Enhancement of the CO2 adsorption and hydrogenation to CH4 capacity of Ru-Na-Ca/γ-Al2O3 dual function material by controlling the Ru calcination atmosphere.

Integrated CO2 capture and utilization (ICCU) technology requires dual functional materials (DFMs) to carry out the process in a single reaction system. The influence of the calcination atmosphere on efficiency of 4% Ru-8% Na2CO3-8% CaO/γ-Al2O3 DFM is studied. The adsorbent precursors are first co-impregnated onto alumina and calcined in air. Then, Ru precursor is impregnated and four aliquotes are subjected to different calcination protocols: static air in muffle or under different mixtures (10% H2/N2, 50% H2/N2 and N2) streams. Samples are characterized by XRD, N2 adsorption-desorption, H2 chemisorption, TEM, XPS, H2-TPD, H2-TPR, CO2-TPD and TPSR. The catalytic behavior is evaluated, in cycles of CO2 adsorption and hydrogenation to CH4, and temporal evolution of reactants and products concentrations is analyzed. The calcination atmosphere influences the physicochemical properties and, ultimately, activity of DFMs. Characterization data and catalytic performance discover the acccomodation of Ru nanoparticles disposition and basic sites is mostly influencing the catalytic activity. DFM calcined under N2 flow (RuNaCa-N2) shows the highest CH4 production (449 µmol/g at 370°C), because a well-controlled decomposition of precursors which favors the better accomodation of adsorbent and Ru phases, maximizing the specific surface area, the Ru-basic sites interface and the participation of different basic sites in the CO2 methanation reaction. Thus, the calcination in a N2 flow is revealed as the optimal calcination protocol to achieve highly efficient DFM for integrated CO2 adsorption and hydrogenation applications.

Impact of Treatment with Antioxidants as an Adjuvant to Standard Therapy in Patients with Septic Shock: Analysis of the Correlation between Cytokine Storm and Oxidative Stress and Therapeutic Effects.

Cellular homeostasis is lost or becomes dysfunctional during septic shock due to the activation of the inflammatory response and the deregulation of oxidative stress. Antioxidant therapy administered alongside standard treatment could restore this lost homeostasis. We included 131 patients with septic shock who were treated with standard treatment and vitamin C (Vit C), vitamin E (Vit E), N-acetylcysteine (NAC), or melatonin (MT), in a randomized trial. Organ damage quantified by Sequential Organ Failure Assessment (SOFA) score, and we determined levels of Interleukins (IL) IL1ß, Tumor necrosis factor alpha (TNFα), IL-6, monocyte chemoattractant protein-1 (MCP-1), Transforming growth factor B (TGFß), IL-4, IL-10, IL-12, and Interferon-γ (IFNγ). The SOFA score decreased in patients treated with Vit C, NAC, and MT. Patients treated with MT had statistically significantly reduced of IL-6, IL-8, MCP-1, and IL-10 levels. Lipid peroxidation, Nitrates and nitrites (NO3- and NO2-), glutathione reductase, and superoxide dismutase decreased after treatment with Vit C, Vit E, NAC, and MT. The levels of thiols recovered with the use of Vit E, and all patients treated with antioxidants maintained their selenium levels, in contrast with controls (p = 0.04). The findings regarding oxidative stress markers and cytokines after treatment with antioxidants allow us to consider to future the combined use of antioxidants in a randomized clinical trial with a larger sample to demonstrate the reproducibility of these beneficial effects.

An electrochemical alternative for evaluating the antioxidant capacity in walnut kernel extracts.

A fast, precise and inexpensive alternative for evaluating the antioxidant activity (AA) in walnut kernel extracts is proposed. Traditional ABTS assay and an electrochemical index approach have been applied to evaluate the AA in walnuts. A fast and efficient defatting of the walnuts by ultrasound assisted extraction (UAE) was carried out. Later, for the extraction of polyphenolic compounds, a procedure based on UAE in ethanolic medium was used. The AA of the sample ethanolic extracts was expressed as both % of inhibition by the ABTS spectrophotometric method and the electrochemical index approach (EI) obtained by the ratio between current and potential peak values using differential pulse voltammetry (DPV) at a Sonogel-Carbon electrode. The behaviour of the EI approach have been explored using six polyphenols standards and walnut kernel extracts at pH 2. All the polyphenols appeared at an oxidation potential between 0.476 and 0.778 V. Eleven samples available to consumers were analysed. A high significant correlation (R2 = 0.927) between the spectrophotometric measurements and the EI approach of the walnut extracts was obtained.

