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The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 [+ or -] 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 [+ or -] 0.5 µmol/L vs 0.53 ± 0.14 µmol/L; p < 0.01), HCys (15 ± 7.6 µmol/L vs 6.8 ± 3 µmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations. Key words: adenosine, homocysteine, coronary artery disease. Le role de l'hyperhomocysteinemie dans la coronaropathie n'a toujours pas ete precise. La presente etude vise a evaluer le lien entre les concentrations plasmatiques d'homocysteine (HCys), d'adenosine (CPA), d'acide urique et la gravite de la coronaropathie a l'aide du score SYNTAX. Nous avons aussi evalue in vitro l'influence de l'adenosine sur la production d'HCys par les cellules d'hepatome en culture (HuH7). Nous avons inscrit a l'etude 78 patients (moyenne d'age ± E-T : 66,3 ± 11,3; score SYNTAX moyen: 19,9 ± 12,3) et 30 sujets en bonne sante (moyenne d'age : 61 ± 13). Par ailleurs, nous avons fait incuber des cellules HuH7 en presence d'adenosine a des concentrations croissantes et evalue son effet sur la concentration d'HCys dans le surnageant de culture cellulaire. Les concentrations plasmatiques des elements suivants etaient plus elevees chez les patients que chez les temoins: adenosine (0,82 ± 0,5 µmol/L p/r a 0,53 ± 0,14 µmol/L, p < 0,01), HCys (15 ± 7,6 µmol/L p/r a 6,8 [+ or -] 3 µmol/L, p < 0,0001) et acide urique (242,6 ± 97 p/r a 202 ± 59, p < 0,05). L'augmentation de la CPA etait proportionnelle a celles des concentrations d'HCys et d'acide urique chez les patients (R de Pearson : 0,65 et 0,52, respectivement; p < 0,0001) et l'augmentation du score SYNTAX etait proportionnelle a celle des concentrations d'HCys. En culture cellulaire, nous avons observe une augmentation, dependante du temps et de la dose, des concentrations d'HCys en presence d'adenosine. Nos donnees laissent entendre que la CPA est associee aux concentrations d'HCys et d'acide urique chez les patients presentant une coronaropathie. Par ailleurs, d'autres etudes seraient necessaries pour savoir si la CPA participe a l'atherosclerose ou si, inversement, elle contribue a un processus de protection regulateur. [Traduit par la Redaction] Mots-cles: adenosine, homocysteine, coronaropathie., Introduction Hyperhomocysteinemia is associated with cardiovascular disease (Hoogeveen et al. 2000; Kumakura et al. 2015; McCully 1969; Refsum et al. 1998; Riksen et al. 2003) and a predictor for death [...]

The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 ± 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 ± 0.5 μmol/L vs 0.53 ± 0.14 μmol/L; p < 0.01), HCys (15 ± 7.6 μmol/L vs 6.8 ± 3 μmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The aim of the present study was to validate an experimental model of heterotopic renal allotransplantation. Such a model, more relevant to the human situation, has never been previously described. Materials and Methods: Pietrin pigs (40 to 50 kg) were used in the study. Through a midline incision, the left kidney was removed, washed, and preserved in a standard preservation solution (Celsior, Genzyme, France) for 20 hours at 4°C. Heterotopic autotransplantation was performed into the right iliac fossa onto the external iliac vessels with an end-to-side anastomosis and a nonstented uretero-ureteral anastomosis was performed. Results: Twenty-five renal allotransplantations were performed over a 5-month time period. Mean operating time progressively decreased and stabilized after 15 procedures (mean ± SD: 78.2 ± 19 minutes and 187.4 ± 18 minutes for left nephrectomy and transplantation, respectively) as morbidity decreased concomitantly. Suturing times for end-to-side anastomosis of the renal artery and vein onto the external iliac artery and vein were 21.9 ± 7 minutes and 34 ± 8 minutes (mean ± SD), respectively. Ten pigs died before the end of the experiment. ConcIusions: We have developed and validated the first nonrodent animal model of heterotopic renal autotransplantation relevant to the human anatomy and physiology. The procedure was easy to learn and safe. This model could be used to teach junior surgeons renal transplantation techniques and could also be used as a model to study ischemia-reperfusion injury in renal transplantation. [Copyright &y& Elsevier]

