Clinical Significance of HMGB-1 and TGF-ß Level in Serum and BALF of Advanced Non-Small Cell Lung Cancer.

Lung cancer is associated with poor prognosis. The aim of this study was to evaluate the clinical usefulness of HMGB-1 (high-mobility group protein B1) and TGF-ß (transforming growth factor beta) in patients with advanced non-small cell lung cancer (NSCLC). We studied 45 patients with NSCLC prior to chemotherapy, 23 patients with Besnier-Boeck-Schaumann (BBS) disease (sarcoidosis), and 15 healthy volunteers. HMGB-1 and TGF-ß levels were measured in serum and BALF samples using ELISA method. A higher serum HMGB-1 and TGF-ß levels were in NSCLC patients compared with the other groups. TGF-ß concentration in BALF was significantly higher in NSCLC than in healthy controls (p=0.047) but lower than in BBS (p=0.016). Serum HMGB-1 in NSCLC correlated with age and gender while its level in BALF was associated with distant metastasis. A higher levels of HMGB-1 in the serum of NSCLC patients with progressive disease was linked with shorter overall survival and disease-free survival. We found a positive correlation between HMGB-1 and TGF-ß in BALF of IIIB NSCLC group and overall survival (p=0.04; p=0.003). Our findings confirmed that the measurement of HMGB-1 and TGF-ß levels in serum and BALF of patients with NSCLC prior to treatment may have clinical usefulness and predict poor prognosis.

Adenine, guanine and pyridine nucleotides in blood during physical exercise and restitution in healthy subjects.

Maximal physical exertion is accompanied by increased degradation of purine nucleotides in muscles with the products of purine catabolism accumulating in the plasma. Thanks to membrane transporters, these products remain in an equilibrium between the plasma and red blood cells where they may serve as substrates in salvage reactions, contributing to an increase in the concentrations of purine nucleotides. In this study, we measured the concentrations of adenine nucleotides (ATP, ADP, AMP), inosine nucleotides (IMP), guanine nucleotides (GTP, GDP, GMP), and also pyridine nucleotides (NAD, NADP) in red blood cells immediately after standardized physical effort with increasing intensity, and at the 30th min of rest. We also examined the effect of muscular exercise on adenylate (guanylate) energy charge--AEC (GEC), and on the concentration of nucleosides (guanosine, inosine, adenosine) and hypoxanthine. We have shown in this study that a standardized physical exercise with increasing intensity leads to an increase in IMP concentration in red blood cells immediately after the exercise, which with a significant increase in Hyp concentration in the blood suggests that Hyp was included in the IMP pool. Restitution is accompanied by an increase in the ATP/ADP and ADP/AMP ratios, which indicates an increase in the phosphorylation of AMP and ADP to ATP. Physical effort applied in this study did not lead to changes in the concentrations of guanine and pyridine nucleotides in red blood cells.

Plasma concentrations of TNF-alpha and its soluble receptors sTNFR1 and sTNFR2 in patients with coronary artery disease.

Tumour necrosis factor alpha (TNF-alpha) is implicated in post-ischemic myocardial dysfunction. Two distinct TNF-alpha receptors are shed from cell membranes and circulate in plasma as soluble sTNFR1 and sTNFR2 proteins. The aim of the study was to establish factors associated with plasma concentrations of TNF-alpha and its receptors in patients with coronary artery disease (CAD). Since adenosine inhibits the expression of TNF-alpha, two functional polymorphisms in genes encoding enzymes participating in adenosine metabolism, i.e. AMP deaminase-1 (AMPD1, C34T) and adenosine deaminase (ADA, G22A), were analyzed. Plasma concentrations of TNF-alpha, sTNFR1, and sTNFR2 were measured using ELISA in 167 patients with CAD. Common factors significantly associated with higher TNF-alpha, sTNFR1, and sTNFR2 were lower glomerular filtration rate (GFR), older age, higher BNP, lower blood haemoglobin, and the presence of asthma or chronic obstructive pulmonary disease (COPD). Higher TNF-alpha and sTNFR1 concentrations were also associated with the presence of heart failure (HF), lower ejection and shortening fraction, the presence of diabetes or metabolic syndrome, lower serum HDL cholesterol, and higher uric acid. In multivariate analysis the common independent predictors of higher TNF-alpha, sTNFR1, and sTNFR2 were lower GFR, lower HDL cholesterol, higher BNP, and the presence of asthma or COPD. There were no associations between AMPD1 C34T or ADA G22A genotypes and TNF-alpha or its receptors. In conclusion, the concentrations of TNF-alpha, sTNFR1, and sTNFR2 reflect the impairment of cardiac and renal function in patients with CAD. Metabolic syndrome and diabetes are associated with higher plasma concentrations of TNF-alpha and its receptors.

