The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

Predictive value of cervical cytokine, antimicrobial and microflora levels for pre-term birth in high-risk women

Spontaneous preterm birth (sPTB, delivery <37 weeks gestation), accounts for approximately 10% of births worldwide; the aetiology is multifactorial with intra-amniotic infection being one contributing factor. This study aimed to determine whether asymptomatic women with a history of sPTB or cervical surgery have altered levels of inflammatory/antimicrobial mediators and/or microflora within cervical fluid at 22-24 weeks gestation. External cervical fluid was collected from women with history of previous sPTB and/or cervical surgery at 22-24 weeks gestation (n = 135). Cytokine and antimicrobial peptides were measured on a multiplex platform or by ELISA. qPCR was performed for detection of 7 potentially pathogenic bacterial species. IL-8 and IL-1β levels were lower in women who delivered preterm compared to those who delivered at term (IL-8 P = 0.02; IL-1β P = 0.04). There were no differences in elafin or human beta defensin-1 protein levels between the two groups. Multiple bacterial species were detected in a higher proportion of women who delivered preterm than in those who delivered at term (P = 0.005). Cervical fluid IL-8 and IL-1β and microflora have the potential to be used as biomarkers to predict sPTB in high risk women

Feeding Blueberry Diets in Early Life Prevent Senescence of Osteoblasts and Bone Loss in Ovariectomized Adult Female Rats

Appropriate nutrition during early development is essential for maximal bone mass accretion; however, linkage between early nutrition, childhood bone mass, peak bone mass in adulthood, and prevention of bone loss later in life has not been studied.In this report, we show that feeding a high quality diet supplemented with blueberries (BB) to pre-pubertal rats throughout development or only between postnatal day 20 (PND20) and PND34 prevented ovariectomy (OVX)-induced bone loss in adult life. This protective effect of BB is due to suppression of osteoblastic cell senescence associated with acute loss of myosin expression after OVX. Early exposure of pre-osteoblasts to serum from BB-fed rats was found to consistently increase myosin expression. This led to maintenance osteoblastic cell development and differentiation and delay of cellular entrance into senescence through regulation of the Runx2 gene. High bone turnover after OVX results in insufficient collagenous matrix support for new osteoblasts and their precursors to express myosin and other cytoskeletal elements required for osteoblast activity and differentiation.These results indicate: 1) a significant prevention of OVX-induced bone loss from adult rats can occur with only 14 days consumption of a BB-containing diet immediately prior to puberty; and 2) the molecular mechanisms underlying these effects involves increased myosin production which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence

Pessimism and the risk for coronary heart disease among middle-aged and older Finnish men and women: a ten-year follow-up study

This was a ten-year prospective cohort study on a regional sample of three cohorts aged 52–56, 62–66 and 72–76 years at baseline (N = 2815). The study groups were personally interviewed four times (in 2002, 2005, 2008 and 2012). The revised Life Orientation Test (LOT-R) was completed at the first appointment to determine the level of dispositional optimism or pessimism. During the ten-year follow-up, the incidence of new cases of coronary heart diseases was measured. The association between dispositional optimism/pessimism and the incidence of CHD during the follow-up was studied with logistic regression. Results Those who developed coronary heart disease during the ten-year follow-up were significantly more pessimistic at baseline than the other subjects. Using multivariate logistic regression models separately for men and women, we noticed no elevated risk for CHD in the pessimistic women compared to the non-pessimistic women. However, among men in the highest quartile of pessimism, the risk for CHD was approximately four-fold (OR 4.11, 95 % CI 1.68–11.04) that of the men in the lowest quartile. Optimism did not seem to have any role in the risk for developing CHD. Discussion Our main finding is that pessimism seemed to be a clear risk factor for coronary heart disease in men even after adjusting for classical well-known risk factors while optimism did not seem to be a protective factor. Connection between pessimism and coronary heart disease was not detectable among women. Similar gender differences between psychosocial factors and overall well-being have been noticed in some earlier studies, too. The mechanism of this gender difference is not fully understood. Differences between men and women in somatic responses to stress found in earlier studies may at least partly explain this phenomenon. The impact of optimism and pessimism on cardiovascular disease has been studied earlier and several possible mechanisms have been discovered but it seems clear that they cannot fully explain the association. For example, optimists have healthier lifestyles which lowers the risk for coronary heart disease, but pessimism was established to be a risk factor for cardiovascular disease in our study even in logistic regressions including the best known classical risk factors, e.g. smoking and high level of blood glucose. According to our study it is important to pay attention also to the psychosocial components in addition to the well-known risk factors when planning the prevention of coronary heart disease. Measuring pessimism is quite easy and it consumes very little time. Once the amount of pessimism is ascertained, it is easier to define who is in the greatest need of preventive actions concerning coronary heart disease. Conclusions Pessimism seems to be a substantial risk factor for CHD, and as an easily measured variable it might be a very useful tool together with the well-known physiological risk factors to determine the risk for developing CHD, at least among men.BioMed Central open acces

