The efficacy of antihypertensiye drugs in chronic intermittent hypoxia conditions

The authors would like to thank the Portuguese Fundacao para a Ciencia e a Tecnologia (FCT) and CEDOC (Chronic Diseases Research Centre, Lisbon, Portugal). Lucilia N. Diogo is supported by an FCT fellowship (SFRH/BD/48335/2008; PTDC/SAU-TOX/112264/2009).Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CRAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT.publishersversionpublishe

Comparative analysis of

A quantitative analysis of 137Cs bioavailability in forest soils in the long term after the Chernobyl NPP accident based on a 3 years (1996-1998) investigation is presented. Five sites with different trees composition and properties of soil were studied to identify factors determining radiocaesium transfer to trees and different under story species. The following parameters were investigated: 137Cs activity concentrations and its speciation in various horizons of forest soil, accumulation of this radionuclide by different species of under story vegetation and distribution of their root biomass in the soil profile. It has been shown that one decade after the deposition maximum 137Cs activity in soil of the experimental sites considered is located in different soil layers dependent on moisture regime, characteristics of litter and soil properties. High level of heterogeneity of 137Cs specific activity in different parts of tree, which is related to physiological peculiarities of their functions, has been shown. The data obtained have demonstrated a non-uniform character for 137Cs distribution along trunks, which can be explained by radionuclide fixation by walls of xylem vessels and by changes in geometry along the tree trunk. It has been found that the radial distribution of 137Cs in the tree trunk is dependent on the availability of 137Cs in soil, which governs the transfer of this radionuclide via xylem sap, and on the properties of the xylem. The accumulation of 137Cs by both trees and under story species was influenced by 137Cs vertical distribution and availability in soil as well as by the root (mycelia) biomass distribution in different soil horizons. A "bioavailability factor", which takes into account the above factors, is proposed for comparative analyses of 137Cs transfer from soil to plants in different types of forest ecosystems

Isotope dilution tandem mass spectrometric method for T4/T3

BACKGROUND: The thyroid hormones thyroxine (T4) and 3,5,3′-triidothyronine (T3) are essential for regulating a number of biological processes, including growth, neurodevelopment, carbohydrate metabolism, oxygen consumption and protein synthesis. Immunoassays are the current methods for thyroid hormone measurement and suffer from a lack of specificity. Our objective was to simultaneously measure T4 and T3 using isotope dilution tandem mass spectrometry within a single run. To compare the results obtained by this MS/MS method with those obtained by an immunoassay procedure on the same samples (DPC Immulite for T3, Diagnostics Product, and Dade RxL Dimension for T4, Dade-Behring). METHODS: An API-3000 tandem mass spectrometer (SCIEX, Toronto, Canada) equipped with TurboIonSpray and Shimadzu HPLC system was used employing isotope dilution with deuterium-labeled internal standard (l-thyroxin-d(2)). The method requires 100 µl of serum and involves addition of internal standard, precipitation of proteins with methanol and injection of the supernatant onto a C-18 column. After washing, the switch valve is activated and T4 and T3 eluted using a methanol gradient. T4 and T3 by immunoassay were performed using the Dade RxL Dimension and the DPC Immulite, respectively. RESULTS AND CONCLUSIONS: An isotope dilution tandem mass spectrometry method for the simultaneous determination of total T4 and T3 in serum is described which is accurate, specific, precise (%CVs 3.5–9.0), simple and fast (< 7 min)