AlphaV beta3 (αvβ3) integrin inhibition reduces leukocyte–endothelium interaction in a pressure-induced reperfusion model

The leukocyte-endothelium interaction is known to contribute to reperfusion injury, which is considered to participate in the pathophysiology of pressure ulcers, and integrin alphaV beta3 (alphavbeta3) has been shown to mediate the processes of cellular adhesion in various types of cells. This study aims to clarify leukocyte behavior in our original microcirculatory pressure-induced reperfusion model, which can visualize the microcirculation in vivo. We also estimated the effect of alphavbeta3 integrin inhibition on the reduction of the leukocyte-endothelium interaction. Mice with dorsal skinfold chambers were divided into three groups: the baseline group (n=6), in which animals received no compression; the compression-reperfusion group (n=6), in which animals underwent 2-hour compression of the dorsal skin, followed by release, and the inhibitor-treated group (n=7), in which an alphavbeta3 inhibitor, CP4715, was administered in addition to the compression-release procedure. Staining with rhodamine 6G quantitatively visualized leukocyte behavior under the intravital fluorescent microscope. Compression-reperfusion induced a significant increase in rolling, sticking, and extravasation of the leukocytes. Treatment with the inhibitor strikingly reduced leukocyte sticking and extravasation. The present experiment has provided evidence that alphavbeta3 inhibition reduces leukocyte-endothelium interaction in our original pressure-induced reperfusion model.     

Fluoride uptake and retention at various stages of rat molar enamel development

Suckling rat pups were given intraperitoneal fluoride injections at selected ages so that we could study fluoride uptake in the enamel of the maxillary first molar at various stages of enamel development. Plasma fluoride levels in six-day-old and 11-day-old pups were monitored following the intraperitoneal injection of fluoride. The findings indicate that: (1) fluoride was more easily taken up and retained during the early stages of enamel formation, but fluoride uptake can occur during all stages of enamel formation; (2) when injections were started early in enamel formation, more fluoride was contained in the enamel of the maxillary first molar at 13 days of age; and (3) the same dose of fluoride per gram body weight resulted in greater exposure to elevated plasma fluoride levels in six-day-old pups than in 11-day-old pups.     

Raf-1 kinase,epidermal growth factor receptors,and mutant ras proteins in colonic carcinomas

Epidermal growth factor receptors (EGFR) andras mutations are known to play a significant role in controlling cell growth and tumor promotion. Both of them transmit mitogenic signals to the nucleus by activation of Raf-1 kinase. In this study, the expression of EGFR and mutant Ras proteins, and, for the first time, the expression, phosphorylation and kinase activity of Raf-1 kinase have been determined in paired samples of colorectal cancer and mucosa. The tumor and mucosa samples did not differ significantly with regard to Raf-1 kinase content and activity. A major difference between tumors and mucosa was found, however, in the phosphorylation of Raf-1. Most of the mucosa samples (13/20), but only 1/20 of the cancer samples, contained hyperphosphorylated Raf-1. EGFR were significantly (p=0.0025) decreased in the tumors. The decreased phosphorylation of Raf-1 in colonic carcinomas could be the result of activation of Raf-1 phosphatases or inactivation of kinases phosphorylating Raf-1. New forms of treatment based on EGFR overexpression do not seem to be suitable for the majority of colonic cancers.This work was supported by the state of Baden-Württemberg (Verbundforschungsprojekt: Aufklärung von Mechanismen der Tumorentstehung und Tumorabwehr).     

Retinoblastoma. The relationship of proliferating cells to blood vessels

In 150 retinoblastomas the authors found a uniform thickness of the cuff of viable retinoblastoma cells that surrounds blood vessels. The mean thickness was 98.7 microns with a standard deviation of 11.9 microns. The cross-sectional area of the cuff was negatively correlated with the mitotic activity in the cuff and positively correlated with the diameter of the central vessel. The mitotic activity in the cuff of cells was inversely related to the distance from the central blood vessel. When the cuff was divided into three concentric rings, the inner ring contained a mean of 6.2 mitotic figures, the middle ring contained a mean of 2.9 mitotic figures, and the outer ring contained a mean of 0.6 mitotic figures. This pattern of growth is similar to that observed in other rapidly growing neoplasms in humans and experimental animals. In these tumors this pattern results from reduction in oxygen tension with increased distance from the central blood vessel.     

Analysis of ischemia-reperfusion injury in a microcirculatory model of pressure ulcers

The aim of this study was to establish a pressure ulcer model that visualizes the microcirculation, and to examine the participation of ischemia-reperfusion injury in the pathophysiology of pressure ulcers. An original system composed of a new skin fold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia-reperfusion injury, animals were divided into two groups: the compression-release group (n = 8), in which the animals received four cycles of compression-release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group (n = 8) in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day 1 (35 hours) after the first evaluation. The cyclic compression-release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia-reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. This finding supports the significant contribution of ischemia-reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

Conversion of choledochojejunostomy stents to jejunal feeding tubes for postoperative enteral alimentation

The problem of protein calorie malnutrition following major gastrointestinal surgery can be treated with central venous or enteric alimentation, with the latter being preferred. The authors describe a simple technique for the conversion of biliary stents placed after pancreaticoduodenal surgery into jejunal feeding tubes when the stenting function is no longer needed. Three illustrative cases are presented. In each case, the procedure took less than 30 min and had no associated morbidity. This technique allows early conversion from central venous to enteric alimentation without the need to create a second surgical enterostomy.     

