Sex differences in circulating proteins of patients with rheumatoid arthritis: A cohort study.

OBJECTIVES: Differences in proteomic profiles between men and women may provide insights into the biological pathways that contribute to known sex differences in rheumatoid arthritis (RA). Studies focusing on sex differences in circulating proteins in RA patients are scarce. Our objective was to investigate the sex differences in circulating proteins of RA patients. METHODS: Cohort study enrolling 399 RA patients. Ninety-four circulating protein-biomarkers (92CVDIIOlink®  + troponin-T + C-reactive protein) were measured. Clinical, demographic, and echocardiographic characteristics were compared between men and women. Sex differences in biomarker expression were assessed using regression modeling. RESULTS: In all, 306 (76.7%) patients were women. Compared with men, women had less visceral fat, smoked less, had diabetes and chronic obstructive pulmonary disease less frequently, and expressed more fatigue, anxiety, and depression. The association with cardiovascular outcomes did not differ between sexes. After adjusting for potential confounders, women expressed higher levels of circulating proteins related to adipokine signaling and vascular function (eg, leptin and vascular endothelial growth factor), whereas men expressed higher levels of circulating proteins related to extracellular matrix organization and inflammation (eg, matrix metalloproteinase-2 and C-reactive protein). These results were not found in patients without RA. CONCLUSION: Sex differences in circulating proteins reflect distinct pathways implicated in the pathogenesis of RA, including inflammation, adiposity, angiogenesis, and extracellular matrix organization. These findings may help further investigations into factors underlying sex-based differences and allow future studies focused on sex-specific personalized treatment approaches in RA. CLINICALTRIALS: gov ID: NCT03960515.

Prediction of the phenol removal capacity from water by adsorption on activated carbon.

High-performance sulfonated polysulfone (SPSf) mixed-matrix membranes (MMMs) were fabricated via a nonsolvent-induced phase separation (NIPS) method using zeolitic imidazolate frameworks-67 (ZIF-67) as a crosslinker. Acid-base crosslinking occurred between the sulfonic acid groups of SPSf and the tertiary amine groups of the embedded ZIF-67, which improved the dispersion of ZIF-67 and simultaneously improved the membrane strzcture and permselectivity. The dispersion of ZIF-67 in the MMMs and the acid-base crosslinking reaction were verified by energy-dispersive X-ray spectroscopy (EDX), X-ray diffractometry (XRD), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The pore structure analysis of MMMs indicated that filling ZIF-67 into SPSf enhanced the average surface pore sizes, surface porosities and more micropore in cross-sections. The crossflow filtrations showed the MMMs have higher pure water fluxes (57 to 111 L m-2 h-1) than the SPSf membrane (55 L m-2 h-1) but also higher bovine serum albumin (BSA) rejection rate of 93.9-95.8%, a model protein foulant. The MMMs showed a higher water contact angle than the SPSf membrane due to the addition of hydrophobic ZIF-67 and acid-base crosslinking, and also maintained high thermal stability evidenced by the thermogravimetric analysis (TGA) results. At the optimal ZIF-67 concentration of 0.3 wt%, the water flux of the SPSf-Z67-0.3 membrane was 82 L m-2 h-1 with a high BSA rejection rate of 95.3% at 0.1 MPa and better antifouling performance (FRR = 70%).

In Silico Pharmacokinetic Study of Vancomycin Using PBPK Modeling and Therapeutic Drug Monitoring.

BACKGROUND: Vancomycin has been in clinical use for nearly 50 years and remains the first-line treatment option for Gram-positive infections, including methicillin-resistant Staphylococcus aureus (MRSA). There are multiple strategies to monitor therapy and adjust the dose of this antibiotic. AUC24/MIC ratio has been demonstrated to be the best parameter to predict the effectiveness and safety of vancomycin, and a target ratio of ≥400 is recommended. Still, trough and peak serum levels at steady-state conditions have been used in clinical settings as an accurate and practical method to monitor vancomycin. METHODS: In this work, we collected and analyzed clinical information of patients being treated in a hospital center in Porto (Portugal) and studied the pharmacokinetics of vancomycin in silico, developing several physiologically based pharmacokinetic (PBPK) models using simulation software GastroPlus™. Different dosages and treatment regimens were studied, and the influence of patients' age, weight and renal function was evaluated; a simulation population was also performed. RESULTS: A linear effect of dose and a significant influence of weight and renal function in plasmatic levels of vancomycin was observed. CONCLUSION: The results of this work corroborate the accumulation of vancomycin in plasma and identify some parameters that influence the pharmacokinetics of this antibiotic. The importance of therapeutic monitoring of vancomycin is highlighted, and the usefulness of in silico tools, namely PBPK modeling, is demonstrated.

