Explore the vast range of titles available.

The majority of peritoneal dialysates use glucose to generate an osmotic gradient for the convective removal of water and Na. Although glucose can potentially be absorbed, previous studies have failed to establish whether this leads to increased fat weight gain. We measured body composition using bioimpedance in peritoneal dialysis (PD) patients, electively starting PD, attending for their first assessment of peritoneal membrane function after 2–3 months, and then after 12 months. We studied 143 patients: eighty-nine (62·2 %) males, fifty-three (37·1 %) diabetics, mean age 61·3 ( SD 14·9) years, with ninety (62·1 %) patients treated by automated PD cyclers with a daytime icodextrin exchange and thirty-seven (25·9 %) by continuous ambulatory PD. Median fat mass increased by 1·8 (–0·5 to 4·1) kg, whereas fat-free mass fell –1·3 (–2·9 to 1·0) kg, and the increase in fat mass was negatively associated with the fall in soft lean mass ( r –0·41, P < 0·001). Increased fat mass was associated with measured peritoneal glucose absorption ( r 0·69, P < 0·001), and glucose absorption was associated with the amount of 22·7 g/l glucose dialysate (OR 2·0, 95 % CI 1·5, 2·5, P < 0·001), peritoneal urea clearance (OR 9·5, 95 % CI 2·4, 37·1, P = 0·001) and male sex (OR 4·8, 95 % CI 1·5, 14·9, P = 0·008). We report an observational study in prevalent PD patients following body composition from their first assessment of PD membrane function for approximately 12 months, and despite the majority of patients prescribed icodextrin, we have demonstrated not only an association between intra-peritoneal glucose absorption and fat weight gain but also loss of fat-free mass.

Peritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a three-pore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haploinsufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small-solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open-state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated.

Background Intraperitoneal chemotherapy is limited by tissue penetration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been shown to improve drug uptake by utilizing the physical properties of gas and pressure. This study investigated the effect of adding electrostatic precipitation to further enhance the pharmacologic properties of this technique. Methods A comparative study was performed using an in vivo porcine model. There were 3 cases in each group, PIPAC and electrostatic precipitation pressurized intraperitoneal aerosol chemotherapy (ePIPAC), plus 1 negative control comparing intraperitoneal distribution and tissue uptake of 2 tracer substances (toluidine blue and DT01). Tracer uptake was determined by measuring DT01 in tissue and peritoneal fluid at the end of each procedure. Results Electrostatic precipitation of the aerosol was technically feasible in all ePIPAC animals. The aerosol was cleared completely from the visual field within 15 s in the ePIPAC group versus 30 min in the PIPAC group. The peritoneal surface was homogeneously stained in both groups. After 30 min, 1.5 % remaining DT01 was measured in samples of ePIPAC-treated peritoneal fluid versus 15 % in PIPAC animals ( p  = 0.01). Tissue concentration was increased after ePIPAC versus PIPAC ( p  = 0.06). Conclusions ePIPAC is technically feasible and improves tissue uptake of 2 tracer substances compared to PIPAC by up to tenfold. Intraperitoneal distribution was homogeneous in both groups. ePIPAC has the potential to allow more efficient drug uptake, further dose reduction, a significant shortening of the time required for PIPAC application, and improved health and safety measures.

Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long‐term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP‐7 levels markedly increased in the patients with PD, and the elevated MMP‐7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP‐7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP‐7 activated mitogen‐activated protein kinases (MAPKs)‐extracellular signal‐regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin‐1 (AQP‐1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP‐7‐mediating AQP‐1 up‐regulation and cellular homeostasis. In summary, all the findings indicate that MMP‐7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP‐7 might be a non‐invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.