Circulating adhesion molecules and purine nucleotides during kidney allograft reperfusion.

The impairment of organ function due to ischemia-reperfusion injury is still an important problem in solid organ transplantation. Numerous experimental and clinical studies of native organs have shown that ischemia-reperfusion constitutes an acute inflammatory process involving cell surface adhesion molecule expression. These markers are crucial for the recruitment and infiltration of effector cells into the postischemic tissue. Purines released by the postischemic tissue as the products of the degradation of high-energy nucleotides can be regarded as markers of disturbed energy metabolism. The aim of this study was to examine the correlation between circulating adhesion molecules and purine metabolites in graft renal vein plasma during 49 cases of kidney reperfusion. E-selectin, ICAM-1, and VCAM-1 concentrations correlated positively with hypoxanthine concentrations during reperfusion, whereas the concentrations of ICAM-1 correlated negatively with xanthine concentrations. The results of the present study suggested that the concentrations of adhesion molecules in the renal vein during reperfusion correlated with purine metabolites, reflecting metabolic changes in renal tissue.

Development of an adjustable Kirkpatrick-Baez microscope for laser driven x-ray sources.

A prototype of a highly adjustable Kirkpatrick-Baez (KB) microscope has been designed, built, and tested in a number of laser driven x-ray experiments using the high power (200 TW) VEGA-2 laser system of the Spanish Centre for Pulsed Lasers (CLPU). The presented KB version consists of two, perpendicularly mounted, 500 µm thick silicon wafers, coated with a layer of platinum, a few tens of nanometers thick. Unlike the usual millimeter thick glass substrate, this design allows for a larger bending flexibility and large adjustment range. According to simulations, this KB microscope offers broadband multikiloelectron volt reflection spectra (1 eV-20 keV), allowing more spectral tunability than conventional Bragg crystals. In addition to be vacuum compatible, this prototype is characterized by a relatively small size (21 cm × 31 cm × 27 cm) and permits remote control and modification both of the radii of curvature (down to 10 m) and of the grazing incidence angle (up to 60 mrad). A few examples of focusing performance tests and experimental results are discussed.

Comparison of human erythrocyte purine nucleotide metabolism and blood purine and pyrimidine degradation product concentrations before and after acute exercise in trained and sedentary subjects.

