Strong-Isospin-Breaking Correction to the Muon Anomalous Magnetic Moment from Lattice QCD at the Physical Point.

All lattice-QCD calculations of the hadronic-vacuum-polarization contribution to the muon's anomalous magnetic moment to date have been performed with degenerate up- and down-quark masses. Here we calculate directly the strong-isospin-breaking correction to a_{µ}^{HVP} for the first time with physical values of m_{u} and m_{d} and dynamical u, d, s, and c quarks, thereby removing this important source of systematic uncertainty. We obtain a relative shift to be applied to lattice-QCD results obtained with degenerate light-quark masses of δa_{µ}^{HVP,m_{u}≠m_{d}}=+1.5(7)%, in agreement with estimates from phenomenology.

Replacement of dietary fish oil by vegetable oils affects humoral immunity and expression of pro-inflammatory cytokines genes in gilthead sea bream Sparus aurata.

Commercial gilthead sea bream feeds are highly energetic, fish oil traditionally being the main lipid source. But the decreased fish oil production together with the increased prices of this oil encourages its substitution by vegetable oils, imposing new nutritional habits to aquaculture species. Partial replacement of fish oil by vegetable oils in diets for marine species allows good feed utilization and growth but may affect fish health, since imbalances in dietary fatty acids may alter fish immunological status. The effect of dietary oils on different aspects of fish immune system has been reported for some species, but very little is known about the effect of dietary oils on immune-related genes expression in fish. Thus, the objective of this study was to elucidate the role of dietary oils on the expression of two pro-inflammatory cytokines, Tumor Necrosis Factor-α (TNF-α) and Interleukine 1ß (IL-1ß) on intestine and head kidney after exposure to the bacterial pathogen Photobacterium damselae sp. piscicida. For that purpose, 5 iso-nitrogenous and iso-lipidic diets (45% crude protein, 22% crude lipid content) were formulated. Anchovy oil was the only lipid source used in the control diet (FO), but in the other diets, fish oil was totally (100%) or partially (70%) substituted by linseed (rich in n-3 fatty acids) or soybean (rich in n-6 fatty acids) (100L, 100S, 70L, 70S). Fish were fed experimental diets during 80 days and after this period were exposed to an experimental intestinal infection with the pathogen. Serum and tissue samples were obtained at pre-infection and after 1, 3 and 7 days of infection. RNA was extracted and cDNA was synthesized by reverse transcription from intestine and head kidney and the level expression of TNF-α and IL-1ß were assayed by using quantitative real time PCR. The expression level of genes analysed was represented as relative value, using the comparative Ct method (2(-ΔΔCt)). Serum anti-bacterial activity was measured as serum bactericidal capacity and lysozyme activity. Reduction of FO tends to reduce basal (pre-infection) genetic expression of both cytokines. However, complete FO replacement caused an over expression of both pro-inflammatory cytokines, particularly after 3 days of induced infection in fish fed soybean oil based diets. On the other hand, fish fed diets with low content of n-6 fatty acids showed better serum bactericidal capacity after infection, suggesting that the substitution of fish oil by vegetable oils containing high levels of n-6 fatty acids may induce imbalances on fish immune response, leading to a lower potential response against infections.

Acquired chronic hepatocerebral degeneration due to cirrhosis from non-alcoholic steatohepatitis.

INTRODUCTION AND OBJECTIVE: Acquired chronic hepatocerebral degeneration, acquired hepatolenticular degeneration or pseudo-Wilson is an infrequent disorder with a hepatic origin. Cases in the literature are scarce and it is frequently confused with hepatic encephalopathy and Wilson s disease. The aim of this essay is to report a patient suffering from this disorder due to cirrhosis from non-alcoholic steatohepatitis. CASE REPORT: We present a 54-year-old man diagnosed from cirrhosis grade B9 of the Child Pugh classification. He progressively developed a picture with bradylalia, mild postural and action tremor and spatial and temporal disorientation. Further studies demonstrated an increase of the values of hepatic transaminases and a hyperintensity in the basal nuclei in the cerebral magnetic resonance imaging. Clinical and radiological data established the diagnosis of hepatocerebral degeneration. CONCLUSIONS: Acquired chronic hepatocerebral degeneration is a disorder rarely reported in the literature that it is usually confused with other diseases. We alert about the need of having this diagnosis into account with patients developing neurological symptoms after hepatic disease.

