5-chloropentylphosphonate but chemotactic activity is not.

The kampo medicine Daikenchuto inhibits peritoneal fibrosis in mice.

PubMed

Kitamura, Mineaki; Nishino, Tomoya; Obata, Yoko; Oka, Satoru; Abe, Shinichi; Muta, Kumiko; Ozono, Yoshiyuki; Koji, Takehiko; Kohno, Shigeru

2015-01-01

Long-term peritoneal dialysis therapy causes inflammation and histological changes in the peritoneal membrane. Inflammation generally activates fibroblasts and results in fibroblast-myofibroblast differentiation. Heat-shock protein 47 (HSP 47), a collagen-specific molecular chaperone, is localized in myofibroblasts and is involved in the progression of peritoneal fibrosis. Daikenchuto (DKT), a Kampo medicine, is used to prevent postoperative colon adhesion. It inhibits inflammation and HSP 47 expression in the gastrointestinal tract. We examined the effect of DKT on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in mice injected with 0.1% CG dissolved in 15% ethanol. DKT was dissolved in the drinking water. Histological changes were assessed using Masson trichrome staining. Cells expressing α-smooth muscle actin (α-SMA), HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 were examined immunohistochemically. Compared with the control group, the peritoneal tissues of the CG group were markedly thickened, and the number of cells expressing α-SMA, HSP 47, phospho-Smad 2/3, F4/80, and monocyte chemotactic protein-1 was significantly increased. However, these changes were inhibited in the DKT-treated group. These results indicate that DKT can prevent peritoneal fibrosis by inhibiting inflammation and HSP 47 expression.

ANTI HISTAMINIC ACTIVITY OF CISSUS QUADRAGULARIS

PubMed Central

Begum, V. Hazeena; Sadique, J.

1999-01-01

Anti histaminic activity of cissus quadrangularis stem powder was carried out determining the histamine activity and histamine content in carrageenin induced rat paw swelling model and formalin induced peritonitis respectively. The crude powder at the dose of 100mg/1QQ00 gm exerted reduction to the maximum of 44% in the early hisamine phase swelling. Further it significantly reduced the histamine content in the peritoneal fluid. For comparison standard steroidal drug hydrocortisone and avil were used. PMID:22556903

Effects of Citral on Lipopolysaccharide-Induced Inflammation in Human Umbilical Vein Endothelial Cells.

PubMed

Song, Yan; Zhao, Hongfeng; Liu, Jinyang; Fang, Chao; Miao, Renying

2016-04-01

Citral is an active compound of lemongrass oil which has been reported to have anti-inflammatory effects. In this study, we investigated the effects of citral on lipopolysaccharide (LPS)-induced inflammatory response in a rat model of peritonitis and human umbilical vein endothelial cells (HUVECs). LPS was intraperitoneally injected into rats to establish a peritonitis model. The HUVECs were treated with citral for 12 h before exposure to LPS. The levels of TNF-α and IL-8 were measured using ELISA. Western blotting was used to detect the expression of VCAM-1, ICAM-1, NF-κB, and PPAR-γ. The results showed that citral had a protective effect against LPS-induced peritonitis. Citral decreased the levels of WBCs and inflammatory cytokines TNF-α and IL-6. Citral also inhibited LPS-induced myeloperoxidase (MPO) activity in the peritoneal tissue. Treatment of HUVECs with citral significantly inhibited TNF-α and IL-8 expression induced by LPS. LPS-induced VCAM-1 and ICAM-1 expression were also suppressed by citral. Meanwhile, we found that citral inhibited LPS-induced NF-κB activation in HUVECs. Furthermore, we found that citral activated PPAR-γ and the anti-inflammatory effects of citral can be reversed by PPAR-γ antagonist GW9662. In conclusion, citral inhibits LPS-induced inflammatory response via activating PPAR-γ which attenuates NF-κB activation and inflammatory mediator production.

Physical Activity in Patients Treated With Peritoneal Dialysis: A Protocol for a Systematic Review.

PubMed

Thangarasa, Tharshika; Imtiaz, Rameez; Hiremath, Swapnil; Zimmerman, Deborah

2017-01-01

Patients with chronic diseases are known to benefit from exercise. Despite a lack of compelling evidence, patients with end-stage kidney disease treated with peritoneal dialysis are often discouraged from participating in exercise programs that include resistance training due to concerns about the development of hernias and leaks. The actual effects of physical activity with or without structured exercise programs for these patients remain unclear. The purpose of this study is to more completely define the risks and benefits of physical activity in the end-stage kidney disease population treated with peritoneal dialysis. We will conduct a systematic review examining the effects of physical activity on end-stage kidney disease patients treated with peritoneal dialysis. For the purposes of this review, exercise will be considered a purposive subcategory of physical activity. The primary objective is to determine if physical activity in this patient population is associated with improvements in mental health, physical functioning, fatigue and quality of life and if there is an increase in adverse outcomes. With the help of a skilled librarian, we will search MEDLINE, EMBASE, CINAHL, and Cochrane Central Register of Controlled Trials for randomized trials and observational studies. We will include adult end-stage kidney disease patients treated with peritoneal dialysis that have participated in an exercise training program or had their level of physical activity assessed directly or by self-report. The study must include an assessment of the association between physical activity and one of our primary or secondary outcomes measures. We will report study quality using the Cochrane Risk of Bias Assessment Tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. Quality across studies will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The results of this review may help to inform guideline development for exercise recommendations specific to this patient population. PROSPERO:CRD42016041695.

Experimental infections in Venezuelan lizards by Trypanosoma cruzi.

PubMed

Urdaneta-Morales, S; McLure, I

1981-06-01

Virulent trypomastigotes of the Y strain of Trypanosoma cruzi were administered to Tropidurus hispidus, Ameiva ameiva, Cnemidophorus lemniscatus, Polychrus marmoratus, and Phyllodactylus ventralis (Sauria). Intraperitoneal and subcutaneous inoculations of lizards with mouse blood or with feces of infected Rhodnius prolixus (Reduviidae, Triatominae), as well as forced ingestion of triturated Rhodnius, produced no parasitaemias detectable either directly or by xenodiagnosis, while control mice became parasitized. Pretreatment with the immunosuppressive drug Fluocinolone acetonide led to establishing patent infections in inoculated lizards. Cryptic infections were established by inoculation of 1 X 10(6) parasites from Davis' medium, or by 95 X 10(3) parasites from lizard tissue culture. Parasites were not seen in tissues. Mice inoculated with blood or tissue homogenates from these lizards became parasitized. Parasites from Davis' medium inoculated into the peritoneal cavity of lizards were capable, to a very low degree, of penetrating the free peritoneal macrophages and changing into amastigotes. The factors possibly responsible for the natural resistance of poikilothermic vertebrates to T. cruzi are discussed.

Enhancing effects of gamma interferon on phagocytic cell association with and killing of Trypanosoma cruzi

NASA Technical Reports Server (NTRS)

Wirth, J. J.; Kierszenbaum, F.; Sonnenfeld, G.; Zlotnik, A.

1985-01-01

Results are reported from a study of the influence gamma interferon (GIFN) and interleukin 2 (IL2) have on the capability of P388D1 cells and mouse resident peritoneal macrophages (MPM) to attach to the blood-resident parasites Trypanosoma cruzi and kill them. Cultures of trypomastigote forms of the Tulahuen strain of T. cruzi grown in bovine serum were introduced into peritoneal cells of mice, along with P388D1 cells incubated with GIFN, IL2 and both. Control cells were also maintained. Statistical analysis were then performed on data on counts of the number of dead T. Cruzi cells. The GIFN enhanced the interaction of MPM and P388D1 cells with the surface of T. Cruzi, provided the interaction was given over 12 hr to take place. A depression of the cytotoxicity of P388D1 cells was attributed to mediation by H2O2, an effect partially offset by incubation with the lymphokine GIFN.

Protective capacity of antibodies to outer-membrane components of Escherichia coli in a systemic mouse peritonitis model.

PubMed

Vuopio-Varkila, J; Karvonen, M; Saxén, H

1988-02-01

Antibody-mediated protection was studied in an experimental murine model of peritonitis-septicaemia with Escherichia coli O18:K1. Protection from lethal intraperitoneal challenge was achieved by passive immunisation with horse anti-K1 capsular antiserum (H46) or rabbit antiserum to the homologous O18 antigen. The maximum increase in LD50 achieved with anti-K1 and anti-O18 antibodies was 10- and 5-fold, respectively. The protective capacity of the anti-O serum was found to be in the IgG fraction. Rabbits were also immunised with various semi-purified or purified outer-membrane-protein preparations (porins and OmpA protein) from rough E. coli or Salmonella strains or with whole E. coli J5 bacteria. Although this immunisation resulted in high antibody titres to homologous and, to a lesser extent, also to heterologous antigens, none of the antisera protected against challenge with the capsulate E. coli O18:K1 bacteria.

Macrophage genetic reprogramming during chronic peritonitis is augmented by LPS pretreatment.

PubMed

Kanaan, Ziad; Gardner, Sarah; Carruba, Christopher; Mattingly, Jameson; Druen, Devin; Cheadle, William G

2012-06-15

Persistent and tertiary chronic peritonitis is a clinically challenging problem especially in those who are critically ill. This could be attributed to a state of immune-paralysis, known as microbial tolerance. Microbial tolerance is the diminished pro-inflammatory protein response following repeated stimulation by numerous pathogen-associated molecular patterns (PAMPs) of varying origins, which we have shown in this novel model of chronic peritonitis. We aimed in this study to investigate the molecular mechanisms behind microbial tolerance and the early innate immune response resolution in this model. C57BL/6 mice were pretreated intra-peritoneally (IP) with saline or endotoxin LPS 10 mg/kg (LPS 10). Following pretreatment, peritonitis was induced 24 h later injecting 10(3)Klebsiella pneumonia CFU IP. Gentamicin was administered 4 h prior to infection and BID thereafter. Peritoneal exudate cells (PEC) were obtained through peritoneal lavage and RNA was isolated (n = 3) at 4, 24, and 48 h following infection. SA Biosciences© RT2-Profiler PCR array mouse Toll-like receptor signaling pathway (PAMM_018A) data were further analyzed by Ingenuity Pathway Inc. analysis (IPA). Of the 89 genes studied, 26 were significantly up-regulated (fold change > 1.2 and P value < 0.05) in the saline pretreated group at 4, 24, and 48 h after infection. There were no down-regulated genes. In the LPS-pretreated group, 35 genes were significantly up-regulated; of these genes, 13 were not increased in the saline pretreated infected mice. This left 22 up-regulated genes in both infected groups. At 4 h, 6 of these 22 genes (CHUK, HMGB1, HSPD1, IRAK2, LY96, and TLR4) were further 2-fold increased in the LPS pretreatment group compared with the saline pretreatment group. Only IRAK2 was 2-fold increased at 24 h. By 48 h, no LPS effect was seen. When applying IPA analysis, six main canonical pathways were constantly dysregulated in the same significance order in both the saline and LPS group at 4, 24, and 48 h. These were: Toll-like receptor and NF-κB signaling, hepatic cholestasis, interleukin-6, and LPS-mediated MAPK signaling pathways, and pattern recognition receptors of bacterial pathway. Peritonitis increased PEC gene expression associated with sepsis and a pro-inflammatory response, which was further augmented by LPS pretreatment over 24 h only. Prior exposure to LPS did not induce PEC gene tolerance to subsequent infection with Klebsiella at the mRNA level. Post-transcriptional modification as microRNA down-regulation of inflammatory cytokines could possibly explain such phenomena. Published by Elsevier Inc.

A novel synthetic derivative of melatonin, 5-hydroxy-2’-isobutyl-streptochlorin (HIS), inhibits inflammatory responses via regulation of TRIF-dependent signaling and inflammasome activation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shim, Do-Wan; Shin, Hee Jae; Han, Ji-Won

Melatonin is substantially reported to possess anti-inflammatory properties. In the present study, we synthesized a novel melatonin derivative, 5-hydroxy-2′-isobutyl-streptochlorin (HIS), which displayed superior anti-inflammatory properties to its parent compound. Further, we explored its underlying mechanisms in cellular and experimental animal models. Lipopolysaccharide was used to induce in vitro inflammatory responses in RAW 264.7 macrophages. LPS-primed macrophages were pulsed with biologically unrelated toxic molecules to evaluate the role of HIS on inflammasome activation. In vivo verifications were carried out using acute lung injury (ALI) and Escherichia coli-induced septic shock mouse models. HIS inhibited the production of proinflammatory mediators and cytokines suchmore » as nitric oxide, cyclooxygenase 2, IL-1β, IL-6 and TNF-α in LPS-stimulated RAW 264.7 macrophages. HIS suppressed the infiltration of immune cells into the lung and the production of pro-inflammatory cytokines such as IL-6 and TNF-α in broncho-alveolar lavage fluid in the ALI mouse model. Mechanistic studies revealed that the inhibitory effects of HIS were mediated through the regulation of the TIR domain-containing, adaptor-inducing, interferon-β (TRIF)-dependent signaling pathway from toll-like receptors. Further, HIS attenuated IL-1β secretion via the inhibition of NLRP3 inflammasome activation independent of mitochondrial ROS production. Furthermore, HIS suppressed IL-1β, IL-6 and interferon-β production in peritoneal lavage in the Escherichia coli-induced sepsis mouse model. In conclusion, HIS exerted potent anti-inflammatory effects via the regulation of TRIF-dependent signaling and inflammasome activation. Notably, the superior anti-inflammatory properties of this derivative compared with its parent compound could be a promising lead for treating various inflammatory-mediated diseases. - Highlights: • Νovel compound, 5-hydroxy-2′-isobutyl-streptochlorin (HIS) was synthesized. • HIS inhibited TRIF-dependent signaling induced by LPS stimulation. • HIS inhibited NLRP3 inflammasome activation. • HIS inhibited acute lung injury and Escherichia coli-induced septic shock.« less

Microdistribution of fluorescently-labeled monoclonal antibody in a peritoneal dissemination model of ovarian cancer

NASA Astrophysics Data System (ADS)

Kosaka, Nobuyuki; Ogawa, Mikako; Paik, David S.; Paik, Chang H.; Choyke, Peter L.; Kobayashi, Hisataka

2010-02-01

The microdistribution of therapeutic monoclonal antibodies within a tumor is important for determining clinical response. Nonuniform microdistribution predicts therapy failure. Herein, we developed a semiquantitative method for measuring microdistribution of an antibody within a tumor using in situ fluorescence microscopy and sought to modulate the microdistribution by altering the route and timing of antibody dosing. The microdistribution of a fluorescently-labeled antibody, trastuzumab (50-μg and 150-μg intraperitoneal injection (i.p.), and 100-μg intravenous injection (i.v.)) was evaluated in a peritoneal dissemination mouse model of ovarian cancer. In addition, we evaluated the microdistribution of concurrently-injected (30-μg i.p. and 100-μg i.v.) or serial (two doses of 30-μg i.p.) trastuzumab using in situ multicolor fluorescence microscopy. After the administration of 50-μg i.p. and 100-μg i.v. trastuzumab fluorescence imaging showed no significant difference in the central to peripheral signal ratio (C/P ratio) and demonstrated a peripheral-dominant accumulation, whereas administration of 150-μg i.p. trastuzumab showed relatively uniform, central dominant accumulation. With concurrent-i.p.-i.v. injections trastuzumab showed slightly higher C/P ratio than concurrently-injected i.p. trastuzumab. Moreover, in the serial injection study, the second injection of trastuzumab distributed more centrally than the first injection, while no difference was observed in the control group. Our results suggest that injection routes do not affect the microdistribution pattern of antibody in small peritoneal disseminations. However, increasing the dose results in a more uniform antibody distribution within peritoneal nodules. Furthermore, the serial i.p. injection of antibody can modify the microdistribution within tumor nodules. This work has implications for the optimal delivery of antibody based cancer therapies.

Some characteristics of histamine secretion from rat peritoneal mast cells stimulated with nerve growth factor.

PubMed Central

Pearce, F L; Thompson, H L

1986-01-01

Nerve growth factor (NGF) isolated from mouse submandibular gland or from snake venom produced a dose-dependent release of histamine from isolated rat peritoneal mast cells. The response was almost totally dependent on the presence of extracellular calcium ions and on added phosphatidylserine or its lyso-derivative. At high concentrations, strontium ions could substitute for calcium. The process was non-cytotoxic, relatively slow, pH dependent and blocked by polyclonal antibodies to NGF. Binding of NGF to the mast cell was not dependent on added calcium. The release was unaffected by low molecular weight glucose polymers or specific quaternary ammonium salts and thus differed from that evoked by clinical dextran or polyamines. The release was not inhibited by soluble rat IgE or IgG and was unimpaired in mast cells recovered from specific pathogen free rats. As such it did not appear to be mediated through interaction with cell-fixed antibodies. The process further differed from anaphylactic histamine release in that there was no accompanying change in the intracellular level of adenosine 3',5'-cyclic monophosphate (cyclic AMP), the activated state induced by NGF was much more persistent than that evoked by antigen, and there was no cross-desensitization between the two latter stimuli. In total, these data suggest that NGF may induce secretion from rat mast cells by interaction with a specific receptor on the plasma membrane, possibly similar to that present on sensory and sympathetic neurones. PMID:2425086

Investigation into metastatic processes and the therapeutic effects of gemcitabine on human pancreatic cancer using an orthotopic SUIT-2 pancreatic cancer mouse model

PubMed Central

Higuchi, Tamami; Yokobori, Takehiko; Naito, Tomoharu; Kakinuma, Chihaya; Hagiwara, Shinji; Nishiyama, Masahiko; Asao, Takayuki

2018-01-01

Prognosis of pancreatic cancer is poor, thus the development of novel therapeutic drugs is necessary. During preclinical studies, appropriate models are essential for evaluating drug efficacy. The present study sought to determine the ideal pancreatic cancer mouse model for reliable preclinical testing. Such a model could accurately reflect human pancreatic cancer phenotypes and predict future clinical trial results. Systemic pathology analysis was performed in an orthotopic transplantation model to prepare model mice for use in preclinical studies, mimicking the progress of human pancreatic cancer. The location and the timing of inoculated cancer cell metastases, pathogenesis and cause of fatality were analyzed. Furthermore, the efficacy of gemcitabine, a key pancreatic cancer drug, was evaluated in this model where liver metastasis and peritoneal dissemination occur. Results indicated that the SUIT-2 orthotopic pancreatic cancer model was similar to the phenotypic sequential progression of human pancreatic cancer, with extra-pancreatic invasion, intra-peritoneal dissemination and other hematogenous organ metastases. Notably, survival was prolonged by administering gemcitabine to mice with metastasized pancreatic cancer. Furthermore, the detailed effects of gemcitabine on the primary tumor and metastatic tumor lesions were pathologically evaluated in mice. The present study indicated the model accurately depicted pancreatic cancer development and metastasis. Furthermore, the detailed effects of pancreatic cancer drugs on the primary tumor and on metastatic tumor lesions. We present this model as a potential new standard for new drug development in pancreatic cancer. PMID:29435042

High mobility group box (HMGB) proteins of Plasmodium falciparum: DNA binding proteins with pro-inflammatory activity.

PubMed

Kumar, Krishan; Singal, Ankita; Rizvi, M Moshahid A; Chauhan, Virander S

2008-06-01

High mobility group box chromosomal protein 1 (HMGB1), known as an abundant, non-histone architectural chromosomal protein, is highly conserved across different species. Homologues of HMGB1 were identified and cloned from malaria parasite, Plasmodium falciparum. Sequence analyses showed that the P. falciparum HMGB1 (PfHMGB1) exhibits 45, 23 and 18%, while PfHMGB2 shares 42, 21 and 17% homology with Saccharomyces cerevisiae, human and mouse HMG box proteins respectively. Parasite PfHMGB1and PfHMGB2 proteins contain one HMG Box domain similar to B-Box of mammalian HMGB1. Electrophoretic Mobility Shift Assay (EMSA) showed that recombinant PfHMGB1 and PfHMGB2 bind to DNA. Immunofluorescence Assay using specific antibodies revealed that these proteins are expressed abundantly in the ring stage nuclei. Significant levels of PfHMGB1 and PfHMGB2 were also present in the parasite cytosol at trophozoite and schizont stages. Both, PfHMGB1 and PfHMGB2 were found to be potent inducers of pro-inflammatory cytokines such as TNFalpha from mouse peritoneal macrophages as analyzed by both reverse transcription PCR and by ELISA. These results suggest that secreted PfHMGB1 and PfHMGB2 may be responsible for eliciting/ triggering host inflammatory immune responses associated with malaria infection.

Enhanced superoxide anion production in activated peritoneal macrophages from English sole (Pleuronectes vetulus) exposed to PACs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clemons, E.; Arkoosh, M.; Casillas, E.

In fish, as in mammals, macrophages play a vital role in the destruction of infective organisms. The purpose of this study was to determine if peritoneal macrophages (M{O}s) from English sole (Pleuronectes vetulus), a marine benthic fish, have an altered ability to produce cytotoxic reactive oxygen intermediates (ROIs) after exposure to polycyclic aromatic compounds (PACs). ROIs are the principle product of M{O}s used to destroy engulfed organisms. Assay conditions, including the concentration of M{O}s, type of in vitro stimulant, tissue culture media, and incubation time were optimized to measure the production of superoxide anion (O{sub 2}{minus}), the progenitor ROI, inmore » English sole M{O}s. English sole were injected with an organic solvent extract of a PAH-contaminated sediment, equivalent to 20g sediment/kg fish, via their dorsal lymphatic sinus, and peritoneal M{O}s were harvested on days 1, 3, 5, 7, and 14 post injection. Activated peritoneal M{O}s from English sole injected with the sediment extract produced significantly more superoxide radicals after stimulation in vitro with either opsonized zymosan (OZ) or phorbol myristate acetate (PMA) than the vehicle injected or control fish. Specifically, activated peritoneal M{O}s stimulated with PMA in vitro produced greater amounts (compared to controls) of O{sub 2}{minus} on days 7 and 14 after exposure, whereas the same cells stimulated with OZ showed heightened production only on day 7 after exposure. No differences in the basal amounts of O{sub 2}{minus} production from activated peritoneal M{O}s between the treatment groups were observed. This study shows that exposure of English sole to PACs altered production of O{sub 2}{minus} by macrophages, however, the consequence to the immunocompetence of exposed fish remains to be elucidated.« less

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis

PubMed Central

Sugahara, Kazuki N.; Scodeller, Pablo; Braun, Gary B.; de Mendoza, Tatiana Hurtado; Yamazaki, Chisato M.; Kluger, Michael D.; Kitayama, Joji; Alvarez, Edwin; Howell, Stephen B.; Teesalu, Tambet; Ruoslahti, Erkki; Lowy, Andrew M.

2015-01-01

Peritoneal carcinomatosis is a major source of morbidity and mortality in patients with advanced abdominal neoplasms. Intraperitoneal chemotherapy (IPC) is an area of intense interest given its efficacy in ovarian cancer. However, IPC suffers from poor drug penetration into peritoneal tumors. As such, extensive cytoreductive surgery is required prior to IPC. Here, we explore the utility of iRGD, a tumor-penetrating peptide, for improved tumor-specific penetration of intraperitoneal compounds and enhanced IPC in mice. Intraperitoneally administered iRGD significantly enhanced penetration of an attached fluorescein into disseminated peritoneal tumor nodules. The penetration was tumor-specific, circulation-independent, and mediated by the neuropilin-binding RXXK tissue-penetration peptide motif of iRGD. Q-iRGD, which fluoresces upon cleavage, including the one that leads to RXXK activation, specifically labeled peritoneal metastases displaying different growth patterns in mice. Importantly, iRGD enhanced intratumoral entry of intraperitoneally co-injected dextran to approximately 300% and doxorubicin to 250%. Intraperitoneal iRGD/doxorubicin combination therapy inhibited the growth of bulky peritoneal tumors and reduced systemic drug toxicity. iRGD delivered attached fluorescein and co-applied nanoparticles deep into fresh human peritoneal metastasis explants. These results indicate that intraperitoneal iRGD co-administration serves as a simple and effective strategy to facilitate tumor detection and improve the therapeutic index of IPC for peritoneal carcinomatosis. PMID:26071630

Haemorrhagic shock in mice--intracellular signalling and immunomodulation of peritoneal macrophages' LPS response.

PubMed

Rani, Meenakshi; Husain, Baher; Lendemans, Sven; Schade, Fritz U; Flohé, Sascha

2006-01-01

Haemorrhagic shock leads to decreased proinflammatory cytokine response which is associated with an increased susceptibility to bacterial infections. In the present study, the effect of GM-CSF on lipopolysaccharide (LPS)-induced TNF-alpha release and MAPkinase activation was analysed on the background of a possible immunostimulating activity of this substance. Male BALB/c mice were bled to a mean arterial blood pressure of 50 mmHg for 45 min followed by resuscitation. Peritoneal macrophages were isolated 20 h after haemorrhage and incubated with 10 ng/ml GM-CSF for 6h before LPS stimulation. TNF-alpha synthesis was studied in the culture supernatants using ELISA. Phosphorylation of ERK, p38MAPK and IkappaBalpha was detected by Western blotting. LPS-induced TNF-alpha production of peritoneal macrophages was significantly decreased 20 h after haemorrhage in comparison to the corresponding cells of sham-operated mice. In parallel the phosphorylation of IkappaBalpha was less in LPS-stimulated peritoneal macrophages from haemorrhagic mice. LPS-induced phosphorylation of ERK1/2 was also decreased in peritoneal macrophages isolated after haemorrhagic shock. In contrast, p38MAPK was phosphorylated more intensely after LPS-stimulation in macrophages collected from shocked mice. GM-CSF incubation elevated LPS-induced TNF-alpha response of macrophages from both sham-operated and shocked mice which was accompanied by an elevated IkappaB and ERK phosphorylation. In general, GM-CSF treatment in vitro enhanced peritoneal macrophages LPS-response both in terms of TNF-alpha synthesis and IkappaB and MAPK signalling, but the levels always stayed lower than those of GM-CSF-treated cells from sham-operated animals. In conclusion, GM-CSF preincubation could partly reactivate the depressed functions of peritoneal macrophages and may therefore exert immunostimulating properties after shock or trauma.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Umikawa, Masato, E-mail: umikawa@med.u-ryukyu.ac.jp; Umikawa, Asako; Asato, Tsuyoshi

Monocytes and macrophages are important effectors and regulators of inflammation, and both their differentiation and activation are regulated strictly in response to environmental cues. Angiopoietin-like protein 2 (Angptl2) is a multifaceted protein, displaying many physiological and pathological functions in inflammation, angiogenesis, hematopoiesis, and tumor development. Although recent studies implicate Angptl2 in chronic inflammation, the mechanisms of inflammation caused by Angptl2 remain unclear. The purpose of the present study was to elucidate the role of Angptl2 in inflammation by understanding the effects of Angptl2 on monocytes/macrophages. We showed that Angptl2 directly activates resident murine peritoneal monocytes and macrophages and induces amore » drastic upregulation of the transcription of several inflammatory genes including nitric oxide synthase 2 and prostaglandin-endoperoxide synthase 2, and several proinflammatory cytokine genes such as interleukin (IL)-1β, IL-6, TNFα, and CSF2, along with activation of ERK, JNK, p38, and nuclear factor kappa B signaling pathways. Concordantly, proinflammatory cytokines IL-1β, IL-6, TNFα, and GM-CSF, were rapidly elevated from murine peritoneal monocytes and macrophages. These results demonstrate a novel role for Angptl2 in inflammation via the direct activation of peritoneal monocytes and macrophages. - Highlights: • Angptl2 directly activates resident murine peritoneal monocytes and macrophages. • Angptl2 induces a drastic upregulation of expression of inflammatory genes. • Angptl2 induces activation of ERK, JNK, p38, and nuclear factor kappa B signaling pathways. • Angptl2 does not activate bone marrow derived macrophages or macrophage cell lines.« less

The effect of CA1 dopaminergic system on amnesia induced by harmane in mice.

PubMed

Nasehi, Mohammad; Hasanvand, Simin; Khakpai, Fatemeh; Zarrindast, Mohammad-Reza

2018-05-16

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12 mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0.25 µg/mouse), dopamine D2 receptor agonist, quinpirole (0.125 and 0.25 µg/mouse) and dopamine D2 receptor antagonist, sulpiride (0.2 and 0.4 µg/mouse) decreased the learning of a single-trial inhibitory avoidance task. Furthermore, pre-training intra-CA1 injection of sub-threshold doses of SKF38393 (0.0625 µg/mouse) or sulpiride (0.1 µg/mouse) increased pre-training harmane (4 and 8 mg/kg, i.p.)-induced amnesia. On the other hand, pre-training intra-CA1 injection of a sub-threshold dose of SCH23390 (0.0625 µg/mouse) reversed amnesia induced by an effective dose of harmane (12 mg/kg; i.p.). In addition, Pre-training intra-CA1 injection of quinpirole (0.0625 µg/mouse) had no effect on memory impairment induced by harmane. These findings indicate the involvement of CA1 dopaminergic system on harmane-induced impairment of memory acquisition.

Glucose-Based Peritoneal Dialysis Fluids Downregulate Toll-Like Receptors and Trigger Hyporesponsiveness to Pathogen-Associated Molecular Patterns in Human Peritoneal Mesothelial Cells▿

PubMed Central

Wu, Jun; Yang, Xiao; Zhang, Yun-Fang; Wang, Ya-Ning; Liu, Mei; Dong, Xiu-Qing; Fan, Jin-Jin; Yu, Xue-Qing

2010-01-01

The objective of this study was to investigate the effects of glucose-based peritoneal dialysis (PD) fluids and icodextrin-based PD fluids on the expression of Toll-like receptor 2 (TLR2)/TLR4 and subsequent ligand-induced mitogen-activated protein kinase (MAPK) and NF-κB signaling and tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) mRNA expression in human peritoneal mesothelial cells (HPMCs). A human peritoneal mesothelial cell line (HMrSV5) was stimulated with glucose-based and icodextrin-based peritoneal dialysis fluids. Cell viability was assessed using MTT [3-(4,5-dimethylthiazolyl)-2,5-diphenyl-2H-tetrazolium bromide]. TLR2/TLR4 expression was determined by real-time PCR, Western blotting, and an immunofluorescence assay. In addition, cells were pretreated with different PD solutions and then incubated with Pam3CSK4 or lipopolysaccharide (LPS), and the degrees of MAPK and NF-κB activation were reflected by detecting the phosphorylation levels of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), p38, and p65, using a Western blot method. TNF-α and IL-1β mRNA expression was measured by real-time PCR. Glucose-based peritoneal dialysis fluids suppressed the expression of TLR2 and TLR4 proteins in HPMCs. Challenge of cells with either Pam3CSK4 or LPS resulted in impaired TNF-α and IL-1β production. Moreover, reduced TLR2 and TLR4 levels in glucose-based peritoneal dialysis solution-treated mesothelial cells were accompanied by reduced p42/44 (ERK1/2), JNK, p38 MAPK, and NF-κB p65 phosphorylation upon TLR ligand engagement. No significant changes in MAPK and NF-κB signaling and TNF-α and IL-1β mRNA expression were observed in icodextrin-based PD solution-treated mesothelial cells. Glucose-based PD solution, but not icodextrin-based PD solution, downregulates expression of TLR2/TLR4 by human peritoneal mesothelial cells and triggers hyporesponsiveness to pathogen-associated molecular patterns. PMID:20200188

Complement Factor B is the Downstream Effector of Toll-Like Receptors and Plays an Important Role in a Mouse Model of Severe Sepsis¶

PubMed Central

Zou, Lin; Feng, Yan; Li, Yan; Zhang, Ming; Chen, Chan; Cai, Jiayan; Gong, Yu; Wang, Larry; Thurman, Joshua M.; Wu, Xiaobo; Atkinson, John P.; Chao, Wei

2013-01-01

Severe sepsis involves massive activation of the innate immune system and leads to high mortality. Previous studies have demonstrated that various types of Toll-like receptors (TLRs) mediate a systemic inflammatory response and contribute to organ injury and mortality in animal models of severe sepsis. However, the downstream mechanisms responsible for TLR-mediated septic injury are poorly understood. Here, we show that activation of TLR2, TLR3 and TLR4 markedly enhanced complement factor B (cfB) synthesis and release by macrophages and cardiac cells. Polymicrobial sepsis, created by cecal ligation and puncture (CLP) in a mouse model, augmented cfB levels in the serum, peritoneal cavity and major organs including the kidney and heart. CLP also led to the alternative pathway (AP) activation, C3 fragment deposition in the kidney and heart, and cfB-dependent C3dg elevation. Bacteria isolated from septic mice activated the serum AP via a factor D-dependent manner. MyD88 deletion attenuated cfB/C3 up-regulation as well as cleavage induced by polymicrobial infection. Importantly, during sepsis, absence of cfB conferred a protective effect with improved survival and cardiac function, and markedly attenuated acute kidney injury. cfB deletion also led to increased neutrophil migratory function during the early phase of sepsis, decreased local and systemic bacterial load, attenuated cytokine production and reduced neutrophil reactive oxygen species production. Together, our data indicate that cfB acts as a downstream effector of TLR signaling and plays a critical role in the pathogenesis of severe bacterial sepsis. PMID:24154627

Kupffer cells express a unique combination of phenotypic and functional characteristics compared with splenic and peritoneal macrophages.

PubMed

Movita, Dowty; Kreefft, Kim; Biesta, Paula; van Oudenaren, Adri; Leenen, Pieter J M; Janssen, Harry L A; Boonstra, Andre

2012-10-01

The immunostimulatory role of Kupffer cells in various inflammatory liver diseases is still not fully understood. In this study, phenotypic and functional aspects of Kupffer cells from healthy C57BL/6 mice were analyzed and compared with those of splenic and peritoneal macrophages to generate a blueprint of the cells under steady-state conditions. In the mouse liver, only one population of Kupffer cells was identified as F4/80(high)CD11b(low) cells. We observed that freshy isolated Kupffer cells are endocytic and show a relatively high basal ROS content. Interestingly, despite expression of TLR mRNA on Kupffer cells, ligation of TLR4, TLR7/8, and TLR9 resulted in a weak induction of IL-10, low or undetectable levels of IL-12p40 and TNF, and up-regulation of CD40 on the surface. Kupffer cells and splenic macrophages show functional similarities, in comparison with peritoneal macrophages, as reflected by comparable levels of TLR4, TLR7/8, and TLR9 mRNA and low or undetectable levels of TNF and IL-12p40 produced upon TLR ligation. The unique, functional characteristics of Kupffer cells, demonstrated in this study, suggest that Kupffer cells under steady-state conditions are specialized as phagocytes to clear and degrade particulates and only play a limited immunoregulatory role via the release of soluble mediators.

SAHA Suppresses Peritoneal Fibrosis in Mice

PubMed Central

Io, Kumiko; Nishino, Tomoya; Obata, Yoko; Kitamura, Mineaki; Koji, Takehiko; Kohno, Shigeru

2015-01-01

♦ Objective: Long-term peritoneal dialysis causes peritoneal fibrosis in submesothelial areas. However, the mechanism of peritoneal fibrosis is unclear. Epigenetics is the mechanism to induce heritable changes without any changes in DNA sequences. Among epigenetic modifications, histone acetylation leads to the transcriptional activation of genes. Recent studies indicate that histone acetylation is involved in the progression of fibrosis. Therefore, we examined the effect of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on the progression of peritoneal fibrosis in mice. ♦ Methods: Peritoneal fibrosis was induced by the injection of chlorhexidine gluconate (CG) into the peritoneal cavity of mice every other day for 3 weeks. SAHA, or a dimethylsulfoxide and saline vehicle, was administered subcutaneously every day from the start of the CG injections for 3 weeks. Morphologic peritoneal changes were assessed by Masson’s trichrome staining, and fibrosis-associated factors were assessed by immunohistochemistry. ♦ Results: In CG-injected mice, a marked thickening of the submesothelial compact zone was observed. In contrast, the administration of SAHA suppressed the progression of submesothelial thickening and type III collagen accumulation in CG-injected mice. The numbers of fibroblast-specific protein-1-positive cells and α-smooth muscle actin α-positive cells were significantly decreased in the CG + SAHA group compared to that of the CG group. The level of histone acetylation was reduced in the peritoneum of the CG group, whereas it was increased in the CG + SAHA group. ♦ Conclusions: Our results indicate that SAHA can suppress peritoneal thickening and fibrosis in mice through up-regulation of histone acetylation. These results suggest that SAHA may have therapeutic potential for treating peritoneal fibrosis. PMID:24584598

Effects of spironolactone on residual renal function and peritoneal function in peritoneal dialysis patients.

PubMed

Yelken, Berna; Gorgulu, Numan; Gursu, Meltem; Yazici, Halil; Caliskan, Yasar; Telci, Aysegul; Ozturk, Savas; Kazancioglu, Rumeyza; Ecder, Tevfik; Bozfakioglu, Semra

2014-01-01

There is increasing evidence that long-term peritoneal dialysis (PD) is associated with structural changes in the peritoneal membrane. Inhibition of the renin-angiotensin system has been demonstrated to lessen peritoneal injury and to slow the decline in residual renal function. Whether spironolactone affects residual renal function in addition to the peritoneal membrane is unknown. We evaluated 23 patients (13 women) with a glomerular filtration rate of 2 mL/min/1.73 m2 or more who were receiving PD. Patients with an active infection or peritonitis episode were excluded. Baseline measurements were obtained for serum high-sensitivity C-reactive protein (hs-CRP), vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-beta), and connective tissue growth factor (CTGF); for daily ultrafiltration (in milliliters); for end-to-initial dialysate concentration of glucose (4/D0 glucose), Kt/V, and peritoneal transport status; and for dialysate cancer antigen 125 (CA125). Spironolactone therapy (25 mg) was given daily for 6 months, after which all measurements were repeated. Mean age of the patients was 46 +/- 13 years. Duration of PD was 15 +/- 21 months (range: 2-88 months). After spironolactone therapy, mean dialysate CA125 was significantly increased compared with baseline (20.52 +/- 12.06 U/mL vs. 24.44 +/- 13.97 U/mL, p = 0.028). Serum hs-CRP, VEGF, TGF-beta, CTGF, daily ultrafiltration, D/Do glucose, Kt/V and peritoneal transport status were similar at both times. At the end of the study period, residual glomerular filtration rate in the patients was lower. In PD patients, treatment with spironolactone seems to slow the decline of peritoneal function, suppress the elevation of profibrotic markers, and increase mesothelial cell mass.

Blockade by fenspiride of endotoxin-induced neutrophil migration in the rat.

PubMed

Cunha, F Q; Boukili, M A; da Motta, J I; Vargaftig, B B; Ferreira, S H

1993-07-06

Fenspiride, an antiinflammatory drug with low anti-cyclooxygenase activity, administered orally at 60-200 mg/kg inhibited neutrophil migration into peritoneal and air pouches cavities as well as exudation into peritoneal cavities induced by endotoxin but not induced by carrageenin. Up to 100 microM, fenspiride failed to inhibit the in vitro release of a neutrophil chemotactic activity by endotoxin-stimulated macrophages and the in vivo migration into the peritoneal cavities induced by the supernatant of those macrophages. The release of tumour necrosis factor by stimulated macrophages was inhibited by fenspiride in a dose-dependent manner. These results suggest that the antiinflammatory effects of fenspiride are associated with the inhibition of the tumour necrosis factor release by resident macrophages.

Preclinical activity of melflufen (J1) in ovarian cancer.

PubMed

Carlier, Charlotte; Strese, Sara; Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P; Gullbo, Joachim

2016-09-13

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration.

Preclinical activity of melflufen (J1) in ovarian cancer

PubMed Central

Viktorsson, Kristina; Velander, Ebba; Nygren, Peter; Uustalu, Maria; Juntti, Therese; Lewensohn, Rolf; Larsson, Rolf; Spira, Jack; De Vlieghere, Elly; Ceelen, Wim P.; Gullbo, Joachim

2016-01-01

Ovarian cancer carries a significant mortality. Since symptoms tend to be minimal, the disease is often diagnosed when peritoneal metastases are already present. The standard of care in advanced ovarian cancer consists of platinum-based chemotherapy combined with cytoreductive surgery. Unfortunately, even after optimal cytoreduction and adjuvant chemotherapy, most patients with stage III disease will develop a recurrence. Intraperitoneal administration of chemotherapy is an alternative treatment for patients with localized disease. The pharmacological and physiochemical properties of melflufen, a peptidase potentiated alkylator, raised the hypothesis that this drug could be useful in ovarian cancer and particularily against peritoneal carcinomatosis. In this study the preclinical effects of melflufen were investigated in different ovarian cancer models. Melflufen was active against ovarian cancer cell lines, primary cultures of patient-derived ovarian cancer cells, and inhibited the growth of subcutaneous A2780 ovarian cancer xenografts alone and when combined with gemcitabine or liposomal doxorubicin when administered intravenously. In addition, an intra- and subperitoneal xenograft model showed activity of intraperitoneal administered melflufen for peritoneal carcinomatosis, with minimal side effects and modest systemic exposure. In conclusion, results from this study support further investigations of melflufen for the treatment of peritoneal carcinomatosis from ovarian cancer, both for intravenous and intraperitoneal administration. PMID:27528037

Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum.

PubMed

Combet, S; Ferrier, M L; Van Landschoot, M; Stoenoiu, M; Moulin, P; Miyata, T; Lameire, N; Devuyst, O

2001-10-01

Advanced glycation end products (AGE), growth factors, and nitric oxide contribute to alterations of the peritoneum during peritoneal dialysis (PD). These mediators are also involved in chronic uremia, a condition associated with increased permeability of serosal membranes. It is unknown whether chronic uremia per se modifies the peritoneum before PD initiation. A rat model of subtotal nephrectomy was used to measure peritoneal permeability after 3, 6, and 9 wk, in parallel with peritoneal nitric oxide synthase (NOS) isoform expression and activity and structural changes. Uremic rats were characterized by a higher peritoneal permeability for small solutes and an increased NOS activity due to the up-regulation of endothelial and neuronal NOS. The permeability changes and increased NOS activities correlated with the degree of renal failure. Focal areas of vascular proliferation and fibrosis were detected in uremic rats, in relation with a transient up-regulation of vascular endothelial growth factor and basic fibroblast growth factor, as well as vascular deposits of the AGE carboxymethyllysine and pentosidine. Correction of anemia with erythropoietin did not prevent the permeability or structural changes in uremic rats. Thus, in this rat model, uremia induces permeability and structural changes in the peritoneum, in parallel with AGE deposits and up-regulation of specific NOS isoforms and growth factors. These data suggest an independent contribution of uremia in the peritoneal changes during PD and offer a paradigm to better understand the modifications of serosal membranes in uremia.

Structural analyses and immunomodulatory properties of fructo-oligosaccharides from onion (Allium cepa).

PubMed

Kumar, V Prasanna; Prashanth, K V Harish; Venkatesh, Y P

2015-03-06

Onion (Allium cepa) is an immune-boosting food rich in fructans. The major aim of this study is to characterize and investigate the immunomodulatory properties of onion fructo-oligosaccharides (FOS). FOS was isolated from onion bulbs by hot 80% ethanol extraction (yield: ∼4.5 g/100 g fw) followed by gel permeation chromatography. NMR of onion FOS revealed unusual β-D-Glc terminal residue at the non-reducing end. TLC and ESI-MS analyses showed that onion FOS ranged from trisaccharides to hexasaccharides. Onion FOS (50 μg/mL) significantly increased (∼3-fold) the proliferation of mouse splenocytes/thymocytes vs. control. Further, onion FOS enhanced (∼2.5-fold) the production of nitric oxide by peritoneal exudates cells (PECs) from Wistar rats; intracellular free radicals production and phagocytic activity of isolated murine PECs were also augmented. Our structural and in vitro results indicate that onion FOS comprising of tri- to hexasaccharide units belongs to inulin-type fructans, and possess immunostimulatory activities towards murine lymphocytes and macrophages. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gamma irradiation reduces the immunological toxicity of doxorubicin, anticancer drug

NASA Astrophysics Data System (ADS)

Kim, Jae-Hun; Sung, Nak-Yun; Raghavendran, H. Balaji; Yoon, Yohan; Song, Beom-Seok; Choi, Jong-il; Yoo, Young-Choon; Byun, Myung-Woo; Hwang, Young-Jeong; Lee, Ju-Woon

2009-07-01

Doxorubicin (DOX) is a widely used anticancer agent, but exhibits some immunological toxicity to patients during chemotherapy. The present study was conducted to evaluate the effect of gamma irradiation on the immunological response and the inhibition activity on in vivo tumor mass of DOX. The results showed that DOX irradiated at 10 and 20 kGy reduce the inhibition of mouse peritoneal macrophage proliferation and induce the release of cytokines (TNF-α and IL-6) when compared with non-irradiated DOX. The cytotoxicity against human breast (MCF-7), murine colon adenocarcinoma (Colon 26) and human monocytic (THP-1) tumor cell were not significantly different between non-irradiated and irradiated DOX ( P<0.05). In vivo study on the tumor mass inhibition, gamma-irradiated DOX showed a considerable inhibition of tumor mass and this effect was statistically non-significant as compared with non-irradiated DOX. In conclusion, gamma irradiation could be regarded as a potential method for reducing the immunological toxicity of DOX. Further researches is needed to reveal the formation and activity of radiolysis products by gamma irradiation.

Amelioration of Ischemia/Reperfusion Injury During Resuscitation from Hemorrhage by Induction of Heme Oxygenase-1 (HO-1) in a Conscious Mouse Model of Uncontrolled Hemorrhage

DTIC Science & Technology

2013-10-01

gauze. For bioluminescence imaging, mice were anes1hetized with isoflurane/a1r and injected ,v; th I 00 µ I of lucifcnn (dissolved m phosphate...buffered salme mto the peritoneal cavity. F1\\ e min after luciferin injection , mice "’ere imaged for 1-5 minutes. Photons emitted from specific regions...kidney. spleen, duodenum, jejunum, ileum, stomach, brain. salivary gland, skeletal muscle, and testes) were removed 5 min following injection of

Effect of lipopolysaccharide on protein accumulation by murine peritoneal macrophages: the correlation to activation for macrophage tumoricidal function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tannenbaum, C.S.

1987-01-01

The protein synthetic patterns of tumoricidal murine peritoneal macrophage populations have been compared to those of non-tumoricidal populations utilizing two dimensional polyacrylamide gel electrophoresis (2D PAGE) of (/sup 35/S)-methionine-labeled proteins. While the protein synthetic patterns exhibited by resident, inflammatory and activated macrophages had numerous common features which distinguished them from the other normal non-macrophage cell types examined, unique proteins also distinguished each macrophage population from the others. Peritoneal macrophages elicited by treatment with heat killed Propionibacterium acnes, the live, attenuated Mycobacterium bovis strain BCG, Listeria monocytogenes and the protozoan flagellate Trypanosoma rhodesiense, all exhibited tumoricidal activity in 16h or 72hmore » functional assays, and shared a common protein synthetic profile which differentiated them from the synthetic patterns characteristic of the non-tumoricidal resident and inflammatory macrophages.« less

As-CATH1-6, novel cathelicidins with potent antimicrobial and immunomodulatory properties from Alligator sinensis, play pivotal roles in host antimicrobial immune responses.

PubMed

Chen, Yan; Cai, Shasha; Qiao, Xue; Wu, Mali; Guo, Zhilai; Wang, Renping; Kuang, Yi-Qun; Yu, Haining; Wang, Yipeng

2017-08-10

Crocodilians are regarded as possessing a powerful immune system. However, the composition and action of the crocodilian immune system have remained unclear until now. Cathelicidins, the principal family of host defense peptides, play pivotal roles in vertebrate immune defense against microbial invasions. However, cathelicidins from crocodilians have not been extensively studied to date. In the present study, six novel cathelicidins (As-CATH1-6) were identified and characterized from the endangered Chinese alligator ( Alligator sinensis ). As-CATH1-6 exhibit no sequence similarity with any of the known cathelicidins. Structure analysis indicated that As-CATH1-3 adopt a random coil secondary conformation, whereas As-CATH4-6 were predicted to mainly adopt an amphipathic α-helix conformation. Among them, As-CATH4-6 exhibited potent, broad-spectrum and rapid antimicrobial activity by inducing the disruption of cell membrane integrity. They also exhibited strong ability to prevent the formation of bacterial biofilms and eradicate preformed biofilms. Furthermore, As-CATH4-6 exhibited potent anti-inflammatory activity by inhibiting the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and pro-inflammatory cytokines in mouse peritoneal macrophages. They directly neutralized LPS toxicity and therefore inhibited the binding of LPS to the TLR4 receptor and the subsequent activation of inflammatory response pathways. In a peritonitis mice model, As-CATH2-6 provided effective protection against bacterial infection through enhanced immune cell recruitment. In the host Chinese alligator, As-CATH1-6 are mainly expressed in immune organs and epithelial tissues. Bacterial infection significantly enhances their expression, which implies an important role in host anti-infective response. Taken together, the diversity and multiple functions of As-CATH1-6 partially reveal the powerful immune system of the Chinese alligator. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Osthole pretreatment alleviates TNBS-induced colitis in mice via both cAMP/PKA-dependent and independent pathways.

PubMed

Sun, Wu; Cai, Yun; Zhang, Xin-Xin; Chen, Hao; Lin, Yan-Die; Li, Hao

2017-08-01

Osthole, a natural coumarin found in traditional Chinese medicinal plants, has shown multiple biological activities. In the present study, we investigated the preventive effects of osthole on inflammatory bowel disease (IBD). Colitis was induced in mice by infusing TNBS into the colonic lumen. Before TNBS treatment, the mice received osthole (100 mg·kg -1 ·d -1 , ip) for 3 d. Pretreatment with osthole significantly ameliorated the clinical scores, colon length shortening, colonic histopathological changes and the expression of inflammatory mediators in TNBS-induced colitis. Pretreatment with osthole elevated serum cAMP levels; but treatment with the PKA inhibitor H89 (10 mg·kg -1 ·d -1 , ip) did not abolish the beneficial effects of osthole on TNBS-induced colitis. In mouse peritoneal macrophages, pretreatment with osthole (50 μmol/L) significantly attenuated the LPS-induced elevation of cytokines at the mRNA level; inhibition of PKA completely reversed the inhibitory effects of osthole on IL-1β, IL-6, COX2, and MCP-1 but not on TNFα. In Raw264.7 cells, the p38 inhibitor SB203580 markedly suppressed LPS-induced upregulation of the cytokines, whereas the PKA inhibitors H89 or KT5720 did not abolish the inhibitory effects of SB203580. Moreover, in LPS-stimulated mouse peritoneal macrophages, SB203580 strongly inhibited the restored expression of IL-1β, IL-6, COX2, and MCP-1, which was achieved by abolishing the suppressive effects of osthole with the PKA inhibitors. Western blot analysis showed that osthole significantly suppressed the phosphorylation of p38, which was induced by TNBS in mice or by LPS in Raw264.7 cells. Inhibition of PKA partially reversed the suppressive effects of osthole on p38 phosphorylation in LPS-stimulated cells. Collectively, our results suggest that osthole is effective in the prevention of TNBS-induced colitis by reducing the expression of inflammatory mediators and attenuating p38 phosphorylation via both cAMP/PKA-dependent and independent pathways, among which the cAMP/PKA-independent pathway plays a major role.

Experimental animal models of encapsulating peritoneal sclerosis.

