Human Peritonitis Research Articles

Establishment of a novel mouse peritoneal dialysis-associated peritoneal injury model.

Peritoneal fibrosis induced by various factors during peritoneal dialysis (PD) can eventually lead to ultrafiltration failure and termination of PD treatment. The existing animal models are caused by a single stimulus, and cannot accurately simulate complex pathogenesis of peritoneal injury and fibrosis. We aim to develop an efficient and realistic mouse model of PD-associated peritoneal injury using daily intraperitoneal injection (I.P.) of human peritonitis PD effluent. Eight-week-old male C57BL/6 mice were classified into six groups: saline control; 2.5% PD fluid; 2.5% PD fluid + lipopolysaccharide (LPS); 4.25% PD fluid; 4.25% PD fluid + LPS; and peritonitis effluent. Mice received daily I.P. for 6weeks, and were sacrificed to determine peritoneal structural and functional damage, inflammation, and fibrosis. Mice in the peritonitis effluent group had low mortality. The submesothelial thickness in the peritonitis effluent group was significantly greater than that in the 2.5% PD fluid group. The peritonitis effluent group had increased expression of fibrosis markers (α-SMA, Collagen I, etc.), neutrophil granulocytes (MPO), and macrophages (CD68, F4/80) in the peritoneum based on immunohistochemical staining; and significantly higher expression of inflammation markers (IL-1β, IL-6, etc.) and fibrosis markers (TGF-β1, α-SMA, etc.) based on real-time qPCR. Modified peritoneal equilibration tests (PET) demonstrated that I.P. of peritonitis effluent reduced peritoneal ultrafiltration. Our novel animal model of PD-associated peritoneal injury faithfully simulates the clinical pathophysiological process. This animal model may be useful for study of the pathogenesis of PD-associated peritoneal injury and identification of novel treatments.

POS-729 MSC exosomes protect mouse peritoneal injury induced by human peritonitis dialysis effluent

Peritoneal fibrosis is a severe complication of peritoneal dialysis, but there are few effective therapies for it. The purpose of this study was to investigate the protective effect of exosomes secreted by mouse bone marrow mesenchymal stem cells on peritoneal fibrosis and to reveal the mechanism.

Antimicrobial Resistance of Aeromonas Species Isolated from Cultured Indian Major Carp, Labeo rohita: Possible Public Health Concern

In India, Labeo rohita is widely cultured and consumed freshwater fish. Aeromonads are etiological agents of major bacterial fish diseases like furunculosis, haemorrhagic septicaemia, skin ulcers, fin/tail rot and dropsy, causing significant economic losses in carp culture. Aeromonas species are widely distributed in aquatic environment which is considered as important vehicle of Aeromonas infections to fish and humans. Some of the Aeromonas spp. causes gastroenteritis, septicaemia, peritonitis, meningitis and eye infections in humans. In the present study Aeromonas species were isolated from diseased freshwater fish Labeo rohita collected from two districts viz., West Godavari and SPSR Nellore of Andhra Pradesh, India. A Total of 12 Aeromonas spp. were isolated and identified by biochemical tests. A. veronii bv. veronii (35%) was dominant when compared to other Aeromonas spp. Further, Antimicrobial resistance and multiple Antimicrobial resistance (MAR) of all Aeromonas spp. were tested against 17 antibiotics being frequently used for human diseases. The Antimicrobial resistance of all the 12 Aeromonas spp. have shown significantly high (p<0.05) resistance (100%) to ampicillin, amoxyclave and oxytetracycline except A. cavernicola when compared to other antibiotics. The MAR index of Aeromonas spp. ranged from 0.18-0.76, which indicates origination of isolated Aeromonas spp. from high risk sources of contamination. A. hydrophila, A. veronii bv. sobria, A. veronii bv. veronii, A. schubertii and A. jandaei isolated in this study were found to be pathogenic to humans also. The results revealed the pathogenic potential of Aeromonas infections in freshwater fish culture and emerging threats to public health.