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs.

Histone deacetylases (HDACs) catalyse the removal of acetyl groups from the N-terminal tails of histones. All known HDACs can be categorized into one of four classes (I-IV). The class III HDAC or silencing information regulator 2 (Sir2) family exhibits characteristics consistent with a distinctive role in regulation of chromatin structure. Accumulating data suggest that these deacetylases acquired new roles as genomic complexity increased, including deacetylation of non-histone proteins and functional diversification in mammals. However, the intrinsic regulation of chromatin structure in species as diverse as yeast and humans, underscores the pressure to conserve core functions of class III HDACs, which are also known as Sirtuins. One of the key factors that might have contributed to this preservation is the intimate relationship between some members of this group of proteins (SirT1, SirT2 and SirT3) and deacetylation of a specific residue in histone H4, lysine 16 (H4K16). Evidence accumulated over the years has uncovered a unique role for H4K16 in chromatin structure throughout eukaryotes. Here, we review the recent findings about the functional relationship between H4K16 and the Sir2 class of deacetylases and how that relationship might impact aging and diseases including cancer and diabetes.

Bisanthracycline WP631 inhibits basal and Sp1-activated transcription initiation in vitro.

An in vitro transcription assay was used to compare the capacity of the bisintercalating anthracycline WP631 (which displays a remarkably high DNA-binding affinity) and the monointercalating anthracycline daunomycin to inhibit transcription initiation of the adenovirus major late promoter linked to a G-less transcribed DNA template. Both drugs inhibit basal RNA synthesis in a concentration-dependent way, and the drug concentrations required to inhibit transcription initiation are similar. However, in this study WP631 was around 15 times more efficient at inhibiting transcription initiation when used with an adenovirus promoter containing an upstream Sp1-protein binding site under experimental conditions in which the Sp1 protein acted as a transactivator in vitro. The differences in the ability of each drug to inhibit transcription initiation were related to the competition between Sp1 and the drugs for the same binding site. Concentrations of WP631 as low as 60 nM could inhibit the Sp1-activated transcription initiation in vitro. In contrast, the concentration of daunomycin required to inhibit Sp1-activated transcription by 50% was almost the same as the concentration required to inhibit basal transcription. The efficiency of WP631 at displacing Sp1 from its putative binding site was confirmed using gel retardation and footprinting assays. These results are the first unequivocal example of a direct effect of an intercalator on activated transcription initiation.

Hemopoietic stem cell transplantation in childhood: reduction in mortality and improvement of survival over the years.

Stem cell transplantation (SCT) is an effective treatment for life-threatening hematologic and nonhematologic pediatric diseases. Reducing transplant-related mortality (TRM), a major complication of SCT, to improve long-term survival, therefore, is one of the main objectives of transplantation teams. We analyzed TRM and overall survival (OS) over the years in children undergoing SCT in our center. From June 1998 to October 2002, 156 consecutive children, 105 boys and 51 girls, median age 10 years (range, 2-18), with different diagnoses underwent SCT (100 autologous and 56 allogeneic). OS and TRM were analyzed in 2 different periods (June 1989-December 1998 and January 1999-October 2002) and grouped according to the different SCT modalities. The median follow-up was 18 months (range, 1-160). Autologous TRM showed a statistically significant improvement within 1999-2002 (0%) compared with 1989-1998 (12.2%) (P < .05). There were no statistical differences for allogeneic SCT. OS was 34% in the first period and 80.4% in the second period (P < .01), the improvement being for both autologous and allogeneic SCT. In our study, TRM decreased significantly for those children receiving autologous SCT in recent years. OS was significantly better in the latter period (1999-2002), both globally and for each SCT modality.