Congruence of tissue expression profiles from Gene Expression Atlas, SAGEmap and TissueInfo databases

BACKGROUND: Extracting biological knowledge from large amounts of gene expression information deposited in public databases is a major challenge of the postgenomic era. Additional insights may be derived by data integration and cross-platform comparisons of expression profiles. However, database meta-analysis is complicated by differences in experimental technologies, data post-processing, database formats, and inconsistent gene and sample annotation. RESULTS: We have analysed expression profiles from three public databases: Gene Expression Atlas, SAGEmap and TissueInfo. These are repositories of oligonucleotide microarray, Serial Analysis of Gene Expression and Expressed Sequence Tag human gene expression data respectively. We devised a method, Preferential Expression Measure, to identify genes that are significantly over- or under-expressed in any given tissue. We examined intra- and inter-database consistency of Preferential Expression Measures. There was good correlation between replicate experiments of oligonucleotide microarray data, but there was less coherence in expression profiles as measured by Serial Analysis of Gene Expression and Expressed Sequence Tag counts. We investigated inter-database correlations for six tissue categories, for which data were present in the three databases. Significant positive correlations were found for brain, prostate and vascular endothelium but not for ovary, kidney, and pancreas. CONCLUSION: We show that data from Gene Expression Atlas, SAGEmap and TissueInfo can be integrated using the UniGene gene index, and that expression profiles correlate relatively well when large numbers of tags are available or when tissue cellular composition is simple. Finally, in the case of brain, we demonstrate that when PEM values show good correlation, predictions of tissue-specific expression based on integrated data are very accurate

Pregnane X Receptor and Yin Yang 1 Contribute to the Differential Tissue Expression and Induction of CYP3A5 and CYP3A4

The hepato-intestinal induction of the detoxifying enzymes CYP3A4 and CYP3A5 by the xenosensing pregnane X receptor (PXR) constitutes a key adaptive response to oral drugs and dietary xenobiotics. In contrast to CYP3A4, CYP3A5 is additionally expressed in several, mostly steroidogenic organs, which creates potential for induction-driven disturbances of the steroid homeostasis. Using cell lines and mice transgenic for a CYP3A5 promoter we demonstrate that the CYP3A5 expression in these organs is non-inducible and independent from PXR. Instead, it is enabled by the loss of a suppressing yin yang 1 (YY1)-binding site from the CYP3A5 promoter which occurred in haplorrhine primates. This YY1 site is conserved in CYP3A4, but its inhibitory effect can be offset by PXR acting on response elements such as XREM. Taken together, the loss of YY1 binding site from promoters of the CYP3A5 gene lineage during primate evolution may have enabled the utilization of CYP3A5 both in the adaptive hepato-intestinal response to xenobiotics and as a constitutively expressed gene in other organs. Our results thus constitute a first description of uncoupling induction from constitutive expression for a major detoxifying enzyme. They also suggest an explanation for the considerable tissue expression differences between CYP3A5 and CYP3A4