PubMed

Hoff, Catherine M

2005-04-01

Encapsulating peritoneal sclerosis (EPS) is an infrequent, but extremely serious complication of long-term peritoneal dialysis. The cause of EPS is unclear, but the low incidence suggests that it is most likely multifactorial. The elucidation of developmental pathways and predictive markers of EPS would facilitate the identification and management of high-risk patients. Animal models are often used to define pathways of disease progression and to test strategies for treatment and prevention in the patient population. Ideally such models could help to define the cause of EPS and its developmental pathways, to facilitate the identification of contributing factors and predictive markers, and to provide a system to test therapeutic strategies. Researchers have studied several rodent models of EPS that rely on chronic chemical irritation (for example, bleach, low-pH solution, chlorhexidine gluconate) to induce peritoneal sclerosis and abdominal encapsulation. Development in all models is progressive, with inflammation giving way to peritoneal fibrosis or sclerosis with accumulating membrane damage, culminating in cocoon formation. Microscopic findings are similar to those proposed as diagnostic criteria for clinical EPS: an initial inflammatory infiltrate and submesothelial thickening, collagen deposition, and activation and proliferation of peritoneal fibroblasts. The potential to block progression of peritoneal sclerosis in these models by anti-inflammatory, antifibrotic, and anti-angiogenic agents, and by inhibitors of the renin-angiotensin system have been demonstrated. Animal models based on clinically relevant risk factors (for example, uremia, peritonitis, and long-term exposure to dialysis solutions) now represent the next step in model development.

Effects of Thalidomide on Intracellular Mycobacterium leprae in Normal and Activated Macrophages

PubMed Central

Tadesse, A.; Shannon, E. J.

2005-01-01

Thalidomide is an effective drug for the treatment of erythema nodosum leprosum (ENL). ENL is an inflammatory reaction that may occur in multibacillary leprosy patients. Its cause(s) as well as the mechanism of thalidomide in arresting this condition are not fully understood. It has been suggested that ENL is an immune complex-mediated hypersensitivity precipitated by the release of Mycobacterium leprae from macrophages. The released antigen may complex with precipitating antibodies, initiating complement fixation and the production of inflammatory cytokines like tumor necrosis factor alpha (TNF-α). Thalidomide has been shown in vitro to reduce antigen- or mitogen-activated macrophage production of TNF-α. We investigated if thalidomide could also influence the viability of intracellular M. leprae. Mouse peritoneal macrophages were infected with M. leprae, activated with gamma interferon and endotoxin, or nonactivated, and treated with thalidomide. Intracellular bacilli were recovered, and metabolic activity was assessed by a radiorespirometric procedure. Thalidomide did not possess antimicrobial action against M. leprae in normal and activated host macrophages. This suggests that thalidomide does not retard the release of mycobacterial antigens, a possible prelude or precipitating factor for ENL. A distinct sequence of events explaining the mechanism of action for thalidomide's successful treatment of ENL has yet to be established. PMID:15642997

Naringin Decreases TNF-α and HMGB1 Release from LPS-Stimulated Macrophages and Improves Survival in a CLP-Induced Sepsis Mice

PubMed Central

Hong, Sang Bum; Lee, Kyung Jin

2016-01-01

Naringin, a flavanone glycoside extracted from various plants, has a wide range of pharmacological effects. In the present study, we investigated naringin’s mechanism of action and its inhibitory effect on lipopolysaccharide-induced tumor necrosis factor-alpha and high-mobility group box 1 expression in macrophages, and on death in a cecal ligation and puncture induced mouse model of sepsis. Naringin increased heme oxygenase 1 expression in peritoneal macrophage cells through the activation of adenosine monophosphate-activated protein kinase, p38, and NF-E2-related factor 2. Inhibition of heme oxygenase 1 abrogated the naringin’s inhibitory effect on high-mobility group box 1 expression and NF-kB activation in lipopolysaccharide-stimulated macrophages. Moreover, mice pretreated with naringin (200 mg/kg) exhibited decreased sepsis-induced mortality and lung injury, and alleviated lung pathological changes. However, the naringin’s protective effects on sepsis-induced lung injury were eliminated by zinc protoporphyrin, a heme oxygenase 1 competitive inhibitor. These results revealed the mechanism underlying naringin’s protective effect in inflammation and may be beneficial for the treatment of sepsis. PMID:27716835

Peritoneal Macrophage-Specific TNF-α Gene Silencing in LPS-Induced Acute Inflammation Model Using CD44 Targeting Hyaluronic Acid Nanoparticles.

PubMed

Kosovrasti, Verbena Y; Nechev, Lubomir V; Amiji, Mansoor M

2016-10-03

The main goal of this study was to evaluate tumor necrosis factor-alpha (TNF-α) gene silencing in peritoneal macrophages upon activation with lipopolysaccharide (LPS), using CD44-targeting hyaluronic acid (HA)-based nanoparticles encapsulating TNF-α-specific small interfering RNA (siTNF-α). HA nanoparticles were formulated by blending hyaluronic acid-poly(ethylene imine) (HA-PEI), hyaluronic acid-hexyl fatty acid (HA-C6), and hyaluronic acid-poly(ethylene glycol) (HA-PEG) in 3:2:1 weight ratio, and encapsulating siTNF-α to form spherical particles of 78-90 nm diameter. Following intraperitoneal (IP) administration in LPS-treated C57BL/6 mice, the nanoparticles were actively taken up by macrophages and led to a significant downregulation of peritoneal TNF-α level. Downregulation of peritoneal macrophage-specific TNF-α also had a significant impact on other pro-inflammatory cytokine and chemokine levels in the serum. The C57BL/6 group of mice challenged with 5 mg/kg LPS had a significantly higher survival rate when they were treated with 3 mg/kg siTNF-α, either prior or simultaneously with the LPS administration, as compared to the LPS-challenged mice, which were treated with controls including the scrambled siRNA formulation. Overall, the results of this study demonstrate that CD44 targeting HA nanoparticles can selectively deliver siTNF-α to peritoneal macrophages leading to downregulation of pro-inflammatory cytokines in the peritoneal fluid and in the serum. This RNAi strategy could potentially provide an important therapeutic modality for acute inflammatory diseases, such as septic shock.

Lack of galectin-3 up-regulates IgA expression by peritoneal B1 lymphocytes during B cell differentiation.

PubMed

Oliveira, Felipe L; Bernardes, Emerson S; Brand, Camila; dos Santos, Sofia N; Cabanel, Mariana P; Arcanjo, Kátia D; Brito, José M; Borojevic, Radovan; Chammas, Roger; El-Cheikh, Márcia C

2016-02-01

Galectin-3 is a β-galactoside-binding protein with an inhibitory role in B cell differentiation into plasma cells in distinct lymphoid tissues. We use a model of chronic schistosomiasis, a well-characterized experimental disease hallmarked by polyclonal B cell activation, in order to investigate the role of galectin-3 in controlling IgA production through peritoneal B1 cells. Chronically infected, galectin-3-deficient mice (Lgals3(-/-)) display peritoneal fluid hypercellularity, increased numbers of atypical peritoneal IgM(+)/IgA(+) B1a and B1b lymphocytes and histological disturbances in plasma cell niches when compared with Lgals3(+/+) mice. Similar to our infection model, peritoneal B1 cells from uninfected Lgals3(-/-) mice show enhanced switching to IgA after in vitro treatment with interleukin-5 plus transforming growth factor-β (IL-5 + TGF-β1). A higher number of IgA(+) B1a lymphocytes was found in the peritoneal cavity of Lgals3(-/-)-uninfected mice at 1 week after i.p. injection of IL-5 + TGF-β1; this correlates with the increased levels of secreted IgA detected in the peritoneal fluid of these mice after cytokine treatment. Interestingly, a higher number of degranulated mast cells is present in the peritoneal cavity of uninfected and Schistosoma mansoni-infected Lgals3(-/-) mice, indicating that, at least in part, mast cells account for the enhanced differentiation of B1 into IgA-producing B cells found in the absence of galectin-3. Thus, a novel role is revealed for galectin-3 in controlling the expression of surface IgA by peritoneal B1 lymphocytes; this might have important implications for manipulating the mucosal immune response.

Effect of pyrazinamide and probenecid on peritoneal urate transport kinetics during continuous ambulatory peritoneal dialysis.

PubMed

Spaia, S; Magoula, I; Tsapas, G; Vayonas, G

2000-01-01

We administered pyrazinamide (PZA) and probenecid (PB) --two well-known modulators of urate transport via the proximal tubules - to evaluate their impact on urate transport through the peritoneal membrane and to clarify mechanisms affecting peritoneal transport. A continuous ambulatory peritoneal dialysis (CAPD) unit in 2nd Hospital of IKA (Social Services Institute), Greece. In 20 stable CAPD patients, on the study day, a 4-hour, 2-L, 1.36% glucose exchange was performed (control exchange). Pyrazinamide 3 g was given orally and another identical exchange was performed (study exchange). The same protocol was repeated with 2 g PB. KtN, peritoneal clearances of urea, creatinine, and urate for each exchange, and mass transfer area coefficients (MTAC) for the three solutes and their dialysate-to-plasma concentration (D/P) ratios were used to estimate peritoneal transport. Administration of PZA resulted in decreased clearances and MTAC values for the three solutes. The D/P ratio decreased significantly only for urate, indicating a more intense influence of PZA on urate. After PB administration, clearances of urea, creatinine, and urate were increased. MTAC and DIP ratio increased significantly only for urate (p < 0.05), demonstrating an action similar to that exerted on renal tubules. These findings provide evidence that unrestricted diffusion is not the only transport mechanism in the case of urate, and demonstrate the existence of an active mechanism in peritoneal urate transport with a reabsorptive and, probably, a secretive component that resembles that of renal tubule urate transport. Attention should be given in the case of CAPD patients undergoing antituberculous (PZA) treatment: it might have a negative impact on urea, creatinine, and urate peritoneal transport rates.

Educational strategies and challenges in peritoneal dialysis: a qualitative study of renal nurses' experiences.

PubMed

Bergjan, Manuela; Schaepe, Christiane

2016-06-01

The aim of the study was to explore renal nurses' experiences, strategies and challenges with regard to the patient education process in peritoneal dialysis. Patient education in peritoneal dialysis is essential to developing a successful home-based peritoneal dialysis program. In this area research is scarce and there is a particular lack of focus on the perspective of the renal nurse. Qualitative design formed by thematic qualitative text analysis. Five group interviews (n = 20) were used to explore the challenges peritoneal dialysis nurses face and the training strategies they use. The interviews were analyzed with thematic qualitative content analysis using deductive and inductive subcategory application. The findings revealed the education barriers perceived by nurses that patients may face. They also showed that using assessment tools is important in peritoneal dialysis patient education, as is developing strategies to promote patient self-management. There is a need for a deeper understanding of affective learning objectives, and existing teaching activities and materials should be revised to incorporate the patient's perspective. Patients usually begin having questions about peritoneal dialysis when they return home and are described as feeling overwhelmed. Adapting existing conditions is considered a major challenge for patients and nurses. The results provided useful insights into the best approaches to educating peritoneal dialysis patients and served to raise awareness of challenges experienced by renal nurses. Findings underline the need for nosogogy - an approach of teaching adults (andragogy) with a chronic disease. Flexibility and cooperation are competencies that renal nurses must possess. Still psychomotor skills dominate peritoneal dialysis patient training, there is a need of both a deeper understanding of affective learning objectives and the accurate use of (self-)assessment tools, particularly for health literacy. © 2016 John Wiley & Sons Ltd.

Anti-inflammatory and anti-granuloma activity of Berberis aristata DC. in experimental models of inflammation

PubMed Central

Kumar, Rohit; Gupta, Yogendra Kumar; Singh, Surender

2016-01-01

Objective: Berberis aristata (Berberidaceae) is an important medicinal plant used in traditional system of medicine for the treatment of rheumatoid arthritis and other inflammatory disorders. The aim of the present study is to scientifically validate the traditional use of BA in the treatment of inflammatory disorders. Materials and Methods: Anti-inflammatory and anti-granuloma activity of BA hydroalcoholic extract (BAHE) were evaluated in experimental models, viz., carrageenan-induced paw edema, cotton pellet-induced granuloma formation, and complete Freund's adjuvant-induced stimulation of peritoneal macrophages in rats. Expression of inflammatory mediators, viz., tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-10, TNF-R1, and cyclooxygenase-2 (COX-2) was carried out in serum and peritoneal macrophages to derive the plausible mechanism of BAHE in activated peritoneal macrophages. Results: Pretreatment with BAHE produced a dose-dependent reduction (P < 0.01) in carrageenan-induced paw edema and cotton pellet-induced granuloma model. BAHE treatment produced significant (P < 0.01) reduction in serum inflammatory cytokine levels as compared to control. Protein expression of pro-inflammatory markers, IL-1β, IL-6, TNF-R1, and COX-2, was found to be reduced in stimulated macrophages whereas anti-inflammatory cytokine, IL-10, was upregulated in peritoneal macrophages. Conclusion: The result of the present study thus demonstrates the anti-inflammatory and anti-granuloma activity of BAHE which may be attributed to its inhibitory activity on macrophage-derived cytokine and mediators. PMID:27114638

The Secretory Response of Rat Peritoneal Mast Cells on Exposure to Mineral Fibers.

PubMed

Borelli, Violetta; Trevisan, Elisa; Francesca, Vita; Zabucchi, Giuliano

2018-01-10

Exposure to mineral fibers is of substantial relevance to human health. A key event in exposure is the interaction with inflammatory cells and the subsequent generation of pro-inflammatory factors. Mast cells (MCs) have been shown to interact with titanium oxide (TiO₂) and asbestos fibers. In this study, we compared the response of rat peritoneal MCs challenged with the asbestos crocidolite and nanowires of TiO₂ to that induced by wollastonite employed as a control fiber. Rat peritoneal MCs (RPMCs), isolated from peritoneal lavage, were incubated in the presence of mineral fibers. The quantities of secreted enzymes were evaluated together with the activity of fiber-associated enzymes. The ultrastructural morphology of fiber-interacting RPMCs was analyzed with electron microscopy. Asbestos and TiO₂ stimulate MC secretion. Secreted enzymes bind to fibers and exhibit higher activity. TiO₂ and wollastonite bind and improve enzyme activity, but to a lesser degree than crocidolite. (1) Mineral fibers are able to stimulate the mast cell secretory process by both active (during membrane interaction) and/or passive (during membrane penetration) interaction; (2) fibers can be found to be associated with secreted enzymes-this process appears to create long-lasting pro-inflammatory environments and may represent the active contribution of MCs in maintaining the inflammatory process; (3) MCs and their enzymes should be considered as a therapeutic target in the pathogenesis of asbestos-induced lung inflammation; and (4) MCs can contribute to the inflammatory effect associated with selected engineered nanomaterials, such as TiO₂ nanoparticles.

Prior reproductive experience alters prolactin-induced macrophage responses in pregnant rats.

PubMed

Carvalho-Freitas, Maria Isabel Roth; Anselmo-Franci, Janete A; Palermo-Neto, João; Felicio, Luciano F

2013-09-01

Reproductive experience (i.e., pregnancy and lactation) induces physiological changes in mammals. A previous reproductive experience was recently shown to modulate the activity of dopaminergic hypothalamic systems while decreasing serum prolactin levels and oxidative burst activity in peritoneal macrophages. Dopamine receptor antagonists increase serum prolactin levels, and both prolactin and dopamine receptors may be involved in the modulation of macrophage activity, providing a means of communication between the nervous and immune systems. The present study evaluated the in vitro effects of prolactin and a dopamine D2 receptor antagonist on the peritoneal activity of macrophages from primigravid and multigravid female rats during the third trimester of pregnancy. Oxidative bursts and phagocytosis in peritoneal macrophages were evaluated by flow cytometry. Primigravid and multigravid Wistar rats, during the third trimester of pregnancy (i.e., days 17-21), were used. Peritoneal fluid samples from these rats were first incubated with prolactin (10 and 100 nM) for different periods of time. The same procedure was repeated to evaluate the effects of domperidone (10 and 100 nM) on macrophage activity. Our results showed that macrophages from multigravid rats responded more effectively to in vitro incubation with prolactin, especially with regard to the intensity and percentage of phagocytosis. Additionally, these effects were more pronounced after incubation periods of 30 min or 4 h. These data suggest that macrophages during a second pregnancy become more sensitive to the phagocytotic effects of prolactin. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Fetal and Placental DNA Stimulation of TLR9: A Mechanism Possibly Contributing to the Pro-inflammatory Events During Parturition.

PubMed

Goldfarb, Ilona Telefus; Adeli, Sharareh; Berk, Tucker; Phillippe, Mark

2018-05-01

While there is evidence for a relationship between cell-free fetal DNA (cffDNA) and parturition, questions remain regarding whether cffDNA could trigger a pro-inflammatory response on the pathway to parturition. We hypothesized that placental and/or fetal DNA stimulates toll-like receptor 9 (TLR9) leading to secretion of pro-inflammatory cytokines by macrophage cells. Four in vitro DNA stimulation studies were performed using RAW 264.7 mouse peritoneal macrophage cells incubated in media containing the following DNA particles: an oligodeoxynucleotide (ODN2395), intact genomic DNA (from mouse placentas, fetuses and adult liver), mouse DNA complexed with DOTAP (a cationic liposome forming compound), and telomere-depleted mouse DNA. Interleukin 6 (IL6) secretion was measured in the media by enzyme-linked immunosorbent assay; and the cell pellet was homogenized for protein content (picograms IL6/mg protein). Robust IL6 secretion was observed in response to ODN2395 (a CpG-rich TLR9 agonist), mouse DNA-DOTAP complexes, and telomere-depleted mouse DNA in concentrations of 5 to 15 μg/mL. In contrast, ODN A151 (containing telomere sequence motifs), intact genomic mouse DNA, and restriction enzyme-digested DNA had no effect on IL6 secretion. The IL6 response was significantly inhibited by chloroquine (10 μg/mL), thereby confirming the important role for TLR9 in the response by macrophage cells. DNA derived from mouse placentas and fetuses, and depleted of telomeric sequences, stimulates a robust pro-inflammatory response by macrophage cells, thereby supporting the hypothesis that cffDNA is able to stimulate an innate immune response that could trigger the onset of parturition. These findings are of clinical importance, as we search for effective treatment/prevention of preterm parturition.

Regulation of complement C3 and C4 synthesis in human peritoneal mesothelial cells by peritoneal dialysis fluid

PubMed Central

TANG, S; LEUNG, J C K; CHAN, L Y Y; TSANG, A W L; CHEN, C X R; ZHOU, W; LAI, K N; SACKS, S H

2004-01-01

Although complement is activated in the peritoneal cavity during chronic peritoneal dialysis (PD), little is known about its role in peritoneal defence and injury related to long-term PD. We examined the impact of glucose and commercial peritoneal dialysis solutions on complement expression in HPMCs obtained by primary culture from omental tissues of consented patients undergoing elective abdominal surgery. Constitutive expression of C3 and C4 mRNA in HPMCs was up-regulated upon exposure to 75 mm glucose in a time-dependent manner. C3 and C4 protein was secreted in both apical and basolateral directions. Glucose doses beyond 100 mm markedly down-regulated C3 and C4 expression, and stimulated LDH release dose-dependently. Such cytotoxic effects were attenuated using equivalent doses of mannitol instead of glucose. Treatment with conventional lactate-buffered dialysis solution gave rise to down-regulation of C3 and C4 expression, and heightened LDH release in HPMCs. These effects correlated with the glucose strength of the solution, persisted despite replacement with a bicarbonate-buffered solution, aggravated by glycated albumin, and were partially abrogated by supplementation with 10% fetal bovine serum in the culture system. Our findings suggest that the artificial conditions imposed by PD lead to alterations in local complement synthesis that have implications for the role of the peritoneal mesothelium in both inflammation and defence. PMID:15030518

Comparative activation states of tumor-associated and peritoneal macrophages from mice bearing an induced fibrosarcoma.

PubMed

Valdez, J C; de Alderete, N; Meson, O E; Sirena, A; Perdigon, G

1990-11-01

Balb/c mice bearing a methylcholanthrene-induced fibrosarcoma were used to compare the activation levels of tumor-associated and peritoneal macrophages. Two stages of tumor growth were examined, namely "small" and "large" tumors, with average diameters of 10 and 30 mm, respectively. The activation state, determined by measurement of both phagocytic index and beta-glucuronidase content, was found to be markedly higher in tumor-associated macrophages than in their peritoneal counterparts and it was, in addition, independent of tumor progression. The percentage of tumor-associated macrophages, which were detected on the basis of Fc receptor expression, remained constant in the growing neoplasm, at approximately 23% of total cell population. None of these parameters were affected by inoculation with an immunopotentiating dose of heat-killed Candida albicans which, on the other hand, seemed not to alter the course of the tumor. These data suggest that within the tumor microenvironment macrophages would somehow be maintained at a constant proportion and at a highly activated state, while outside the tumor they would be at a lower activation level. Our results also suggest that TAM would not possess antitumor activity in vivo, although we have found this activity in vitro.

[Formation of endogenous pyrogen by mononuclear phagocytes].

PubMed

Agasarov, L G

1980-03-01

Incubation of alveolar macrophages of rabbits and peritoneal macrophages of the abdominal cavity washing of albino mice does not lead to endogenous pyrogen release. Peritoneal macrophages obtained after peritoneal administration to mice of thioglycollate, glycogen or heterologous blood cells do not discharge pyrogen either during incubation without additional stimulation. Macrophages isolated after intraperitoneal administration of heterologous blood cells do not exhibit pyrogenic activity possibly because of a long period of time elapsed after phagocytosis of foreign agents. The triggering of pyrogen formation by macrophages can be effected by means of in vitro phagocytosis of corpuscular particles: staphylococci or heterologous blood cells.

TNFα-induced IKKβ complex activation influences epithelial, but not stromal cell survival in endometriosis.

PubMed

Kocbek, Vida; Grandi, Giovanni; Blank, Fabian; Wotzkow, Carlos; Bersinger, Nick A; Mueller, Michael D; Kyo, Satoru; McKinnon, Brett D

2016-11-01

Can the activity of the IκB kinase (IKKβ) complex in endometriotic cells contribute to endometriotic lesion survival? There is a constitutive activity of the IKKβ catalytic complex in peritoneal and deeply infiltrating lesions that can influence epithelial, but not stromal cell viability. Endometriotic lesions exist in an inflammatory microenvironment with higher local concentrations of cytokines, such as tumour necrosis factor α (TNFα). TNFα stimulates the activation of the IKKβ complex, an important nodal point in multiple signalling pathways that influence gene transcription, proliferation and apoptosis. However, few data on the regulation of IKKβ in endometriotic tissue are currently available. A retrospective analysis of endometriotic tissue from peritoneal, ovarian and deeply infiltrating lesions from 37 women. Basal and activated (phosphorylated) IKKβ concentrations were analysed by western blotting and immunohistochemistry. The relationship between the expression and activation of these proteins and peritoneal fluid (TNFα) concentrations, measured via ELISA, was examined. A subsequent in vitro analysis of TNFα treatment on the activation of IKKβ and the effect on epithelial and stromal cell viability by its inhibition with PS1145 was also performed. Levels of the phosphorylated IKKβ complex in endometriotic lesions had a significant positive correlation with peritoneal fluid TNFα concentrations. Phosphorylated IKKβ complex was more prevalent in peritoneal and deeply infiltrating endometriosis lesions compared with ovarian lesions. IKKβ was present in both epithelial and stromal cells in all lesions but active IKKβ was limited to epithelial cells. TNFα stimulated an increased expression of phosphorylated IKKβ and the inhibition of this kinase with PS1145 significantly influenced ectopic epithelial cells viability but not eutopic epithelial cells, or endometrial stromal cells. In vitro analysis on epithelial cells was performed with immortalized cell lines and not primary cell cultures and only low sample numbers were available for the study. The regulation of aberrant signalling pathways represents a promising yet relatively unexplored area of endometriosis progression. The IKKβ complex is activated by inflammation and is critical nodal point of numerous downstream kinase-signalling pathways, including NFκB (nuclear factor κB), mTOR (mammalian target of rapamycin) and BAD (Bcl2-antagonist of cell death). This study shows a significant relationship between peritoneal fluid TNFα and IKKβ activation in epithelial cells that will have significant consequences for the continued survival of these cells at ectopic locations through the regulation of downstream pathways. None. The study was funded by the Swiss National Science Foundation (Grant Number 320030_140774). The authors have no conflict of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Vaccine-induced modulation of gene expression in turbot peritoneal cells. A microarray approach.

PubMed

Fontenla, Francisco; Blanco-Abad, Verónica; Pardo, Belén G; Folgueira, Iria; Noia, Manuel; Gómez-Tato, Antonio; Martínez, Paulino; Leiro, José M; Lamas, Jesús

2016-07-01

We used a microarray approach to examine changes in gene expression in turbot peritoneal cells after injection of the fish with vaccines containing the ciliate parasite Philasterides dicentrarchi as antigen and one of the following adjuvants: chitosan-PVMMA microspheres, Freund́s complete adjuvant, aluminium hydroxide gel or Matrix-Q (Isconova, Sweden). We identified 374 genes that were differentially expressed in all groups of fish. Forty-two genes related to tight junctions and focal adhesions and/or actin cytoskeleton were differentially expressed in free peritoneal cells. The profound changes in gene expression related to cell adherence and cytoskeleton may be associated with cell migration and also with the formation of cell-vaccine masses and their attachment to the peritoneal wall. Thirty-five genes related to apoptosis were differentially expressed. Although most of the proteins coded by these genes have a proapoptotic effect, others are antiapoptotic, indicating that both types of signals occur in peritoneal leukocytes of vaccinated fish. Interestingly, many of the genes related to lymphocytes and lymphocyte activity were downregulated in the groups injected with vaccine. We also observed decreased expression of genes related to antigen presentation, suggesting that macrophages (which were abundant in the peritoneal cavity after vaccination) did not express these during the early inflammatory response in the peritoneal cavity. Finally, several genes that participate in the inflammatory response were differentially expressed, and most participated in resolution of inflammation, indicating that an M2 macrophage response is generated in the peritoneal cavity of fish one day post vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Calibration of a semi-automated segmenting method for quantification of adipose tissue compartments from magnetic resonance images of mice.

PubMed

Garteiser, Philippe; Doblas, Sabrina; Towner, Rheal A; Griffin, Timothy M

2013-11-01

To use an automated water-suppressed magnetic resonance imaging (MRI) method to objectively assess adipose tissue (AT) volumes in whole body and specific regional body components (subcutaneous, thoracic and peritoneal) of obese and lean mice. Water-suppressed MR images were obtained on a 7T, horizontal-bore MRI system in whole bodies (excluding head) of 26 week old male C57BL6J mice fed a control (10% kcal fat) or high-fat diet (60% kcal fat) for 20 weeks. Manual (outlined regions) versus automated (Gaussian fitting applied to threshold-weighted images) segmentation procedures were compared for whole body AT and regional AT volumes (i.e., subcutaneous, thoracic, and peritoneal). The AT automated segmentation method was compared to dual-energy X-ray (DXA) analysis. The average AT volumes for whole body and individual compartments correlated well between the manual outlining and the automated methods (R2>0.77, p<0.05). Subcutaneous, peritoneal, and total body AT volumes were increased 2-3 fold and thoracic AT volume increased more than 5-fold in diet-induced obese mice versus controls (p<0.05). MRI and DXA-based method comparisons were highly correlative (R2=0.94, p<0.0001). Automated AT segmentation of water-suppressed MRI data using a global Gaussian filtering algorithm resulted in a fairly accurate assessment of total and regional AT volumes in a pre-clinical mouse model of obesity. © 2013 Elsevier Inc. All rights reserved.

Effects of Taraxacum officinale on fatigue and immunological parameters in mice.

PubMed

Lee, Bo-Ra; Lee, Jong-Hyun; An, Hyo-Jin

2012-11-07

In Korean herbal medicine dandelion (Taraxacum officinale, TO) has been used to improve energy levels and health. However, the effects of TO in experimental models remain unclear. We examined the anti-fatigue and immune-enhancing effects of TO in mice by performing a forced swimming test (FST) and in vitro by using peritoneal macrophages, respectively. After daily oral administration of TO, blood biochemical parameters related to fatigue were measured after the FST. FST immobility time was significantly decreased in the TO-treated group (100 mg/kg) on the tenth day. TO (10 and 100 mg/kg) treatment significantly increased glucose levels, acting as an energy source. The level of lactic dehydrogenase, which is an accurate indicator of muscle damage, tended to decline after TO administration (10 and 100 mg/kg). When TO (100 mg/kg) was orally administered to mice, blood urea nitrogen levels decreased significantly. We also examined the effect of TO on the production of cytokines and nitric oxide (NO) in mouse peritoneal macrophages. When TO was used in combination with recombinant interferon-gamma (rIFN-γ), a noticeable cooperative induction of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-12p70, and IL-10 production was observed. Furthermore, in peritoneal macrophages, rIFN-γ plus TO treatment significantly increased the production of NO through inducible nitric oxide synthase (iNOS) induction. Taken together, these results suggest that TO improves fatigue-related indicators and immunological parameters in mice.

Hemojuvelin regulates the innate immune response to peritoneal bacterial infection in mice.

PubMed

Wu, Qian; Shen, Yuanyuan; Tao, Yunlong; Wei, Jiayu; Wang, Hao; An, Peng; Zhang, Zhuzhen; Gao, Hong; Zhou, Tianhua; Wang, Fudi; Min, Junxia

2017-01-01

Hereditary hemochromatosis and iron imbalance are associated with susceptibility to bacterial infection; however, the underlying mechanisms are poorly understood. Here, we performed in vivo bacterial infection screening using several mouse models of hemochromatosis, including Hfe ( Hfe -/- ), hemojuvelin ( Hjv -/- ), and macrophage-specific ferroportin-1 ( Fpn1 fl/fl ; LysM-Cre + ) knockout mice. We found that Hjv -/- mice, but not Hfe -/- or Fpn1 fl/fl ; LysM-Cre + mice, are highly susceptible to peritoneal infection by both Gram-negative and Gram-positive bacteria. Interestingly, phagocytic cells in the peritoneum of Hjv -/- mice have reduced bacterial clearance, IFN-γ secretion, and nitric oxide production; in contrast, both cell migration and phagocytosis are normal. Expressing Hjv in RAW264.7 cells increased the level of phosphorylated Stat1 and nitric oxide production. Moreover, macrophage-specific Hjv knockout mice are susceptible to bacterial infection. Finally, we found that Hjv facilitates the secretion of IFN-γ via the IL-12/Jak2/Stat4 signaling pathway. Together, these findings reveal a novel protective role of Hjv in the early stages of antimicrobial defense.

Involvement of the Receptor for Formylated Peptides in the in Vivo Anti-Migratory Actions of Annexin 1 and its Mimetics

PubMed Central

Perretti, Mauro; Getting, Stephen J.; Solito, Egle; Murphy, Philip M.; Gao, Ji-Liang

2001-01-01

An innovative avenue for anti-inflammatory therapy is inhibition of neutrophil extravasation by potentiating the action of endogenous anti-inflammatory mediators. The glucocorticoid-inducible protein annexin 1 and derived peptides are effective in inhibiting neutrophil extravasation. Here we tested the hypothesis that an interaction with the receptor for formylated peptide (FPR), so far reported only in vitro, could be the mechanism for this in vivo action. In a model of mouse peritonitis, FPR antagonists abrogated the anti-migratory effects of peptides Ac2-26 and Ac2-12, with a partial reduction in annexin 1 effects. A similar result was obtained in FPR (knock-out) KO mice. Binding of annexin 1 to circulating leukocytes was reduced (>50%) in FPR KO mice. In vitro, annexin binding to peritoneal macrophages was also markedly reduced in FPR KO mice. Finally, evidence of direct annexin 1 binding to murine FPR was obtained with HEK-293 cells transfected with the receptor. Overall, these results indicate a functional role for FPR in the anti-migratory effect of annexin 1 and derived peptides. PMID:11395373

Effects of Corynebacterium parvum treatment and Toxoplasma gondii infection on macrophage-mediated cytostasis of tumour target cells.

PubMed Central

Krahenbuhl, J L; Lambert, L H; Remington, J S

1976-01-01

Injection of mice with Corynebacterium parvum or living or killed Toxoplasma gondii was studied to determine the efficacy of these treatments in activating peritoneal macrophages to inhibit the uptake of [3H]TdR (cytostasis) by tumour target cells in vitro. In the presence of activated macrophages from mice treated i.p. with a wide dose range of either C. parvum or living Toxoplasma, cytostasis was usually greater than 99%. This population of activated macrophages was transient in C. parvum-treated mice, but persists, probably for life, in Toxoplasma-infected mice. Whereas the i.p. route of administration of C. parvum was more efficient in activating macrophages than the i.v. route, the s.c. route appeared to be relatively ineffective. Treatment with killed Toxoplasma by any route was also relatively ineffective in activating macrophages. In contrast Toxoplasma infection resulted in highly activated peritoneal macrophages, regardless of the route of administration. Depending upon the route of initial treatment, the route of readministration of C. parvum had either no appreciable effect or resulted in a marked alteration in the cytostatic capacity of peritoneal macrophages. PMID:992714

A cell-ELISA for the quantification of adherent murine macrophages and the surface expression of antigens.

PubMed

Nibbering, P H; Van de Gevel, J S; Van Furth, R

1990-07-20

The present study was performed in order to establish whether a cell-ELISA could be used to determine the expression of antigens by adherent murine peritoneal macrophages and also quantify the numbers of such macrophages. Accurate determination of the number of adherent macrophages proved to be possible with a cell-ELISA designed to assess complement receptor type III (CRIII) expression. Expression of CRIII was considerably more sensitive than determination of the cell-protein or DNA content as a measure of the number of adherent macrophages. For the calculation of the expression of CRIII, Ia antigen, and antigen F4/80 by resident and activated macrophages, use was made of the linear part of the curve obtained when the numbers of macrophages were plotted against the absorbance values for each of the antigens. The values for CRIII expression did not differ significantly between resident macrophages, macrophages activated with recombinant interferon-gamma (rIFN-gamma) and macrophages activated with BCG/PPD. IFN-gamma-activated and BCG/PPD-activated macrophages expressed Ia antigen significantly more intensely than did resident peritoneal macrophages. In contrast the activated macrophages expressed F4/80 significantly less intensely than resident peritoneal macrophages.

Tetrahydrocannabinol-induced suppression of macrophage spreading and phagocytic activity in vitro.

PubMed

Lopez-Cepero, M; Friedman, M; Klein, T; Friedman, H

1986-06-01

The effects of tetrahydrocannabinol (THC) on several parameters of macrophage function in vitro were assessed. Delta 9 THC added to cultures of normal mouse peritoneal cells in vitro affected the ability of the cells to spread on glass surfaces and also had some effect on their ability to phagocytize yeast. These effects were dose related. A concentration of 20 micrograms of THC almost completely inhibited macrophage spreading, but it also decreased viability and the total number of these cells. Doses of 10 or 5 micrograms of THC also inhibited spreading but had little effect on cell viability or number. A dose of 1.0 microgram of THC had some inhibitory effect on spreading and the lowest dose affecting spreading appeared to be about 0.05 micrograms per culture. Higher doses of THC were necessary to inhibit phagocytosis of yeast particles as determined by direct microscopic examination or use of radiolabeled yeast as the test particles. These results indicate that several readily measured functions of macrophages may be suppressed by THC.

2-Thioxanthines Are Mechanism-based Inactivators of Myeloperoxidase That Block Oxidative Stress during Inflammation*

PubMed Central

Tidén, Anna-Karin; Sjögren, Tove; Svensson, Mats; Bernlind, Alexandra; Senthilmohan, Revathy; Auchère, Francoise; Norman, Henrietta; Markgren, Per-Olof; Gustavsson, Susanne; Schmidt, Staffan; Lundquist, Stefan; Forbes, Louisa V.; Magon, Nicholas J.; Paton, Louise N.; Jameson, Guy N. L.; Eriksson, Håkan; Kettle, Anthony J.

2011-01-01

Myeloperoxidase (MPO) is a prime candidate for promoting oxidative stress during inflammation. This abundant enzyme of neutrophils uses hydrogen peroxide to oxidize chloride to highly reactive and toxic chlorine bleach. We have identified 2-thioxanthines as potent mechanism-based inactivators of MPO. Mass spectrometry and x-ray crystal structures revealed that these inhibitors become covalently attached to the heme prosthetic groups of the enzyme. We propose a mechanism whereby 2-thioxanthines are oxidized, and their incipient free radicals react with the heme groups of the enzyme before they can exit the active site. 2-Thioxanthines inhibited MPO in plasma and decreased protein chlorination in a mouse model of peritonitis. They slowed but did not prevent neutrophils from killing bacteria and were poor inhibitors of thyroid peroxidase. Our study shows that MPO is susceptible to the free radicals it generates, and this Achilles' heel of the enzyme can be exploited to block oxidative stress during inflammation. PMID:21880720

Neutrophils Are Central to Antibody-Mediated Protection against Genital Chlamydia.

PubMed

Naglak, Elizabeth K; Morrison, Sandra G; Morrison, Richard P

2017-10-01

Determining the effector populations involved in humoral protection against genital chlamydia infection is crucial to development of an effective chlamydial vaccine. Antibody has been implicated in protection studies in multiple animal models, and we previously showed that the passive transfer of immune serum alone does not confer immunity in the mouse. Using the Chlamydia muridarum model of genital infection, we demonstrate a protective role for both Chlamydia -specific immunoglobulin G (IgG) and polymorphonuclear neutrophils and show the importance of an antibody/effector cell interaction in mediating humoral immunity. While neutrophils were found to contribute significantly to antibody-mediated protection in vivo , natural killer (NK) cells were dispensable for protective immunity. Furthermore, gamma interferon (IFN-γ)-stimulated primary peritoneal neutrophils (PPNs) killed chlamydiae in vitro in an antibody-dependent manner. The results from this study support the view that an IFN-γ-activated effector cell population cooperates with antibody to protect against genital chlamydia and establish neutrophils as a key effector cell in this response. Copyright © 2017 Naglak et al.

IL-23-induced macrophage polarization and its pathological roles in mice with imiquimod-induced psoriasis.

PubMed

Hou, Yuzhu; Zhu, Linnan; Tian, Hongling; Sun, Hai-Xi; Wang, Ruoyu; Zhang, Lianfeng; Zhao, Yong

2018-03-05

Macrophages acquire distinct phenotypes during tissue stress and inflammatory responses. Macrophages are roughly categorized into two different subsets named inflammatory M1 and anti-inflammatory M2 macrophages. We herein identified a unique pathogenic macrophage subpopulation driven by IL-23 with a distinct gene expression profile including defined types of cytokines. The freshly isolated resting mouse peritoneal macrophages were stimulated with different cytokines in vitro, the expression of cytokines and chemokines were detected by microarray, real-time PCR, ELISA and multiple colors flow cytometry. Adoptive transfer of macrophages and imiquimod-induced psoriasis mice were used. In contrast to M1- and M2-polarized macrophages, IL-23-treated macrophages produce large amounts of IL-17A, IL-22 and IFN-γ. Biochemical and molecular studies showed that IL-23 induces IL-17A expression in macrophages through the signal transducer and activator of transcription 3 (STAT3)-retinoid related orphan receptor-γ T (RORγT) pathway. T-bet mediates the IFN-γ production in IL-23-treated macrophages. Importantly, IL-23-treated macrophages significantly promote the dermatitis pathogenesis in a psoriasis-like mouse model. IL-23-treated resting macrophages express a distinctive gene expression prolife compared with M1 and M2 macrophages. The identification of IL-23-induced macrophage polarization may help us to understand the contribution of macrophage subpopulation in Th17-cytokines-related pathogenesis.

Identification of a Novel Pathway of Transforming Growth Factor-β1 Regulation by Extracellular NAD+ in Mouse Macrophages

PubMed Central

Zamora, Ruben; Azhar, Nabil; Namas, Rajaie; Metukuri, Mallikarjuna R.; Clermont, Thierry; Gladstone, Chase; Namas, Rami A.; Hermus, Linda; Megas, Cristina; Constantine, Gregory; Billiar, Timothy R.; Fink, Mitchell P.; Vodovotz, Yoram

2012-01-01

Extracellular β-nicotinamide adenine dinucleotide (NAD+) is anti-inflammatory. We hypothesized that NAD+ would modulate the anti-inflammatory cytokine Transforming Growth Factor (TGF)-β1. Indeed, NAD+ led to increases in both active and latent cell-associated TGF-β1 in RAW 264.7 mouse macrophages as well as in primary peritoneal macrophages isolated from both C3H/HeJ (TLR4-mutant) and C3H/HeOuJ (wild-type controls for C3H/HeJ) mice. NAD+ acts partially via cyclic ADP-ribose (cADPR) and subsequent release of Ca2+. Treatment of macrophages with the cADPR analog 3-deaza-cADPR or Ca2+ ionophores recapitulated the effects of NAD+ on TGF-β1, whereas the cADPR antagonist 8-Br-cADPR, Ca2+ chelation, and antagonism of L-type Ca2+ channels suppressed these effects. The time and dose effects of NAD+ on TGF-β1 were complex and could be modeled both statistically and mathematically. Model-predicted levels of TGF-β1 protein and mRNA were largely confirmed experimentally but also suggested the presence of other mechanisms of regulation of TGF-β1 by NAD+. Thus, in vitro and in silico evidence points to NAD+ as a novel modulator of TGF-β1. PMID:22829588

Identification of a novel pathway of transforming growth factor-β1 regulation by extracellular NAD+ in mouse macrophages: in vitro and in silico studies.

PubMed

Zamora, Ruben; Azhar, Nabil; Namas, Rajaie; Metukuri, Mallikarjuna R; Clermont, Thierry; Gladstone, Chase; Namas, Rami A; Hermus, Linda; Megas, Cristina; Constantine, Gregory; Billiar, Timothy R; Fink, Mitchell P; Vodovotz, Yoram

2012-09-07

Extracellular β-nicotinamide adenine dinucleotide (NAD(+)) is anti-inflammatory. We hypothesized that NAD(+) would modulate the anti-inflammatory cytokine Transforming Growth Factor (TGF)-β1. Indeed, NAD(+) led to increases in both active and latent cell-associated TGF-β1 in RAW 264.7 mouse macrophages as well as in primary peritoneal macrophages isolated from both C3H/HeJ (TLR4-mutant) and C3H/HeOuJ (wild-type controls for C3H/HeJ) mice. NAD(+) acts partially via cyclic ADP-ribose (cADPR) and subsequent release of Ca(2+). Treatment of macrophages with the cADPR analog 3-deaza-cADPR or Ca(2+) ionophores recapitulated the effects of NAD(+) on TGF-β1, whereas the cADPR antagonist 8-Br-cADPR, Ca(2+) chelation, and antagonism of L-type Ca(2+) channels suppressed these effects. The time and dose effects of NAD(+) on TGF-β1 were complex and could be modeled both statistically and mathematically. Model-predicted levels of TGF-β1 protein and mRNA were largely confirmed experimentally but also suggested the presence of other mechanisms of regulation of TGF-β1 by NAD(+). Thus, in vitro and in silico evidence points to NAD(+) as a novel modulator of TGF-β1.

Immunomodulatory Effects of Kuseonwangdogo-Based Mixed Herbal Formula Extracts on a Cyclophosphamide-Induced Immunosuppression Mouse Model

PubMed Central

Kim, Joo Wan; Seol, Du Jin; Choung, Jai Jun

2018-01-01

Aim Kuseonwangdogo is a traditional Korean immunomodulatory polyherbal prescription. However, there are no systemic findings on its complex immunomodulatory effects on in vivo models. In this study, we observed the immunomodulatory effects of Kuseonwangdogo-based mixed herbal formula aqueous extracts (MHFe) on cyclophosphamide- (CPA-) induced immunosuppression mouse model. Methods In total, 60 male 6-week-old ICR mice (10 mice/group) were selected based on body weight 24 h after the second CPA treatment and used in this experiment. Twelve hours after the end of the last (fourth) oral administration of MHFe, the animals were sacrificed. Results Following CPA treatment, a noticeable decrease in the body, thymus, spleen, and submandibular lymph node (LN) weights; white blood cell, red blood cell, platelet number, hemoglobin, and hematocrit concentrations; serum interferon-γ levels; splenic tumor necrosis factor-α, interleukin- (IL-) 1β, and IL-10 content; and peritoneal and splenic natural killer cell activities was observed. Depletion of lymphoid cells in the thymic cortex, splenic white pulp, and submandibular LN-related atrophic changes were also observed. However, these CPA-induced myelosuppressive signs were markedly and dose-dependently inhibited by the oral administration of 125, 250, and 500 mg/kg MHFe. Conclusion MHFe can be a promising, potent immunomodulatory therapeutic agent for various immune disorders. PMID:29849713

Toll-like receptor 4-dependent adjuvant activity of Kakkon-to extract exists in the high molecular weight polysaccharide fraction.

PubMed

Ishijima, Y; Kawamura, T; Kimura, A; Kohno, A; Okada, T; Tsuji, T; Watanabe, Y

2011-01-01

Kakkon-to, a traditional herbal medicine (Kampo formula), has been used historically in China and Japan for the treatment of infectious diseases such as influenza and the common cold. However, the biological mechanism of its therapeutic action has not yet been elucidated. In this study, we investigated the immunological function of Kakkon-to and found that the high molecular weight fraction of the extract activated macrophages in vitro. This fraction was found to be composed primarily of saccharides and in vitro intensively stimulated mouse peritoneal macrophages that produce Th1 inflammatory cytokines such as tumor necrosis factor α (TNFalpha), interleukin-1beta (IL-1beta), interferon-gamma (IFN-gamma), and interleukin-6 (IL-6). The fraction did not activate macrophages from C3H/HeJ lacking Toll-like receptor 4 (TLR4) or MyD88-deficient mice, indicating that macrophage activation by the fraction was mediated by TLR4. The route of administration of the fraction into mice regulated the kinetics of TNFalpha production in immune organs. Intravenous administration induced TNFalpha production in the four target organs of spleen, liver, lung, and Peyer’s patch; however, the most abundant production occurred in the liver and peaked at 30-60 min post administration. Peritoneal administration induced similar kinetics but the most abundant production occurred in the spleen. In contrast, oral administration induced TNFalpha production in the liver, lung, and Peyer’s patch, but not in the spleen. Although liver and lung are TNFalpha-abundant organs, production peaks in these organs occurred later than in Peyer’s patch. We also found that the fraction induced antibody production as an adjuvant against a specific antigen ovalbumin (OVA) when administered simultaneously and subcutaneously in a dose-dependent manner. Interestingly, the fraction induced IgG-class antibody in response to low doses of the antigen, which induced only IgM-class antibody when administered alone, suggesting that the fraction induces a class switch of immunoglobulin as an adjuvant in vivo. The high molecular weight fraction of Kakkon-to extract could be applicable as a potent immunostimulating drug and adjuvant.

A pilot study of an anti-MRSA bio-engineered lacteal complex (anti-MRSA BLC) in a murine septicemia model.

PubMed

Stoff, Jesse A; Nix, David E; DeYoung, D W

2006-01-01

Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen of humans and other animals, causing septicemia, abcessation, toxemia, and other infectious diseases. Refined bioengineered lacteal complex (BLC), made specifically against MRSA, is a novel complex of low molecular weight immunogenic and antimicrobial molecules. It was evaluated in vivo using a mouse model of MRSA-induced peritonitis. Intraperitoneal dosing of anti-MRSA BLC demonstrated a therapeutic effect (83% survival) against an intraperitoneal MRSA challenge that caused 100% mortality in untreated animals. Anti-MRSA BLC is a promising therapeutic modality for MRSA infection.

Evidence of NK1 and NK2 Tachykinin Receptors and their Involvement in Histamine Release in a Murine Mast Cell Line

DTIC Science & Technology

1992-01-01

either human p ~ulmo(nary,. Delectaible in the absence of estrmcclular CaCI’. i’Potent 4.23ug/105 cells, or rat peritoneal mast cells. bousbesin...ABSTRACT (Maximum 200 words) Abstract-Binding of )kH substance P (SP) and histamine release were examined using a cloned mouse mast cell line SP binding...the cells with the NK2 antagonist peptide A reduced NKA-induced histamine release ID.Arg’,D.Phe’,D-Trp 0 3 .Leu t )nsu b s tance P , a putative SP

Effect of pH and glucose on cultured human peritoneal mesothelial cells.

PubMed

Shao, J C; Yorioka, N; Nishida, Y; Yamakido, M

1999-08-01

We investigated the effects of various pH and glucose concentrations on the growth of human peritoneal mesothelial cells and on coagulation and fibrinolytic factors. Cells were cultured at various pH values in Ham's F-12 medium containing 1.0% foetal calf serum and supplemented with D-glucose or D-mannitol at various concentrations. After 4-48 h, cell proliferation and 3H-thymidine incorporation were determined. Coagulation and fibrinolytic factors were measured after 48 h. Glucose caused concentration-dependent inhibition of cell growth at all pH values, but the deleterious effect of low pH on cell proliferation was faster and stronger than that of high glucose. At a similar osmolality, mannitol caused less inhibition of cell proliferation than glucose. There was a glucose concentration-dependent increase of thrombin-antithrombin III complex production at all pH values. At pH 5.2, tissue-type plasminogen activator production was far lower than at higher pH values, and production of the plasminogen activator inhibitor showed a glucose concentration-dependent increase. At pH 6.5 or 7.3, however, the plasminogen activator inhibitor production decreased and tissue-type plasminogen activator production increased in a glucose concentration-dependent manner. Low pH and/or high glucose culture medium had an inhibitory effect on peritoneal mesothelial cells, with the effect of high glucose being partially related to hyperosmolality. These cells may modulate peritoneal coagulant and fibrinolytic activity, with the balance between coagulation and fibrinolysis being disturbed by low pH and/or high glucose.

[Updated treatment of peritoneal carcinomas: a review].

PubMed

Deraco, M; Laterza, B; Kusamura, S; Baratti, D

2007-12-01

Peritoneal surface malignancy (PSM) is a clinical entity with an unfavourable prognosis, which characterizes the evolution of neoplastic diseases from the abdominal and/or pelvic organs and could also be the terminal stage of extra-abdominal tumors. Examples of diseases that can spread mainly within the peritoneal cavity are appendiceal tumors, ovarian cancer, colorectal cancer, abdominal sarcomatosis, gastric cancer and peritoneal mesothelioma. The locoregional therapy is defined as the combination of cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). The rationale of this combined therapy for PSM is based on the natural history of this clinical entity that remains confined in the peritoneal cavity for most of its natural history. This pattern of spread would seem to indicate the potential usefulness of selectively increasing drug concentration in the tumour-bearing area by direct intraperitoneal chemotherapy instillation. This approach led to these outcomes: the median survival of colorectal carcinoma and ovarian cancer was 32 months; patients with peritoneal mesothelioma showed 57% survival at 5 years, while in patients with appendiceal mucinous tumors and pseudomyxoma peritonei (PMP) the 10 years overall survival was 78%. A significant improvement in survival was associated with hyperthermic intra-peritoneal chemotherapy (HIPEC) in patients with gastric cancer. Considering the constant increasing of diseases treatable with this procedure, more centres should be activated. The establishment of a clear policy and scientific guidelines is mandatory, in order to perform the CRS+HIPEC safely, minimizing treatment-related morbidity and mortality and maximizing the results in terms of survival and quality of life.

Pelvic drainage during removal of dialysis catheter decreases the risk of subsequent intra-abdominal complications in refractory peritoneal dialysis-related peritonitis.

