10 research outputs found
Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women
BACKGROUND: The Glu27Glu genotype in the beta-2-adrenergic receptor (ADRB2) is associated with fat mass, body mass index and obesity in females. In our population, we previously found an association of higher body mass index (BMI) among women who reported more physical activity and carried the Glu27 allele as compared to non carriers with the same level of activity.
OBJECTIVE: To examine the lipid metabolism differences, both at rest and during submaximal exercise in ADRB2 Glu27Glu vs Gln27Gln obese women.
SUBJECTS: Eight obese women with the Glu27Glu genotype (age, 43±5 y; body mass index (BMI), 31.7±0.9 kg/m2; percentage fat mass, 42.0±1.3; WHR, 0.83±0.02; and VO2max, 21.6±0.9 ml/kg/min) were compared with seven obese women with the Gln27Gln genotype (age, 43±5 y; BMI, 33.9±1.3 kg/m2; percentage fat mass, 41.6±1.2; WHR, 0.83±0.02; and VO2max, 20.6±0.8 ml/kg/min).
MEASUREMENTS: The ADRB2 polymorphism was identified by PCR-RFLP. Respiratory quotient was determined by indirect calorimetry at baseline, during 1 h of walking on a treadmill and 1 h after the exercise. Plasma triglycerides, glycerol, FFA, hydroxybutyrate, glucose and lactate were assayed by spectrophotometric methods. Insulin, leptin and progesterone were measured by radioimmunoassay. Adrenaline and noradrenaline were quantified by high performance liquid chromatography.
RESULTS: The ADRB2 Glu27Glu subjects had lower plasma glycerol (P=0.047) and lower hydroxybutyrate (P=0.001) throughout the study than the Gln27Gln group. Plasma triglycerides (P=0.001), lactate (P<0.05) and serum insulin (P<0.05) remained higher in the Glu27Glu group vs the Gln27Gln group. The respiratory quotient (RQ) was higher in the Glu27Glu obese women along the study (P=0.046), and fat oxidation was significantly lower in this group during the recovery (P=0.048). The other variables did not differ statistically between groups.
CONCLUSION: These data suggest that both lipolysis and fat oxidation promoted by an acute submaximal exercise intervention could be blunted in the polymorphic ADRB2 Glu27Glu group of our female obese population
Involvement of the subthalamic nucleus in impulse control disorders associated with Parkinson’s disease
Behavioural abnormalities such as impulse control disorders may develop when patients with Parkinson’s disease receive
dopaminergic therapy, although they can be controlled by deep brain stimulation of the subthalamic nucleus. We have recorded
local field potentials in the subthalamic nucleus of 28 patients with surgically implanted subthalamic electrodes. According to
the predominant clinical features of each patient, their Parkinson’s disease was associated with impulse control disorders
(n = 10), dyskinesias (n = 9) or no dopaminergic mediated motor or behavioural complications (n = 9). Recordings were obtained
during the OFF and ON dopaminergic states and the power spectrum of the subthalamic activity as well as the subthalamocortical
coherence were analysed using Fourier transform-based techniques. The position of each electrode contact was determined
in the postoperative magnetic resonance image to define the topography of the oscillatory activity recorded in each
patient. In the OFF state, the three groups of patients had similar oscillatory activity. By contrast, in the ON state, the patients
with impulse control disorders displayed theta-alpha (4–10 Hz) activity (mean peak: 6.71 Hz) that was generated 2–8mm below
the intercommissural line. Similarly, the patients with dyskinesia showed theta-alpha activity that peaked at a higher frequency
(mean: 8.38 Hz) and was generated 0–2mm below the intercommissural line. No such activity was detected in patients that
displayed no dopaminergic side effects. Cortico-subthalamic coherence was more frequent in the impulsive patients in the
4–7.5 Hz range in scalp electrodes placed on the frontal regions anterior to the primary motor cortex, while in patients with
dyskinesia it was in the 7.5–10 Hz range in the leads overlying the primary motor and supplementary motor area. Thus,
dopaminergic side effects in Parkinson’s disease are associated with oscillatory activity in the theta-alpha band, but at different
frequencies and with different topography for the motor (dyskinesias) and behavioural (abnormal impulsivity) manifestations.
These findings suggest that the activity recorded in parkinsonian patients with impulse control disorders stems from the
associative-limbic area (ventral subthalamic area), which is coherent with premotor frontal cortical activity. Conversely, in
patients with L-dopa-induced dyskinesias such activity is recorded in the motor area (dorsal subthalamic area) and it is coherent
with cortical motor activity. Consequently, the subthalamic nucleus appears to be implicated in the motor and behavioural
complications associated with dopaminergic drugs in Parkinson’s disease, specifically engaging different anatomo-functional
territories
Increased sympathetic and decreased parasympathetic cardiac tone in patients with sleep related alveolar hypoventilation
Patients with SRAH exhibited an abnormal cardiac tone during sleep. This fact appears to be related to the severity of nocturnal oxygen desaturation. Moreover, there were no differences between OSA and SRAH, supporting the hypothesis that autonomic changes in OSA are primarily related to a reduced nocturnal oxygen saturation, rather than a consequence of other factors such as nocturnal respiratory event
Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women
BACKGROUND: The Glu27Glu genotype in the beta-2-adrenergic receptor (ADRB2) is associated with fat mass, body mass index and obesity in females. In our population, we previously found an association of higher body mass index (BMI) among women who reported more physical activity and carried the Glu27 allele as compared to non carriers with the same level of activity.
OBJECTIVE: To examine the lipid metabolism differences, both at rest and during submaximal exercise in ADRB2 Glu27Glu vs Gln27Gln obese women.