Robot-Assisted Radical Prostatectomy After Prior Transurethral Resection of Prostate: An Analysis of Perioperative, Functional, Pathologic, and Oncologic Outcomes.

Background: We performed a retrospective comparison of surgical, oncologic, and functional outcomes after robot-assisted radical prostatectomy between patients who have undergone prior transurethral resection of prostate (TURP) to TURP-naive patients. Methods: Past robotic prostatectomy hospital data were scrutinized to form two matched groups of patients: those who have undergone prior TURP and TURP-naive patients. The perioperative and pathologic data along with functional and oncologic outcomes for a period of 3 years were compared between groups. Results: Compared with TURP-naive patients, prior TURP patients experienced longer robot-assisted laparoscopic prostatectomy times (p < 0.001), increased incidence of bladder neck reconstruction (p = 0.03), greater blood loss (p = 0.0001), and lesser nerve sparing (p < 0.01). Complication rates (p = 0.3), positive surgical margin (p = 0.4), extracapsular disease (p = 0.3), or seminal vesicle invasion (p = 0.1) were comparable between groups. Continence (p = 0.5) and potency (p = 0.1) at 1 year were not different between groups. Biochemical recurrence rates were not different at 3 years (p = 0.9). Diabetes slowed recovery of continence in patients with prior TURP compared with TURP-naive patients until 6 months after surgery. Conclusion: Although prior TURP makes subsequent robotic prostatectomy more technically demanding, it can be safely performed by experienced surgeons without compromising long-term functional or oncologic outcomes.

Antioxidants and pentoxifylline as coadjuvant measures to standard therapy to improve prognosis of patients with pneumonia by COVID-19.

The type 2 coronavirus causes severe acute respiratory syndrome (SARS-CoV-2) and produces pneumonia with pulmonary alveolar collapse. In some cases it also causes sepsis and septic shock. There is no specific treatment for coronavirus disease 2019 (COVID-19). Vitamin C (Vit C), Vitamin E (Vit E), N-acetylcysteine (NAC) and Melatonin (MT) increase the intracellular content of GSH, kidnap free radicals and protect DNA, proteins in the cytosol and lipids in cell membranes. Pentoxifylline (Px) has anti-inflammatory activities. Here we evaluate the effect of Vit C, Vit E, NAC, and MT plus Px in COVID-19 patients with moderate and severe pneumonia. 110 patients of either sex were included. They were divided into five groups with 22 patients each. Group 1 received Vit C + Px, group 2 Vit E + Px, group 3 NAC + Px, group 4 MT + Px, and group 5 only Px. Oxidative stress (OS) markers such as lipid peroxidation (LPO) levels, total antioxidant capacity (TAC) and nitrites (NO2 -) were evaluated in plasma. The antioxidant therapy improved the survival scores including the Sequential Organ Failure Assessment (SOFA), the Acute Physiology and chronic Health Evaluation II (Apache II), the Simplified Acute Physiology Score II (SAPS II), the Critical Illness Risk Score, Launched during COVID-19 crisis (COVIDGRAM) and the Glasgow Coma Scale (GCS). We found that LPO (p≤0.04) and inflammation markers such as interleukin-6 (IL-6, p≤ 0.01), C reactive protein (CRP, p ≤ 0.01) and procalcitonin (PCT, p ≤ 0.05) were elevated. TAC (p ≤ 0.03) and NO2 - (p ≤ 0.04) found themselves diminished in diminished in COVID-19 patients upon admission to the hospital. The different antioxidants reversed this alteration at the end of the treatment. The treatment with antioxidant supplements such as Vit C, E, NAC, and MT plus Px could decelerate the aggressive and lethal development of COVID-19. Antioxidant therapy can be effective in this pandemia since it improves the survival scores including SOFA, Apache II, SAPS II, COVIDGRAM, GCS by lowering the LPO, IL-6, CRP, PCT and increasing systemic TAC and NO2 -.

Self-regulatory biofeedback training: an intervention to reduce school burnout and improve cardiac functioning in college students.