PubMed

Hsu, Chih-Yang; Huang, Wei-Chieh; Huang, Chun-Kai; Huang, Chien-Wei; Chou, Nan-Hua; Lee, Po-Tsang; Fang, Hua-Chang; Chou, Kang-Ju; Chen, Chien-Liang

2015-11-01

Some patients with refractory peritoneal dialysis-related peritonitis continue to develop intra-abdominal complications despite removal of the peritoneal catheter. Repeated percutaneous drainage or open laparotomy is often required, and mortality is not uncommon. The benefits of pelvic drainage placement during catheter removal in decreasing these complications and interventions remain unproven. Forty-six patients with refractory peritonitis who underwent removal of a Tenckhoff catheter between 1991 and 2013 were reviewed retrospectively. Twelve patients had pelvic drainage using closed active suction devices during catheter removal (drainage group). The remaining 34 patients underwent catheter removal without drainage (non-drainage group). The outcomes measured were the development of intra-abdominal complications and the requirement for repeated percutaneous drainage or open laparotomy within 90 days after the catheter removal. Baseline characteristics were similar with the exception of a higher median number of previous peritonitis episodes in the drainage group compared with the non-drainage group (2 vs 0, P = 0.02). During the follow-up period, intra-abdominal complications occurred in 15 (44%) of 34 patients in the non-drainage group, compared with one (8%) of 12 patients in the drainage group (P = 0.03). Twelve (35%) patients in the non-drainage group required repeated percutaneous drainage or open laparotomy for management, compared with zero (0%) patients in the drainage group (P = 0.02). Drain tubes were removed at a median of 6 days (inter-quartile range: 5-10) without complications. In the management of refractory peritonitis, pelvic drainage during removal of dialysis catheter decreases the risk of subsequent intra-abdominal complications and invasive interventions. © 2015 Asian Pacific Society of Nephrology.

The TGF-beta-induced gene product, betaig-h3: its biological implications in peritoneal dialysis.

PubMed

Park, Sun-Hee; Choi, Soon-Youn; Kim, Mi-Hyung; Oh, Eun-Joo; Ryu, Hye Myung; Kim, Chan-Duck; Kim, In-San; Kim, Yong-Lim

2008-01-01

TGF-beta is involved in peritoneal changes during long-term peritoneal dialysis (PD). TGF-beta induces betaig-h3 in several cell lines, and betaig-h3 may be a marker for biologically active TGF-beta. However, no study has reported induction of betaig-h3 in human peritoneal mesothelial cells (HPMCs) or its involvement in PD-related peritoneal membrane changes. We used cultured HPMCs to investigate the biological roles of betaig-h3 during mesothelial cell injury and repair, employing the adhesion, spreading, scratching and cell migration assays. Changes in betaig-h3 expression after high glucose exposure in vivo were also evaluated using an animal chronic PD model. In vitro, TGF-beta1 induced betaig-h3 in cultured HPMCs, and betaig-h3-mediated mesothelial cell adhesion occurred via alphavbeta3 integrin. betaig-h3 enhanced mesothelial cell adhesion and migration and, in part, wound healing during mesothelial cell injury. The animal study demonstrated that compared to the control group, betaig-h3 concentrations in the dialysate effluent increased in the dialysis group with alterations in peritoneal structure and function during PD, and betaig-h3 positively correlated with peritoneal solute transport. Immunohistochemical and immunoblotting results showed that betaig-h3 localizes in the mesothelium and submesothelial matrix of the parietal peritoneum, and in the vascular endothelium of omentum. betaig-h3 protein expression was higher in the dialysis group. In vitro, betaig-h3 induced by TGF-beta1 in HPMCs improved adhesion and migration of HPMCs during wound healing. In the chronic infusion model of PD, betaig-h3 played a role in the functional deterioration of the peritoneal membrane, which is associated with fibrosis.

Cola-colored dialysate as a gastrointestinal sequelae of cardiac surgery in a patient who underwent peritoneal dialysis.

PubMed

Ling, Eng-Kian; Lin, Bing-Shi; Chiang, Shou-Shan; Tsai, Ming-Hsien

2012-01-01

The discoloration of effluent peritoneal dialysate, which is transparent in origin, is seen in some particular conditions including chyloperitoneum, calcium channel blocker usage, hemoperitoneum, perforated cholecystitis, iron administration, and hemorrhagic pancreatitis. We report a case of a 60-year-old woman who underwent peritoneal dialysis for 3 years and presented with conspicuous cola-colored (brownish-black) dialysate after a cardiac surgery. The findings of the dialysate analysis and the abdominal computed tomography showed that this discoloration could be due to the presence of methemalbumin caused by pancreatitis (not hemorrhagic) combined with intra-abdominal bleeding-both of which are rare gastrointestinal complications of cardiac surgery. She eventually died of pulseless electrical activity due to severe sepsis with profound shock. Therefore, the rare event of cola-colored peritoneal dialysate could present as severe gastrointestinal sequelae of cardiac surgery and may indicate a poor prognosis.

Rapamycin inhibits epithelial-to-mesenchymal transition of peritoneal mesothelium cells through regulation of Rho GTPases.

PubMed

Xiang, Shilong; Li, Meng; Xie, Xishao; Xie, Zhoutao; Zhou, Qin; Tian, Yuanshi; Lin, Weiqiang; Zhang, Xiaohui; Jiang, Hong; Shou, Zhangfei; Chen, Jianghua

2016-06-01

Epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells (PMCs) is a key process of peritoneal fibrosis. Rapamycin has been previously shown to inhibit EMT of PMCs and prevent peritoneal fibrosis. In this study, we investigated the undefined molecular mechanisms by which rapamycin inhibits EMT of PMCs. To define the protective effect of rapamycin, we initially used a rat PD model which was daily infused with 20 mL of 4.25% high glucose (HG) dialysis solution for 6 weeks to induce fibrosis. The HG rats showed decreased ultrafiltration volume and obvious fibroproliferative response, with markedly increased peritoneal thickness and higher expression of α-smooth muscle actin (α-SMA) and transforming growth factor-β1. Rapamycin significantly ameliorated those pathological changes. Next, we treated rat PMCs with HG to induce EMT and/or rapamycin for indicated time. Rapamycin significantly inhibited HG-induced EMT, which manifests as increased expression of α-SMA, fibronectin, and collagen I, decreased expression of E-cadherin, and increased mobility. HG increased the phosphorylation of PI3K, Akt, and mTOR. Importantly, rapamycin inhibits the RhoA, Rac1, and Cdc42 activated by HG. Moreover, rapamycin repaired the pattern of F-actin distribution induced by HG, reducing the formation of stress fiber, focal adhesion, lamellipodia, and filopodia. Thus, rapamycin shows an obvious protective effect on HG-induced EMT, by inhibiting the activation of Rho GTPases (RhoA, Rac1, and Cdc42). © 2016 Federation of European Biochemical Societies.

Arctigenin ameliorates inflammation in vitro and in vivo by inhibiting the PI3K/AKT pathway and polarizing M1 macrophages to M2-like macrophages.

PubMed

Hyam, Supriya R; Lee, In-Ah; Gu, Wan; Kim, Kyung-Ah; Jeong, Jin-Ju; Jang, Se-Eun; Han, Myung Joo; Kim, Dong-Hyun

2013-05-15

Seeds of Arctium lappa, containing arctigenin and its glycoside arctiin as main constituents, have been used as a diuretic, anti-inflammatory and detoxifying agent in Chinese traditional medicine. In our preliminary study, arctigenin inhibited IKKβ and NF-κB activation in peptidoglycan (PGN)- or lipopolysaccharide (LPS)-induced peritoneal macrophages. To understand the anti-inflammatory effect of arctigenin, we investigated its anti-inflammatory effect in LPS-stimulated peritoneal macrophages and on LPS-induced systemic inflammation as well as 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Arctigenin inhibited LPS-increased IL-1β, IL-6 and TNF-α expression in LPS-stimulated peritoneal macrophages, but increased LPS-reduced IL-10 and CD204 expression. Arctigenin inhibited LPS-induced PI3K, AKT and IKKβ phosphorylation, but did not suppress LPS-induced IRAK-1 phosphorylation. However, arctigenin did not inhibit NF-κB activation in LPS-stimulated PI3K siRNA-treated peritoneal macrophages. Arctigenin suppressed the binding of p-PI3K antibody and the nucleus translocation of NF-κB p65 in LPS-stimulated peritoneal macrophages. Arctigenin suppressed blood IL-1β and TNF-α level in mice systemically inflamed by intraperitoneal injection of LPS. Arctigenin also inhibited colon shortening, macroscopic scores and myeloperoxidase activity in TNBS-induced colitic mice. Arctigenin inhibited TNBS-induced IL-1β, TNF-α and IL-6 expression, as well as PI3K, AKT and IKKβ phosphorylation and NF-κB activation in mice, but increased IL-10 and CD204 expression. However, it did not affect IRAK-1 phosphorylation. Based on these findings, arctigenin may ameliorate inflammatory diseases, such as colitis, by inhibiting PI3K and polarizing M1 macrophages to M2-like macrophages. Copyright © 2013 Elsevier B.V. All rights reserved.

BOT-4-one attenuates NLRP3 inflammasome activation: NLRP3 alkylation leading to the regulation of its ATPase activity and ubiquitination.

PubMed

Shim, Do-Wan; Shin, Woo-Young; Yu, Sang-Hyeun; Kim, Byung-Hak; Ye, Sang-Kyu; Koppula, Sushruta; Won, Hyung-Sik; Kang, Tae-Bong; Lee, Kwang-Ho

2017-11-08

The ATPase activity of NLRP3 has pivotal role in inflammasome activation and is recognized as a good target for the development of the NLRP3 inflammasome-specific inhibitor. However, signals in the vicinity of the ATPase activity of NLRP3 have not been fully elucidated. Here, we demonstrate NLRP3 inflammasome-specific action of a benzoxathiole derivative, BOT-4-one. BOT-4-one exhibited an inhibition of NLRP3 inflammasome activation, which was attributable to its alkylating capability to NLRP3. In particular, the NLRP3 alkylation by BOT-4-one led to an impaired ATPase activity of NLRP3, thereby obstructing the assembly of the NLRP3 inflammasome. Additionally, we found that NLRP3 alkylators, including BOT-4-one, enhance the ubiquitination level of NLRP3, which might also contribute to the inhibition of NLRP3 inflammasome activation. Finally, BOT-4-one appeared to be superior to other known NLRP3 alkylators in inhibiting the functionality of the NLRP3 inflammasome and its resulting anti-inflammatory activity was confirmed in vivo using a monosodium urate-induced peritonitis mouse model. Collectively, the results suggest that NLRP3 alkylators function by inhibiting ATPase activity and increasing the ubiquitination level of NLRP3, and BOT-4-one could be the type of NLRP3 inhibitor that may be potentially useful for the novel development of a therapeutic agent in controlling NLRP3 inflammasome-related diseases.

Primary bacterial peritonitis in dogs and cats: 24 cases (1990-2006).

PubMed

Culp, William T N; Zeldis, Tracy E; Reese, Michael S; Drobatz, Kenneth J

2009-04-01

To determine clinical characteristics of primary bacterial peritonitis (infection of the peritoneal cavity with no identifiable intraperitoneal source of infection) and compare characteristics of primary and secondary peritonitis in dogs and cats. Retrospective case series. 24 (primary peritonitis) and 60 (secondary peritonitis) client-owned dogs and cats. Data from medical records of dogs and cats with primary and secondary peritonitis were reviewed for descriptive information regarding primary peritonitis and for comparison between the 2 forms of peritonitis. 15 dogs and 9 cats met inclusion criteria for primary peritonitis, and 49 dogs and 11 cats met inclusion criteria for secondary peritonitis. The most common historical findings in dogs and cats with primary and secondary peritonitis were lethargy, vomiting, and anorexia. Dogs with secondary peritonitis more often developed peritoneal exudates than those with primary peritonitis, and dogs with primary peritonitis were more often infected with gram-positive bacteria than those with secondary peritonitis. No difference in outcome was detected between all animals with primary versus secondary peritonitis; however, dogs with secondary peritonitis treated with surgery were more commonly discharged than those with primary peritonitis treated with surgery. Differences in primary and secondary peritonitis related to historical, physical examination, and clinical laboratory findings; bacteriologic findings; peritoneal effusion characteristics; and outcome were detected. However, larger case numbers are needed before alternative recommendations, such as avoidance of surgery, can be made.

Impact of Global Economic Disparities on Practices and Outcomes of Chronic Peritoneal Dialysis in Children: Insights from the International Pediatric Peritoneal Dialysis Network Registry

PubMed Central

Schaefer, Franz; Borzych-Duzalka, Dagmara; Azocar, Marta; Munarriz, Reyner Loza; Sever, Lale; Aksu, Nejat; Barbosa, Lorena Sànchez; Galan, Yajaira Silva; Xu, Hong; Coccia, Paula A.; Szabo, Attila; Wong, William; Salim, Rosana; Vidal, Enrico; Pottoore, Stephen; Warady, Bradley A.

2012-01-01

♦ Background, Objectives, and Methods: The number of patients on chronic peritoneal dialysis (CPD) is increasing rapidly on a global scale. We analyzed the International Pediatric Peritoneal Dialysis Network (IPPN) registry, a global database active in 33 countries spanning a wide range in gross national income (GNI), to identify the impact of economic conditions on CPD practices and outcomes in children and adolescents. ♦ Results: We observed close associations of GNI with the fraction of very young patients on dialysis, the presence and number of comorbidities, the prevalence of patients with unexplained causes of end-stage kidney disease, and the rate of culture-negative peritonitis. The prevalence of automated PD increased with GNI, but was 46% even in the lowest GNI stratum. The GNI stratum also affected the use of biocompatible peritoneal dialysis fluids, enteral tube feeding, calcium-free phosphate binders, active vitamin D analogs, and erythropoiesis-stimulating agents (ESAs). Patient mortality was strongly affected by GNI (hazard ratio per $10 000: 3.3; 95% confidence interval: 2.0 to 5.5) independently of young patient age and the number of comorbidities present. Patients from low-income countries tended to die more often from infections unrelated to CPD (5 of 9 vs 15 of 61, p = 0.1). The GNI was also a strong independent predictor of standardized height (p < 0.0001), adding to the impact of congenital renal disease, anuria, age at PD start, and dialysis vintage. Patients from the lower economic strata (GNI < $18 000) had higher serum parathyroid hormone (PTH) and lower serum calcium, and achieved lower hemoglobin concentrations. No impact of GNI was observed with regard to CPD technique survival or peritonitis incidence. ♦ Conclusions: We conclude that CPD is practiced successfully, albeit with major regional variation related to economic differences, in children around the globe. The variations encompass the acceptance of very young patients and those with associated comorbidities to chronic dialysis programs, the use of automated PD and expensive drugs, and the diagnostic management of peritonitis. These variations in practice related to economic difference do not appear to affect PD technique survival; however, economic conditions seem to affect mortality on dialysis and standardized height, a marker of global child morbidity. PMID:22859840

Impact of global economic disparities on practices and outcomes of chronic peritoneal dialysis in children: insights from the International Pediatric Peritoneal Dialysis Network Registry.

PubMed

Schaefer, Franz; Borzych-Duzalka, Dagmara; Azocar, Marta; Munarriz, Reyner Loza; Sever, Lale; Aksu, Nejat; Barbosa, Lorena Sànchez; Galan, Yajaira Silva; Xu, Hong; Coccia, Paula A; Szabo, Attila; Wong, William; Salim, Rosana; Vidal, Enrico; Pottoore, Stephen; Warady, Bradley A

2012-01-01

BACKGROUND, OBJECTIVES, AND METHODS: The number of patients on chronic peritoneal dialysis (CPD) is increasing rapidly on a global scale. We analyzed the International Pediatric Peritoneal Dialysis Network (IPPN) registry, a global database active in 33 countries spanning a wide range in gross national income (GNI), to identify the impact of economic conditions on CPD practices and outcomes in children and adolescents. We observed close associations of GNI with the fraction of very young patients on dialysis, the presence and number of comorbidities, the prevalence of patients with unexplained causes of end-stage kidney disease, and the rate of culture-negative peritonitis. The prevalence of automated PD increased with GNI, but was 46% even in the lowest GNI stratum. The GNI stratum also affected the use of biocompatible peritoneal dialysis fluids, enteral tube feeding, calcium-free phosphate binders, active vitamin D analogs, and erythropoiesis-stimulating agents (ESAs). Patient mortality was strongly affected by GNI (hazard ratio per $10 000: 3.3; 95% confidence interval: 2.0 to 5.5) independently of young patient age and the number of comorbidities present. Patients from low-income countries tended to die more often from infections unrelated to CPD (5 of 9 vs 15 of 61, p = 0.1). The GNI was also a strong independent predictor of standardized height (p < 0.0001), adding to the impact of congenital renal disease, anuria, age at PD start, and dialysis vintage. Patients from the lower economic strata (GNI < $18 000) had higher serum parathyroid hormone (PTH) and lower serum calcium, and achieved lower hemoglobin concentrations. No impact of GNI was observed with regard to CPD technique survival or peritonitis incidence. We conclude that CPD is practiced successfully, albeit with major regional variation related to economic differences, in children around the globe. The variations encompass the acceptance of very young patients and those with associated comorbidities to chronic dialysis programs, the use of automated PD and expensive drugs, and the diagnostic management of peritonitis. These variations in practice related to economic difference do not appear to affect PD technique survival; however, economic conditions seem to affect mortality on dialysis and standardized height, a marker of global child morbidity.

Oral administration of FAK inhibitor TAE226 inhibits the progression of peritoneal dissemination of colorectal cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Hui-fang; Takaoka, Munenori; Bao, Xiao-hong

2012-07-13

Highlights: Black-Right-Pointing-Pointer A novel FAK inhibitor TAE226 suppressed FAK activity in HCT116 colon cancer cells. Black-Right-Pointing-Pointer TAE226 suppressed proliferation and migration, with a modest effect on adhesion. Black-Right-Pointing-Pointer Silencing of FAK by siRNA made no obvious difference on cancer cell attachment. Black-Right-Pointing-Pointer TAE226 treatment suppressed the progression of peritoneal dissemination. Black-Right-Pointing-Pointer Oral administration of TAE226 prolonged the survival of tumor-bearing mice. -- Abstract: Peritoneal dissemination is one of the most terrible types of colorectal cancer progression. Focal adhesion kinase (FAK) plays a crucial role in the biological processes of cancer, such as cell attachment, migration, proliferation and survival, all ofmore » which are essential for the progression of peritoneal dissemination. Since we and other groups have reported that the inhibition of FAK activity exhibited a potent anticancer effect in several cancer models, we hypothesized that TAE226, a novel ATP-competitive tyrosine kinase inhibitor designed to target FAK, can prevent the occurrence and progression of peritoneal dissemination. In vitro, TAE226 greatly inhibited the proliferation and migration of HCT116 colon cancer cells, while their adhesion on the matrix surface was minimally inhibited when FAK activity and expression was suppressed by TAE226 and siRNA. In vivo, when HCT116 cells were intraperitoneally inoculated in mice, the cells could attach to the peritoneum and begin to grow within 24 h regardless of the pretreatment of cells with TAE226 or FAK-siRNA, suggesting that FAK is not essential, at least for the initial integrin-matrix contact. Interestingly, the treatment of mice before and after inoculation significantly suppressed cell attachment to the peritoneum. Furthermore, oral administration of TAE226 greatly reduced the size of disseminated tumors and prolonged survival in tumor-bearing mice. Taken together, a possible strategy for inhibiting peritoneal dissemination by targeting FAK with TAE226 appears to be applicable through anti-proliferative and anti-invasion/anti-migration mechanisms.« less

ASK1-dependent endothelial cell activation is critical in ovarian cancer growth and metastasis

PubMed Central

Yin, Mingzhu; Zhou, Huanjiao Jenny; Zhang, Jiqin; Lin, Caixia; Li, Hongmei; Li, Xia; Li, Yonghao; Zhang, Haifeng; Breckenridge, David G.; Ji, Weidong

2017-01-01

We have recently reported that tumor-associated macrophages (TAMs) promote early transcoelomic metastasis of ovarian cancer by facilitating TAM–ovarian cancer cell spheroid formation. ASK1 is known to be important for macrophage activation and inflammation-mediated tumorigenesis. In the present study, we show that ASK1 deficiency attenuates TAM-spheroid formation and ovarian cancer progression in an orthotopic ovarian cancer model. Interestingly, ASK1 in stroma, but not in TAMs, is critical for peritoneal tumor growth of ovarian cancer. Moreover, overexpression of an ASK1 inhibitory protein (suppressor of cytokine signaling-1; SOCS1) in vascular endothelium attenuates vascular permeability, TAM infiltration, and ovarian cancer growth. Mechanistically, we show that ASK1 mediates degradation of endothelial junction protein VE-cadherin via a lysosomal pathway to promote macrophage transmigration. Importantly, a pharmacological ASK1 inhibitor prevents tumor-induced vascular leakage, macrophage infiltration, and tumor growth in two mouse models. Since transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our study provides ASK1 as a therapeutic target for the treatment of ovarian cancer and other transcoelomic metastasis cancers. PMID:28931753

The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY.

PubMed

Sasidhar, Manda V; Itoh, Noriko; Gold, Stefan M; Lawson, Gregory W; Voskuhl, Rhonda R

2012-08-01

Many autoimmune diseases are characterised by a female predominance. This may be caused by sex hormones, sex chromosomes or both. This report uses a transgenic mouse model to investigate how sex chromosome complement, not confounded by differences in gonadal type, might contribute to lupus pathogenesis. Transgenic NZM2328 mice were created by deletion of the Sry gene from the Y chromosome, thereby separating genetic from gonadal sex. Survival, renal histopathology and markers of immune activation were compared in mice carrying the XX versus the XY(-) sex chromosome complement, with each genotype being ovary bearing. Mice with XX sex chromosome complement compared with XY(-) exhibited poorer survival rates and increased kidney pathology. Splenic T lymphocytes from XX mice demonstrated upregulated X-linked CD40 ligand expression and higher levels of activation markers ex vivo. Increased MMP, TGF and IL-13 production was found, while IL-2 was lower in XX mice. An accumulation of splenic follicular B cells and peritoneal marginal zone B cells was observed, coupled with upregulated costimulatory marker expression on B cells in XX mice. These data show that the XX sex chromosome complement, compared with XY(-), is associated with accelerated spontaneous lupus.

Leishmanicidal activity of polyphenolic-rich extract from husk fiber of Cocos nucifera Linn. (Palmae).

PubMed

Mendonça-Filho, Ricardo R; Rodrigues, Igor A; Alviano, Daniela S; Santos, André L S; Soares, Rosangela M A; Alviano, Celuta S; Lopes, Angela H C S; Rosa, Maria do Socorro S

2004-04-01

The available therapy for leishmaniasis, which affects 2 million people per annum, still causes serious side effects. The polyphenolic-rich extract from the husk fiber of Cocos nucifera Linn. (Palmae) presents antibacterial and antiviral activities, also inhibiting lymphocyte proliferation, as shown by our group in previous works. In the present study, the in vitro leishmanicidal effects of C. nucifera on Leishmania amazonensis were evaluated. The minimal inhibitory concentration of the polyphenolic-rich extract from C. nucifera to completely abrogate parasite growth was 10 microg/ml. Pretreatment of peritoneal mouse macrophages with 10 microg/ml of C. nucifera polyphenolic-rich extract reduced approximately 44% the association index between these macrophages and L. amazonensis promastigotes, with a concomitant increase of 182% in nitric oxide production by the infected macrophage in comparison to nontreated macrophages. These results provide new perspectives on drug development against leishmaniasis, since the extract of C. nucifera at 10 microg/ml is a strikingly potent leishmanicidal substance which inhibited the growth of both promastigote and amastigote developmental stages of L. amazonensis after 60 min, presenting no in vivo allergenic reactions or in vitro cytotoxic effects in mammalian systems.

Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model.

PubMed

Basel, Matthew T; Balivada, Sivasai; Wang, Hongwang; Shrestha, Tej B; Seo, Gwi Moon; Pyle, Marla; Abayaweera, Gayani; Dani, Raj; Koper, Olga B; Tamura, Masaaki; Chikan, Viktor; Bossmann, Stefan H; Troyer, Deryl L

2012-01-01

Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer.

Experimental Streptococcus pneumoniae infection in mice for studying correlation of in vitro and in vivo activities of penicillin against pneumococci with various susceptibilities to penicillin.

PubMed Central

Knudsen, J D; Frimodt-Møller, N; Espersen, F

1995-01-01

The purpose of the study was to investigate the correlation of in vitro activity with the in vivo effect and the pharmacokinetics of penicillin in the treatment of infections with pneumococci with various susceptibilities to penicillin. We used 10 pneumococcal strains for which penicillin MICs ranged from 0.016 to 8 micrograms/ml. Time-kill curve experiments were performed with all strains. We found that the effect of penicillin in vitro is concentration independent, with a maximum effect at two to four times the MIC for penicillin-susceptible as well as penicillin-resistant pneumococci. The mouse peritonitis model with an inoculum of approximately 10(6) CFU, to which mucin was added, resulted in a reproducible lethal infection with the pneumococci. The 50% effective dose was determined for each strain, and we found a highly significant correlation between the log MIC and the log 50% effective dose of penicillin against these strains (P < 0.01). Furthermore, it was shown that the most important pharmacokinetic parameter determining the effect of penicillin in vivo was the time that the concentration of penicillin in serum was greater than the MIC. PMID:7574511

OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models

PubMed Central

Shi, Jun; Wei, Pin-Kang; Zhang, Shen; Qin, Zhi-Feng; Li, Jun; Sun, Da-Zhi; Xiao, Yan; Yu, Zhi-Hong; Lin, Hui-Ming; Zheng, Guo-Jing; Su, Xiao-Mei; Chen, Ya-Lin; Liu, Yan-Fang; Xu, Ling

2008-01-01

AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique. METHODS: Using OB glue paste technique, orthotopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice. Biological features, growth of the implanted tumors, the success rate of transplantation and the rate of auto-metastasis of the two models were observed. RESULTS: The success rates of orthotopic transplan-tation of the two models were 94.20% and 96%. The rates of hepatic metastasis, pulmonary metastasis, peritoneal metastasis, lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%, 48.43% and 57.97%, 30.83% and 36.96%, 67.30% and 84.06%, and 59.75% and 10.53%, respectively. The occurrence of ascites was 47.80% and 36.96%. CONCLUSION: OB glue paste technique is easy to follow. The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer, and, therefore, can be used as an ideal model for experimental research of proliferative metastasis of tumors. PMID:18720543

Apocynin suppresses the progression of atherosclerosis in apoE-deficient mice by inactivation of macrophages

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinoshita, Hiroyuki; Matsumura, Takeshi, E-mail: takeshim@gpo.kumamoto-u.ac.jp; Ishii, Norio

Highlights: ► We examined the anti-athrogenic effect of apocynin in atherosclerotic model mice. ► Apocynin prevented atherosclerotic lesion formation. ► Apocynin suppressed ROS production in aorta and in macrophages. ► Apocynin suppressed cytokine expression and cell proliferation in macrophages. ► Apocynin may be beneficial compound for the prevention of atherosclerosis. -- Abstract: Production of reactive oxygen species (ROS) and other proinflammatory substances by macrophages plays an important role in atherogenesis. Apocynin (4-hydroxy-3-methoxy-acetophenone), which is well known as a NADPH oxidase inhibitor, has anti-inflammatory effects including suppression of the generation of ROS. However, the suppressive effects of apocynin on the progressionmore » of atherosclerosis are not clearly understood. Thus, we investigated anti-atherosclerotic effects of apocynin using apolipoprotein E-deficient (apoE{sup –/–}) mice in vivo and in mouse peritoneal macrophages in vitro. In atherosclerosis-prone apoE{sup –/–} mice, apocynin suppressed the progression of atherosclerosis, decreased 4-hydroxynonenal-positive area in atherosclerotic lesions, and mRNA expression of monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) in aorta. In mouse peritoneal macrophages, apocynin suppressed the Ox-LDL-induced ROS generation, mRNA expression of MCP-1, IL-6 and granulocyte/macrophage colony-stimulating factor, and cell proliferation. Moreover, immunohistochemical studies revealed that apocynin decreased the number of proliferating cell nuclear antigen-positive macrophages in atherosclerotic lesions of apoE{sup –/–} mice. These results suggested that apocynin suppressed the formation of atherosclerotic lesions, at least in part, by inactivation of macrophages. Therefore, apocynin may be a potential therapeutic material to prevent the progression of atherosclerosis.« less

Upregulated expression of substance P (SP) and NK1R in eczema and SP-induced mast cell accumulation.

PubMed

Zhan, Mengmeng; Zheng, Wenjiao; Jiang, Qijun; Zhao, Zuotao; Wang, Zhiyun; Wang, Junling; Zhang, Huiyun; He, Shaoheng

2017-08-01

Substance P (SP) was reported to be associated with eczema and acts as a potent skin mast cell secretagogue. However, little is known of its expression in inflammatory cells in eczema and its ability in induction of mast cell accumulation. In the present study, we investigated expression of SP and neurokinin-1 receptor (NK1R) on peripheral blood leukocytes and mast cells from patients with eczema and influence of SP on mast cell accumulation by using flow cytometry analysis, trans-epithelial cell migration assay and mouse peritoneal model. The results showed that plasma SP and IL-17A levels in eczema patients were higher than that in healthy control subject. The percentages of SP+ and NK1R+ expression populations of monocytes, helper T cells, natural killer T cells and basophils in peripheral blood of eczema patients were markedly elevated. It was observed that not only absolute number of mast cells but also SP+ and NK1R+ mast cells are enhanced in the lesion skin of eczema. SP showed a potent chemoattractant action on mast cells as assessed by a mouse peritoneal model and a trans-endothelium cell migration assay. SP-induced mast cell accumulation appears a CD18/CD11a complex, L-selectin and ICAM-1-dependent event which can be blocked by a NK-1R antagonist RP67580. In conclusion, elevated expression of SP in patients with eczema and the ability of SP in induction of mast cell accumulation indicate strongly that SP is a potent proinflammatory mediator, which contributes to the pathogenesis of eczema. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of eczema.

Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model.

PubMed

Renner, Christof; Zemitzsch, Nadine; Fuchs, Beate; Geiger, Kathrin D; Hermes, Matthias; Hengstler, Jan; Gebhardt, Rolf; Meixensberger, Jürgen; Gaunitz, Frank

2010-01-06

It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 microl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo. As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

Monocyte migration explains the changes in macrophage arachidonate metabolism during the immune response.

PubMed Central

Tripp, C S; Unanue, E R; Needleman, P

1986-01-01

The profile of arachidonic acid metabolites in resident peritoneal macrophages is distinctly different from the profile of macrophages isolated after an acute bacterial infection. The latter produce decreased prostaglandins E2 and I2 and leukotriene C4 while conserving the synthesis of thromboxane A2. We show here that the initial changes in peritoneal macrophage arachidonate metabolism during the immune response appear to be the result of the large influx of blood monocytes, which have a characteristic metabolism distinct from resident macrophages. We demonstrate that the initial decrease in peritoneal macrophage arachidonate metabolism and the increase in macrophage numbers occur simultaneously after infection with Listeria monocytogenes. Also the macrophage arachidonate metabolism seen at the height of the peritoneal cellular influx is the same as that of purified blood monocytes. Both Listeria peritoneal macrophages and blood monocytes produce equal or greater quantities of thromboxane A2 relative to prostaglandins I2 and E2 or leukotriene C4 whereas resident cells produce 1/10 to 1/25 as much thromboxane A2 compared to the other products. Furthermore, the changes in peritoneal macrophage arachidonate metabolism in response to Listeria infection do not occur if the influx of blood monocytes is stopped by irradiating the mice prior to infection implying that the cellular influx is necessary to see the changes in arachidonate metabolism. Finally, activation of peritoneal macrophages, measured as an increase in Ia expression, occurs 36 hr after the influx of monocytes from the blood and the resultant shift in arachidonate metabolism during Listeria infection. PMID:3099288

A Strategy Using Photodynamic Therapy and Clofibric Acid to Treat Peritoneal Dissemination of Ovarian Cancer.

PubMed

Yokoyama, Yoshihito; Shigeto, Tatsuhiko; Miura, Rie; Kobayashi, Asami; Mizunuma, Makito; Yamauchi, Aisa; Futagami, Masayuki; Mizunuma, Hideki

2016-01-01

The current study examined the effectiveness of concurrent therapy using photodynamic therapy (PDT) and clofibric acid (CA) to treat peritoneal carcinomatosis resulting from ovarian cancer. Nude rats were used to create a model of peritoneal carcinomatosis resulting from ovarian cancer and the effectiveness of PDT with 5-aminolevulinic acid methyl ester hydrochloride (methyl-ALA-PDT) was determined. The survival time of rats receiving that therapy was compared to the survival time of a control group. Rats with peritoneal carcinomatosis resulting from ovarian cancer were divided into 3 groups: a group that received debulking surgery (DS) alone, a group that received DS+methyl-ALA-PDT, and a group that received DS+methyl-ALA-PDT+CA. The survival time of the 3 groups was compared. Protoporphyrin, a metabolite of methyl-ALA, produces a photochemical action when activated by light. The level of protoporphyrin (the concentration) that reached organs in the abdomen was measured with HPLC. Rats receiving methyl- ALA-PDT had a significantly longer survival time compared to the controls. Rats with peritoneal carcinomatosis that received DS+methyl-ALA-PDT+CA had a significantly longer survival time compared to the rats that received DS alone. Some of the rats that received concurrent therapy survived for a prolonged period. Protoporphyrin was highly concentrated in peritoneal metastases, but only small amounts reached major organs in the abdomen. PDT was not found to result in necrosis in the intestines. The results indicated that concurrent therapy consisting of PDT with methyl-ALA and CA is effective at treating peritoneal carcinomatosis resulting from ovarian cancer without damaging organs.

Peritoneal dialysis-related peritonitis: challenges and solutions

PubMed Central

Salzer, William L

2018-01-01

Peritoneal dialysis is an effective treatment modality for patients with end-stage renal disease. The relative use of peritoneal dialysis versus hemodialysis varies widely by country. Data from a 2004 survey reports the percentage of patients with end-stage renal disease treated with peritoneal dialysis to be 5%–10% in economically developed regions like the US and Western Europe to as much as 75% in Mexico. This disparity is probably related to the availability and access to hemodialysis, or in some cases patient preference for peritoneal over hemodialysis. Peritoneal dialysis-related peritonitis remains the major complication and primary challenge to the long-term success of peritoneal dialysis. Fifty years ago, with the advent of the Tenckhoff catheter, patients averaged six episodes of peritonitis per year on peritoneal dialysis. In 2016, the International Society for Peritoneal Dialysis proposed a benchmark of 0.5 episodes of peritonitis per year or one episode every 2 years. Despite the marked reduction in peritonitis over time, peritonitis for the individual patient is problematic. The mortality for an episode of peritonitis is 5% and is a cofactor for mortality in another 16% of affected patients. Prevention of peritonitis and prompt and appropriate management of peritonitis is essential for the long-term success of peritoneal dialysis in all patients. In this review, challenges and solutions are addressed regarding the pathogenesis, clinical features, diagnosis, treatment, and prevention of peritoneal dialysis-related peritonitis from the viewpoint of an infectious disease physician.

A Peritoneal Dialysis Regimen Low in Glucose and Glucose Degradation Products Results in Increased Cancer Antigen 125 and Peritoneal Activation

PubMed Central

le Poole, Caatje Y.; Welten, Angelique G.A.; ter Wee, Piet M.; Paauw, Nanne J.; Djorai, Amina N.; Valentijn, Rob M.; Beelen, Robert H.J.; van den Born, Jacob; van Ittersum, Frans J.

2012-01-01

♦ Background: Glucose and glucose degradation products (GDPs) in peritoneal dialysis fluids (PDFs) are both thought to mediate progressive peritoneal worsening. ♦ Methods: In a multicenter, prospective, randomized crossover study, incident continuous ambulatory peritoneal dialysis patients were treated either with conventional lactate-buffered PDF (sPD regimen) or with a regimen low in glucose and GDPs: Nutrineal×1, Extraneal×1, and Physioneal×2 (NEPP regimen; all solutions: Baxter Healthcare, Utrecht, Netherlands). After 6 months, patients were switched to the alternative regimen for another 6 months. After 6 weeks of run-in, before the switch, and at the end of the study, 4-hour peritoneal equilibration tests were performed, and overnight effluents were analyzed for cells and biomarkers. Differences between the regimens were assessed by multivariate analysis corrected for time and regimen sequence. ♦ Results: The 45 patients who completed the study were equally distributed over both groups. During NEPP treatment, D4/D0 glucose was lower (p < 0.01) and D/P creatinine was higher (p = 0.04). In NEPP overnight effluent, mesothelial cells (p < 0.0001), cancer antigen 125 (p < 0.0001), hyaluronan (p < 0.0001), leukocytes (p < 0.001), interleukins 6 (p = 0.001) and 8 (p = 0.0001), and vascular endothelial growth factor (VEGF, p < 0.0001) were increased by a factor of 2 – 3 compared with levels in sPD effluent. The NEPP regimen was associated with higher transport parameters, but that association disappeared after the addition of VEGF to the model. The association between NEPP and higher effluent levels of VEGF could not be attributed to glucose and GDP loads. ♦ Conclusions: Study results indicate preservation of the mesothelium and increased peritoneal activation during NEPP treatment. Whether the increase in VEGF reflects an increase in mesothelial cell mass or whether it points to another, undesirable mechanism cannot be determined from the present study. Longitudinal studies are needed to finally evaluate the usefulness of the NEPP regimen for further clinical use. PMID:22045100

The cannabinoid WIN55,212-2 protects against oxidized LDL-induced inflammatory response in murine macrophages[S

PubMed Central

Hao, Ming-xiu; Jiang, Li-sheng; Fang, Ning-yuan; Pu, Jun; Hu, Liu-hua; Shen, Ling-Hong; Song, Wei; He, Ben

2010-01-01

The endocannabinoid system has recently been attracted interest for its anti-inflammatory and anti-oxidative properties. In this study, we investigated the role of the endocannabinoid system in regulating the oxidized low-density lipoprotein (oxLDL)-induced inflammatory response in macrophages. RAW264.7 mouse macrophages and peritoneal macrophages isolated from Sprague-Dawley (SD) rats were exposed to oxLDL with or without the synthetic cannabinoid WIN55,212-2. To assess the inflammatory response, reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF- α) levels were determined, and activation of the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B signaling pathways were assessed. We observed that: i) oxLDL strongly induced ROS generation and TNF- α secretion in murine macrophages; ii) oxLDL-induced TNF- α and ROS levels could be lowered considerably by WIN55,212-2 via inhibition of MAPK (ERK1/2) signaling and NF-kappa B activity; and iii) the effects of WIN55212-2 were attenuated by the selective CB2 receptor antagonist AM630. These results demonstrate the involvement of the endocannabinoid system in regulating the oxLDL-induced inflammatory response in macrophages, and indicate that the CB2 receptor may offer a novel pharmaceutical target for treating atherosclerosis. PMID:20305287

Tumor-environment biomimetics delay peritoneal metastasis formation by deceiving and redirecting disseminated cancer cells.

PubMed

De Vlieghere, Elly; Gremonprez, Félix; Verset, Laurine; Mariën, Lore; Jones, Christopher J; De Craene, Bram; Berx, Geert; Descamps, Benedicte; Vanhove, Christian; Remon, Jean-Paul; Ceelen, Wim; Demetter, Pieter; Bracke, Marc; De Geest, Bruno G; De Wever, Olivier

2015-06-01

Peritoneal metastasis is life threatening and is the result of an extensive communication between disseminated cancer cells, mesothelial cells and cancer-associated fibroblasts (CAF). CAFs secrete extracellular matrix (ECM) proteins creating a receptive environment for peritoneal implantation. Considering cancer as an ecosystem may provide opportunities to exploit CAFs to create biomimetic traps to deceive and redirect cancer cells. We have designed microparticles (MP) containing a CAF-derived ECM-surface that is intended to compete with natural niches. CAFs were encapsulated in alginate/gelatine beads (500-750 μm in diameter) functionalised with a polyelectrolyte coating (MP[CAF]). The encapsulated CAFs remain viable and metabolically active (≥35 days), when permanently encapsulated. CAF-derived ECM proteins are retained by the non-biodegradable coating. Adhesion experiments mimicking the environment of the peritoneal cavity show the selective capture of floating cancer cells from different tumor origins by MP[CAF] compared to control MP. MP[CAF] are distributed throughout the abdominal cavity without attachment to intestinal organs and without signs of inflammatory reaction. Intraperitoneal delivery of MP[CAF] and sequential removal redirects cancer cell adhesion from the surgical wound to the MP[CAF], delays peritoneal metastasis formation and prolongs animal survival. Our experiments suggest the use of a biomimetic trap based on tumor-environment interactions to delay peritoneal metastasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of electrolyzed strong acid water on peritoneal irrigation of experimental perforated peritonitis.

PubMed

Kubota, Akio; Nose, Keisuke; Yonekura, Takeo; Kosumi, Takuya; Yamauchi, Katsuji; Oyanagi, Harumasa

2009-01-01

Electrolyzed strong acid water (ESAW) is generated by the electrolysis of a weak sodium chloride solution. Although ESAW is known to have a strong bactericidal activity and to be harmless to the living body, its effectiveness and safety in the treatment of perforated peritonitis has not been well established. Male Wistar rats were used for the study. Three hours after cecal ligation and puncture, the cecum was resected and the peritoneal cavity was irrigated with 50 ml of saline (Group S, n=12) or ESAW (Group E, n=14). The 5-day survival rate was compared between the two groups. In another pair of animals (n=10 each), bacteria in the ascitic fluid were counted at 6 and 18 h after irrigation. No adverse effects of ESAW were observed in the experimental group. The 5-day survival rate was 25% (3/12) and 85.7% (12/14) in Groups S and E, respectively (P < 0.01). The bacterial count at 18 h after the irrigation in Groups S and E was (5.0 +/- 2.5) x 10(5)/ml and (2.2 +/- 2.0) x 10(4)/ml, respectively (P < 0.0001). Peritoneal lavage with ESAW had no adverse effect, and achieved more effective decontamination than saline for perforated peritonitis. Therefore, the results of this study are considered to warrant and support the clinical application of ESAW.

Viridans Streptococci in Peritoneal Dialysis Peritonitis: Clinical Courses and Long-Term Outcomes

PubMed Central

Chao, Chia-Ter; Lee, Szu-Ying; Yang, Wei-Shun; Chen, Huei-Wen; Fang, Cheng-Chung; Yen, Chung-Jen; Chiang, Chih-Kang; Hung, Kuan-Yu; Huang, Jenq-Wen

2015-01-01

♦ Background: The clinical courses and long-term outcomes of viridans streptococcus (VS) peritoneal dialysis (PD) peritonitis remain unclear. ♦ Methods: We conducted a retrospective analysis of all PD patients in a single center with gram-positive cocci (GPC) peritonitis between 2005 and 2011, and divided them into 3 groups: VS, other streptococci and other GPC (apart from VS). Clinical characteristics and outcomes of the VS group were compared with the other streptococci and other GPC groups, with prognostic factors determined. ♦ Results: A total of 140 patients with 168 episodes of GPC peritonitis (44% of all peritonitis) were identified over 7 years. Among these, 18 patients (13%) developed VS peritonitis, while 14 patients (10%) developed other streptococcal peritonitis. Patients with VS peritonitis had a high cure rate by antibiotic alone (94%), despite a high polymicrobial yield frequency (28%). We found that VS peritonitis carried a lower risk of Tenckhoff catheter removal and relapsing episodes than other GPC peritonitis (6% vs 11%), and a lower mortality than other streptococci peritonitis (0% vs 7%). However, after the index peritonitis episodes, VS, other streptococci, and other GPC group had a significantly increased peritonitis incidence compared with the period before the index peritonitis (all p < 0.01). Patients with VS peritonitis had a significantly higher incidence of refractory peritonitis compared with other streptococci or other GPC peritonitis in the long term (both p < 0.01). ♦ Conclusions: VS poses a higher risk of subsequent refractory peritonitis after the index episode as compared with other streptococcal or GPC peritonitis. It might be prudent to monitor the technique of these patients with VS peritonitis closely to avoid further peritonitis episodes. PMID:24497584

Activation of Peroxisome Proliferator-activated Receptor γ (PPARγ) and CD36 Protein Expression

PubMed Central

Yang, Xiaoxiao; Zhang, Wenwen; Chen, Yuanli; Li, Yan; Sun, Lei; Liu, Ying; Liu, Mengyang; Yu, Miao; Li, Xiaoju; Han, Jihong; Duan, Yajun

2016-01-01

Progesterone or its analog, one of components of hormone replacement therapy, may attenuate the cardioprotective effects of estrogen. However, the underlying mechanisms have not been fully elucidated. Expression of CD36, a receptor for oxidized LDL (oxLDL) that enhances macrophage/foam cell formation, is activated by the transcription factor peroxisome proliferator-activated receptor γ (PPARγ). CD36 also functions as a fatty acid transporter to influence fatty acid metabolism and the pathophysiological status of several diseases. In this study, we determined that progesterone induced macrophage CD36 expression, which is related to progesterone receptor (PR) activity. Progesterone enhanced cellular oxLDL uptake in a CD36-dependent manner. Mechanistically, progesterone increased PPARγ expression and PPARγ promoter activity in a PR-dependent manner and the binding of PR with the progesterone response element in the PPARγ promoter. Specific deletion of macrophage PPARγ (MφPPARγ KO) expression in mice abolished progesterone-induced macrophage CD36 expression and cellular oxLDL accumulation. We also determined that, associated with gestation and increased serum progesterone levels, CD36 and PPARγ expression in mouse adipose tissue, skeletal muscle, and peritoneal macrophages were substantially activated. Taken together, our study demonstrates that progesterone can play dual pathophysiological roles by activating PPARγ expression, in which progesterone increases macrophage CD36 expression and oxLDL accumulation, a negative effect on atherosclerosis, and enhances the PPARγ-CD36 pathway in adipose tissue and skeletal muscle, a protective effect on pregnancy. PMID:27226602

On the Functional Overlap between Complement and Anti-Microbial Peptides.

PubMed

Zimmer, Jana; Hobkirk, James; Mohamed, Fatima; Browning, Michael J; Stover, Cordula M

2014-01-01

Intriguingly, activated complement and anti-microbial peptides share certain functionalities; lytic, phagocytic, and chemo-attractant activities and each may, in addition, exert cell instructive roles. Each has been shown to have distinct LPS detoxifying activity and may play a role in the development of endotoxin tolerance. In search of the origin of complement, a functional homolog of complement C3 involved in opsonization has been identified in horseshoe crabs. Horseshoe crabs possess anti-microbial peptides able to bind to acyl chains or phosphate groups/saccharides of endotoxin, LPS. Complement activity as a whole is detectable in marine invertebrates. These are also a source of anti-microbial peptides with potential pharmaceutical applicability. Investigating the locality for the production of complement pathway proteins and their role in modulating cellular immune responses are emerging fields. The significance of local synthesis of complement components is becoming clearer from in vivo studies of parenchymatous disease involving specifically generated, complement-deficient mouse lines. Complement C3 is a central component of complement activation. Its provision by cells of the myeloid lineage varies. Their effector functions in turn are increased in the presence of anti-microbial peptides. This may point to a potentiating range of activities, which should serve the maintenance of health but may also cause disease. Because of the therapeutic implications, this review will consider closely studies dealing with complement activation and anti-microbial peptide activity in acute inflammation (e.g., dialysis-related peritonitis, appendicitis, and ischemia).

Induction of histamine release in vitro from rat peritoneal mast cells by extracts of grain dust.

PubMed Central

Warren, C P; Holford-Strevens, V

1986-01-01

The ability of extracts of grain dust and wheat to induce histamine release from rat peritoneal cells was investigated. Some grain dusts, with a high endotoxin content, were found to produce cytotoxic histamine release. Extract of wheat dust, with a low endotoxin release, produced noncytotoxic histamine release from peritoneal cells but not from purified mast cells. This reaction was dependent on the presence of phosphatidyl serine. The agent did not appear to be a lectin because histamine release was not enhanced by passive sensitization of mast cells with IgE. The activity occurred only over a narrow range of concentrations of the extract of wheat. The cause was unclear. PMID:2423321

Fluorescence-guided surgery for cancer patients: a proof of concept study on human xenografts in mice and spontaneous tumors in pets

PubMed Central

Mery, Eliane; Golzio, Muriel; Guillermet, Stephanie; Lanore, Didier; Naour, Augustin Le; Thibault, Benoît; Tilkin-Mariamé, Anne Françoise; Bellard, Elizabeth; Delord, Jean Pierre; Querleu, Denis; Ferron, Gwenael; Couderc, Bettina

2017-01-01

Surgery is often the first treatment option for patients with cancer. Patient survival essentially depends on the completeness of tumor resection. This is a major challenge, particularly in cases of peritoneal carcinomatosis, where tumors are widely disseminated in the large peritoneal cavity. Any development to help surgeons visualize these residual cells would improve the completeness of the surgery. For non-disseminated tumors, imaging could be used to ensure that the tumor margins and the draining lymph nodes are free of tumor deposits. Near-infrared fluorescence imaging has been shown to be one of the most convenient imaging modalities. Our aim was to evaluate the efficacy of a near-infrared fluorescent probe targeting the αvβ3 integrins (Angiostamp™) for intraoperative detection of tumors using the Fluobeam® device. We determined whether different human tumor nodules from various origins could be detected in xenograft mouse models using both cancer cell lines and patient-derived tumor cells. We found that xenografts could be imaged by fluorescent staining irrespective of their integrin expression levels. This suggests imaging of the associated angiogenesis of the tumor and a broader potential utilization of Angiostamp™. We therefore performed a veterinary clinical trial in cats and dogs with local tumors or with spontaneous disseminated peritoneal carcinomatosis. Our results demonstrate that the probe can specifically visualize both breast and ovarian nodules, and suggest that Angiostamp™ is a powerful fluorescent contrast agent that could be used in both human and veterinary clinical trials for intraoperative detection of tumors. PMID:29312629

Malignant mesothelioma induced by asbestos and zeolite in the mouse peritonenal cavity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Y.; Kohyama, N.

1984-10-01

The carcinogenicity of asbestos (amosite and chrysotile) and zeolite (fibrous erionite, mordenite, and synthetic zeolite 4A) were studied in the peritoneum of 586 BALB/C male mice after a single intraperitoneal or intraabdominal wall injection. Tumors developed in 93 of 394 animals (23.6%) treated with asbestos or fibrous erionite 7 months or more after administration. All of the induced peritoneal tumors were intimately associated with marked peritoneal fibrosis, in which asbestos or erionite fibers were regularly detected. Histopathologically, 83 of 93 were consistent with malignant mesotheliomas. Other tumors consisted of 6 plasmacytomas, 1 histiocytoma, 1 liposarcoma, 1 osteosarcoma, and 1 adenocarcinomamore » of the pancreas. Two of the cases of mesotheliomas were associated with plasmacytoma. In many instances, the primary site of the mesotheliomas seemed to be multiple, the favorite sites being the omentum, mesentery, serosae of the gastrointestinal and genital organs, the diaphragm, the capsule of the liver and spleen, and the abdominal wall peritoneum. In addition to the 93 peritoneal tumors, 3 extraperitoneal tumors (1 fibrosarcoma and 2 rhabdomyosarcomas) were induced by amosite which was probably accidentally injected into the extraperitoneal connective tissue and the striated muscle tissue of the abdominal wall, respectively. These three tumors were also intimately associated with focal fibrosis in which amosite fibers were detected. Among the three different types of zeolite, only fibrous erionite showed striking carcinogenicity and marked fibrogenicity. The erionite-induced mesotheliomas were similar to those induced by asbestos in exhibiting long latency, in gross appearance, in histology, and in close association with fibrosis.« less

Telomerase reverse transcriptase (TERT) expression and role of vincristine sulfate in mouse model of malignancy related peritoneal ascites: an experimental metastatic condition.