Purpose Paclitaxel (PTX) is currently used in combination with cisplatin for Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis. Albumin-bound PTX is a promising new drug for HIPEC because of its easy solubility in aqueous perfusion medium and possibly because of the tendency of albumin to cross physiological barriers and accumulate in tumor tissue. Methods We tested the feasibility of using nab- paclitaxel in rabbits treated by HIPEC for 60 min compared with the classical formulation at an equivalent PTX dose. Samples of perfusate and blood were collected at different time points and peritoneal tissues were collected at the end of perfusion. PTX concentrations were determined by HPLC. The depth of paclitaxel penetration through the peritoneal barrier was assessed by mass spectrometry imaging. Results PTX after nab- paclitaxel treatment penetrated up to 0.63 mm in the peritoneal wall, but after CRE-paclitaxel, it was not detectable in the peritoneum. Moreover, the peritoneal concentration after nab- paclitaxel was five times that after paclitaxel classical formulation. Despite the high levels reached in the peritoneum, systemic exposure of PTX was low. Conclusions Our results show that nab- paclitaxel penetrates into the abdominal wall better than CRE-paclitaxel, in terms of effective penetration and peritoneal tissue concentration.

The incidence of colorectal cancer (CRC) has been on the rise, which is linked to the increasing prevalence of obesity, based on global epidemiological evidence. Although chronic inflammation is implicated in tumor development, the mechanisms underlying obesity‐associated CRC remain unknown. Here, we sought to identify the inflammatory cytokines and their roles in obesity‐related colorectal tumorigenesis using cytokine array analyses in a mouse model. Colorectal tumorigenesis was induced through i.p. injection of azoxymethane once a week for 6 weeks in 6‐week‐old female WT C57Black/6J mice and the obesity diabetes model mouse KK/TaJcl, KK‐Ay/TaJcl. The formation of aberrant crypt foci and colorectal tumors were more frequent in obese mice compared with WT mice, and both serum interleukin (IL)‐13 and IL‐13 receptor (R) expression in the normal intestinal mucosal epithelium were significantly increased in the obese mice. Furthermore, addition of IL‐13 to a human CRC cell line and a human colon organoid culture altered the phenotype of intestinal epithelial cells. Knockdown experiments further revealed that IL‐13Rα1 dominantly induced mucosal proliferation. Collectively, These results suggest an association between anti‐inflammatory cytokines and colorectal carcinogenesis, and provide new research directions for cancer prevention strategies. In particular, inflammation provoked by obesity, notably by increased expression of the cytokine IL‐13, could play an important role in the carcinogenesis of obesity‐related CRC. Interleukin (IL)‐13 and IL‐13 receptor expression in normal intestinal mucosal epithelium were significantly increased in obese mice. Inflammation provoked by obesity, notably an increased expression of the cytokine IL‐13, could play an important role in the carcinogenesis of obesity‐related colorectal cancer.

We reported the first comprehensive autopsy case of death due to intravenous injection of nicotine. We examined the distribution of nicotine in the body tissues and fluid and exposed the pathophysiology of nicotine poisoning. A 19-year-old woman was rushed to the hospital in cardiorespiratory arrest and was confirmed dead upon arrival. Liquid nicotine, hydrogen peroxide water, and a syringe were found in the hotel room where she stayed. On autopsy, nicotine concentration was the highest (15,023 μg/mg) in the tissue around the injection mark on the right upper arm. Among the body fluids, the intraperitoneal fluid had the highest, whereas the pericardial fluid had the lowest (0.736 μg/mL) nicotine concentration. Among the organs, the brain had the highest (11.637 μg/mg), whereas the fat tissue had the lowest (1.307 μg/mg) nicotine concentration. The concentration of cotinine, which is the metabolite of nicotine, was the highest in the tissue around the injection mark on the right arm (5.495 μg/mg) and was almost the same among the other body fluids and organs. The respective concentrations of nicotine and cotinine were 1.529 μg/mL and 0.019 μg/mL in the left heart blood and 3.157 μg/mL and 0.002 μg/mL in right heart blood. In this case, the nicotine concentrations in blood reached the lethal level. The distributions of nicotine and cotinine, as indicated by the intravenous injection, were related to the distribution of organs that metabolize nicotine and the distribution of nicotinic acetylcholine receptors.