With the detrimental relationship between school burnout and physiological and cognitive functioning now well documented, interventions to ameliorate school burnout symptomology are needed. This study examined the effectiveness of a self-regulatory biofeedback intervention program (Heart Rate Variability Coherence Biofeedback Training [HRVCB]) in contrast to a protocol demonstrated to produce cognitive and physiological improvements (a high intensity interval training protocol [HIIT]) as well as a wait-list control condition at decreasing school burnout in an American collegiate sample (N = 90). Intervention training was conducted over a 4-week span (three sessions per week) with accompanying baseline and post-intervention assessments. In addition to measurements of school burnout and negative affect (depression and anxiety), intervention influences on cognition (via a serial subtraction task) and physiology (hemodynamics, electrocardiography, and a submaximal cardiorespiratory fitness test) were explored. Findings indicate HRVCB training significantly decreased school burnout and increased mathematical performance from pre- to post-intervention measurement. These changes did not occur for HIIT or waitlist participants. Brachial and aortic systolic blood pressure decreased pre to post-intervention for HRVCB but not HIIT or waitlist participants. Cardiovascular fitness (VO2max) improved pre to post-intervention for HIIT but not HRVCB or waitlist participants. Also, both HRVCB and HIIT training participants decreased heart rate from pre to post-intervention but not waitlist participants. Finally, all participants decreased cardiac sympathovagal tone from pre to post-intervention. These findings provide evidence that HRVCB training programs can decrease school burnout as well as improve components associated with cardiac health. Study limitations and directions for future research are discussed.

Acupuncture therapy improves vascular hemodynamics and stiffness in middle-age hypertensive individuals.

Acupuncture (ACU) is becoming a more common practice among hypertensive individuals. However, the reported therapeutic effects of ACU in lowering brachial blood pressure (BP) are ambiguous. Therefore, evaluating more sensitive markers of arterial functioning might unveil the protective effects of ACU on hypertension. We examined the effects of an 8-week ACU therapy intervention on vascular hemodynamics and stiffness in middle-age hypertensive individuals. Participants were randomly assigned to either ACU (n = 23) or a control group (n = 22). Brachial and aortic BP, wave reflection (AIx) and arterial stiffness (SI) were measured before and after 8 weeks. There was a significant group x time interaction (P < 0.05) for brachial and aortic BP, AIx and SI which significantly decreased (P < 0.05) following ACU but not after control. ACU led to reductions in brachial and aortic BP, wave reflection and arterial stiffness in middle-age hypertensive individuals. ACU might be effective in the prevention and treatment of hypertension.

Effectiveness of Tai Chi on Cardiac Autonomic Function and Symptomatology in Women With Fibromyalgia: A Randomized Controlled Trial.

The present study examined the effects of a 12-week Tai Chi (TC) training regimen on heart rate variability (HRV), symptomatology, muscle fitness and body composition in women with fibromyalgia. Participants were randomly assigned to either a TC training group (n = 18) or a control group (n = 19). HRV, symptomatology, muscle fitness and body composition were measured before and after 12 weeks. There were significant decreases (p < 0.05) in sympathovagal balance (LnLF/LnHF), sympathetic tone (LnLF, nLF), pain, and fatigue, and significant increases (p < 0.05) in parasympathetic tone (LnHF, nHF), strength and flexibility following TC compared with no changes after control. The changes in LnLF and LnLF/LnHF were correlated with changes in pain. There were no significant changes in HR, sleep quality and body composition after TC or control. TC may be an effective therapeutic intervention for improving sympathovagal balance, pain, fatigue, strength and flexibility in women with fibromyalgia.

The Effects of Stretching Training on Cardiac Autonomic Function in Obese Postmenopausal Women.