PubMed

Chaklader, M; Das, P; Pereira, J A; Chatterjee, S; Basak, P; Law, A; Banerjee, T; Chauhan, S; Law, S

2011-06-01

To evaluate the efficacy of intraperitoneal vincristine administration into ascitic sarcoma-180 bearing mice as a model of human malignant ascites regarding various peritoneal/retroperitoneal sarcomatosis, and to evaluate the flowcytometric telomerase reverse transcriptase expression for the diagnostic and prognostic purposes. Present study included disease induction by intraperitoneal homologous ascitic sarcoma-180 transplantation followed by in vivo intraperitoneal drug administration to study mitotic index, flowcytometric cell cycle and telomerase reverse transcriptase expression pattern, erythrosin-B dye exclusion study for malignant cell viability assessment. Besides, in vitro malignant ascite culture in presence and absence of vincristine sulfate and survival study were also taken into consideration. Intraperitoneal vincristine administration (concentration 0.5 mg/kg body weight) significantly diminished the mitotic index in diseased subjects in comparison to untreated control subjects. Treated group of animals showed increased life span and median survival time. Cell viability assessment during the course of drug administration also revealed gradual depression on cell viability over time. Flowcytometric cell cycle analysis showed a good prognostic feature of chemotherapeutic administration schedule by representing high G2/M phase blocked cells along with reduced telomerase reverse transcriptase positive cells in treated animals. We conclude that long term administration of vincristine sulfate in small doses could be a good pharmacological intervention in case of malignant peritoneal ascites due to sarcomatosis as it indirectly reduced the level of telomerase reverse transcriptase expression in malignant cells by directly regulating cell cycle and simultaneously increased the life expectancy of the diseased subjects.

Anticancer effect of a Kampo preparation Daikenchuto.

PubMed

Nagata, Takuya; Toume, Kazufumi; Long, Lv Xiao; Hirano, Katsuhisa; Watanabe, Toru; Sekine, Shinichi; Okumura, Tomoyuki; Komatsu, Katsuko; Tsukada, Kazuhiro

2016-07-01

No traditional Japanese and Chinese herbal preparations have been shown to be effective antitumor agents, and a Japanese herbal therapy (Kampo medicine) for cancer that causes fewer adverse drug reactions than orthodox pharmaceuticals is desired. Our present study demonstrated that a Kampo preparation Daikenchuto (DKT) exerts an antitumor effect against various cancer cells. We also discovered an antitumor factor in Japanese Zanthoxylum peel, which is an ingredient of DKT. Breast, esophageal, gastric, and colon cancer cell lines were individually incubated with DKT for 1-72 h, followed by assessment of tumor growth inhibition by MTT assay. The cancer cells were also analyzed for apoptotic changes after DKT treatment. Nude mice were used to establish a model of gastric cancer tumor growth and peritoneal disseminated metastasis, in which the number of peritoneal disseminations was evaluated after oral administration of DKT for 4 weeks. In addition, the antitumor effects of the individual DKT ingredients (viz., ginseng, Japanese Zanthoxylum peel, and processed ginger) and other Kampo preparations were also analyzed. The antitumor effect of DKT was demonstrated in gastric, breast, esophageal, and colon cancer cells. DKT treatment induced apoptosis in these cells. Oral administration of DKT had a tendency to reduce the growth and significantly reduced the peritoneal dissemination of gastric cancer in the nude mouse model compared with control. DKT exhibited a higher antitumor effect than other Kampo preparations. Furthermore, Japanese Zanthoxylum peel, an ingredient of DKT, showed a particularly potent antitumor effect. Our study indicated that DKT is useful as a Kampo preparation for cancer therapy. We also showed that Japanese Zanthoxylum peel, an ingredient of DKT, contains an antitumor factor.

Peritonitis outcomes in patients with HIV and end-stage renal failure on peritoneal dialysis: a prospective cohort study.

PubMed

Ndlovu, Kwazi C Z; Sibanda, Wilbert; Assounga, Alain

2017-02-03

Few studies have investigated the management of human immunodeficiency virus (HIV)-associated end-stage renal failure particularly in low-resource settings with limited access to renal replacement therapy. We aimed to evaluate the effects of HIV infection on continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis outcomes and technique failure in highly active antiretroviral therapy (HAART)-treated HIV-positive CAPD populations. We conducted a single-center prospective cohort study of consecutive incident CAPD patients recruited from two hospitals in Durban, South Africa from September 2012-February 2015. Seventy HIV-negative and 70 HIV-positive end-stage renal failure patients were followed monthly for 18 months at a central renal clinic. Primary outcomes of peritonitis and catheter failure were assessed for the first 18 months of CAPD therapy. We assessed risk factors for peritonitis and catheter failure using Cox regression survival analysis. The HIV-positive cohort had a significantly increased rate of peritonitis compared to the HIV-negative cohort (1.86 vs. 0.76 episodes/person-years, respectively; hazard ratio [HR], 2.41; 95% confidence interval [CI], 1.69-3.45, P < 0.001). When the baseline CD4 count was below 200 cells/μL, the peritonitis rate rose to 3.69 episodes/person-years (HR 4.54, 95% CI 2.35-8.76, P < 0.001), while a baseline CD4 count above 350 cells/μL was associated with a peritonitis rate of 1.60 episodes/person-years (HR 2.10, CI 1.39-3.15, P = 0.001). HIV was associated with increased hazards of peritonitis relapse (HR, 3.88; CI, 1.37-10.94; P = 0.010). Independent predictors associated with increased peritonitis risk were HIV (HR, 1.84; CI, 1.07-3.16; P = 0.027), diabetes (HR, 2.09; CI, 1.09-4.03; P = 0.027) and a baseline CD4 count < 200 cells/μL (HR, 3.28; CI, 1.42-7.61; P = 0.006). Catheter failure rates were 0.34 (HIV-positive cohort) and 0.24 (HIV-negative cohort) episodes/person-years (HR, 1.42; 95% CI, 0.73-2.73; P = 0.299). Peritonitis (HR, 14.47; CI, 2.79-75.00; P = 0.001), average hemoglobin concentrations (HR, 0.75; CI, 0.59-0.95; P = 0.016), and average serum C-reactive protein levels were independent predictors of catheter failure. HIV infection in end-stage renal disease patients managed by CAPD was associated with increased peritonitis risk; however, HIV infection did not increase the risk for CAPD catheter failure rate at 18 months.

Peritonitis - spontaneous bacterial

MedlinePlus

Spontaneous bacterial peritonitis (SBP); Ascites - peritonitis; Cirrhosis - peritonitis ... who are on peritoneal dialysis for kidney failure. Peritonitis may have other causes . These include infection from ...

Tamoxifen Activation of Cre-Recombinase Has No Persisting Effects on Adult Neurogenesis or Learning and Anxiety

PubMed Central

Rotheneichner, Peter; Romanelli, Pasquale; Bieler, Lara; Pagitsch, Sebastian; Zaunmair, Pia; Kreutzer, Christina; König, Richard; Marschallinger, Julia; Aigner, Ludwig; Couillard-Després, Sébastien

2017-01-01

Adult neurogenesis is a tightly regulated process continuously taking place in the central nervous system of most mammalian species. In neuroscience research, transgenic animals bearing the tamoxifen-inducible CreERT2-Lox system are widely used. In this study, we made use of a Nestin-CreERT2/R26R-YFP transgenic mouse model in which the CreERT2 activates the expression of YFP in multipotent neural stem cells upon tamoxifen application. Humoral factors, such as the levels of estrogens, have been reported to affect the hippocampal neurogenesis. The application of tamoxifen, a mixed agonist/antagonist of the estrogen receptor that permeates the blood-brain-barrier, could thus influence adult neurogenesis. Although the functions of adult neurogenesis are yet to be fully deciphered, a reciprocal interaction between rates of neurogenesis on the one hand and learning and mood regulation on the other hand, has been suggested. The impact of tamoxifen on neurogenesis and behavior was therefore addressed following five daily applications according to the open field test, the elevated plus maze, and Morris water maze. In addition, the impact of short-term tamoxifen application on progenitor cell proliferation, morphology, and fate in the neurogenic niche of the dentate gyrus were investigated. Finally, the influence of the route of administration (oral vs. intra-peritoneal) and gender-specific response were scrutinized. The sub-acute analysis did neither reveal significant differences in behavior, such as voluntary motor activity, anxiety behavior, and spatial learning, nor in cell proliferation, cell survival, dendritic arborization or maturation rate within the dentate gyrus between saline solution-, corn oil-, and tamoxifen-treated groups. Finally, neither the route of application, nor the gender of treated mice influenced the response to tamoxifen. We conclude that short tamoxifen treatments used to activate the CreERT2 system in transgenic mouse models does not have a measurable impact on adult neurogenesis or the here tested behavior, and is therefore appropriate for most studies in the field. PMID:28203140

Vernix caseosa peritonitis after vaginal delivery.

PubMed

Sadath, Shameema A; Abo Diba, Fathiya I; Nayak, Surendra; Shamali, Iman Al; Diejomaoh, Michael F

2013-01-01

Vernix caseosa peritonitis (VCP) is a very unusual complication caused by inflammatory response to amniotic fluid spilled into the maternal peritoneal cavity. Twenty-seven cases have been reported, and all occurred after cesarean section. We present a case of VCP following vaginal delivery; this may be the first case reported after vaginal delivery. Mrs. A, 28 years old, gravida 3, para 2, with one previous cesarean section, was admitted at 41 weeks gestation in active labor. Vacuum extraction was performed to deliver a healthy male baby, 4.410 kg, Apgar scores 7, 8. She developed fever, acute abdominal pain, and distension about 3 hours after delivery. A diagnosis of acute abdomen was made. Laparotomy was performed and it revealed neither uterine scar rupture nor other surgical emergencies, but 500 mL of turbid fluid and some cheesy material on the serosal surface of all viscera. Biopsies were taken. She had a course of antibiotics and her recovery was complete. Histology of the peritoneal fluid and tissue biopsy resulted in a diagnosis of VCP. Clinical diagnosis of peritonitis due to vernix caseosa should be considered in patients presenting postpartum with an acute abdomen after vaginal delivery.

Effects of platelet rich plasma on fascial healing in rats with fecal peritonitis

PubMed

Girgin, Mustafa; Binnetoglu, Kenan; Duman, Kazim; Kanat, Burhan Hakan; Cetinkaya, Ziya; Ayten, Refik; Ilhan, Yavuz Selim; Ilhan, Necip; Seker, Ibrahim; Timurkaan, Necati

2016-05-01

To evaluate the effects of platelet rich plasma (PRP) on the healing of fascia wherein peritonitis has been created. Twenty eight Wistar Albino rats were divided into four groups. Only a primary fascial repair following laparotomy was performed on Group 1, a primary fascial repair performed and PRP treatment applied following laparotomy on Group 2, and a fecal peritonitis created following laparotomy and a primary fascial repair carried out on Group 3. A fecal peritonitis was created following laparotomy and primary fascial repair and PRP treatment on the fascia was carried out on Group 4. TNF-α was found to be significantly lower in the control group (Group 1). It was detected at the highest level in the group in which fecal peritonitis was created and PRP applied (Group 4). TGF-β was determined as being significantly higher only in Group 4. Histopathologically, the differences between the groups in terms of cell infiltration and collagen deposition were not found to be significant. When platelet rich plasma was given histologically and biochemicaly as wound healing parameters cellular infiltration, collagen accumulation, and tissue hydroxyiproline levels were not increased but neovascularization, fibroblast activation and TNF Alfa levels were increased and PRP accelerated wound healing.

The time for surgery of peritonitis associated with peritoneal dialysis.

PubMed

Mihalache, O; Bugă, C; Doran, H; Catrina, E; Bobircă, F; Andreescu, A; Mustățea, P; Pătrașcu, T

2016-01-01

Peritonitis is the main complication of peritoneal dialysis (PD) and also an important factor for raising the cost of the method to the level of hemodialysis. Associated with PD, peritonitis is responsible for the increase of morbidity and mortality of the procedure and, at the same time, the main cause of the technique failure. Severe and prolonged peritonitis or repeated episodes of peritonitis lead to ultrafiltration failure. Peritonitis treatment should aim for a rapid remission of inflammation in order to preserve the peritoneal membrane functional integrity. The treatment of PD peritonitis consists mainly of antibiotic therapy, surgical intervention not being usually required. However, it is of outmost importance to differentiate the so-called "catheter related" peritonitis from secondary peritonitis due to visceral lesions, in which the surgical treatment comes first. The confusion between secondary and "catheter related" peritonitis may lead to serious errors in choosing the correct treatment, endangering the patient's life. The differential diagnosis between a refractory or secondary peritonitis in a peritoneal dialyzed patient may be very difficult. In front of a refractory PD peritonitis, surgical exploration must not be delayed. Also we have to keep in mind that the aim of peritonitis treatment is the saving of the peritoneal membrane and not the catheter.

Predictors of Peritonitis and the Impact of Peritonitis on Clinical Outcomes of Continuous Ambulatory Peritoneal Dialysis Patients in Taiwan—10 Years’ Experience in a Single Center

PubMed Central

Hsieh, Yao-Peng; Chang, Chia-Chu; Wen, Yao-Ko; Chiu, Ping-Fang; Yang, Yu

2014-01-01

♦ Objective: Peritoneal dialysis (PD) has become more prevalent as a treatment modality for end-stage renal disease, and peritonitis remains one of its most devastating complications. The aim of the present investigation was to examine the frequency and predictors of peritonitis and the impact of peritonitis on clinical outcomes. ♦ Methods: Our retrospective observational cohort study enrolled 391 patients who had been treated with continuous ambulatory PD (CAPD) for at least 90 days. Relevant demographic, biochemical, and clinical data were collected for an analysis of CAPD-associated peritonitis, technique failure, drop-out from PD, and patient mortality. ♦ Results: The peritonitis rate was 0.196 episodes per patient-year. Older age (>65 years) was the only identified risk factor associated with peritonitis. A multivariate Cox regression model demonstrated that technique failure occurred more often in patients experiencing peritonitis than in those free of peritonitis (p < 0.001). Kaplan-Meier analysis revealed that the group experiencing peritonitis tended to survive longer than the group that was peritonitis-free (p = 0.11). After multivariate adjustment, the survival advantage reached significance (hazard ratio: 0.64; 95% confidence interval: 0.46 to 0.89; p = 0.006). Compared with the peritonitis-free group, the group experiencing peritonitis also had more drop-out from PD (p = 0.03). ♦ Conclusions: The peritonitis rate was relatively low in the present investigation. Elderly patients were at higher risk of peritonitis episodes. Peritonitis independently predicted technique failure, in agreement with other reports. However, contrary to previous studies, all-cause mortality was better in patients experiencing peritonitis than in those free of peritonitis. The underlying mechanisms of this presumptive “peritonitis paradox” remain to be clarified. PMID:24084840

Regulation of apoptosis by somatostatin and substance P in peritoneal macrophages.

PubMed

Kang, B N; Jeong, K S; Park, S J; Kim, S J; Kim, T H; Kim, H J; Ryu, S Y

2001-09-15

Recent studies have shown that somatostatin (SOM) inhibits interleukin 6 (IL-6) and interferon gamma (IFNgamma) production by lymphocytes and peritoneal macrophages, whereas substance P (SP) enhances these cytokines production. To define the mechanism of the cytokine production enhancements and inhibitions by SOM and SP, we examined the expression of apoptosis modulator, p53, Bcl-2, Bax, inducible nitric oxide synthase (iNOS), Fas, caspase-8 and nitric oxide (NO) in thioglycolate-elicited peritoneal macrophages. SOM caused up-regulation of p53, Bcl-2, Fas and caspase-8 activities, and down-regulation of iNOS expression and NO production. On the other hand, SP slightly induces p53 and highly induces Bcl-2, iNOS expression and NO production. These data suggest that apoptosis by SOM may occur by a Bax- and NO-independent p53 accumulation, and through Fas and caspase-8 activation pathways, and that the inducible expression of Bcl-2 and NO production by SP may contribute to prevent the signals of apoptosis by Bax, and via Fas and caspase-8 activation.

Piperine metabolically regulates peritoneal resident macrophages to potentiate their functions against bacterial infection

PubMed Central

Huang, Mei-Yun; Zha, Qing-Bing; Zhao, Gao-Xiang; Hou, Xiao-Feng; Shi, Zi-Jian; Lin, Qiu-Ru; Ouyang, Dong-Yun; He, Xian-Hui

2015-01-01

Pepper, a daily-used seasoning for promoting appetite, is widely used in folk medicine for treating gastrointestinal diseases. Piperine is the major alkaloid in pepper and possesses a wide range of pharmacological activities. However, the mechanism for linking metabolic and medicinal activities of piperine remains unknown. Here we report that piperine robustly boosts mTORC1 activity by recruiting more system L1 amino acid transporter (SLC7A5/SLC3A2) to the cell membrane, thus promoting amino acid metabolism. Piperine-induced increase of mTORC1 activity in resident peritoneal macrophages (pMΦs) is correlated with enhanced production of IL-6 and TNF-α upon LPS stimulation. Such an enhancement of cytokine production could be abrogated by inhibitors of the mTOR signaling pathway, indicating mTOR's action in this process. Moreover, piperine treatment protected resident pMΦs from bacterium-induced apoptosis and disappearance, and increased their bacterial phagocytic ability. Consequently, piperine administration conferred mice resistance against bacterial infection and even sepsis. Our data highlight that piperine has the capacity to metabolically reprogram peritoneal resident macrophages to fortify their innate functions against bacterial infection. PMID:26439699

Intraperitoneal IL-6 Signaling in Incident Patients Treated with Icodextrin and Glucose Bicarbonate/Lactate–Based Peritoneal Dialysis Solutions

PubMed Central

Opatrna, Sylvie; Lysak, Daniel; Trefil, Ladislav; Parker, Clare; Topley, Nicholas

2012-01-01

♦ Objective: In this study, we compared the activity of interleukin-6 (IL-6), a marker of ongoing peritoneal inflammation and biocompatibility, and its other signaling components, the soluble IL-6 receptor (sIL-6R) and soluble Gp130 (sGp130), in peritoneal effluent from patients treated with icodextrin-based (E) peritoneal dialysis (PD) solution and glucose-based bicarbonate/lactate–buffered (P) solution. ♦ Methods: Using baseline peritoneal ultrafiltration capacity, 33 stable incident PD patients were allocated either to P only (n = 20) or to P plus E for the overnight dwell (n = 13). We used ELISA to determine IL-6, sIL-6R, and sGp130 in timed overnight effluent at 1, 6, and 12 months after PD initiation. Flow cytometry was used to measure expression of IL-6R and Gp130 on isolated peritoneal leukocytes at the same time points. Peritonitis was an exclusion criterion. ♦ Results: At all time points, levels of IL-6 and sIL-6R, and the appearance rates of IL-6 (90.5 pg/min vs. 481.1 pg/min, p < 0.001; 138.6 pg/min vs. 1187.5 pg/min, p < 0.001; and 56.1 pg/min vs. 1386.0 pg/min, p < 0.001), sIL-6R (2035.3 pg/min vs. 4907.0 pg/min, p < 0.01; 1375.0 pg/min vs. 6348.4 pg/min, p < 0.01; and 1881.3 pg/min vs. 5437.8 pg/min, p < 0.01), and sGp130 (37.6 ng/min vs. 65.4 ng/min, p < 0.01; 39.2 ng/min vs. 80.6 ng/min, p < 0.01; 27.8 ng/min vs. 71.0 ng/min, p < 0.01) were significantly higher in peritoneal effluent from E-treated patients than from P-treated patients. Expression of IL6-R and Gp130 on individual leukocyte types isolated from PD effluent did not differ between E- and P-treated patients. The numbers of white blood cells present in effluent were higher in E-treated than in P-treated patients at all time points, but no significant differences were seen in the differential counts or in the number of exfoliated mesothelial cells. The IL-6 parameters in effluent from E-treated patients correlated with their plasma C-reactive protein. Despite the increased activation of the IL-6 system, no increase in peritoneal permeability as assessed by the dialysate-to-plasma ratio of creatinine in E effluent or by systemic inflammation was observed throughout the study. ♦ Conclusions: Higher levels of IL-6, its soluble receptors, and leukocyte expression were observed in E-treated than in P-treated patients, but this difference was not associated with alterations in peritoneal permeability or systemic inflammation during 1 year of follow-up. Leukocyte counts in effluent from E-treated patients were within the normal range previously reported for glucose solutions. This lack of clinical consequences may be a result of a parallel rise in sIL-6R and sGp130, which are known to control the biologic activity of IL-6. The utility of IL-6 level determinations, in isolation, for assessing the biocompatibility of PD solutions is questionable. PMID:22302924

Effect of iNOS inhibitor LNMMA along with antibiotics Chloramphenicol or Ofloxacin in murine peritoneal macrophages regulates S.aureus infection as well as inflammation: An in vitro study.

PubMed

Dey, Somrita; Bishayi, Biswadev

2017-04-01

Death due to sepsis by S. aureus is rapidly increasing because of their potent weaponries against macrophage mediated killing. Macrophages serve as intracellular reservoirs of S. aureus. Although significant resources have been invested during the last decade in new treatments for sepsis, only antibiotic therapy has failed to improve outcomes. Moreover the host pathogen interaction resulted in host cell death triggering inflammation. So, successful therapy requires amalgamation of therapies to delineate pathogen along with providing protection to host cell. With this idea, LNMMA, the iNOS inhibitor is used along with antibiotics Ofloxacin or Chloramphenicol on S. aureus infected mouse peritoneal macrophage. ROS like H 2 O 2 , O 2 - production has been measured. NO inhibition by iNOS inhibitor and antioxidant levels has been analysed. COX2, TLR2 and iNOS expression along with proinflammatory cytokine level was studied. It was found that the use of iNOS inhibitor LNMMA along with antibiotics not only enhances bacterial clearance but also decreases proinflammatory responses in Staphylococcus aureus infected macrophages. Inhibition of TLR2 as well as COX2 has also been found in combined treatment groups. The use of iNOS inhibitor LNMMA plus Ofloxacin or Chloramphenicol pretreatment enhanced bacterial clearance by increasing ROS. Decreases in NO protect the cell from harmful peroxynitril as well as inflammatory damage by changes in iNOS, COX2 activity along with reduced proinflammatory cytokines like TNFα, IFNγ, IL1-β etc. Changes in antioxidant level has been found. This in-vitro realm of augmented bacterial clearance and regulated inflammation may be considered as a novel and important therapeutic intervention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of dichloromethylene bisphosphonate on the in vitro phagocytosis of hydroxyapatite particles by rat peritoneal exudate cells: an electron microscopic and chemiluminescence study.

PubMed Central

Hyvönen, P M; Kowolik, M J

1992-01-01

Transmission electron microscopy and standard chemiluminescence assays were used to investigate the in vivo effect of dichloromethylene bisphosphonate (clodronate) on the phagocytosis of pure hydroxyapatite particles by rat peritoneal macrophages and the production of chemiluminescence by the peritoneal exudate cells. Hydroxyapatite (control) and a hydroxyapatite/clodronate suspension (28 mumol clodronate per gram of hydroxyapatite, experimental) were injected into the peritoneum of rats, the clodronate dose being 10 micrograms/kg. Macrophages were harvested at 12, 24, 48, and 96 hours after injection and the particle phagocytosis was assessed by transmission electron microscopy. Hydroxyapatite alone was completely phagocytosed by 24 hours and hydroxyapatite reacted with clodronate was completely phagocytosed by 48 hours. From 48 hours onwards hydroxyapatite particle dissolution was observed in the phagosomes of cells in the two groups. At 48 hours the chemiluminescence produced by the peritoneal exudate cells was also measured. Clodronate and clodronate/hydroxyapatite enhanced cell activity on subsequent challenge with phorbol myristate acetate or zymosan. Clodronate seemed to exhibit an inhibitory effect on the phagocytic activity and an enhancement of the chemiluminescence production by the cells in this model, indicating that it was modifying the inflammatory cell response. Images PMID:1532298

Effect of gastric acid suppressants and prokinetics on peritoneal dialysis-related peritonitis

PubMed Central

Kwon, Ji Eun; Koh, Seong-Joon; Chun, Jaeyoung; Kim, Ji Won; Kim, Byeong Gwan; Lee, Kook Lae; Im, Jong Pil; Kim, Joo Sung; Jung, Hyun Chae

2014-01-01

AIM: To investigate the effect of gastric acid suppressants and prokinetics on peritonitis development in peritoneal dialysis (PD) patients. METHODS: This was a single-center, retrospective study. The medical records of 398 PD patients were collected from January 2000 to September 2012 and analyzed to compare patients with at least one episode of peritonitis (peritonitis group, group A) to patients who never had peritonitis (no peritonitis group, group B). All peritonitis episodes were analyzed to compare peritonitis caused by enteric organisms and peritonitis caused by non-enteric organisms. RESULTS: Among the 120 patients who met the inclusion criteria, 61 patients had at least one episode of peritonitis and 59 patients never experienced peritonitis. Twenty-four of 61 patients (39.3%) in group A and 15 of 59 patients (25.4%) in group B used gastric acid suppressants. Only the use of H2-blocker (H2B) was associated with an increased risk of PD-related peritonitis; the use of proton pump inhibitors, other antacids, and prokinetics was not found to be a significant risk factor for PD-related peritonitis. A total of 81 episodes of peritonitis were divided into enteric peritonitis (EP) or non-enteric peritonitis, depending on the causative organism, and gastric acid suppressants and prokinetics did not increase the risk of EP in PD patients. CONCLUSION: The use of H2B showed a trend for an increased risk of overall PD-related peritonitis, although further studies are required to clarify the effects of drugs on PD-related peritonitis. PMID:25057226

Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

PubMed Central

Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

2011-01-01

Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies based on stimulation of effective responses and blockade of evasion mechanisms. PMID:21912714

Perioperative Systemic Therapy and Surgery Versus Surgery Alone for Resectable Colorectal Peritoneal Metastases.

ClinicalTrials.gov

2017-05-05

Colorectal Cancer; Colorectal Neoplasms; Colorectal Carcinoma; Colorectal Adenocarcinoma; Colorectal Cancer Metastatic; Peritoneal Carcinoma; Peritoneal Neoplasms; Peritoneal Cavity Cancer; Peritoneal Carcinomatosis; Peritoneal Metastases

Pathophysiological Changes to the Peritoneal Membrane during PD-Related Peritonitis: The Role of Mesothelial Cells

PubMed Central

Yung, Susan; Chan, Tak Mao

2012-01-01

The success of peritoneal dialysis (PD) is dependent on the structural and functional integrity of the peritoneal membrane. The mesothelium lines the peritoneal membrane and is the first line of defense against chemical and/or bacterial insult. Peritonitis remains a major complication of PD and is a predominant cause of technique failure, morbidity and mortality amongst PD patients. With appropriate antibiotic treatment, peritonitis resolves without further complications, but in some PD patients excessive peritoneal inflammatory responses lead to mesothelial cell exfoliation and thickening of the submesothelium, resulting in peritoneal fibrosis and sclerosis. The detrimental changes in the peritoneal membrane structure and function correlate with the number and severity of peritonitis episodes and the need for catheter removal. There is evidence that despite clinical resolution of peritonitis, increased levels of inflammatory and fibrotic mediators may persist in the peritoneal cavity, signifying persistent injury to the mesothelial cells. This review will describe the structural and functional changes that occur in the peritoneal membrane during peritonitis and how mesothelial cells contribute to these changes and respond to infection. The latter part of the review discusses the potential of mesothelial cell transplantation and genetic manipulation in the preservation of the peritoneal membrane. PMID:22577250

Macrophage interleukin-6 and tumour necrosis factor-α are induced by coronavirus fixation to Toll-like receptor 2/heparan sulphate receptors but not carcinoembryonic cell adhesion antigen 1a

PubMed Central

Jacques, Alexandre; Bleau, Christian; Turbide, Claire; Beauchemin, Nicole; Lamontagne, Lucie

2009-01-01

A rapid antiviral immune response may be related to viral interaction with the host cell leading to activation of macrophages via pattern recognition receptors (PPRs) or specific viral receptors. Carcinoembryonic cell adhesion antigen 1a (CEACAM1a) is the specific receptor for the mouse hepatitis virus (MHV), a coronavirus known to induce acute viral hepatitis in mice. The objective of this study was to understand the mechanisms responsible for the secretion of high-pathogenic MHV3-induced inflammatory cytokines. We report that the induction of the pro-inflammatory cytokines interleukin (IL)-6 and tumour necrosis factor (TNF)-α in peritoneal macrophages does not depend on CEACAM1a, as demonstrated in cells isolated from Ceacam1a−/− mice. The induction of IL-6 and TNF-α production was related rather to the fixation of the spike (S) protein of MHV3 on Toll-like receptor 2 (TLR2) in regions enriched in heparan sulphate and did not rely on viral replication, as demonstrated with denatured S protein and UV-inactivated virus. High levels of IL-6 and TNF-α were produced in livers from infected C57BL/6 mice but not in livers from Tlr2−/− mice. The histopathological observations were correlated with the levels of those inflammatory cytokines. Depending on mouse strain, the viral fixation to heparan sulfate/TLR2 stimulated differently the p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB in the induction of IL-6 and TNF-α. These results suggest that TLR2 and heparan sulphate receptors can act as new viral PPRs involved in inflammatory responses. PMID:19740307

Lung-Restricted Macrophage Activation in the Pearl Mouse Model of Hermansky-Pudlak Syndrome1

PubMed Central

Young, Lisa R.; Borchers, Michael T.; Allen, Holly L.; Gibbons, Reta S.; McCormack, Francis X.

2013-01-01

Pulmonary inflammation, abnormalities in alveolar type II cell and macrophage morphology, and pulmonary fibrosis are features of Hermansky-Pudlak Syndrome (HPS). We used the naturally occurring “pearl” HPS2 mouse model to investigate the mechanisms of lung inflammation observed in HPS. Although baseline bronchoalveolar lavage (BAL) cell counts and differentials were similar in pearl and strain-matched wild-type (WT) mice, elevated levels of proinflammatory (MIP1γ) and counterregulatory (IL-12p40, soluble TNFr1/2) factors, but not TNF-α, were detected in BAL from pearl mice. After intranasal LPS challenge, BAL levels of TNF-α, MIP1α, KC, and MCP-1 were 2- to 3-fold greater in pearl than WT mice. At baseline, cultured pearl alveolar macrophages (AMs) had markedly increased production of inflammatory cytokines. Furthermore, pearl AMs had exaggerated TNF-α responses to TLR4, TLR2, and TLR3 ligands, as well as increased IFN-γ/LPS-induced NO production. After 24 h in culture, pearl AM LPS responses reverted to WT levels, and pearl AMs were appropriately refractory to continuous LPS exposure. In contrast, cultured pearl peritoneal macrophages and peripheral blood monocytes did not produce TNF-α at baseline and had LPS responses which were no different from WT controls. Exposure of WT AMs to heat- and protease-labile components of pearl BAL, but not WT BAL, resulted in robust TNF-α secretion. Similar abnormalities were identified in AMs and BAL from another HPS model, pale ear HPS1 mice. We conclude that the lungs of HPS mice exhibit hyperresponsiveness to LPS and constitutive and organ-specific macrophage activation. PMID:16547274

The First Peritonitis Episode Alters the Natural Course of Peritoneal Membrane Characteristics in Peritoneal Dialysis Patients

PubMed Central

van Diepen, Anouk T.N.; van Esch, Sadie; Struijk, Dirk G.; Krediet, Raymond T.

2015-01-01

♦ Objective: Little or no evidence is available on the impact of the first peritonitis episode on peritoneal transport characteristics. The objective of this study was to investigate the importance of the very first peritonitis episode and distinguish its effect from the natural course by comparison of peritoneal transport before and after infection. ♦ Participants: We analyzed prospectively collected data from 541 incident peritoneal dialysis (PD) patients, aged > 18 years, between 1990 and 2010. Standard Peritoneal Permeability Analyses (SPA) within the year before and within the year after (but not within 30 days) the first peritonitis were compared. In a control group without peritonitis, SPAs within the first and second year of PD were compared. ♦ Main outcome measurements: SPA data included the mass transfer area coefficient of creatinine, glucose absorption and peritoneal clearances of β-2-microglobulin (b2m), albumin, IgG and α-2-macroglobulin (a2m). From these clearances, the restriction coefficient to macromolecules (RC) was calculated. Also, parameters of fluid transport were determined: transcapillary ultrafiltration rate (TCUFR), lymphatic absorption (ELAR), and free water transport. Crude and adjusted linear mixed models were used to compare the slopes of peritoneal transport parameters in the peritonitis group to the control group. Adjustments were made for age, sex and diabetes. ♦ Results: Of 541 patients, 367 experienced a first peritonitis episode within a median time of 12 months after the start of PD. Of these, 92 peritonitis episodes were preceded and followed by a SPA within one year. Forty-five patients without peritonitis were included in the control group. Logistic reasons (peritonitis group: 48% vs control group: 83%) and switch to hemodialysis (peritonitis group: 22% vs control group: 3%) were the main causes of missing SPA data post-peritonitis and post-control. When comparing the slopes of peritoneal transport parameters in the peritonitis group and the control group, a first peritonitis episode was associated with faster small solute transport (glucose absorption, p = 0.03) and a concomitant lower TCUFR (p = 0.03). In addition, a discreet decrease in macromolecular transport was seen in the peritonitis group: mean difference in post- and pre-peritonitis values: IgG: -8 μL/min (p = 0.01), a2m: -4 μL/min (p = 0.02), albumin: -10 μL/min (p = 0.04). Accordingly, the RC to macromolecules increased after peritonitis: 0.09, p = 0.04. ♦ Conclusions: The very first peritonitis episode alters the natural course of peritoneal membrane characteristics. The most likely explanation might be that cured peritoneal infection later causes long-lasting alterations in peritoneal transport state. PMID:24711641

Cranberry Proanthocyanidins - Protein complexes for macrophage activation.

PubMed

Carballo, Sergio M; Haas, Linda; Krueger, Christian G; Reed, Jess D

2017-09-20

In this work we characterize the interaction of cranberry (Vaccinium macrocarpon) proanthocyanidins (PAC) with bovine serum albumin (BSA) and hen egg-white lysozyme (HEL) and determine the effects of these complexes on macrophage activation and antigen presentation. We isolated PAC from cranberry and complexed the isolated PAC with BSA and HEL. The properties of the PAC-protein complexes were studied by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), gel electrophoresis and zeta-potential. The effects of PAC-BSA complexes on macrophage activation were studied in RAW 264.7 macrophage like cells after treatment with lipopolysaccharide (LPS). Fluorescence microscopy was used to study the endocytosis of PAC-BSA complexes. The effects of the PAC complexes on macrophage antigen presentation were studied in an in vitro model of HEL antigen presentation by mouse peritoneal mononuclear cells to a T-cell hybridoma. The mass spectra of the PAC complexes with BSA and HEL differed from the spectra of the proteins alone by the presence of broad shoulders on the singly and doubly charged protein peaks. Complexation with PAC altered the electrophoretic mobility shift assay in native agarose gel and the electrophoretic mobility (ζ-potential) values. These results indicate that the PAC-protein complexes are stable and alter the protein structure without precipitating the protein. Fluorescence microscopy showed that the RAW 264.7 macrophages endocytosed BSA and PAC-BSA complexes in discrete vesicles that surrounded the nucleus. Macrophages treated with increasing amounts of PAC-BSA complexes had significantly reduced COX-2 and iNOS expression in response to treatment with lipopolysaccharide (LPS) in comparison to the controls. The PAC-HEL complexes modulated antigen uptake, processing and presentation in murine peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL alone, whereas the PAC-HEL complex had already reached the maximum IL-2 expression. Cranberry PAC may increase the rate of endocytosis of HEL and subsequent expression of IL-2 by the T-cell hybridomas. These results suggest that PAC-protein complexes modulate aspects of innate and acquired immune responses in macrophages.

Earth Mover's Distance (EMD): A True Metric for Comparing Biomarker Expression Levels in Cell Populations.

PubMed

Orlova, Darya Y; Zimmerman, Noah; Meehan, Stephen; Meehan, Connor; Waters, Jeffrey; Ghosn, Eliver E B; Filatenkov, Alexander; Kolyagin, Gleb A; Gernez, Yael; Tsuda, Shanel; Moore, Wayne; Moss, Richard B; Herzenberg, Leonore A; Walther, Guenther

2016-01-01

Changes in the frequencies of cell subsets that (co)express characteristic biomarkers, or levels of the biomarkers on the subsets, are widely used as indices of drug response, disease prognosis, stem cell reconstitution, etc. However, although the currently available computational "gating" tools accurately reveal subset frequencies and marker expression levels, they fail to enable statistically reliable judgements as to whether these frequencies and expression levels differ significantly between/among subject groups. Here we introduce flow cytometry data analysis pipeline which includes the Earth Mover's Distance (EMD) metric as solution to this problem. Well known as an informative quantitative measure of differences between distributions, we present three exemplary studies showing that EMD 1) reveals clinically-relevant shifts in two markers on blood basophils responding to an offending allergen; 2) shows that ablative tumor radiation induces significant changes in the murine colon cancer tumor microenvironment; and, 3) ranks immunological differences in mouse peritoneal cavity cells harvested from three genetically distinct mouse strains.

A mouse air pouch model for evaluating the immune response to Taenia crassiceps infection.

PubMed

Gaspar, Emanuelle B; Sakai, Yuriko I; Gaspari, Elizabeth De

2014-02-01

The experimental system of Taenia crassiceps cysticerci infection in BALB/c mice is considered to be the most representative model of cysticercosis. In our work, mice were sacrificed 7 and 30days after infection, and pouch fluid was collected to determine the number of accumulated cells and the concentrations of IFNγ, IL-2, IL-4, IL-6, IL-10 and nitric oxide. The injection of 50 nonbudding cysticerci into normal mouse dorsal air pouches induced a high level of IFNγ and nitric oxide production relative to the parasite load. The air pouch provides a convenient cavity that allows studying the cellular immunological aspects of the T. crassiceps parasite. The nonbudding cysticerci recovered from the air pouches contained cells that can reconstitute complete cysts in the peritoneal cavity of mice. In conclusion, these results demonstrate that the air pouch model is an alternative tool for the evaluation of the immune characteristics of T. crassiceps infection. Copyright © 2013 Elsevier Inc. All rights reserved.

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

PubMed Central

Cakmak, Hakan; Basar, Murat; Seval-Celik, Yasemin; Osteen, Kevin G.; Duleba, Antoni J.; Taylor, Hugh S.; Lockwood, Charles J.; Arici, Aydin

2012-01-01

Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future. PMID:22267540

Non-covalent pomegranate (Punica granatum) hydrolyzable tannin-protein complexes modulate antigen uptake, processing and presentation by a T-cell hybridoma line co-cultured with murine peritoneal macrophages.

PubMed

Madrigal-Carballo, Sergio; Haas, Linda; Vestling, Martha; Krueger, Christian G; Reed, Jess D

2016-12-01

In this work we characterize the interaction of pomegranate hydrolyzable tannins (HT) with hen egg-white lysozyme (HEL) and determine the effects of non-covalent tannin-protein complexes on macrophage endocytosis, processing and presentation of antigen. We isolated HT from pomegranate and complex to HEL, the resulting non-covalent tannin-protein complex was characterized by gel electrophoresis and MALDI-TOF MS. Finally, cell culture studies and confocal microscopy imaging were conducted on the non-covalent pomegranate HT-HEL protein complexes to evaluate its effect on macrophage antigen uptake, processing and presentation to T-cell hybridomas. Our results indicate that non-covalent pomegranate HT-HEL protein complexes modulate uptake, processing and antigen presentation by mouse peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL alone, whereas a non-covalent pomegranate HT-HEL complex had already reached maximum IL-2 expression. Pomegranate HT may increase rate of endocytose of HEL and subsequent expression of IL-2 by the T-cell hybridomas.

Impaired B cell development in the absence of Krüppel-like factor 3.

PubMed

Vu, Thi Thanh; Gatto, Dominique; Turner, Vivian; Funnell, Alister P W; Mak, Ka Sin; Norton, Laura J; Kaplan, Warren; Cowley, Mark J; Agenès, Fabien; Kirberg, Jörg; Brink, Robert; Pearson, Richard C M; Crossley, Merlin

2011-11-15

Krüppel-like factor 3 (Klf3) is a member of the Klf family of transcription factors. Klfs are widely expressed and have diverse roles in development and differentiation. In this study, we examine the function of Klf3 in B cell development by studying B lymphopoiesis in a Klf3 knockout mouse model. We show that B cell differentiation is significantly impaired in the bone marrow, spleen, and peritoneal cavity of Klf3 null mice and confirm that the defects are cell autonomous. In the bone marrow, there is a reduction in immature B cells, whereas recirculating mature cells are noticeably increased. Immunohistology of the spleen reveals a poorly structured marginal zone (MZ) that may in part be caused by deregulation of adhesion molecules on MZ B cells. In the peritoneal cavity, there are significant defects in B1 B cell development. We also report that the loss of Klf3 in MZ B cells is associated with reduced BCR signaling strength and an impaired ability to respond to LPS stimulation. Finally, we show increased expression of a number of Klf genes in Klf3 null B cells, suggesting that a Klf regulatory network may exist in B cells.

Release of lysosomal enzymes in Candida albicans phagocytosis by rat peritoneal macrophages.

PubMed

Fontenla de Petrino, S E; Sirena, A

1984-02-15

The present paper reports the in vitro release of lysosomal enzymes in the supernatant of cultures of rat peritoneal macrophages, with the addition of Candida albicans cells. Macrophages were taken from the rat peritoneal cavity 72 hr after non-specific activation with Brain-Heart-Infusion (B.H.I.) broth containing 10% proteose-peptone No. 3. They were then cultured in Parker medium No. 199 (TC 199). After 24 hr a suspension of Candida albicans cells, in a determined concentration, was added to the peritoneal macrophage cultures. At that time, and during pre-determined periods, the following enzymes in the culture supernatants were studied using colorimetric methods: beta-glucuronidase, beta-galactosidase and acid phosphatase. It is concluded that, under identical conditions, the release of beta-galactosidase and acid phosphatase is higher than for beta-glucuronidase. The release rate of all three enzymes is the highest at a 6 hr incubation period, after which, a gradual decrease leads to the rate down to 50% at 24 hr.

Prolonged peritoneal gene expression using a helper-dependent adenovirus.

PubMed

Liu, Limin; Shi, Chang-Xin; Ghayur, Ayesha; Zhang, Claire; Su, Je Yen; Hoff, Catherine M; Margetts, Peter J

2009-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare complication of peritoneal dialysis. The causes of EPS are not well defined and are likely multifactorial. A suitable animal model would facilitate research into the pathophysiology and treatment of EPS. We developed a helper-dependent adenovirus that expresses both green fluorescent protein (GFP) and active transforming growth factor-beta (TGF-beta1; HDAdTGF-beta1). Mice were administered HDAdTGF-beta1 via intraperitoneal injection and the response was compared with mice administered either first-generation adenovirus expressing TGF-beta1 (AdTGF-beta1) or control adenovirus (AdGFP). HDAdTGF-beta1-treated mice continued to express the GFP reporter transgene to day 74, the end of the observation period. Transgene expression lasted less than 28 days in the animals treated with first-generation adenoviruses. Animals treated with first-generation AdTGF-beta1 demonstrated submesothelial thickening and angiogenesis at day 7, with almost complete resolution by day 28. The HDAdTGF-beta1-treated mice demonstrated progressive peritoneal fibrosis with adhesion formation and encapsulation of bowels. Weight gain was significantly reduced in animals treated with HDAdTGF-beta1 compared to both the control-treated animals and the AdTGF-beta1-treated animals. Inflammation was not a major component of the fibroproliferative response. Peritoneal administration of a first-generation AdTGF-beta1 leads to transient gene expression, resulting in a resolving fibrotic response and histology similar to that seen in simple peritoneal sclerosis. Prolonged TGF-beta1 expression induced by the helper-dependent HDAdTGF-beta1 led to changes in peritoneal morphology resembling EPS. This suggests that TGF-beta1 may be a contributing factor in both simple peritoneal sclerosis and EPS. This model will be useful for elucidation of the mechanism of EPS and evaluation of potential treatment.

Azithromycin: an assessment of its pharmacokinetics and therapeutic potential in CAPD.

PubMed

Kent, J R; Almond, M K; Dhillon, S

2001-01-01

Azithromycin is an azalide antibiotic with a similar antibacterial spectrum to erythromycin but with greater gram-negative activity. Azithromycin displays a favorable pharmacokinetic profile, with improved absorption and higher sustained tissue concentrations compared with erythromycin. This results in a prolonged elimination half-life, suggesting a potential for treating continuous ambulatory peritoneal dialysis (CAPD) peritonitis. This study aimed to define the potential role of azithromycin in treating CAPD peritonitis. The pharmacokinetics and peritoneal dialysis (PD) clearance of azithromycin were studied following a single 500-mg oral dose of azithromycin. Blood and dialysate samples were taken over a 10-day period and assayed using high-pressure liquid chromatography. The study took place within the Renal Unit at Southend Hospital NHS Trust, a district general hospital in the United Kingdom. Eight patients with oliguric end-stage renal failure without peritonitis maintained on CAPD (3 x 2 L/day). Peak plasma concentrations occurred at 2-3 hours with 0.35-1.35 microg/mL (mean 0.75). The mean elimination half-life was 84.55 hrs, and plasma clearance was 21.93 L/hour. This compares with values of greater than 40 hours and 40.8 L/hour reported in healthy volunteers. After 8 hours, the mean dialysate concentration was 0.07 microg/mL; PD clearance was 0.06 L/hr. Azithromycin is not substantially removed by CAPD in the absence of peritonitis and cannot be recommended for widespread use in this setting at present. However, the successful use of azithromycin in CAPD peritonitis, due possibly to an intracellular drug transport mechanism, has been reported. Future research should address this possibility.

CD22 expression mediates the regulatory functions of peritoneal B-1a cells during the remission phase of contact hypersensitivity reactions.

PubMed

Nakashima, Hiroko; Hamaguchi, Yasuhito; Watanabe, Rei; Ishiura, Nobuko; Kuwano, Yoshihiro; Okochi, Hitoshi; Takahashi, Yoshimasa; Tamaki, Kunihiko; Sato, Shinichi; Tedder, Thomas F; Fujimoto, Manabu

2010-05-01

Although contact hypersensitivity (CHS) has been considered a prototype of T cell-mediated immune reactions, recently a significant contribution of regulatory B cell subsets in the suppression of CHS has been demonstrated. CD22, one of the sialic acid-binding immunoglobulin-like lectins, is a B cell-specific molecule that negatively regulates BCR signaling. To clarify the roles of B cells in CHS, CHS in CD22(-/-) mice was investigated. CD22(-/-) mice showed delayed recovery from CHS reactions compared with that of wild-type mice. Transfer of wild-type peritoneal B-1a cells reversed the prolonged CHS reaction seen in CD22(-/-) mice, and this was blocked by the simultaneous injection with IL-10 receptor Ab. Although CD22(-/-) peritoneal B-1a cells were capable of producing IL-10 at wild-type levels, i.p. injection of differentially labeled wild-type/CD22(-/-) B cells demonstrated that a smaller number of CD22(-/-) B cells resided in lymphoid organs 5 d after CHS elicitation, suggesting a defect in survival or retention in activated CD22(-/-) peritoneal B-1 cells. Thus, our study reveals a regulatory role for peritoneal B-1a cells in CHS. Two distinct regulatory B cell subsets cooperatively inhibit CHS responses. Although splenic CD1d(hi)CD5(+) B cells have a crucial role in suppressing the acute exacerbating phase of CHS, peritoneal B-1a cells are likely to suppress the late remission phase as "regulatory B cells." CD22 deficiency results in disturbed CHS remission by impaired retention or survival of peritoneal B-1a cells that migrate into lymphoid organs.

Use of Gold Nanoparticle Fertilizer Enhances the Ginsenoside Contents and Anti-Inflammatory Effects of Red Ginseng.

PubMed

Kang, Hee; Hwang, Yun-Gu; Lee, Taek-Guen; Jin, Cheng-Ri; Cho, Chi Heung; Jeong, Hee-Yeong; Kim, Dae-Ok

2016-10-28

Red ginseng, a steamed and sun-dried ginseng, is a popular health-promoting food in Korea and other Asian countries. We introduced nanofertilizer technology using gold nanoparticles in an effort to develop red ginseng with an elevated level of ginsenosides, the main active compounds of ginseng. Shoots of 6-year-old ginseng plants were fertilized three times with colloidal gold nanoparticle sprays. Red ginseng extract was prepared from the main roots. The concentrations of gold and ginsenosides were measured following gold nanoparticle treatment. To evaluate the anti-inflammatory effects, mouse peritoneal macrophages of male BALB/c mouse were stimulated with lipopolysaccharide plus interferon-γ in the presence of extracts from red ginseng with or without gold nanoparticle treatment. The content of ginsenosides, such as Rg1, Re, Rf, and Rb1, increased in ginseng treated with gold nanofertilizer whereas the steaming process increased only the levels of Rd and Rg3. The levels of nitric oxide, inducible nitric oxide synthase, and interleukin-6, but not tumor necrosis factor-α, were more suppressed in macrophages treated with extract from gold nanoparticle-treated red ginseng. Our results show that the use of a colloidal gold nanoparticle fertilizer improved the synthesis of ginsenosides in ginseng and enhanced the anti-inflammatory effects of red ginseng. Further research is required to elucidate the causal factors for the gold-induced change in ginsenoside synthesis and to determine the in vivo effect of gold nanoparticle-treated ginseng.

THE INTERACTION OF SOLUBLE HORSERADISH PEROXIDASE WITH MOUSE PERITONEAL MACROPHAGES IN VITRO

PubMed Central

Steinman, Ralph M.; Cohn, Zanvil A.

1972-01-01

The in vitro interaction of soluble horseradish peroxidase (HRP) with homogeneous mono layers of mouse macrophages has been studied using sensitive biochemical and cytochemical techniques. The compartmentalization of HRP in extracellular and intracellular sites has been quantitatively evaluated. A significant fraction is bound to a serum-derived layer, which coats the surface of culture vessels and may be removed by appropriate washes. Macrophages interiorize HRP as a solute in pinocytic vesicles without appreciable binding of the glycoprotein to the plasma membrane. Uptake is directly proportional to the concentration of HRP in the culture medium. 1 x 106 cells ingest 0.0025% of the administered load per hr over a wide range of concentrations. Cytochemically, all demonstrable HRP is sequestered within the endocytic vesicles and secondary lysosomes of the vacuolar apparatus. After uptake, the enzymatic activity of HRP is inactivated exponentially with a half-life of 7–9 hr, until enzyme is no longer detectable. When macrophages have pinocytosed trace-labeled HRP-125I, cell-associated isotope disappears with a t ½ of 20–30 hr and they release monoiodotyrosine-125I into the culture medium. We were unable to obtain evidence that significant amounts of HRP (>2%) can be exocytosed after uptake, can exist intact on the cell surface, or can be digested extracellularly. It is difficult to reconcile these observations with several of the postulated mechanisms whereby macrophages are thought to play a prominent role in the induction of an immune response. PMID:4347251

Isolation of an N-acetyl-DL-phenylalanine beta-naphthyl esterase from rabbit peritoneal polymorphonuclear leukocytes.