Objective: To evaluate the efficacy of full-field optical coherence tomography to differentiate hypertrophic and keloid scars on ex-vivo tissues. Patients and methods: All patients who underwent resection of pathological scar from November 2012 to September 2013 were analyzed. The scars were fixed in formalin and analyzed by conventional histology and full-field optical coherence tomography. The criteria for evaluation were: presence of dermal nodules, presence of cells and hyalinization of collagen. Results: Nineteen pathological scars were analyzed. Histology found 7 keloid scars, 7 mixed and 3 hypertrophic scars. The sensitivity of optical coherence tomography for the detection of dermal nodules was 100%. This technology was not helpful for detection of cells and hyalinized collagen. Conclusion: In the present state of technology, optical coherence tomography did not identify the presence of cells, which makes the differential diagnosis difficult in the case of hypertrophic and keloid scars. [ABSTRACT FROM AUTHOR]

Provitamin A (proVA) carotenoid synthesis and degradation are strongly influenced by environmental factors, including during post-harvest storage. Hypobaric and hyperbaric storages increase the shelf-life of many crops, but their effects on proVA carotenoids are not known. Our aim was to investigate the effects of modifications of atmospheric pressure and composition on α - and β -carotene concentration and bioaccessibility during the post-harvest storage of carrots and sweet potatoes. Vegetables were stored for 11-14 days at 20 °C in the dark in chambers with modified pressure and O 2 concentrations. In carrots, α - and β -carotene concentrations increased significantly during storage, but compared to the control, they were significantly lower in hyperbaria (-23 and -26%, respectively), whereas they did not differ significantly in hypoxia and hypobaria. In sweet potatoes, α - and β -carotene concentrations decreased significantly during storage, but neither hypoxia, hypobaria nor hyperbaria led to any significant change compared to the control. There was a significant increase for carrot α - and β -carotene bioaccessibility in hypobaria and hyperbaria, while there was a significant decrease for sweet potato β -carotene bioaccessibility in hypobaria/hypoxia and normobaria/hypoxia (-45% and -65% vs. control, respectively). Atmospheric pressure and composition during the post-harvest storage of carrots and sweet potatoes modified the concentration and bioaccessibility of proVA carotenoids.

Ischaemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and chronic kidney disease, which consists of cellular damage and renal dysfunction. AKI is a major complication that is of particular concern after cardiac surgery and to a lesser degree following organ transplantation in the immediate post-transplantation period, leading to delayed graft function. Because effective therapies are still unavailable, several recent studies have explored the potential benefit of hypoxic preconditioning (HPC) on IRI. HPC refers to the acquisition of increased organ tolerance to subsequent ischaemic or severe hypoxic injury, and experimental evidences suggest a potential benefit of HPC. There are three experimental forms of HPC, and, for better clarity, we named them as follows: physical HPC, HPC via treated-cell administration and stabilised hypoxia-inducible factor (HIF)-1α HPC, or mimicked HPC. The purpose of this review is to present the latest developments in the literature on HPC in the context of renal IRI in pre-clinical models. The data we compiled suggest that preconditional activation of hypoxia pathways protects against renal IRI, suggesting that HPC could be used in the treatment of renal IRI in transplantation., (© 2021 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Hyperhomocysteinemia is associated with coronary artery disease (CAD). The mechanistic aspects of this relationship are unclear. In CAD patients, homocysteine (HCy) concentration correlates with plasma level of adenosine that controls the coronary circulation via the activation of adenosine A 2A receptors (A 2A R). We addressed in CAD patients the relationship between HCy and A 2A R production, and in cellulo the effect of HCy on A 2A R function. 46 patients with CAD and 20 control healthy subjects were included. We evaluated A 2A R production by peripheral blood mononuclear cells using Western blotting. We studied in cellulo (CEM human T cells) the effect of HCy on A 2A R production as well as on basal and stimulated cAMP production following A 2A R activation by an agonist-like monoclonal antibody. HCy concentration was higher in CAD patients vs controls (median, range: 16.6 [7-45] vs 8 [5-12] µM, P < 0.001). A 2A R production was lower in patients vs controls (1.1[0.62-1.6] vs 1.53[0.7-1.9] arbitrary units, P < 0.001). We observed a negative correlation between HCy concentration and A 2A R production (r = -0.43; P < 0.0001), with decreased A 2A R production above 25 µM HCy. In cellulo, HCy inhibited A 2A R production, as well as basal and stimulated cAMP production. In conclusion, HCy is negatively associated with A 2A R production in CAD patients, as well as with A 2A R and cAMP production in cellulo. The decrease in A 2A R production and function, which is known to hamper coronary blood flow and promote inflammation, may support CAD pathogenesis., (© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Immersion pulmonary edema (IPE) is a serious complication of water immersion during scuba diving. Myocardial ischemia can occur during IPE that worsens outcome. Because myocardial injury impacts the therapeutic management, we aim to evaluate the profile of cardiac markers (creatine phosphokinase (CPK), brain natriuretic peptide (BNP), highly sensitive troponin T (TnT-hs) and ultrasensitive troponin I (TnI-us) of divers with IPE. Twelve male scuba divers admitted for suspected IPE were included. The collection of blood samples was performed at hospital entrance (T0) and 6 h later (T0 + 6 h). Diagnosis was confirmed by echocardiography or computed-tomography scan. Mean ± S.D. BNP (pg/ml) was 348 ± 324 at T0 and 223 ± 177 at T0 + 6 h ( P <0.01), while mean CPK (international units (IUs)), and mean TnT-hs (pg/ml) increased in the same times 238 ± 200 compared with 545 ± 39, ( P =0.008) and 128 ± 42 compared with 269 ± 210, ( P =0.01), respectively; no significant change was observed concerning TnI-us (pg/ml): 110 ± 34 compared with 330 ± 77, P =0.12. At T0 + 6 h, three patients had high TnI-us, while six patients had high TnT-hs. Mean CPK was correlated with TnT-hs but not with TnI-us. Coronary angiographies were normal. The increase in TnT during IPE may be secondary to the release of troponin from non-cardiac origin. The measurement of TnI in place of TnT permits in some cases to avoid additional examinations, especially unnecessary invasive investigations., (© 2018 The Author(s).)

