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).     

SELF-REPORTED HEARING LOSS AMONG WORKERS EXPOSED TO INDUSTRIAL NOISE. ANALYSIS OF U.S. SURVEILLANCE DATA WITH REFERENCE TO THE AUSTRALIAN ENVIRONMENT

Aging and noise are the two main causes of hearing loss. To estimate the extent to which hearing loss is due to noise and is therefore preventable, an analysis was undertaken, using U.S. surveillance data, of the prevalence of hearing loss in workers in industries categorised according to the percentages of the workforce exposed to noise levels of 85 dBA or more. It was estimated that 13 per cent of the U.S. workforce was exposed to these noise levels, and that occupational noise exposure accounted for 20 per cent of self-reported hearing loss in the male workforce. Applying the industry-specific exposures to Australia, it is estimated that some 657,000 workers are exposed to noise levels of 85 dBA or more in this country. Australian Bureau of Statistics data indicate that constant noise accounts for 38 per cent of self-reported hearing loss in Australian adult males (although this figure would include hearing loss due to non-occupational noise). Data from both countries indicate that the prevalence of noise-induced hearing loss in females is negligible.     

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.     

Quantitative structure-activity relationships in MAO-inhibitory 2-phenylcyclopropylamines: Insights into the topography of MAO-A and MAO-B

Ten (E)-and (Z)-isomers of 2-phenylcyclopropylamine (PCA), 1-Me-PCA, 2-Me-PCA, N-Me-PCA, and N, N-diMe-PCA and fifteeno ⁻, m⁻, p⁻ isomers of (E)-PCA with substituents of Me, Cl, F, OMe, OH were synthesized in this laboratory and tested for the inhibition of rat brain mitochondrial MAO-A and MAO-B. The effects of substituents, their positions, and stereochemistry on the inhibition were assessed for the compounds with substituents at cyclopropyl and amino groups and QSAR analyses were performed using the potency data of ring-substituted compounds. The best correlated QSAR equations are as follows: pI₅₀=0.804 Π² Blo−1.069 Blm+0.334 Lp−1.709 HDp+7.897 (r=0.945, s=0.211, F=16.691, p=0.000) for the inhibition of MAO-A; pI₅₀=1.815 π-0.825 Π² R+0.900 Es²+0.869 Es³+0.796 Es⁴−0.992 HDp+0.562 HAo+3.893 (r=0.982, s=0.178, F=23.351, p=0.000) for the inhibition of MAO-B. Based on the potency difference between stereoisomers of cyclopropylamine-modified compounds and on QSAR results, it is proposed that the active sites of MAO-A are composed of one deep hydrophobic cavity near para position, two hydrophobic cavities interacting with Me group, a hydrophobic area accomodating phenyl and cyclopropyl backbone, steric boundaries, a hydrogen-acceptor site near para position, and an amino group binding site and that in addition to the same two hydrophobic cavities, hydrophobic area, steric boundaries, hydrogen-acceptor site, and amino group binding site, another steric boundary near para position and a hydrogen donating site near ortho position constitute active sites of MAO-B.     

Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.     

抗凝血酶Ⅲ测定在评价肝脏功能中的应用

测定110例肝病的抗凝血酶Ⅲ(AT-Ⅲ)活性,62例低于正常(56.4％),均值为60.1±38.2％。50例正常对照为100.0±26.7％。重症肝炎、慢性活动性肝炎及失代偿期肝硬化活性显著下降,均值分别为12.9±13.0％、51.0±34.6％、43.3±29.6％.AT-Ⅲ活性在评价肝脏功能方面较凝血酶原时间敏感,具有一定的实用意义。