ß-Adrenoceptor Activation in Breast MCF-10A Cells Induces a Pattern of Catecholamine Production Similar to that of Tumorigenic MCF-7 Cells.

Adrenaline, which participates in the neuroendocrine response that occurs during stress and perimenopause, may be tumorigenic. This exploratory study aimed at investigating whether non-tumorigenic and tumorigenic human breast epithelial cell lines are able to synthesize adrenaline. The study was carried out in non-tumorigenic (MCF-10A) and tumorigenic (MCF-7) human breast cell lines. Expression of enzymes involved in adrenaline synthesis was characterized by RT-qPCR, immunocytochemistry and western blot. Catecholamines and analogue compounds were quantified by HPLC-ECD. Functional assessment of the impact of drugs on cells' tumorigenic potential was assessed by determination of cell viability and clonogenic ability. Both MCF-10A and MCF-7 cells produce catecholamines, but the capacity to produce adrenaline is lower in MCF-10A cells. ß-adrenoceptor activation increases the capacity of MCF-10A cells to produce adrenaline and favor both cell viability and colony formation. It is concluded that exposure of human breast epithelial cells to ß-adrenoceptor agonists increases cell proliferation and the capacity to produce adrenaline, creating an autocrine potential to spread these adrenergic effects in a feed-forward loop. It is conceivable that these effects are related to tumorigenesis, bringing a new perspective to understand the claimed anticancer effects of propranolol and the increase in breast cancer incidence caused by stress or during perimenopause.

Low Overall Survival in Women With De Novo Metastatic Breast Cancer: Does This Reflect Tumor Biology or a Lack of Access to Health Care?

PURPOSE: As a result of its epidemiologic and therapeutic aspects, metastatic breast cancer (MBC) is a highly relevant clinical condition. This study aimed to estimate overall survival (OS) in women with de novo MBC in a Brazilian population. PATIENTS AND METHODS: Patients were identified in the Goiânia population-based cancer registry between 1995 and 2011. All women with metastatic disease at diagnosis were included in the study. OS was analyzed at 5 and 10 years of follow-up. We used the Kaplan-Meier estimator and Cox regression for statistical analysis. RESULTS: Over the 16-year period covered by the study, 5,289 women were diagnosed with breast cancer in Goiânia. Of these, 277 women (5.2%) had MBC. OS rates at 5 and 10 years were 19.9% and 7.3%, respectively. The mean OS time of women treated in the public health system was 7.5 months shorter than in women who had private health care (19.7 v 27.2 months, respectively). In the univariable analysis, the following factors were statistically significant for OS: T3/4 staging, histologic grade 3, progesterone receptor status, tumor phenotype, breast surgery, CNS metastasis at initial presentation, and surgery for resection of metastasis. In multivariable analysis, initial CNS metastasis (hazard ratio, 3.09; 95% CI, 1.16 to 8.19) and breast surgery (hazard ratio, 0.45; 95% CI, 0.25 to 0.78) remained independent prognostic factors. CONCLUSION: OS was lower than rates found in specialist centers in Brazil and in developed countries. Several intrinsic and extrinsic factors were significant in predicting OS. Despite the difference in the 5-year survival rate, the type of access to health care was not significant in the multivariable analysis of the entire period.

New loricariid fishes from headwaters on Serra da Mantiqueira and Complexo do Espinhaço, Minas Gerais State, Brazil (Teleostei: Siluriformes: Loricariidae).