FC 098MESENCHYMAL STEM CELL EXOSOMES AMELIORATE MICE PERITONEAL FIBROSIS INDUCED BY HUMAN PERITONITIS DIALYSIS EFFLUENT

Abstract Background and Aims Peritoneal fibrosis is a severe complication of peritoneal dialysis, but there are few effective therapies for it. The purpose of this study was to investigate the protective effect of exosomes secreted by mouse bone marrow mesenchymal stem cells on peritoneal fibrosis and to reveal the mechanism. Method Forty-two male C57BL/6 mice were randomly divided into a normal group, a control group (2.5% glucose dialysate), a peritonitis-effluent group (The overnight 2.5% glucose dialysate of patients with peritonitis), a high glucose dialysate group (4.25% glucose concentration), a peritonitis-dialysate + exosome group, and a high glucose dialysate + exosome group. The mouse model of peritoneal fibrosis was constructed by intraperitoneal injection of human peritonitis effusion continuously for 42 days. The mice in the exosome treatment group received intraperitoneal injection of mesenchymal stem cell (MSC)-exosomes twice. The level of peritoneal structural and functional damage, inflammation, fibrosis and mesothelial cell damage of peritoneum were detected. Furthermore, the effect of MSC-exosomes was validated in vitro. Results Peritoneal transport was significantly impaired and peritoneal thickness was significantly increased in the peritonitis-effluent group and the high glucose dialysate group after 42 days. The degree of peritoneal inflammation and fibrosis in the two groups was significantly higher than the control group. The results suggested that human peritonitis dialysis effluent could be used to construct a mouse model of peritoneal fibrosis. Masson staining results showed that the fibrosis degree of peritonitis - effluent + exosome group was significantly less than the peritonitis - effluent group. Immunohistochemical analysis showed that the expression levels of mesothelial markers E-cadherin and ZO-1, neutrophil granulocytes (MPO) and macrophages (F4/80), and fibrosis markers collagen I and a-SMA in the peritonitis - effluent + exosome group were significantly lower than those in the peritonitis - effluent group. Similarly, the high glucose dialysate + exosome group mice showed significantly lower levels of peritoneal inflammation and fibrosis than the high glucose dialysate group mice. In vitro experiments showed that exosomes could down-regulate the secretion of IL-1, IL-6 and TGF- by renal tubular cells stimulated by high glucose dialysate, maintain the expression of mesenchymal cell marker (E-cadherin), and inhibit the mesenchymal marker (-SMA), suggesting that exosomes could inhibit the transdifferentiation of peritoneal mesenchymal cell-mesenchymal cells (MMT). Conclusion MSC-exosomes can alleviate peritoneal fibrosis by inhibiting peritoneal mesothelial cell-mesenchymal cell transdifferentiation.

The Peritonitis as a Casuistic Clinical Manifestation of the New Coronavirus Disease SARS-CoV-2 COVID-19

Since the announcement of the COVID-19 pandemic (March 11, 2020), the focus of the study of complications of this new coronavirus disease has been on pneumonia and acute respiratory distress syndrome. Meanwhile, with COVID-19, acute abdominal surgical diseases develop, presumably due to the tropism of the COVID-19 virus to angiotensin-converting enzyme receptors in the digestive tract. In principle, previously known coronaviruses could cause infectious peritonitis, however, such cases of coronavirus peritonitis were observed exclusively in animals. In particular, FIPV - coronavirus is the direct cause of feline infectious peritonitis. This article describes a rare, alarming case of serous fibrinous peritonitis as a casuistic manifestation of a new coronavirus infection COVID-19 directly in humans: a 55-year-old female patient. Surgical diseases that could cause the development of this peritonitis in this patient were excluded. The purpose of the article is to point out the possibility of the development of this surgical disease, as a direct complication of the new coronavirus infection COVID-19. The article also presents the author's attempt to explain in general terms the pathogenesis of the development of peritonitis in COVID-19 in humans. Observing the second year of the pandemic, extremely rare mentions in medical scientific articles of cases of primary peritonitis in COVID-19, we can conclude that this complication is not typical in this new infection. However, given the too short period since the emergence of a new coronavirus infection COVID-19 (less than two years), as well as the ability of a new strain of coronavirus to mutate, we can assume that, in principle, the possibility of developing coronavirus peritonitis in humans is not excluded in the future.