PubMed

Tsung, P; Kegeles, S W; Showell, H J; Becker, E L

1975-09-22

An N-acetyl-DL-phenylalanine beta-naphthyl esterase has been purified 26-fold from rabbit peritoneal polymorphonuclear leukocytes. The purified enzyme was inhibited by 10(-7) M p-nitrophenylethyl-5-chloropentylphosphonate. The apparent Km for hydrolysis of N-acetyl-DL-phenylalanine beta-naphthyl ester is 71 muM. Optimal reaction rates were observed at pH 6-8. No divalent cation requirement for the activation of the enzyme activity was observed. The esterase activity was neither inhibited nor stimulated by bacterial factor, complement component C5a, guanosine 3',5'-monophosphate (cyclic GMP) and adenosine 3',5'-monophosphate (cyclic AMP) which are attractants or repellents for polymorphonuclear leukocytes. High chemotactic activity was observed in the partially purified fraction of the enzyme. The chemotactic activity, like the enzyme activity, was completely inhibited by 10(-7) M phosphonate.

Peritoneal small solute transport rate is related to the malnutrition inflammation score in peritoneal dialysis patients.

PubMed

Sezer, Siren; Elsurer, Rengin; Afsar, Baris; Arat, Zubeyde; Ozdemir, Nurhan F; Haberal, Mehmet

2007-01-01

A high peritoneal membrane transport status and peritoneal albumin leakage are determinants of morbidity and mortality in patients receiving continuous ambulatory peritoneal dialysis. In this study, we analyzed the relationship between the malnutrition inflammation score, peritoneal transport status, and 24-hour peritoneal albumin leakage in patients receiving peritoneal dialysis. Sixty-six patients receiving peritoneal dialysis (male-female ratio 30/36; age 46.2 +/- 14.1 years; mean duration of peritoneal dialysis 32.4 +/- 23.9 months) who had experienced no attacks of peritonitis within the prior 6 months were included. The malnutrition inflammation score was positively correlated with the serum C-reactive protein concentration, dialysate/plasma creatinine ratio, and 24-hour peritoneal albumin leakage. Triceps and biceps skinfold thicknesses and serum concentrations of prealbumin, total cholesterol, and triglyceride were negatively correlated with the malnutrition inflammation score. Multiple linear regression analysis showed that the malnutrition inflammation score was independently associated with the dialysate/plasma creatinine ratio (p = 0.039) and 24-hour peritoneal albumin amount (p = 0.005). High peritoneal transport status and peritoneal albumin leakage are significantly associated with the malnutrition inflammation score. (c) 2007 S. Karger AG, Basel

The Negative Impact of Early Peritonitis on Continuous Ambulatory Peritoneal Dialysis Patients

PubMed Central

Hsieh, Yao-Peng; Wang, Shu-Chuan; Chang, Chia-Chu; Wen, Yao-Ko; Chiu, Ping-Fang; Yang, Yu

2014-01-01

♦ Background: Peritonitis rate has been reported to be associated with technique failure and overall mortality in previous literatures. However, information on the impact of the timing of the first peritonitis episode on continuous ambulatory peritoneal dialysis (CAPD) patients is sparse. The aim of this research is to study the influence of time to first peritonitis on clinical outcomes, including technique failure, patient mortality and dropout from peritoneal dialysis (PD). ♦ Methods: A retrospective observational cohort study was conducted over 10 years at a single PD unit in Taiwan. A total of 124 patients on CAPD with at least one peritonitis episode comprised the study subjects, which were dichotomized by the median of time to first peritonitis into either early peritonitis patients or late peritonitis patients. Cox proportional hazard model was used to analyze the correlation of the timing of first peritonitis with clinical outcomes. ♦ Results: Early peritonitis patients were older, more diabetic and had lower serum levels of creatinine than the late peritonitis patients. Early peritonitis patients were associated with worse technique survival, patient survival and stay on PD than late peritonitis patients, as indicated by Kaplan-Meier analysis (log-rank test, p = 0.04, p < 0.001, p < 0.001, respectively). In the multivariate Cox regression model, early peritonitis was still a significant predictor for technique failure (hazard ratio (HR), 0.54; 95% confidence interval (CI), 0.30 - 0.98), patient mortality (HR, 0.34; 95% CI, 0.13 - 0.92) and dropout from PD (HR, 0.50; 95% CI, 0.30 - 0.82). In continuous analyses, a 1-month increase in the time to the first peritonitis episode was associated with a 2% decreased risk of technique failure (HR, 0.98; 95% CI, 0.97 - 0.99), a 3% decreased risk of patient mortality (HR, 0.97; 95% CI, 0.95 - 0.99), and a 2% decreased risk of dropout from PD (HR, 98%; 95% CI, 0.97 - 0.99). Peritonitis rate was inversely correlated with time to first peritonitis according to the Spearman analysis (r = -0.64, p < 0.001). ♦ Conclusions: Time to first peritonitis is significantly correlated with clinical outcomes of peritonitis patients with early peritonitis patients having poor prognosis. Patients with shorter time to first peritonitis were prone to having a higher peritonitis rate. PMID:24497590

Coxiella burnetii Avirulent Nine Mile Phase II Induces Caspase-1-Dependent Pyroptosis in Murine Peritoneal B1a B Cells.

PubMed

Schoenlaub, Laura; Cherla, Rama; Zhang, Yan; Zhang, Guoquan

2016-12-01

Our recent study demonstrated that virulent Coxiella burnetii Nine Mile phase I (NMI) is capable of infecting and replicating within peritoneal B1a cells and that B1a cells play an important role in host defense against C. burnetii infection in mice. However, it remains unknown if avirulent Nine Mile phase II (NMII) can infect and replicate in B1a cells and whether NMI and NMII can differentially interact with B1a cells. In this study, we examined if NMI and NMII can differentially modulate host cell apoptotic signaling in B1a cells. The results showed that NMII induced dose-dependent cell death in murine peritoneal B1a cells but NMI did not, suggesting that NMI and NMII may differentially activate host cell apoptotic signaling in B1a cells. Western blotting indicated that NMII-induced B1a cell death was not dependent on either caspase-3 or PARP-1 cleavage, but cleavage of caspase-1 was detected in NMII-infected B1a cells. In addition, inhibition or deficiency of caspase-1 activity blocked NMII-induced B1a cell death. These results suggest that NMII induces a caspase-1-dependent pyroptosis in murine peritoneal B1a cells. We also found that heat-killed NMII and type 4 secretion system (T4SS) mutant NMII were unable to induce B1a cell death and that NMII infection did not induce cell death in peritoneal B1a cells from Toll-like receptor 2 (TLR-2)- or NLRP3 inflammasome-deficient mice. These data suggest that NMII-induced caspase-1-dependent pyroptosis may require its T4SS and activation of the TLR-2 and NLRP3 signaling pathways. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Advantages of laparoscopic compared to conventional surgery are not related to an innate immune response of peritoneal immune activation: an animal study in rats.

PubMed

Lingohr, Philipp; Dohmen, Jonas; Matthaei, Hanno; Schwandt, Timo; Stein, Kathy; Hong, Gun-Soo; Steitz, Julia; Longerich, Thomas; Bölke, Edwin; Wehner, Sven; Kalff, Jörg C

2017-06-01

Laparoscopic surgery (LS) has proved superior compared to conventional surgery (CS) regarding morbidity, length of hospital stay, rate of wound infection and time until recovery. An improved preservation of the postoperative immune function is assumed to contribute to these benefits though the role of the local peritoneal immune response is still poorly understood. Our study investigates the peritoneal immune response subsequent to abdominal surgery and compares it between laparoscopic and conventional surgery to find an immunological explanation for the clinically proven benefits of LS. Wistar rats (N = 140) underwent laparoscopic cecum resection (LCR; N = 28), conventional cecum resection (CCR; N = 28), laparoscopic sham operation (LSO; N = 28), conventional sham operation (CSO; N = 28), or no surgical treatment (CTRL; N = 28). Postoperatively, peritoneal lavages were performed, leukocytes isolated and analyzed regarding immune function and phagocytosis activity. Immune function was inhibited postoperatively in animals undergoing LCR or CCR compared to CTRL reflected by a lower TNF-α (CTRL 3956.65 pg/ml, LCR 2018.48 pg/ml (p = 0.023), CCR 2793.78 pg/ml (n.s.)) and IL-6 secretion (CTRL 625.84 pg/ml, LCR 142.84 pg/ml (p = 0.009), CCR 169.53 pg/ml (p = 0.01)). Phagocytosis was not affected in rats undergoing any kind of surgery compared to CTRL. Neither cytokine secretion nor phagocytosis activity differed significantly between laparoscopic and conventional surgery. According to our findings the benefits associated with LS compared to CS cannot be explained by differences in the postoperative peritoneal innate immune response. Further studies are needed to elucidate the causes for a more favorable postoperative outcome in patients after LS compared to CS.

Metformin suppresses cancer initiation and progression in genetic mouse models of pancreatic cancer.

PubMed

Chen, Ke; Qian, Weikun; Jiang, Zhengdong; Cheng, Liang; Li, Jie; Sun, Liankang; Zhou, Cancan; Gao, Luping; Lei, Meng; Yan, Bin; Cao, Junyu; Duan, Wanxing; Ma, Qingyong

2017-07-24

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-associated mortality worldwide with an overall five-year survival rate less than 7%. Accumulating evidence has revealed the cancer preventive and therapeutic effects of metformin, one of the most widely prescribed medications for type 2 diabetes mellitus. However, its role in pancreatic cancer is not fully elucidated. Herein, we aimed to further study the preventive and therapeutic effects of metformin in genetically engineered mouse models of pancreatic cancer. LSL-Kras G12D/+ ; Pdx1-Cre (KC) mouse model was established to investigate the effect of metformin in pancreatic tumorigenesis suppression; LSL-Kras G12D/+ ; Trp53 fl/+ ; Pdx1-Cre (KPC) mouse model was used to evaluate the therapeutic efficiency of metformin in PDAC. Chronic pancreatitis was induced in KC mice by peritoneal injection of cerulein. Following metformin treatment, pancreatic acinar-to-ductal metaplasia (ADM) and mouse pancreatic intraepithelial neoplasia (mPanIN) were decreased in KC mice. Chronic pancreatitis induced a stroma-rich and duct-like structure and increased the formation of ADM and mPanIN lesions, in line with an increased cytokeratin 19 (CK19)-stained area. Metformin treatment diminished chronic pancreatitis-mediated ADM and mPanIN formation. In addition, it alleviated the percent area of Masson's trichrome staining, and decreased the number of Ki67-positive cells. In KPC mice, metformin inhibited tumor growth and the incidence of abdominal invasion. More importantly, it prolonged the overall survival. Metformin inhibited pancreatic cancer initiation, suppressed chronic pancreatitis-induced tumorigenesis, and showed promising therapeutic effect in PDAC.

Diet and Physical Activity Change or Usual Care in Improving Progression-Free Survival in Patients With Previously Treated Stage II, III, or IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2018-02-14

Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Brenner Tumor; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Adenocarcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Stage IIA Fallopian Tube Cancer AJCC v6 and v7; Stage IIA Ovarian Cancer AJCC V6 and v7; Stage IIB Fallopian Tube Cancer AJCC v6 and v7; Stage IIB Ovarian Cancer AJCC v6 and v7; Stage IIC Fallopian Tube Cancer AJCC v6 and v7; Stage IIC Ovarian Cancer AJCC v6 and v7; Stage IIIA Fallopian Tube Cancer AJCC v7; Stage IIIA Ovarian Cancer AJCC v6 and v7; Stage IIIA Primary Peritoneal Cancer AJCC v7; Stage IIIB Fallopian Tube Cancer AJCC v7; Stage IIIB Ovarian Cancer AJCC v6 and v7; Stage IIIB Primary Peritoneal Cancer AJCC v7; Stage IIIC Fallopian Tube Cancer AJCC v7; Stage IIIC Ovarian Cancer AJCC v6 and v7; Stage IIIC Primary Peritoneal Cancer AJCC v7; Stage IV Fallopian Tube Cancer AJCC v6 and v7; Stage IV Ovarian Cancer AJCC v6 and v7; Stage IV Primary Peritoneal Cancer AJCC v7; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

Nanoparticle as a novel tool in hyperthermic intraperitoneal and pressurized intraperitoneal aerosol chemotheprapy to treat patients with peritoneal carcinomatosis

PubMed Central

Nowacki, Maciej; Peterson, Margarita; Kloskowski, Tomasz; McCabe, Eleanor; Guiral, Delia Cortes; Polom, Karol; Pietkun, Katarzyna; Zegarska, Barbara; Pokrywczynska, Marta; Drewa, Tomasz; Roviello, Franco; Medina, Edward A.; Habib, Samy L.; Zegarski, Wojciech

2017-01-01

The treatment of peritoneal surface malignances has changed considerably over the last thirty years. Unfortunately, the palliative is the only current treatment for peritoneal carcinomatosis (PC). Two primary intraperitoneal chemotherapeutic methods are used. The first is combination of cytoreductive surgery (CRS) and Hyperthermic IntraPEritoneal Chemotherapy (HIPEC), which has become the gold standard for many cases of PC. The second is Pressurized IntraPeritoneal Aerosol Chemotheprapy (PIPAC), which is promising direction to minimally invasive as safedrug delivery. These methods were improved through multicenter studies and clinical trials that yield important insights and solutions. Major method development has been made through nanomedicine, specifically nanoparticles. Here, we are presenting the latest advances of nanoparticles and their application to precision diagnostics and improved treatment strategies for PC. These advances will likely develop both HIPEC and PIPAC methods that used for in vitro and in vivo studies. Several benefits of using nanoparticles will be discussed including: 1) Nanoparticles as drug delivery systems; 2) Nanoparticles and Near Infrred (NIR) Irradiation; 3) use of nanoparticles in perioperative diagnostic and individualized treatment planning; 4) use of nanoparticles as anticancer dressing’s, hydrogels and as active beeds for optimal reccurence prevention; and 5) finally the curent in vitro and in vivo studies and clinical trials of nanoparticles. The current review highlighted use of nanoparticles as novel tools in improving drug delivery to be effective for treatment patients with peritoneal carcinomatosis. PMID:29100461

Studies on the pathogenesis of fever. XV. The production of endogenous pyrogen by peritoneal macrophages.

PubMed

Hahn, H H; Char, D C; Postel, W B; Wood, W B

1967-08-01

Macrophages from oil-induced peritoneal exudates in rabbits produce endogenous pyrogen when first activated by incubation in 4 hr exudate fluid and then stimulated by incubation in potassium-free isotonic sodium chloride solution. The failure of earlier investigators to obtain pyrogen from macrophages is explained, and the relevance of macrophage pyrogen to fevers of agranulocytosis and other diseases, in which mononuclear rather than granulocytic exudates predominate, is discussed.

Campylobacter jejuni: A rare agent in a child with peritoneal dialysis-related peritonitis.

PubMed

Tural Kara, Tugce; Yilmaz, Songul; Ozdemir, Halil; Birsin Ozcakar, Zeynep; Derya Aysev, Ahmet; Ciftci, Ergin; Ince, Erdal

2016-10-01

Peritonitis is a serious problem in children receiving peritoneal dialysis. Campylobacter jejuni is an unusual cause of peritonitis. A 10-year-old boy who had end stage renal failure due to atypical hemolytic uremic syndrome was admitted to our hospital with abdominal pain and fever. Peritoneal dialysis fluid was cloudy and microscopic examination showed abundant leukocytes. Intraperitoneal cefepime treatment was started. Campylobacter jejuni was isolated from peritoneal dialysis fluid culture and oral clarithromycin was added to the treatment. At the end of therapy, peritoneal fluid culture was negative. To our knowledge, C. jejuni peritonitis was not reported in children previously. Although C. jejuni peritonitis is rarely encountered in children, it should be considered as an etiologic factor for peritonitis. Sociedad Argentina de Pediatría.

Curvularia lunata, a rare fungal peritonitis in continuous ambulatory peritoneal dialysis (CAPD); a rare case report.

PubMed

Subramanyam, Haritha; Elumalai, Ramprasad; Kindo, Anupma Jyoti; Periasamy, Soundararajan

2016-01-01

Peritonitis is an inflammation of the peritoneum that occurs in patients with end-stage renal disease (ESRD) treated by peritoneal dialysis. Fungal peritonitis is a dreaded complication of peritoneal dialysis. Curvularia lunata is known to cause extra renal disease like endocarditis, secondary allergic bronchopulmonary aspergillosis and endophthalmitis. This case report presents a case of continuous ambulatory peritoneal dialysis peritonitis with this disease and its management. This case is of a 45-year-old man, presented with ESRD, secondary to diabetic nephropathy. After 3 months of hemodialysis the patient was put on continuous ambulatory peritoneal dialysis (CAPD). Local Examination at catheter site showed skin excoriation and purulent discharge. Further peritoneal dialysis (PD) fluid analysis showed neutrophilic leukocytosis and diagnosis of Curvularia lunata PD peritonitis.

Mycobacterial peritonitis: difference between non-tuberculous mycobacteria and Mycobacterium tuberculosis.

PubMed

Shu, C-C; Wang, J-T; Wang, J-Y; Yu, C-J; Lee, L-N

2012-03-01

Unlike tuberculous peritonitis, peritonitis due to non-tuberculous mycobacteria (NTM) has unclear clinical manifestations. This study aimed to clarify the clinical manifestations and laboratory results of NTM peritonitis and compare it to tuberculous peritonitis. This retrospective study was conducted from 2000 to 2008 in a medical centre in Taiwan. Patients with mycobacteria isolated from ascites were identified and compared according to causative pathogens (Mycobacterium tuberculosis or NTM). Those with NTM peritonitis were further classified into the 'probable' and 'possible' groups based on diagnostic evidence. Twenty-five patients with NTM peritonitis and 65 with tuberculous peritonitis were reviewed. Mycobacterium avium complex was the most common NTM pathogen (52%). There was no obvious difference between the 'probable' and 'possible' NTM peritonitis groups regarding age and laboratory data. Patients with NTM peritonitis and those with tuberculous peritonitis had no differences in age or gender but varied in symptoms and serum laboratory data. NTM peritonitis was 100% associated with underlying co-morbidities and had lower proportions of lymphocytes and albumin level in ascites. Twelve (48%) NTM peritonitis and 21 (32%) tuberculous peritonitis patients died during the 6-month follow-up. Anti-mycobacterial treatment, but not mycobacterial species, was correlated with better 6-month survival. In Taiwan, NTM is responsible for 28% of mycobacterial peritonitis cases, which have a poor prognosis if untreated. There are some differences in clinical manifestations between NTM and tuberculous peritonitis. NTM peritonitis should be considered in patients with peritonitis but without causative microorganisms identified other than NTM. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Knowledge, understanding and experiences of peritonitis amongst patients, and their families, undertaking peritoneal dialysis: A mixed methods study protocol.

PubMed

Baillie, Jessica; Gill, Paul; Courtenay, Molly

2018-01-01

This article is a report of a study protocol designed to examine patients' and families' knowledge and experiences of peritoneal dialysis-associated peritonitis. Peritonitis is a considerable problem for people using peritoneal dialysis, leading to antibiotics, hospitalization and decreased quality of life. For some patients, peritonitis requires changing renal replacement therapy and can be fatal. Peritonitis is distressing and some patients are unfamiliar with the signs and symptoms. Patients with better knowledge of peritonitis and adherence to peritoneal dialysis procedures have lower rates of peritonitis. Little is known about patients' and families' knowledge and experience of peritoneal dialysis-associated peritonitis in the United Kingdom. Ethical approval was gained in March 2017. To meet the study aim, a two-phase sequential explanatory mixed methods study is proposed. Phase One: An author-developed questionnaire will be sent to patients using peritoneal dialysis at five sites in England and Wales. Patients will be asked to consider inviting a relative to participate. The questionnaire will assess peritonitis knowledge and experience. Data will be analysed statistically. Phase Two: Semi-structured interviews will be conducted with a purposive sample of Phase One participants (n = 30) to explore their experiences of peritonitis in further depth. The data will be analysed thematically using Wolcott's (1994) approach. Data from the two phases will be synthesized to identify patients' and families' peritonitis information needs, to ensure they are appropriately supported to prevent, monitor, identify and report peritonitis. © 2017 John Wiley & Sons Ltd.

Alterations of erythrocyte rheology and cellular susceptibility in end stage renal disease: Effects of peritoneal dialysis.

PubMed

Ertan, Nesrin Zeynep; Bozfakioglu, Semra; Ugurel, Elif; Sinan, Mukaddes; Yalcin, Ozlem

2017-01-01

In this study, we investigated the effects of peritoneal dialysis on hemorheological and hematological parameters and their relations with oxidant and antioxidant status of uremic patients. Hemorheological parameters (erythrocyte deformability, erythrocyte aggregation, osmotic deformability, blood and plasma viscosity) were measured in patients with renal insufficiency undergoing peritoneal dialysis (PD) and volunteers. Erythrocyte deformability, osmotic deformability and aggregation in both autologous plasma and 3% dextran 70 were measured by laser diffraction ektacytometry. Enzyme activities of glutathione peroxidase, superoxide dismutase and catalase were studied in erythrocytes; lipid peroxidation was studied by measuring the amount of malondialdehyde in both erythrocytes and plasma samples. Blood viscosity at native hematocrit was significantly lower in PD patients at all measured shear rates compared to controls, but it was high in PD patients at corrected (45%) hematocrit. Erythrocyte deformability did not show any difference between the two groups. Osmotic deformability was significantly lower in PD patients compared to controls. Aggregation index values were significantly high in PD patients in plasma Catalase and glutathione peroxidase activities in erythrocytes were decreased in PD patients whereas superoxide dismutase activity was increased compared to controls. Malondialdehyde was significantly increased in erythrocytes and plasma samples of PD patients which also shows correlations with aggregation parameters. It has been concluded that erythrocytes in PD patients are more prone to aggregation and this tendency could be influenced by lipid peroxidation activity in patient's plasma. These results imply that uremic conditions, loss of plasma proteins and an increased risk of oxidative stress because of decreasing levels of antioxidant enzymes affect erythrocyte rheology during peritoneal dialysis. This level of distortion may have crucial effects, impairing the blood flow dynamics and causing inadequate microcirculatory perfusion.

[Fungal peritonitis due to Rhodotorula mucilaginosa in a patient with automated peritoneal dialysis: Literature review].

PubMed

Verdugo, Fernando J; Briones, Eduardo; Porte, Lorena; Amaro, José; Fica, Alberto

2016-04-01

Fungal peritonitis is a major complication of peritoneal dialysis associated with high mortality. Most survivors have a high rate of abandonment of peritoneal dialysis. We report a case of fungal peritonitis due to an unusual agent. An 83 year-old woman, with a history of type 2 diabetes mellitus and multiple episodes of bacterial peritonitis associated to technical flaws in the implementation of automated peritoneal dialysis, was admitted due to abdominal pain and cloudy peritoneal fluid. Rhodotorula mucilaginosa was identified in the peritoneal fluid by MALDI-TOF. She was treated with catheter removal and oral posaconazole for 14 days showing clinical resolution and non-recurrence.

Peritonitis due to Curvularia inaequalis in an elderly patient undergoing peritoneal dialysis and a review of six cases of peritonitis associated with other Curvularia spp.

PubMed

Pimentel, Jason D; Mahadevan, Kumar; Woodgyer, Alan; Sigler, Lynne; Gibas, Connie; Harris, Owen C; Lupino, Michael; Athan, Eugene

2005-08-01

Fungal peritonitis due to Curvularia species in patients undergoing peritoneal dialysis is a very rare problem. We report a case of peritonitis caused by Curvularia inaequalis. This is the first report in the English literature of this species causing human infection. We also review the six previously reported cases of continuous ambulatory peritoneal dialysis peritonitis caused by other Curvularia species.

Desertification of the peritoneum by thin-film evaporation during laparoscopy.

PubMed

Ott, Douglas E

2003-01-01

To assess the effects of gas flow during insufflation on peritoneal fluid and peritoneal tissue regarding transient thermal behavior and thin-film evaporation. The effects of laparoscopic gas on peritoneal cell desiccation and peritoneal fluid thin-film evaporation were analyzed. Measurment of tissue and peritoneal fluid and analysis of gas flow dynamics during laparoscopy. High-velocity gas interface conditions during laparoscopic gas insufflation result in peritoneal surface temperature and decreases up to 20 degrees C/second due to rapid thin-film evaporation of the peritoneal fluid. Evaporation of the thin film of peritoneal fluid extends quickly to the peritoneal cell membrane, causing peritoneal cell desiccation, internal cytoplasmic stress, and disruption of the cell membrane, resulting in loss of peritoneal surface continuity and integrity. Changing the gas conditions to 35 degrees C and 95% humidity maintains normal peritoneal fluid thin-film characteristics, cellular integrity, and prevents evaporative losses. Cold, dry gas and the characteristics of the laparoscopic gas delivery apparatus cause local peritoneal damaging alterations by high-velocity gas flow with extremely dry gas, creating extreme arid surface conditions, rapid evaporative and hydrological changes, tissue desiccation, and peritoneal fluid alterations that contribute to the process of desertification and thin-film evaporation. Peritoneal desertification is preventable by preconditioning the gas to 35 degrees C and 95% humidity.

The Natural Time Course of Membrane Alterations During Peritoneal Dialysis Is Partly Altered by Peritonitis.

PubMed

van Esch, Sadie; Struijk, Dirk G; Krediet, Raymond T

2016-01-01

♦ The quality of the peritoneal membrane can deteriorate over time. Exposure to glucose-based dialysis solutions is the most likely culprit. Because peritonitis is a common complication of peritoneal dialysis (PD), distinguishing between the effect of glucose exposure and a possible additive effect of peritonitis is difficult. The aim of the present study was to compare the time-course of peritoneal transport characteristics in patients without a single episode of peritonitis-representing the natural course-and in patients who experienced 1 or more episodes of peritonitis during long-term follow-up. ♦ This prospective, single-center cohort study enrolled incident adult PD patients who started PD during 1990-2010. A standard peritoneal permeability analysis was performed in the first year of PD treatment and was repeated every year. The results in patients without a single episode of peritonitis ("no-peritonitis group") were compared with the results obtained in patients who experienced 1 or more peritonitis episodes ("peritonitis group") during a follow-up of 4 years. ♦ The 124 patients analyzed included 54 in the no-peritonitis group and 70 in the peritonitis group. The time-course of small-solute transport was different in the groups, with the peritonitis group showing an earlier and more pronounced increase in the mass transfer area coefficient for creatinine (p = 0.07) and in glucose absorption (p = 0.048). In the no-peritonitis group, the net ultrafiltration rate (NUFR) and the transcapillary ultrafiltration rate (TCUFR) both showed a steep increase from the 1st to the 2nd year of PD that was absent in the peritonitis group. Both groups showed a decrease in the NUFR after year 3. A decrease in the TCUFR occurred only in the peritonitis group. That decrease was already present after the year 1 in patients with severe peritonitis. The time-course of free water transport showed a continuous increase in the patients without peritonitis, but a decrease in the patients who experienced peritonitis (p < 0.01). No difference was observed in the time-course of the effective lymphatic absorption rate. The time-courses of immunoglobulin G and α2-macroglobulin clearances showed a decrease in both patient groups, with a concomitant increase of the restriction coefficient. Those changes were not evidently influenced by peritonitis. The two groups showed a similar decrease in the mesothelial cell mass marker cancer antigen 125 during follow-up. ♦ On top of the natural course of peritoneal function, peritonitis episodes to some extent influence the time-course of small-solute and fluid transport-especially the transport of solute-free water. Those modifications increase the risk for overhydration. Copyright © 2016 International Society for Peritoneal Dialysis.

The impact of peritoneal dialysis-related peritonitis on mortality in peritoneal dialysis patients.

PubMed

Ye, Hongjian; Zhou, Qian; Fan, Li; Guo, Qunying; Mao, Haiping; Huang, Fengxian; Yu, Xueqing; Yang, Xiao

2017-06-05

Results concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up. This retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality. A total of 1321 patients were included. The mean age was 48.1 ± 15.3 years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21-48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46-2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28-2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47-9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2 years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2 years. Peritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration.

Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and Peritoneal Dialysis Prescription.

PubMed

Courivaud, Cecile; Davenport, Andrew

2016-01-01

♦ Interventional trials failed to demonstrate that increasing urea clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia is a well-recognized predictor of cardiovascular and all-cause mortality in PD patients. Simplification of PD small solute clearance targets focuses away from larger solutes, including phosphate. In the US and UK, increasing use of automated peritoneal dialysis (APD) cyclers with shorter dwell times could also potentially reduce peritoneal phosphate removal compared to continuous ambulatory peritoneal dialysis (CAPD). ♦ Total phosphate and peritoneal phosphate clearances were measured in a prospective observational cohort of 380 adult PD patients attending a tertiary university hospital between 1996 and 2013 for routine assessment of PD adequacy. ♦ Eighty-seven patients (22.9%) were hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%) were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%], respectively, for peritoneal creatinine transporter status). Faster peritoneal phosphate transporter status was associated with over-hydration (odds ratio [OR] = 2.45 [1.43 - 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and peritoneal weekly creatinine clearance did not differ between those who were hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p = 0.06 respectively). We found greater peritoneal phosphate clearance for patients choosing CAPD compared to APD, irrespective of the peritoneal phosphate transporter status. ♦ Peritoneal creatinine transporter status and creatinine clearance cannot be used as surrogate markers of peritoneal phosphate transport and clearance. Hyperphosphatemia was more common in PD patients with slower peritoneal transporter status and lower peritoneal phosphate clearance. Greater peritoneal phosphate clearance was achieved with CAPD prescriptions. Slower peritoneal transporters should be advised to choose CAPD to improve serum phosphate control. Copyright © 2016 International Society for Peritoneal Dialysis.

Evaluation of continuous ambulatory peritoneal dialysis fluid C-reactive protein in patients with peritonitis.

PubMed

Ramanathan, Kumaresan; Padmanabhan, Giri; Vijayaraghavan, Bhooma

2016-05-01

Severe peritonitis causing death is one of the most devastating complications of peritoneal dialysis (PD). Since the predictive value of C-reactive protein (CRP) in PD fluid has not been assessed, the objective of the present study is to evaluate its predictive value and clinical correlation in patients on PD with peritonitis. One hundred and twenty patients on continuous ambulatory PD (CAPD) were enrolled and their serum and fluid CRP (Fl. CRP) were evaluated at the start of CAPD. All patients who developed peritonitis were further evaluated for serum and fluid CRP. The patients were categorized into four groups, namely: normal patients (control group), patients with peritonitis, patients with peritonitis leading to catheter removal, and death due to peritonitis. Sixty-five patients developed peritonitis of whom, catheter removal was performed in eight patients. Five patients died due to peritonitis-related complications. Fl. CRP showed a significant difference among the three groups, unlike S. CRP. Estimation of CRP in the peritoneal fluid may be a useful marker to monitor the onset of peritonitis.

Myths in peritoneal dialysis.

PubMed

Lee, Martin B; Bargman, Joanne M

2016-11-01

To clarify misconceptions about the feasibility and risks of peritoneal dialysis that unnecessarily limit peritoneal dialysis uptake or continuation in patients for whom peritoneal dialysis is the preferred dialysis modality. The inappropriate choice of haemodialysis as a result of these misconceptions contributes to low peritoneal dialysis penetrance, increases transfer from peritoneal dialysis to haemodialysis, increases expenditure on haemodialysis and compromises quality of life for these patients. Peritoneal dialysis is an excellent renal replacement modality that is simple, cost-effective and provides comparable clinical outcomes to conventional in-centre haemodialysis. Unfortunately, many patients are deemed unsuitable to start or continue peritoneal dialysis because of false or inaccurate beliefs about peritoneal dialysis. Here, we examine some of these 'myths' and critically review the evidence for and against each of them. We review the feasibility and risk of peritoneal dialysis in patients with prior surgery, ostomies, obesity and mesh hernia repairs. We examine the fear of mediastinitis with peritoneal dialysis after coronary artery bypass graft surgery and the belief that the use of hypertonic glucose dialysate causes peritoneal membrane failure. By clarifying common myths about peritoneal dialysis, we hope to reduce overly cautious practices surrounding this therapy.

French National Registry of Rare Peritoneal Surface Malignancies

ClinicalTrials.gov

2017-08-18

Rare Peritoneal Surface Malignancies; Pseudomyxoma Peritonei; Peritoneal Mesothelioma; Desmoplastic Small Round Cell Tumor; Psammocarcinoma; Primary Peritoneal Serous Carcinoma; Diffuse Peritoneal Leiomyomatosis; Appendiceal Mucinous Neoplasms

A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo

PubMed Central

Ge, Xiangting; Feng, Zhiguo; Xu, Tingting; Wu, Beibei; Chen, Hongjin; Xu, Fengli; Fu, Lili; Shan, Xiaoou; Dai, Yuanrong; Zhang, Yali; Liang, Guang

2016-01-01

Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases. PMID:27390516

A novel imidazopyridine derivative, X22, attenuates sepsis-induced lung and liver injury by inhibiting the inflammatory response in vitro and in vivo.

PubMed

Ge, Xiangting; Feng, Zhiguo; Xu, Tingting; Wu, Beibei; Chen, Hongjin; Xu, Fengli; Fu, Lili; Shan, Xiaoou; Dai, Yuanrong; Zhang, Yali; Liang, Guang

2016-01-01

Sepsis remains a leading cause of death worldwide. Despite years of extensive research, effective drugs to treat sepsis in the clinic are lacking. In this study, we found a novel imidazopyridine derivative, X22, which has powerful anti-inflammatory activity. X22 dose-dependently inhibited lipopolysaccharide (LPS)-induced proinflammatory cytokine production in mouse primary peritoneal macrophages and RAW 264.7 macrophages. X22 also downregulated the LPS-induced proinflammatory gene expression in vitro. In vivo, X22 exhibited a significant protection against LPS-induced death. Pretreatment or treatment with X22 attenuated the sepsis-induced lung and liver injury by inhibiting the inflammatory response. In addition, X22 showed protection against LPS-induced acute lung injury. We additionally found that pretreatment with X22 reduced the inflammatory pain in the acetic acid and formalin models and reduced the dimethylbenzene-induced ear swelling and acetic acid-increased vascular permeability. Together, these data confirmed that X22 has multiple anti-inflammatory effects and may be a potential therapeutic option in the treatment of inflammatory diseases.

Plasmid-determined cytotoxicity in Yersinia pestis and Yersinia pseudotuberculosis.

PubMed Central

Goguen, J D; Walker, W S; Hatch, T P; Yother, J

1986-01-01

Yersinia pestis KIM5 was found to be cytotoxic for the IC21 and P388D1 mouse macrophage cell lines, as well as for resident peritoneal macrophages from C57BL/6 mice. Affected cells phagocytosed KIM5 inefficiently, became spherical, detached readily from culture dishes, and retained 51Cr poorly. The cytotoxic effect was dependent on the presence of the 75-kilobase plasmid pCD1. Because this plasmid also encodes the low calcium response (LCR), three Mu d1 insertion mutants previously shown to be LCR- and of reduced virulence in mice were examined for cytotoxicity; all were found to be atoxic. The insertions in these mutants lie within three distinct LCR loci (lcrB, C, and D). Like LCR, cytotoxicity was expressed only at 37 degrees C. Unlike LCR, it was not influenced by Ca2+ concentration, indicating that the V and W antigens are probably not involved. Yersinia pseudotuberculosis was found to have a similar plasmid-dependent cytotoxicity. Thus, biological activity observed as cytotoxicity in vitro may well be a common feature contributing to virulence of the yersiniae. Images PMID:3949380

Center-Specific Factors Associated with Peritonitis Risk-A Multi-Center Registry Analysis.

PubMed

Nadeau-Fredette, Annie-Claire; Johnson, David W; Hawley, Carmel M; Pascoe, Elaine M; Cho, Yeoungjee; Clayton, Philip A; Borlace, Monique; Badve, Sunil V; Sud, Kamal; Boudville, Neil; McDonald, Stephen P

♦ Previous studies have reported significant variation in peritonitis rates across dialysis centers. Limited evidence is available to explain this variability. The aim of this study was to assess center-level predictors of peritonitis and their relationship with peritonitis rate variations. ♦ All incident peritoneal dialysis (PD) patients treated in Australia between October 2003 and December 2013 were included. Data were accessed through the Australia and New Zealand Dialysis and Transplant Registry. The primary outcome was peritonitis rate, evaluated in a mixed effects negative binomial regression model. Peritonitis-free survival was assessed as a secondary outcome in a Cox proportional hazards model. ♦ Overall, 8,711 incident PD patients from 51 dialysis centers were included in the study. Center-level predictors of lower peritonitis rates included smaller center size, high proportion of PD, low peritoneal equilibration test use at PD start, and low proportion of hospitalization for peritonitis. In contrast, a low proportion of automated PD exposure, high icodextrin exposure and low or high use of antifungal prophylaxis at the time of peritonitis were associated with a higher peritonitis rate. Similar results were obtained for peritonitis-free survival. Overall, accounting for center-level characteristics appreciably decreased peritonitis variability among dialysis centers (p = 0.02). ♦ This study identified specific center-level characteristics associated with the variation in peritonitis risk. Whether these factors are directly related to peritonitis risk or surrogate markers for other center characteristics is uncertain and should be validated in further studies. Copyright © 2016 International Society for Peritoneal Dialysis.

Synergy of anti-CD40, CpG and MPL in activation of mouse macrophages

PubMed Central

Shi, Yongyu; Felder, Mildred A.R.; Sondel, Paul M.; Rakhmilevich, Alexander L.

2015-01-01

Activation of macrophages is a prerequisite for their antitumor effects. Several reagents, including agonistic anti-CD40 monoclonal antibody (anti-CD40), CpG oligodeoxynucleotides (CpG) and monophosphoryl lipid A (MPL), can stimulate activation of macrophages. Our previous studies showed synergy between anti-CD40 and CpG and between anti-CD40 and MPL in macrophage activation and antitumor efficacy in mice. In the present study, we asked whether there was synergy among these three reagents. The activation of adherent peritoneal exudate cells (PEC) obtained from mice injected with anti-CD40 and then treated with CpG and/or MPL in vitro was determined by their ability to suppress proliferation of tumor cells and to produce various cytokines and chemokines in vitro. Cell sorting and histology followed by functional testing showed that macrophages were the main cell population in PEC activated by CD40 ligation in vivo. A combination of anti-CD40, CpG or MPL activated PEC to suppress proliferation of B16 cells and produce nitric oxide far greater than the single reagents or any of the double combinations of these reagents. In addition, the combination of all three reagents activated PEC to secrete IL-12, IFN-γ and MCP-1 to a greater degree than any single reagent or any two combined reagents. These results demonstrate that macrophages can be synergistically activated by anti-CD40, CpG and MPL, suggesting that this novel combined approach might be further investigated as potential cancer therapy. PMID:25829245

Synergy of anti-CD40, CpG and MPL in activation of mouse macrophages.

PubMed

Shi, Yongyu; Felder, Mildred A R; Sondel, Paul M; Rakhmilevich, Alexander L

2015-08-01

Activation of macrophages is a prerequisite for their antitumor effects. Several reagents, including agonistic anti-CD40 monoclonal antibody (anti-CD40), CpG oligodeoxynucleotides (CpG) and monophosphoryl lipid A (MPL), can stimulate activation of macrophages. Our previous studies showed synergy between anti-CD40 and CpG and between anti-CD40 and MPL in macrophage activation and antitumor efficacy in mice. In the present study, we asked whether there was synergy among these three reagents. The activation of adherent peritoneal exudate cells (PEC) obtained from mice injected with anti-CD40 and then treated with CpG and/or MPL in vitro was determined by their ability to suppress proliferation of tumor cells and to produce various cytokines and chemokines in vitro. Cell sorting and histology followed by functional testing showed that macrophages were the main cell population in PEC activated by CD40 ligation in vivo. A combination of anti-CD40, CpG or MPL activated PEC to suppress proliferation of B16 cells and produce nitric oxide far greater than the single reagents or any of the double combinations of these reagents. In addition, the combination of all three reagents activated PEC to secrete IL-12, IFN-γ and MCP-1 to a greater degree than any single reagent or any two combined reagents. These results demonstrate that macrophages can be synergistically activated by anti-CD40, CpG and MPL, suggesting that this novel combined approach might be further investigated as potential cancer therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

A Rare Reason of Ileus in Renal Transplant Patients With Peritoneal Dialysis History: Encapsulated Peritoneal Sclerosis.

PubMed

Gökçe, Ali Murat; Özel, Leyla; İbişoğlu, Sevinç; Ata, Pınar; Şahin, Gülizar; Gücün, Murat; Kara, V Melih; Özdemir, Ebru; Titiz, M İzzet

2015-12-01

Encapsulating peritoneal sclerosis is a rare complication of long-term peritoneal dialysis ranging from moderate inflammation of peritoneal structures to severe sclerosing peritonitis and encapsulating peritoneal sclerosis. Complicated it, ileus may occur during or after peritoneal dialysis treatment or after kidney transplant. We sought to evaluate 3 posttransplant encapsulating peritoneal sclerosis through clinical presentation, radiologic findings, and outcomes. We analyzed 3 renal transplant patients with symptoms of encapsulating peritoneal sclerosis admitted posttransplant to our hospital with ileus between 2012 and 2013. Conservative treatment was applied to the patients whenever necessary to avoid surgery. One patient improved with medical therapy. Surgical treatment was delayed and we decided it as a last resort, in 2 cases with no response to conservative treatment for a long time. Finally, patients with peritoneal dialysis history should be searched carefully before renal transplant for intermittent bowel obstruction story.

Anti-inflammatory activity of dried flower extracts of Aegle marmelos in Wistar rats.

PubMed

Kumari, K D K P; Weerakoon, T C S; Handunnetti, S M; Samarasinghe, K; Suresh, T S

2014-02-12

Almost all part of the plant Aegle marmelos (Bael tree) has been used in the traditional medicine systems of Asian countries to treat various diseases over many centuries. The water extract of the dried flowers of Aegle marmelos is a commonly used beverage among Sri Lankan population in rural areas. Although extensive investigations done on many parts of the plant there are no experimental data available on the extracts of flowers. Anti-inflammatory effect of the water extract of dried flowers of Aegle marmelos (WEAM) was evaluated in the present study. The anti-inflammatory effect of the WEAM was evaluated by inhibition of the rat paw oedema, induced by carrageenan. The mechanism of the anti-inflammatory effect was assessed by the inhibition of production of nitric oxide (NO) by rat peritoneal cells, infiltration of rat peritoneal cells, anti-histamine effect, membrane stabilization activity, the antioxidant capacity and inhibition of lipid peroxidation by the WEAM. The maximum percentage inhibition of paw oedema was exhibited by the dose of 200 mg/kg at 2 h. The WEAM showed a significant increment of rat peritoneal cell infiltration, inhibition of NO production by rat peritoneal cells and inhibition of wheal formation on the skin of the rat after injection of histamine. The WEAM protected the erythrocyte membrane from heat-induced lysis in a dose-dependent manner and showed a significant anti-oxidant effect and lipid peroxidation inhibition activity. The WEAM possesses significant anti-inflammatory effect by multiple mechanisms in Wistar rats. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Pneumococcal LytA Autolysin, a Potent Therapeutic Agent in Experimental Peritonitis-Sepsis Caused by Highly β-Lactam-Resistant Streptococcus pneumoniae▿

PubMed Central

Rodríguez-Cerrato, Violeta; García, Pedro; Huelves, Lorena; García, Ernesto; del Prado, Gema; Gracia, Matilde; Ponte, Carmen; López, Rubens; Soriano, Francisco

2007-01-01

The in vitro and in vivo antipneumococcal activities of the main pneumococcal autolysin (LytA) and Cpl-1, a lysozyme encoded by phage Cp-1, were studied. Intraperitoneal therapy with LytA or high-dose Cpl-1 remarkably reduced peritoneal bacterial counts (>5 log10 CFU/ml) compared with those for the controls. After intravenous injection, LytA was the most effective treatment. PMID:17576844

Peritoneal Cell-free DNA: an innovative method for determining acute cell damage in peritoneal membrane and for monitoring the recovery process after peritonitis.

PubMed

Virzì, Grazia Maria; Milan Manani, Sabrina; Brocca, Alessandra; Cantaluppi, Vincenzo; de Cal, Massimo; Pastori, Silvia; Tantillo, Ilaria; Zambon, Roberto; Crepaldi, Carlo; Ronco, Claudio

2016-02-01

Cell-free DNA (cfDNA) is present in the peritoneal effluent of stable peritoneal dialysis (PD) patients, but there are no data on cfDNA in PD patients with peritonitis. We investigated the variation of peritoneal cfDNA levels subsequent to peritonitis in PD patients. We enrolled 53 PD patients: 30 without any history of systemic inflammation or peritonitis in the last 3 months (group A) and 23 with acute peritonitis (group B). CfDNA was quantified in the peritoneal effluent. Peritoneal samples on days 1, 3, 10, 30 and until day 120 from the start of peritonitis were collected for white blood cells (WBC) count and cfDNA evaluation in group B. Quantitative analysis of cfDNA showed significantly higher levels in group B on day 1, 3, 10 and 30 compared with group A (p < 0.05). A significant positive correlation was observed between cfDNA concentration and WBC on day 1 (rho = 0.89) and day 3 (rho = 0.5) (both, p < 0.05). However, no significant correlation was observed between cfDNA and WBC on days 10 and 30. In group B, peritoneal cfDNA levels tended to progressively decline during follow-up of peritonitis. From this decreasing curve, we estimated that 49 days are necessary to reach the value of 51 genome equivalents (GE)/ml (75th percentile in controls) and 63 days to reach 31 GE/ml (median). Our results demonstrate that cfDNA increases in peritoneal effluent of PD patients with peritonitis and tends to progressively decline in step with peritonitis resolution and membrane repair process. Peritoneal cfDNA quantification could be an innovative method to determine acute damage and an inverse index of the repair process.

Phosphate Removal by Peritoneal Dialysis: The Effect of Transporter Status and Peritoneal Dialysis Prescription

PubMed Central

Courivaud, Cecile; Davenport, Andrew

2016-01-01

♦ Background: Interventional trials failed to demonstrate that increasing urea clearance improved peritoneal dialysis (PD) patient survival. Hyperphosphatemia is a well-recognized predictor of cardiovascular and all-cause mortality in PD patients. Simplification of PD small solute clearance targets focuses away from larger solutes, including phosphate. In the US and UK, increasing use of automated peritoneal dialysis (APD) cyclers with shorter dwell times could also potentially reduce peritoneal phosphate removal compared to continuous ambulatory peritoneal dialysis (CAPD). ♦ Methods: Total phosphate and peritoneal phosphate clearances were measured in a prospective observational cohort of 380 adult PD patients attending a tertiary university hospital between 1996 and 2013 for routine assessment of PD adequacy. ♦ Results: Eighty-seven patients (22.9%) were hyperphosphatemic. Taking the mean 4-hour dialysate to plasma (D/P) ratio for phosphate, 193 (50.8%) were fast and fast-average transporters and 187 (49.2%) were slow and slow-average transporters (compared to 276 [72.6%] and 104 [27.4%], respectively, for peritoneal creatinine transporter status). Faster peritoneal phosphate transporter status was associated with over-hydration (odds ratio [OR] = 2.45 [1.43 – 4.20], p = 0.001). Whereas the 4-hour D/P creatinine and peritoneal weekly creatinine clearance did not differ between those who were hyperphosphatemic or not, the hyperphosphatemic patients had lower 4-hour D/P phosphate and lower peritoneal weekly phosphate clearance (p = 0.019, and p = 0.06 respectively). We found greater peritoneal phosphate clearance for patients choosing CAPD compared to APD, irrespective of the peritoneal phosphate transporter status. ♦ Conclusion: Peritoneal creatinine transporter status and creatinine clearance cannot be used as surrogate markers of peritoneal phosphate transport and clearance. Hyperphosphatemia was more common in PD patients with slower peritoneal transporter status and lower peritoneal phosphate clearance. Greater peritoneal phosphate clearance was achieved with CAPD prescriptions. Slower peritoneal transporters should be advised to choose CAPD to improve serum phosphate control. PMID:26224788

Novel fabrication method of the peritoneal dialysis filter using silk fibroin with urease fixation system.

PubMed

Moon, Bo Mi; Choi, Myung-Jin; Sultan, Md Tipu; Yang, Jae Won; Ju, Hyung Woo; Lee, Jung Min; Park, Hyun Jung; Park, Ye Ri; Kim, Soo Hyeon; Kim, Dong Wook; Lee, Min Chae; Jeong, Ju Yeon; Lee, Ok Joo; Sung, Gun Yong; Park, Chan Hum

2017-10-01

During the last decade, there has been a great advance in the kidney dialysis system by wearable artificial kidney (WAK) system for end-stage renal disease patients. Uremic solute removal and water regeneration system are the most prerequisite for WAK to work properly. In this study, we designed a filtering membrane system by using immobilized urease silk fibroin filter and evaluated its comparative effectiveness with a PVDF filtering system in peritoneal dialysate regeneration system by urea removal efficacy. We evaluated this membrane's characteristic and performances by conducting SEM-EDX analyze, water-binding abilities and porosity test, removal abilities of urea, cytotoxicity assay and enzyme activity assay. Under the condition for optimization of urease, the percentage removal of urea was about 40% and 60% in 50 mg/dL urea solution by urease immobilized PVDF and silk fibroin scaffolds, respectively. The batch experimental result showed that immobilized filter removed more than 50% of urea in 50 mg/dL urea solution. In addition silk fibroin with urease filter removed 90 percent of urea in the peritoneal dialysate after 24 h filtration. We suggest that silk fibroin with urease fixation filter can be used more effectively for peritoneal dialysate regeneration system, which have hydrophilic property and prolonged enzyme activity. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2136-2144, 2017. © 2016 Wiley Periodicals, Inc.

Humanized Mouse Model of Skin Inflammation Is Characterized by Disturbed Keratinocyte Differentiation and Influx of IL-17A Producing T Cells

PubMed Central

de Oliveira, Vivian L.; Keijsers, Romy R. M. C.; van de Kerkhof, Peter C. M.; Seyger, Marieke M. B.; Fasse, Esther; Svensson, Lars; Latta, Markus; Norsgaard, Hanne; Labuda, Tord; Hupkens, Pieter; van Erp, Piet E. J.; Joosten, Irma; Koenen, Hans J. P. M.