Three new species, of three different genera of loricariids, are described from the headwaters of Serra da Mantiqueira and Cadeia do Espinhaço, in Southeastern Minas Gerais State, Brazil. In this region, the Serra da Mantiqueira and the Complexo do Espinhaço are the highest points of the Brazilian Shield and delimits the headwaters of four drainages: São Francisco, Paraná, Doce and Paraíba do Sul basins. Harttia intermontana, n. sp., is described from the headwaters of the Rio Doce basin and is the first record of the genus in this basin. The new species can be distinguished from its congeners by the pattern of abdominal covering, presence of preanal plates, presence and pattern of ornamentation of canal plate, and some characteristics related to sexual dimorphism. Pareiorhaphis togoroi, n. sp., is described from the headwaters of the Rio das Mortes basin, tributary to the Rio Grande, in the upper Rio Paraná drainage, and represents the first record of the genus to this drainage, thus expanding its geographic distribution. It can be distinguished from most congeners by the absence of preadipose azygous plates, and characteristics related to secondary sexual characters of mature males: presence of odontodes on the lateral margin of head plus the absence of long hypertrophied odontodes on pectoral-fin spine. Neoplecostomus pirangaensis, n. sp., is described from the headwaters of the Rio Piranga, Rio Doce basin. The new species differs from all congeners by the much-reduced dermal platelets on the abdomen, devoid of developed odontodes between the insertions of the pectoral and pelvic fins. Neoplecostomus pirangaensis can also be distinguished from all congeners, except N. botucatu and N. paranensis, due to the complete absence of vestiges of the adipose fin (vs. vestiges, or adipose fin moderate to well developed and always present). The new species differs from N. botucatu by the absence of conspicuous dark spots all over the body and the presence of common dorsal bands in juveniles, and almost totally black in adults. It differs from N. paranensis by the bigger and less numerous teeth. Additionally, the new species differs from Neoplecostomus doceensis by the absence of enlarged fleshy folds between dentaries, and absence of a lateronasal plate.

Carbidopa Alters Tryptophan Metabolism in Breast Cancer and Melanoma Cells Leading to the Formation of Indole-3-Acetonitrile, a Pro-Proliferative Metabolite.

Carbidopa is used for the treatment of Parkinson's disease (PD) as an inhibitor of DOPA decarboxylase, and PD patients taking carbidopa have a lower incidence of various tumors, except for breast cancer and melanoma. Recently, it was shown that carbidopa inhibits tryptophan-2,3-dioxygenase (TDO) and kynureninase enzymes. In the present study, the effect of carbidopa on the viability and metabolic profile of breast cancer MCF-7 and melanoma A375 cells was investigated. Carbidopa was not effective in inhibiting MCF-7 and A375 proliferation. Liquid chromatography and mass spectrometry revealed a new compound, identified as indole-3-acetonitrile (IAN), which promoted a concentration-dependent increase in the viability of both cell lines. The results suggest that treatment with carbidopa may alter tryptophan (Trp) metabolism in breast cancer and melanoma leading to the formation of a pro-proliferative Trp metabolite, which may contribute to its failure in reducing breast cancers and melanoma incidence in PD patients taking carbidopa.

Advanced Glycation End Products Evolution after Pancreas-Kidney Transplantation: Plasmatic and Cutaneous Assessments.

Diabetes mellitus leads to increased Advanced Glycation End Products (AGE) production, which has been associated with secondary diabetic complications. Type 1 diabetic patients undergoing pancreas-kidney transplantation (SPKT) can restore normoglycemia and renal function, eventually decreasing AGE accumulation. We aimed to prospectively study AGE evolution after SPKT. Circulating AGE were assessed in 20 patients, at time 0 (T0), 3 months (T3), 6 months (T6), and 12 months (T12) after successful SPKT. Global AGE and carboxymethyllysine (CML) were analyzed, as well as advanced oxidation protein products (AOPP). Skin biopsies were obtained at T0 and T12. Immunohistochemistry with anti-AGE antibody evaluated skin AGE deposition. AGE mean values were 16.8 ± 6.4 µg/mL at T0; 17.1 ± 3.8 µg/mL at T3; 17.5 ± 5.6 µg/mL at T6; and 16.0 ± 5.2 µg/mL at T12. CML mean values were 0.94 ± 0.36 ng/mL at T0; 1.11 ± 0.48 ng/mL at T3; 0.99 ± 0.42 ng/mL at T6; and 0.78 ± 0.38 ng/mL at T12. AOPP mean values were 130.1 ± 76.8 µMol/L at T0; 137.3 ± 110.6 µMol/L at T3; 116.4 ± 51.2 µMol/L at T6; and 106.4 ± 57.9 µMol/L at T12. CML variation was significant (P = 0.022); AOPP variation was nearly significant (P = 0.076). Skin biopsies evolved mostly from a cytoplasmic diffuse to a peripheral interkeratinocytic immunoreaction pattern; in 7 cases, a reduction in AGE immunoreaction intensity was evident at T12. In conclusion, glycoxidation markers decrease, plasmatic and on tissues, may start early after SPKT. Studies with prolonged follow-up may confirm these data.