1726. Candida albicans Virulence Genes Induced During Intra-abdominal Candidiasis (IAC) in the Absence of Antifungal Exposure Mediate Echinocandin Resistance

BackgroundWe developed and validated a mouse model of C. albicans IAC that mimics peritonitis and abscesses (IAA) in humans, and that is amenable to temporal–spatial transcriptional profiling and virulence studies.MethodsWe measured C. albicans SC5314 gene expression by RNA-Seq (RiboPure extraction; Illumina MiSeq) in triplicate during early peritonitis (within 30 minutes of infection), late peritonitis (24 hours) and IAA (48 hours). Differential expression was defined by ≥2-fold differences at false discovery rate ≤0.01.Results≥7 million C. albicans reads were detected in each experiment. 67% of C. albicans reads mapped to coding sequences, covering 93% of open reading frames. The 50 C. albicans genes most highly expressed during early peritonitis were associated with pH (including RIM101 and PHR1) and oxidative stress responses, and adhesion/hyphal growth (e.g., ALS3, HWP1, ECM331, SAP6). The corresponding 50 C. albicans late peritonitis genes were associated with neutrophil/macrophage responses and nutrient acquisition (glyoxylate cycle, fatty acid β-oxidation, iron homeostasis). Responses within IAA included DNA damage and iron metabolism, reflecting stress response and nutrient/metal limitation. The top 50 core gene responses for all stages were associated with adhesion, stress response, and glucose transport. Among the most up-regulated genes in late peritonitis and IAA compared with early peritonitis were those involved antifungal drug resistance (CDR family, MDR1, FLU1, and ERG family), although mice were not exposed to antifungals. Null and reconstitution mutants for genes involved in adhesion (ALS3), copper transport (CCC2), DNA (DDI1) and cell wall damage responses (DAP1 homologs), and glycerol biosynthesis (RHR2) were attenuated for virulence in temporal-spatial fashion during peritonitis and IAA, and/or hyper-susceptible to phagocytosis and echinocandins (table).Conclusion C. albicans relies upon diverse biologic processes to cause peritonitis and IAA. Multiple genes induced in response to stress during IAC mediate virulence, phagocyte, and echinocandin resistance. Therefore, pathogenic strategies used by C. albicans during IAC may lessen responses to echinocandin treatment, even in the absence of drug exposure or FKS mutations. Disclosures All authors: No reported disclosures.

Bone marrow vs Wharton\u2019s jelly mesenchymal stem cells in experimental sepsis: a comparative study

BackgroundThe use of mesenchymal stem cells (MSCs) is being extensively studied in clinical trials in the setting of various diseases including diabetes, stroke, and progressive multiple sclerosis. The unique immunomodulatory properties of MSCs also point them as a possible therapeutic tool during sepsis and septic shock, a devastating syndrome associated with 30–35% mortality. However, MSCs are not equal regarding their activity, depending on their tissue origin. Here, we aimed at comparing the in vivo properties of MSCs according to their tissue source (bone marrow (BM) versus Wharton’s jelly (WJ)) in a murine cecal ligation and puncture (CLP) model of sepsis that mimics a human peritonitis. We hypothesized that MSC properties may vary depending on their tissue source in the setting of sepsis.MethodsCLP, adult, male, C57BL/6 mice were randomized in 3 groups receiving respectively 0.25 × 106 BM-MSCs, 0.25 × 106 WJ-MSCs, or 150 μL phosphate-buffered saline (PBS) intravenously 24 h after the CLP procedure.ResultsWe observed that both types of MSCs regulated leukocyte trafficking and reduced organ dysfunction, while only WJ-MSCs were able to improve bacterial clearance and survival.ConclusionThis study highlights the importance to determine the most appropriate source of MSCs for a given therapeutic indication and suggests a better profile for WJ-MSCs during sepsis.

