The volume of the carotid bodies and blood pressure variability and pulse pressure in patients with essential hypertension.

AIM: To assess the relationship between the volume of the carotid bodies (VrCB+lCB) examined by means of computed tomography angiography (CTA) and blood pressure variability and pulse pressure (PP) in 24-hour ambulatory blood pressure monitoring (ABPM) in patients with essential hypertension. MATERIALS AND METHODS: A group of 52 patients with essential hypertension was examined (mean age: 68.32±12.31 years), the sizes of carotid bodies were measured by means of carotid artery CTA, and 24-hour ABPM was carried out. The 24-hour ABPM established systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), PP, SBP variability (SBPV), and DBP variability (DBPV). RESULTS: SBP, MAP, and SBPV were significantly higher in the group of hypertension patients with VrCB+lCB equal to or above the median than in the group of hypertension patients with VrCB+lCB less than the median, as well as in the group of hypertension patients with oversized carotid bodies, than in the group of hypertension patients with normal VrCB+lCB. Moreover, the PP was statistically significantly higher in the group of hypertension patients with VrCB+lCB equal to or above the median than in the group of hypertension patients with VrCB+lCB less than the median. The existence of statistically significant positive linear relationships was revealed between VrCB+lCB and SBP, PP, and SBPV. A higher body mass index, older age, smoking, and higher VrCB+lCB are independent risk factors increasing SBPV in the research group. CONCLUSION: A positive relationship between the size of the carotid bodies and variability of the SBP and PP is observed in patients with essential hypertension.

Unnatural amino acids increase sensitivity and provide for the design of highly selective caspase substrates.

Traditional combinatorial peptidyl substrate library approaches generally utilize natural amino acids, limiting the usefulness of this tool in generating selective substrates for proteases that share similar substrate specificity profiles. To address this limitation, we synthesized a Hybrid Combinatorial Substrate Library (HyCoSuL) with the general formula of Ac-P4-P3-P2-Asp-ACC, testing the approach on a family of closely related proteases - the human caspases. The power of this library for caspase discrimination extends far beyond traditional PS-SCL approach, as in addition to 19 natural amino acids we also used 110 diverse unnatural amino acids that can more extensively explore the chemical space represented by caspase-active sites. Using this approach we identified and employed peptide-based substrates that provided excellent discrimination between individual caspases, allowing us to simultaneously resolve the individual contribution of the apical caspase-9 and the executioner caspase-3 and caspase-7 in the development of cytochrome-c-dependent apoptosis for the first time.

The relationship between environmental exposure to cadmium and lead and blood selenium concentration in randomly selected population of children inhabiting industrial regions of Silesian Voivodship (Poland).

This study aimed at determining the relationship between environmental exposure to lead (Pb) and cadmium (Cd) and blood selenium (Se) concentration in randomly selected population of children inhabiting the industrial regions of Silesian Voivodship, Poland. The study was conducted on a group of consecutive randomly selected 349 children aged below 15 years and inhabiting the industrial regions in Upper Silesia. The examined variables included whole blood Cd concentration (Cd-B), whole blood Pb concentration (Pb-B) and whole blood Se concentration (Se-B). The concentration of Cd-B, Pb-B and Se-B in the studied group of children amounted to 0.26 ± 0.14, 37.62 ± 25.30 and 78.31 ± 12.82 µg/L, respectively. In the entire examined group a statistically significant negative linear relationship was noted between Pb-B and Se-B (r = -0.12, p < 0.05). Also, a statistically insignificant negative correlation was detected between Cd-B and Se-B (r = -0.02, p > 0.05) and a statistically insignificant positive correlation between Pb-B and Cd-B (r = 0.08, p > 0.05). A multivariate backward stepwise regression analysis demonstrated that in the studied group of children higher Pb-B and a more advanced age-represented independent risk factors for a decreased Se-B. Environmental exposure to Pb may represent an independent risk factor for Se deficit in blood of the studied population of children. In children, the lowered Se-B may create one of the mechanisms in which Pb unfavourably affects human body.

Role of fatty acid transport protein 4 in oleic acid-induced glucagon-like peptide-1 secretion from murine intestinal L cells.