Small ligands that neither bind to nor alter the structure of d(GA x TC)n sequences in DNA.

Three minor-groove binding ligands have been used to study the characteristics of two d(GA x CT)n DNAs embedded in longer DNA fragments. The binding of mithramycin, netropsin or Thia-Net to these sequences has been studied using DNAse I footprinting. None of these ligands appeared to bind to d(GA x CT)5 nor to d(GA x CT)22 extensively, although with mithramycin some protected bonds were detected at the very edge of these sequences. In general, these small ligands did not enhance the DNAse I cleavage patterns at the alternating d(GA x CT)n flanking sequences located near DNA regions where the drug was bound. The d(GA x CT)n sequences could act as a rigid block in which it is not easy to propagate structural changes, whereas other sequences flanking the binding sites showed cleavage enhancements.

Analysis of the effects of daunorubicin and WP631 on transcription.

The proficiency with which anthracyclines and other DNA-binding drugs target certain sequences in eukaryotic promoters offers a potential approach to interfere with the mechanisms that regulate gene expression in tumor cells. An in vitro transcription assay has been used to compare the ability of the bisintercalating anthracycline WP631 and the monointercalating anthracycline daunorubicin in terms of their ability to inhibit initiation of transcription of the adenovirus major late promoter linked to a G-less transcribed DNA template. Both drugs inhibit basal transcription by RNA polymerase II. However, WP631 is approximately 15 times more efficient at inhibiting transcription initiation from an adenovirus promoter containing an upstream Sp1-protein binding site. The differences in the ability of each drug to inhibit transcription initiation appear to be related to the competition between Sp1 and the anthracyclines for binding to the same site. To see whether WP631's strong effect on transcription can also be observed in cells, we compared the effects of WP631 and other anthracyclines on the transcription of the c-myc gene, which promoter contains Sp1 binding sites. The resulting data suggest that WP631 might circumvent some kinds of tumor resistance at rather low drug concentrations, inhibit c-myc expression in some cell lines, and exert its antitumoral effect by inducing apoptosis.

Progressive multifocal leukoencephalopathy in HIV infection presenting as Balint's syndrome.

We report a patient with AIDS presenting with Balint's syndrome. CT and MRI showed the characteristic lesions of a progressive multifocal leukoencephalopathy, which was confirmed by histologic examination.

Relationship between lactate and ammonia thresholds in heart transplant patients.

The purpose of this investigation was to study the relationship between both blood ammonia thresholds (AmT) and lactate thresholds (LT) during dynamic exercise in cardiac transplant patients (CTPs). Eleven male patients who had undergone orthotopic cardiac transplantation (age: 54 +/- 11 years, mean +/- SD; height: 165.1 +/- 6.6 cm; body mass: 78.3 +/- 16.1 kg) participated in this study. Each of them performed a bicycle ergometer test (ramp protocol) until volitional fatigue. During each test, gas exchange parameters and ECG responses were determined continuously. In addition, blood lactate and ammonia concentrations were measured every 2 min for determination of both LT and AmT, respectively. Peak values of oxygen uptake (Vo2), respiratory exchange ratio, ventilation, and heart rate averaged 15.9 +/- 3.03 mL.Kg-1.min-1, 1.02 +/- 0.06, 46.69 +/- 5.69 L.min-1, and 124 +/- 16 beats per minute, respectively. However, blood concentrations of lactate and ammonia at peak exercise were 3.7 +/- 0.4 mmol.L-1 and 85.6 +/- 31.7 micrograms.dL-1, respectively. LT and AmT were detected in 8 (72.7% of total) and 9 (81.8% of total) of 11 subjects, respectively. No significant differences were found between mean values of LT and AmT, when both were expressed either as Vo2 (10.01 +/- 1.19 vs 10.5 +/- 2.38 mL.kg-1.min-1, respectively) or as percent Vo2 peak (64.62 +/- 11.362 vs 66.48 +/- 9.19%, respectively). In addition, LT and AmT were significantly correlated (p < 0.05) when both were expressed either as Vo2 (mL.kg-1.min-1) or as percent Vo2 peak (r = 0.70 and r = 0.68, respectively). Our findings suggest that in CTPs, both LT and AmT occur at similar workloads, probably as a result of skeletal muscle alterations associated with chronic deconditioning and immunosuppressive therapy.

