p-Dimethylaminobenzaldehyde-reactive substances in tail tendon collagen of streptozotocin-diabetic rats: temporal relation to biomechanical properties and advanced glycation endproduct (AGE)-related fluorescence

AbstractIn the present work, pepsin digests of tail tendons from streptozotocin-diabetic rats were found to contain material that reacted rapidly at room temperature with p-dimethylaminobenzaldehyde (Ehrlich’s reagent) to give an adduct with an absorbance spectrum characteristic of the Ehrlich chromogen of pyrrolic nature determined in ageing collagens. A significant correlation of the Ehrlich adduct with tendon mechanical strength and collagen fluorescence characteristic of advanced glycation endproducts was observed. Collagen content of the Ehrlich-positive material was found to be significantly elevated in tendons of diabetic rats compared with age-matched healthy controls. The results indicate that the p-dimethylaminobenzaldehyde-reactive pyrrole moieties may contribute to the increased cross-linking of diabetic matrix collagen. Profound inhibitory effect of aminoguanidine was observed, underlining the role of non-enzymatic mechanisms of advanced glycation in pyrrolisation and cross-linking of collagen exposed to hyperglycaemia. It is hypothesised that quantification of the p-dimethylaminobenzaldehyde-reactive material in matrix collagen may provide a tissue measure of integrated hyperglycaemia over prolonged periods of time. Further research is to assess the significance of p-dimethylaminobenzaldehyde-reactive substances in diabetic collagen tissues and to reveal their relationship to enzyme-mediated physiological pyrrolisation of ageing collagens

Distinctive Left-Sided Distribution of Adrenergic-Derived Cells in the Adult Mouse Heart

Adrenaline and noradrenaline are produced within the heart from neuronal and non-neuronal sources. These adrenergic hormones have profound effects on cardiovascular development and function, yet relatively little information is available about the specific tissue distribution of adrenergic cells within the adult heart. The purpose of the present study was to define the anatomical localization of cells derived from an adrenergic lineage within the adult heart. To accomplish this, we performed genetic fate-mapping experiments where mice with the cre-recombinase (Cre) gene inserted into the phenylethanolamine-n-methyltransferase (Pnmt) locus were cross-mated with homozygous Rosa26 reporter (R26R) mice. Because Pnmt serves as a marker gene for adrenergic cells, offspring from these matings express the β-galactosidase (βGAL) reporter gene in cells of an adrenergic lineage. βGAL expression was found throughout the adult mouse heart, but was predominantly (89%) located in the left atrium (LA) and ventricle (LV) (p<0.001 compared to RA and RV), where many of these cells appeared to have cardiomyocyte-like morphological and structural characteristics. The staining pattern in the LA was diffuse, but the LV free wall displayed intermittent non-random staining that extended from the apex to the base of the heart, including heavy staining of the anterior papillary muscle along its perimeter. Three-dimensional computer-aided reconstruction of XGAL+ staining revealed distribution throughout the LA and LV, with specific finger-like projections apparent near the mid and apical regions of the LV free wall. These data indicate that adrenergic-derived cells display distinctive left-sided distribution patterns in the adult mouse heart

The M235T Polymorphism in the AGT Gene and CHD Risk: Evidence of a Hardy-Weinberg Equilibrium Violation and Publication Bias in a Meta-Analysis

BACKGROUND: The M235T polymorphism in the AGT gene has been related to an increased risk of hypertension. This finding may also suggest an increased risk of coronary heart disease (CHD). METHODOLOGY/PRINCIPAL FINDINGS: A case-cohort study was conducted in 1,732 unrelated middle-age women (210 CHD cases and 1,522 controls) from a prospective cohort of 15,236 initially healthy Dutch women. We applied a Cox proportional hazards model to study the association of the polymorphism with acute myocardial infarction (AMI) (n = 71) and CHD. In the case-cohort study, no increased risk for CHD was found under the additive genetic model (hazard ratio [HR] = 1.20; 95% confidence interval [CI], 0.86 to 1.68; P = 0.28). This result was not changed by adjustment (HR = 1.17; 95% CI, 0.83 to 1.64; P = 0.38) nor by using dominant, recessive and pairwise genetic models. Analyses for AMI risk under the additive genetic model also did not show any statistically significant association (crude HR = 1.14; 95% CI, 0.93 to 1.39; P = 0.20). To evaluate the association, a comprehensive systematic review and meta-analysis were undertaken of all studies published up to February 2007 (searched through PubMed/MEDLINE, Web of Science and EMBASE). The meta-analysis (38 studies with 13284 cases and 18722 controls) showed a per-allele odds ratio (OR) of 1.08 (95% CI, 1.01 to 1.15; P = 0.02). Moderate to large levels of heterogeneity were identified between studies. Hardy-Weinberg equilibrium (HWE) violation and the mean age of cases were statistically significant sources of the observed variation. In a stratum of non-HWE violation studies, there was no effect. An asymmetric funnel plot, the Egger's test (P = 0.066), and the Begg-Mazumdar test (P = 0.074) were all suggestive of the presence of publication bias. CONCLUSIONS/SIGNIFICANCE: The pooled OR of the present meta-analysis, including our own data, presented evidence that there is an increase in the risk of CHD conferred by the M235T variant of the AGT gene. However, the relevance of this weakly positive overall association remains uncertain because it may be due to various residual biases, including HWE-violation and publication biases