The antidiabetic intestinal L cell hormone glucagon-like peptide-1 (GLP-1) enhances glucose-dependent insulin secretion and inhibits gastric emptying. GLP-1 secretion is stimulated by luminal oleic acid (OA), which crosses the cell membrane by an unknown mechanism. We hypothesized that L cell fatty acid transport proteins (FATPs) are essential for OA-induced GLP-1 release. Therefore, the murine GLUTag L cell model was used for immunoblotting, [(3)H]OA uptake assay, and GLP-1 secretion assay as determined by radioimmunoassay following treatment with OA ± phloretin, sulfo-N-succinimidyl oleate, or siRNA against FATP4. FATP4(-/-) and cluster-of-differentiation 36 (CD36)(-/-) mice received intraileal OA, and plasma GLP-1 was measured by sandwich immunoassay. GLUTag cells were found to express CD36, FATP1, FATP3, and FATP4. The cells demonstrated specific (3)H[OA] uptake that was dose-dependently inhibited by 500 and 1,000 µM unlabeled OA (P < 0.001). Cell viability was not altered by treatment with OA. Phloretin and sulfo-N-succinimidyl oleate, inhibitors of protein-mediated transport and CD36, respectively, also decreased [(3)H]OA uptake, as did knockdown of FATP4 by siRNA transfection (P < 0.05-0.001). OA dose-dependently increased GLP-1 secretion at 500 and 1,000 µM (P < 0.001), whereas phloretin, sulfo-N-succinimidyl oleate, and FATP4 knockdown decreased this response (P < 0.05-0.01). FATP4(-/-) mice displayed lower plasma GLP-1 at 60 min in response to intraileal OA (P < 0.05), whereas, unexpectedly, CD36(-/-) mice displayed higher basal GLP-1 levels (P < 0.01) but a normal response to intraileal OA. Together, these findings demonstrate a key role for FATP4 in OA-induced GLP-1 secretion from the murine L cell in vitro and in vivo, whereas the precise role of CD36 remains unclear.

Current strategies for probing substrate specificity of proteases.

In this review we describe in detail the available technologies used for investigating the substrate specificity of proteases. Critical comparison of the available detection methods and their choice for certain type of screening is discussed. We present successful strategies along with appropriate examples for the design and synthesis of combinatorial libraries of substrates using both chemical and biological approaches. Proteomic tools for the identification of natural substrates of proteases are also discussed.

Angiogenic and coagulation-fibrinolysis factors in non Hodgkin's lymphoma.

High serum VEGF and bFGF levels are independent prognostic factors of poor prognosis in NHL patients. There is growing evidence that both angiogenesis and haemostatic aberrancies are integral parts of the pathobiology of cancer growth and dissemination. The purpose of the study was: (a) to analyze relations of VEGF and bFGF serum levels, fibrinogen and D-dimer plasma levels with lymphoma Ann Arbor Staging System (AASS) and International Prognostic Index (IPI) and, (b) to evaluate correlations between serum levels of angiogenic cytokines and plasma levels of coagulation-fibrinolysis factors in 52 previously untreated NHL patients included to the study. The control group consisted of 23 healthy volunteers. Serum VEGF, bFGF and plasma D-dimer levels were measured by enzyme-linked immunosorbent assay (ELISA). Plasma levels of fibrinogen were determined on Behring Coagulation System (BCS) equipment. In lymphoma group serum VEGF and bFGF levels were significantly higher than in the control. Differences in concentrations of VEGF, bFGF between II, III and IV stage of disease acc. AASS were not statistically significant. Plasma levels of fibrinogen and D-dimer were elevated in lymphoma patients when compared with the control. Fibrinogen plasma levels were similar in all stages. The D-dimer level was significantly higher in patients with IV stage in comparison to stage II and III. Statistically significant differences of VEGF and bFGF serum levels were observed only between intermediate/high and high risk groups acc. IPI. Fibrinogen plasma levels were significantly higher in high risk group than in low risk group. D-dimer plasma levels were significantly higher in high risk group than in low risk group and low/intermediate group. We observed positive correlation between serum level of VEGF and plasma level of fibrinogen, and between serum level of bFGF and plasma level of fibrinogen. There was also negative correlation between serum level of VEGF and plasma level of D-dimer, and between serum level of bFGF and plasma level of D- dimer. Our study indicates that D-dimer level, but not VEGF, bFGF and fibrinogen correlates with AASS and IPI in NHL patients. Significant correlations between levels of VEGF/bFGF and fibrinogen/D-dimer suggest specific interactions between angiogenic and coagulation-fibrinolysis system.