2012-01-01

Humanized mouse models offer a challenging possibility to study human cell function in vivo. In the huPBL-SCID-huSkin allograft model human skin is transplanted onto immunodeficient mice and allowed to heal. Thereafter allogeneic human peripheral blood mononuclear cells are infused intra peritoneally to induce T cell mediated inflammation and microvessel destruction of the human skin. This model has great potential for in vivo study of human immune cells in (skin) inflammatory processes and for preclinical screening of systemically administered immunomodulating agents. Here we studied the inflammatory skin response of human keratinocytes and human T cells and the concomitant systemic human T cell response. As new findings in the inflamed human skin of the huPBL-SCID-huSkin model we here identified: 1. Parameters of dermal pathology that enable precise quantification of the local skin inflammatory response exemplified by acanthosis, increased expression of human β-defensin-2, Elafin, K16, Ki67 and reduced expression of K10 by microscopy and immunohistochemistry. 2. Induction of human cytokines and chemokines using quantitative real-time PCR. 3. Influx of inflammation associated IL-17A-producing human CD4+ and CD8+ T cells as well as immunoregulatory CD4+Foxp3+ cells using immunohistochemistry and -fluorescence, suggesting that active immune regulation is taking place locally in the inflamed skin. 4. Systemic responses that revealed activated and proliferating human CD4+ and CD8+ T cells that acquired homing marker expression of CD62L and CLA. Finally, we demonstrated the value of the newly identified parameters by showing significant changes upon systemic treatment with the T cell inhibitory agents cyclosporine-A and rapamycin. In summary, here we equipped the huPBL-SCID-huSkin humanized mouse model with relevant tools not only to quantify the inflammatory dermal response, but also to monitor the peripheral immune status. This combined approach will gain our understanding of the dermal immunopathology in humans and benefit the development of novel therapeutics for controlling inflammatory skin diseases. PMID:23094018

Development of a murine model of blunt hepatic trauma.

PubMed

Nemzek-Hamlin, Jean A; Hwang, Haejin; Hampel, Joseph A; Yu, Bi; Raghavendran, Krishnan

2013-10-01

Despite the prevalence of blunt hepatic trauma in humans, there are few rodent models of blunt trauma that can be used to study the associated inflammatory responses. We present a mouse model of blunt hepatic trauma that was created by using a cortical contusion device. Male mice were anesthetized with ketamine-xylazine-buprenorphine and placed in left lateral recumbency. A position of 2 mm ventral to the posterior axillary line and 5 mm caudal to the costal margin on the right side was targeted for impact. An impact velocity of 6 m/s and a piston depth of 12 mm produced a consistent pattern of hepatic injury with low mortality. All mice that recovered from anesthesia survived without complication for the length of the study. Mice were euthanized at various time points (n = 5 per group) until 7 d after injury for gross examination and collection of blood and peritoneal lavage fluids. Some mice were reanesthetized for serial monitoring of hepatic lesions via MRI. At 2 h after trauma, mice consistently displayed laceration, hematoma, and discoloration of the right lateral and caudate liver lobes, with intraabdominal hemorrhage but no other gross injuries. Blood and peritoneal lavage fluid were collected from all mice for cytokine analysis. At 2 h after trauma, there were significant increases in plasma IL10 as well as peritoneal lavage fluid IL6 and CXCL1/KC; however, these levels decreased within 24 h. At 7 d after trauma, the mice had regained body weight, and the hepatic lesions, which initially had increased in size during the first 48 h, had returned to their original size. In summary, this technique produced a reliable, low mortality, murine model that recreates features of blunt abdominal liver injury in human subjects with similar acute inflammatory response.

Recent Peritonitis Associates with Mortality among Patients Treated with Peritoneal Dialysis

PubMed Central

Kemp, Anna; Clayton, Philip; Lim, Wai; Badve, Sunil V.; Hawley, Carmel M.; McDonald, Stephen P.; Wiggins, Kathryn J.; Bannister, Kym M.; Brown, Fiona G.; Johnson, David W.

2012-01-01

Peritonitis is a major complication of peritoneal dialysis, but the relationship between peritonitis and mortality among these patients is not well understood. In this case-crossover study, we included the 1316 patients who received peritoneal dialysis in Australia and New Zealand from May 2004 through December 2009 and either died on peritoneal dialysis or within 30 days of transfer to hemodialysis. Each patient served as his or her own control. The mean age was 70 years, and the mean time receiving peritoneal dialysis was 3 years. In total, there were 1446 reported episodes of peritonitis with 27% of patients having ≥2 episodes. Compared with the rest of the year, there were significantly increased odds of peritonitis during the 120 days before death, although the magnitude of this association was much greater during the 30 days before death. Compared with a 30-day window 6 months before death, the odds for peritonitis was six-fold higher during the 30 days immediately before death (odds ratio, 6.2; 95% confidence interval, 4.4–8.7). In conclusion, peritonitis significantly associates with mortality in peritoneal dialysis patients. The increased odds extend up to 120 days after an episode of peritonitis but the magnitude is greater during the initial 30 days. PMID:22626818

Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression.

PubMed

Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

2015-08-01

Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte recruitment during atherosclerotic plaque progression. Systemic IgE-mediated mast cell activation in apoE(-/-)μMT mice resulted in an increase in atherosclerotic lesion size as compared to control mice, and interestingly, the number of neutrophils was highly increased in these lesions. In addition, peritoneal mast cell activation led to a massive neutrophil influx into the peritoneal cavity in C57Bl6 mice, whereas neutrophil numbers in mast cell deficient Kit(W(-sh)/W(-sh)) mice were not affected. Within the newly recruited neutrophil population, increased levels of CXCR2(+) and CXCR4(+) neutrophils were observed after mast cell activation. Indeed, mast cells were seen to contain and release CXCL1 and CXCL12, the ligands for CXCR2 and CXCR4. Intriguingly, peritoneal mast cell activation in combination with anti-CXCR2 receptor antagonist resulted in decreased neutrophil recruitment, thus establishing a prominent role for the CXCL1/CXCR2 axis in mast cell-mediated neutrophil recruitment. Our data suggest that chemokines, and in particular CXCL1, released from activated mast cells induce neutrophil recruitment to the site of inflammation, thereby aggravating the ongoing inflammatory response and thus affecting plaque progression and destabilization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

PubMed

Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

2014-04-01

The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

Microbiology of Peritonitis in Peritoneal Dialysis Patients with Multiple Episodes

PubMed Central

Nessim, Sharon J.; Nisenbaum, Rosane; Bargman, Joanne M.; Jassal, Sarbjit V.

2012-01-01

♦ Background: Peritoneal dialysis (PD)–associated peritonitis clusters within patients. Patient factors contribute to peritonitis risk, but there is also entrapment of organisms within the biofilm that forms on PD catheters. It is hypothesized that this biofilm may prevent complete eradication of organisms, predisposing to multiple infections with the same organism. ♦ Methods: Using data collected in the Canadian multicenter Baxter POET (Peritonitis, Organism, Exit sites, Tunnel infections) database from 1996 to 2005, we studied incident PD patients with 2 or more peritonitis episodes. We determined the proportion of patients with 2 or more episodes caused by the same organism. In addition, using a multivariate logistic regression model, we tested whether prior peritonitis with a given organism predicted the occurrence of a subsequent episode with the same organism. ♦ Results: During their time on PD, 558 patients experienced 2 or more peritonitis episodes. Of those 558 patients, 181 (32%) had at least 2 episodes with the same organism. The organism most commonly causing repeat infection was coagulase-negative Staphylococcus (CNS), accounting for 65.7% of cases. Compared with peritonitis caused by other organisms, a first CNS peritonitis episode was associated with an increased risk of subsequent CNS peritonitis within 1 year (odds ratio: 2.1; 95% confidence interval: 1.5 to 2.8; p < 0.001). Among patients with repeat CNS peritonitis, 48% of repeat episodes occurred within 6 months of the earlier episode. ♦ Conclusions: In contrast to previous data, we did not find a high proportion of patients with multiple peritonitis episodes caused by the same organism. Coagulase-negative Staphylococcus was the organism most likely to cause peritonitis more than once in a given patient, and a prior CNS peritonitis was associated with an increased risk of CNS peritonitis within the subsequent year. PMID:22215659

Curcumin Suppresses IL-1β Secretion and Prevents Inflammation through Inhibition of the NLRP3 Inflammasome.

PubMed

Yin, Haipeng; Guo, Qiang; Li, Xin; Tang, Tiantian; Li, Cuiling; Wang, Hengxiao; Sun, Yuanxin; Feng, Qi; Ma, Chunhong; Gao, Chengjiang; Yi, Fan; Peng, Jun

2018-04-15

Turmeric is traditionally used as a spice and coloring in foods. Curcumin is the primary active ingredient in the turmeric, and compelling evidence has shown that it has the ability to inhibit inflammation. However, the mechanism mediating its anti-inflammatory effects are not fully understood. We report that curcumin inhibited caspase-1 activation and IL-1β secretion through suppressing LPS priming and the inflammasome activation pathway in mouse bone marrow-derived macrophages. The inhibitory effect of curcumin on inflammasome activation was specific to the NLRP3, not to the NLRC4 or the AIM2 inflammasomes. Curcumin inhibited the NLRP3 inflammasome by preventing K + efflux and disturbing the downstream events, including the efficient spatial arrangement of mitochondria, ASC oligomerization, and speckle formation. Reactive oxygen species, autophagy, sirtuin-2, or acetylated α-tubulin was ruled out as the mechanism by which curcumin inhibits the inflammasome. Importantly, in vivo data show that curcumin attenuated IL-1β secretion and prevented high-fat diet-induced insulin resistance in wide-type C57BL/6 mice but not in Nlrp3 -deficient mice. Curcumin also repressed monosodium urate crystal-induced peritoneal inflammation in vivo. Taken together, we identified curcumin as a common NLRP3 inflammasome activation inhibitor. Our findings reveal a mechanism through which curcumin represses inflammation and suggest the potential clinical use of curcumin in NLRP3-driven diseases. Copyright © 2018 by The American Association of Immunologists, Inc.

The Association between Peritoneal Dialysis Modality and Peritonitis

PubMed Central

Johnson, David W.; McDonald, Stephen P.; Boudville, Neil; Borlace, Monique; Badve, Sunil V.; Sud, Kamal; Clayton, Philip A.

2014-01-01

Background and objectives There is conflicting evidence comparing peritonitis rates among patients treated with continuous ambulatory peritoneal dialysis (CAPD) or automated peritoneal dialysis (APD). This study aims to clarify the relationship between peritoneal dialysis (PD) modality (APD versus CAPD) and the risk of developing PD-associated peritonitis. Design, setting, participants, & measurements This study examined the association between PD modality (APD versus CAPD) and the risks, microbiology, and clinical outcomes of PD-associated peritonitis in 6959 incident Australian PD patients between October 1, 2003, and December 31, 2011, using data from the Australia and New Zealand Dialysis and Transplant Registry. Median follow-up time was 1.9 years. Results Patients receiving APD were younger (60 versus 64 years) and had fewer comorbidities. There was no association between PD modality and time to first peritonitis episode (adjusted hazard ratio [HR] for APD versus CAPD, 0.98; 95% confidence interval [95% CI], 0.91 to 1.07; P=0.71). However, there was a lower hazard of developing Gram-positive peritonitis with APD than CAPD, which reached borderline significance (HR, 0.90; 95% CI, 0.80 to 1.00; P=0.05). No statistically significant difference was found in the risk of hospitalizations (odds ratio, 1.12; 95% CI, 0.93 to 1.35; P=0.22), but there was a nonsignificant higher likelihood of 30-day mortality (odds ratio, 1.33; 95% CI, 0.93 to 1.88; P=0.11) at the time of the first episode of peritonitis for patients receiving APD. For all peritonitis episodes (including subsequent episodes of peritonitis), APD was associated with lower rates of culture-negative peritonitis (incidence rate ratio [IRR], 0.81; 95% CI, 0.69 to 0.94; P=0.002) and higher rates of gram-negative peritonitis (IRR, 1.28; 95% CI, 1.13 to 1.46; P=0.01). Conclusions PD modality was not associated with a higher likelihood of developing peritonitis. However, APD was associated with a borderline reduction in the likelihood of a first episode of Gram-positive peritonitis compared with CAPD, and with lower rates of culture-negative peritonitis and higher rates of Gram-negative peritonitis. Peritonitis outcomes were comparable between both modalities. PMID:24626434

Clinical and microbiological characteristics of peritoneal dialysis-related peritonitis caused by Escherichia coli in southern Taiwan.

PubMed

Lin, Wei-Hung; Tseng, Chin-Chung; Wu, An-Bang; Chang, Yu-Tzu; Kuo, Te-Hui; Chao, Jo-Yen; Wang, Ming-Cheng; Wu, Jiunn-Jong

2018-06-21

Peritonitis is a serious complication and major cause of treatment failure in patients undergoing peritoneal dialysis (PD). Escherichia coli is the major pathogen in extraintestinal Gram-negative infections, including PD-related peritonitis. The outcomes of E. coli peritonitis in PD varied from relatively favorable outcomes to a higher incidence of treatment failure. The aim of this study was to investigate the impact of bacterial virulence and host characteristics on the outcomes of PD-related peritonitis caused by E. coli. From January 2000 to June 2016, a total of 47 episodes of monomicrobial and 10 episodes of polymicrobial E. coli PD-related peritonitis, as well as 89 episodes of monomicrobial Gram-positive (56 Staphylococcus spp. and 33 Streptococcus spp.) PD-related peritonitis cases, were retrospectively enrolled. Clinical features, E. coli bacterial virulence, and outcomes were analyzed. Compared to Streptococcus spp. peritonitis, E. coli peritonitis had a higher peritoneal catheter removal rate (38 versus 12%; P = 0.0115). Compared to the monomicrobial group, patients in polymicrobial group were older and had higher peritoneal catheter removal rate (80 versus 38%; P = 0.0324). Treatment failure of E. coli peritonitis was associated with more polymicrobial peritonitis and immunocompromised comorbidity, longer duration of PD therapy, and more antimicrobial resistance. E. coli isolates with more iron-related genes had higher prevalence of phylogenetic group B2 and papG II, iha, ompT, and usp genes. This study demonstrates the important roles of clinical and bacterial characteristics in the outcomes of monomicrobial and polymicrobial E. coli PD-related peritonitis.

The Role of NGAL in Peritoneal Dialysis Effluent in Early Diagnosis of Peritonitis: Case-Control Study in Peritoneal Dialysis Patients.

PubMed

Martino, Francesca; Scalzotto, Elisa; Giavarina, Davide; Rodighiero, Maria Pia; Crepaldi, Carlo; Day, Sonya; Ronco, Claudio

2015-01-01

Peritoneal dialysis (PD) is frequently complicated by high rates of peritonitis, which result in hospitalization, technique failure, transfer to hemodialysis, and increased mortality. Early diagnosis, and identification of contributing factors are essential components to increasing effectiveness of care. In previous reports, neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin which is a key player in innate immunity and rapidly detectable in peritoneal dialysis effluent (PDE), has been demonstrated to be a useful tool in the early diagnosis of peritonitis. This study investigates predictive value of PDE NGAL concentration as a prognostic indicator for PD-related peritonitis. A case-control study with 182 PD patients was conducted. Plasma and PDE were analyzed for the following biomarkers: C-reactive protein (CRP), blood procalcitonin (PCT), leucocytes and NGAL in PDE. The cases consisted of patients with suspected peritonitis, while controls were the patients who came to our ambulatory clinic for routine visits without any sign of peritonitis. The episodes of peritonitis were defined in agreement with International Society for Peritoneal Dialysis guidelines. Continuous variables were presented as the median values and interquartile range (IQR). Mann-Whitney U test was used to compare continuous variables. Univariate and multivariate logistic regression were used to evaluate the association of biomarkers with peritonitis. Receiver operating characteristic (ROC) curve analysis was used to calculate area under curve (AUC) for biomarkers. Finally we evaluated sensitivity, and specificity for each biomarker. All statistical analyses were performed with SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). During the 19-month study, of the 182 patients, 80 had a clinical diagnosis of peritonitis. C-reactive protein levels (p < 0.001), PCT (p < 0.001), NGAL in PDE (p < 0.001), and white blood cells (WBC) in PDE (p < 0.001) were all significantly different in patients with and without peritonitis. In univariate analysis, CRP (odds ratio [OR] 1,339; p = 0.001), PCT (OR 2,473; p < 0,001), WBC in PDE (OR 3,986; p < 0,001), and NGAL in PDE (OR 36.75 p < 0.001) were significantly associated with episodes of peritonitis. In multivariate regression analysis, only WBC (OR 24.84; p = 0,012), and peritoneal NGAL levels (OR 136.6; p = 0,01) were independent predictors of peritonitis events. Moreover, AUC for NGAL in peritoneal effluent was 0,936 (p < 0.001) while AUC for CRP, PCT, and WBC count in peritoneal effluent were 0,704 (p = 0.001), 0.762 (p = 0.039), 0,975 (p < 0.001), respectively. Finally, combined WBC and peritoneal NGAL test increased the specificity (= 96%) of the single test. These results identify NGAL in peritoneal effluent as a reliable marker of peritonitis episodes in PD patients. Collectively, our findings demonstrate that the use of peritoneal NGAL cooperatively with current clinical diagnostic tools as a prognostic indicator, presents a valuable diagnostic tool in PD-associated peritonitis. Copyright © 2015 International Society for Peritoneal Dialysis.

Activation of Peroxisome Proliferator-activated Receptor γ (PPARγ) and CD36 Protein Expression: THE DUAL PATHOPHYSIOLOGICAL ROLES OF PROGESTERONE.

PubMed

Yang, Xiaoxiao; Zhang, Wenwen; Chen, Yuanli; Li, Yan; Sun, Lei; Liu, Ying; Liu, Mengyang; Yu, Miao; Li, Xiaoju; Han, Jihong; Duan, Yajun

2016-07-15

Progesterone or its analog, one of components of hormone replacement therapy, may attenuate the cardioprotective effects of estrogen. However, the underlying mechanisms have not been fully elucidated. Expression of CD36, a receptor for oxidized LDL (oxLDL) that enhances macrophage/foam cell formation, is activated by the transcription factor peroxisome proliferator-activated receptor γ (PPARγ). CD36 also functions as a fatty acid transporter to influence fatty acid metabolism and the pathophysiological status of several diseases. In this study, we determined that progesterone induced macrophage CD36 expression, which is related to progesterone receptor (PR) activity. Progesterone enhanced cellular oxLDL uptake in a CD36-dependent manner. Mechanistically, progesterone increased PPARγ expression and PPARγ promoter activity in a PR-dependent manner and the binding of PR with the progesterone response element in the PPARγ promoter. Specific deletion of macrophage PPARγ (MφPPARγ KO) expression in mice abolished progesterone-induced macrophage CD36 expression and cellular oxLDL accumulation. We also determined that, associated with gestation and increased serum progesterone levels, CD36 and PPARγ expression in mouse adipose tissue, skeletal muscle, and peritoneal macrophages were substantially activated. Taken together, our study demonstrates that progesterone can play dual pathophysiological roles by activating PPARγ expression, in which progesterone increases macrophage CD36 expression and oxLDL accumulation, a negative effect on atherosclerosis, and enhances the PPARγ-CD36 pathway in adipose tissue and skeletal muscle, a protective effect on pregnancy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Vaccine Therapy and IDO1 Inhibitor INCB024360 in Treating Patients With Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Are in Remission

ClinicalTrials.gov

2013-12-17

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Epithelial Cancer; Stage IA Primary Peritoneal Cavity Cancer; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Epithelial Cancer; Stage IB Primary Peritoneal Cavity Cancer; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Epithelial Cancer; Stage IC Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

An intra-abdominal abscess or "rind" as a consequence of peritoneal dialysis-associated pseudomonas peritonitis.

PubMed

Culpepper, R Michael; Gore, Sarah; Rutecki, Gregory W

2013-01-01

Abdominal CT imaging has defined characteristics of two pathological entities specific to peritoneal dialysis patients. Both are associated with serious peritoneal complications. One is comprised of ascites accompanied by septation and loculated fluid pockets as a complication of bacterial peritonitis. The other is the syndrome of encapsulating peritoneal sclerosis. We present the evolution of a single, thick-walled fluid collection as a consequence of relapsing Pseudomonas aeruginosa peritonitis. The entity had distinctive features differing from either of the two previously described entities, and to our knowledge, has not been described previously. Our patient's radiological evolution resembled the formation of a pleural or peritoneal "rind." Peritonitis, as a result of Pseudomonas aeruginosa , may lead to "rind" formation as described with empyemas and is distinct from previously described intra-abdominal pathologies in peritoneal dialysis patients.

Risk Factors for Early-Onset Peritonitis in Southern Chinese Peritoneal Dialysis Patients.

PubMed

Wu, Haishan; Huang, Rong; Yi, Chunyan; Wu, Juan; Guo, Qunying; Zhou, Qian; Yu, Xueqing; Yang, Xiao

♦ BACKGROUND: Early peritonitis was confirmed to be associated with a higher risk of early technique failure. However, literature concerning peritonitis within the first 3 months of peritoneal dialysis (PD) initiation is scarce. The present study was to investigate risk factors associated with early-onset peritonitis in PD patients. ♦ METHODS: In this retrospective observational cohort study, all incident PD patients from January 1, 2006, to December 31, 2013, were recruited and followed up until December 31, 2014. According to time-to-first episode of peritonitis, patients were divided into early-onset (≤ 3 months) peritonitis and late-onset (> 3 months) peritonitis. Baseline demographic, clinical, and laboratory data, as well as episodes of peritonitis, were collected. Risk factors associated with early-onset peritonitis were evaluated using logistic regression model. ♦ RESULTS: Of 1,690 patients on PD, 503 (29.8%) developed at least 1 episode of peritonitis and 118 (7.0%) patients presented the first episodes of peritonitis within the first 3 months. A multivariate logistic analysis showed that higher body mass index (BMI) (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.01 - 1.15, p = 0.034), hypoalbuminemia (OR 1.75, 95% CI 1.11 - 2.78, p = 0.017), and catheter exit-site infection (OR 4.14, 95% CI 2.45 - 7.00, p < 0.001) were risk factors independently associated with early-onset peritonitis. Compared to those with late-onset, patients with early-onset peritonitis had a higher overall peritonitis rate (0.76 vs 0.38 per patient-year, p < 0.001) and worse technique survival (p < 0.001), while patient survival did not differ significantly between the 2 groups during the long-term follow-up (p > 0.05). ♦ CONCLUSIONS: Higher BMI, hypoalbuminemia, and catheter exit-site infection were the risk factors associated with early-onset peritonitis in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

Acute Peritonitis Caused by Staphylococcus capitis in a Peritoneal Dialysis Patient.

PubMed

Basic-Jukic, Nikolina

Acute peritonitis remains the most common complication of peritoneal dialysis (PD), with coagulase-negative staphylococci (CoNS) reported to account for more than 25% of peritonitis episodes (1). Staphylococcus capitis is a gram-positive, catalase-positive CoNS that was originally identified as a commensal on the skin of the human scalp (2). Advancement of microbiological technologies for bacterial identification enables diagnosis of previously unknown causes of acute peritonitis. This is the first reported case of acute peritonitis in a PD patient caused by S. capitis. Copyright © 2017 International Society for Peritoneal Dialysis.

[Infectious peritonitis in peritoneal dialysis: an over-emphasized complication].

PubMed

Vakilzadeh, N; Burnier, M; Halabi, G

2013-02-27

Peritoneal dialysis is an extrarenal epuration modality which uses physiological properties of peritoneum as a dialysis membrane. Despite the improvement of peritoneal dialysis techniques in the last ten years, peritonitis remains one of the most redoubt complications. Peritonitis may sometimes lead to technical failures, which need catheter removing, but rarely lead to death. Our retrospective study at the dialysis center of CHUV has analyzed factors which can predict this kind of complication. It calculates peritonitis rate and median peritonitis free-survival for different groups of patients. It also describes causatives organisms and their sensitivity to antibiotics.

A contemporary approach to the prevention of peritoneal dialysis-related peritonitis in children: the role of improvement science.

PubMed

Redpath Mahon, Allison; Neu, Alicia M

2017-08-01

Peritonitis is a leading cause of hospitalizations, morbidity, and modality change in pediatric chronic peritoneal dialysis (CPD) patients. Despite guidelines published by the International Society for Peritoneal Dialysis aimed at reducing the risk of peritonitis, registry data have revealed significant variability in peritonitis rates among centers caring for children on CPD, which suggests variability in practice. Improvement science methods have been used to reduce a variety of healthcare-associated infections and are also being applied successfully to decrease rates of peritonitis in children. A successful quality improvement program with the goal of decreasing peritonitis will not only include primary drivers directly linked to the outcome of peritonitis, but will also direct attention to secondary drivers that are important for the achievement of primary drivers, such as health literacy and patient and family engagement strategies. In this review, we describe a comprehensive improvement science model for the reduction of peritonitis in pediatric patients on CPD.

Outcomes of single organism peritonitis in peritoneal dialysis: gram negatives versus gram positives in the Network 9 Peritonitis Study.

PubMed

Bunke, C M; Brier, M E; Golper, T A

1997-08-01

The use of the "peritonitis rate" in the management of patients undergoing peritoneal dialysis is assuming importance in comparing the prowess of facilities, care givers and new innovations. For this to be a meaningful outcome measure, the type of infection (causative pathogen) must have less clinical significance than the number of infections during a time interval. The natural history of Staphylococcus aureus, pseudomonas, and fungal peritonitis would not support that the outcome of an episode of peritonitis is independent of the causative pathogen. Could this concern be extended to other more frequently occurring pathogens? To address this, the Network 9 Peritonitis Study identified 530 episodes of single organism peritonitis caused by a gram positive organism and 136 episodes caused by a single non-pseudomonal gram negative (NPGN) pathogen. Coincidental soft tissue infections (exit site or tunnel) occurred equally in both groups. Outcomes of peritonitis were analyzed by organism classification and by presence or absence of a soft tissue infection. NPGN peritonitis was associated with significantly more frequent catheter loss, hospitalization, and technique failure and was less likely to resolve regardless of the presence or absence of a soft tissue infection. Hospitalization and death tended to occur more frequently with enterococcal peritonitis than with other gram positive peritonitis. The outcomes in the NPGN peritonitis group were significantly worse (resolution, catheter loss, hospitalization, technique failure) compared to coagulase negative staphylococcal or S. aureus peritonitis, regardless of the presence or absence of a coincidental soft tissue infection. Furthermore, for the first time, the poor outcomes of gram negative peritonitis are shown to be independent of pseudomonas or polymicrobial involvement or soft tissue infections. The gram negative organism appears to be the important factor. In addition, the outcome of peritonitis caused by S. aureus is worse than that of other staphylococci. Thus, it is clear that all peritonitis episodes cannot be considered equivalent in terms of outcome. The concept of peritonitis rate is only meaningful when specific organisms are considered.

A study on the information-motivation-behavioural skills model among Chinese adults with peritoneal dialysis.

PubMed

Chang, Tian-Ying; Zhang, Yi-Lin; Shan, Yan; Liu, Sai-Sai; Song, Xiao-Yue; Li, Zheng-Yan; Du, Li-Ping; Li, Yan-Yan; Gao, Douqing

2018-05-01

To examine whether the information-motivation-behavioural skills model could predict self-care behaviour among Chinese peritoneal dialysis patients. Peritoneal dialysis is a treatment performed by patients or their caregivers in their own home. It is important to implement theory-based projects to increase the self-care of patients with peritoneal dialysis. The information-motivation-behavioural model has been verified in diverse populations as a comprehensive, effective model to guide the design, implementation and evaluation of self-care programmes. A cross-sectional, observational study. A total of 201 adults with peritoneal dialysis were recruited at a 3A grade hospital in China. Participant data were collected on demographics, self-care information (knowledge), social support (social motivation), self-care attitude (personal motivation), self-efficacy (behaviour skills) and self-care behaviour. We also collected data on whether the recruited patients had peritoneal dialysis-associated peritonitis from electronic medical records. Measured variable path analysis was performed using mplus 7.4 to identify the information-motivation-behavioural model. Self-efficacy, information and social motivation predict peritoneal dialysis self-care behaviour directly. Information and personal support affect self-care behaviour through self-efficacy, whereas peritoneal dialysis self-care behaviour has a direct effect on the prevention of peritoneal dialysis-associated peritonitis. The information-motivation-behavioural model is an appropriate and applicable model to explain and predict the self-care behaviour of Chinese peritoneal dialysis patients. Poor self-care behaviour among peritoneal dialysis patients results in peritoneal dialysis-associated peritonitis. The findings suggest that self-care education programmes for peritoneal dialysis patients should include strategies based on the information-motivation-behavioural model to enhance knowledge, motivation and behaviour skills to change or maintain self-care behaviour. © 2018 John Wiley & Sons Ltd.

Association Between Peritoneal Glucose Exposure and Peritonitis in Peritoneal Dialysis Patients: The balANZ Trial.

PubMed

Nataatmadja, Melissa; Cho, Yeoungjee; Pascoe, Elaine M; Darssan, Darsy; Hawley, Carmel M; Johnson, David W

2017-01-01

Glucose is the primary osmotic medium used in most peritoneal dialysis (PD) solutions, and exposure to glucose has been shown to exert detrimental effects both locally, at the peritoneal membrane, and systemically. Moreover, high dialysate glucose exposure may predispose patients to an increased risk of peritonitis, perhaps as a result of impaired host defences, vascular disease, and damage to the peritoneal membrane. In this post-hoc analysis of a multicenter, multinational, open-label randomized controlled trial of neutral pH, low-glucose degradation product (GDP) versus conventional PD solutions ( bal ANZ trial), the relationship between peritonitis rates of low (< 123.1 g/day) versus high (≥ 123.1 g/day) dialysate glucose exposure was evaluated in 177 incident PD patients over a 2-year study period. Peritonitis rates were 0.44 episodes per patient-year in the low-glucose exposure group and 0.31 episodes per patient-year in the high-glucose exposure group, (incidence rate ratio [IRR] 0.69, p = 0.09). There was no significant association between dialysate glucose exposure and peritonitis-free survival on univariable analysis (high glucose exposure hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.40 - 1.08) or on multivariable analysis (adjusted HR 0.64, 95% CI 0.39 - 1.05). Moreover, there was no relationship between peritoneal glucose exposure and type of organism causing peritonitis. Physician-rated severity of first peritonitis episodes was similar between groups, as was rate and duration of hospital admission. Overall, this study did not identify an association between peritoneal dialysate glucose exposure and peritonitis occurrence, severity, hospitalization, or outcomes. A further large-scale, prospective, randomized controlled trial evaluating patient-level outcomes is merited. Copyright © 2017 International Society for Peritoneal Dialysis.

PHAGOCYTIN: A BACTERICIDAL SUBSTANCE FROM POLYMORPHONUCLEAR LEUCOCYTES

PubMed Central

Hirsch, James G.

1956-01-01

A technique has been developed for collecting large numbers of polymorphonuclear leucocytes from peritoneal exudates in rabbits. These cells are obtained essentially free from other cell types and from debris. When microphages so procured are disrupted by physical methods and extracted with aqueous salt solutions, the soluble fraction manifests striking bactericidal activity, especially on Gram-negative enteric bacilli. The susceptible microorganisms are not lysed. This bactericidal substance, which has been called phagocytin, appears to be limited in distribution mainly to the polymorphonuclear leucocyte. No phagocytin is present in extracts of rabbit heart, kidney, or skeletal muscle, and rabbit liver and spleen contain much less than do packed leucocytes. Extracts of human and of guinea pig microphages show less bactericidal activity than rabbit cell preparations. Similar extracts of rat and mouse polymorphonuclear leucocytes contain no demonstrable phagocytin. As indicated by its behavior on dialysis, on exposure to proteolytic enzymes, and on salt fractionation, phagocytin appears to be a protein with general properties characteristic of a globulin. It is clearly different from lysozyme and from properdin. Although phagocytin is reasonably stable at temperatures of 65°C. and lower for several hours, solutions of it gradually lose bactericidal activity on standing for prolonged periods at 4°C. This instability, and also the ease with which phagocytin is inactivated, presumably by adsorption, on exposure to a variety of materials, have thus far rendered fruitless efforts to isolate it. PMID:13319580

Cell-delivered magnetic nanoparticles caused hyperthermia-mediated increased survival in a murine pancreatic cancer model

PubMed Central

Basel, Matthew T; Balivada, Sivasai; Wang, Hongwang; Shrestha, Tej B; Seo, Gwi Moon; Pyle, Marla; Abayaweera, Gayani; Dani, Raj; Koper, Olga B; Tamura, Masaaki; Chikan, Viktor; Bossmann, Stefan H; Troyer, Deryl L

2012-01-01

Using magnetic nanoparticles to absorb alternating magnetic field energy as a method of generating localized hyperthermia has been shown to be a potential cancer treatment. This report demonstrates a system that uses tumor homing cells to actively carry iron/iron oxide nanoparticles into tumor tissue for alternating magnetic field treatment. Paramagnetic iron/ iron oxide nanoparticles were synthesized and loaded into RAW264.7 cells (mouse monocyte/ macrophage-like cells), which have been shown to be tumor homing cells. A murine model of disseminated peritoneal pancreatic cancer was then generated by intraperitoneal injection of Pan02 cells. After tumor development, monocyte/macrophage-like cells loaded with iron/ iron oxide nanoparticles were injected intraperitoneally and allowed to migrate into the tumor. Three days after injection, mice were exposed to an alternating magnetic field for 20 minutes to cause the cell-delivered nanoparticles to generate heat. This treatment regimen was repeated three times. A survival study demonstrated that this system can significantly increase survival in a murine pancreatic cancer model, with an average post-tumor insertion life expectancy increase of 31%. This system has the potential to become a useful method for specifically and actively delivering nanoparticles for local hyperthermia treatment of cancer. PMID:22287840

Effects of BCG infection on the susceptibility of mouse macrophages to endotoxin.

PubMed Central

Peavy, D L; Baughn, R E; Musher, D M; Musher, D M

1979-01-01

Mice infected intravenously with Mycobacterium bovis (BCG) are 100 to 1,000 times more sensitive to the lethal effects of bacterial lipopolysaccharides (LPS). Since BCG infection results in macrophage activation and LPS may cause pathophysiological effects through interaction with this cell type, it was of interest to determine whether macrophages from BCG-infected animals were more susceptible to the toxic effects of LPS in vitro. When LPS-susceptible, C57BL/6 mice were infected with BCG, a significant reduction in the 50% lethal dose of LPS was first observed after 7 days and persisted for several weeks. Macrophages from these animals had greatly increased susceptibility to LPS in vitro, which correlated with the development of acquired cellular resistance as determined by their ability to inhibit the growth of Listeria monocytogenes. In contrast, BCG infection of C3H/HeJ mice, a strain resistant to LPS, did not alter the 50% lethal dose of LPS for these animals or increase the sensitivity of their peritoneal macrophages to LPS in vitro. These results indicate that susceptibility of BCG-infected mice to the lethal effects of LPS parallels the susceptibility of their macrophages in vitro; release of vasoactive substances from LPS-susceptible activated macrophages in vivo may be, in part, responsible for lethality. PMID:378847

[Circumscribed and diffuse peritonitis: severe complications in bariatric and metabolic surgery; specifics related to their diagnosis and therapy].

PubMed

Špička, P; Vaverka, P; Gryga, A; Malý, T

Cases of localized and diffuse peritonitis are severe surgical conditions. Despite expanding possibilities for the diagnosis and therapy, patients with peritonitis, its diffuse form in particular, still suffer from high morbidity and mortality. The management of this condition, both in the healthy and especially seriously ill population, is not satisfactory. Recently, we have witnessed an increase in bariatric and metabolic surgery in response to an ever rising number of extremely obese patients worldwide. Bariatric patients belong to a group of seriously ill patients with a significant risk of post-operative complications due to an infection. Although their treatment is identical to that of the normal population, a great emphasis is put on early recognition of complications, and the decision on any potential surgical revision should be actively approached, often necessitating the absence of frequently lengthy paraclinical assessments. We conducted a retrospective analysis of 346 obese bariatric patients undergoing surgical treatment for morbid obesity between August 2011 and August 2015. A total of 6 patients experienced severe complications including two cases of diffuse peritonitis, two cases of localized peritonitis and two cases of intraperitoneal bleeding. One patient died after her discharge from hospital due to toxic shock caused by stomach perforation. We describe two case reports in greater detail to highlight the importance of early detection of complications and a timely surgical intervention. In principle, bariatric patients are a severely ill population where standard diagnostic procedures for post-operative complications often fail. Clinical findings and the surgeons experience are commonly the only diagnostic signs that trigger a surgical revision. In contrast, surgical treatment of post-operative complications in obese patients with peritonitis is virtually identical to that in patients with normal or slightly increased BMI. It involves thorough toilette of the abdominal cavity, lavage and drainage. Due to high morbidity and large peritoneal surface, obese patients may deteriorate rapidly. Timely surgical intervention is thus the only proper therapeutic approach, even without any, often lengthy paraclinical assessments. peritonitis - bariatric surgery - complications in bariatric surgery.

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan

PubMed Central

Lee, Cheng-Chia; Wu, Patricia W.; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei

2017-01-01

Background Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. Methods This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Results Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. Conclusions The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients. PMID:28301536

Outcomes of Peritonitis in Children on Peritoneal Dialysis: A 25-Year Experience at Severance Hospital

PubMed Central

Lee, Kyong Ok; Park, Se Jin; Kim, Ji Hong; Lee, Jae Seung; Kim, Pyung Kil

2013-01-01

Purpose Relatively little is known on the microbiology, risk factors and outcomes of peritoneal dialysis (PD)-associated peritonitis in Korean children. We performed this study in order to evaluate the incidence, treatment and clinical outcomes of peritonitis in pediatric PD patients at Severance Hospital. Materials and Methods We analyzed data from 57 PD patients younger than 18 years during the period between June 1, 1986 and December 31, 2011. The collected data included gender, age at commencement of PD, age at peritonitis, incidence of peritonitis, underlying causes of end stage renal disease, microbiology of peritonitis episodes, antibiotics sensitivity, modality and outcomes of PD. Results We found 56 episodes of peritonitis in 23 of the 57 PD patients (0.43 episodes/patient-year). Gram-positive bacteria were the most commonly isolated organisms (40 episodes, 71.4%). Peritonitis developed in 17 patients during the first 6 months following initiation of PD (73.9%). Peritonitis episodes rarely resulted in relapse or the need for permanent hemodialysis and no patient deaths were directly attributable to peritonitis. Antibiotic regimens included cefazolin+tobramycin from the years of 1986 to 2000 and cefazolin+ceftazidime from the years of 2001 to 2011. While antibiotic therapy was successful in 48 episodes (85.7%), the treatment was ineffective in 8 episodes (14.3%). The rate of continuous ambulatory PD (CAPD) peritonitis was statistically higher than that of automated PD (APD) (p=0.025). Conclusion Peritonitis was an important complication of PD therapy and we observed a higher incidence of PD peritonitis in patients with CAPD when compared to APD. PMID:23709435

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan.

PubMed

Lu, Yueh-An; Tu, Kun-Hua; Lee, Cheng-Chia; Wu, Patricia W; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei; Chu, Pao-Hsien

2017-01-01

Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients.

Cisplatin and Flavopiridol in Treating Patients With Advanced Ovarian Epithelial Cancer or Primary Peritoneal Cancer

ClinicalTrials.gov

2014-05-06

Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Case report. Candida lusitaniae peritonitis in a patient on continuous ambulatory peritoneal dialysis.

PubMed

Cinar, S; Nedret Koç, A; Taşkapan, H; Dogukan, A; Tokgöz, B; Utaş, C

2002-04-01

We report a case of Candida lusitania peritonitis in continuous ambulatory peritoneal dialysis. Since fluconazole therapy was not successful in this patient, the peritoneal catheter was removed and antifungal therapy continued, and the patient was then converted to haemodialysis. This treatment protocol was successful. We suggest that early peritoneal catheter removal should be considered in such cases.

Risk factors and outcomes of high peritonitis rate in continuous ambulatory peritoneal dialysis patients: A retrospective study.

PubMed

Tian, Yuanshi; Xie, Xishao; Xiang, Shilong; Yang, Xin; Zhang, Xiaohui; Shou, Zhangfei; Chen, Jianghua

2016-12-01

Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients' technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients.This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes.During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality.We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality.These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes.

Risk factors and outcomes of high peritonitis rate in continuous ambulatory peritoneal dialysis patients

PubMed Central

Tian, Yuanshi; Xie, Xishao; Xiang, Shilong; Yang, Xin; Zhang, Xiaohui; Shou, Zhangfei; Chen, Jianghua

2016-01-01

Abstract Peritonitis remains a major complication of peritoneal dialysis (PD). A high peritonitis rate (HPR) affects continuous ambulatory peritoneal dialysis (CAPD) patients’ technique survival and mortality. Predictors and outcomes of HPR, rather than the first peritonitis episode, were rarely studied in the Chinese population. In this study, we examined the risk factors associated with HPR and its effects on clinical outcomes in CAPD patients. This is a single center, retrospective, observational cohort study. A total of 294 patients who developing at least 1 episode of peritonitis were followed up from March 1st, 2002, to July 31, 2014, in our PD center. Multivariate logistic regression was used to determine the factors associated with HPR, and the Cox proportional hazard model was conducted to assess the effects of HPR on clinical outcomes. During the study period of 2917.5 patient-years, 489 episodes of peritonitis were recorded, and the total peritonitis rate was 0.168 episodes per patient-year. The multivariate analysis showed that factors associated with HPR include a quick occurrence of peritonitis after CAPD initiation (shorter than 12 months), and a low serum albumin level at the start of CAPD. In the Cox proportional hazard model, HPR was a significant predictor of technique failure. There were no differences between HPR and low peritonitis rate (LPR) group for all-cause mortality. However, when the peritonitis rate was considered as a continuous variable, a positive correlation was observed between the peritonitis rate and mortality. We found the quick peritonitis occurrence after CAPD and the low serum albumin level before CAPD were strongly associated with an HPR. Also, our results verified that HPR was positively correlated with technique failure. More importantly, the increase in the peritonitis rate suggested a higher risk of all-cause mortality. These results may help to identify and target patients who are at higher risk of HPR at the start of CAPD and to take interventions to reduce peritonitis incidence and improve clinical outcomes. PMID:27930566

Contrasting intra- and extracellular distribution of catalytic ferrous iron in ovalbumin-induced peritonitis.

PubMed

Ito, Fumiya; Nishiyama, Takahiro; Shi, Lei; Mori, Masahiko; Hirayama, Tasuku; Nagasawa, Hideko; Yasui, Hiroyuki; Toyokuni, Shinya

2016-08-05

Iron is an essential nutrient for every type of life on earth. However, excess iron is cytotoxic and can lead to an increased cancer risk in humans. Catalytic ferrous iron [Fe(II)] is an initiator of the Fenton reaction, which causes oxidative stress by generating hydroxyl radicals. Recently, it became possible to localize catalytic Fe(II) in situ with a turn-on fluorescent probe, RhoNox-1. Here, we screened each organ/cell of rats to globally evaluate the distribution of catalytic Fe(II) and found that eosinophils showed the highest abundance. In various cells, lysosomes were the major organelle, sharing ∼40-80% of RhoNox-1 fluorescence. We then used an ovalbumin-induced allergic peritonitis model to study the dynamics of catalytic Fe(II). Peritoneal lavage revealed that the total iron contents per cell were significantly decreased, whereas an increase in the number of inflammatory cells (macrophages, neutrophils, eosinophils and lymphocytes) resulted in an increased total iron content of the peritoneal inflammatory cells. Notably, macrophages, eosinophils and neutrophils exhibited significantly increased catalytic Fe(II) with increased DMT1 expression and decreased ferritin expression, though catalytic Fe(II) was significantly decreased in the peritoneal lavage fluid. In conclusion, catalytic Fe(II) in situ more directly reflects cellular activity and the accompanying pathology than total iron does. Copyright © 2016 Elsevier Inc. All rights reserved.

Rationale and design of the balANZ trial: a randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function.

PubMed

Johnson, David W; Clarke, Margaret; Wilson, Vanessa; Woods, Feidhlim; Brown, Fiona G

2010-09-16

The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance) or conventional dialysis solution (Stay.safe) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527.

Abundance and Localization of Progesterone Receptor Isoforms in Endometrium in Women With and Without Endometriosis and in Peritoneal and Ovarian Endometriotic Implants

PubMed Central

Bedaiwy, Mohamed A.; Dahoud, Wissam; Skomorovska-Prokvolit, Yelena; Yi, Lijuan; Liu, James H.; Falcone, Tommaso; Hurd, William W.; Mesiano, Sam

2015-01-01

Background: Several studies suggest that resistance to progesterone may contribute to the pathophysiology of endometriosis. Progesterone mediates its biological activity via the 2 progesterone receptor (PR) isoforms (PR-A and PR-B). Effects of progesterone are determined by the PR-A:PR-B ratio such that a PR-B-dominant state promotes progesterone signaling, whereas a PR-A-dominant state decreases progesterone responsiveness. Our objective was to compare the abundance and cellular localization of the PR isoforms in endometrium and endometriotic lesions from women with and without peritoneal and ovarian endometriosis. Methods: This in vitro study was conducted in a tertiary care facility. Reproductive-age women with surgically diagnosed endometriosis (n = 18) and asymptomatic control individuals (n = 20) were prospectively recruited at the late proliferative and the early secretory phases. At laparoscopy, samples of eutopic endometrium, peritoneal and ovarian endometriosis, and disease-free peritoneum were obtained for subsequent immunohistochemical and immunoblot analysis of PR-B and total PR localization and PR-A and PR-B abundance, respectively. Results: The PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis but not in disease-free peritoneum from patients with and without endometriosis. In peritoneal endometriosis, PR-A was the predominant isoform detected, whereas both receptors were detected in ovarian endometriosis and eutopic endometrium. In eutopic endometrium, levels of PR-A were significantly elevated in women with endometriosis compared with women without disease, regardless of menstrual phase. The PR-A levels were significantly elevated in ovarian endometriosis compared with peritoneal endometriosis. Conclusions: Endometriotic lesions and eutopic endometrium from women with endometriosis are uniform in a PR-A-dominant state. The data suggest that menstrual efflux of a PR-A-dominant endometrial tissue into the peritoneal cavity may play a role in the pathophysiology of endometriosis. PMID:26037298

Rationale and design of the balANZ trial: A randomised controlled trial of low GDP, neutral pH versus standard peritoneal dialysis solution for the preservation of residual renal function

PubMed Central

2010-01-01

Background The main hypothesis of this study is that neutral pH, low glucose degradation product (GDP) peritoneal dialysis (PD) fluid better preserves residual renal function in PD patients over time compared with conventional dialysate. Methods/Design Inclusion criteria are adult PD patients (CAPD or APD) aged 18-81 years whose first dialysis was within 90 days prior to or following enrolment and who have a residual GFR ≥ 5 ml/min/1.73 m2, a urine output ≥ 400 ml/day and an ability to understand the nature and requirements of this trial. Pregnant or lactating patients or individuals with an active infection at the time of enrolment, a contra-indication to PD or participation in any other clinical trial where an intervention is designed to moderate rate of change of residual renal function are excluded. Patients will be randomized 1:1 to receive either neutral pH, low GDP dialysis solution (Balance®) or conventional dialysis solution (Stay.safe®) for a period of 2 years. During this 2 year study period, urinary urea and clearance measurements will be performed at 0, 3, 6, 9, 12, 18 and 24 months. The primary outcome measure will be the slope of residual renal function decline, adjusted for centre and presence of diabetic nephropathy. Secondary outcome measures will include time from initiation of peritoneal dialysis to anuria, peritoneal small solute clearance, peritoneal transport status, peritoneal ultrafiltration, technique survival, patient survival, peritonitis rates and adverse events. A total of 185 patients has been recruited into the trial. Discussion This investigator-initiated study has been designed to provide evidence to help nephrologists determine the optimal dialysis solution for preserving residual renal function in PD patients. Trial Registration Australian New Zealand Clinical Trials Registry Number: ACTRN12606000044527 PMID:20843375

Peritonitis related to percutaneous endoscopic gastrostomy using the direct method for cancer patients.

PubMed

Osera, Shozo; Yano, Tomonori; Odagaki, Tomoyuki; Oono, Yasuhiro; Ikematsu, Hiroaki; Ohtsu, Atsushi; Kaneko, Kazuhiro

2015-10-01

Percutaneous endoscopic gastrostomy (PEG) using the direct method is generally indicated for cancer patients. However, there are little available data about peritonitis related to this method. The aim of this retrospective analysis was to assess peritonitis related to PEG using the direct method in patients with cancer. We assessed the prevalence of peritonitis and the relationship between peritonitis and patients' backgrounds, as well as the clinical course after peritonitis. Between December 2008 and December 2011, peritonitis was found in 9 (2.1 %) of 421 patients. Of the 9 patients with peritonitis, 4 had received PEG prior to chemoradiotherapy. Emergency surgical drainage was required in 1 patient, and the remaining 8 recovered with conservative treatment. Peritonitis occurred within 8 days of PEG for 8 of the 9 patients and occurred within 2 days of suture removal for 4 of the 9 patients. Peritonitis related to PEG using the direct method was less frequent for cancer patients. Peritonitis tended to occur within a few days after removal of securing suture and in patients with palliative stage.

Effects of intraperitoneal and intranasal application of Lentinan on cellular response in rats.

PubMed

Markova, Nadya; Kussovski, Vesselin; Radoucheva, Tatyana; Dilova, Krasimira; Georgieva, Neli

2002-11-01

Lentinan (Ajinomoto, Japan) was administrated intraperitoneally (i.p.) and intranasally (i.n.) at different doses (1, 5 and 10 mg/kg) to rats. Effectiveness of Lentinan treatment was evaluated by comparative testing of cell activation (establishing the number, glycolytic and acid phosphatase activity, H2O2 production and killing ability against Salmonella enteritidis and Staphylococcus aureus) at two different compartments--peritoneal and broncho-alveolar cavities. The results indicated that Lentinan induced high-grade activation of peritoneal cells (PCs) and especially of broncho-alveolar cells (BACs) with markedly enhanced effector function (killing ability against S. aureus). Generally, Lentinan, known usually with its parenteral routes of application, can be successful to stimulate the host cell response in the respiratory tract by intranasal route of administration.

Icodextrin does not impact infectious and culture-negative peritonitis rates in peritoneal dialysis patients: a 2-year multicentre, comparative, prospective cohort study

PubMed Central

Vychytil, Andreas; Remón, César; Michel, Catherine; Williams, Paul; Rodríguez-Carmona, Ana; Marrón, Belén; Vonesh, Ed; van der Heyden, Synke; Filho, Jose C. Divino

2008-01-01

Background. Icodextrin is a glucose polymer derived by hydrolysis of cornstarch. The different biocompatibility profile of icodextrin-containing peritoneal dialysis (PD) solutions may have a positive influence on peritoneal host defence. Furthermore, cases of sterile peritonitis potentially associated with icodextrin have been reported. Methods. The primary objective of this multicentre, longitudinal, observational, non-interventional, prospective cohort study, which included 722 PD patients, was to evaluate the incidence of overall peritonitis in patients treated with icodextrin-containing PD solutions (Extraneal™) used during one long-dwell exchange/day compared with those treated with non-icodextrin-containing PD solutions. The secondary objective was to determine if culture-negative peritonitis rates differed between patients treated with icodextrin from two independent manufacturers. All peritonitis episodes were assessed by a Steering Committee in a blind manner. Results. There was no significant difference between icodextrin-treated and control patients in the adjusted overall, culture-positive or culture-negative peritonitis rates. When stratified by the icodextrin supplier, there was no significant difference in the adjusted rate of culture-negative peritonitis episodes between groups. Conclusion. Subjects receiving icodextrin as part of their PD regimen experienced neither a higher rate of culture-negative peritonitis nor a lower rate of infectious peritonitis compared with non-icodextrin users. There was no significant influence of the icodextrin raw material supplier on peritonitis rates. PMID:18556747

[Inhibition of phospholipase A2 of peritoneal macrophages in rats by 1,2-di-O-hexadecyl-rac-glycero-3-phosphocholine].

