Differentiating multi-MeV, multi-ion spectra with CR-39 solid-state nuclear track detectors.

The development of high intensity petawatt lasers has created new possibilities for ion acceleration and nuclear fusion using solid targets. In such laser-matter interaction, multiple ion species are accelerated with broad spectra up to hundreds of MeV. To measure ion yields and for species identification, CR-39 solid-state nuclear track detectors are frequently used.

Design and commissioning of a neutron counter adapted to high-intensity laser matter interactions.

The advent of multi-PW laser facilities world-wide opens new opportunities for nuclear physics. With this perspective, we developed a neutron counter taking into account the specifics of a high-intensity laser environment. Using GEANT4 simulations and prototype testings, we report on the design of a modular neutron counter based on boron-10 enriched scintillators and a high-density polyethylene moderator.

Impact of Clomiphene Citrate on the Steroid Profile in Dysmetabolic Men with Low Testosterone Levels.

Clomiphene citrate (CC) in male hypogonadism increases testosterone (T) and estrogen levels by stimulating pituitary gonadotropin release. Our group confirmed these hormonal changes in a randomized, cross-over, double-blind trial of CC versus placebo in addition to metformin, conducted in 21 obese dysmetabolic men with low T levels. However, we hypothesize that based on its mechanism of action, CC may directly or indirectly affect adrenal steroidogenesis.

Steroid reference intervals in women: influence of menopause, age and metabolism.

Objective: To investigate the impact of age, obesity and metabolic parameters on 13 circulating steroids in reproductive and menopausal age. To define reference intervals (RIs).

Design: Cross-sectional.

Impact of age, body weight and metabolic risk factors on steroid reference intervals in men.

Objective: To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men.

Design: Cross-sectional study.

Methods: Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation.

Female and male serum reference intervals for challenging sex and precursor steroids by liquid chromatography - tandem mass spectrometry.

Measuring some sex and precursor steroids is still challenging even by liquid chromatography - tandem mass spectrometry (LC-MS/MS), and few normal values are available. We developed a LC-MS/MS method for estradiol, estrone, dihydrotestosterone and 17-hydroxypregnenolone measurement, compared it with direct immunoassays, and generated sex, age, menopausal and menstrual status specific reference intervals. Liquid-liquid extraction was optimized on 300 μL serum spiked with isotopic internal standards.

Salivary cortisol and cortisone responses to short-term psychological stress challenge in late adolescent and young women with different hyperandrogenic states.

Hyperandrogenic disorders have been associated with psychological distress, reduced quality of life, anxiety and depression. The hypothalamic-pituitary-adrenal (HPA) axis plays a pivotal role in the adaptive response to stressor events. Salivary cortisol (SalF) and cortisone (SalE) testing have been proven to be useful in the evaluation of HPA-axis activity.

Clomiphene citrate effect in obese men with low serum testosterone treated with metformin due to dysmetabolic disorders: A randomized, double-blind, placebo-controlled study.

Context: Low testosterone (T) levels are often found in obese men with impaired glucose tolerance (IGT) and overt type 2 diabetes (T2DM); however, the mechanisms underlying this condition and its correct therapy are still under debate.

Objective: To evaluate the effectiveness of clomiphene citrate (CC) in increasing endogenous T levels in obese men with low serum T and with IGT or T2DM treated with metformin (MET).

Design: Cross-over, randomized, double-blind, placebo-controlled study.

Parallel diurnal fluctuation of testosterone, androstenedione, dehydroepiandrosterone and 17OHprogesterone as assessed in serum and saliva: validation of a novel liquid chromatography-tandem mass spectrometry method for salivary steroid profiling.

Background: Salivary androgen testing represents a valuable source of biological information. However, the proper measurement of such low levels is challenging for direct immunoassays, lacking adequate accuracy. In the last few years, many conflicting findings reporting low correlation with the serum counterparts have hampered the clinical application of salivary androgen testing.