Context • Menopause and obesity are associated with autonomic dysfunction. Unconventional exercise modalities that include an important flexibility component seem to improve cardiac autonomic function by lowering sympathetic tone and increasing vagal modulation of the heart rate (HR). Yet clear evidence of the effects of stretching training (ST) on cardiac autonomic modulation is limited. Objective • The present study intended to examine the effects of ST on HR variability (HRV) and flexibility in obese postmenopausal women. Design • The research team designed a randomized, controlled trial. Setting • The study was conducted at the Florida State University (Tallahassee, FL, USA). Participants • Twenty-four obese, postmenopausal women, aged 50-65 y with a body mass index of >30 but <40 kg/m2 participated in the study. Intervention • Participants were randomly assigned either to an ST group (n = 12) or a no-exercise control group (n = 12). The study was 8 wk in duration. Outcome Measures • Participant HRV and sit-and-reach scores (SRSs) were measured at baseline and after 8 wk of training. Results • Significant decreases occurred for the ST group between baseline and postintervention in sympathetic activity, as measured by normalized low frequency (nLF) power, and in sympathovagal balance, as measured by the ratio of the natural logarithm low frequency (LnLF) activity to the natural logarithm high frequency (LnHF) power, with P < .01 for both measures. The decreases for the ST group were significantly greater than those for the control group for the nLF and LnLF/LnHF, with P < .05 for both measures. Significant increases in vagal tone occurred for the ST group between baseline and postintervention, as measured by the normalized high frequency (nHF) power, with P < .01, and in SRS following ST, with P < .001. The increases for the ST group were significantly greater than those for the control group for the nHF and SRS, with P < .05 for both measures. The changes in SRS were correlated with the changes in the LnLF/LnHF power, with r = .65 and P < .03 negatively correlated. Conclusions • The findings indicated that ST can improve cardiac autonomic modulation by increasing vagal tone and decreasing sympathetic activity in obese postmenopausal women. The improvement in SRS partially explained the decrease in the sympathovagal balance. Because older or obese individuals have a higher risk of developing cardiovascular diseases, they could potentially benefit from ST.

Understanding the physiology of mindfulness: aortic hemodynamics and heart rate variability.

Data were collected to examine autonomic and hemodynamic cardiovascular modulation underlying mindfulness from two independent samples. An initial sample (N = 185) underwent laboratory assessments of central aortic blood pressure and myocardial functioning to investigated the association between mindfulness and cardiac functioning. Controlling for religiosity, mindfulness demonstrated a strong negative relationship with myocardial oxygen consumption and left ventricular work but not heart rate or blood pressure. A second sample (N = 124) underwent a brief (15 min) mindfulness inducing intervention to examine the influence of mindfulness on cardiovascular autonomic modulation via blood pressure variability and heart rate variability. The intervention had a strong positive effect on cardiovascular modulation by decreasing cardiac sympathovagal tone, vasomotor tone, vascular resistance and ventricular workload. This research establishes a link between mindfulness and cardiovascular functioning via correlational and experimental methodologies in samples of mostly female undergraduates. Future directions for research are outlined.

A brief review: the implications of iron supplementation for marathon runners on health and performance.

The marathon is considered one of the most demanding endurance events, imposing an enormous amount of physiological stress on bodily structures, the metabolic machinery, and organ systems. Scientific evidence has conclusively shown that marathoners are in need of special nutritional strategies to maintain performance and health. Indeed, among competitive athletes, marathoners are at greater risk to develop anemia, bone mineral density loss, immunosuppression, and other clinical syndromes that may affect performance. Inadequate dietary intake of the micronutrient iron has been identified as one key factor in the development of the above mentioned anomalies. In fact, iron is one of the few nutrients recommended as a supplement by the American College of Sports Medicine (ACSM), the Academy of Nutrition and Dietetics (AND), and Dietitians of Canada. Therefore, the aim of this review article is to discuss the role of iron on the marathoner's health and performance. Special emphasis will be given to the physiological mechanisms accounting for the additional iron need in this group of athletes and the nutritional strategies intended to counteract iron deficiency.

Effects of watermelon supplementation on arterial stiffness and wave reflection amplitude in postmenopausal women.