Electrolyte concentration in sweat depends on environmental context and physical condition but also on the pathophysiological status. Sweat analyzers may be therefore the future way for biological survey although how sweat electrolyte composition can reflect plasma composition remains unclear. We recruited 10 healthy subjects and 6 patients to have a broad range of plasma electrolyte concentrations (chloride, potassium and sodium) and pH. These variables were compared to those found in sweat produced following cycling exercise or pilocarpine iontophoresis, a condition compatible with operating a wearable device. We found no correlation between plasma and sweat parameters when exercise-induced sweat was analyzed, and we could identify a correlation only between plasma and sweat potassium concentration (R = 0.78, p < 0.01) when sweat was induced using pilocarpine iontophoresis. We tested measurement repeatability in sweat at 24hr-interval for 3 days in 4 subjects and found a great intra-individual variability regarding all parameters in exercise-induced sweat whereas similar electrolyte levels were measured in pilocarpine-induced sweat. Thus, electrolyte concentration in sweat sampled following physical activity does not reflect concentration in plasma while pilocarpine iontophoresis appears to be promising to reproducibly address sweat electrolytes, and to make an indirect evaluation of plasma potassium concentration in chronic kidney disease and arrhythmia.

During exercise, cardiac oxygen-consumption increases and the resulting low oxygen level in myocardium triggers coronary vasodilation. This response to hypoxia is controlled notably by the vasodilator adenosine and its A 2A receptor (A 2A R). According to the "spare receptor" pharmacological model, a strong A 2A R-mediated response can occur in the context of a large number of receptors remaining unoccupied, activation of only a weak fraction of A 2A R (evaluated using K D ) resulting in maximal cAMP production (evaluated using EC 50 ), and hence in maximal coronary vasodilation. In coronary artery disease (CAD), myocardial ischemia limits adaptation to exercise, which is commonly detected using the exercise stress test (EST). We hypothesized that spare A 2A R are present in CAD patients to correct ischemia. Seventeen patients with angiographically-documented CAD and 17 control subjects were studied. We addressed adenosine-plasma concentration and A 2A R-expression at the mononuclear cell-surface, which reflects cardiovascular expression. The presence of spare A 2A R was tested using an innovative pharmacological approach based on a homemade monoclonal antibody with agonist properties. EST was positive in 82% of patients, and in none of the controls. Adenosine plasma-concentration increased by 60% at peak exercise in patients only (p<0.01). Most patients (65%), and none of the controls, had spare A 2A R (identified when EC 50 /K D ≤0.1) and a low A 2A R-expression (mean: -37% vs controls; p<0.01). All patients with spare A 2A R had a positive EST whereas the subjects without spare A 2A R had a negative EST (p<0.05). Spare A 2A R are therefore associated with positive EST in CAD patients and their detection may be used as a diagnostic marker.