PubMed

Boucrot, P; Khettab, E N; Petit, J Y; Welin, L

1993-01-01

The 1-O-stearoyl-2-O-[3H] arachidonyl-sn-glycero-3-phosphocholine, introduced in the culture medium, was taken up by the peritoneal macrophages activated by the ionophore A 23187. After intracellular phospholipase A2 activity, the [3H] arachidonic acid was found in cells and in extracellular fluids. It also reached the eicosanoid synthesis. When it was introduced in the culture medium with the tritiated phospholipid, the 1, 2 di-O-hexadecyl-rac-glycero-3-phosphocholine, which has a non hydrolysable alkylated structure in the 2 position of the glycerol, inhibited the intracellular phospholipase A2, then contributed to lower the eicosanoid synthesis.

33 Years of Peritoneal Dialysis-Associated Peritonitis: A Single-Center Study in Japan.

PubMed

Nakao, Masatsugu; Yamamoto, Izumi; Maruyama, Yukio; Nakashima, Akio; Matsuo, Nanae; Tanno, Yudo; Ohkido, Ichiro; Ikeda, Masato; Yamamoto, Hiroyasu; Yokoyama, Keitaro; Yokoo, Takashi

2016-02-01

Peritoneal dialysis-associated peritonitis (PD-associated peritonitis) could influence the outcome of PD patients, including technique survival. Although the use of the twin-bag system has decreased the incidence of peritonitis, the effects of biocompatible PD solutions are controversial. Additionally, since both infection-causing microorganisms and antimicrobial therapies have changed over time, the duration of treatment of peritonitis (the duration of peritonitis) seems to have changed. The study included 527 patients who received PD between January 1980 and December 2012 at a single center. We divided patients undergoing PD into three groups according to the type of PD system used, namely single-bag and conventional PD solutions (S+C group, N = 145), twin-bag and conventional PD solutions (T+C group, N = 171) and twin-bag and biocompatible PD solutions (T+B group, N = 211), and analyzed PD-associated peritonitis incidences. Incidences of PD-associated peritonitis (times per patient-months) and peritonitis-free time were 1/59.4, 1/70.6 and 1/103.1, and 52, 97, and 100 months for the S+C, T+C and T+B groups, respectively. The duration of peritonitis, has thus, become dramatically shorter in recent years. Streptococcus sp. were associated with shortest and fungi with longest durations of peritonitis. Staphylococcus sp. and Pseudomonas aeruginosa were predominant in the S+C group. The twin-bag system has made a greater contribution to reductions in PD-associated peritonitis than biocompatible PD solutions. Furthermore, changes in microorganisms, antimicrobial therapies, patient education and improved PD system devices have presumably affected the reduction in the duration of peritonitis. © 2015 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

Hydration status measured by BCM: A potential modifiable risk factor for peritonitis in patients on peritoneal dialysis.

PubMed

Santhakumaran, Territa; Samad, Nasreen; Fan, Stanley L

2016-05-01

Peritoneal dialysis peritonitis and fluid overhydration (OH) are frequent problems in peritoneal dialysis. The latter can cause gut wall oedema or be associated with malnutrition. Both may lead to increased peritonitis risk. We wished to determine if OH is an independent risk factor for peritonitis (caused by enteric organisms). Retrospectively study of patients with >2 bioimpedance assessments (Body Composition Monitor). We compared peritonitis rates of patients with above or below the median time-averaged hydration parameter (OH/extracellular water, OH/ECW). Multivariate analysis was performed to determine independent risk factors for peritonitis by enteric organism. We studied 580 patients. Peritonitis was experienced by 28% patients (followed up for an average of 17 months). The overall peritonitis rate was 1:34 patient months. Patients with low OH/ECW values had significantly lower rates of peritonitis from enteric organisms than overhydrated patients (incident rate ratio 1.53, 95% confidence interval 1.38-1.70, P < 0.001). Hydration remained an independent predictor of peritonitis from enteric organisms when multivariate model included demographic parameters (odds ratio for a 1% increment of OH/ECW was 1.05; 95% confidence interval 1.01-1.10, P < 0.02). However, including biochemical parameters of malnutrition reduced the predictive power of overhydration. We found an association between overhydration and increased rates of peritonitis. While this may partly be due to the high co-morbidity of patients (advanced age and diabetes), on multivariate analysis, only inclusion of nutritional parameters reduced this association. It remains to be determined if overhydration will prove to be a modifiable risk factor for peritonitis or whether malnutrition will prove to be more important. © 2015 Asian Pacific Society of Nephrology.

[Peritonitis in pediatric patients receiving peritoneal dialysis].

PubMed

Jellouli, Manel; Ferjani, Meriem; Abidi, Kamel; Hammi, Yosra; Boutiba, Ilhem; Naija, Ouns; Zarrouk, Chokri; Ben Abdallah, Taieb; Gargah, Tahar

2015-12-01

Peritonitis on catheter of dialysis represents the most frequent complication of the peritoneal dialysis (PD) in the pediatric population. It remains a significant cause of morbidity and mortality. In this study, we investigated the risk factors for peritonitis in children. In this study, we retrospectively collected the records of 85 patients who were treated with PD within the past ten years in the service of pediatrics of the University Hospital Charles-Nicolle of Tunis. Peritonitis rate was 0.75 episode per patient-year. Notably, peritonitis caused by Gram-positive organisms were more common. Analysis of infection risk revealed three significant independent factors: the poor weight (P=0.0045), the non-automated PD (P=0.02) and the short delay from catheter insertion to starting PD (P=0.02). The early onset peritonitis was significantly associated with frequent peritonitis episodes (P=0.0008). The mean duration between the first and second episode of peritonitis was significantly shorter than between PD commencement and the first episode of peritonitis. We revealed a significant association between Gram-negative peritonitis and the presence of ureterostomy (0.018) and between Gram-positive peritonitis and the presence of exit-site and tunnel infections (0.02). Transition to permanent hemodialysis was needed in many children but no death occurred in patients with peritonitis. Considering the important incidence of peritonitis in our patients, it is imperative to establish a targeted primary prevention. Nutritional care must be provided to children to avoid poor weight. The automated dialysis has to be the modality of choice. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

Adherence to peritoneal dialysis training schedule.

PubMed

Chow, Kai Ming; Szeto, Cheuk Chun; Leung, Chi Bon; Law, Man Ching; Kwan, Bonnie Ching-Ha; Li, Philip Kam-Tao

2007-02-01

Shortening behaviour during peritoneal dialysis training can be easily measured, and likened to the skipping behaviour in haemodialysis subjects, although its effect on peritoneal dialysis outcomes is now well understood. We studied the clinical impact of failing to adhere to a peritoneal dialysis training programme among incident dialysis patients. This study included 159 consecutive inception peritoneal dialysis patients in a single centre from September 1999 through November 2002. We evaluated the effects of behavioural compliance quantified by the per cent time arriving late for scheduled peritoneal dialysis training. The patients were categorized by whether they arrived late in >20% of their peritoneal dialysis training sessions. Of the 159 incident peritoneal dialysis patients (mean age 57 +/- 13 years) who attended peritoneal dialysis training, 70 subjects (44%) arrived late in >20% of the sessions. They were younger by 5 years than patients who arrived late < or =20%. Mean peritonitis-free time for subjects who arrived late for training in >20% the of sessions was 30.9 months, as compared with 41.8 months in subjects with < or =20% late attendance behaviour (log rank test, P = 0.038). Multivariable Cox proportional hazards analysis showed that late attendance behaviour and baseline serum albumin were the only independent risk factors for the time to a first peritonitis after adjustment for diabetes mellitus and relevant coexisting medical factors. Late arrival in >20% of the peritoneal dialysis training sessions was associated with >50% increased likelihood of subsequent peritonitis, with an adjusted risk ratio of 1.56 (95% confidence interval, 1.02-2.39; P = 0.04). These findings show that the behavioural measure of late attendance for peritoneal dialysis training has a crucial role in predicting peritonitis. It may therefore represent a practical strategy for identifying poor adherence or predicting medical outcomes.

Higher expression of vascular endothelial growth factor (VEGF) and its receptor VEGFR-2 (Flk-1) and metalloproteinase-9 (MMP-9) in a rat model of peritoneal endometriosis is similar to cancer diseases

PubMed Central

2010-01-01

Background Endometriosis is a common disease characterized by the presence of a functional endometrium outside the uterine cavity, causing pelvic pain, dysmenorrheal, and infertility. This disease has been associated to development of different types of malignancies; therefore new blood vessels are essential for the survival of the endometrial implant. Our previous observations on humans showed that angiogenesis is predominantly found in rectosigmoid endometriosis, a deeply infiltrating disease. In this study, we have established the experimental model of rat peritoneal endometriosis to evaluate the process of angiogenesis and to compare with eutopic endometrium. Methods We have investigated the morphological characteristics of these lesions and the vascular density, VEGF and its receptor Flk-1 and MMP-9 expression, and activated macrophage distribution, using immunohistochemistry and RT-PCR. Results As expected, the auto-transplantation of endometrium pieces into the peritoneal cavity is a well-established method for endometriosis induction in rats. The lesions were cystic and vascularized, and demonstrated histological hallmarks of human pathology, such as endometrial glands and stroma. The vascular density and the presence of VEGF and Flk-1 and MMP-9 were significantly higher in endometriotic lesions than in eutopic endometrium, and confirmed the angiogenic potential of these lesions. We also observed an increase in the number of activated macrophages (ED-1 positive cells) in the endometriotic lesions, showing a positive correlation with VEGF. Conclusion The present endometriosis model would be useful for investigation of the mechanisms of angiogenesis process involved in the peritoneal attachment of endometrial cells, as well as of the effects of therapeutic drugs, particularly with antiangiogenic activity. PMID:20085636

Immune cells tracing using quantum dots

NASA Astrophysics Data System (ADS)

Hoshino, Akiyoshi; Fujioka, Kouki; Kawamura, Yuki I.; Toyama-Sorimachi, Noriko; Yasuhara, Masato; Dohi, Taeko; Yamamoto, Kenji

2006-02-01

Fluorescent nanoparticles, such as nanocrystal quantum dots (QDs), have potential to be applied to molecular biology and bioimaging, since some nanocrystals emit higher and longer lasting fluorescence than conventional organic probes do. Here we report an example of labeling immune cells by QDs. We collected splenic CD4 + T-lymphocyte and peritoneal macrophages from mice. Then cells were labeled with QDs. QDs are incorporated into the T-lymphocyte and macrophages immediately after addition and located in the cytoplasm via endocytosis pathway. The fluorescence of QDs held in the endosomes was easily detected for more than a week. In addition, T-lymphocytes labeled with QDs were stable and cell proliferation or cytokine production including IL-2 and IFN-γ was not affected. When QD-labeled T-lymphocytes were adoptively transferred intravenously to mice, they remained in the peripheral blood and spleen up to a week. Using QD-labeled peritoneal macrophages, we studied cell traffic during inflammation on viscera in peritoneum cavity. QD-labeled macrophages were transplanted into the peritoneum of the mouse, and colitis was induced by intracolonic injection of a hapten, trinitrobenzensulfonic acid. With the aid of stong signals of QDs, we found that macrophage accumuled on the inflammation site of the colon. These results suggested that fluorescent probes of QDs might be useful as bioimaging tools for tracing target cells in vivo.

Sirolimus and Vaccine Therapy in Treating Patients With Stage II-IV Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cavity Cancer

ClinicalTrials.gov

2018-03-28

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIA Primary Peritoneal Cavity Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIB Primary Peritoneal Cavity Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIC Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Risk Factors for and Outcomes of Catheter-Associated Peritonitis in Children: The SCOPE Collaborative.

PubMed

Sethna, Christine B; Bryant, Kristina; Munshi, Raj; Warady, Bradley A; Richardson, Troy; Lawlor, John; Newland, Jason G; Neu, Alicia

2016-09-07

The Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative is a quality improvement initiative that aims to reduce peritoneal dialysis-associated infections in pediatric patients on chronic peritoneal dialysis. Our objectives were to determine whether provider compliance with peritoneal dialysis catheter care bundles was associated with lower risk for infection at the individual patient level and describe the epidemiology, risk factors, and outcomes for peritonitis in the Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative. We collected peritoneal dialysis characteristics, causative organisms, compliance with care bundles, and outcomes in children with peritonitis between October of 2011 and September of 2014. Chi-squared tests, t tests, and generalized linear mixed models were used to assess risk factors for peritonitis. Of 734 children enrolled (54% boys; median age =9 years old; interquartile range, 1-15) from 29 centers, 391 peritonitis episodes occurred among 245 individuals over 10,130 catheter-months. The aggregate annualized peritonitis rate was 0.46 episodes per patient-year. Rates were highest among children ≤2 years old (0.62 episodes per patient-year). Gram-positive peritonitis predominated (37.8%) followed by culture-negative (24.7%), gram-negative (19.5%), and polymicrobial (10.3%) infections; fungal only peritonitis accounted for 7.7% of episodes. Compliance with the follow-up bundle was associated with a lower rate of peritonitis (rate ratio, 0.49; 95% confidence interval, 0.30 to 0.80) in the multivariable model. Upward orientation of the catheter exit site (rate ratio, 4.2; 95% confidence interval, 1.49 to 11.89) and touch contamination (rate ratio, 2.22; 95% confidence interval, 1.44 to 3.34) were also associated with a higher risk of peritonitis. Infection outcomes included resolution with antimicrobial treatment alone in 76.6%, permanent catheter removal in 12.2%, and catheter removal with return to peritoneal dialysis in 6% of episodes. Lower compliance with standardized practices for follow-up peritoneal dialysis catheter care in the Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative was associated with higher risk of peritonitis. Quality improvement and prevention strategies have the potential to reduce peritoneal dialysis-associated peritonitis. Copyright © 2016 by the American Society of Nephrology.

Risk Factors for and Outcomes of Catheter-Associated Peritonitis in Children: The SCOPE Collaborative

PubMed Central

Bryant, Kristina; Munshi, Raj; Warady, Bradley A.; Richardson, Troy; Lawlor, John; Newland, Jason G.; Neu, Alicia

2016-01-01

Background and objectives The Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative is a quality improvement initiative that aims to reduce peritoneal dialysis–associated infections in pediatric patients on chronic peritoneal dialysis. Our objectives were to determine whether provider compliance with peritoneal dialysis catheter care bundles was associated with lower risk for infection at the individual patient level and describe the epidemiology, risk factors, and outcomes for peritonitis in the Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative. Design, setting, participants, & measurements We collected peritoneal dialysis characteristics, causative organisms, compliance with care bundles, and outcomes in children with peritonitis between October of 2011 and September of 2014. Chi-squared tests, t tests, and generalized linear mixed models were used to assess risk factors for peritonitis. Results Of 734 children enrolled (54% boys; median age =9 years old; interquartile range, 1–15) from 29 centers, 391 peritonitis episodes occurred among 245 individuals over 10,130 catheter-months. The aggregate annualized peritonitis rate was 0.46 episodes per patient-year. Rates were highest among children ≤2 years old (0.62 episodes per patient-year). Gram-positive peritonitis predominated (37.8%) followed by culture-negative (24.7%), gram-negative (19.5%), and polymicrobial (10.3%) infections; fungal only peritonitis accounted for 7.7% of episodes. Compliance with the follow-up bundle was associated with a lower rate of peritonitis (rate ratio, 0.49; 95% confidence interval, 0.30 to 0.80) in the multivariable model. Upward orientation of the catheter exit site (rate ratio, 4.2; 95% confidence interval, 1.49 to 11.89) and touch contamination (rate ratio, 2.22; 95% confidence interval, 1.44 to 3.34) were also associated with a higher risk of peritonitis. Infection outcomes included resolution with antimicrobial treatment alone in 76.6%, permanent catheter removal in 12.2%, and catheter removal with return to peritoneal dialysis in 6% of episodes. Conclusions Lower compliance with standardized practices for follow-up peritoneal dialysis catheter care in the Standardizing Care to Improve Outcomes in Pediatric ESRD Collaborative was associated with higher risk of peritonitis. Quality improvement and prevention strategies have the potential to reduce peritoneal dialysis–associated peritonitis. PMID:27340282

Tumor-Targeting Salmonella typhimurium A1-R Promotes Tumoricidal CD8+ T Cell Tumor Infiltration and Arrests Growth and Metastasis in a Syngeneic Pancreatic-Cancer Orthotopic Mouse Model.

PubMed

Murakami, Takashi; Hiroshima, Yukihiko; Zhang, Yong; Zhao, Ming; Kiyuna, Tasuku; Hwang, Ho Kyoung; Miyake, Kentaro; Homma, Yuki; Mori, Ryutaro; Matsuyama, Ryusei; Chishima, Takashi; Ichikawa, Yasushi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Hoffman, Robert M

2018-01-01

The present study determined the effect of the tumor-targeting strain Salmonella typhimurium A1-R (S. typhimurium A1-R) on CD8 + tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic-cancer orthotopic mouse model. The effect of tumor-targeting S. typhimurium A1-R on CD8 + TILs was determined on the Pan02 murine pancreatic-adenocarcinoma implanted orthotopically in the pancreatic tail of C57BL/6 immunocompromised mice. Three weeks after orthotopic implantation, mice were randomized as follows G1: untreated control group (n = 8); and G2: S. typhimurium A1-R-treatment group (n = 8, 1 × 10 7 colony forming units [CFU]/body, iv, weekly, 3 weeks). On the 22nd day from initial treatment, all mice were sacrificed and tumors were harvested. The tumor-volume ratio was defined as ratio of tumor volume on the 22nd day relative to the 1st day. The tumor volume ratio was significantly lower in the S. typhimurium A1-R-treated group (G2) (3.0 ± 2.8) than the untreated control (G1) (39.9 ± 30.7, P < 0.01). Hematoxylin and easin (H&E) staining on tumor sections was performed to evaluate tumor destruction which was classified according to the Evans grading system and found to be much greater in the S. typhimurium A1-R-treated mice (G2). Six mice in G1 had peritoneal dissemination, whereas no mice showed peritoneal dissemination in G2 (P < 0.01). Immunohistochemical staining with anti-mouse CD8 + antibody was performed in order to detect TILs determined by calculating the average number of CD8 + cells in three high power fields (200×) in the treated and untreated tumors. The TIL score was significantly higher in G2 (133.5 ± 32.2) than G1 (45.1 ± 19.4, P < 0.001). The present study demonstrates that S. typhimurium A1-R promotes CD8 + T cell infiltration and inhibition of tumor growth and metastasis. J. Cell. Biochem. 119: 634-639, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Degenrative Fibroid and Sclerosing Peritonitis

PubMed Central

Critchley, Michael; Bagley, John; Iqbal, Pervis

2012-01-01

Sclerosing peritonitis is a rare condition characterised by ascites, peritoneal and bowel wall thickening. Causes reported in the literature include luteal ovarian the comas, peritoneal dialysis, peritoneal chemotherapy and liver cirrhosis. We report an interesting case of a woman presenting with diarrhoea, abdominal distension, ascites and pleural effusion. She was subsequently diagnosed with Sclerosing Peritonitis caused by a degenerating fibroid which was successfully treated by Total Abdominal Hysterectomy and Bilateral Salpingoophrectomy. PMID:22928130

Accelerated recovery from Candida peritonitis of enteric origin by early surgical drainage in a peritoneal dialysis patient.

PubMed

Kazama, Itsuro; Muto, Shigeaki; Inoue, Makoto; Fukui, Taro; Kotoda, Atsushi; Takemura, Katsumi; Kimura, Takaaki; Ishikawa, Nobuo; Yagisawa, Takashi; Yumura, Wako; Kusano, Eiji

2011-12-01

A 62-year-old man on continuous ambulatory peritoneal dialysis was transferred to our hospital with recurrent abdominal pain and a cloudy peritoneal effluent. Three weeks before the transfer, his symptoms were successfully treated with broad-spectrum antibiotics. However, their effectiveness was lost for his recurrent symptoms. Fungal peritonitis was diagnosed because of an increased white blood cell count in the peritoneal fluid on admission and isolation of Candida albicans from a peritoneal fluid culture. Intravenous fos-fluconazole was immediately started, although it was ineffective for his deteriorating symptoms. The concomitant isolation of Candida albicans in a stool culture suggested that fungal peritonitis had an enteric origin. An emergency laparotomy revealed multiple diverticulosis and sigmoid colon diverticulitis. A surgical drainage was performed in addition to peritoneal catheter removal. Postoperatively, the patient's symptoms improved rapidly and there were no signs of recurrence with continuous administration of fos-fluconazole. Surgical drainage accelerated the recovery from fungal peritonitis. This patient is the first case showing the usefulness of stool culture in the diagnosis of fungal peritonitis secondary to prior bacterial peritonitis. This case also demonstrated the importance of laparotomy to confirm the enteric origin of the fungus, and the efficacy of early surgical drainage for the treatment.

CCL19/CCR7 contributes to the pathogenesis of endometriosis via PI3K/Akt pathway by regulating the proliferation and invasion of ESCs.

PubMed

Diao, Ruiying; Wei, Weixia; Zhao, Jinghui; Tian, Fuying; Cai, Xueyong; Duan, Yong-Gang

2017-11-01

The level of CCL19 increased in the peritoneal fluid of women with endometriosis, but the precise mechanism of CCL19/CCR7 in the pathogenesis of endometriosis remains unknown. ELISA and immunohistochemistry were performed to analyze CCL19/CCR7 expressions in peritoneal fluid and endometrium from women with endometriosis (n = 38) and controls (n = 32). Cell proliferation and transwell invasion assays were applied to detect proliferation and invasion of human endometrial stromal cells (ESCs). Expressions of Bcl2, MMP2, MMP9, and p-AKT/AKT were analyzed by Western blot. Peritoneal fluid concentration of CCL19 in patients with endometriosis was higher than that in controls. Those patients with moderate/severe endometriosis had significantly higher peritoneal fluid concentrations of CCL19 compared to those with minimal/mild endometriosis. Higher CCL19 and CCR7 were found in the endometrium with endometriosis compared to control. CCL19 significantly enhanced ESC proliferation and invasion through CCR7 via activating PI3K/Akt signal pathways. CCL19/CCR7 interaction significantly enhanced phosphorylation of Akt, Bcl2, MMP2, and MMP9 in ESCs. These data indicate CCL19/CCR7 contributes to proliferation and invasion of ESCs, which are conducive to the pathogenesis of endometriosis through activating PI3K/Akt pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of peritonitis rates and patient survival in automated and continuous ambulatory peritoneal dialysis: a 10-year single center experience.

PubMed

El-Reshaid, Wael; Al-Disawy, Hanan; Nassef, Hossameldeen; Alhelaly, Usama

2016-09-01

Peritonitis is a common complication in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). In this retrospective study, peritonitis rates and patient survival of 180 patients on CAPD and 128 patients on APD were compared in the period from January 2005 to December 2014 at Al-Nafisi Center in Kuwait. All patients had prophylactic topical mupirocin at catheter exit site. Patients on CAPD had twin bag system with Y transfer set. The peritonitis rates were 1 in 29 months in CAPD and 1 in 38 months in APD (p < 0.05). Percentage of peritonitis free patients over 10-year period in CAPD and APD were 49 and 60%, respectively (p < 0.05). Time to develop peritonitis was 10.25 ± 3.1 months in CAPD compared to 16.1 ± 4 months in APD (p < 0.001). Relapse and recurrence rates were similar in both groups. Median patient survival in CAPD and APD groups with peritonitis was 13.1 ± 1 and 14 ± 1.4 months respectively (p = 0.3) whereas in peritonitis free patients it was 15 ± 1.4 months in CAPD and 23 ± 3.1 months in APD (p = 0.025). APD had lower incidence rate of peritonitis than CAPD. Patient survival was better in APD than CAPD in peritonitis free patients but was similar in patients who had peritonitis.

The Association of Individual and Regional Socioeconomic Status on Initial Peritonitis and Outcomes in Peritoneal Dialysis Patients: A Propensity Score-Matched Cohort Study.

PubMed

Wang, Qin; Hu, Ke-Jie; Ren, Ye-Ping; Dong, Jie; Han, Qing-Feng; Zhu, Tong-Ying; Chen, Jiang-Hua; Zhao, Hui-Ping; Chen, Meng-Hua; Xu, Rong; Wang, Yue; Hao, Chuan-Ming; Zhang, Xiao-Hui; Wang, Mei; Tian, Na; Wang, Hai-Yan

2016-01-01

♦ Research indicates that the socioeconomic status (SES) of individuals and the area where they live are related to initial peritonitis and outcomes in peritoneal dialysis (PD). We conducted a retrospective, multi-center cohort study in China to examine these associations. ♦ Data on 2,171 PD patients were collected from 7 centers, including baseline demographic, socioeconomic, and laboratory data. We explored the potential risk factors for initial peritonitis and outcomes using univariate Cox regression and unadjusted binary logistic regression. Then, we used propensity score matching to balance statistically significant risk factors for initial peritonitis and outcomes, and Kaplan-Meier survival analysis to compare differences in peritonitis-free rates between different groups of participants after matching. ♦ A total of 563 (25.9%) initial episodes of peritonitis occurred during the study period. The Kaplan-Meier peritonitis-free rate curve showed high-income patients had a significantly lower risk than low-income patients (p = 0.007) after matching for age, hemoglobin, albumin, and regional SES and PD center. The risk of treatment failure was significantly lower in the high-income than the low-income group after matching for the organism causing peritonitis and PD center: odds ratio (OR) = 0.27 (0.09 - 0.80, p = 0.018). Regional SES and education were not associated with initial peritonitis and outcomes. ♦ Our study demonstrates low individual income is a risk factor for the initial onset of peritonitis and treatment failure after initial peritonitis. Copyright © 2016 International Society for Peritoneal Dialysis.

A retrospective assessment of risk factors for peritonitis among an urban CAPD population.

PubMed

Korbet, S M; Vonesh, E F; Firanek, C A

1993-01-01

Peritonitis is a major reason why patients transfer from peritoneal dialysis (PD) to hemodialysis. We evaluated the peritonitis infection rates in 146 peritoneal dialysis patients who underwent dialysis at our facility between 1 January 1981 and 31 December 1989. Peritonitis was the primary cause for changing treatment, with 24 (16.4%) of the patients transferring because of this complication. This represented 54.5% of all patients discontinuing CAPD due to method failure. A gamma-Poisson regression analysis was performed in an attempt to identify potential risk factors associated with an increased incidence of peritonitis. The results indicated that race, education level, and PD system used were significantly associated with the rate at which peritonitis occurred in our patient population. There was an almost twofold increase in the rate of peritonitis among blacks as compared to whites (2.2 vs 1.2 episodes/patient year). The level of education completed at the start of dialysis had a negative correlation with peritonitis rates. Patients with < or = 8, 9-12, and > or = 13 years of education had peritonitis rates of 2.4, 1.8, and 1.2 episodes/patient year, respectively. Finally, the system used had a significant effect with our patients on CCPD having lower peritonitis rates as compared to patients on either a connect or disconnect system (0.6 vs 2.5 vs 1.8 episodes/patient year, respectively). Recognizing potential risk factors for peritonitis will help us better understand and address this significant problem in our PD programs. Reducing peritonitis rates should facilitate a decrease in patient transfer due to method failure.

Loss of Proliferation and Antigen Presentation Activity following Internalization of Polydispersed Carbon Nanotubes by Primary Lung Epithelial Cells

PubMed Central

Kumari, Mandavi; Sachar, Sumedha; Saxena, Rajiv K.

2012-01-01

Interactions between poly-dispersed acid functionalized single walled carbon nanotubes (AF-SWCNTs) and primary lung epithelial (PLE) cells were studied. Peritoneal macrophages (PMs, known phagocytic cells) were used as positive controls in this study. Recovery of live cells from cultures of PLE cells and PMs was significantly reduced in the presence of AF-SWCNTs, in a time and dose dependent manner. Both PLE cells as well as PMs could take up fluorescence tagged AF-SWCNTs in a time dependent manner and this uptake was significantly blocked by cytochalasin D, an agent that blocks the activity of acto-myosin fibers and therefore the phagocytic activity of cells. Confocal microscopic studies confirmed that AF-SWCNTs were internalized by both PLE cells and PMs. Intra-trachially instilled AF-SWCNTs could also be taken up by lung epithelial cells as well as alveolar macrophages. Freshly isolated PLE cells had significant cell division activity and cell cycling studies indicated that treatment with AF-SWCNTs resulted in a marked reduction in S-phase of the cell cycle. In a previously standardized system to study BCG antigen presentation by PLE cells and PMs to sensitized T helper cells, AF-SWCNTs could significantly lower the antigen presentation ability of both cell types. These results show that mouse primary lung epithelial cells can efficiently internalize AF-SWCNTs and the uptake of nanotubes interfered with biological functions of PLE cells including their ability to present BCG antigens to sensitized T helper cells. PMID:22384094

Modulation of Neutrophil Motility by Curcumin: Implications for Inflammatory Bowel Disease

PubMed Central

Larmonier, C.B.; Midura-Kiela, M.T.; Ramalingam, R.; Laubitz, D.; Janikashvili, N.; Larmonier, N.; Ghishan, F.K.; Kiela, P.R.

2010-01-01

Background Neutrophils (PMN) are the first cells recruited at the site of inflammation. They play a key role in the innate immune response by recognizing, ingesting and eliminating pathogens and participate in the orientation of the adaptive immune responses. However, in Inflammatory Bowel Disease (IBD), transepithelial neutrophil migration leads to an impaired epithelial barrier function, perpetuation of inflammation and tissue destruction via oxidative and proteolytic damage. Curcumin (diferulolylmethane) displays a protective role in mouse models of IBD and in human ulcerative colitis, a phenomenon consistently accompanied by a reduced mucosal neutrophil infiltration. Methods We investigated the effect of curcumin on mouse and human neutrophil polarization and motility in vitro and in vivo. Results Curcumin attenuated LPS-stimulated expression and secretion of MIP-2, IL-1β, KC and MIP-1α in colonic epithelial cells (CEC) and in macrophages. Curcumin significantly inhibited PMN chemotaxis against MIP-2, KC or against conditioned media from LPS-treated macrophages or CEC, a well as the IL-8-mediated chemotaxis of human neutrophils. At non-toxic concentrations, curcumin inhibited random neutrophil migration suggesting a direct effect on neutrophil chemokinesis. Curcumin-mediated inhibition of PMN motility could be attributed to a downregulation of PI3K activity, AKT phosphorylation and F-actin polymerization at the leading edge. The inhibitory effect of curcumin on neutrophil motility was further demonstrated in vivo in a model of aseptic peritonitis. Conclusion Our results indicate that curcumin interferes with colonic inflammation partly through inhibition of the chemokine expression and through direct inhibition of neutrophil chemotaxis and chemokinesis. PMID:20629184

Intraperitoneal Administration of a Tumor-Associated Antigen SART3, CD40L, and GM-CSF Gene-Loaded Polyplex Micelle Elicits a Vaccine Effect in Mouse Tumor Models

PubMed Central

Furugaki, Kouichi; Cui, Lin; Kunisawa, Yumi; Osada, Kensuke; Shinkai, Kentaro; Tanaka, Masao; Kataoka, Kazunori; Nakano, Kenji

2014-01-01

Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3), adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF) as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when re-challenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype. PMID:25013909

[Spontaneous bacterial peritonitis: impact of microbiological changes].

PubMed

Almeida, Paulo Roberto Lerias de; Camargo, Nutianne Schneider; Arenz, Maximilhano; Tovo, Cristiane Valle; Galperim, Bruno; Behar, Paulo

2007-01-01

Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and the changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used in the treatment. To evaluate the change in the epidemiology and antibiotic resistance of the bacteria causing spontaneous bacterial peritonitis in a 7 years period. All the cases of cirrhotic patients with spontaneous bacterial peritonitis with positive cultural examination were retrospectively studied. Two periods were evaluated: 1997-1998 and 2002-2003. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. In the first period (1997-1998) there were 33 cases, 3 (9%) with polymicrobial infection. The most common were: E.coli in 13 (36,11%), Staphylococcus coagulase-negative in 6 (16,66%), K. pneumoniae in 5 (13,88%), S. aureus in 4 (11,11%) and S. faecalis in 3 (8,33%). In 2003-2004, there were 43 cases, 2 (5%) with polymicrobial infection. The most frequent were: Staphylococus coagulase-negative in 16 (35,55%), S. aureus in 8 (17,77%), E. coli in 7 (15,55%) and K. pneumoniae in 3 (6,66%). No one was using antibiotic prophilaxys. The prevalence of S. aureus methicillin-resitant to quinolone and trimethoprim-sulfamethoxazole changed from 25% to 50%, and vancomicin was the only one with absolute activity during all the period. In the same way, the prevalence of E. coli resistant to third generation cephalosporin and to quinolone changed from 0% to 16%. There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug against gram-positive organisms in the empiric treatment of spontaneous bacterial peritonitis.

Transferrin-derived synthetic peptide induces highly conserved pro-inflammatory responses of macrophages.

PubMed

Haddad, George; Belosevic, Miodrag

2009-02-01

We examined the induction of macrophage pro-inflammatory responses by transferrin-derived synthetic peptide originally identified following digestion of transferrin from different species (murine, bovine, human N-lobe and goldfish) using elastase. The mass spectrometry analysis of elastase-digested murine transferrin identified a 31 amino acid peptide located in the N2 sub-domain of the transferrin N-lobe, that we named TMAP. TMAP was synthetically produced and shown to induce a number of pro-inflammatory genes by quantitative PCR. TMAP induced chemotaxis, a potent nitric oxide response, and TNF-alpha secretion in different macrophage populations; P338D1 macrophage-like cells, mouse peritoneal macrophages, mouse bone marrow-derived macrophages (BMDM) and goldfish macrophages. The treatment of BMDM cultures with TMAP stimulated the production of nine cytokines and chemokines (IL-6, MCP-5, MIP-1 alpha, MIP-1 gamma, MIP-2, GCSF, KC, VEGF, and RANTES) that was measured using cytokine antibody array and confirmed by Western blot. Our results indicate that transferrin-derived peptide, TMAP, is an immunomodulating molecule capable of inducing pro-inflammatory responses in lower and higher vertebrates.

Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes.

PubMed

Mauel, J; Buchmüller, Y; Behin, R

1978-08-01

When cultures of normal mouse peritoneal macrophages were infected with the intracellular protozoan parasite Leishmania enrietti, the micro-organism was found to survive intracellularly for several days, apparently without multiplication. However, exposure of infected macrophages to certain stimuli led to rapid parasite killing and digestion, providing a sensitive assay with which the mechanisms of macrophage activation can be studied. Microbicidal activity was induced by incubation of macrophages with syngeneic spleen lymphocytes, which were stimulated either by allogeneic cells in mixed lymphocyte culture (MLC) or by the plant lectin concanavalin A (Con A). Cocultivation with MLCs led to parasite killing within 48-72 h, whereas exposure of infected cells to Con A-stimulated lymphocytes resulted in substantial destruction of the micro-organism within less than 24 h, an effect which was dependent on the presence of thymus-derived lymphocytes and was inhibited by alpha methyl-mannoside. Incubation with Con A-stimulated lymphocytes also led to lysis of part of the macrophage monolayer. However, parasite killing did not result from decreased macrophage survival, as destruction of the micro-organism was highest under culture conditions which were the least detrimental to the phagocytes. Conversely, excess numbers of Con A-stimulated lymphocytes were less efficient at inducing macrophage activation and displayed marked toxicity to the macrophage monolayer. When spleen cells were stimulated by Con A at concentrations above 10 mug/ml, a decrease was noted in the capacity of macrophages to destroy the parasite, probably reflecting a toxicity of the lectin for lymphocytes resulting in impaired activating capacity.

Ouabain Modulates Zymosan-Induced Peritonitis in Mice

PubMed Central

Leite, Jacqueline Alves; Alves, Anne Kaliery De Abreu; Galvão, José Guilherme Marques; Teixeira, Mariana Pires; Rumjanek, Vivian Mary; Rodrigues-Mascarenhas, Sandra

2015-01-01

Ouabain, a potent inhibitor of the Na+, K+-ATPase, was identified as an endogenous substance. Recently, ouabain was shown to affect various immunological processes. We have previously demonstrated the ability of ouabain to modulate inflammation, but little is known about the mechanisms involved. Thus, the aim of the present work is to evaluate the immune modulatory role of ouabain on zymosan-induced peritonitis in mice. Our results show that ouabain decreased plasma exudation (33%). After induction of inflammation, OUA treatment led to a 46% reduction in the total number of cells, as a reflex of a decrease of polymorphonuclear leukocytes, which does not appear to be due to cell death. Furthermore, OUA decreased TNF-α (57%) and IL-1β (58%) levels, without interfering with IL-6 and IL-10. Also, in vitro experiments show that ouabain did not affect endocytic capacity. Moreover, electrophoretic mobility shift assay (EMSA) shows that zymosan treatment increased (85%) NF-κB binding activity and that ouabain reduced (30%) NF-κB binding activity induced by zymosan. Therefore, our data suggest that ouabain modulated acute inflammatory response, reducing the number of cells and cytokines levels in the peritoneal cavity, as well as NFκB activation, suggesting a new mode of action of this substance. PMID:26078492

CT, MRI and PET imaging in peritoneal malignancy

PubMed Central

Sahdev, Anju; Reznek, Rodney H.

2011-01-01

Abstract Imaging plays a vital role in the evaluation of patients with suspected or proven peritoneal malignancy. Nevertheless, despite significant advances in imaging technology and protocols, assessment of peritoneal pathology remains challenging. The combination of complex peritoneal anatomy, an extensive surface area that may host tumour deposits and the considerable overlap of imaging appearances of various peritoneal diseases often makes interpretation difficult. Contrast-enhanced multidetector computed tomography (MDCT) remains the most versatile tool in the imaging of peritoneal malignancy. However, conventional and emerging magnetic resonance imaging (MRI) and positron emission tomography (PET)/CT techniques offer significant advantages over MDCT in detection and surveillance. This article reviews established and new techniques in CT, MRI and PET imaging in both primary and secondary peritoneal malignancies and provides an overview of peritoneal anatomy, function and modes of disease dissemination with illustration of common sites and imaging features of peritoneal malignancy. PMID:21865109

Non Candida albicans fungal peritonitis in continuous ambulatory peritoneal dialysis patients.

PubMed

Kleinpeter, M A; Butt, A A

2001-01-01

We report four episodes of non Candida albicans peritonitis (NCAP) in 3 patients on continuous ambulatory peritoneal dialysis (CAPD). Risk factors for NCAP included diabetes mellitus and prior antibiotic use in half of the cases. The antibiotic treatment was prescribed for exit-site infection (ESI) or peritonitis in the patient. Treatment for NCAP included antifungal therapy with oral fluconazole or intravenous amphotericin B. The NCAP resulted in catheter loss in 100% of the patients over time. Initial catheter salvage in one patient was followed 6 months later by catheter loss following treatment of a bacterial peritonitis that was complicated by the development of Candida (Torulopsis) glabrata peritonitis unresponsive to treatment with intravenous amphotericin B. Although the literature suggests that Candida peritonitis responds to oral fluconazole with and without catheter removal, this series suggests that the treatment of NCAP includes removal of the peritoneal dialysis catheter with appropriate antifungal agents.

Water and solute transport across the peritoneal membrane.

PubMed

Morelle, Johann; Devuyst, Olivier

2015-09-01

We review the molecular mechanisms of peritoneal transport and discuss how a better understanding of these mechanisms is relevant for dialysis therapy. Peritoneal dialysis involves diffusion and osmosis through the highly vascularized peritoneal membrane. Computer simulations, expression studies and functional analyses in Aqp1 knockout mice demonstrated the critical role of the water channel aquaporin-1 (AQP1) in water removal during peritoneal dialysis. Pharmacologic regulation of AQP1, either through increased expression or gating, is associated with increased water transport in rodent models of peritoneal dialysis. Water transport is impaired during acute peritonitis, despite unchanged expression of AQP1, resulting from the increased microvascular area that dissipates the osmotic gradient across the membrane. In long-term peritoneal dialysis patients, the fibrotic interstitium also impairs water transport, resulting in ultrafiltration failure. Recent data suggest that stroke and drug intoxications might benefit from peritoneal dialysis and could represent novel applications of peritoneal transport in the future. A better understanding of the regulation of osmotic water transport across the peritoneum offers novel insights into the role of water channels in microvascular endothelia, the functional importance of structural changes in the peritoneal interstitium and the transport of water and solutes across biological membranes in general.

Risk of Peritoneal Dialysis-Related Peritonitis in a Multi-Racial Asian Population.

PubMed

Ong, Loke Meng; Ch'ng, Chin Chin; Wee, Hong Chin; Supramaniam, Premaa; Zainal, Hadzlinda; Goh, Bak Leong; Bavanandan, Sunita; Mushahar, Lily; Hooi, Lai Seong; Ahmad, Ghazali

♦ BACKGROUND: Peritonitis is one of the most common complications of peritoneal dialysis (PD). Understanding the risk factors of peritonitis in a multi-racial Asian population may help to improve outcomes on PD. ♦ METHODS: We conducted a prospective observational study to identify risk factors for PD-related peritonitis over a 1-year period in 15 adult PD centers. All peritonitis episodes were independently adjudicated. ♦ RESULTS: A total of 1,603 participants with a mean age of 51.6 years comprising 52.7% females, 62.6% ethnic Malays, 27.0% Chinese, and 8.1% Indians were recruited. The overall peritonitis rate was 1 episode per 44.0 patient-months with 354 episodes recorded in 282 (17.6%) patients over 15,588 patient-months. Significant risk factors of peritonitis were severe obesity (incidence-rate ratio [IRR] 3.32, 95% confidence interval [CI]: 1.30, 8.45), hypoalbuminemia (IRR 1.61, 95% CI: 1.06, 2.46), Staphylococcus aureus nasal carriage (IRR 2.26, 95% CI: 1.46, 3.50), and use of Fresenius system (Fresenius Medical Care North America, Waltham, MA, USA) (IRR 2.49, 95% CI: 1.27, 4.89). The risk of peritonitis was lower in those on automated PD compared with standard PD (IRR 0.43, 95% CI: 0.25, 0.74), and in centers with a patient-staff ratio of 15 to 29.9 (IRR 0.67, 95% CI: 0.49, 0.90) and ≥ 30 (IRR 0.52, 95% CI: 0.34, 0.80). Prevalent patients and exit-site care with topical antibiotics were also protective against peritonitis. Peritonitis rates varied between racial groups. The IRRs of overall peritonitis and gram-positive peritonitis in Chinese versus other racial groups were 0.65 (95% CI: 0.46, 0.90) and 0.47 (95% CI: 0.24, 0.91), respectively. ♦ CONCLUSIONS: Multiple patient, center, and PD-system factors influence the risk of peritonitis. In the Asian population, there are racial differences in the risk of peritonitis. Copyright © 2017 International Society for Peritoneal Dialysis.

[Peritonitis in diverticulitis: the Bern concept].

PubMed

Seiler, C A; Brügger, L; Maurer, C A; Renzulli, P; Büchler, M W

1998-01-01

The colon is the most frequent origine for a diffuse peritonitis and diverticular perforation is again the most common source of a spontaneous secondary peritonitis. This paper first focuses on the treatment of peritonitis and secondly on the strategies of source control in peritonitis with special emphasis on the tactics (primary anastomosis vs. Hartmann procedure with colostomy) for surgical source control. Prospective analysis of 404 patients suffering from peritonitis (11/93-2/98), treated with an uniform treatment concept including early operation, source control and extensive intraoperative lavage (20 to 30 liters) as a standard procedure. Other treatment measures were added in special indications "on demand" only. Peritonitis was graded with the Mannheim Peritonitis Index (MPI). Tactics of source control in peritonitis due to diverticulitis were performed according to "general condition" respectively the MPI of the patient. The 404 patients averaged a MPI of 19 (0-35) in "local" peritonitis and a MPI of 26 (11-43) in "diffuse" peritonitis. The colon as a source of peritonitis resulted in MPI of 16 (0-33) in the case of "local" respectively 27 (11-43) in "diffuse" peritonitis. From 181 patients suffering from diverticulitis 144 needed an operation and in 78 (54%) peritonitis was present. Fourty-six percent (36) of the patients suffered from "local", 54% (42) from "diffuse" peritonitis. Resection with primary anastomosis was performed in 26% (20/78) whereas in 74% (58/78) of the patients a Hartmann procedure with colostomy was performed. The correlating MPI was 16 (0-28) vs. 23 (16-27) respectively. The analysis of complications and mortality based on the MPI showed a decent discrimination potential for primary anastomosis vs Hartmann procedure: morbidity 35% vs. 41%; reoperation 5% vs. 5%; mortality 0% vs. 14%. In case of peritonitis due to diverticulitis the treatment of peritonitis comes first. Thanks to advances in intensive care and improved anti-inflammatory care, a more conservative surgical concept nowadays is accepted. In the case of diverticulitis the MPI is helpful to choose between primary anastomosis vs. Hartmann procedure with colostomy as source control. The MPI includes the "general condition" of the patient into the tactical decision how to attain source control.

Anti-granuloma activity of Coriandrum sativum in experimental models

PubMed Central

Nair, Vinod; Singh, Surender; Gupta, Yogendra Kumar

2013-01-01

Background: Coriandrum sativum has been used in the traditional systems of medicine for management of arthritis and other inflammatory disorders. Objectives: In this study, we have evaluated the anti-inflammatory and anti-granuloma activities of Coriandrum sativum hydroalcoholic extract (CSHE) in experimental models. Materials and Methods: The anti-inflammatory activity of CSHE was evaluated using carrageenan-induced paw edema model and the anti-granuloma activity of CSHE was evaluated using the subcutaneous cotton pellet implantation-induced granuloma formation and stimulation of peritoneal macrophages with complete Freund's adjuvant. Serum tumor necrosis factor-α (TNF-α), IL-6, IL-1 β levels, and peritoneal macrophage expression of TNF-R1 were evaluated as markers of global inflammation. Results: CSHE at the highest dose tested (32 mg/kg) produced a significant reduction (P < 0.05) in paw edema after carrageenan administration. CSHE treatment also reduced dry granuloma weight in all treated animals. Serum IL-6 and IL-1 β levels were significantly (P < 0.05) lower in the CSHE (32 mg/kg)-treated group as compared to control. Although there was an increase in serum TNF-α level in the CSHE-treated group as compared to control, TNF-R1 expression on peritoneal macrophages was found to be reduced. Conclusion: Thus, the result of this study demonstrates the anti-inflammatory and anti-granuloma activities of CSHE in experimental models, and validates its traditional use for the management of arthritis and other inflammatory disorders. PMID:23741156

The Effects of Biocompatible Compared with Standard Peritoneal Dialysis Solutions on Peritonitis Microbiology, Treatment, and Outcomes: the balANZ Trial

PubMed Central

Johnson, David W.; Brown, Fiona G.; Clarke, Margaret; Boudville, Neil; Elias, Tony J.; Foo, Marjorie W.Y.; Jones, Bernard; Kulkarni, Hemant; Langham, Robyn; Ranganathan, Dwarakanathan; Schollum, John; Suranyi, Michael G.; Tan, Seng H.; Voss, David

2012-01-01

♦ Background: A multicenter, multi-country randomized controlled trial (the balANZ study) recently reported that peritonitis rates significantly improved with the use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation products (“biocompatible”) compared with standard solutions. The present paper reports a secondary outcome analysis of the balANZ trial with respect to peritonitis microbiology, treatment, and outcomes. ♦ Methods: Adult incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. ♦ Results: The safety population analysis for peritonitis included 91 patients in each group. The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95% confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p = 0.01]. When specific causative organisms were examined, the rates of culture-negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes were not significantly different between the biocompatible and control groups, although the biocompatible group did experience a significantly lower rate of non-pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p = 0.03). Initial empiric antibiotic regimens were comparable between the groups. Biocompatible fluid use did not significantly reduce the risk of peritonitis-associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but did result in a shorter median duration of peritonitis-associated hospitalization (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis-associated technique failures and peritonitis-related deaths were comparable in the two groups. ♦ Conclusions: Biocompatible PD fluid use was associated with a broad reduction in gram-positive, gram-negative, and culture-negative peritonitis that reached statistical significance for non-pseudomonal gram-negative organisms. Peritonitis hospitalization duration was shorter, and peritonitis severity was more commonly rated as mild in patients receiving biocompatible PD fluids, although other peritonitis outcomes were comparable between the groups. PMID:22991015

Environmental and occupational exposure to bisphenol A and endometriosis: urinary and peritoneal fluid concentration levels.

PubMed

Simonelli, Angela; Guadagni, Rossella; De Franciscis, Pasquale; Colacurci, Nicola; Pieri, Maria; Basilicata, Pascale; Pedata, Paola; Lamberti, Monica; Sannolo, Nicola; Miraglia, Nadia

2017-01-01

The study aimed to give a first data set of bisphenol A (BPA) levels in the peritoneal fluid of patients suffering from endometriosis and to investigate the relationship between BPA exposure and endometriosis. A questionnaire investigating the occupational context, life environment, and habits was administered to 68 patients suffering from endometriosis and 60 endometriosis-free subjects (control group). Urine and peritoneal fluids samples were collected and analysed by GC/MSMS for BPA dosage. Some of the investigated environmental/lifestyle risk factors (closeness to industries/activities at risk) were associated with an increase in endometriosis; smoking resulted as protective factor; others (use of food plastic boxes) did not seem to influence the onset of pathology. The association between the occupational exposure summarising all examined risk factors (working activity, personal protective equipment, seniority) and endometriosis was statistically significant (χ 2  = 5.252, p = 0.02). Contrasting results were obtained when specific activities were examined. Detectable urinary BPA levels were found in all analysed samples (patients: 1.17-12.68 pg/µl; mean ± SD, 5.31 ± 3.36 pg/µl; control group: 1.28-2.35 pg/µl; mean ± SD, 1.64 ± 0.49 pg/µl; median; 1.46 pg/µl), with a statistically significant difference between patients and controls, showing an association between BPA exposure and endometriosis. Only a few subjects from the control group supplied peritoneal fluid; hence, no comparison test with patients (range 0.39-1.46 pg/µl; mean ± SD, 0.67 ± 0.30 pg/µl; median, 0.58 pg/µl) was carried out. Results highlight the potential association between BPA exposure and endometriosis, as well as the current lack of knowledge regarding occupational exposure to BPA and the need of epidemiological studies focused on single activities/occupations, such as housewives, cleaners, students.

Effect of assistance on peritonitis risk in diabetic patients treated by peritoneal dialysis: report from the French Language Peritoneal Dialysis Registry.