This study aimed at evaluating the concentration of erythrocyte purine nucleotides (ATP, ADP, AMP, IMP) in trained and sedentary subjects before and after maximal physical exercise together with measuring the activity of purine metabolism enzymes as well as the concentration of purine (hypoxanthine, xanthine, uric acid) and pyrimidine (uridine) degradation products in blood. The study included 15 male elite rowers [mean age 24.3 ± 2.56 years; maximal oxygen uptake (VO2max) 52.8 ± 4.54 mL/kg/min; endurance and strength training 8.2 ± 0.33 h per week for 6.4 ± 2.52 years] and 15 sedentary control subjects (mean age 23.1 ± 3.41 years; VO2max 43.2 ± 5.20 mL/kg/min). Progressive incremental exercise testing until refusal to continue exercising was conducted on a bicycle ergometer. The concentrations of ATP, ADP, AMP, IMP and the activities of adenine phosphoribosyltransferase (APRT), hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and phosphoribosyl pyrophosphate synthetase (PRPP-S) were determined in erythrocytes. The concentrations of hypoxanthine, xanthine, uric acid and uridine were determined in the whole blood before exercise, after exercise, and 30 min after exercise testing. The study demonstrated a significantly higher concentration of ATP in the erythrocytes of trained subjects which, in part, may be explained by higher metabolic activity on the purine re-synthesis pathway (significantly higher PRPP-S, APRT and HGPRT activities). The ATP concentration, just as the ATP/ADP ratio, as well as an exercise-induced increase in this ratio, correlates with the VO2max level in these subjects which allows them to be considered as the important factors characterising physical capacity and exercise tolerance. Maximal physical exercise in the group of trained subjects results not only in a lower post-exercise increase in the concentration of hypoxanthine, xanthine and uric acid but also in that of uridine. This indicates the possibility of performing high-intensity work with a lower loss of not only purine but also pyrimidine.

Calibration of the low-energy channel Thomson parabola of the LMJ-PETAL diagnostic SEPAGE with protons and carbon ions.

The SEPAGE diagnostic will detect charged particles (electrons, protons, and ions) accelerated in the interaction of the PETAL (PETawatt Aquitaine Laser) laser with its targets on the LMJ (Laser MegaJoule)-PETAL laser facility. SEPAGE will be equipped with a proton-radiography front detector and two Thomson parabolas (TP), corresponding to different ranges of the particle energy spectra: Above 0.1 MeV for electrons and protons in the low-energy channel, with a separation capability between protons and 12C6+ up to 20 MeV proton energy and above 8 MeV for the high-energy channel, with a separation capability between protons and 12C6+ up to 200 MeV proton kinetic energy. This paper presents the calibration of the SEPAGE's low-energy channel TP at the Tandem facility of Orsay (France) with proton beams between 3 and 22 MeV and carbon-ion beams from 5.8 to 84 MeV. The magnetic and electric fields' integrals were determined with an accuracy of 10-3 by combining the deflections measured at different energies with different target thicknesses and materials, providing different in-target energy losses of the beam particles and hence different detected energies for given beam energies.

Purine and cytokine concentrations in the renal vein of the allograft during reperfusion.

The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for subsequent damage during the reperfusion phase. The aim of present study was to examine the association between changes in cytokine and purine metabolite concentrations in graft renal vein during reperfusion. The study included 17 recipients of cadaveric renal grafts: 10 men and seven women of overall mean age of 49 +/- 7 years and cold ischemia time 25 +/- 3 hour. The levels of interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, interferon (INF)-gamma, tumor necrosis factor (TNF)-beta, and TNF-alpha in renal graft vein plasma during 5 first minutes of reperfusion were quantified by flow cytometry. Increased concentrations of IL-6, TNF-alpha, and IL-1beta were observed during reperfusion. The IFN-gamma concentrations correlated negatively with xanthine (Xan) concentrations in renal vein blood during reperfusion, whereas there was a positive correlation between IL-2 and Xan concentrations. Moreover, the concentrations of IL-6 and IL-10 correlated negatively with hypoxanthine concentrations, and the concentrations of IL-4 also correlated negatively with Xan concentrations. The results of this study indicated the enhanced release of some cytokines during kidney graft reperfusion. It occurred in association with release of purine metabolites-the markers of energy status of renal tissue. Therefore, the enhanced cytokine production during reperfusion might influence ischemia-reperfusion injury and the early graft function.

Calibration of imaging plate detectors to mono-energetic protons in the range 1-200 MeV.