OBJECTIVE: Postmenopausal women have increased arterial stiffness (brachial-ankle pulse wave velocity [baPWV]) and wave reflection. L-Citrulline supplementation reduces baPWV but not brachial blood pressure. Peripheral vasodilators decrease wave reflection amplitude or second systolic peak (SBP2) in radial artery and aorta, which are related to aortic systolic blood pressure (SBP). We examined the effects of L-citrulline-rich watermelon supplementation on baPWV, wave reflection characteristics, and aortic SBP in postmenopausal women. METHODS: In a randomized cross-over study, 12 postmenopausal women (mean [SE] age, 57 [1] y; mean [SE] body mass index, 38.1 [2.1] kg/m; mean [SE] SBP, 153 [4] mm Hg) were assigned to watermelon supplementation (L-citrulline/L-arginine 6 g/d) or placebo supplementation for 6 weeks. Before and after each intervention, baPWV, aortic SBP, aortic diastolic blood pressure, aortic SBP2, radial SBP2, and aortic and radial augmentation indices were measured using applanation tonometry. RESULTS: baPWV (-1.2 [0.3] m/s, P < 0.001), aortic SBP (-10 [3] mm Hg, P < 0.01), and aortic diastolic blood pressure (-7 [1] mm Hg, P < 0.001) decreased after watermelon supplementation compared with placebo. Although radial and aortic augmentation indices were unaffected, radial and aortic SBP2 decreased (-10 [3] mm Hg, P < 0.01) after watermelon supplementation compared with placebo. The reduction in aortic SBP was correlated with reductions in radial SBP2 (r = 0.99, P < 0.001) and aortic SBP2 (r = 0.98, P < 0.001). The decreases in baPWV correlated with reductions in radial SBP2 (r = 0.57, P < 0.01) and aortic SBP2 (r = 0.64, P < 0.01). CONCLUSIONS: Watermelon supplementation reduces arterial stiffness and aortic SBP by reducing pressure wave reflection amplitude in obese postmenopausal women with hypertension.

Watermelon extract supplementation reduces ankle blood pressure and carotid augmentation index in obese adults with prehypertension or hypertension.

BACKGROUND: Ankle-brachial index (ABI) and ankle blood pressure (BP) are associated with increased carotid wave reflection (augmentation index, AIx). Oral L-citrulline and L-arginine from synthetic or watermelon sources have reduced brachial BP, aortic BP, and aortic AIx. A directly measured carotid AIx (cAIx) rather than aortic AIx has been proposed as a better measurement of central AIx. We evaluated the effects of watermelon extract on ankle BP and cAIx in individuals with normal ABI and prehypertension or stage 1 hypertension. METHODS: Ankle and brachial systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), cAIx, ABI, and heart rate (HR) were evaluated in the supine position in 14 adults (11 women/3 men, age 58 ± 1 years) with prehypertension or stage 1 hypertension (153 ± 4 mm Hg). Subjects were randomly assigned to 6 weeks of watermelon extract supplementation (L-citrulline/L-arginine, 6 g daily) or placebo followed by a 2-week washout period and then crossover. RESULTS: Ankle and brachial SBP (-11.5 ± 3.8 and -15.1 ± 2.8 mm Hg), DBP (-7.8 ± 2.3 and -7.6 ± 1.8 mm Hg), and MAP (-9.8 ± 2.6 and -7.3 ± 1.8 mm Hg), and cAIx (-8.8 ± 2.6 %) decreased significantly (P < 0.05) after watermelon supplementation compared to placebo. Watermelon supplementation had no significant effect (P > 0.05) on ABI and HR. CONCLUSIONS: This study shows that watermelon extract supplementation reduces ankle BP, brachial BP, and carotid wave reflection in obese middle-aged adults with prehypertension or stage 1 hypertension and normal ABI, which may reflect improved arterial function.

Creatine supplementation attenuates hemodynamic and arterial stiffness responses following an acute bout of isokinetic exercise.

Arterial stiffness and hemodynamics may be increased following a bout of resistance exercise. Oral creatine supplementation (Cr) may attenuate cardiovascular responses after exercise via improved anaerobic metabolism. This study was aimed to determine the effect of Cr on hemodynamic and arterial stiffness responses after acute isokinetic exercise. Sixteen healthy males (22.6 ± 0.6 year) were randomly assigned to either placebo (Pl, n = 8) or Cr (n = 8) (2 × 5 g/day) for 3 weeks. Brachial systolic blood pressure (SBP), heart rate (HR), brachial-ankle pulse wave velocity (baPWV), and leg PWV were measured in the supine position at rest before and after the interventions. After the supplementation period, parameters were also measured 5 min (PE5) and 15 min (PE15) after two sets of leg isokinetic exercise. There was no difference between the groups in resting measurements before and after the supplementation. Compared with the Pl group, the Cr group had attenuated (P < 0.05) increases in SBP at PE5 (Pl 14.0 ± 2.5, Cr 5.6 ± 2.3 mmHg), HR at both P5 (Pl 28 ± 4 vs. Cr 16 ± 2 beats/min) and PE15 (Pl 21 ± 3, Cr 11 ± 2 beats/min) and rate pressure product at P5 (Pl 45.8 ± 6.4, Cr 24.8 ± 2.2) and P15 (Pl 34.2 ± 5.0, Cr 15.9 ± 6.0). Compared with the Pl group, the Cr group had suppressed increases in baPWV at PE5 (Pl 1.5 ± 0.4, Cr -0.1 ± 0.4 m/s) and PE15 (Pl 1.1 ± 0.2, Cr -0.3 ± 0.3 m/s) and returned SBP to pre-exercise values at PE15 (Pl 10.6 ± 2.8, Cr 2.1 ± 2.6 mmHg). PWV in the exercised leg decreased at PE5 in both groups. These findings suggest that Cr supplementation attenuates the hemodynamic and baPWV responses after acute isokinetic exercise.

