Evaluation of breviscapine on prevention of experimentally induced abdominal adhesions in rats

Background

Adhesion formation, which results from mechanical peritoneal damage, tissue ischemia, or the presence of foreign materials, is a complicated process. The formation of adhesions is associated with inflammatory response and extracellular matrix deposition in response to injury. Although the pathophysiology of adhesion formation is widely understood, an absolute solution to this problem does not exist yet. As a main component of Erigeron breviscapus, breviscapine has exhibited the ability of anti-inflammatory and antifibrosis on many diseases. The purpose of this study was to investigate the effect of breviscapine on the development of postoperative intra-abdominal adhesions in Wistar rats.

Methods

Abdominal adhesions were induced by scraping the cecum in rats. Various dosages of breviscapine drugs were administered for 10 days after surgery. On the 11th day after surgery, the levels of interleukin (IL) 18, IL-6, tumor necrosis factor α in blood serum and transforming growth factor β₁ (TGF-β₁), connective tissue growth factor, tissue plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) in peritoneal fluid were determined by enzyme linked immunosorbent assay. The expression of Smad7 and TGF-β₁ in rat cecum tissue was evaluated by Western blot analysis. Grades of intestinal adhesion were ranked by macroscopic observation.

Results

The intraperitoneal administration of breviscapine is effective on the prevention of the formation of postoperative adhesions in rats. Breviscapine decreased the levels of IL-18, IL-6, and tumor necrosis factor-α in blood serum and TGF-β₁, connective tissue growth factor, PAI-1 in peritoneal fluid. But the levels of tPA and the ratio of tPA and PAI-1 in peritoneal fluid were increased. In addition, breviscapine significantly inhibited the expression of TGF-β₁ and increased the level of Smad7 in the rat cecum tissue.

Conclusions

These results suggested that intraperitoneal administration of breviscapine was effective in preventing intra-abdominal adhesion formation in rats. Breviscapine appears to have synergetic effects which could decrease fibrosis by inhibiting inflammation, upregulating peritoneal fibrinolytic activity and regulating the TGF and/or Smad signaling pathway. These data indicated a potential new therapeutic use of breviscapine on adhesion prevention.     

Normal saline induces oxidative stress in peritoneal mesothelial cells

Background

Peritoneal adhesions are the most common complication of the abdominal surgery. Normal saline is frequently used to rinse the peritoneal cavity during abdominal surgery, although there is no well-established data describing effect of such procedure on the process of formation of peritoneal adhesions.

Methods

Effect of 0.9% NaCl solution on viability, oxidative stress, and fibrinolytic activity of human peritoneal mesothelial cells maintained in in vitro culture was evaluated.

Results

Exposure of mesothelial cells to 0.9% NaCl induces oxidative stress, derangement of their structure with subsequent increased release of tissue factor (+75%) and plasminogen activator inhibitor-1 (+19%), and simultaneous suppression of tissue plasminogen activator release (−39%). In effect, ration tissue plasminogen activator/plasminogen activator inhibitor-1 was reduced in 0.9% NaCl-treated cells by 50%. Pretreatment of cells with precursor of glutathione synthesis: l-2-oxothiazolidine-4-carboxylic acid prevented these changes.

Conclusions

Oxidative stress in the peritoneal mesothelium caused by 0.9% NaCl activates their procoagulant activity and impairs fibrinolytic properties of these cells. These effects disqualify 0.9% NaCl as rinsing solution during abdominal surgery.     

Cytokine Gene Polymorphisms in Kidney Transplantation

Background

Acute and chronic rejections remain an important cause of graft loss after renal transplantation. It has been suggested that cytokine genotyping may have a predictive role to identify patients at greater risk of rejection regardless of human leukocyte antigen (HLA) compatibility and/or the presence of anti-HLA antibodies before the renal allograft.

Objectives

We sought to investigate polymorphisms of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1, interleukin (IL)-10, IL-6, and interferon (IFN)-γ as indices of differential cytokine production in kidney transplantation and to examine their predictive roles for acute or chronic rejection.

