Undiagnosed Periprosthetic Infections in First-Time Aseptic Revision Hip Arthroplasties.

: Unexpected infections diagnosed after intraoperative cultures in aseptic revision hip arthroplasties are infrequent, but the features and outcomes of culture-positive cases are still poorly understood. A single-center retrospective study was conducted to assess the following: (1) the incidence, (2) the profile of the cases, and (3) the outcomes of the revision hips performed for presumed aseptic reasons that became septic after intraoperative cultures. Instances of first-time aseptic revision hips (a retrospective cohort study) in the hospital database were reviewed.

Cementless Primary Stems in Revision Hip Arthroplasty: A Narrative Review.

Cementless primary stems in revision hip arthroplasties may be conservative options to preserve bone stock and provide adequate reconstruction of the hip biomechanics. However, there is still little evidence about indications, limitations, and outcomes. This narrative review showed that conventional standard stems were adopted in different revision settings, up to Paprosky IIIA grade bone defects.

Saccadic eye movement performance reduces visual manipulation influence and center of pressure displacements in older fallers.

This study examined changes in postural control and gaze performance of faller and non-faller older adults under conditions of visual tasks and optical flow manipulations. Fifteen older non-fallers (69.8 years, ± 3.

Platelet-Rich Plasma Combined with Hyaluronic Acid versus Leucocyte and Platelet-Rich Plasma in the Conservative Treatment of Knee Osteoarthritis. A Retrospective Study.

: Knee osteoarthritis (KO) is one of the most common joint diseases, determining knee pain and reduction of mobility, with a negative effect on quality of life. Intra-articular injections of different formulations of platelet-rich plasma (PRP) are an increasingly common non-surgical treatment for KO. Recently, in order to combine the anti-inflammatory effect of platelet rich plasma and the viscosupplementation effect of hyaluronic acid, a formulation of PRP combined with hyaluronic acid (PRP + HA) has been proposed.

Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/CXCR2 non-competitive allosteric inhibitor.

Background And Purpose: DF 2156A is a new dual inhibitor of IL-8 receptors CXCR1 and CXCR2 with an optimal pharmacokinetic profile. We characterized its binding mode, molecular mechanism of action and selectivity, and evaluated its therapeutic potential.

Experimental Approach: The binding mode, molecular mechanism of action and selectivity were investigated using chemotaxis of L1.

Protective effect of an inhibitor of interleukin-8 (meraxin) from ischemia and reperfusion injury in a rat model of kidney transplantation.

Introduction: Since the ischemia and reperfusion injury is one of the main causes of delayed graft function after transplantation, research efforts have focused on studying the molecules involved in this inflammatory process. The chemokine interleukin-8 (IL-8) seems to be the main one responsible through a chemoattractive action toward neutropils. Therefore, one of the strategies adopted to prevent this process is blocking the binding between IL-8 and its receptors.

Reparixin, an inhibitor of CXCR2 function, attenuates inflammatory responses and promotes recovery of function after traumatic lesion to the spinal cord.

It has been shown that the blockade of CXCR1 and CXCR2 receptors prevents ischemia/reperfusion damage in several types of vascular beds. Reparixin is a recently described inhibitor of human CXCR1/R2 and rat CXCR2 receptor activation. We applied reparixin in rats following traumatic spinal cord injury and determined therapeutic temporal and dosages windows.

The interleukin-8 (IL-8/CXCL8) receptor inhibitor reparixin improves neurological deficits and reduces long-term inflammation in permanent and transient cerebral ischemia in rats.

Leukocyte infiltration is viewed as a pharmacological target in cerebral ischemia. We previously reported that reparixin, a CXCL8 receptor blocker that inhibits neutrophil infiltration, and related molecules can reduce infarct size in a rat model of transient middle cerebral artery occlusion (MCAO). The study aims were to compare the effects of reparixin in transient and permanent MCAO using varied treatment schedules and therapeutic windows to evaluate effects on long-term neurological deficits and late inflammatory response.

Neutrophil recruitment in the reperfused-injured rat liver was effectively attenuated by repertaxin, a novel allosteric noncompetitive inhibitor of CXCL8 receptors: a therapeutic approach for the treatment of post-ischemic hepatic syndromes.