Effects of watermelon supplementation on aortic blood pressure and wave reflection in individuals with prehypertension: a pilot study.

BACKGROUND: Oral L-citrulline is efficiently converted to L-arginine, the precursor for endothelial nitric oxide (NO) synthesis. Oral L-arginine supplementation reduces brachial blood pressure (BP). We evaluated the effects of watermelon supplementation on aortic BP and arterial function in individuals with prehypertension. METHODS: Heart rate (HR), brachial systolic BP (bSBP), brachial pulse pressure (bPP), aortic SBP (aSBP), aortic PP (aPP), augmentation index (AIx), AIx adjusted for HR of 75 beats/min (AIx@75), amplitude of the first (P1) and second (P2) systolic peaks, reflection time (Tr), and carotid-femoral pulse wave velocity (PWV) were evaluated in the supine position in nine subjects (four men/five women, age 54 ± 3 years) with prehypertension (134/77 ± 5/3 mm Hg). Subjects were randomly assigned to 6 weeks of watermelon supplementation (L-citrulline/L arginine, 2.7 g/1.3 g/day) or placebo followed by a 4-week washout period and then crossover. RESULTS: There was a significant treatment effect (change in the value of watermelon minus placebo from baseline to 6 weeks) on bPP (-8 ± 3 mm Hg, P < 0.05), aSBP (-7 ± 2 mm Hg, P < 0.05), aPP (-6 ± 2 mm Hg, P < 0.01), AIx (-6 ± 3%, P < 0.05), AIx@75 (-4 ± 2%, P < 0.05), and P2 (-2 ± 1 mm Hg, P < 0.05). There was no significant treatment effect (P > 0.05) on bSBP, brachial diastolic BP (DBP), aortic DBP, Tr, P1, HR, and carotid-femoral PWV. CONCLUSIONS: This pilot study shows that watermelon supplementation improves aortic hemodynamics through a decrease in the amplitude of the reflected wave in individuals with prehypertension.

Oral L-citrulline supplementation attenuates blood pressure response to cold pressor test in young men.

BACKGROUND: Oral L-citrulline is efficiently converted to L-arginine, which has been shown to decrease brachial blood pressure (BP) at rest and during the cold pressor test (CPT). However, aortic BP may better reflect cardiovascular risk than brachial BP. The purpose of this study was to test the hypothesis that oral L-citrulline supplementation attenuates brachial BP and aortic hemodynamic responses to CPT. METHODS: Brachial BP, aortic BP, stroke volume (SV), and wave reflection at rest and during CPT were evaluated in 17 young (21.6 +/- 0.9 years) normotensive men. Subjects were randomly assigned to 4 weeks of oral L-citrulline (6 g/day) or placebo in a crossover design. Hemodynamic responses to CPT were reevaluated after each treatment. RESULTS: During CPT, there were significant (P < 0.05) increases in brachial and aortic BP [systolic (SBP), diastolic (DBP), and pulse pressure (PP)], augmentation index (AIx), SV, and a decrease in transit time of the reflected wave (Tr) from baseline. Compared to placebo, oral L-citrulline treatment decreased (P < 0.05) brachial SBP (-6 +/- 11 mm Hg), aortic SBP (-4 +/- 10 mm Hg), and aortic PP (-3 +/- 6 mm Hg) during CPT but not at rest. There was an inverse correlation (r = -0.40, P < 0.05) between changes in aortic SBP and Tr during CPT after L-citrulline supplementation. CONCLUSIONS: We conclude that oral L-citrulline supplementation attenuates the brachial SBP, aortic SBP, and aortic PP responses to CPT in young normotensive men. Increased wave reflection time contributes to the reduction in aortic SBP response to CPT.