Patients and Methods

TNF-α (G/A -308), TGF -β1 (haplotype codon 10/codon 25), IL-10 (haplotype-1082, −819, −592), IL-6 (C/G -174), and IFN-γ (T/A +874) single nucleotide polymorphisms (SNPs) were detected using polymerase chain reaction (PCR)-specific sequence primers (SSP) in 231 kidney transplant recipients (KTR) including 106 treated with mycophenolate mofetil (MMF+).

Results

We observed no significant associations of any of investigated polymorphism taken alone with acute rejection episodes (ARE) or chronic allograft dysfunction (CAD). Nevertheless, TGF-β1 Low (L) production was correlated with greater graft survival at 20 years (81.8%) compared with intermediate (L) or high (H) levels (56.1%), affect that the difference was not significant (P = .2). Cytokine haplotype analysis in KTR (MMF−) without HLA-mismatches or presynthesized anti-HLA antibodies (n = 32) showed ARE to be significantly more prevalent among the TNF-α*H/TGF- β1*H/IL-10*H production haplotype (75%) compared with the other haplotypes (16%; P = .03).

Conclusion

The presence of TGF-β1-H secretion profile may protect the kidney graft. TNF-α*H/TGF-β1*H/IL-10*H haplotype was associated with a higher risk of ARE and with poorer graft survival.     

Ischemic Reperfusion Injury–Induced Oxidative Stress and Pro-inflammatory Mediators in Liver Transplantation Recipients

Objective

Liver ischemic reperfusion injury is harmful to transplant recipients, and is associated with postoperative morbidity and mortality. Our study was designed to investigate the oxidative stress and pro-inflammatory mediators in liver transplant recipients.

Methods

We prospectively analyzed 14 recipients who underwent liver transplantation by measuring their blood levels of malondialdehyde (MDA) and cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, at nine time points perioperatively. We also evaluated the correlations between oxidative stress (MDA levels) and the characteristics of the recipient or the donated graft.

Results

These parameters significantly increased from 1 minute before reperfusion, and the values peaked within 3 to 30 minutes after reperfusion. On the time point at 5 minutes after reperfusion, the MDA levels which were the highest in the recipients correlated with the values of preoperative direct/and total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), model for end-stage liver disease (MELD) score, international normalized ratio (INR), and surgical blood loss.

Conclusion

The levels of MDA, TNF-α, IL-1β, and IL-6 greatly increased with the ischemic reperfusion insult. Recipients with higher values of preoperative direct/and total bilirubin, AST, ALT, MELD score, INR, and surgical blood loss tended to have higher levels of MDA and may suffer more injury from this insult.     

Time course of pro- and anti-inflammatory cytokine levels in patients with burns—Prognostic value of interleukin-10

Introduction

Trends and the prognostic value of cytokine responses to severe burns have not been fully examined in humans. Therefore, the aim of this study was to determine the time course and prognostic value of pro- and anti-inflammatory cytokines in the immediate post-burn period.

Patients and methods

Blood samples were taken for measuring IL-1β, IL-6, IL-8, IL-10, IL-12p70 and TNF-α concentrations from patients with more than 20% burned surface area on admission and on 5 consecutive days. Development of sepsis was assessed using standard criteria twice a day.

Results

IL-12p70 remained under assay detection levels in the study period. IL-1β and TNF-α could be detected in stimulated blood samples with higher levels in survivors (n = 21). IL-6 on days 4–5 and IL-8 on days 4–6 in non-stimulated plasma showed significant elevation in non-survivors (n = 18) whereas in stimulated blood its levels did not differ significantly. IL-10 levels were significantly higher in non-survivors during the study period in non-stimulated, and except day 6 in stimulated blood. Using the cut-off level of 14 pg ml⁻¹ for IL-10 predicted ICU mortality with 85.4% sensitivity and 84.2% specificity on admission.

Conclusion

Early anti-inflammatory excess had a bad prognosis for patients suffering from severe burns.     