TEMPORAL LINKS BETWEEN ENDOTOXIN ACTIVITY LEVELS AND INTERLEUKIN 6 CONCENTRATIONS IN ABDOMINAL SEPSIS.

In severe human peritonitis, the precise pathophysiological importance of endotoxin is controversial. Prognostic and therapeutic studies have yielded conflicting results. The current study wanted to investigate qualitative, quantitative, and temporal associations between blood endotoxin activity (EA) levels and acute inflammatory reactions. We conducted a prospective observational study in 30 patients with intra-abdominal infections who had undergone specific focus therapies (surgical/radiological/pharmaceutical interventions) and who required intensive care therapy. We performed sequential postinterventional measurements of blood EA levels and plasma interleukin 6 (IL-6) concentrations until recurrence or cure. There was no association between daily EA levels and IL-6 concentrations, or daily EA levels and changes in IL-6 concentrations on subsequent days. We found, however, a significant association between EA levels and IL-6 concentrations, when newly changing EA levels were referred to subsequent changes in IL-6 concentrations (P < 0.05). Increasing EA levels were followed by a 90% increase of subsequent IL-6 concentrations during the next 24 to 48 h, whereas decreasing/stable EA levels were associated with slightly decreasing IL-6 concentrations (P < 0.05). Our findings suggest an altered response of the innate immune system because postinterventional EA levels did not vary with concomitant or subsequent inflammatory reactions and because inflammatory responses to newly increasing EA levels were delayed and comparatively small. Still, our results support the concept that endotoxin is a trigger of inflammatory reactions in human peritonitis.

Complete genome and gene expression analyses of Asaia bogorensis reveal unique responses to culture with mammalian cells as a potential opportunistic human pathogen.

Asaia bogorensis, a member of acetic acid bacteria (AAB), is an aerobic bacterium isolated from flowers and fruits, as well as an opportunistic pathogen that causes human peritonitis and bacteraemia. Here, we determined the complete genomic sequence of the As. bogorensis type strain NBRC 16594, and conducted comparative analyses of gene expression under different conditions of co-culture with mammalian cells and standard AAB culture. The genome of As. bogorensis contained 2,758 protein-coding genes within a circular chromosome of 3,198,265 bp. There were two complete operons encoding cytochrome bo3-type ubiquinol terminal oxidases: cyoABCD-1 and cyoABCD-2. The cyoABCD-1 operon was phylogenetically common to AAB genomes, whereas the cyoABCD-2 operon belonged to a lineage distinctive from the cyoABCD-1 operon. Interestingly, cyoABCD-1 was less expressed under co-culture conditions than under the AAB culture conditions, whereas the converse was true for cyoABCD-2. Asaia bogorensis shared pathogenesis-related genes with another pathogenic AAB, Granulibacter bethesdensis, including a gene coding pathogen-specific large bacterial adhesin and additional genes for the inhibition of oxidation and antibiotic resistance. Expression alteration of the respiratory chain and unique hypothetical genes may be key traits that enable the bacterium to survive under the co-culture conditions.

Diagnostic accuracy of a urine reagent strip to identify bacterial peritonitis in dogs with ascites

The leukocyte esterase test pad on a urine dipstick has been used as a preliminary test for bacterial peritonitis in humans but has not previously been evaluated in dogs. Here, free abdominal fluid from 60 dogs was tested on the leukocyte esterase test pad and results were compared with culture and microscopic analysis. Depending on the ‘gold standard’ comparator, the dipstick had sensitivity of ~60–75%, specificity of ~91–92%, positive predictive value of ~69%, and negative predictive value of ~87–94%. Based on these data, it appears that the leukocyte esterase test pad is most useful for tentative identification of cases in which bacterial infection is unlikely. Therefore a negative test may aid in re-directing clinician attention to alternative diagnoses in dogs with free abdominal effusion, whereas a positive result implies the necessity for further diagnostic tests.

