Cytotoxicity, thiol depletion and inhibition of O6-methylguanine-DNA methyltransferase by various aldehydes in cultured human bronchial fibroblasts

Lipid peroxidation aldehydes of the 4-hydroxy-, ß-unsaturatedtype, as well as the tobacco-smoke related , ß-unsaturatedaldehyde, acrolein, were highly cytotoxic and decreased theintracellular thiol content in cultured human bronchial fibroblastsafter treatment with micromolar concentrations. In comparison,formaldehyde and acetaldehyde were less toxic and 100- to 300-foldhigher doses were required to affect cell survival or thiollevels. The unsaturated aldehydes also markedly inhibited theDNA repair enzyme O⁶-methylguanine-DNA methyltransferase knownto have a cysteine residue in its active site, but had no effecton the activity of uracil-DNA glycosylase. Our results indicatethat reactive aldehydes of either exogenous or endogenous originhave direct cytotoxic effects and may also make cells more susceptibleto other toxic chemicals due to an impairment in cellular defensemechanisms, e.g., DNA repair and detoxification by systems requiringglutathione.     

A Novel HR-pQCT Image Registration Approach Reveals Sex-Specific Changes in Cortical Bone Retraction With Aging

During aging, changes in endosteal and periosteal boundaries of cortical bone occur that differ between men and women. We here develop a new procedure that uses high-resolution peripheral quantitative CT (HR-pQCT) imaging and 3D registration to identify such changes within the timescale of longitudinal studies. A first goal was to test the sensitivity of the approach. A second goal was to assess differences in periosteal/endosteal expansion over time between men and women. Rigid 3D registration was used to transform baseline and all follow-up (FU) images to a common reference configuration for which the region consisting of complete slices (largest common height) was determined. Periosteal and endosteal contours were transformed to the reference position to determine the net periosteal and endosteal expansion distances. To test the sensitivity, images from a short-term reproducibility study were used (15 female, aged 21 to 47 years, scanned three times). To test differences between men and women, images from a subset of the Geneva Retirees Cohort were used (248 female, 61 male, average age 65 years, 3.5 and 7 years FU). The sensitivity study indicated a least significant change for detecting periosteal/endosteal expansion of 41/31 microns for the radius and 17/26 microns for the tibia. Results of the cohort study showed significant net endosteal retraction only in females at the radius and tibia after 3.5 years (38.0 and 38.4 microns, respectively) that further increased at 7 years FU (70.4 and 70.8 microns, respectively). No significant net periosteal changes were found for males or females at 7 years. The results demonstrate that it is possible to measure changes in endosteal contours in longitudinal studies within several years. For the investigated cohort, significant endosteal retraction was found in females but not in males. Whether these changes in cortical geometry are related to fracture risk remains to be investigated in larger cohorts © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Reported disease and psychological well-being in Swiss adults

Summary In Switzerland, and in many other countries as well, the distribution of morbidity and perceived health in the general population and their determining factors have not been systematically studied so far. This article reports an exploratory study of prevalence of two complex health indicators, longstanding disease (Disease) and psychological well-being (Well-being) and of their environmental, person-specific and behavioural determinants. Data from a health survey conducted in five cantons and three language regions as part of the Swiss Intercantonal Health Indicators Project were used. Whereas distributions of prevalence of Disease according to gender, age, level of education and place of living confirm results of other studies, unexpected prevalence patterns were found for Well-being, especially with regard to gender differences. Multivariate analyses by general linear models (independent sub-samples of the study population were used to develop and validate models) showed different sets of environmental, person-specific and behavioural factors to explain inter-individual differences of Disease and Well-being, both in the total validation sample and in sub-samples of women and men. The results are discussed with regard to implications for socioepidemiological health research.