Die Auswirkungen von der Auswahl der Vertragsarten der Sicherstellung der Verkehrsleistungen auf die Ansprüche der Leistungbesteller

The paper deals with the issue of the influence of contract form choice of the transport services ensuring on performance contracting entity requirement. In the first part, it describes the current state of transport services financing in the Slovak Republic and risk analysis, which is related to conclusion of the service contract in the transport services ensuring. The rest of the paper defines the impact of services contracts of ensuring the transport services on performance contracting entity requirement.Beitrag beschäftigt sich mit dem Problem der Auswirkungen von der Auswahl der Vertragsarten der Sicherstellung der Verkehrsleistungen auf die Ansprüche der Leistungbesteller. Der erste Teil beschreibt den aktuellen Stand der Transportdienstleistungen Finanzierungen in der Slowakischen Republik und die Risikoanalyse, die im Zusammenhang mit Abschluß des Dienstleistungsvertrags in der Sicherstellung der Verkehrsleistungen ist. Der Rest des Betrags definiert die Auswirkungen der Vertragen der Sicherstellung der Verkehrsleistungen auf die Ansprüche der Leistungbesteller

Wpływ metody zamówień usług transportowych na wymagania finansowe umowy o wydajności podmiotu

The paper deals with the issue of the impact of procurement method of the transport services to the financial requirement of performance contracting entity. In the first part, it describes the current state of transport services financing in the Slovak Republic and risk analysis, which is related to transport services procurement and conclusion of the service contract in the transport services ensuring. The rest of the paper defines the impact of procurement method of the transport services to the financial requirement of performance contracting entity.Artykuł ten mierzy się z problemem wpływu metody zamówień usług transportowych na wymagania finansowe umowy o wydajności podmiotu. W pierwszej części, opisany został obecny stan usług transportowych finansowanych na Słowacji i analizy ryzyka, które jest powiązane z zamówieniami usług transportowych i wnioski z umowy o świadczeniu usług w ubezpieczeniu usług transportowych. Reszta artykułu definiuje wpływ metody zamówień usług transportowych na wymagania finansowe umowy o wydajności podmiotu

Effect of novel stressors on tyrosine hydroxylase gene expression in the adrenal medulla of repeatedly immobilized rats

The activity of the sympathetic-adrenomedullary system in rats submitted to novel stressors after prior repeated or chronic stress exposure is poorly understood. The purpose of the present work was to investigate changes in adrenomedullary (AM) tyrosine hydroxylase (TH) gene expression after a single or long-term repeated exposure of rats to immobilization stress (IMMO; 42 times), as well as in repeatedly immobilized rats (41 times) exposed once to various novel heterotypic stressors. Cold exposure for 5 h, administration of insulin (INS, 5IU), or 2-deoxyglucose (2DG, 500 mg/kg) were used as novel stressors. A single exposure to cold, INS, or 2DG produced transient increases in TH mRNA levels in AM. Animals e: posed to repeated homotypic IMMO stress showed permanently increased TH mRNA levels, TH activity, and protein levels; however, an exposure of such animals to heterotypic novel stressors did not induce any further changes. Thus the observed differences in TH mRNA levels in the AM of control rats and long-term repeatedly IMMO rats suggest that an adaptation to this stressor is displayed by a permanently increased TH gene expression, TH activity, and protein level. The exposure of repeatedly IMMO rats to a single episode of novel stressor does not induce exaggerated responses in TH gene expression, as some other stressors do. The mechanism of this finding could involve a central regulation and/or adrenomedullary signaling pathway(s), leading to additional modifications or accumulation of transcription factors. The precise mechanism(s) of this phenomenon remains to be elucidated