High homocysteine (HCy) levels are associated with lymphocyte-mediated inflammatory responses that are sometimes in turn related to hypoxia. Because adenosine is a potent lymphocyte suppressor produced in hypoxic conditions and shares metabolic pathways with HCy, we addressed the influence of high HCy levels on the hypoxia-induced, adenosine-mediated, alteration of lymphocyte viability. We treated mitogen-stimulated human lymphocytes isolated from healthy individuals and the human lymphoma T-cell line CEM with cobalt chloride (CoCl2 )to reproduce hypoxia. We found that CoCl2 -altered cell viability was dose-dependently reversed using HCy. In turn, the HCy effect was inhibited using DL-propargylglycine, a specific inhibitor of the hydrogen sulphide (H2 S)-synthesizing enzyme cystathionine-γ-lyase involved in HCy catabolism. We then addressed the intracellular metabolic pathway of adenosine and HCy, and the role of the adenosine A2A receptor (A2 A R). We observed that: (i) hypoxic conditions lowered the intracellular concentration of HCy by increasing adenosine production, which resulted in high A2 A R expression and 3', 5'-cyclic adenosine monophosphate production; (ii) increasing intracellular HCy concentration reversed the hypoxia-induced adenosinergic signalling despite high adenosine concentration by promoting both S-adenosylhomocysteine and H2 S production; (iii) DL-propargylglycine that inhibits H2 S production abolished the HCy effect. Together, these data suggest that high HCy levels prevent, via H2 S production and the resulting down-regulation of A2 A R expression, the hypoxia-induced adenosinergic alteration of lymphocyte viability. We point out the relevance of these mechanisms in the pathophysiology of cardiovascular diseases., (© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Background: In kidney transplantation, the conditions of organ preservation following removal influence function recovery. Current static preservation procedures are generally based on immersion in a cold-storage solution used under atmospheric air (approximately 78 kPa N2, 21 kPa O2, 1 kPa Ar). Research on static cold-preservation solutions has stalled, and modifying the gas composition of the storage medium for improving preservation was considered. Organoprotective strategies successfully used noble gases and we addressed here the effects of argon and xenon on graft preservation in an established preclinical pig model of autotransplantation., Methods: The preservation solution Celsior saturated with pure argon (Argon-Celsior) or xenon (Xenon-Celsior) at atmospheric pressure was tested versus Celsior saturated with atmospheric air (Air-Celsior). The left kidney was removed, and Air-Celsior (n = 8 pigs), Argon-Celsior (n = 8) or Xenon-Celsior (n = 6) was used at 4 °C to flush and store the transplant for 30 h, a duration that induced ischemic injury in our model when Air-Celsior was used. Heterotopic autotransplantation and contralateral nephrectomy were performed. Animals were followed for 21 days., Results: The use of Argon-Celsior vs. Air-Celsior: (1) improved function recovery as monitored via creatinine clearance, the fraction of excreted sodium and tubulopathy duration; (2) enabled diuresis recovery 2-3 days earlier; (3) improved survival (7/8 vs. 3/8 pigs survived at postoperative day-21); (4) decreased tubular necrosis, interstitial fibrosis, apoptosis and inflammation, and preserved tissue structures as observed after the natural death/euthanasia; (5) stimulated plasma antioxidant defences during the days following transplantation as shown by monitoring the "reduced ascorbic acid/thiobarbituric acid reactive substances" ratio and Hsp27 expression; (6) limited the inflammatory response as shown by expression of TNF-alpha, IL1-beta and IL6 as observed after the natural death/euthanasia. Conversely, Xenon-Celsior was detrimental, no animal surviving by day-8 in a context where functional recovery, renal tissue properties and the antioxidant and inflammation responses were significantly altered. Thus, the positive effects of argon were not attributable to the noble gases as a group., Conclusions: The saturation of Celsior with argon improved early functional recovery, graft quality and survival. Manipulating the gas composition of a preservation medium constitutes therefore a promising approach to improve preservation.