Electromyographic response to exercise in cardiac transplant patients: a new method for anaerobic threshold determination?

The purpose of this study was to investigate the possible use of integrated surface electromyography (iEMG) in cardiac transplant patients (CTPs) as a new noninvasive determinant of the metabolic response to exercise by studying the relationship between the iEMG threshold (iEMGT) and other more conventional methods for anaerobic threshold (AT) determination, such as the lactate threshold (LT) and the ventilatory threshold (VT). Thirteen patients (age: 57+/-7 years, mean+/-SD; height: 163+/-7 cm; body mass: 70.5+/-8.6 kg; posttransplant time: 87+/-49 weeks) were selected as subjects. Each of them performed a ramp protocol on a cycle ergometer (starting at 0 W, the workload was increased in 10 W/min). During the tests, gas exchange data, blood lactate levels, and iEMG of the vastus lateralis were collected to determine VT, LT, and iEMGT, respectively. The results evidenced no significant difference between mean values of VT, LT, or iEMGT, when expressed either as oxygen uptake (11.1+/-2.4, 11.7+/-2.3, and 11.0+/-2.8 mL/kg/min, respectively) or as percent maximum oxygen uptake (61.6+/-7.5, 62.2+/-7.7, and 59.6+/-8.2%, respectively). In conclusion, our findings suggest that iEMG might be used as a complementary, noninvasive method for AT determination in CTPs. In addition, since the aerobic impairment of these patients is largely due to peripheral limitation, determination of iEMGT could be used to assess the effectiveness of an exercise rehabilitation program to improve muscle aerobic capacity in CTPs.

Saliva composition and exercise.

Little attention has been directed toward identifying the changes which occur in salivary composition in response to exercise. To address this, our article first refers to the main aspects of salivary gland physiology. A knowledge of the neural control of salivary secretion is especially important for the understanding of the effects of exertion on salivary secretion. Both salivary output and composition depend on the activity of the autonomic nervous system and any modification of this activity can be observed indirectly by alternations in the salivary excretion. The effects of physical activity (with reference to factors such as exercise intensity and duration, or type of exercise protocol) on salivary composition are then considered. Exercise might indeed induce changes in several salivary components such as immunoglobulins, hormones, lactate, proteins and electrolytes. Saliva composition might therefore be used as an alternative noninvasive indicator of the response of the different body tissues and systems to physical exertion. In this respect, the response of salivary amylase and salivary electrolytes to incremental levels of exercise is of particular interest. Beyond a certain intensity of exercise, and coinciding with the accumulation of blood lactate (anaerobic threshold or AT), a 'saliva threshold' (Tsa) does indeed exist. Tsa is the point during exercise at which the levels of salivary alpha-amylase and electrolytes (especially Na+) also begin to rise above baseline levels. The occurrence of the 2 thresholds (AT and Tsa) might, in turn, be attributable to the same underlying mechanism, that of increased adrenal sympathetic activity at high exercise intensities.

Parkinsonism unmasked by verapamil.

We report the case of a 55-year-old man who had a parkinsonian syndrome unresponsive to levodopa for 5 years and had been taking verapamil during the past 8 years. Parkinsonian signs improved markedly after withdrawal of verapamil, suggesting its role in unmasking the parkinsonism. To our knowledge, this side effect of verapamil has not been described previously.

Drug-induced parkinsonism in a movement disorders unit: A four-year survey.

