Intracranial circulation: pulse-sequence considerations in three- dimensional (volume) MR angiography

The technique and feasibility of magnetic resonance (MR) angiography of intracranial vessels were studied in 35 healthy volunteers. Variations in image orientation, repetition time (TR), and flip angle were evaluated to determine their effects on flow-related enhancement. Gradient modifications--including echo time (TE), motion compensation, bandwidth, and field of view--were also studied in an effort to reduce motion-induced phase shifts. Results indicated that a FISP (fast imaging with steady precession) sequence with a TR of 50 msec, TE of 15 msec, velocity compensation in the read and section-select directions, acceleration compensation in the read direction, anisotropic volume, and a 1.25-mm partition thickness produced three-dimensional angiographic MR images that were accurate and reproducible in the depiction of the major intracranial vessels. Difficulties with field of view, persistent signal void secondary to higher-order motion, and spatial resolution remain major problems requiring additional study.     

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.     

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).     

Lung re-expansion and urinary lipid peroxidation in neonatal pneumothorax.

AIM: Experiential studies suggest that re-expansion of a collapsed lung may result in pulmonary ischaemia-reperfusion injury. We aimed to evaluate the effect of lung re-expansion on urinary lipid peroxidation products in neonates with pneumothorax. METHODS: This study included 20 mechanically ventilated neonates with pneumothorax, and 18 healthy neonates (controls). A chest tube was inserted immediately following the diagnosis of pneumothorax. Urine samples were obtained just before tube thoracostomy (first period), after one hour (second period), every 12 hours by complete reexpansion (third period). Vital signs and ventilatory parameters were recorded. Urinary lipid peroxidation was evaluated by measurement of thiobarbituric acid-reacting substances (TBARS). RESULTS: No significant difference was found between urinary TBARS concentrations in the first, second and third periods (4.08 +/- 2.4 nmol/L, 2.8 +/- 2.3 nmol/L and 3.3 +/- 2.1 nmol/L, respectively). Control TBARS levels (4.1 +/- 2.1 nmol/L) did not significantly differ from those of the neonates with pneumothorax (p > 0.05). The neonates with pneumothorax had higher heart rates compared to the controls (p < 0.01). When compared with controls, the systolic pressure was lower in all periods (p < 0.01), and diastolic blood pressure was lower only in the first and second period (p < 0.05). Oxygen saturation significantly decreased in the first period compared to saturation of the second period and of controls (p < 0.01). Ventilatory parameters did not show any significant difference between the periods. CONCLUSIONS: This prospective study showed that re-expansion of the lung did not significantly affect urinary TBARS concentration in neonatal pneumothorax. Indirectly, short-term lung collapse followed by re-expansion might not cause a clinically significant reperfusion injury in newborns.     

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.     

Influences of central gray matter stimulation on thalamic neuron responses to high- and low-threshold stimulation of trigeminal nerve structures

Responses of the thalamic non-specific medial nuclei and relay ventral posteromedial nucleus neurons evoked by stimulation of the teeth pulp of A alpha and A sigma fibers of infraorbital nerve and caudal nucleus of the spinal trigeminal tract were studied in cats under thiopental-chloralose anesthesia. Three groups of neurons were revealed: low-threshold, high-threshold and convergent. In medial nuclei, 29% of neurons formed the low-threshold group, 12% made up the high-threshold group and 59% were convergent. In the ventral posteromedial nucleus 47% of neurons formed the low-threshold group, 4% made up the high-threshold group and 49% were convergent. Ninety per cent of the medial nuclei neurons and 79% of the ventral posteromedial nucleus neurons responded to stimulation of the caudal nucleus spinal trigeminal tract. The conditioning central gray matter stimulation could suppress responses of low-threshold, high-threshold and convergent neuron groups. In medial nuclei 100% of responses induced by stimulation of teeth pulp and A sigma fibers of the infraorbital nerve were completely suppressed and 86% of responses induced by stimulation of the A alpha fibers of the infraorbital nerve stimulation were also completely suppressed. In the ventral posteromedial nucleus 40% of responses induced by stimulation of teeth pulp and A sigma fibers of the infraorbital nerve were completely suppressed and 26.4% of responses induced by stimulation of the A alpha fibers of the infraorbital nerve were completely suppressed. Conditioning stimulation of the central gray matter suppressed responses evoked by stimulation of the caudal nucleus spinal trigeminal tract and in the most part neurons of the medial nuclei and neuron responses of the ventral posteromedial nucleus. The inhibitory influence of central gray matter stimulation on neuronal responses evoked by stimulation of the caudal nucleus spinal trigeminal tract shows that the central gray matter had a direct influence on the activity of thalamic neurons.     

Effect of the stimulation of the central gray substance of the midbrain on the neuronal responses of the trigeminal caudal nucleus during peripheral excitations

Experiment on cats under chloralose-nembutal anaesthesia has shown that 65% responses of caudal trigeminal nucleus neurons to the activation of the tooth pulp, A alpha and/or A delta infraorbital nerve afferents were completely suppressed by conditioning stimulation of the central grey matter (CGM) by a train of stimuli (10-20) that followed with the rate of 200-400/s, if the interval between conditioning and testing stimuli did not exceed 100 ms. Conditioning stimulation of the CGM inhibited responses of the "convergent" neurons to the activation of tooth pulp most efficiently (0.76) and those to the activation of A alpha afferents more weakly (0.6). Effectiveness of "high-threshold" neurons inhibition under the effect of CGM stimulation was 0.71 and that of "low-threshold" neurons--0.48. Ten caudal trigeminal nucleus neurons were activated by the CGM stimulation with the latency of 7.5-20 ms. These neurons did not respond to peripheral nerve stimulation for 200-450 ms after CGM activation. A possible role of caudal trigeminal nucleus neurons in the CGM inhibition of jaw opening reflexes is discussed.