Insulin Resistance in Nondiabetic Peritoneal Dialysis Patients: Associations with Body Composition, Peritoneal Transport, and Peritoneal Glucose Absorption.

BACKGROUND AND OBJECTIVES: Insulin resistance has been associated with cardiovascular disease in peritoneal dialysis patients. Few studies have addressed the impact of fast transport status or dialysis prescription on insulin resistance. The aim of this study was to test whether insulin resistance is associated with obesity parameters, peritoneal transport rate, and glucose absorption. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Insulin resistance was evaluated with homeostasis model assessment method (HOMA-IR), additionally corrected by adiponectin (HOMA-AD). Enrolled patients were prevalent nondiabetics attending at Santo António Hospital Peritoneal Dialysis Unit, who were free of hospitalization or infectious events in the previous 3 months (51 patients aged 50.4 ± 15.9 years, 59% women). Leptin, adiponectin, insulin-like growth factor-binding protein 1 (IGFBP-1), and daily glucose absorption were also measured. Lean tissue index, fat tissue index (FTI), and relative fat mass (rel.FM) were assessed using multifrequency bioimpedance. Patients were categorized according to dialysate to plasma creatinine ratio at 4 hours, 3.86% peritoneal equilibration test, and obesity parameters. RESULTS: Obesity was present in 49% of patients according to rel.FM. HOMA-IR correlated better with FTI than with body mass index. Significant correlations were found in obese, but not in nonobese patients, between HOMA-IR and leptin, leptin/adiponectin ratio (LAR), and IGFBP-1. HOMA-IR correlated with HOMA-AD, but did not correlate with glucose absorption or transport rate. There were no significant differences in insulin resistance indices, glucose absorption, and body composition parameters between fast and nonfast transporters. A total of 18 patients (35.3%) who had insulin resistance presented with higher LAR and rel.FM (7.3 [12.3, interquartile range] versus 0.7 [1.4, interquartile range], P<0.001, and 39.4 ± 10.1% versus 27.2 ± 11.5%, P=0.002, respectively), lower IGFBP-1 (8.2 ± 7.2 versus 21.0 ± 16.3 ng/ml, P=0.002), but similar glucose absorption and small-solute transport compared with patients without insulin resistance. FTI and LAR were independent correlates of HOMA-IR in multivariate analysis adjusted for glucose absorption and small-solute transport (r=0.82, P<0.001). CONCLUSIONS: Insulin resistance in nondiabetic peritoneal dialysis patients is associated with obesity and LAR independent of glucose absorption and small-solute transport status. Fast transport status was not associated with higher likelihood of obesity or insulin resistance.

Hepatocyte growth factor signalizes peritoneal membrane failure in peritoneal dialysis.

BACKGROUND: Hepatocyte growth factor (HGF) counteracts peritoneal fibrosis in animal models and in-vitro studies, but no study explored effluent HGF in peritoneal dialysis (PD) patients with ultrafiltration failure (UFF). Our aim was to assess the relationship between effluent HGF with UF profile, free water transport (FWT) and small-solute transport. METHODS: We performed 4-hour, 3.86% PET with additional UF measurement at 60 minutes in 68 PD patients. MTACcreatinine, FWT, small-pore ultrafiltration, and effluent HGF were quantified. RESULTS: Effluent HGF negatively correlated with UF (r=-0.80, p=0.009) and FWT (r=-0.69, p=0.04). Patients with UFF had higher dialysate HGF (103 pg/mL vs 77 pg/mL, p=0.018) and, although not statistically significant, those with FWT compromise had also higher dialysate HGF compared with subgroup of UFF without FWT compromise (104 pg/mL vs 88 pg/mL, p=0.08). FWT≤45% without clinical UFF was documented in some patients who also had increased effluent HGF. CONCLUSIONS: Dialysate HGF concentration is significantly higher among patients with UFF, specially, if FWT is impaired, being a sign of peritoneal membrane deterioration.