The nucleoside adenosine acts on the nervous and cardiovascular systems via the A2A receptor (A2AR). In response to oxygen level in tissues, adenosine plasma concentration is regulated in particular via its synthesis by CD73 and via its degradation by adenosine deaminase (ADA). The cell-surface endopeptidase CD26 controls the concentration of vasoactive and antioxidant peptides and hence regulates the oxygen supply to tissues and oxidative stress response. Although overexpression of adenosine, CD73, ADA, A2AR, and CD26 in response to hypoxia is well documented, the effects of hyperoxic and hyperbaric conditions on these elements deserve further consideration. Rats and a murine Chem-3 cell line that expresses A2AR were exposed to 0.21 bar O2, 0.79 bar N2 (terrestrial conditions; normoxia); 1 bar O2 (hyperoxia); 2 bar O2 (hyperbaric hyperoxia); 0.21 bar O2, 1.79 bar N2 (hyperbaria). Adenosine plasma concentration, CD73, ADA, A2AR expression, and CD26 activity were addressed in vivo, and cAMP production was addressed in cellulo. For in vivo conditions, 1) hyperoxia decreased adenosine plasma level and T cell surface CD26 activity, whereas it increased CD73 expression and ADA level; 2) hyperbaric hyperoxia tended to amplify the trend; and 3) hyperbaria alone lacked significant influence on these parameters. In the brain and in cellulo, 1) hyperoxia decreased A2AR expression; 2) hyperbaric hyperoxia amplified the trend; and 3) hyperbaria alone exhibited the strongest effect. We found a similar pattern regarding both A2AR mRNA synthesis in the brain and cAMP production in Chem-3 cells. Thus a high oxygen level tended to downregulate the adenosinergic pathway and CD26 activity. Hyperbaria alone affected only A2AR expression and cAMP production. We discuss how such mechanisms triggered by hyperoxygenation can limit, through vasoconstriction, the oxygen supply to tissues and the production of reactive oxygen species., (Copyright © 2015 the American Physiological Society.)

Ischaemia-modified albumin (IMA) is a marker of the release of reactive oxygen species (ROS) during hypoxaemia. In elite divers, breath-hold induces ROS production. Our aim was to evaluate the kinetics of IMA serum levels during apnea. Twenty breath-hold divers were instructed to perform a submaximal static breath-hold. Twenty non-diver subjects served as controls. Blood samples were collected at rest, every minute, at the end of breath-hold, and 10 min after recovery. The IMA level increased after 1 min of breath-hold (p < 0.003) and remained high until recovery. Divers were separated into 2 groups: subjects who held their breath for less than 4 min (G-4) and those who held it for more than 4 min (G+4). After 3 min of apnoea, the increase of IMA was higher in the G-4 group than in the G+4 group (p < 0.008). However, at the end of apnoea, the IMA level did not differ between groups. If IMA level was globally correlated with the apnoea duration, it is interesting to note that the higher IMA level was not found in the best divers. Similarly, if arterial blood oxygen saturation (SpO2) was globally inversely correlated with apnoea duration, the lowest SpO2 at the end of breath-hold was not found in the divers that performed the best apnoea. We concluded that these divers save their oxygen. The IMA level provides a useful measure of resistance to hypoxaemia.

Introduction: Scleroderma is characterized by cutaneous manifestations that mainly affect the hands, arms and face. As of today, there is no treatment for fibrotic skin lesions of scleroderma. Previously we generated and validated a model of scleroderma-like skin sclerosis in nude mice, appropriate to inject human derived products. We showed that the subcutaneous injection of micro-fat (MF), purified and injected using small caliber cannulas, have anti-fibrotic and pro-angiogenic effects and appears more suitable for the treatment of skin lesions of scleroderma compared to the gold standard (Coleman's technique or macro-fat). Here we compared the long-term efficacy of micro-fat "enriched" with other therapeutic products including the stromal vascular fraction (SVF) of fat and platelet-rich plasma (PRP) from blood in our murine model of scleroderma., Methods: We used 72 nude mice in this study. We formed six experimental groups: Macro-fat, MF, SVF, PRP, MF + SVF, MF + PRP. This project has three phases: i) Induction of skin sclerosis by daily subcutaneous injections of bleomycin (BLM) for 4 weeks in nude mice; ii) Purification and injection of the different cell therapy products; iii) Histological analyses done 8 weeks post-injections., Results: MF + SVF and MF + PRP significantly reversed dermal and epidermal sclerosis (P <0.01). Macro-fat, SVF, PRP only corrected the dermal sclerosis (P <0.05). Epidermal sclerosis was reduced in treatments containing MF (P <0.01). MF was more stable. Products containing the SVF were associated with a significant increase of the local vascularization (P <0.01)., Conclusions: All tested substances were effective in treating skin-induced lesions of scleroderma with different levels of fibrosis and vascular improvement; MF derived products are more stable and SVF demonstrated better pro-angiogenic effects. The observed efficacy of this combination of products in the animal model provides a rationale for potential clinical applications to treat human disease.

