Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells

Leukocyte adhesion contributes to perfusion abnormalities and tissue damage during trauma, shock or overwhelming inflammation. This study was performed to determine whether the lipoxygenase inhibitor phenidone and derivatives decrease the expression of adhesion molecules on tumor necrosis factor-α (TNF-α) stimulated endothelial cells and attenuate leukocyte-endothelial interactions under flow in vitro. TNF-α stimulated human umbilical venous endothelial cells (HUVECs) were incubated with phenidone, 4-methyl-phenidone, 4-4-dimethyl-phenidone, 5-methyl-phenidone, 5-phenyl-phenidone, and 5-methyl-1,(2,5-di-chloro-phenyl)-3-pyrazolidone. We tested the inhibition of adhesion molecule expression at different inhibitor concentrations before, during, and after the stimulation of HUVECs. The inhibition of endothelial cell expression on HUVECs was measured by flow cytometry. Rolling and firm adhesion of leukocytes to pretreated endothelium was examined in a parallel plate flow chamber. Phenidone inhibited the expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial-leukocyte adhesion molecule-1 on HUVECs when added prior to HUVEC stimulation. The inhibitory effect of phenidone was still observed when added simultaneously, but not when added after HUVEC stimulation. 4-4-dimethyl-phenidone and 5-phenyl-phenidone inhibited the expression of adhesion molecules more effectively than phenidone. The attenuation of leukocyte rolling under flow conditions was also significantly more effective with 4-4-dimethyl-phenidone than with phenidone. Lipoxygenase inhibitors might be of therapeutically interest for the treatment of overwhelming systemic inflammation during shock, trauma, and sepsis

Influence of fluid resuscitation on renal microvascular PO(2 )in a normotensive rat model of endotoxemia

INTRODUCTION: Septic renal failure is often seen in the intensive care unit but its pathogenesis is only partly understood. This study, performed in a normotensive rat model of endotoxemia, tests the hypotheses that endotoxemia impairs renal microvascular PO(2 )(μPO(2)) and oxygen consumption (VO(2,ren)), that endotoxemia is associated with a diminished kidney function, that fluid resuscitation can restore μPO(2), VO(2,ren )and kidney function, and that colloids are more effective than crystalloids. METHODS: Male Wistar rats received a one-hour intravenous infusion of lipopolysaccharide, followed by resuscitation with HES130/0.4 (Voluven(®)), HES200/0.5 (HES-STERIL(® )(® )6%) or Ringer's lactate. The renal μPO(2 )in the cortex and medulla and the renal venous PO(2 )were measured by a recently published phosphorescence lifetime technique. RESULTS: Endotoxemia induced a reduction in renal blood flow and anuria, while the renal μPO(2 )and VO(2,ren )remained relatively unchanged. Resuscitation restored renal blood flow, renal oxygen delivery and kidney function to baseline values, and was associated with oxygen redistribution showing different patterns for the different compounds used. HES200/0.5 and Ringer's lactate increased the VO(2,ren), in contrast to HES130/0.4. CONCLUSION: The loss of kidney function during endotoxemia could not be explained by an oxygen deficiency. Renal oxygen redistribution could for the first time be demonstrated during fluid resuscitation. HES130/0.4 had no influence on the VO(2,ren )and restored renal function with the least increase in the amount of renal work

Effects of different leukocyte subpopulations and flow conditions on leukocyte accumulation during reperfusion

Background/Aims: The study examined the interdependent effects of shear stress and different leukocyte subpopulations on endothelial cell activation and cell interactions during low flow and reperfusion. Methods: Human umbilical venous endothelial cells were perfused with either neutrophils or monocytes at different shear stress (2-0.25 dyn/cm 2) and adhesion was quantified by microscopy. Effects of adherent neutrophils and monocytes on endothelial cell adhesion molecule expression were analyzed by flow cytometry after 4-hour static coincubation. After coincubation, the cocultures were reperfused with labeled neutrophils at 2 dyn/cm 2 and their adhesion was quantified selectively. For the control, endothelium monocultures with and without lipopolysaccharide activation were used. Results: At 2 dyn/cm 2, adhesion did not exceed baseline levels on nonactivated endothelium. Decreasing shear stress to 0.25 dyn/cm 2 largely increased the adhesion of both leukocyte subpopulations, similar to the effect of lipopolysaccharide at 2 dyn/cm 2. However, only adherent monocytes increased adhesion molecule expression, whereas neutrophils had no effect. As a functional consequence, adherent monocytes largely increased neutrophil adhesion during reperfusion, whereas adherent neutrophils did not. Conclusion: Compromised shear stress is an autonomous trigger of leukocyte adhesion even in the absence of additional activators. Exceeding this immediate effect, adherent monocytes induce further endothelial activation and enhance further neutrophil adhesion during reperfusion. Copyrigh