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Zusammenfassung Wie in zahlreichen anderen Ländern so sind bisher in der Schweiz die Verteilung und die Determinanten von Morbidität und wahrgenommener Gesundheit in der Gesamtbevölkerung nicht systematisch untersucht worden. Die vorliegende Arbeit berichtet über eine explorative Studie über die Prävalenz zweier komplexer Gesundheitsindikatoren, länger andauernde Krankheit (Disease) und psychisches Wohlbefinden (Well-being), und über deren jeweilige umweltbedingte, personale und verhaltensbezogene Einflußfaktoren. Grundlage dafür waren Daten, die in einer Bevölkerungsbefragung in 5 Kantonen und 3 Sprachregionen im Rahmen des Interkantonalen Gesundheitsindikatorenprojekts (IGIPPROMES) erhoben wurden. Während die Verteilung der Prävalenz von Krankheit nach Geschlecht, Alter, Bildungsstatus und Wohnortgrösse den Ergebnissen anderer Studien entspricht, ergaben sich bei der Prävalenz von Wohlbefinden unerwartete Verteilungsmuster, insbesondere Unterschiede zwischen Frauen und Männern. Eine Analyse interindividueller Unterschiede von Krankheit und Wohlbefinden mit Hilfe eines allgemeinen linearen Modells (Modellentwicklung und Validierung an unabhängigen Teilstichproben) zeigte, dass diese durch jeweils spezifische Konstellationen von Umwelt-, Personen- und Verhaltensfaktoren erklärt werden können, sowohl in der gesamten Validierungsstichprobe als auch in den Teilstichproben für Frauen und Männer. Die Ergebnisse der Studie werden in Hinblick auf die Weiterentwicklung der sozialepidemiologischen Gesundheitsforschung diskutiert.

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Résumé En Suisse, comme dans beaucoup d'autres pays, la morbidité et le bien-être psychologique de la population générale n'ont presque pas été étudiés jusqu'à présent. Dans ce rapport, les résultats d'une étude exploratoire sur deux indicateurs complexes de santé, maladie chronique (Disease) et bien-être psychologique (Well-being) et sur les facteurs de l'environnement, de la personnalité et du comportement qui influencent ces deux indicateurs sont présentés. Cette étude faisait part du projet intercantonal sur les indicateurs de santé (IGIP-PROMES) et se base sur les données tirées d'une enquête auprès des populations de cinq cantons et trois régions linguistique de la Suisse. Tandis que la prévalence de l'indicateur «maladie» par sexe, age, degré de formation et dimension du lieu de résidence était conforme aux résultats d'autres études, des distributions inattendues de la prévalence de «bien-être psychologique», notamment des différences entre hommes et femmes ont été trouvées. Une analyse des différences entre individue de «maladie» et «bien-être» au moyen d'un modèle linéaire généralisi — le développement et l'évaluation duquel ont été faits à l'aide de deux échantillons d'occasion indépendents — a montré que des constellations spécifiques constituées de facteurs de l'environnement, de la personnalité et du comportement, peuvent expliquer ces différences, soit dans l'échantillon d'évaluation totale, soit dans les échantillons partiels de femmes et d'hommes. Ces résultats sont discutés par rapport à l'évolution de la recherche socio-épidémiologique.

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Paper presented at a symposium on The Public Health Perspective of Social and Preventive Medicine, in celebration of the 20th anniversary of the Department of Social and Preventive Medicine, University of Berne, 25 June 1992 in Berne.     

Surgical Decompression of the Eighth Nerve for Tinnitus

This article reports two cases of vascular decompression for tinnitus, both of which were successful. The pathophysiology of vascular compression syndromes in general and specifically eighth nerve vascular compression syndromes is reviewed. The anatomy of the anterior inferior cerebellar artery and its relationship to the eighth nerve complex is discussed in detail and the literature of vascular compression syndrome reviewed. Although no unequivocal definitive test procedure is available for preoperative diagnosis of vascular compression syndrome, the presence of the following features makes the diagnosis more likely: I-III interpeak latency abnormalities on auditory brain stem response (ABR), abnormalities of stapedius reflex, unilateral sensorineural hearing loss, ipsilateral electronystagmography (ENG) abnormalities, especially spontaneous nystagmus, and radiographic visualization of a vessel contacting the eighth nerve complex.     

Cationic-amphiphilic arpromidine-derived guanidines and a histamine trifluoromethyl-toluidide derivative may activate pertussis toxin-sensitive G-proteins by a receptor-independent mechanism