Responses of Fuji Imaging Plates (IPs) to proton have been measured in the range 1-200 MeV. Mono-energetic protons were produced with the 15 MV ALTO-Tandem accelerator of the Institute of Nuclear Physics (Orsay, France) and, at higher energies, with the 200-MeV isochronous cyclotron of the Institut Curie-Centre de Protonthérapie d'Orsay (Orsay, France). The experimental setups are described and the measured photo-stimulated luminescence responses for MS, SR, and TR IPs are presented and compared to existing data. For the interpretation of the results, a sensitivity model based on the Monte Carlo GEANT4 code has been developed. It enables the calculation of the response functions in a large energy range, from 0.1 to 200 MeV. Finally, we show that our model reproduces accurately the response of more complex detectors, i.e., stack of high-Z filters and IPs, which could be of great interest for diagnostics of Petawatt laser accelerated particles.

Metabolism of eicosanoids and their action on renal function during ischaemia and reperfusion: the effect of alprostadil.

Eicosanoids, active metabolites of arachidonic acid (AA), play an important role in the regulation of renal haemodynamics and glomerular filtration. Our study verified the hypothesis on the positive action of exogenously administered PGE(1) on renal function during an operation with temporary ischaemia of the lower half of the body. Also the effect of alprostadil (prostaglandin E(1) analogue) administered during the operation of an abdominal aorta aneurysm on the postoperative systemic metabolism of AA and the glomerular filtration rate (GFR) was investigated. The study included 42 patients with a diagnosed abdominal aorta aneurysm who have been qualified for the operation of implantation of the aortic prosthesis. The patients were randomly assigned to two groups: the study group (I) receiving alprostadil and the control group (II) without alprostadil. The levels of hydroxyeicosatetraenoic acids (15-HETE, 12-HETE, 5-HETE) were determined by RP-HPLC and the level of thromboxane B(2) (TxB(2)) was determined by ELISA in the plasma of the blood drawn from vena cava superior immediately before aortic clamping (A) and 5 min after aortic declamping (B). The administration of PGE(1) affects the metabolism of 15-HETE in a manner dependent on the baseline value of GFR but does not significantly change the postoperative renal function. The metabolism of 15-HETE is affected by the baseline value of GFR1 and a longer period of ischaemia is correlated with lower concentrations of 5-HETE during reperfusion. The results of our studies indicate that TxB(2) influences the postoperative function of kidneys.

Hypoxanthine as a graft ischemia marker stimulates catalase activity in the renal vein during reperfusion in humans.

BACKGROUND: The impairment of organ function derived from ischemia-reperfusion injury is still an important problem in solid organ transplantation. Cell alterations induced by ischemia prime the tissue for subsequent damage occurring during the reperfusion phase. Purine nucleotides and oxypurines are products of adenine nucleotide degradation. Reperfusion and reoxygenation are characterized by great production of reactive oxygen species and free radicals. On the contrary, superoxide dismutase, catalase, glutathione, and glutathione peroxidase are involved in protecting against free radicals. The aim of the study was to examine the correlation between concentrations of ischemia markers (hypoxanthine or inosine) and the activity of erythrocyte superoxide dismutase, catalase, or glutathione peroxidase. PATIENTS AND METHODS: The study included 40 renal transplant recipients. Before anastomosis of the kidney vessels with the recipient's iliac vessels, a "0" blood sample was taken from the iliac vein. Then, after anastomosis, the renal vein of the graft was cannulated and blood samples I, II, and III were obtained. The reperfusion of the transplanted kidney was measured with a thermovision camera ThermaCAM SC500. RESULTS: The plasma concentrations of hypoxanthine and inosine increased in statistically significant fashion immediately after total tissue reperfusion (P < .0001). Catalase activity at 4 minutes after total tissue reperfusion correlated positively with hypoxanthine concentrations immediately after total tissue reperfusion (Rs = +0.49), 2 minutes after total tissue reperfusion (Rs = +0.47), and 4 minutes after total tissue reperfusion (Rs = +0.46). There were no statistically significant correlations between hypoxanthine or inosine concentrations or superoxide dismutase or glutathione peroxidase activities. CONCLUSIONS: The results of the present study suggest that catalase activity may correlate with the concentration of hypoxanthine in the graft renal vein and other mediators of oxidative stress.

The GEMpix detector as new soft X-rays diagnostic tool for laser produced plasmas.