Surface receptor CD177/NB1 does not confer a recruitment advantage to neutrophilic granulocytes during human peritonitis

Surface receptor <scp>CD</scp>177/<scp>NB</scp>1 does not confer a recruitment advantage to neutrophilic granulocytes during human peritonitis

Local and systemic innate immune response to secondary human peritonitis

IntroductionOur aim was to describe inflammatory cytokines response in the peritoneum and plasma of patients with peritonitis. We also tested the hypothesis that scenarios associated with worse outcome would result in different cytokine release patterns. Therefore, we compared cytokine responses according to the occurrence of septic shock, mortality, type of peritonitis and peritoneal microbiology.MethodsPeritoneal and plasma cytokines (interleukin (IL) 1, tumor necrosis factor α (TNFα), IL-6, IL-10, and interferon γ (IFNγ)) were measured in 66 patients with secondary peritonitis.ResultsThe concentration ratio between peritoneal fluid and plasma cytokines varied from 5 (2 to 21) (IFNγ) to 1310 (145 to 3888) (IL-1). There was no correlation between plasma and peritoneal fluid concentration of any cytokine. In the plasma, TNFα, IL-6, IFNγ and IL-10 were higher in patients with shock versus no shock and in nonsurvivors versus survivors (P ≤0.03). There was no differential plasma release for any cytokine between community-acquired and postoperative peritonitis. The presence of anaerobes or Enterococcus species in peritoneal fluid was associated with higher plasma TNFα: 50 (37 to 106) versus 38 (29 to 66) and 45 (36 to 87) versus 39 (27 to 67) pg/ml, respectively (P = 0.02). In the peritoneal compartment, occurrence of shock did not result in any difference in peritoneal cytokines. Peritoneal IL-10 was higher in patients who survived (1505 (450 to 3130) versus 102 (9 to 710) pg/ml; P = 0.04). The presence of anaerobes and Enterococcus species was associated with higher peritoneal IFNγ: 2 (1 to 6) versus 10 (5 to 28) and 7 (2 to 39) versus 2 (1 to 6), P = 0.01 and 0.05, respectively).ConclusionsPeritonitis triggers an acute systemic and peritoneal innate immune response with a simultaneous release of pro and anti-inflammatory cytokines. Higher levels of all cytokines were observed in the plasma of patients with the most severe conditions (shock, non-survivors), but this difference was not reflected in their peritoneal fluid. There was always a large gradient in cytokine concentration between peritoneal and plasma compartments highlighting the importance of compartmentalization of innate immune response in peritonitis.

Human CD16+ and CD16– monocyte subsets display unique effector properties in inflammatory conditions in vivo

Two major subsets of human Mo are identified based on CD14 and CD16 expression: the classical CD16(-) Mo and the minor CD14(+)CD16(+) Mo. In vitro studies suggested distinct function and differentiation potential for each cell population. However, the in vivo relevance of these findings remains unclear. To evaluate the development and function of human Mo in an in vivo model, we transferred both Mo subpopulations into the peritoneum of immunocompromised mice in homeostatic or inflammatory conditions. Inflammation was induced with soluble LPS or particulate zymosan. CD16(+) were more phagocytic and produced higher amounts of TNF and IL-6 than CD16(-) Mo early after transfer with zymosan. They also produced higher levels of β2-defensin in any condition evaluated, which could represent a new marker for this subpopulation. In contrast, differentiating CD16(-) Mo (24 h after transfer) acquired greater APC capacity in LPS-induced peritonitis, whereas none of the Mo subsets attained this ability with zymosan. CX(3)CL1 supported the survival of both Mo subsets in vivo. Similar Mo subpopulations were present in human peritonitis. These results support the idea of specialized roles of the Mo subset, where CD16(+) might act in an immediate innate immune response, whereas CD16(-) could have a major role as APCs.