UNLABELLED: To establish the frequency of drug-induced parkinsonism (DIP) and the drugs responsible for this side-effect we reviewed the database of our Movement Disorders Unit during the first 4 years of its use. The diagnostic criteria for DIP included: (1) the presence of two or more cardinal symptoms of parkinsonism, (2) an absence of parkinsonian symptoms before the exposure to the offending drug, (3) a disappearance or significant improvement in parkinsonism after withdrawal of the offending drug, (4) no better explanation for the parkinsonism. One-hundred and five patients fulfilled the diagnostic criteria for DIP (16.3% of total patients referred and 33.8% of patients with parkinsonian syndromes). Drug-induced parkinsonism was related to 1, 2, 3, 4, 5 and 7 drugs in 62, 30, 9, 1, 2 and 1 patients, respectively. The most frequently offending drugs were: calcium-channel blockers (61 cases), antipsychotic drugs (29 cases), thiethylperazine (18 cases), clebopride (14 cases), and sulpiride (10 cases). When compared with idiopathic Parkinson's disease patients, DIP patients were predominantly female and showed an older age at the onset of parkinsonian signs. Parkinsonian signs only disappeared completely in 41 patients (39.0%). IN CONCLUSION: (1) DIP was a frequent cause of parkinsonism in our Movement Disorder Unit, (2) calcium-channel blockers, and/or orthopramides and substituted benzamides were a frequent cause of DIP in our series, (3) old age and the female gender were frequent among DIP patients, (4) DIP is not always reversible.

[Arterial hypertension and exercise]. / Hipertensión arterial y ejercicio.

Both dynamic and static exercise increase blood pressure in normotensive and hypertensive patients, but the change varies among these two main forms of exercise. The validity of the blood pressure response to acute exercise as a predictor for the future development of hypertension in normotensives, or of the degree of target organ damage in hypertensives is still not clear. This acute response could be an independent predictor of mortality or cardiovascular events in the normotensives. The postexercise hypotension could work as a beneficial mechanism to reduce the reduce the rise in pressure that occurs with time. While epidemiological studies suggest an inverse relationship between physical activity or fitness and blood pressure, longitudinal studies seem to confirm the hypotensive effect of dynamic aerobic training. Though possibly in a lesser degree, strength training has also been proved to be effective. Among the responsible mechanisms, a decrease in sympathetic nerve activity is most likely involved. Hypertension seems to be also associated with a lower maximal capacity, that could be even more adversely affected by the action of certain antihypertensive drugs such as diuretics or beta-blockers. All of these aspects have led to the acceptance of physical exercise among the non-pharmacological measures for the treatment of hypertension.

[Rehabilitation in the heart transplant patient]. / Rehabilitación en el paciente trasplantado de corazón.

Cardiac transplantation should not only enlarge life time but additionally should provide the patient with good quality of life and a satisfactory rehabilitation level. An integrated rehabilitation program can help to the process of recovery. In spite of the multiple factors which modify the physiological response during exercise, an appropriate training can be reached by many patients. Nevertheless the physiological rehabilitation is one of the components of the patients global restitution in order to reach satisfactory life style after transplantation.

[The importance of determining oxygen consumption in the indications for a heart transplant]. / Importancia de la determinación del consumo de oxígeno en las indicaciones del trasplante cardíaco.

Maximal exercise performance in patients with chronic heart failure, as determined by peak oxygen consumption (VO2max.) during exercise testing has been shown to correlate well with mortality and its use as primary determining factor in the selection of patients for heart transplant has been advocated. Patients with a VO2max of less than 14 ml/kg/min appear at particularly high risk for mortality. Exercise performance can be influenced by a number of independent factors including subject motivation, peripheral deconditioning or other intrinsic abnormalities of skeletal muscle, and primary respiratory disease. It appears to be a precise gauge of functional impairment. VO2max can be used to accurately and reproducibly place an individual in a predefined functional class.

Azelastine does not adversely affect aerobic performance.