Molecular cloning of an Onchocerca volvulus extracellular Cu-Zn superoxide dismutase.

Onchocerca volvulus, a human parasitic nematode, is the third leading cause of preventable blindness worldwide. This study describes the molecular cloning of a novel superoxide dismutase (SOD) from the parasite. This putative O. volvulus extracellular SOD (OvEcSOD) is 628 nucleotides (nt) long, including a 22-nt 5' spliced leader (SL1) and a portion encoding an N-terminal hydrophobic 42-amino-acid signal peptide. The remainder of the cDNA shares 71% identity with an O. volvulus cytosolic SOD sequence and is 3 nt longer. All residues involved in metal ion binding, active site formation, folding, and dimer formation in SODs are conserved. Data indicate the OvEcSOD and O. volvulus cytosolic SOD are separate gene products and that the OvEcSOD appears to possess the characteristics of a membrane-bound or secreted enzyme which may be involved in the parasite defense against phagocyte-generated reactive oxygen species.     

Head injuries in infants and children: Measures to reduce mortality and morbidity in road accidents

In the 6-year period from 1983 to 1988, 12 infants (<24 months of age) and 103 children (2 to 14 years of age) were killed in road crashes in South Australia. This represents an annual incidence of 6.4 deaths per 100,000 children at risk. At least 4 other children were killed in off-road vehicle-related accidents. Of these deaths, approximately half were car passengers, one third pedestrians, and one sixth pedal cyclists. Most of these infants and children died at the accident site or soon after, but 26 of them survived long enough to be admitted to hospitals with neurosurgical units and an audit of these patients suggests that there were at least 3 preventable deaths. However, autopsies of 78 patients show that the great majority of these deaths resulted from devastating brain and/or trunk visceral injuries. Better emergency care and the use of neurosurgical retrieval teams may save some lives. But more lives might be saved by the use of appropriate restraints for infants and children in cars, by reducing the exposure of child pedestrians and cyclists to road traffic, and by mandatory use of helmets by child cyclists. Off-road vehicular accidents are not as a rule included in road crash statistics; the practice of giving small motorcycles to young children has created a new category of vehicular accidents sometimes causing severe head injury.

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Resumen En el período de seis anños 1983–1988, murieron 12 infantes (edades menores de 24 meses) y 103 niños (edades 2–14 años) en accidentes viales en el Sur de Australia, lo cual representa una incidencia anual de 6.4 muertes por 100,000 miños en riesgo. Por lo menos cuatro niños más murieron en accidentes fuera de carreteras pero relacionados con automotores. De tales muertes, approximadamente la mitad correspondió a pasajeros en carros, una tercera parte a peatones y una sexta parte a ciclistas. La mayoría murió en el lugar del accidente o poco tiempo después, pero 26 sobrevivieron un tiempo sufiente para ser hospitalizados en instituciones con unidades neurológicas; una auditoría de tales casos sugiere que por lo menos hubo tres muertes prevenibles. Sin embargo, la autopsia de 78 casos demostró que la mayoría de estas muertes se debió a lesiones devastadores del cerebro y/o las vísceras corporales. Mejores servicios de urgencia y la utilización de equipos de resucitación neuroquirúrgica pueden salvar algunas vidas, pero más vidas pueden ser salvadas mediante el uso de sistemas adecuados de seguridad para infantes y para niños instalados en los carros, reduciendo la exposición de peatones y ciclistas infantiles al tráfico víal y mediante el uso obligatorio de cascos por los ciclistas infantiles. Los accidentes que ocurren por fuera de las carreteras generalmente no son incluídos en las estadísticas de siniestros víales; la costumbre de obsequiar pequeñas motocicletas a niños pequeños ha creado una nueva categoría de accidentes vehículares que en ocasiones causan grave trauma craneano.

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Résumé Pendant la période de six ans allant de 1983 à 1988, 12 enfants âgés de moins de 24 mois et 103 enfants âgés de 2 à 14 ans ont été tués dans un accident de la route en Australie du Sud. Ceci représente une incidence annuelle de 6.4 morts par 100,000 enfants à risque. Au moins quatre autres enfants ont été dans un accident dû à un véhicule motorisé mais hors de la route. Parmi ces morts, la moitié, environ, était des passagers de la voiture, un tiers, des piétons, et un sixième, des cyclistes. La plupart sont morts sur le lieu de l'accident, mais 26 ont survécu suffisamment pour être transportés dans un Hôpital comportant une service de neurochirurgie avant de décéder. Une évaluation de ces accidents mortels a montré qu'au moins trois décès eux étaient évitables. L'autopsie de 78 de ces enfants a démontré que la plupart des décès étaient dus soit à des lésions cérébrales, soit à des lésions viscérales ou du tronc. De meilleurs soins en urgence, et un meilleur déploiment des équipes neurochirurgicales pourraient éviter quelques morts, mais aussi, un certain nombre de morts pourraient être évitées en utilisant correctement less ceintures de sécurité adaptées aux enfants dans les voitures, en réduisant l'exposition aux accidents de ces enfants, ainsi qu'en rendant obligatoire le port de casque pour les enfants se déplacant à vélo. Les accidents qui n'ont pas lieu sur les routes ne sont pas habituelement inclus dans ces statistiques. La croissance de l'utilisation de petits véhicules motorisés par de très jeunes enfants a créé une nouvelle catégorie d'accidents pouvant parfois être responsables de traumatismes crâniens graves.