Intestine as Source of Cytokines and Growth Factors

Background

The activation status of intestinal immune system cells is much higher than that of analogous peripheral cells. Increased serum concentrations of proinflammatory cytokines have been reported in various pathologic conditions; however, the source of these mediators has not been elucidated.

Objective

To assess the role of the human intestine and its lymphatic system in production of growth factors and proinflammatory cytokines.

Material and Methods

Twenty liver transplant recipients and 20 donors were included in the study. Blood samples were obtained from the artery supplying the intestine, the portal vein, and a peripheral vein during liver harvesting in donors and after transplantation in recipients. An enzyme-linked immunosorbent assay was used to assess serum concentrations of IL-6, tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), and hepatocyte growth factor (HGF).

Results

In transplant recipients, IL-6 concentration in arterial blood was lower than that in portal blood (P < .049), whereas in donors, there was no significant difference in these concentrations. Neither recipients nor donors demonstrated significant differences in arterial or portal blood concentrations of TNF-α, TGF-β, or HGF.

Conclusions

In healthy human beings, the intestine is not a substantial source of IL-6, TNF-α, TGF-β, or HGF. However, in patients with liver cirrhosis, the intestine is an important source of IL-6 but not of the other studied growth factors and cytokines.     

The neurokinin 1 receptor regulates peritoneal fibrinolytic activity and postoperative adhesion formation

Background

Intra-abdominal adhesions are a common source of postoperative morbidity. Previous studies in our laboratory have shown that a neurokinin 1 receptor antagonist (NK-1RA) reduces abdominal adhesion formation and increases peritoneal fibrinolytic activity. However, the cellular pathway by which the antagonist exerts its effects is unclear, as cultured peritoneal mesothelial cells exposed to the NK-1RA show increases in fibrinolytic activity despite having very low expression of neurokinin 1 receptor (NK-1R) messenger RNA and protein. Our aim was to determine whether the NK-1R plays an essential role in the adhesion-reducing effects of the NK-1RA, or if the NK-1RA is acting independently of the receptor.

Methods

Homozygous NK-1R knockout mice and age matched wild-type mice underwent laparotomy with cecal cautery to induce adhesions. At the time of surgery, mice received a single intraperitoneal dose of either NK-1RA (25 mg/kg) or saline alone. Adhesion severity at the site of cecal cautery was assessed on postoperative day 7. In a separate experiment, peritoneal fluid was collected from wild type and NK-1R knockout mice 24 h after laparotomy with cecal cautery and administration of either NK-1RA or saline. Tissue plasminogen activator levels, representative of total fibrinolytic activity, were then measured in peritoneal fluid.

Results

In wild-type mice, NK-1RA administration significantly decreased adhesion formation compared with saline controls. Among the NK-1R knockout mice, there was no significant reduction in adhesion formation by the NK-1RA. Fibrinolytic activity increased 244% in wild-type mice administered NK-1RA compared with saline controls; however, the NK-1RA did not raise fibrinolytic activity above saline controls in NK-1R knockout mice.

Conclusions

These data indicate that the NK-1R mediates the adhesion-reducing effects of the NK-1RA, in part, by the upregulation of peritoneal fibrinolysis, and suggest that the NK-1R is a promising therapeutic target for adhesion prevention.     

Pioglitazone attenuates lung injury by modulating adipose inflammation

Background

Pioglitazone modulates adipocyte differentiation and enhances adiponectin promoter activity to increase plasma adiponectin levels. We investigated the effects of pioglitazone on cecal ligation and puncture (CLP)-induced visceral-adipose-tissue inflammation and lung injury in mice.

Materials and methods

Eight-wk-old male mice were assigned to three groups: (1) a sham-operated control group, (2) a CLP group, and (3) a pioglitazone-treated CLP group. Pioglitazone (10 mg/kg) was injected intraperitoneally for 7 d. Serum, lung, and visceral adipose tissue were collected 24 h after surgery. Tumor necrosis factor α (TNF-α) levels in peritoneal lavage fluid were measured by an enzyme-linked immunosorbent assay, and TNF-α and interleukin 6 messenger RNA (mRNA) expression levels in visceral adipose tissue were quantified by real-time polymerase chain reaction. Lung tissue specimens were stained with hematoxylin-eosin, and the terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling method was used to evaluate tissue damage.