Formyl peptides activate superoxide anion (O₂ ^–) formation in human neutrophils and in HL-60 cells via pertussis toxin (PTX)-sensitive guanine nucleotide-binding proteins (G-proteins), and histamine (HA) mediates inhibition of O₂ ^– formation via H₂-receptors. We have studied the effects of lipophilic arpromidine-derived guanidines, which are potent, full H₂-receptor agonists in the guinea pig atrium, on O₂ ^– formation and on activation of G-proteins in HL-60 membranes and on purified G-proteins. We have also studied the effects of a HA trifluoromethyl-toluidide derivative (HTMT), a cationic-amphiphilic HA derivative which activates O₂ ^– formation in HL-60 cells through a mechanism which is independent of known HA receptor subtypes, on G-protein activation. Guanidines, at concentrations, up to 30 mol/l inhibited and, at concentrations above 30 mol/l, enhanced formyl peptide-induce O₂ ^– formation in neutrophils. In HL-60 cells, guanidines per se activated O₂ ^– formation. The stimulatory effects of guanidines on O₂ ^– formation were not inhibited by H₁- or H₂-receptor antagonists. In HL-60 membranes, guanidines and HTMT, activated high-affinity GTPase in a PTX-sensitive manner. These substances also increased GTP hydrolysis effected by transducin and G_i/G_o-proteins. Our data suggest that lipophilic guanidines and HTMT may act as receptor-independent activators of PTX-sensitive G-proteins, resulting in stimulation of O ₂ ^– formation.     

Parameters affecting cellular adhesion to polylactide films

Absorbable biomaterials have been recently incorporated into the field of tissue engineering. Little work has been performed, even with the clinically acceptable absorbables, concerning their tissue promoting capability or lack, thereof. Furthermore, the relative attractions of cells to these implants may be largely disguised by the presence of serum. This research involved the development of an adhesion assay to compare the adhesion behavior of two cell types to two different polylactides in a serum free environment. The results showed that the attachment behavior depends not only on the cell or the polymer but a combination of the two.     

Three-dimensional analysis of the width of the subacromial space in healthy subjects and patients with impingement syndrome

OBJECTIVE: The aim of this study was to per form a three-dimensional analysis of the width of the subacromial space during passive and active arm abduction in healthy volunteers and patients with impingement syndrome. SUBJECTS AND METHODS: The shoulders of 10 healthy subjects and 10 patients with impingement syndrome were imaged with an open MR system during abduction, with and without activation of the shoulder muscles. An apparatus was designed for applying an adduction force of 10 N to the distal humerus during image acquisition, and the minimal acromiohumeral distance was measured after three-dimensional reconstruction. RESULTS: In the 10 healthy volunteers, muscle activity led to a significant decrease (-32%; p < .05) of the acromiohumeral distance at 60 degrees of abduction, whereas at 120 degrees of abduction the distance was significantly increased (+44%; p < .05). In these volunteers, muscle activation caused no significant effect at 90 degrees of abduction. However, in the 10 patients with impingement syndrome, muscle activity led to a significant decrease in the width of the subacromial space compared with that of the healthy contralateral side (-68%; p < .05). CONCLUSION: Muscle activity and arm position were found to cause systematic changes in the width of the subacromial space. However, functional deficits of the supraspinous muscle in patients with early-stage impingement syndrome were not apparent during muscle relaxation.     

Neuronal correlates of real and illusory contour perception: functional anatomy with PET

Illusory contours provide a striking example of the visual system's ability to extract a meaningful representation of the surroundings from fragmented visual stimuli. Psychophysical and neurophysiological data suggest that illusory contours are processed in early visual cortical areas, and neuroimaging studies in humans have shown that Kanizsa-type illusory contours activate early retinotopic visual areas that are also activated by real contours. It is not known whether other types of illusory contours are processed by the same mechanisms, nor is it clear to what extent attentional effects may have influenced these results, as no attempt was made to match the salience of real and illusory stimuli in previous imaging studies. It therefore remains an open question whether there are any brain regions specifically involved in the perception of illusory contours. To address these questions, we have used 15O-butanol positron emission tomography (PET) and a novel kind of illusory contour stimulus that is induced only by aligned line ends. By employing a form discrimination task that was matched for attention and stimulus salience across conditions we were able to directly contrast perception of real and illusory contours. We found that the regions activated by illusory contour perception were the same as those activated by real contours. Only one region, located in the right fusiform gyrus, was significantly more strongly activated by perception of illusory contours than by real contours. In addition, a principal component analysis suggested that illusory contour perception is associated with a change in the correlation between V1 and V2. We conclude that different kinds of illusory contours are processed by the same cortical regions and that these regions overlap extensively with those involved in processing of real contours. At the regional level, perception of illusory contours thus appears to differ from perception of real contours by the degree of involvement of higher visual areas as well as by the nature of interaction between early visual areas.