BACKGROUND: The effect of the treatment of allergic rhinitis with azelastine on physiological indicators of aerobic performance such as VO2 max and ventilatory threshold (VT) were evaluated. The clinical efficacy of azelastine was also established. EXPERIMENTAL DESIGN: fifteen physically active males with allergic rhinitis or rhinoconjunctivitis were selected as subjects (experimental group, EXP). Fifteen physically active, healthy subjects served as controls. Subjects performed a maximal incremental exercise test on a bicycle ergometer (ramp protocol) before and after a 5-day treatment period. During the 5 days, EXP group subjects were treated with azelastine (intranasal dose of 0.56 mg/day). The following variables were recorded before and after treatment: power output (W), HR (beats.min-1), VO2 (ml.kg-1.min-1), minute ventilation (VE, in 1.min-1), and oxygen pulse (VO2.HR-1, in ml.beat -1). Blood lactate concentrations (mmol.l-1) were also determined using capillary blood samples (25 microliters). RESULTS: No significant difference was found between pre- and post-trial variables in control subjects. However, peak HR values were lower in EXP subjects after treatment with azelastine (190 +/- 6 beats.min-1 pre-treatment vs 186 +/- 56 beats.min-1 post-treatment; p < 0.05). In addition, VE values at the exercise intensity corresponding to VT were higher in EXP after treatment (54.7 +/- 12.8 l.min-1 pre-treatment vs 60.2 +/- 14.6 l.min-1 post-treatment, p < 0.05). CONCLUSIONS: These findings suggest that the intranasal administration of azelastine used for the treatment of allergic symptoms of the upper respiratory tract in physically active subjects, does not seem to adversely affect maximal aerobic capacity or submaximal aerobic performance.

Lactic threshold vs ventilatory threshold during a ramp test on a cycle ergometer.

OBJECTIVE: The purpose of this investigation was to study the relationship between the lactate (LT) and the ventilatory threshold (VT) during a ramp protocol in cycle ergometry. PARTICIPANTS: Thirty nine trained male subjects were selected as subjects. EXPERIMENTAL DESIGN: All the subjects performed a maximal ergometric test on a cycle ergometer consisting of a ramp protocol (increases of 25 W.min-1). The anaerobic threshold (AT) was determined using both ventilatory gas analysis (VT) and lactate measurement (LT). All the data related to the VT and LT were expressed in work rate (W), VO2 (ml.kg-1.min-1) and heart rate (bpm) and expressed as mean and standard deviation. Lactate threshold (LT) and ventilatory threshold (VT) were compared using the Student's "t"-test for paired data. Correlation coefficients between both variables were also calculated. Statistical significance was accepted at the 5% level. RESULTS: Results showed significant differences (p < 0.05) between mean values of VT and LT when both expressed either as heart rate (bpm), work rate (W), or VO2 (ml.kg-1.min-1). CONCLUSIONS: It was concluded that LT and VT occur at different exercise intensities during ramp protocol exercise on a cycle ergometer.

The use of a fixed value of RPE during a ramp protocol. Comparison with the ventilatory threshold.

BACKGROUND: The purpose of our investigation was to assess the use of a fixed value (12-13) of the Rating of Perceived Exertion (RPE) scale (6-20) as a valid method for the determination of the workload corresponding to the ventilatory threshold (VT) during a ramp protocol on a cycle ergometer. METHODS: Eleven trained cyclists (22 +/- 3 years of age; VO2max: 65.2 +/- 12.4 ml.kg-1.min-1) were selected as subjects. DESIGN: Each of the subjects performed a ramp protocol on a cycle ergometer (starting at 25 W, with increases of 25 W.min-1 until exhaustion). Gas exchange data were analysed continually during the test to detect the ventilatory threshold (VT) of the subjects. In addition values of RPE were obtained from each subject in the last 15 sec of each 2-minute-interval during the tests, and immediately after exhaustion. The RPE threshold (RPET) was defined as a constant value of 12-13. Mean values of VT and RPET were expressed as VO2 (ml.kg-1.min-1), %VO2max, heart rate (bpm) and power output (W), and were compared using a paired "t"-test. RESULTS: No significant difference (p < 0.05) was found between mean values of VT and RPET, when both parameters where expressed either as VO2, %VO2max, heart rate, or power output. CONCLUSIONS: In conclusion, a fixed value (12-13) of the RPE scale might be used to detect the exercise intensity corresponding to VT. Such parameter may therefore be used for exercise prescription in substitution to more sophisticated methodologies.