Results

TNF-α levels in peritoneal lavage fluid were significantly higher in the CLP group than in the sham group. TNF-α levels in the pioglitazone-treated CLP group were significantly lower than those in the CLP group. TNF-α and interleukin 6 mRNA expression levels of visceral adipose tissue were significantly higher in the CLP group than in the sham group. Pioglitazone treatment decreased the mRNA expression levels of these cytokines compared with the respective values in the CLP group. Histopathologic analysis of lung tissue revealed significantly increased numbers of terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling–positive cells in the CLP group compared with the sham group.

Conclusions

Pioglitazone effectively prevents lung injury caused by CLP-induced sepsis by maintaining the anti-inflammatory status of visceral adipose tissue.     

Role of neutrophil elastase in lung injury induced by burn–blast combined injury in rats

Objective

Neutrophil elastase (NE) takes part in the pathogenesis of acute lung injury. However, its role in lung injury of burn–blast combined injury is unclear. Our objective was to assess the role of NE, and effect of sivelestat, a specific NE inhibitor, in lung injury induced by burn–blast combined injury in rats.

Methods

One hundred and sixty male Sprague-Dawley rats were randomly subjected to burn–blast combined injury (BB) group, burn–blast combined injury plus sivelestat treatment (S) group or control (C) group. Blood gas, protein concentration and NE activity in bronchoalveolar lavage fluid (BALF), pulmonary myeloperoxidase (MPO) activity, serum concentrations of TNF-α and IL-8, etc. were investigated from 0 h to 7 d post-injury.

Results

In BB group, PaO₂ decreased, while NE activity in BALF, total protein concentration in BALF, pulmonary MPO activity and W/D ratio, serum concentrations of TNF-α and IL-8 increased with neutrophil infiltration, progressive bleeding and pulmonary oedema. Compared with BB group, sivelestat treatment decreased the NE activity and ameliorated the above indexes.

Conclusion

Sivelestat, exerts a protective effect in lung injury after burn–blast combined injury through inhibiting NE activity to decrease pulmonary vascular permeability, neutrophil sequestration, and production of TNF-α and IL-8.     

Early-phase peritoneal drainage and lavage in a rat model of severe acute pancreatitis

Purpose

To evaluate the effects of early-phase drainage on the survival rates and pancreatic pathological changes associated with severe acute pancreatitis (SAP) in a rat model.

Methods

Sprague–Dawley rats were divided into the following groups: SAP model (control), early drainage and delayed drainage. The 24-h survival rates were compared among the groups. In addition, the serum and ascites concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-α were measured, and pancreatic pathological changes were observed.

Results

The survival rate significantly improved in the early drainage group. Compared with that observed in the control group, the serum TNF-α and IL-8 concentrations in the early drainage group decreased, while the serum IL-10 levels increased, and the ascites concentrations of IL-1β, IL-6, IL-8 and TNF-α decreased, while that of IL-10 increased significantly. In the delayed drainage group, only the ascites concentrations of TNF-α decreased. Meanwhile, the pancreatic pathological changes at 3, 6 and 24 h worsened in the early drainage group; however, the pancreatic lesions in the early drainage group were less mild than those seen in the control group.

Conclusions

Rebalancing the cytokine levels in ascites after early drainage may be a key factor for enhancing the survival rate in rats.

     

The effects of ulinastatin on systemic inflammation,visceral vasopermeability and tissue water content in rats with scald injury

Background

The aim of this study was to examine whether administration of ulinastatin inhibits pro-inflammatory mediators and ameliorate visceral vasopermeability both in a rat model of major burn, and also in rat cultured endothelial cells stimulated with permeability-evoking mediators.

Methods

Plasma levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), myeloperoxidase (MPO), microvascular permeability, and water content of organ tissues were evaluated in a rodent model of a 55% TBSA full-thickness scald injury. Microvascular permeability was also evaluated with a cultured pulmonary microvascular endothelial cells (PMECs) monolayer after stimulation with trypsin, bradykinin, histamine, prostaglandin E2 and burn serum.