Hepatic reperfusion injury represents a crucial problem in several clinical situations including liver transplantation, extensive hepatectomy and hypovolemic shock with resuscitation. Repertaxin is a new non-competitive allosteric blocker of interleukin-8 (CXCL8) receptors, which by locking CXCR1/R2 in an inactive conformation, prevents receptor signaling and polymorphonuclear leukocyte (PMN) chemotaxis. The present study shows that repertaxin dramatically prevents rat post-ischemic hepatocellular necrosis (80% of inhibition) and PMN infiltration (96% of inhibition) at a clinically-relevant time (24 h) of reperfusion.

Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2.

Repertaxin is a new non-competitive allosteric blocker of interleukin-8 (CXCL8/IL-8) receptors (CXCR1/R2), which by locking CXCR1/R2 in an inactive conformation prevents receptor signaling and human polymorphonuclear leukocyte (PMN) chemotaxis. Given the unique mode of action of repertaxin it was important to examine the ability of repertaxin to inhibit a wide range of biological activities induced by CXCL8 in human leukocytes. Our results show that repertaxin potently and selectively blocked PMN adhesion to fibrinogen and CD11b up-regulation induced by CXCL8.

Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury.

The chemokine CXC ligand 8 (CXCL8)/IL-8 and related agonists recruit and activate polymorphonuclear cells by binding the CXC chemokine receptor 1 (CXCR1) and CXCR2. Here we characterize the unique mode of action of a small-molecule inhibitor (Repertaxin) of CXCR1 and CXCR2. Structural and biochemical data are consistent with a noncompetitive allosteric mode of interaction between CXCR1 and Repertaxin, which, by locking CXCR1 in an inactive conformation, prevents signaling.

Ischaemic preconditioning modulates the activity of Kupffer cells during in vivo reperfusion injury of rat liver.

This work was performed to elucidate further the main cellular events underlying the protective effect of ischaemic preconditioning in an in vivo rat liver model of 90 min ischaemia followed by 30 min reperfusion. A significant attenuation of the various aspects of post-ischaemic injury, namely necrosis and the levels of hydrogen peroxide and 5- and 15-hydroperoxyeicosatetraenoic acids, was afforded by the prior application of a short cycle of ischaemia/reperfusion (10 + 10 min) or when rats were previously treated with gadolinium chloride. However, when preconditioning was applied on Kupffer cell-depleted livers, no additional level of ischaemic tolerance was obtained.

Ischemic preconditioning attenuates the oxidant-dependent mechanisms of reperfusion cell damage and death in rat liver.

In an in vivo rat model of liver ischemia followed by reperfusion a consistent appearance of necrosis and activation of biochemical pathways of apoptosis was reproduced and monitored after 30 minutes reperfusion. Preconditioning by application of a short cycle of ischemia-reperfusion (10 minutes + 10 minutes) positively conditioned recovery of the organ at reperfusion, attenuating both necrotic and apoptotic events. Preconditioning at least halved cell oxidative damage occurring early at reperfusion, and as a major consequence, the increase of cytolysis and apoptosis occurring at reperfusion was about 50% less.

Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning.

Hepatic ischemia/reperfusion injury has immediate and deleterious effects on the outcome of patients after liver surgery. The precise mechanisms leading to the damage have not been completely elucidated. However, there is substantial evidence that the generation of oxygen free radicals and disturbances of the hepatic microcirculation are involved in this clinical syndrome.

Evidence of an increased nitric oxide production in primary biliary cirrhosis.

Objective: Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation.

Methods: Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis.

Lidocaine inhibition of the hyperpolarization-activated current (I(f)) in sinoatrial myocytes.

The aim of this study was to provide information on the dose dependence and biophysical details of lidocaine blockade of the hyperpolarization-activated current (I(f)) in the sinoatrial node. Isolated rabbit sinoatrial myocytes were patch-clamped in the whole-cell configuration at 36+/-0.5 degrees C, in the presence of 1 mM Ba2+ and 2 mM Mn2+ to minimize contamination by K+ and Ca2+ currents, respectively.