Rare Case of Trichomonal Peritonitis

Rare Case of Trichomonal Peritonitis

Faecal shedding of Arcobacter species following experimental infection in rats: Public health implications

Abstract Arcobacter spp. are emerging food borne pathogens associated with prolonged diarrhea and occasional systemic infections such as bactereamia and peritonitis in humans. Information on faecal shedding patterns to assess the potential role they play within the intestine however, is lacking. This study was designed to investigate faecal shedding of local isolates of Arcobacter spp. Using real time PCR for confirmation, A. cryaerophilus and A. butzleri were isolated from the stool of healthy chickens. Pathogenicity of the organisms was tested by administering a single oral challenge of 102–109 cfu/ml to 45 healthy adult male albino rats divided equally among 5 groups. Uninfected rats were used as the control group. A. cryaerophilus and A. butzleri produced infection in 100% of the animals. Experimental infection was dose dependent and caused diarrheal illness and faecal shedding was noted up to 5 weeks post infection. The present study demonstrates that rats can act as a reservoir and potential source of Arcobacter infection in humans and animals exposed to this pathogen.

Haemagglutination assay of some human and animal arcobacter specie

Arcobacter are emerging food borne enteropathogens which can cause severe diarrhea and occasional systemic infection such as bacteraemia and peritonitis in humans. To understand the pathogenicity of this emerging pathogen, putative adhesive factors in the organism were studied by examining their ability to agglutinate erythrocytes from humans and other animal species. A total of 10 Arcobacter species from which four strains were obtained from humans and one from pigs in France. Five isolates were obtained from stool of healthy pigs and chicken in Nigeria. They were identified and confirmed by phenotypic and PCR techniques. Bacteria cells were washed in PBS by centrifugation. 20 μl of bacteria cells was reacted with equal volume of erythrocytes. Macroscopic haemagglutination was scored as either positive or negative after 5 minutes of mixing at room temperature. To understand the nature of red cell receptor for haemagglutinin, various sugars was used to inhibit previously positive haemagglutination reaction. Fresh cultures of all strains agglutinated erythrocytes from humans (blood group A+), sheep, guinea-pig and chicken. 20μl of all suspension containing 10 cells\ml gave a strong microscopic haemagglutination within 5 minutes after mixing with an equal volume of 3% erythrocytes suspension on a clean microscopic slide. No inhibition was observed with D glucose and mannose on previously positive haemagglutinating strains, but galactose inhibited by the same 50/50% (v|v). The result of this experiment provides a basis for further development of specific immunogen required for a more detailed study of characterization of specific adhesins. Keywords : Arcobacter, Haemagglutination, Adhesive factors, Nigeria

Nonresolving Inflammation in gp91phox−/− Mice, a Model of Human Chronic Granulomatous Disease, Has Lower Adenosine and Cyclic Adenosine 5′-Monophosphate

In chronic granulomatous disease (CGD), there is failure to generate reactive oxygen metabolites, resulting in recurrent infections and persistent inflammatory events. Because responses to sterile stimuli in murine models of CGD also result in nonresolving inflammation, we investigated whether defects in endogenous counterregulatory mechanisms and/or proresolution pathways contribute to the etiology of CGD. To this end, we conducted a series of experiments finding, in the first instance that adenosine and cAMP, which dampen innate immune-mediated responses, show a biphasic profile in resolving peritonitis; peaking at onset, waning as inflammation progresses, and rising again at resolution. We also found elevations in adenosine and cAMP in resolving human peritonitis. In gp91(phox-/-) mice, an experimental model of CGD, levels of adenosine and cAMP were significantly lower at onset and again at resolution. Corroborating the finding of others, we show that adenosine, signaling through its A(2A) receptor and therefore elevating cAMP, is not only anti-inflammatory, but, importantly, it does not impair proresolution pathways, properties typical of nonsteroidal anti-inflammatory drugs. Conversely, antagonizing the A(2A) receptor worsens acute inflammation and prolongs resolution. Taking this further, activating the A(2A) receptor in gp91(phox-/-) mice was dramatically anti-inflammatory regardless of the phase the inflammatory response A(2A) agonists were administered, i.e., onset or resolution, demonstrating wide and robust pharmacological flexibility that is unlikely to subvert proresolution pathways. Therefore, we describe the biphasic profile of adenosine and cAMP throughout the time course of acute inflammation that is dysregulated in CGD.

