Emerging role of Lipopolysaccharide binding protein in sepsis-induced acute kidney injury

Sepsis remains a serious cause of morbidity and mortality in critically ill patients, with limited therapeutic options available. Of the several disorders connected with sepsis, acute kidney injury (AKI) is one of the major complications. The pathophysiology of sepsis-induced AKI is characterized by severe inflammation in renal parenchyma with endothelial dysfunction, intra-glomerular thrombosis and tubular injury. Endothelial dysfunction is regulated by several mechanisms implicated in cellular de-differentiation, such as endothelial-to-mesenchymal transition (EndMT). Gram-negative bacteria and their cell wall component lipopolysaccharides (LPSs) are frequently involved in the pathogenesis of AKI. The host recognition of LPS requires a specific receptor, which belongs to the Toll-like receptor (TLR) family of proteins, called TLR4, and two carrier proteins, namely the LPS-binding protein (LBP) and cluster of differentiation 14 (CD14). In particular, LBP is released as a consequence of Gram-negative infection and maximizes the activation of TLR4 signalling. Recent findings regarding the emerging role of LBP in mediating sepsis-induced AKI, and the possible beneficial effects resulting from the removal of this endogenous adaptor protein, will be discussed in this review

Exposure to low- vs iso-osmolar contrast agents reduces NADPH-dependent reactive oxygen species generation in a cellular model of renal injury.

Contrast-induced nephropathy represents the third cause of hospital-acquired acute renal failure. This study investigated the effects of low- vs iso-osmolar contrast medium (CM) exposure on NADPH-dependent reactive oxygen species (ROS) generation by tubular cells. X-ray attenuation of iohexol, iopamidol, and iodixanol was assessed at equimolar iodine concentrations and their effects on human renal proximal tubular cells (PTCs) were evaluated with equally attenuating solutions of each CM. Cytotoxicity, apoptosis, and necrosis were investigated by trypan blue exclusion, MTT assay, and annexin V/propidium iodide assay, respectively. ROS production was assessed by DCF assay, NADPH oxidase activity by the lucigenin-enhanced chemiluminescence method, and Nox4 expression by immunoblot. Yielding the same X-ray attenuation, CM cytotoxicity was assessed in PTCs at equimolar iodine concentrations. More necrosis was present after incubation with iohexol and iopamidol than after incubation with equal concentrations of iodixanol. Iohexol and iodixanol at low iodine concentrations induced less cytotoxicity than iopamidol. Moreover, both iohexol and iopamidol induced more apoptosis than iodixanol, with a dose-dependent effect. ROS generation was significantly higher with iopamidol and iohexol compared to iodixanol. NADPH oxidase activity and Nox4 protein expression significantly increased after exposure to iopamidol and iohexol, with a dose-dependent effect, compared with iodixanol. CM-induced Nox4 expression and activity depended upon Src activation. In conclusion, at angiographic concentrations, iodixanol induces fewer cytotoxic effects on cultured tubular cells than iohexol and iopamidol along with a lower induction of Nox4-dependent ROS generation. This enzyme may, thus, represent a potential therapeutic target to prevent iodinated CM-related oxidative stress

PROTEIN WITH APOPTOTIC ACTIVITY ON CANCER CELLS, ITS PREPARATION AND USE

There is described a protein capable of performing an apoptotic action on various line of cancer cells

Emerging role of Lipopolysaccharide binding protein in sepsis-induced acute kidney injury

Sepsis remains a serious cause of morbidity and mortality in critically ill patients, with limited therapeutic options available. Of the several disorders connected with sepsis, acute kidney injury (AKI) is one of themajor complications. The pathophysiology of sepsis-induced AKI is characterized by severe inflammation in renal parenchyma with endothelial dysfunction, intra-glomerular thrombosis and tubular injury. Endothelial dysfunction is regulated by several mechanisms implicated in cellular de-differentiation, such as endothelial-to-mesenchymal transition (EndMT). Gram-negative bacteria and their cell wall component lipopolysaccharides (LPSs) are frequently involved in the pathogenesis of AKI. The host recognition of LPS requires a specific receptor, which belongs to the Toll-like receptor (TLR) family of proteins, called TLR4, and two carrier proteins, namely the LPS-binding protein (LBP) and cluster of differentiation 14 (CD14). In particular, LBP is released as a consequence of Gram-negative infection and maximizes the activation of TLR4 signalling. Recent findings regarding the emerging role of LBP in mediating sepsis-induced AKI, and the possible beneficial effects resulting from the removal of this endogenous adaptor protein, will be discussed in this review

Acute kidney injury in high-risk cardiac surgery patients: Roles of inflammation and coagulation

Aims Acute kidney injury (AKI) is a common complication following cardiac surgery. Cardiopulmonary bypass elicits coagulation and inflammation activation and oxidative stress, all involved in AKI but never simultaneously assessed. We aimed to evaluate relations between oxidative stress, inflammatory and coagulation systems activation and postoperative renal function in patients with normal preoperative renal function. Methods Forty-one high-risk patients (EuroSCORE >6 and preoperative haemoglobin <12 g/dl in women and <13g/dl in men) were prospectively enrolled. Prothrombin fragment 1.2 (coagulation marker), interleukin-6 and interleukin-10 (pro/anti-inflammatory markers) and 8-oxo-20-deoxyguanosine (oxidative stress marker) were evaluated until postoperative day 5. Results Patients were divided into two groups according to estimated glomerular filtration rate reduction observed postoperatively (reduction <25% in 26 patients: NO-AKI group; reduction >25% in 15 patients: AKI group). No differences were found for inflammatory markers. Oxidative stress slightly increased in the AKI group. Twenty-four hours after the operation prothrombin fragment 1.2 levels were significantly higher in the AKI group (506.6 W548 vs. 999 W 704.1 pmol/l; P =0.018), and they were independently associated with estimated glomerular filtration rate reduction, with an area under the receiving operating characteristic of 0.744. Conclusion Thrombin generation is higher in patients with renal function worsening, and it is an independent risk factor for AKI in patients with anaemia, possibly leading to microcirculation impairment and tubular cells damage