SUBJECTS: Eight obese women with the Glu27Glu genotype (age, 43±5 y; body mass index (BMI), 31.7±0.9 kg/m2; percentage fat mass, 42.0±1.3; WHR, 0.83±0.02; and VO2max, 21.6±0.9 ml/kg/min) were compared with seven obese women with the Gln27Gln genotype (age, 43±5 y; BMI, 33.9±1.3 kg/m2; percentage fat mass, 41.6±1.2; WHR, 0.83±0.02; and VO2max, 20.6±0.8 ml/kg/min).
MEASUREMENTS: The ADRB2 polymorphism was identified by PCR-RFLP. Respiratory quotient was determined by indirect calorimetry at baseline, during 1 h of walking on a treadmill and 1 h after the exercise. Plasma triglycerides, glycerol, FFA, hydroxybutyrate, glucose and lactate were assayed by spectrophotometric methods. Insulin, leptin and progesterone were measured by radioimmunoassay. Adrenaline and noradrenaline were quantified by high performance liquid chromatography.
RESULTS: The ADRB2 Glu27Glu subjects had lower plasma glycerol (P=0.047) and lower hydroxybutyrate (P=0.001) throughout the study than the Gln27Gln group. Plasma triglycerides (P=0.001), lactate (P<0.05) and serum insulin (P<0.05) remained higher in the Glu27Glu group vs the Gln27Gln group. The respiratory quotient (RQ) was higher in the Glu27Glu obese women along the study (P=0.046), and fat oxidation was significantly lower in this group during the recovery (P=0.048). The other variables did not differ statistically between groups.
CONCLUSION: These data suggest that both lipolysis and fat oxidation promoted by an acute submaximal exercise intervention could be blunted in the polymorphic ADRB2 Glu27Glu group of our female obese population
Increased sympathetic and decreased parasympathetic cardiac tone in patients with sleep related alveolar hypoventilation
Patients with SRAH exhibited an abnormal cardiac tone during sleep. This fact appears to be related to the severity of nocturnal oxygen desaturation. Moreover, there were no differences between OSA and SRAH, supporting the hypothesis that autonomic changes in OSA are primarily related to a reduced nocturnal oxygen saturation, rather than a consequence of other factors such as nocturnal respiratory event
PERTINENT - PERindopril-Thrombosis, InflammatioN, endothelial dysfunction and neurohormonal activation trial: A sub-study of the EUROPA study
BACKGROUND: Markers of thrombosis, inflammation, endothelial dysfunction and neurohumoral activation such as fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A are reported to be linked to the increase of cardiovascular risk for atherosclerosis progression and events in patients with cardiovascular diseases. METHODS: EUROPA is a double blind, placebo-controlled trial on 12,231 patients that evaluates the effect of an angiotensin converting enzyme inhibitor--perindopril--on prevention of cardiovascular events in patients with coronary artery disease. PERTINENT is a sub-study of EUROPA that evaluates (a) in Part A (300 patients): the influence of perindopril vs. placebo on fibrinogen, D-dimer, C-reactive protein, von Willebrand factor, tumour necrosis factor-alpha and chromogranin-A. In addition, NOS expression and induction of apoptosis on human umbilical vein endothelial cells and angiotensin converting enzyme levels are also studied; (b) in Part B (about 1200 patients): the predictive role of plasma levels of C-reactive protein and von Willebrand factor on the occurrence of cardiovascular events. To this end, matched case-control analyses are planned (patients with vs. patients without events). STATUS OF PERTINENT: Blood analyses are in progress in four specialised laboratories: (a) Gaubius Laboratory, Leiden, TNO-PG, The Netherlands; (b) University Department of Medicine, Birmingham, UK; (c) University of Pavia, Italy; (d) Fondazione Salvatore Maugeri, Cardiovascular Research Centre, Gussago, Italy. CONCLUSIONS: The PERTINENT sub-study might help elucidating the phenomena contributing to the pathophysiology of cardiovascular events in patients with coronary artery disease and the role of perindopril in such context
Heart Rate and Mortality in Patients With Acute Symptomatic Pulmonary Embolism
International audienc
Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study)
BACKGROUND: Treatment with angiotensin-converting-enzyme (ACE) inhibitors reduces the rate of cardiovascular events among patients with left-ventricular dysfunction and those at high risk of such events. We assessed whether the ACE inhibitor perindopril reduced cardiovascular risk in a low-risk population with stable coronary heart disease and no apparent heart failure. METHODS: We recruited patients from October, 1997, to June, 2000. 13655 patients were registered with previous myocardial infarction (64%), angiographic evidence of coronary artery disease (61%), coronary revascularisation (55%), or a positive stress test only (5%). After a run-in period of 4 weeks, in which all patients received perindopril, 12218 patients were randomly assigned perindopril 8 mg once daily (n=6110), or matching placebo (n=6108). The mean follow-up was 4.2 years, and the primary endpoint was cardiovascular death, myocardial infarction, or cardiac arrest. Analysis was by intention to treat. FINDINGS: Mean age of patients was 60 years (SD 9), 85% were male, 92% were taking platelet inhibitors, 62% beta blockers, and 58% lipid-lowering therapy. 603 (10%) placebo and 488 (8%) perindopril patients experienced the primary endpoint, which yields a 20% relative risk reduction (95% CI 9-29, p=0.0003) with perindopril. These benefits were consistent in all predefined subgroups and secondary endpoints. Perindopril was well tolerated. INTERPRETATION: Among patients with stable coronary heart disease without apparent heart failure, perindopril can significantly improve outcome. About 50 patients need to be treated for a period of 4 years to prevent one major cardiovascular event. Treatment with perindopril, on top of other preventive medications, should be considered in all patients with coronary heart disease