Objectives The aim of this study was to assess the exposure of patients to organic substances produced and identified in surgical smoke formed in the abdominal cavity during laparoscopic cholecystectomy. Material and Methods Identification of these substances in surgical smoke was performed by the use of gas chromatography-mass spectrometry (GC-MS) with selective ion monitoring (SIM). The selected biomarkers of exposure to surgical smoke included benzene, toluene, ethylbenzene and xylene. Their concentrations in the urine samples collected from each patient before and after the surgery were determined by SPME-GC/MS. Results Qualitative analysis of the smoke produced during laparoscopic procedures revealed the presence of a wide variety of potentially toxic chemicals such as benzene, toluene, xylene, dioxins and other substances. The average concentrations of benzene and toluene in the urine of the patients who underwent laparoscopic cholecystectomy, in contrast to the other determined compounds, were significantly higher after the surgery than before it, which indicates that they were absorbed. Conclusions The source of the compounds produced in the abdominal cavity during the surgery is tissue pyrolysis in the presence of carbon dioxide atmosphere. All patients undergoing laparoscopic procedures are at risk of absorbing and excreting smoke by-products. Exposure of the patient to emerging chemical compounds is usually a one-time and short-term incident, yet concentrations of benzene and toluene found in the urine were significantly higher after the surgery than before it.

Background. Previous studies assessing various cytokines in the critically ill/injured have been uninformative in terms of translating to clinical care management. Animal abdominal sepsis work suggests that enhanced intraperitoneal (IP) clearance of Damage-Associated Molecular Patterns (DAMPs) improves outcome. Thus measuring the responses of DAMPs offers alternate potential insights and a representative DAMP, High Mobility Group Box-1 protein (HMGB-1), was considered. While IP biomediators are being recognized in critical illness/trauma, HMGB-1 behaviour has not been examined in open abdomen (OA) management. Methods. A modified protocol for HMGB-1 detection was used to examine plasma/IP fluid samples from 44 critically ill/injured OA patients enrolled in a randomized controlled trial comparing two negative pressure peritoneal therapies (NPPT): Active NPPT (ANPPT) and Barker’s Vacuum Pack NPPT (BVP). Samples were collected and analyzed at the time of laparotomy and at 24 and 48 hours after. Results. There were no statistically significant differences in survivor versus nonsurvivor HMGB-1 plasma or IP concentrations at baseline, 24 hours, or 48 hours. However, plasma HMGB-1 levels tended to increase continuously in the BVP cohort. Conclusions. HMGB-1 appeared to behave differently between NPPT cohorts. Further studies are needed to elucidate the relationship of HMGB-1 and outcomes in septic/injured patients.

Background: A high peritoneal transport status in continuous ambulatory peritoneal dialysis (CAPD) patients is associated with a markedly increased morbidity and mortality. While the causes are as yet unknown, overall the proportion of deaths due to cardiovascular disease is estimated at 40–50% among dialysis patients. Arterial stiffness has been established as a cardiovascular risk factor, while the links between peritoneal transport status and aortic stiffness have not yet been investigated. Methods: We included 65 prevalent CAPD patients (24 males/41 females) from our center in a cross-sectional study. Arterial stiffness was assessed by brachial pulse pressure (PP) and carotid-femoral pulse wave velocity (C-F PWV). The patients’ peritoneal fluid transport was assessed by kinetic modeling. The patients’ peritoneal small solute transport rate was assessed by D/P cr at 4 h. Extracellular water to total body water (E/T) ratio was assessed by means of bioimpedance analysis. C-reactive protein was also measured. Results: C-F PWV was positively correlated with patients’ age (r = 0.489, p < 0.01), diabetic status (r = 0.327, p < 0.01), peritoneal fluid absorption rate (Ke; r = 0.251, p < 0.05), PP (r = 0.483, p < 0.01), and E/T (r = 0.517, p < 0.01). Multivariate regression analysis showed that C-F PWV was independently related to E/T (p < 0.01), PP (p < 0.01), age (p < 0.05), and Ke (p < 0.05). Conclusion: Peritoneal fluid transport (Ke), as well as E/T, age and PP were found to be independent predictors of elevated C-F PWV in CAPD patients, suggesting that there might be a link between high aortic stiffness and increased Ke rate, hypothetically through generalized vasculopathy.