Cephalometric Evaluation of Maxillary Incisors Torque and Vertical Changes Utilizing Standard Edgewise Mechanics

In 1995 Gebeck & Merrifield studied a successful and unsuccessful treated Class I and Class IIÕs samples; they found a -1.33 mm intrusion in the former and a 0.80 mm extrusion in the latter. The purpose of this article was to perform a cephalometric evaluation of maxillary incisors torque and vertical changes. We studied a sample of 129 patients, 30 males and 99 females, taken from The Charles H. Tweed Foundation Long Term Study, at tretreatment mean age 12.93 years, posttreatment mean age 16.19 years and follow up post retention mean age 29.83 years, a 13.88 years interval. The records were collected from private practitioners across the North American continent who used Standard Edgewise Mechanics and were members of the Charles H. Tweed Foundation. All patients were Class I and II American whites treated with the extraction of 4 premolars. We found an Upper anterior incisal edge to PP vertical linear measurement 28.7 and 29.2 mm, +0.53 mm (p<0.019) from pretreatment to posttreatment. The average Upper 1 to SN angle was 103.2° at pretreatment and 100.1° at posttreatment, -3.2° (p<0.000), Upper 1 to PP 111.0° and 108.9°, -2.2° (p<0.000), the three of them statistically significant. Conversely, Upper 1 to commissure was not. The four measurements were also statistically significant posttreatment to follow up, upper anteriors kept losing torque after posttreatment, and less upper anteriors surface was below the commissure. Some torque loss and vertical extrusion can be expected while treating patients with extractions of four premolars, therefore, upper incisor inclination increase and vertical change by itself cannot determine the success of treatmen

Perioperative fluid and volume management: physiological basis, tools and strategies

Fluid and volume therapy is an important cornerstone of treating critically ill patients in the intensive care unit and in the operating room. New findings concerning the vascular barrier, its physiological functions, and its role regarding vascular leakage have lead to a new view of fluid and volume administration. Avoiding hypervolemia, as well as hypovolemia, plays a pivotal role when treating patients both perioperatively and in the intensive care unit. The various studies comparing restrictive vs. liberal fluid and volume management are not directly comparable, do not differ (in most instances) between colloid and crystalloid administration, and mostly do not refer to the vascular barrier's physiologic basis. In addition, very few studies have analyzed the use of advanced hemodynamic monitoring for volume management

El programa académico Conservación y Restauración de Bienes Culturales Muebles” de la UNEFM, un aporte para mantener la obra de arte en el tiempo

The present research aims to present in an orderly way the current structural philosophy of the program, as far as the managerial and academic contribution, as well as from extension and research. All of this action plan was presented to the Educational Sciences Department in a responsible manner and organized with the various coordinations and functions taught by the same teachers attached to the program, with the help of UNEFM units and other institutions that Support it, maintaining working ties in search of a win-win. As far as the academics were concerned about the inclusion of new students, it was reorganized and conditioned the spaces of the headquarters for a better use of them in search of an educational quality, in addition, the students of the last semester are conserving and restoring works of Art of the eighteenth century coming from the ecclesiastical institutions and museums of the city of Coro amplifying on the part of the society the receptivity and attachment to the program.La presente investigación tiene como objetivo presentar en forma ordenada la actual filosofía estructural del programa, en cuanto el aporte gerencial y académico, como también, desde la extensión y la investigación. Todo este plan de acción se presentó un organigrama al decanato de Ciencias de la Educación de manera responsable y organizada con las diversas coordinaciones y funciones impartidas por los mismos docentes adscrito al programa, esto con la ayuda de las dependencias de la UNEFM y otras instituciones que lo apoyan, manteniendo lazos de trabajo en busca de un ganar- ganar. En cuanto a los académico se preocupó por la inclusión de nuevos estudiantes, se reambientó y acondicionó los espacios de la sede para un mejor aprovechamiento de los mismos en búsqueda de una calidad educativa, además, los estudiantes del último semestre están conservando y restaurando obras de arte del siglo XVIII proveniente de las instituciones eclesiásticas y museos de la ciudad de Coro ampliando por parte de la sociedad la receptividad y apego al programa