Inhibition of proteasome by bortezomib causes intracellular aggregation of hepatic serpins and increases the latent circulating form of antithrombin.

Conformational diseases include heterogeneous disorders sharing a similar pathological mechanism, leading to intracellular aggregation of proteins with toxic effects. Serpins are commonly involved in these diseases. These are structurally sensitive molecules that modify their folding under even minor genetic or environmental variations. Indeed, under normal conditions, the rate of misfolding of serpins is high and unfolded serpins must be degraded by the proteasome system. Our aim was to study the effects of bortezomib, a proteasome inhibitor, on conformationally sensitive serpins. The effects of bortezomib were analysed in patients with multiple myeloma, HepG2 cells, and Swiss mice, as well as in vitro. Levels, anti-FXa activity, heparin affinity, and conformational features of antithrombin, a relevant anticoagulant serpin, were analysed. Histological, ultrastructural features and immunohistological distribution of antithrombin and alpha1-antitrypsin (another hepatic serpin) were evaluated. We also studied the intracellular accumulation of conformationally sensitive (fibrinogen) or non-sensitive (prothrombin) hepatic proteins. The inhibition of the proteasome caused intracellular accumulation and aggregation of serpins within the endoplasmic reticulum that was associated with confronting cisternae and Mallory body formation. These effects were accompanied by a heat stress response. Bortezomib also increased the levels of intracellular fibrinogen, but has no significant effect on prothrombin. Finally, bortezomib had only minor effects on the mature circulating antithrombin, with increased amounts of latent antithrombin in plasma. These results suggest that the impairment of proteasomal activities leads to an intracellular accumulation of conformationally sensitive proteins and might facilitate the release of misfolded serpins into circulation where they adopt more stable conformations.

Using quantification of the PML-RARalpha transcript to stratify the risk of relapse in patients with acute promyelocytic leukemia.

BACKGROUND AND OBJECTIVES: The detection of PML-RARalpha by real-time polymerase chain reaction (RQ-PCR) is becoming an important tool for monitoring minimal residual disease (MRD) in patients with acute promyelocytic leukemia (APL). However, its clinical value remains to be determined. Our aim was to analyze any associations between the risk of relapse and RQ-PCR results in different phases of treatment, comparing these data with those yielded by conventional qualitative reverse transcriptase-PCR. DESIGN AND METHODS: Follow-up samples from 145 APL patients treated with the PETHEMA protocols were evaluated by the RQ-PCR protocol (Europe Against Cancer program) and by the RT-PCR method (BIOMED-1 Concerted Action). Hematologic and molecular relapses and relapse-free survival were recorded. We then looked for associations between relapse risk and RQ-PCR results. RESULTS: After induction therapy, no association was found between positive RQ-PCR results and relapse. The PCR result here did not imply any change in the scheduled therapy. After the third consolidation course, two out of three cases with positive RQ-PCR relapsed in contrast to 16 out of 119 (13%) patients with negative RQ-PCR. During maintenance therapy and out-of treatment, all patients with >10 PML-RARalpha normalized copy number (NCN) (n=19) relapsed while all patients with <1 NCN at the end of the study remained in hematologic remission (p<0.0001). In the intermediate group (NCN 1-10) (n=18), the relapse-free survival at 5 years was 60%. Hematologic relapses were predicted if a positive RQ-PCR result had been obtained in a follow-up sample within the previous 4 months. INTERPRETATION AND CONCLUSIONS: Based on the information provided by RQ-PCR in samples obtained after the end of consolidation and subsequently, a relapse risk stratification could be established for APL patients. This stratification divides patients into three groups: those at high risk of relapse, those with an intermediate risk and those with a low risk of relapse.

[Palilalia due to thalamic infarctions]. / Palilalia tras infartos talámicos.

A 45-years-old woman developed palilalia without other neurologic symptoms or signs. Cranial MR and CT scan showed only bilateral thalamic infarcts; the SPECT showed bilateral frontoparietal hypoactivity. We conclude that involvement of the supplementary motor area by diaschisis after bilateral thalamic lesions may produce palilalia.