Laser produced plasmas lend to several interesting applications. The study of X-ray emission from this kind of plasmas is important not only to characterize plasmas itself but also to study the application of these particular plasmas as intense X-ray sources. In particular several emission configurations can be obtained using different kinds of targets and tuning the characteristics of the laser pulse delivered to the target. Typically, laser pulse duration ranges between a few tens of femtoseconds and tens of nanoseconds, with energies from few mJ to tens of kJ. X-ray photon emissions last for times comparable to the laser pulses and during this time a great number of photons can be emitted. The following paper presents a measure of the soft-X-ray emission on the ECLIPSE laser facility realized with a new triple-GEM gas detector (GEMpix). It is a hybrid gas detector with a C-MOS front-end electronics based on Medipix chips. In the present work, different targets have been used in order to test X-rays of different energies. In this paper, in particular, we present results obtained for copper and iron targets. GEMpix is able to realize a 2D imaging of the X-ray emission from plasma with a signal proportional to the energy released in the gas of the detector active volume. Then through a preliminary single photon equalization realized at the NIXT lab (ENEA), also the number of photons reaching the area of the detector has been estimated.

Calibration of imaging plates to electrons between 40 and 180 MeV.

This paper presents the response calibration of Imaging Plates (IPs) for electrons in the 40-180 MeV range using laser-accelerated electrons at Laboratoire d'Optique Appliquée (LOA), Palaiseau, France. In the calibration process, the energy spectrum and charge of electron beams are measured by an independent system composed of a magnetic spectrometer and a Lanex scintillator screen used as a calibrated reference detector. It is possible to insert IPs of different types or stacks of IPs in this spectrometer in order to detect dispersed electrons simultaneously. The response values are inferred from the signal on the IPs, due to an appropriate charge calibration of the reference detector. The effect of thin layers of tungsten in front and/or behind IPs is studied in detail. GEANT4 simulations are used in order to analyze our measurements.

Validation of modelled imaging plates sensitivity to 1-100 keV x-rays and spatial resolution characterisation for diagnostics for the "PETawatt Aquitaine Laser".

Thanks to their high dynamic range and ability to withstand electromagnetic pulse, imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. In the framework of the development of the diagnostics for the Petawatt Aquitaine Laser facility, we present an absolute calibration and spatial resolution study of five different available types of IP (namely, MS-SR-TR-MP-ND) performed by using laser-induced K-shell X-rays emitted by a solid silver target irradiated by the laser ECLIPSE at CEntre Lasers Intenses et Applications. In addition, IP sensitivity measurements were performed with a 160 kV X-ray generator at CEA DAM DIF, where the absolute response of IP SR and TR has been calibrated to X-rays in the energy range 8-75 keV with uncertainties of about 15%. Finally, the response functions have been modeled in Monte Carlo GEANT4 simulations in order to reproduce experimental data. Simulations enable extrapolation of the IP response functions to photon energies from 1 keV to 1 GeV, of interest, e.g., for laser-driven radiography.

Study of imaging plate detector sensitivity to 5-18 MeV electrons.

Imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. We calibrated at the ELSA electron beam facility (CEA DIF) the five different available types of IPs (namely, MS-SR-TR-MP-ND) to electrons from 5 to 18 MeV. In the context of diagnostic development for the PETawatt Aquitaine Laser (PETAL), we investigated the use of stacks of IP in order to increase the detection efficiency and get detection response independent from the neighboring materials such as X-ray shielding and detector supports. We also measured fading functions in the time range from a few minutes up to a few days. Finally, our results are systematically compared to GEANT4 simulations in order to provide a complete study of the IP response to electrons over the energy range relevant for PETAL experiments.

[Occupational exposure to n-nitrosamine in the production of automobile tires]. / Narazenie zawodowe na n-nitrozoaminy w przemysle opon samochodowych.