Validation of an LC-MS/MS salivary assay for glucocorticoid status assessment: Evaluation of the diurnal fluctuation of cortisol and cortisone and of their association within and between serum and saliva.

Salivary steroid testing represents a valuable source of biological information; however, the proper measurement of low salivary levels is challenging for direct immunoassays, lacking adequate sensitivity and specificity and causing poor inter-laboratory reproducibility. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has overcome previous analytical limits, often providing results deviating from previous knowledge. Nowadays, LC-MS/MS is being introduced in clinical laboratories for salivary cortisol testing; however, so far only a few studies have reported thorough biological validation based on LC-MS/MS data.

Altered protease-activated receptor-1 expression and signaling in a malignant pleural mesothelioma cell line, NCI-H28, with homozygous deletion of the β-catenin gene.

Protease activated receptors (PARs) are G-protein coupled receptors that are activated by an unique proteolytic mechanism. These receptors play crucial roles in hemostasis and thrombosis but also in inflammation and vascular development. PARs have also been implicated in tumor progression, invasion and metastasis.

Identifying bias in CCR1 antagonists using radiolabelled binding, receptor internalization, β-arrestin translocation and chemotaxis assays.

Background And Purpose: Investigators have suggested that the chemokine receptor CCR1 plays a role in multiple myeloma. Studies using antisense and neutralizing antibodies to CCR1 showed that down-regulation of the receptor altered disease progression in a mouse model. More recently, experiments utilizing scid mice injected with human myeloma cells demonstrated that the CCR1 antagonist BX471 reduced osteolytic lesions, while the CCR1 antagonist MLN-3897 prevented myeloma cell adhesion to osteoclasts.

Modulation of PAR(1) signalling by benzimidazole compounds.

Background And Purpose: Recently, a small molecule (Q94) was reported to selectively block PAR(1) /Gα(q) interaction and signalling. Here, we describe the pharmacological properties of Q94 and two analogues that share its benzimidazole scaffold (Q109, Q89). Q109 presents a modest variation from Q94 in the substituent group at the 2-position, while Q89 has quite different groups at the 1- and 2-positions.

Effects of NCX 4050, a new NO donor, in rabbit and human corpus cavernosum.

The effects of NCX 4050, a drug belonging to a new class of NO donors, was investigated in isolated preparations of human and rabbit corpus cavernosum (CC) and in human foetal corpora cavernosa (hfCC) smooth muscle cells. In strips of rabbit CC, NCX 4050 (0.001-100 microM) induced a concentration-dependent relaxation which was influenced neither by Nw-nitro-l-arginine-methyl-ester (l-NAME; 100 microm) nor by endothelium deprivation.

alpha(1D)-adrenoceptors cause endothelium-dependent vasodilatation in the rat mesenteric vascular bed.

The vasodilator activity of alpha(1)-adrenoceptor agonists was tested in the rat mesenteric vascular bed (MVB), and the mechanism involved was investigated in cultured endothelial cells isolated from the bovine coronary vascular bed. In preparations preconstricted by U46619, noradrenaline and phenylephrine induced a slight relaxant effect at nanomolar concentrations. This effect was abolished in endothelium-denuded preparations and in preparations pretreated with 100 microM N(omega)-nitro-L-arginine methyl ester plus 3 microM indomethacin.

Lack of nitric oxide- and guanosine 3':5'-cyclic monophosphate-dependent regulation of alpha-thrombin-induced calcium transient in endothelial cells of spontaneously hypertensive rat hearts.

While the expression and/or activity of endothelial nitric oxide synthase (eNOS) has been characterized in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rat (WKY) hearts, in coronary endothelial cells (ECs) from both strains, the effect of NO on intracellular calcium concentration ([Ca(2+)](i)) is still unknown. Coronary microvascular ECs were isolated from SHR and WKY and characterized. Immunocytochemistry and Western blot analysis showed that eNOS was similarly expressed in ECs from both strains.