PubMed

Benabed, Anais; Bechade, Clemence; Ficheux, Maxence; Verger, Christian; Lobbedez, Thierry

2016-04-01

Diabetic patients treated by peritoneal dialysis (PD) have been reported to be at an increased risk of peritonitis. This has been attributed to impairment in host defense, visual impairment, disability and muscle wasting, which could compromise ability to safely perform catheter connections. This study aimed to evaluate whether assisted PD is associated with a lower risk of peritonitis in diabetic patients. This was a retrospective study based on data from the French Language Peritoneal Dialysis Registry. We included diabetic patients starting PD between 1 January 2002 and 31 December 2012. The end of the observation period was 31 December 2013. Using complementary regression analysis (Fine and Gray, Hurdle models), we assessed the relationship between peritonitis occurrence, peritonitis number over time and the type of assisted PD. Of the 3598 diabetic patients, there were 2040 patients on nurse-assisted PD. These patients were older, more comorbid and more frequently on continuous ambulatory peritoneal dialysis (CAPD). In the multivariate analysis, nurse assistance was associated with a reduced risk of peritonitis in the Fine and Gray [subdistribution hazard ratio: 0.78 (95% confidence interval, CI, 0.68-0.89)] and in the first component of the Hurdle models [rate ratio: 0.82 (95% CI 0.71-0.93)], but not a lower incidence of peritonitis after an initial episode [rate ratio: 0.82 (95% CI 0.95-1.38)]. Transplant failure, glomerulonephritis and CAPD were associated with an increased risk. In France, nurse-assisted PD is associated with a lower risk of peritonitis in diabetic patients treated by PD but not a lower incidence of peritonitis. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Neighborhood Socioeconomic Status and Barriers to Peritoneal Dialysis: A Mixed Methods Study

PubMed Central

Perzynski, Adam T.; Austin, Peter C.; Wu, C. Fangyun; Lawless, Mary Ellen; Paterson, J. Michael; Quinn, Rob R.; Sehgal, Ashwini R.; Oliver, Matthew James

2013-01-01

Summary Background and objectives The objective of this study was to evaluate the association between neighborhood socioeconomic status and barriers to peritoneal dialysis eligibility and choice. Design, setting, participants, & measurements This study was a mixed methods parallel design study using quantitative and qualitative data from a prospective clinical database of ESRD patients. The eligibility and choice cohorts were assembled from consecutive incident chronic dialysis patients entering one of five renal programs in the province of Ontario, Canada, between January 1, 2004 and December 31, 2010. Socioeconomic status was measured as median household income and percentage of residents with at least a high school education using Statistics Canada dissemination area-level data. Multivariable models described the relationship between socioeconomic status and likelihood of peritoneal dialysis eligibility and choice. Barriers to peritoneal dialysis eligibility and choice were classified into qualitative categories using the thematic constant comparative approach. Results The peritoneal dialysis eligibility and choice cohorts had 1314 and 857 patients, respectively; 65% of patients were deemed eligible for peritoneal dialysis, and 46% of eligible patients chose peritoneal dialysis. Socioeconomic status was not a significant predictor of peritoneal dialysis eligibility or choice in this study. Qualitative analyses identified 16 barriers to peritoneal dialysis choice. Patients in lower- versus higher-income Statistics Canada dissemination areas cited built environment or space barriers to peritoneal dialysis (4.6% versus 2.7%) and family or social support barriers (8.3% versus 3.5%) more frequently. Conclusions Peritoneal dialysis eligibility and choice were not associated with socioeconomic status. However, socioeconomic status may influence specific barriers to peritoneal dialysis choice. Additional studies to determine the effect of targeting interventions to specific barriers to peritoneal dialysis choice in low socioeconomic status patients on peritoneal dialysis use are needed. PMID:23970135

Neighborhood socioeconomic status and barriers to peritoneal dialysis: a mixed methods study.

PubMed

Prakash, Suma; Perzynski, Adam T; Austin, Peter C; Wu, C Fangyun; Lawless, Mary Ellen; Paterson, J Michael; Quinn, Rob R; Sehgal, Ashwini R; Oliver, Matthew James

2013-10-01

The objective of this study was to evaluate the association between neighborhood socioeconomic status and barriers to peritoneal dialysis eligibility and choice. This study was a mixed methods parallel design study using quantitative and qualitative data from a prospective clinical database of ESRD patients. The eligibility and choice cohorts were assembled from consecutive incident chronic dialysis patients entering one of five renal programs in the province of Ontario, Canada, between January 1, 2004 and December 31, 2010. Socioeconomic status was measured as median household income and percentage of residents with at least a high school education using Statistics Canada dissemination area-level data. Multivariable models described the relationship between socioeconomic status and likelihood of peritoneal dialysis eligibility and choice. Barriers to peritoneal dialysis eligibility and choice were classified into qualitative categories using the thematic constant comparative approach. The peritoneal dialysis eligibility and choice cohorts had 1314 and 857 patients, respectively; 65% of patients were deemed eligible for peritoneal dialysis, and 46% of eligible patients chose peritoneal dialysis. Socioeconomic status was not a significant predictor of peritoneal dialysis eligibility or choice in this study. Qualitative analyses identified 16 barriers to peritoneal dialysis choice. Patients in lower- versus higher-income Statistics Canada dissemination areas cited built environment or space barriers to peritoneal dialysis (4.6% versus 2.7%) and family or social support barriers (8.3% versus 3.5%) more frequently. Peritoneal dialysis eligibility and choice were not associated with socioeconomic status. However, socioeconomic status may influence specific barriers to peritoneal dialysis choice. Additional studies to determine the effect of targeting interventions to specific barriers to peritoneal dialysis choice in low socioeconomic status patients on peritoneal dialysis use are needed.

Effects of Climatic Region on Peritonitis Risk, Microbiology, Treatment, and Outcomes: a Multicenter Registry Study

PubMed Central

Cho, Yeoungjee; Badve, Sunil V.; Hawley, Carmel M.; McDonald, Stephen P.; Brown, Fiona G.; Boudville, Neil; Wiggins, Kathryn J.; Bannister, Kym M.; Clayton, Philip; Johnson, David W.

2013-01-01

♦ Background: The impact of climatic variations on peritoneal dialysis (PD)-related peritonitis has not been studied in detail. The aim of the current study was to determine whether various climatic zones influenced the probability of occurrence or the clinical outcomes of peritonitis. ♦ Methods: Using ANZDATA registry data, the study in cluded all Australian patients receiving PD between 1 October 2003 and 31 December 2008. Climatic regions were defined according to the Köppen classification. ♦ Results: The overall peritonitis rate was 0.59 episodes per patient-year. Most of the patients lived in Temperate regions (65%), with others residing in Subtropical (26%), Tropical (6%), and Other climatic regions (Desert, 0.6%; Grassland, 2.3%). Compared with patients in Temperate regions, those in Tropical regions demonstrated significantly higher overall peritonitis rates and a shorter time to a first peritonitis episode [adjusted hazard ratio: 1.15; 95% confidence interval (CI): 1.01 to 1.31]. Culture-negative peritonitis was significantly less likely in Tropical regions [adjusted odds ratio (OR): 0.42; 95% CI: 0.25 to 0.73]; its occurrence in Subtropical and Other regions was comparable to that in Temperate regions. Fungal peritonitis was independently associated with Tropical regions (OR: 2.18; 95% CI: 1.22 to 3.90) and Other regions (OR: 3.46; 95% CI: 1.73 to 6.91), where rates of antifungal prophylaxis were also lower. Outcomes after first peritonitis episodes were comparable in all groups. ♦ Conclusions: Tropical regions were associated with a higher overall peritonitis rate (including fungal peritonitis) and a shorter time to a first peritonitis episode. Augmented peritonitis prophylactic measures such as antifungal therapy and exit-site care should be considered in PD patients residing in Tropical climates. PMID:22942270

Effect of the Dialysis Fluid Buffer on Peritoneal Membrane Function in Children

PubMed Central

Nau, Barbara; Gemulla, Gita; Bonzel, Klaus E.; Hölttä, Tuula; Testa, Sara; Fischbach, Michel; John, Ulrike; Kemper, Markus J.; Sander, Anja; Arbeiter, Klaus; Schaefer, Franz

2013-01-01

Summary Background and objectives Double-chamber peritoneal dialysis fluids exert less toxicity by their neutral pH and reduced glucose degradation product content. The role of the buffer compound (lactate and bicarbonate) has not been defined in humans. Design, setting, participants, & measurements A multicenter randomized controlled trial in 37 children on automated peritoneal dialysis was performed. After a 2-month run-in period with conventional peritoneal dialysis fluids, patients were randomized to neutral-pH, low-glucose degradation product peritoneal dialysis fluids with 35 mM lactate or 34 mM bicarbonate content. Clinical and biochemical monitoring was performed monthly, and peritoneal equilibration tests and 24-hour clearance studies were performed at 0, 3, 6, and 10 months. Results No statistically significant difference in capillary blood pH, serum bicarbonate, or oral buffer supplementation emerged during the study. At baseline, peritoneal solute equilibration and clearance rates were similar. During the study, 4-hour dialysis to plasma ratio of creatinine tended to increase, and 24-hour dialytic creatinine and phosphate clearance increased with lactate peritoneal dialysis fluid but not with bicarbonate peritoneal dialysis fluid. Daily net ultrafiltration, which was similar at baseline (lactate fluid=5.4±2.6 ml/g glucose exposure, bicarbonate fluid=4.9±1.9 ml/g glucose exposure), decreased to 4.6±1.0 ml/g glucose exposure in the lactate peritoneal dialysis fluid group, whereas it increased to 5.1±1.7 ml/g glucose exposure in the bicarbonate content peritoneal dialysis fluid group (P=0.006 for interaction). Conclusions When using biocompatible peritoneal dialysis fluids, equally good acidosis control is achieved with lactate and bicarbonate buffers. Improved long-term preservation of peritoneal membrane function may, however, be achieved with bicarbonate-based peritoneal dialysis fluids. PMID:23124784

Is Peritonitis Risk Increased in Elderly Patients on Peritoneal Dialysis? Report from the French Language Peritoneal Dialysis Registry (RDPLF).

PubMed

Duquennoy, Simon; Béchade, Clémence; Verger, Christian; Ficheux, Maxence; Ryckelynck, Jean-Philippe; Lobbedez, Thierry

2016-01-01

♦ This study was carried out to examine whether or not elderly patients on peritoneal dialysis (PD) had an increased risk of peritonitis. ♦ This was a retrospective cohort study based on data from the French Language Peritoneal Dialysis Registry. We analyzed 8,396 incident patients starting PD between January 2003 and December 2010. The end of the observation period was 31 December 2012. Patients were separated into 2 age groups: up to 75 and over of 75 years old. ♦ Among 8,396 patients starting dialysis there were 3,173 patients older than 75. When using a Cox model, no association was found between age greater than 75 years and increased risk of peritonitis (hazard ratio [HR]: 0.97 [0.88 - 1.07]). Diabetes (HR: 1.14 [1.01 - 1.28] and continuous ambulatory PD (HR: 1.13 [1.04 - 1.23]) were significantly associated with a higher risk of peritoneal infection whereas nurse-assisted PD was associated with a lower risk of peritonitis (HR: 0.85 [0.78 - 0.94]. In the analysis restricted to the 3,840 self-care PD patients, there was no association between age older than 75 years and risk of peritonitis. ♦ The risk of peritonitis is not increased in elderly patients on PD in a country where assisted PD is available. Copyright © 2016 International Society for Peritoneal Dialysis.

Peritonitis as the First Presentation of Disseminated Listeriosis in a Patient on Peritoneal Dialysis-a Case Report.

PubMed

Beckerleg, Weiwei; Keskar, Vaibhav; Karpinski, Jolanta

2017-01-01

Infections with Listeria monocytogenes are uncommon but serious, with mortality rate approaching 30% in cases of systemic involvement despite first-line therapy. They are usually caused by ingestion of contaminated foods, but spontaneous infections have also been described. Listeria monocytogenes is a rare cause of peritonitis, and most of the published cases are in patients with cirrhosis and ascites. There are a few reported cases of Listeria peritonitis associated with peritoneal dialysis (PD), primarily isolated peritonitis.If detected early, Listeria peritonitis can be successfully treated with ampicillin, alone or in combination with gentamicin. Vancomycin has been listed as a second-line agent. However, it has been associated with treatment failure.In this case report, we present a patient who developed disseminated listeriosis, with peritonitis as the first manifestation of disseminated infection. This case illustrates the importance of having a high index of suspicion for L. monocytogenes if patients deteriorate despite empiric therapy for PD-associated peritonitis and serves as a further example demonstrating the inadequate coverage of vancomycin for L. monocytogenes . Copyright © 2017 International Society for Peritoneal Dialysis.

Peritoneal Dialysis

MedlinePlus

... include: Infections. An infection of the abdominal lining (peritonitis) is a common complication of peritoneal dialysis. An ... day. You might have a lower risk of peritonitis because you connect and disconnect to the dialysis ...

Multidirectional approach to study peritoneal dialysis fluid biocompatibility in a chronic peritoneal dialysis model in the rat.

PubMed

Wieczorowska-Tobis, K; Polubinska, A; Wisniewska, J; Pawlaczyk, K; Kuzlan-Pawlaczyk, M; Filas, V; Breborowicz, A; Oreopoulos, D G

2001-03-01

Peritoneal dialysis causes the functional and morphological changes in the peritoneum that result from the bioincompatibility of dialysis solutions. We present a model of chronic peritoneal dialysis in the rat that can be used for testing the biocompatibility of dialysis fluids. Methods and Results. Long-term exposure of the peritoneum to dialysis solutions can be performed in rats with implanted peritoneal catheters. Sampling of the dialysate allows the evaluation of intraperitoneal inflammation by examining cell differential and dialysate cytokine levels. Peritoneal permeability can be evaluated at designed time intervals with the peritoneal equilibration test (PET). At the end of dialysis, peritoneal histology is studied with light and electron microscopy. Such a multidirectional approach is an effective way to test biocompatibility of dialysis solutions.

Factors effective on peritoneal phosphorus transport and clearance in peritoneal dialysis patients
.

PubMed

Cebeci, Egemen; Gursu, Meltem; Uzun, Sami; Karadag, Serhat; Kazancioglu, Rumeyza; Ozturk, Savas

2017-02-01

Transport characteristics of phosphorus are different from other small solutes that are evaluated in routine peritoneal equilibration test (PET) in peritoneal dialysis (PD) patients. We aimed to evaluate peritoneal phosphorus clearance and permeability, and their relationship with peritoneal membrane transport type and creatinine clearance as well as factors affecting peritoneal phosphorus clearance. 70 adult patients on a PD program were included in our study. Phosphorus transport status was classified according to dialysate/plasma (D/P) phosphorus at the 4^th hour of PET as slow transporter (< 0.47), slow-average transporter (0.47 - 0.56), fast-average transporter (0.57 - 0.67), and fast transporter (> 0.67). We evaluated the relationship of peritoneal phosphorus clearance and transport type with PD regime, phosphorus level, and presence of residual renal function in addition to investigating factors that are effective on peritoneal phosphorus clearance. D/P phosphorus and peritoneal phosphorus clearance were positively correlated with D/P creatinine and peritoneal creatinine clearance, respectively. Automated PD and continuous ambulatory PD patients were similar regarding phosphorus and creatinine clearances and transport status based on D/P phosphorus. The major determinant of peritoneal phosphorus clearance was anuria status. Anuric patients had higher dialysate volume (11.6 ± 3.0 L vs. 8.4 ± 2.1 L, p < 0.001) and therefore higher peritoneal phosphorus clearance (61.7 ± 15.1 L/week/1.73 m² vs. 48.4 ± 14.0 L/week/1.73 m², p = 0.001). Hyperphosphatemia was present in 40% and 11% of anuric patients and those with residual renal function, respectively (p = 0.005). Peritoneal phosphorus transport characteristics are similar to that of creatinine. Although increased dialysis dose may increase peritoneal phosphorus clearance, it may be insufficient to prevent hyperphosphatemia in anuric patients.
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Improved Outcome of Enteric Peritonitis in Peritoneal Dialysis Patients Aged 50 Years and Older with Temporary Discontinuation of Peritoneal Dialysis and Intravenous Meropenem.

PubMed

Abrahams, Alferso C; Rüger, Wim; Ter Wee, Pieter M; van Ittersum, Frans J; Boer, Walther H

2017-01-01

♦ BACKGROUND: Peritonitis is a major cause of morbidity, mortality, and technique failure in peritoneal dialysis (PD) patients, especially when caused by enteric microorganisms (EM). We have implemented a treatment protocol specifically aimed at improving the outcome in EM peritonitis. The adapted protocol was applied in all PD patients 50 years and older presenting with peritonitis who were considered to be at risk of EM peritonitis and involves 3 interventions: 1) temporary discontinuation of PD without removing the catheter (peritoneal rest), 2) intravenous meropenem, and 3) meropenem intracatheter as lock (Mero-PerRest protocol). ♦ METHODS: In this observational study, we compared the outcome of 203 peritonitis episodes in 71 patients treated with the Mero-PerRest protocol, with 217 episodes in 104 patients treated with a more traditional intraperitoneal gentamicin-rifampicin-based regimen. ♦ RESULTS: In EM peritonitis episodes, the Mero-PerRest protocol resulted in a higher primary cure rate (90.0% vs 65.3%, adjusted odds ratio [OR] 4.54 [95% confidence interval (CI) 1.46 - 14.15]) and better technique survival (90.0% vs 69.4%, adjusted OR 3.41 [95% CI 1.07 - 10.87]). This effect was most distinct in patients with polymicrobial EM peritonitis (cure rate 87.5% vs 34.8%, p = 0.0003). Interestingly, primary cure rate (95.6% vs 84.7%, adjusted OR 3.92 [95% CI 1.37 - 11.19]) and technique survival (95.6% vs 85.6%, adjusted OR 3.60 [95% CI 1.25 - 10.32]) were also excellent in non-EM peritonitis episodes. Patient survival did not differ significantly. ♦ CONCLUSION: The poor outcome of peritonitis caused by EM in PD patients aged 50 years and older could be improved by applying a treatment protocol involving temporary discontinuation of PD without catheter removal and intravenous and intracatheter meropenem. Copyright © 2017 International Society for Peritoneal Dialysis.

Prophylactic Antibiotics for Endoscopy-Associated Peritonitis in Peritoneal Dialysis Patients

PubMed Central

Wu, Hsin-Hsu; Li, I-Jung; Weng, Cheng-Hao; Lee, Cheng-Chia; Chen, Yung-Chang; Chang, Ming-Yang; Fang, Ji-Tseng; Hung, Cheng-Chieh; Yang, Chih-Wei; Tian, Ya-Chung

2013-01-01

Introduction Continuous ambulatory peritoneal dialysis (CAPD) peritonitis may develop after endoscopic procedures, and the benefit of prophylactic antibiotics is unclear. In the present study, we investigated whether prophylactic antibiotics reduce the incidence of peritonitis in these patients. Patients and methods We retrospectively reviewed all endoscopic procedures, including esophagogastroduodenoscopy (EGD), colonoscopy, sigmoidoscopy, cystoscopy, hysteroscopy, and hysteroscopy-assisted intrauterine device (IUD) implantation/removal, performed in CAPD patients at Chang Gung Memorial Hospital, Taiwan, between February 2001 and February 2012. Results Four hundred and thirty-three patients were enrolled, and 125 endoscopies were performed in 45 patients. Eight (6.4%) peritonitis episodes developed after the examination. Antibiotics were used in 26 procedures, and none of the patients had peritonitis (0% vs. 8.1% without antibiotic use; p = 0.20). The peritonitis rate was significantly higher in the non-EGD group than in the EGD group (15.9% [7/44] vs. 1.2% [1/81]; p<0.005). Antibiotic use prior to non-EGD examinations significantly reduced the endoscopy-associated peritonitis rate compared to that without antibiotic use (0% [0/16] vs. 25% [7/28]; p<0.05). Peritonitis only occurred if invasive procedures were performed, such as biopsy, polypectomy, or IUD implantation, (noninvasive procedures, 0% [0/20] vs. invasive procedures, 30.4% [7/23]; p<0.05). No peritonitis was noted if antibiotics were used prior to examination with invasive procedures (0% [0/10] vs. 53.8% [7/13] without antibiotic use; p<0.05). Although not statistically significant, antibiotics may play a role in preventing gynecologic procedure-related peritonitis (antibiotics, 0% [0/4] vs. no antibiotics, 55.6% [5/9]; p = 0.10). Conclusion Antibiotic prophylaxis significantly reduced endoscopy-associated PD peritonitis in the non-EGD group. Endoscopically assisted invasive procedures, such as biopsy, polypectomy, IUD implantation/removal, and dilatation and curettage (D&C), pose a high risk for peritonitis. Prophylactic antibiotics for peritonitis prevention may be required in colonoscopic procedures and gynecologic procedures. PMID:23936514

High-fat enteral nutrition reduces intestinal mucosal barrier damage after peritoneal air exposure.

PubMed

Tan, Shan-Jun; Yu, Chao; Yu, Zhen; Lin, Zhi-Liang; Wu, Guo-Hao; Yu, Wen-Kui; Li, Jie-Shou; Li, Ning

2016-05-01

Peritoneal air exposure is needed in open abdominal surgery, but long-time exposure could induce intestinal mucosal barrier dysfunction followed by many postoperative complications. High-fat enteral nutrition can ameliorate intestinal injury and improve intestinal function in many gastrointestinal diseases. In the present study, we investigated the effect of high-fat enteral nutrition on intestinal mucosal barrier after peritoneal air exposure and the underlying mechanism. Male adult rats were administrated saline, low-fat or high-fat enteral nutrition via gavage before and after peritoneal air exposure for 3 h. Rats undergoing anesthesia without laparotomy received saline as control. Twenty four hours after surgery, samples were collected to assess intestinal mucosal barrier changes in serum D-lactate levels, intestinal permeability, intestinal tight junction protein ZO-1 and occludin levels, and intestinal histopathology. The levels of malondialdehyde and the activity of superoxide dismutase in the ileum tissue were also measured to assess the status of intestinal oxidative stress. High-fat enteral nutrition significantly decreased the serum D-lactate level and increased the intestinal tight junction protein ZO-1 level when compared to the group treated with low-fat enteral nutrition (P < 0.05). Meanwhile, histopathologic findings showed that the intestinal mucosal injury assessed by the Chiu's score and the intestinal epithelial tight junction were also improved much more in the high-fat enteral nutrition-treated group (P < 0.05). In addition, the intestinal malondialdehyde level was lower, and the intestinal superoxide dismutase activity was higher in the high-fat enteral nutrition-treated group than that in the low-fat enteral nutrition-treated group (P < 0.05). These results suggest that high-fat enteral nutrition could reduce intestinal mucosal barrier damage after peritoneal air exposure, and the underlying mechanism may be associated with its antioxidative action. Perioperative administration of high-fat enteral nutrition may be a promising intervention to preserve intestinal mucosal barrier function in open abdominal surgery. Copyright © 2016 Elsevier Inc. All rights reserved.

Indication for peritoneal biopsy in tuberculous peritonitis.

PubMed

Chow, Kai Ming; Chow, Viola Chi-Ying; Szeto, Cheuk Chun

2003-06-01

With the introduction of effective antituberculous chemotherapy, the clinical outcome of tuberculous peritonitis depends much on the diagnostic accuracy of this disease entity. This review summarizes the current state-of-the-art thinking regarding the protean manifestation and diagnostic modalities of this major infectious disease. This review was compiled after an extensive search of the current and historical literature, comprising 1,070 cases of tuberculous peritonitis. A number of important areas were highlighted, with emphasis on the diagnostic value and clinical impact of peritoneal biopsy. We believe an aggressive diagnostic approach, particularly with peritoneal biopsy, is warranted for the diagnosis and timely treatment of tuberculous peritonitis.

Novel Approaches for Targeting Antiviral Agents in the Treatment of Arena-, Bunya-, Flavi-, and Retroviral Infection

DTIC Science & Technology

1991-08-01

Group 3 on days 2, 4, and 6; and Group 4 on days 2, 4, 6 and 8. An additional group of mice was injected with Propionibacterium acnes (70 mg/kg) as a...with P. acnes exhibited the expected anti-tumor cytotoxic activity (data not shown). Similar results were obtained with CL 246738 (Table 14). C.2.1.4...nor liposome encapsulated drug was able to render peritoneal macrophages cytotoxic. In contrast P. acnes was highly effective. C.2.3.13 Peritoneal

Does the risk of peritoneal dialysis-associated peritonitis vary by time on treatment?

PubMed

Perl, Jeffrey; Parpia, Sameer; Nessim, Sharon J

2016-04-01

Early retraining of patients/caregivers at 3 months after peritoneal dialysis (PD) initiation is recommended to prevent peritonitis. We sought to better understand if the risk of peritonitis was highest early after the initiation of PD and if the risk varied by time on therapy and by organism. Using the multicenter Canadian Baxter POET database, we studied 4,247 incident PD patients. Time on dialysis was divided into 3-month intervals over the first 2 years on PD, with 0 - 3 months serving as the reference period. After creating several organism categories (all organisms, coagulase-negative staphylococcus (CNS), Staphylococcus aureus, streptococcus, Gramnegative, culture-negative, and yeast), time to first peritonitis was analyzed by Kaplan-Meier analysis and using smooth hazard plots. The risk of peritonitis for each of these categories over time was then analyzed in a multivariable model after adjusting for potential confounding variables. The overall risk of peritonitis (all organisms) was greatest in the first 3 months on PD compared with all subsequent 3-month intervals (p = 0.001). Organism-specific analyses revealed an increased risk of culture-negative peritonitis in the first 3 months (p < 0.001) but no increased risk of CNS peritonitis or any of the other pre-specified organism categories. The overall risk of peritonitis was greatest in the first 3 months on PD and was largely driven by an increased risk of culture-negative peritonitis but not by CNS. Better understanding of this increased early peritonitis risk is warranted in order to develop strategies aimed at its prevention.

Peritoneal dialysis peritonitis by anaerobic pathogens: a retrospective case series

PubMed Central

2013-01-01

Background Bacterial infections account for most peritoneal dialysis (PD)-associated peritonitis episodes. However, anaerobic PD peritonitis is extremely rare and intuitively associated with intra-abdominal lesions. In this study, we examined the clinical characteristics of PD patients who developed anaerobic peritonitis. Methods We retrospectively identified all anaerobic PD peritonitis episodes from a prospectively collected PD registry at a single center between 1990 and 2010. Only patients receiving more than 3 months of PD were enrolled. We analyzed clinical features as well as outcomes of anaerobic PD peritonitis patients. Results Among 6 patients, 10 episodes of PD-associated peritonitis were caused by anaerobic pathogens (1.59% of all peritonitis episodes during study the period), in which the cultures from 5 episodes had mixed growth. Bacteroides fragilis was the most common species identified (4 isolates). Only 3 episodes were associated with gastrointestinal lesions, and 4 episodes were related to a break in sterility during exchange procedures. All anaerobic pathogens were susceptible to clindamycin and metronidazole, but penicillin resistance was noted in 4 isolates. Ampicillin/sulbactam resistance was found in 2 isolates. In 5 episodes, a primary response was achieved using the first-generation cephalosporin and ceftazidime or aminoglycoside. In 3 episodes, the first-generation cephalosporin was replaced with aminoglycosides. Tenckhoff catheter removal was necessary in 2 episodes. Only one episode ended with mortality (due to a perforated bowel). Conclusion Anaerobic PD-associated peritonitis might be predominantly caused by contamination, rather than intra-abdominal events. Half of anaerobic PD-associated peritonitis episodes had polymicrobial growth. The overall outcome of anaerobic peritonitis is fair, with a high catheter survival rate. PMID:23705895

Neutral Solution Low in Glucose Degradation Products Is Associated with Less Peritoneal Fibrosis and Vascular Sclerosis in Patients Receiving Peritoneal Dialysis

PubMed Central

Kawanishi, Kunio; Honda, Kazuho; Tsukada, Misao; Oda, Hideaki; Nitta, Kosaku

2013-01-01

♦ Background: The effects of novel biocompatible peritoneal dialysis (PD) solutions on human peritoneal membrane pathology have yet to be determined. Quantitative evaluation of human peritoneal biopsy specimens may reveal the effects of the new solutions on peritoneal membrane pathology. ♦ Methods: Peritoneal specimens from 24 PD patients being treated with either acidic solution containing high-glucose degradation products [GDPs (n = 12)] or neutral solution with low GDPs (n = 12) were investigated at the end of PD. As controls, pre-PD peritoneal specimens, obtained from 13 patients at PD catheter insertion, were also investigated. The extent of peritoneal fibrosis, vascular sclerosis, and advanced glycation end-product (AGE) accumulation were evaluated by quantitative or semi-quantitative methods. The average densities of CD31-positive vessels and podoplanin-positive lymphatic vessels were also determined. ♦ Results: Peritoneal membrane fibrosis, vascular sclerosis, and AGE accumulation were significantly suppressed in the neutral group compared with the acidic group. The neutral group also showed lower peritoneal equilibration test scores and preserved ultrafiltration volume. The density of blood capillaries, but not of lymphatic capillaries, was significantly increased in the neutral group compared with the acidic and pre-PD groups. ♦ Conclusions: Neutral solutions with low GDPs are associated with less peritoneal membrane fibrosis and vascular sclerosis through suppression of AGE accumulation. However, contrary to expectation, blood capillary density was increased in the neutral group. The altered contents of the new PD solutions modified peritoneal membrane morphology and function in patients undergoing PD. PMID:23123670

Non-compliance to the continuous ambulatory peritoneal dialysis procedure increases the risk of peritonitis.

PubMed

Mawar, Shashi; Gupta, Sanjay; Mahajan, Sandeep

2012-08-01

Peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) is the leading cause of technique failure. Information on the impact of non-compliance in performing CAPD exchange on peritonitis is limited. We aimed to find the prevalence of non-compliance to the CAPD procedure and its influence on the incidence of peritonitis. This observational study included 30 adult patients undergoing CAPD. The CAPD exchange procedure was observed at home and assessed as per the structured checklist and categorized into poor, average and good compliance. The compliance was correlated with the episodes of peritonitis in previous 1 year. The patients' mean age was 52 ± 13 years and the mean duration of CAPD was 2.1 ± 0.9 years. Only 16.5% of patients were good performers, while 67% were average performers, and 16.5% were poor performers. The technique skill was similar across all the steps of the procedure. The most common improperly performed steps were: not putting on a face mask in 68%, not flushing the tubing system in 60%, and not washing hands in 24%. Poor adherence to procedure was independent of age, gender, education and duration of dialysis. Ten episodes of peritonitis occurred in 5 patients over 1-year period. Peritonitis occurred in 60% of poor performers, whereas fully compliant patients had no peritonitis. Also 40% of the poorly compliant patients had multiple episodes of peritonitis. Poor compliance in performing the CAPD procedure is a modifiable risk factor for peritonitis. Adherence to recommended aseptic technique is the cornerstone of peritonitis prevention.

Morinda citrifolia Linn. fruit (Noni) juice induces an increase in NO production and death of Leishmania amazonensis amastigotes in peritoneal macrophages from BALB/c.

PubMed

Almeida-Souza, Fernando; de Souza, Celeste da Silva Freitas; Taniwaki, Noemi Nosomi; Silva, João José Mendes; de Oliveira, Renata Mondêgo; Abreu-Silva, Ana Lúcia; Calabrese, Kátia da Silva

2016-08-31

Leishmaniasis is a complex disease that is considered a serious public health problem. Due to the absence of an effective vaccine and debilitating chemotherapy better therapies are urgently needed. This situation has stimulated the search for alternative treatments such as the use of herbal medicines. Several studies conducted with Morinda citrifolia Linn. have shown various biological activities such as antitumor, immunomodulation and antileishmanial activity, however its mechanisms of action are still unknown. This study aimed to analyze the activity of M. citrifolia fruit juice against Leishmania amazonensis and its action on peritoneal macrophages from BALB/c infected with L. amazonensis. Activity against the promastigote forms showed IC50 at 275.3 μg/mL. Transmission electron microscopy was used to evaluate the ultrastructural alterations in the promastigotes treated with the juice and the results showed cytoplasmic vacuolization, lipid inclusion and increased activity of exocytosis. The juice treatment presented an IC50 at 208.4 μg/mL against intracellular amastigotes and led to an increased nitrite production in infected and non-infected macrophages. When macrophages were pre-treated with iNOS inhibitors, aminoguanidine or 1400W, the intracellular amastigotes increased, demonstrating the important role of NO production in M. citrifolia fruit activity. In conclusion, our results reveal that treatment with M. citrifolia fruit juice can increase NO production in peritoneal macrophages and this ability has an important role in the killing of L. amazonensis intracellular amastigotes. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone marrow-derived cultured mast cells and peritoneal mast cells as targets of a growth activity secreted by BALB/3T3 fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jozaki, K.; Kuriu, A.; Hirota, S.

1991-03-01

When fibroblast cell lines were cultured in contact with bone marrow-derived cultured mast cells (CMC), both NIH/3T3 and BALB/3T3 cell lines supported the proliferation of CMC. In contrast, when contact between fibroblasts and CMC was prohibited by Biopore membranes or soft agar, only BALB/3T3 fibroblasts supported CMC proliferation, suggesting that BALB/3T3 but not NIH/3T3 cells secreted a significant amount of a mast cell growth activity. Moreover, the BALB/3T3-derived growth activity induced the incorporation of (3H)thymidine by CMC and the clonal growth of peritoneal mast cells in methylcellulose. The mast cell growth activity appeared to be different from interleukin 3 (IL-3)more » and interleukin 4 (IL-4), because mRNAs for these interleukins were not detectable in BALB/3T3 fibroblasts. Although mast cells are genetically deficient in tissues of W/Wv mice, CMC did develop when bone marrow cells of W/Wv mice were cultured with pokeweed mitogen-stimulated spleen cell-conditioned medium. Because BALB/3T3 fibroblast-conditioned medium (BALB-FCM) did not induce the incorporation of (3H)thymidine by W/Wv CMC, the growth activity in BALB-FCM appeared to be a ligand for the receptor encoded by the W (c-kit) locus. Because CMC and peritoneal mast cells are obtained as homogeneous suspensions rather easily, these cells may be potentially useful as targets for the fibroblast-derived mast cell growth activity.« less

IGFBP-2 Vaccine and Combination Chemotherapy in Treating Patients With Stage III-IV Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Undergoing Surgery

ClinicalTrials.gov

2018-05-01

Stage III Fallopian Tube Cancer; Stage III Ovarian Cancer; Stage III Primary Peritoneal Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

Sunitinib Malate in Treating Patients With Recurrent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

ClinicalTrials.gov

2015-01-15

Recurrent Fallopian Tube Cancer; Recurrent Ovarian Epithelial Cancer; Recurrent Primary Peritoneal Cavity Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Primary Peritoneal Cavity Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Primary Peritoneal Cavity Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Primary Peritoneal Cavity Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Primary Peritoneal Cavity Cancer

Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-β1, and vascular endothelial growth factor.

PubMed

Abrahams, Alferso C; Habib, Sayed M; Dendooven, Amélie; Riser, Bruce L; van der Veer, Jan Willem; Toorop, Raechel J; Betjes, Michiel G H; Verhaar, Marianne C; Watson, Christopher J E; Nguyen, Tri Q; Boer, Walther H

2014-01-01

Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P < 0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P < 0.001), TGFβ1 (24-fold, P < 0.05), and VEGF (77-fold, P < 0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0 ± 4.5 vs. 0.91 ± 0.92 ng/ml, P < 0.01), while plasma CCN2 levels were not increased. Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study.

Patients with Encapsulating Peritoneal Sclerosis Have Increased Peritoneal Expression of Connective Tissue Growth Factor (CCN2), Transforming Growth Factor-β1, and Vascular Endothelial Growth Factor

PubMed Central

Abrahams, Alferso C.; Habib, Sayed M.; Dendooven, Amélie; Riser, Bruce L.; van der Veer, Jan Willem; Toorop, Raechel J.; Betjes, Michiel G. H.; Verhaar, Marianne C.; Watson, Christopher J. E.; Nguyen, Tri Q.; Boer, Walther H.

2014-01-01

Introduction Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Materials and methods Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Results Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P<0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P<0.001), TGFβ1 (24-fold, P<0.05), and VEGF (77-fold, P<0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0±4.5 vs. 0.91±0.92 ng/ml, P<0.01), while plasma CCN2 levels were not increased. Conclusions Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study. PMID:25384022

Escherichia coli Peritonitis in Peritoneal Dialysis: The Prevalence, Antibiotic Resistance and Clinical Outcomes in a South China Dialysis Center

PubMed Central

Feng, Xiaoran; Yang, Xiao; Yi, Chunyan; Guo, Qunying; Mao, Haiping; Jiang, Zongpei; Li, Zhibin; Chen, Dongmei; Cui, Yingpeng; Yu, Xueqing

2014-01-01

♦ Introduction: Escherichia coli (E. coli) peritonitis is a frequent, serious complication of peritoneal dialysis (PD). The extended-spectrum β-lactamase (ESBL)-producing E. coli peritonitis is associated with poorer prognosis and its incidence has been on continuous increase during the last decades. However, the clinical course and outcomes of E. coli peritonitis remain largely unclear. ♦ Methods: All of the E. coli peritonitis episodes that occurred in our dialysis unit from 2006 to 2011 were reviewed. The polymicrobial episodes were excluded. ♦ Results: In total, ninety episodes of monomicrobial E. coli peritonitis occurred in 68 individuals, corresponding to a rate of 0.027 episodes per patient-year. E. coli was the leading cause (59.2%) of monomicrobial gram-negative peritonitis. ESBL-producing strains accounted for 35.5% of E. coli peritonitis. The complete cure rate and treatment failure rate of E. coli peritonitis were 77.8% and 10.0% respectively. Patients with preceding peritonitis had a higher risk of ESBL production as compared to those without peritonitis history [odds ratio (OR): 5.286; 95% confidence interval (CI): 2.018 - 13.843; p = 0.001]. The risk of treatment failure was significantly increased when the patient had a baseline score of Charlson Comorbidity Index (CCI) above 3 (OR: 6.155; 95% CI: 1.198 - 31.612; p = 0.03), or had diabetes mellitus (OR: 8.457; 95% CI: 1.838 - 38.91; p = 0.006), or hypoalbuminemia (≤ 30g/l) on admission (OR: 13.714; 95% CI: 1.602 - 117.428; p = 0.01). Prolonging the treatment course from 2 to 3 weeks or more reduced the risk of relapse and repeat significantly (p < 0.05). ♦ Conclusions: E. coli peritonitis remains a common complication of PD. The clinical outcomes of E. coli peritonitis are relatively favorable despite the high ESBL rate. A history of peritonitis is associated with increased risk for ESBL development. The severity of baseline comorbidities, the presence of diabetes mellitus and hypoalbuminemia at admission are associated with poor outcomes. PMID:24497589

The Association Between Glucose Exposure and the Risk of Peritonitis in Peritoneal Dialysis Patients.

PubMed

van Diepen, Anouk T N; van Esch, Sadie; Struijk, Dirk G; Krediet, Raymond T

♦ Little or no clinical evidence is available on the association between glucose exposure and peritoneal host defense in peritoneal dialysis (PD) patients. The objective of the present study was to quantify the exposure to glucose during the first year on PD and investigate the association with subsequent peritonitis. ♦ We analyzed prospectively collected demographic and peritonitis data from incident adult PD patients between 1990 and 2010. For the present study, we conducted a review of both in- and outpatient medical records of all patients to obtain their day-to-day dialysis schemes during the first year on PD. From these data, the average exposure to glucose was quantified. The exposure was stratified into low- and high-glucose groups based on the median, analyzed per standard deviation and in quartiles. Cox proportional hazard models were used to calculate crude and adjusted hazard ratios (HRs) and 95% confidence intervals for the association between glucose exposure and peritonitis. Adjustments were made for age, sex, primary kidney disease, diabetes mellitus, Davies comorbidity score and the treatment period. ♦ In total, 230 patients were included in the study of whom 151 (66%) experienced a first peritonitis episode. The median follow-up time was 2.6 years (interquartile range [IQR]: 1.9 - 3.8) in the low-glucose group and 3.1 (IQR: 2.1 - 4.2) in the high-glucose group. After adjustment for confounding factors, no association between high glucose exposure and the risk of peritonitis was found (HR: 0.81; 0.55 - 1.17). No association was present when glucose exposure was analyzed per standard deviation (SD) (HR: 0.98; 0.79 - 1.21) or patient quartiles were applied. No association was identified between glucose exposure and severe peritonitis, Staphylococcus aureus peritonitis, or a peritonitis episode that lasted more than 14 days. ♦ Exposure to glucose is not associated with an increased risk of peritonitis. The equilibrium between glycemic harm to peritoneal host defense and detrimental effects of glucose on invading microorganisms may determine the susceptibility to peritoneal infection. Copyright © 2016 International Society for Peritoneal Dialysis.

Benefit of an operating vehicle preventing peritonitis in peritoneal dialysis patients: a retrospective, case-controlled study.

PubMed

Fang, Pan; Lu, Jia; Liu, Ying-Hong; Deng, Hong-Mei; Zhang, Lei; Zhang, Hong-Qing

2018-06-01

Peritonitis, which is one of the leading complications of peritoneal dialysis (PD) worldwide, severely affected morbidity and mortality of the PD patients. Although many efforts have been made to prevent PD-related peritonitis, it seems impossible to prevent it completely. Many causes have been reported to lead to peritonitis, and contamination during bag exchange is one of the important risk factors for peritonitis. Here, we introduce an operating vehicle, which we invented to provide a sterile and safe space for bag exchange. A single-center, retrospective, case-control study was undertaken to determine whether this operating vehicle has a protective role in preventing peritonitis. In total, 462 continuous ambulatory peritoneal dialysis patients were included in this study from October 2014 to March 2017. According to their personal will, these patients chose to use operating vehicle or traditional method during their bag exchange. The demographic, clinical and laboratory data of these patients in the two groups were collected, analyzed and compared. Of 462 patients with home dialysis, operating vehicle group consisted of 61 patients, and control group consisted of 401 patients. In the control group, over 677 patient-years, peritonitis occurred in 69 of 401 patients (17.2%), while in the operating vehicle group, over 60 patient-years, only 4 of 61 patients (6.6%) had episodes of peritonitis. The number of patients suffered from peritonitis was significantly decreased in the operating vehicle group (P = 0.034). Besides, there were a total of 99 episodes of peritonitis, and the rate was 1 episode every 7.2 patient-years in control group and 1 episode every 12 patient-years in the operating vehicle group. There was significant difference between the two groups (0.013). Positive dialysate cultures were obtained in majority of the peritonitis episodes (60.6%). Operating vehicle might help to reduce PD-related peritonitis by preventing contamination during bag exchange. Further studies are still needed to demonstrate the protective role of the operating vehicle in preventing peritonitis.

Increased frequency of human leukocyte antigen-E inhibitory receptor CD94/NKG2A-expressing peritoneal natural killer cells in patients with endometriosis.

PubMed

Galandrini, Ricciarda; Porpora, Maria Grazia; Stoppacciaro, Antonella; Micucci, Federica; Capuano, Cristina; Tassi, Ilaria; Di Felice, Alessia; Benedetti-Panici, Pierluigi; Santoni, Angela

2008-05-01

To analyze the frequency of peritoneal natural killer (NK) cells expressing the human leukocyte antigen (HLA)-E receptor CD94/NKG2A in patients with endometriosis. Case-control study. University hospital. Stage III and stage IV endometriosis, according to the revised American Society for Reproductive Medicine classification, was laparoscopically and histologically confirmed in 11 and 9 patients, respectively; 13 subjects without endometriosis were selected for the control group. Collection of peripheral venous blood, peritoneal fluid, endometriotic tissue, and normal endometrium in subjects undergoing laparoscopy. Surface expression levels of CD94/NKG2A and CD94/NKG2C were detected by three-color cytofluorometric analysis. Semiquantitative HLA-E messenger RNA expression analysis was performed in endometriotic lesions and in eutopic endometrium. NK cell-mediated cytotoxic activity toward HLA-E positive target, DT360 cell line, was also determined. In women with endometriosis, the percentage of CD94/NKG2A-positive peritoneal NK cells was significantly higher than in the control group. The CD94/NKG2A ligand, HLA-E, was detected at high levels in endometriotic tissue as messenger RNA transcript. Target cells bearing HLA-E were resistant to NK cell-mediated lysis in a CD94/NKG2A-dependent manner. Increased expression of CD94/NKG2A in peritoneal NK cells may mediate the resistance of endometriotic tissue to NK cell-mediated lysis, thus contributing to the progression of the disease.

Serum Mannose-binding Lectin in Patients on Peritoneal Dialysis Compared With Healthy Individuals.

PubMed

Akbari, Roghayeh; Najafi, Iraj; Maleki, Suzan; Alizadeh-Navaei, Reza

2016-01-01

The increased susceptibility to infection in patients with end-stage renal disease is probably secondary to the impaired immune defense in uremia. Mannose-binding lectin (MBL) has an important role in host defense through activation of the lectin complement pathway. The aim of this study was to measure serum MBL level in peritoneal dialysis patients and compare it with a healthy group. Seventy peritoneal dialysis patients and 70 healthy individuals were enrolled in this study. Serum MBL levels were measured by an enzyme-linked immunosorbent assay kit using the mannan molecule. In addition, serum C-reactive protein and albumin levels were measured to determine whether there is a correlation between serum MBL level and these two parameters. The mean serum MBL level was 2.32 ± 2.54 µg/mL (range, zero to 6.93 µg/mL) in the patients group and 1.80 ± 2.14 µg/mL (range, zero to 6.97µg/mL) in the control group (P = .19). No significant correlation was detected between age and serum MBL level in either the groups. In the patients group, no significant correlation was found between serum MBL and C-reactive protein levels or MBL and albumin levels. There were no correlation between duration of peritoneal dialysis and MBL or dialysis adequacy and MBL, either. This study did not find MBL deficiency in peritoneal dialysis patients as compared to the healthy individuals.

Cardiac surgery in patients with end-stage renal disease on dialysis.

PubMed

Bäck, Caroline; Hornum, Mads; Møller, Christian Joost Holdflod; Olsen, Peter Skov

2017-12-01

Over the past decade, the number of patients on dialysis and with cardiovascular diseases has steadily increased. This retrospective analysis compares the postoperative mortality after cardiac surgery between patients on hemodialysis and peritoneal dialysis. Between 1998 and 2015, 136 patients with end-stage renal disease initiating dialysis more than one month before surgery underwent cardiac surgery. Demographics, preoperative hemodynamic and biochemical data were collected from the patient records. Vital status and date of death was retrieved from a national register. Hemodialysis was undertaken in 73% and peritoneal dialysis in 22% of patients aged 59.7 ± 12.9 years, mean EuroSCORE 8.6% ± 3.5. Isolated coronary artery bypass graft was performed in 46%, isolated valve procedure in 29% and combined procedures in 24% with no significant statistical difference between groups. The 30-day mortality was 14% for hemodialysis patients and 3% for peritoneal dialysis patients (p = .056). One-year and 5-year mortality were, 30% and 59% in the hemodialysis group, 30% and 57% in the peritoneal dialysis group (p = .975, p = .852). Independent predictors of total mortality were age (p = .001), diabetes (p = .017) and active endocarditis (p = .012). No statistically significant difference in mortality was found between patients in hemo- or peritoneal dialysis. However, we observed that patients with end-stage renal disease on dialysis have two times higher mortality rate than estimated by EuroSCORE.

MicroRNAs Associated with Epithelial-Mesenchymal Transition Can Be Targeted to Inhibit Peritoneal Dissemination of Human Scirrhous Gastric Cancers.

PubMed

Takei, Yoshifumi; Shen, Guodong; Morita-Kondo, Ayami; Hara, Toshifumi; Mihara, Keichiro; Yanagihara, Kazuyoshi

2018-05-30

Scirrhous gastric cancers grow rapidly, and frequently invade the peritoneum. Such peritoneal dissemination properties markedly reduce patient survival. Thus, an effective means for inhibiting peritoneal dissemination is urgently required. We previously established a cell line, HSC-58, from a scirrhous gastric cancer patient, and further successfully isolated a metastatic line, 58As9, in nude mice upon orthotopic inoculation. Using the lines, we examined the mechanism underlying peritoneal dissemination from the viewpoint of microRNA (miRNA) expression. miRNA array and qRT-PCR analysis showed that the expressions of epithelial-mesenchymal transition (EMT)-associated miRNAs such as miR-200c and miR-141 were significantly low in 58As9. Using 58As9 with stably overexpressing miR-200c, miR-141, or both, together with a luciferase reporter assay, we found that miR-200c targeted zinc finger E-box-binding homeobox 1 (ZEB1) and miR-141 targeted ZEB2. The overexpressed lines reversed the EMT status from mesenchymal to epithelial in 58As9, and significantly reduced the invasion activity and peritoneal dissemination for a significant prolongation of survival in the orthotopic tumor models in nude mice. EMT-associated miRNAs such as miR-200c and miR-141 and their target genes ZEB1/ZEB2 have good potential for antiperitoneal dissemination therapy in patients with scirrhous gastric cancers. © 2018 S. Karger AG, Basel.

A case of bacterial peritonitis caused by Roseomonas mucosa in a patient undergoing continuous ambulatory peritoneal dialysis.

PubMed

Matsukuma, Yuta; Sugawara, Koji; Shimano, Shota; Yamada, Shunsuke; Tsuruya, Kazuhiko; Kitazono, Takanari; Higashi, Harumichi

2014-11-01

Bacterial peritonitis remains a life-threatening complication of peritoneal dialysis (PD). Roseomonas is a bacterial genus of pink-pigmented, oxidized, gram-negative coccobacilli that was first named in 1993. Importantly, Roseomonas mucosa exhibits antibiotic resistance, with significant resistance to cephalosporin, which is often selected as an empirical antibiotic regimen for peritonitis in PD patients. We herein report the case of a PD patient with bacterial peritonitis caused by Roseomonas mucosa that was fortunately identified using 16S rRNA gene sequencing and successfully treated with ciprofloxacin. Given that Roseomonas demonstrates resistance to a variety of antibiotics. The administration of empiric antibiotic therapy based on the recommendation of the International Society of Peritoneal Dialysis guidelines occasionally fails, leading to the aggravation of bacterial peritonitis. Hence, nephrologists should consider Roseomonas as one of the potential causative organisms of peritonitis, especially when gram-negative bacilli are resistant to cephalosporin and cannot be identified using standard laboratory methods.

A Novel Mouse Model of Endometriosis Mimics Human Phenotype and Reveals Insights into the Inflammatory Contribution of Shed Endometrium

PubMed Central

Greaves, Erin; Cousins, Fiona L.; Murray, Alison; Esnal-Zufiaurre, Arantza; Fassbender, Amelie; Horne, Andrew W.; Saunders, Philippa T.K.

2015-01-01

Endometriosis is an estrogen-dependent inflammatory disorder characterized by the presence of endometrial tissue outside the uterine cavity. Patients experience chronic pelvic pain and infertility, with the most likely origin of the tissue deposits (lesions) being endometrial fragments shed at menses. Menstruation is an inflammatory process associated with a dramatic increase in inflammatory mediators and tissue-resident immune cells. In the present study, we developed and validated a mouse model of endometriosis using syngeneic menstrual endometrial tissue introduced into the peritoneum of immunocompetent mice. We demonstrate the establishment of endometriotic lesions that exhibit similarities to those recovered from patients undergoing laparoscopy. Specifically, in both cases, lesions had epithelial (cytokeratin+) and stromal (vimentin/CD10+) cell compartments with a well-developed vasculature (CD31+ endothelial cells). Expression of estrogen receptor β was increased in lesions compared with the peritoneum or eutopic endometrium. By performing experiments using mice with green fluorescent protein–labeled macrophages (MacGreen) in reciprocal transfers with wild-type mice, we obtained evidence that macrophages present in the peritoneum and in menses endometrium can contribute to the inflammatory microenvironment of the lesions. In summary, we developed a mouse model of endometriosis that exhibits similarities to human peritoneal lesions with respect to estrogen receptor expression, inflammation, and macrophage infiltration, providing an opportunity for further studies and the possible identification of novel therapies for this perplexing disorder. PMID:24910298