Linear and nonlinear analysis of heart rate variability in healthy subjects and after acute myocardial infarction in patients

The objectives of this study were to evaluate and compare the use of linear and nonlinear methods for analysis of heart rate variability (HRV) in healthy subjects and in patients after acute myocardial infarction (AMI). Heart rate (HR) was recorded for 15 min in the supine position in 10 patients with AMI taking β-blockers (aged 57 ± 9 years) and in 11 healthy subjects (aged 53 ± 4 years). HRV was analyzed in the time domain (RMSSD and RMSM), the frequency domain using low- and high-frequency bands in normalized units (nu; LFnu and HFnu) and the LF/HF ratio and approximate entropy (ApEn) were determined. There was a correlation (P < 0.05) of RMSSD, RMSM, LFnu, HFnu, and the LF/HF ratio index with the ApEn of the AMI group on the 2nd (r = 0.87, 0.65, 0.72, 0.72, and 0.64) and 7th day (r = 0.88, 0.70, 0.69, 0.69, and 0.87) and of the healthy group (r = 0.63, 0.71, 0.63, 0.63, and 0.74), respectively. The median HRV indexes of the AMI group on the 2nd and 7th day differed from the healthy group (P < 0.05): RMSSD = 10.37, 19.95, 24.81; RMSM = 23.47, 31.96, 43.79; LFnu = 0.79, 0.79, 0.62; HFnu = 0.20, 0.20, 0.37; LF/HF ratio = 3.87, 3.94, 1.65; ApEn = 1.01, 1.24, 1.31, respectively. There was agreement between the methods, suggesting that these have the same power to evaluate autonomic modulation of HR in both AMI patients and healthy subjects. AMI contributed to a reduction in cardiac signal irregularity, higher sympathetic modulation and lower vagal modulation.

Hemodynamic mechanisms of the attenuated blood pressure response to mental stress after a single bout of maximal dynamic exercise in healthy subjects

To determine the hemodynamic mechanisms responsible for the attenuated blood pressure response to mental stress after exercise, 26 healthy sedentary individuals (age 29 ± 8 years) underwent the Stroop color-word test before and 60 min after a bout of maximal dynamic exercise on a treadmill. A subgroup (N = 11) underwent a time-control experiment without exercise. Blood pressure was continuously and noninvasively recorded by infrared finger photoplethysmography. Stroke volume was derived from pressure signals, and cardiac output and peripheral vascular resistance were calculated. Perceived mental stress scores were comparable between mental stress tests both in the exercise (P = 0.96) and control (P = 0.24) experiments. After exercise, the blood pressure response to mental stress was attenuated (pre: 10 ± 13 vs post: 6 ± 7 mmHg; P < 0.01) along with lower values of systolic blood pressure (pre: 129 ± 3 vs post: 125 ± 3 mmHg; P < 0.05), stroke volume (pre: 89.4 ± 3.5 vs post: 76.8 ± 3.8 mL; P < 0.05), and cardiac output (pre: 7.00 ± 0.30 vs post: 6.51 ± 0.36 L/min; P < 0.05). Except for heart rate, the hemodynamic responses and the mean values during the two mental stress tests in the control experiment were similar (P > 0.05). In conclusion, a single bout of maximal dynamic exercise attenuates the blood pressure response to mental stress in healthy subjects, along with lower stroke volume and cardiac output, denoting an acute modulatory action of exercise on the central hemodynamic response to mental stress.

Antimicrobial peptides and nitric oxide production by neutrophils from periodontitis subjects