Novel biphasic role for lymphocytes revealed during resolving inflammation

AbstractAcute inflammation is traditionally described as the influx of polymorphonuclear leukocytes (PMNs) followed by monocyte-derived macrophages, leading to resolution. This is a classic view, and despite subpopulations of lymphocytes possessing innate immune-regulatory properties, seldom is their role in acute inflammation and its resolution discussed. To redress this we show, using lymphocyte-deficient RAG1−/− mice, that peritoneal T/B lymphocytes control PMN trafficking by regulating cytokine synthesis. Once inflammation ensues in normal mice, lymphocytes disappear in response to DP1 receptor activation by prostaglandin D2. However, upon resolution, lymphocytes repopulate the cavity comprising B1, natural killer (NK), γ/δ T, CD4+/CD25+, and B2 cells. Repopulating lymphocytes are dispensable for resolution, as inflammation in RAG1−/− and wild-type mice resolve uniformly. However, repopulating lymphocytes are critical for modulating responses to superinfection. Thus, in chronic granulomatous disease using gp91phox−/− mice, not only is resolution delayed compared with wild-type, but there is a failure of lymphocyte re-appearance predisposing to exaggerated immune responses upon secondary challenge that is rescued by resolution-phase lymphocytes. In conclusion, as lymphocyte repopulation is also evident in human peritonitis, we hereby describe a transition in T/B cells from acute inflammation to resolution, with a central role in modulating the severity of early onset and orchestrating responses to secondary infection.

Structural dynamics of a colloidal protein-mineral complex bestowing on calcium phosphate a high solubility in biological fluids

The concentration of mineral solutes in mammalian blood is considerably higher than that predicted by their solubility product. The plasma protein fetuin-A inhibits calcium phosphate deposition by forming colloidal calciprotein particles (CPPs). In this article the authors present a detailed small angle neutron scattering study including contrast variation analysis providing detailed quantitative information on the three-dimensional topology of the CPPs and on their morphogenesis. In detail the authors found the following: (i) A two stage growth process showing spontaneously formed primary particles with a size of about 500 A diameter that subsequently transformed to 1000 A sized particles which were stable for at least 24 h. (ii) A particular shielding topology was observed for the second CPP state, namely, that a densely packed fetuin-A monolayer covers a mineral core and thereby prevents further crystal growth. (iii) Transmission electron microscopy analysis of in vitro synthesized second state CPPs revealed striking similarities to material retrieved from a human peritonitis patient. This latter finding underscores the importance of short- and long-term stabilizations of CPPs by fetuin-A to enable clearing of mineral debris in the body.

Peritonitis due to Cunninghamella bertholletiae in a patient undergoing continuous ambulatory peritoneal dialysis

Peritoneal dialysis-associated peritonitis due to fungi of the class Zygomycetes occurs very rarely. A case of fungal continuous ambulatory peritoneal dialysis peritonitis due to Cunninghamella bertholletiae is reported in a 39-year-old Aboriginal woman with end-stage renal failure and diabetes mellitus. This isolate was found to be resistant in vitro to amphotericin B, 5-fluorocytosine, fluconazole, itraconazole, ketoconazole and voriconazole. However, this patient was successfully treated with voriconazole and removal of the Tenckhoff dialysis catheter. Zygomycoses are an emerging threat among immunocompromised patients, including those with chronic renal failure. Zygomycosis due to C. bertholletiae is frequently fatal and is often non-responsive to systemic antifungal therapy. This is believed to be the first reported case of C. bertholletiae causing peritonitis in humans and one of the minority of cases involving this organism with a successful outcome.