Results

We found that the plasma levels of TNF-α, CRP, MPO, vascular permeability and water content of heart, lung, kidney, and small intestine tissues were significantly increased in animals after scald injury, and administration of ulinastatin lowered the levels TNF-α, CRP, MPO, vascular permeability and water content of those organ tissues. In vitro, ulinastatin lowered the levels of TNF-α, interleukin-6 (IL-6) and attenuated permeability in PMEC monolayers after being stimulated with burn serum or trypsin, but not by bradykinin, histamine or prostaglandin E2.

Conclusions

These results indicate that ulinastatin attenuates the systemic inflammatory response and visceral vasopermeability both in vivo and vitro, and may serve as a therapeutic agent for prevention of systemic inflammatory response and leakage of fluid into tissue after major burn.     

Plasma and urinary levels of cytokines in patients with idiopathic hypercalciuria

Background

Recent studies suggest that cytokines modulate bone turnover. Idiopathic hypercalciuria (IH) seems to be associated with bone mineral loss. Therefore, the aim of this study was to assess cytokines involved in bone turnover in patients with IH.

Methods

Plasma and spot-urine levels of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), transforming growth factor β1 (TGF-β1), and monocyte chemoattractant protein (MCP-1) were measured in 70 children and adolescents with IH and in 37 healthy controls. Patients with IH were subdivided according to their calciuria at the time of sample collection: ≥4 mg/kg/day (persistent IH, n=27) and below 4 mg/kg/day (controlled IH, n=43). Cytokines were determined by enzyme-linked immunoassay.

Results

Plasma and urinary concentrations of IL-1β, IL-6, IL-8, and TNF-α were undetectable in all groups. No differences were found between controlled and persistent hypercalciuria for plasma and urinary levels of MCP-1 and TGF-β1. On the other hand, MCP-1 levels were significantly higher in both subgroups of IH in comparison to healthy controls. Furthermore, urinary MCP-1 levels of IH patients correlated positively with bone mineral content (p=0.013).

Conclusion

Although cytokine measurements did not allow the differentiation between persistent and controlled IH, our findings suggest that MCP-1 might play a role in patients with IH.

     

Cyclooxygenase-2 and vascular endothelial growth factor expressions are involved in ultrafiltration failure

Background

Long-term peritoneal dialysis (PD) is associated with ultrafiltration failure (UFF). The aim of the study was to investigate changes in cyclooxygenase-2 (COX-2), vascular endothelial growth factor A (VEGF-A), and vascular endothelial growth factor C (VEGF-C) expressions in a rat model of UFF induced by PD solution.

Methods

Sprague–Dawley rats were divided into six groups (n = 8/group): normal untreated control group, sham operation group, uremic group (nephrectomy without PD), uremic 2-wk PD group (PD solution for 2 wk), uremic 4-wk PD group (PD solution for 4 wk), and uremic 4-wk PD + celecoxib group (PD solution plus COX-2 inhibitor celecoxib 20 mg/kg for 4 wk). Peritoneal function was determined by peritoneal equilibration test. Peritoneal morphology was determined by hematoxylin and eosin and Masson staining. Microvessel and lymphatic microvessel formation was determined by immunohistochemistry. COX-2, VEGF-A, and VEGF-C expressions were determined by real-time polymerase chain reaction and immunohistochemistry.

Results

Uremic rat model was successfully established. PD-induced peritoneal morphologic changes associated with UFF, characterized by inflammation, edema, and collagen accumulation. PD solution increased the density of microvessels marked by CD31 (microvessel density) and lymphatic microvessels marked by LYVE-1 (lymphatic vessel density) in peritoneum. COX-2, VEGF-A, and VEGF-C expression levels in the uremic 4-wk PD group were higher than those in the uremic group (all P < 0.05). All these changes were partially reversed by celecoxib. VEGF-A and VEGF-C protein expressions were positively correlated with microvessel density and lymphatic vessel density formation.