Analysis of cell proliferation and pattern of invasion in oral squamous cell carcinoma.

Cell proliferation markers play an important role in the biological behavior of neoplasms. This study investigated the immunohistochemical expression of PCNA, Ki-67 and Cyclin B1 proteins based on the pattern of cell invasion in oral squamous cell carcinoma (OSCC). A total of 39 OSCC specimens and 13 samples of normal oral mucosa (control) were immunohistochemically analyzed. Protein expression was evaluated according to World Health Organization - Histological Malignancy Grading (WHO-HMG) and a specific grading system for invasion, graded from 1 to 4, varying from a consistently well-defined "pushing" border to diffuse infiltration and cellular dissociation, and was then correlated with clinical features. We found higher expression of Ki-67 and Cyclin B1 in OSCC when compared with the control group. High Ki-67 expression levels were more commonly seen in the floor of the mouth than in the tongue (P = 0.009). Cyclin B1 showed a positive correlation with histological grade, according to WHO-HMG criteria (P = 0.01). Our results suggest that Cyclin B1 is a reliable proliferation marker for indicating degree of tumor proliferation. Correlations between PCNA, Ki-67, Cyclin B1 and invasive tumor front with overall survival were not observed. Further studies are needed in order to elucidate whether cell proliferation activity at the tumor invasion front is related to prognosis.

Antibacterial and cytotoxic properties of some plant crude extracts used in Northeastern folk medicine / Propriedades antibacterianas e citotóxicas de alguns extratos de plantas usados na medicina popular nordestina

In the present study, 32 hexane and ethanol extracts of Protium bahianum, P. heptaphyllum, Croton sellowii, C. rhamnifolius, C. jacobinensis, C. micans and Muntingia calabura were screened for antibacterial activity by the disc-diffusion method. Cytotoxicity assays using the brine shrimp Artemia salina Leach as a model were performed to determine lethal doses for 50 percent of individuals (LC50 µg/mL). Antibacterial activity was found in flowers hexane extracts of M. calabura against B. subtilis, and leaves ethanol extracts against S. aureus and B. subtilis at concentration of 1mg/mL. Among 32 extracts, 19 showed low or no toxicity (LC50 > 250 µg/mL), 6 showed moderate toxicity (LC50 between 80 µg/mL and 250µg/mL), and 7 were highly toxic (LC50 < 80 µg/mL).

No presente estudo, 32 extratos hexânicos e etanólicos de Protium bahianum, P. heptaphyllum, Croton sellowii, C. rhamnifolius, C. jacobinensis, C. micans e Muntingia calabura, foram avaliados para atividade antibacteriana, pelo método de difusão em disco. Ensaios de citoxicidade foram realizados com o modelo do microcrustáceo Artemia salina Leach para determinar a concentração letal para 50 por cento dos indivíduos (CL50 µg/mL). A presença de atividade antibacteriana foi observada com os extratos hexânicos das flores de M. calabura contra B. subtilis, e extratos etanólicos das folhas contra S. aureus and B. subtilis na concentração de 1 mg/mL. Dentre os 32 extratos, 19 apresentaram toxicidade baixa ou ausente (CL50 > 250 µg/mL), 6 mostraram toxicidade moderada (CL50 entre 80 µg/mL e 250 µg/mL) e 7 foram muito tóxicos (CL50 < 80 µg/mL).

Evaluation of peritoneal transport and membrane status in peritoneal dialysis: focus on incident fast transporters.