Applying the method for determining nitrocompounds, based on gaz chromatography technique with nitro-phosphoric detector, N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosodibutylamine, N-nitrosotetrahydropyrrole were detected in the work environment of the plant under study (method of determining 0.2 micrograms/m3 for 1000 l/air). For qualitative purposes the data obtained were supported by mass spectrometry. Measurements of individual exposure were taken in 35 persons and stationary measurements were also applied. Among nitrosamines detected, N-nitrosodimethylamine (carcinogenic substance) occurred most commonly at working post, and its concentration was the highest (2.1-9.2 micrograms/m3).

[Reliability of routine measurements of atmospheric air pollution using sulfur dioxide as an example]. / Wiarygodnosc analiz podstawowych zanieczyszen powietrza atmosferycznego na przykladzie dwutlenku siarki.

On the basis of an external quality control of sulfur dioxide measurements in the atmospheric air (emission), the preparation of control material, its evaluation and a two-week durability of the material are presented. The results of the control test carried out in autumn 1994 is also discussed.

X-ray crystal spectrometer upgrade for ITER-like wall experiments at JET.

The high resolution X-Ray crystal spectrometer at the JET tokamak has been upgraded with the main goal of measuring the tungsten impurity concentration. This is important for understanding impurity accumulation in the plasma after installation of the JET ITER-like wall (main chamber: Be, divertor: W). This contribution provides details of the upgraded spectrometer with a focus on the aspects important for spectral analysis and plasma parameter calculation. In particular, we describe the determination of the spectrometer sensitivity: important for impurity concentration determination.

Insulin resistance induced by maximal exercise correlates with a post-exercise increase in uridine concentration in the blood of healthy young men.

Uridine is postulated to participate in the development of insulin resistance. Since exercise is an effective tool in the treatment of insulin resistance it appeared justified to assess the impact of maximal exercise on plasma uridine and insulin sensitivity indices (e.g. insulin and HOMA-IR) in healthy subjects. The study included forty-four healthy males (18.5+/-2.92 years, VO2max 50.2+/-6.26 ml kg⁻¹ min⁻¹). Subjects performed a single maximal exercise on a bicycle ergometer. Blood samples were taken three times: immediately before exercise, immediately after exercise and at the 30(th) min of rest. Uridine concentrations were determined in the whole blood using high-performance liquid chromatography. Serum insulin levels were measured by a specific ELISA method. Insulin sensitivity was assessed by homeostasis model assessment method (HOMA-IR). A maximal exercise-induced increase in the concentration of uridine correlated with post-exercise increases in insulin levels and HOMA-IR. Our results indicate a relationship between the concentration of uridine in the blood and indicators of insulin sensitivity in healthy subjects. We are the first to demonstrate that a maximal exercise-induced increase in the concentration of uridine is correlated with post-exercise increases in insulin levels and HOMA-IR in healthy subjects. It appears that uridine may be an indicator of insulin resistance.

Allopurinol intake does not modify the slow component of V(.)O(2) kinetics and oxidative stress induced by severe intensity exercise.

The aim of this study was to test the hypothesis that allopurinol ingestion modifies the slow component of V(.)O(2) kinetics and changes plasma oxidative stress markers during severe intensity exercise. Six recreationally active male subjects were randomly assigned to receive a single dose of allopurinol (300 mg) or a placebo in a double-blind, placebo-controlled crossover design, with at least 7 days washout period between the two conditions. Two hours following allopurinol or placebo intake, subjects completed a 6-min bout of cycle exercise with the power output corresponding to 75 % V(.)O(2)max. Blood samples were taken prior to commencing the exercise and then 5 minutes upon completion. Allopurinol intake caused increase in resting xanthine and hypoxanthine plasma concentrations, however it did not affect the slow component of oxygen uptake during exercise. Exercise elevated plasma inosine, hypoxanthine, and xanthine. Moreover, exercise induced a decrease in total antioxidant status, and sulfhydryl groups. However, no interaction treatment x time has been observed. Short term severe intensity exercise induces oxidative stress, but xanthine oxidase inhibition does not modify either the kinetics of oxygen consumption or reactive oxygen species overproduction.