Conclusions

COX-2 could increase VEGF-A and VEGF-C expressions in peritoneal tissue, resulting in increased formation of peritoneal microvessels and lymphatic microvessels, playing pivotal roles in the development of UFF.     

Cytokine Profile in Pleural Fluid and Serum After Lung Transplantation

Background

Lung transplantation is the procedure of choice in several end-stage lung diseases. Despite improvements in surgical techniques and immunosuppression, early postoperative complications occur frequently.

Objective

To evaluate the pleural inflammatory response after surgery.

Patients and Methods

Twenty patients aged 18 to 63 years underwent unilateral or bilateral lung transplantation between August 2006 and March 2008. Proinflammatory cytokines interleukin (IL)-1β, IL-6, and IL-8 and vascular endothelial growth factor in pleural fluid and serum were analyzed. For cytokine evaluation, 20-mL samples of pleural fluid and blood (right, left, or both chest cavities) were obtained at 6 hours after surgery and daily until removal of the chest tube or for a maximum of 10 days. Data were analyzed using analysis of variance followed by the Holm-Sidak test.

Results

All effusions were exudates according to Light's criteria. Pleural fluid cytokine concentrations were highest at 6 hours after surgery. Serum concentrations were lower than those in pleural fluid, and IL-1β, IL-6, and IL-8 were undetectable at all time points.

Conclusions

There is a peak concentration of inflammatory cytokines in the first 6 hours after transplantation, probably reflecting the effects of surgical manipulation. The decrease observed from postoperative day 1 and thereafter suggests the action of the immunosuppression agents and a temporal reduction in pleural inflammation.     

Angelicin regulates LPS-induced inflammation via inhibiting MAPK/NF-κB pathways

Background

Angelicin is a furocoumarin found in Psoralea corylifolia L. fruit. The purpose of this study was to investigate the protective ability of angelicin against inflammation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells and LPS-induced in vivo acute lung injury model.

Materials and methods

The concentrations of tumor necrosis factor alpha (TNF-α) and interleukin (IL)-6 in the culture supernatants of RAW 264.7 cells were determined 24 h after LPS administration. ALI was induced by intratracheal instillation of LPS. Six hours after LPS inhalation, bronchoalveolar lavage fluid and lung tissue samples were obtained for enzyme-linked immunosorbent assay, histologic, and Western blotting analyses.

Results

The results showed that pretreatment with angelicin markedly downregulated TNF-α and IL-6 levels in vitro and in vivo, and significantly decreased the amount of inflammatory cells, lung wet-to-dry weight ratio, and myeloperoxidase activity in LPS-induced ALI mice. Furthermore, Western blotting analysis results demonstrated that angelicin blocked the phosphorylation of IκBα, NF-κBp65, p38 MAPK, and JNK in LPS-induced ALI.

Conclusions

These results suggest that angelicin was potentially advantageous to prevent inflammatory diseases by inhibiting NF-κB and MAPK pathways. Our data indicated that angelicin might be a potential new agent for prevention of inflammatory reactions and diseases in the clinic.     

Atrial natriuretic peptide attenuates kidney–lung crosstalk in kidney injury

Background

Renal ischemia–reperfusion injury (IRI) is a common cause of acute kidney injury after cardiovascular surgery, which in turn deteriorates oxygenation. Atrial natriuretic peptide (ANP) has natriuretic, diuretic, and anti-inflammatory effects. To elucidate whether renal IRI induces inflammation in the kidney and lung and ANP attenuates kidney–lung crosstalk.

Materials and methods

The rats were anesthetized, tracheostomized, mechanically ventilated, and randomized to four groups: saline + IRI (n = 12), ANP + IRI (n = 12), ANP + sham (n = 6), and saline + sham (n = 6). Saline (6 mL/kg/h) or ANP (0.2 μg/kg/min) at the rate of 6 mL/kg/h was started 5 min before clamping, respectively. Renal IRI was induced by clamping the left renal pedicle for 30 min. The hemodynamics, arterial blood gases, and plasma concentrations of creatinine and lactate were measured at baseline and 1, 2, and 3 h after declamping. Lung wet-to-dry ratio was measured. The mRNA expression of tumor necrosis factor (TNF)-α, interleukin (IL) 1β, and IL-6 and histologic localization of TNF-α in the kidney and lung were measured.