BACKGROUND/AIM: The determinants of baseline fast solute transport are still unclear. We prospectively investigated the relationship of peritoneal solute transport with markers of inflammation, angiogenesis, and membrane status, with a focus on fast transporters. METHODS: Seventy-one incident peritoneal dialysis patients were assessed with baseline and annual peritoneal equilibration tests, using a 3.86% glucose dialysis solution. Residual renal function and markers of inflammation, including systemic and intraperitoneal interleukin-6 (IL-6), effluent cancer antigen 125 (CA-125), and vascular endothelial growth factor (VEGF) appearance rates (ARs), were investigated. The time course of the dialysate-to-plasma ratio of creatinine (D/P creatinine ratio) and its relationship with the biomarkers were investigated by a mixed linear model. RESULTS: Incident fast/fast average transporters had a similar age, diabetes prevalence, and serum and effluent IL-6 levels, but significantly higher levels of CA-125 and VEGF ARs than the slow/slow average group; the D/P creatinine ratio was not correlated with systemic IL-6, but was correlated with effluent CA-125 AR (r = 0.45, p < 0.0001) and VEGF AR (r = 0.52, p < 0.0001). The D/P creatinine ratio decreased with a U-shaped profile (p = 0.02). Intraperitoneal IL-6 was the significant and positive determinant of the time course of the D/P creatinine ratio (p < 0.0001). Effluent CA-125 decreased with time on peritoneal dialysis (p = 0.013). CONCLUSIONS: Baseline peritoneal fast transport was not associated with systemic inflammation, but was related to peritoneal locally produced substances able to mediate transitory hyperpermeability. The D/P creatinine ratio changed during the follow-up period with a U-shaped profile. This was associated with effluent IL-6 and partly with VEGF. CA-125 decreased throughout the follow-up period.

Peritoneal membrane evaluation in routine clinical practice.

BACKGROUND/AIMS: Establishment of reference values for small solute transport, sodium sieving and effluent CA125 with 3.86% (4 h) peritoneal equilibration test (PET), and comparison with fast-fast PET with regard to small solute transport categories. METHODS: Cross-sectional study; 69 prevalent patients. Sodium sieving corrected for sodium diffusion with a formula applicable to the PET. CA125 appearance rate (AR) was measured. Expected and observed 60 min D/P(creatinine) were compared by Bland and Altman. RESULTS: Means (95% CI): D/P(creatinine) 0.73 (0.70-0.76), MTAC(creatinine) 9.6 (8.4-10.9) ml/min, D/D0 glucose 0.30 (0.28-0.31), corrected dip 0.17 (0.15-0.18), CA125 150 (125-176) U/min. Both corrected and uncorrected sodium sieving were informative. Peritoneal transport was faster at 60 min dwell. UFF patients presented very low corrected dip and CA125 AR. CONCLUSION: 3.86% (4 h) PET provided results similar to those from SPA. Correction for diffusion of sodium sieving is dispensable for simple clinical evaluations. D/P(creatinine) at 60 min overestimated small solute transport rate. Effluent CA125 was consistently lower in UFF patients.

Evaluation of effluent markers cancer antigen 125, vascular endothelial growth factor, and interleukin-6: relationship with peritoneal transport.

Peritoneal hyperpermeability has been associated with increased levels of effluent vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). Mesothelial cells can produce various vasoactive substances besides VEGF. A large mesothelial mass may possibly lead to high dialysate VEGF concentrations and may partly explain some cases of peritoneal hyperpermeability during a patient's early months on peritoneal dialysis (PD). Early peritoneal fast transport may therefore not necessarily be associated with systemic inflammation. To investigate the relationship of effluent markers and peritoneal transport, we measured the appearance rates of cancer antigen 125 (CA125), VEGF, and IL-6 in 4-hour effluents from 69 peritoneal equilibration tests (PETs) using 3.86% glucose solution. At the same time, we measured serum VEGF and IL-6. Our analyses included an early group (EG), whose members had been on PD for 4.6 +/- 3.3 months, and a later group (LG), whose members had been on PD for 30 +/- 17 months. In EG, dialysate-to-plasma creatinine at 4 hours (D/P(Cr240)) correlated significantly with effluent CA125/min (r = 0.51, p = 0.006) and VEGF/min (r = 0.57, p = 0.001), but not with serum VEGF or IL-6. The values of CA125/min and VEGF/min also correlated (r = 0.40, p = 0.034). Fast transporters in EG had higher effluent CA125 (p = 0.057) and VEGF (p = 0.0001), but not serum or effluent IL-6. In LG, D/P(Cr240) again correlated significantly with dialysate VEGF (r = 0.51, p = 0.009), but not with CA125. Fast transporters in LG tended to have higher levels of serum and effluent IL-6 and effluent VEGF. We conclude that fast solute transport rates at the beginning of PD are associated with signs of a large mesothelial cell mass and not consistently associated with higher systemic IL-6. The VEGF produced by mesothelial cells can mediate early peritoneal hyperpermeability in some populations. Later, mesothelial mass is lost and is no longer related to increased intraperitoneal VEGF or IL-6.