Inositol phosphate metabolism and nitric-oxide synthase activity in endothelial cells are involved in the vasorelaxant activity of nebivolol.

Nebivolol is a recently developed beta-blocker provided with vasodilator properties. Because the mechanism of the putative endothelium-dependent effect of this beta-adrenoceptor blocker has not been completely elucidated, the aim of this study was to investigate the effects of nebivolol on an isolated resistance vascular bed and on cell messengers and constitutive nitric-oxide synthase activity (cNOS) in endothelial cells. Experiments were carried out using the rat mesenteric vascular bed and cultured bovine coronary postcapillary venular endothelial cells from bovine heart (CVEC).

Plasma and platelet ascorbate pools and lipid peroxidation in insulin-dependent diabetes mellitus.

Background: As diabetes mellitus represents a situation in which production of peroxides is increased, the aim of this study was to investigate the relationship between plasma and platelet levels of ascorbic acid (AA)/dehydroascorbic acid (DHA) and those of malonyldialdehyde (MDA), an indirect marker of lipoperoxides, both assayed using high-performance liquid chromatography (HPLC), in 59 patients with insulin-dependent diabetes mellitus (IDDM) compared with 51 healthy control subjects matched for sex, age, smoking habits, as well as for dietary intake of energy, alcohol and vitamin C.

Results: Mean plasma and platelet MDA were significantly higher in the patients affected with IDDM than in control subjects. Moreover, the diabetic group was characterized by a huge decrease in plasma AA [8.

Calcium waves in unstimulated left ventricular cardiomyocytes isolated from aged spontaneously hypertensive and normotensive rats.

In this work, we described the incidence and the characteristics of calcium waves in cardiomyocytes isolated from aged normotensive rats (Wistar Kyoto, WKY) and age-matched spontaneously hypertensive rats (SHR) using imaging analysis of fura-2-loaded left ventricular cardiomyocytes. Left ventricular cardiomyocytes were isolated by enzymatic digestion from hearts of 18-20 month old WKY and aged-matched SHR. Intracellular calcium concentration did not differ in either strain, whereas the incidence of cells presenting calcium waves was greater in cardiomyocytes isolated from SHR.

Iloprost antagonizes the increase in internal calcium concentration induced by alpha-thrombin in human platelets: a study of desensitization.

We studied the interaction between the synthetic prostacyclin analog iloprost and the aggregating agent alpha-thrombin by measuring the internal calcium ion concentration ([Ca(2+)]i) of human fura-2-loaded platelets. Iloprost (0.003-100 micrograms/l) did not modify the resting calcium level; when added 2 minutes before exposure of the platelets to a submaximally active concentration of alpha-thrombin (10 U/l), iloprost dose-dependently antagonized the increase in [Ca(2+)]i.

No-mimetic furoxans: arylsulphonylfuroxans and related compounds.

A new class of methylfuroxans and methylfurazans arylthio, arylsulphinyl and arylsulphonyl substituted, characterized by vasodilating and antiaggregatory properties, is described. Vasodilating activity, tested on rabbit aortic rings percontracted with 1 microM noradrenaline, is enhanced by N-oxidation of the furazan ring and is maximized by increase of the sulphur atom oxidation level. Compounds 4-methyl-3-(p-methoxyphenylsulphonyl) furoxan 6c, 3-phenyl-4-phenylsulphonylfuroxan 10, 4-phenyl-3-phenylsulphonylfuroxan 11 and 3,4-bis(phenyl-sulphonyl)furoxan 12 (EC50 values ranging between 0.

Release of cytochromes from hypoxic and reoxygenated guinea pig heart.

Isolated, perfused hearts from guinea pigs were subjected to hypoxia for 30 minutes followed by reoxygenation for 30 minutes. Cellular damage was assessed by measuring the release of the cytoplasmic enzyme lactate dehydrogenase and the mitochondrial markers cytochrome c and cytochrome oxidase. The release of the enzymes was correlated with electron microscopy.