Results

Renal IRI induced metabolic acidosis, pulmonary edema, increases in plasma concentrations of creatinine and lactate, and augmentation of the cytokine mRNA expression and histologic localization of TNF-α in the kidney and Renal IRI induced lung. ANP prevented IRI-induced metabolic acidosis, pulmonary edema, increases in creatinine, lactate, and the cytokine mRNA expression, attenuated histologic localization of TNF-α in the kidney and lung, and increased oxygenation.

Conclusions

ANP has renoprotective and anti-inflammatory effects on the kidney and lung in a rat model of renal IRI, suggesting that ANP attenuates kidney–lung crosstalk.     

Differences in peritoneal response after exposure to low-GDP bicarbonate/lactate-buffered dialysis solution compared to conventional dialysis solution in a uremic mouse model

Background

Long-term exposure of conventional peritoneal dialysis (PD) fluid is associated with structural membrane alterations and technique failure. Previously, it has been shown that infiltrating IL-17-secreting CD4+T cells and pro-fibrotic M2 macrophages play a critical role in the PD-induced pathogenesis. Although more biocompatible PD solutions are recognized to better preserve the peritoneal membrane integrity, the impact of these fluids on the composition of the peritoneal cell infiltrate is unknown.

Materials and methods

In a uremic PD mouse model, we compared the effects of daily instillation of standard lactate (LS) or bicarbonate/lactate-buffered solutions (BLS) and respective controls on peritoneal fibrosis, vascularisation, and inflammation.

Results

Daily exposure of LS fluid during a period of 8 weeks resulted in a peritoneal increase of αSMA and collagen accompanied with new vessel formation compared to the BLS group. Effluent from LS-treated mouse showed a higher percentage of CD4⁺ IL-17⁺ cell population while BLS exposure resulted in an increased macrophage population. Significantly enhanced inflammatory cytokines such as TGFβ1, TNFα, INFγ, and MIP-1β were detected in the effluent of BLS-exposed mice when compared to other groups. Further, immunohistochemistry of macrophage subset infiltrates in the BLS group confirmed a higher ratio of pro-inflammatory M1 macrophages over the pro-fibrotic M2 subset compared to LS.

Conclusion

Development of the peritoneal fibrosis and angiogenesis was prevented in the BLS-exposed mice, which may underlie its improved biocompatibility. Peritoneal recruitment of M1 macrophages and lower number of CD4⁺ IL-17⁺ cells might explain the peritoneal integrity preservation observed in BLS-exposed mouse.

     

The Ratio of Plasma Interleukin-18 Is a Sensitive Biomarker for Acute Kidney Injury After Liver Transplantation

Background

Acute kidney injury (AKI) is common after liver transplantation (OLT) and is associated with high morbidity and mortality. Previous studies have shown that interleukin-18 (IL-18) levels are associated with AKI. The purpose of this study was to determine whether plasma IL-18 levels were early predictors for AKI after liver transplantation.

Methods

Plasma samples were obtained from 26 patients who underwent OLT at induction of anesthesia (T1), 1 hour after the surgical incision (T2), the time of reperfusion (T3), as well as 1 (T4), 2 (T5), and 4 hours (T6) after reperfusion. Samples were also obtained at 24 hours after surgery (T7). The AKI criteria were taken according to the Acute Kidney Injury Network criteria.

Results

Twelve patients (46%) developed AKI after OLT. The area under the receiver operating curve of plasma IL-18 concentrations (T4/T1) to predict AKI occurrence was 0.842 at T5, 0.905 at T6, 0.726 at T7, and 0.726 at T5 to T7.

Conclusion

Plasma IL-18 concentrations taken 1 hour after reperfusion were predictive of AKI. Therefore, changing IL-18 ratio may be an early predictor for AKI after OLT.