Hypoxia affects inflammation by modulating T-cell activation via the adenosinergic system. We supposed that, in turn, inflammation influences cell hypoxic behavior and that stimulation of T-cells in inflammatory conditions involves the concerted action of the nuclear factor κB (NF-κB) and the related hypoxia-inducible factor 1α (HIF-1α) on the adenosinergic system. We addressed this hypothesis by monitoring both transcription factors and four adenosinergic signaling parameters - namely adenosine, adenosine deaminase (ADA), adenosine A2A receptor (A2AR) and cAMP - in T-cells stimulated using phorbol myristate acetate and phytohemagglutinin and submitted to hypoxic conditions which were mimicked using CoCl2 treatment. We found that cell viability was more altered in stimulated than in resting cells under hypoxia. Detailed analysis showed that: i) NF-κB activation remained at basal level in resting hypoxic cells but greatly increased following stimulation, stimulated hypoxic cells exhibiting the higher level; ii) HIF-1α production induced by hypoxia was boosted via NF-κB activation in stimulated cells whereas hypoxia increased HIF-1α production in resting cells without further activating NF-κB; iii) A2AR expression and cAMP production increased in stimulated hypoxic cells whereas adenosine level remained unchanged due to ADA regulation; and iv) the presence of H2S, an endogenous signaling molecule in inflammation, reversed the effect of stimulation on cell viability by down-regulating the activity of transcription factors and adenosinergic immunosuppression. We also found that: i) the specific A2AR agonist CGS-21680 increased the suppressive effect of hypoxia on stimulated T-cells, the antagonist ZM-241385 exhibiting the opposite effect; and ii) Rolipram, a selective inhibitor of cAMP-specific phosphodiesterase 4, and 8-Br-cAMP, a cAMP analog which preferentially activates cAMP-dependent protein kinase A (PKA), increased T-cell immunosuppression whereas H-89, a potent and selective inhibitor of cAMP-dependent PKA, restored cell viability. Together, these data indicate that inflammation enhances T-cell sensitivity to hypoxia via NF-κB activation. This process upregulates A2AR expression and enhances cAMP production and PKA activation, resulting in adenosinergic T-cell immunosuppression that can be modulated via H2S., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Severe systemic inflammatory response syndrome (SIRS) occurring after cardiopulmonary bypass (CPB) is a common cause of mortality during cardiac surgery. These syndromes are characterized by vasoplegia and ischemia-reperfusion phenomenom. Adenosine is a strong endogenous vasodilating agent, which may be involved in blood pressure failure during CPB induced by severe SIRS. Ischemia-modified albumin (IMA) is considered as a sensitive marker of tissue ischemia. We examined whether the IMA or adenosine plasma concentrations (APCs) change during a severe SIRS-induced blood pressure failure during CPB., Materials and Methods: Plasma concentration and IMA (median [range]) were measured before, during, and after surgery in 86 patients who underwent coronary revascularization under CBP and were correlated to postoperative clinical course., Results: Preoperative APC values (1.45 [0.52-2.11] μmol L(-1) vs 0.36 [0.12-0.66] μmol L(-1)) and IMA (144 [91-198] IU mL(-1) vs 109 [61-183] U mL(-1)) were significantly increased in patients presenting postoperative severe SIRS. Mean durations of mechanical ventilation, stay in the intensive care unit, and requirement of vasoactive drugs were significantly higher in patients with higher APC and IMA, but APC was the best predictive marker a postoperative severe., Conclusions: Adenosine plasma concentration and IMA concentration are associated with postoperative severe SIRS after CPB., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Seven patients were treated with low dose Ara-C (LDAC). Five patients had acute nonlymphoid leukemia (ANLL), two patients had myelodisplastic syndrome (MDS): refractory anemia (RA) and refractory anemia with excess of blasts in transformation (RAEB-t). Ara-C treatment was given by s.c. injections at a dose of 10-11 mg/m2 every 12 h and only on two occasions by continuous infusion. No improvement, or limited improvement, was observed in five patients and they died of leukemia or of disease-related complications. Two patients with ANLL achieved remission: the first patient after bone marrow aplasia, the second without aplasia but with morphologic evidence of granulocytic differentiation of leukemic cells.