Neutrophils play an important role in periodontitis by producing nitric oxide (NO) and antimicrobial peptides, molecules with microbicidal activity via oxygen-dependent and -independent mechanisms, respectively. It is unknown whether variation in the production of antimicrobial peptides such as LL-37, human neutrophil peptides (HNP) 1-3, and NO by neutrophils influences the pathogenesis of periodontal diseases. We compared the production of these peptides and NO by lipopolysaccharide (LPS)-stimulated neutrophils isolated from healthy subjects and from patients with periodontitis. Peripheral blood neutrophils were cultured with or without Aggregatibacter actinomycetemcomitans-LPS (Aa-LPS), Porphyromonas gingivalis-LPS (Pg-LPS) and Escherichia coli-LPS (Ec-LPS). qRT-PCR was used to determine quantities of HNP 1-3 and LL-37 mRNA in neutrophils. Amounts of HNP 1-3 and LL-37 proteins in the cell culture supernatants were also determined by ELISA. In addition, NO levels in neutrophil culture supernatants were quantitated by the Griess reaction. Neutrophils from periodontitis patients cultured with Aa-LPS, Pg-LPS and Ec-LPS expressed higher HNP 1-3 mRNA than neutrophils from healthy subjects. LL-37 mRNA expression was higher in neutrophils from patients stimulated with Aa-LPS. Neutrophils from periodontitis patients produced significantly higher LL-37 protein levels than neutrophils from healthy subjects when stimulated with Pg-LPS and Ec-LPS, but no difference was observed in HNP 1-3 production. Neutrophils from periodontitis patients cultured or not with Pg-LPS and Ec-LPS produced significantly lower NO levels than neutrophils from healthy subjects. The significant differences in the production of LL-37 and NO between neutrophils from healthy and periodontitis subjects indicate that production of these molecules might influence individual susceptibility to important periodontal pathogens.

Effects of simvastatin/ezetimibe on microparticles, endothelial progenitor cells and platelet aggregation in subjects with coronary heart disease under antiplatelet therapy

It is not known whether the addition of ezetimibe to statins adds cardiovascular protection beyond the expected changes in lipid levels. Subjects with coronary heart disease were treated with four consecutive 1-week courses of therapy (T) and evaluations. The courses were: T1, 100 mg aspirin alone; T2, 100 mg aspirin and 40 mg simvastatin/10 mg ezetimibe; T3, 40 mg simvastatin/10 mg ezetimibe, and 75 mg clopidogrel (300 mg initial loading dose); T4, 75 mg clopidogrel alone. Platelet aggregation was examined in whole blood. Endothelial microparticles (CD51), platelet microparticles (CD42/CD31), and endothelial progenitor cells (CD34/CD133; CDKDR/CD133, or CD34/KDR) were quantified by flow cytometry. Endothelial function was examined by flow-mediated dilation. Comparisons between therapies revealed differences in lipids (T2 and T3T1 and T4, P=0.001). Decreased platelet aggregation was observed after aspirin (arachidonic acid, T1

Effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity in Chinese subjects: an interventional study

Accumulating evidence has suggested that high salt and potassium might be associated with vascular function. The aim of this study was to investigate the effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity (PWV) in Chinese subjects. Forty-nine subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day NaCl), a high-salt diet for an additional 7 days (18.0 g/day NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day NaCl+4.5 g/day KCl). Brachial-ankle PWV was measured at baseline and on the last day of each intervention. Blood pressure levels were significantly increased from the low-salt to high-salt diet, and decreased from the high-salt diet to high-salt plus potassium supplementation. Baseline brachial-ankle PWV in salt-sensitive subjects was significantly higher than in salt-resistant subjects. There was no significant change in brachial-ankle PWV among the 3 intervention periods in salt-sensitive, salt-resistant, or total subjects. No significant correlations were found between brachial-ankle PWV and 24-h sodium and potassium excretions. Our study indicates that dietary salt intake and potassium supplementation, at least in the short term, had no significant effect on brachial-ankle PWV in Chinese subjects.

Inflammatory cytokines and plasma redox status responses in hypertensive subjects after heat exposure

Hypertension is characterized by a pro-inflammatory status, including redox imbalance and increased levels of pro-inflammatory cytokines, which may be exacerbated after heat exposure. However, the effects of heat exposure, specifically in individuals with inflammatory chronic diseases such as hypertension, are complex and not well understood. This study compared the effects of heat exposure on plasma cytokine levels and redox status parameters in 8 hypertensive (H) and 8 normotensive (N) subjects (age: 46.5±1.3 and 45.6±1.4 years old, body mass index: 25.8±0.8 and 25.6±0.6 kg/m2, mean arterial pressure: 98.0±2.8 and 86.0±2.3 mmHg, respectively). They remained at rest in a sitting position for 10 min in a thermoneutral environment (22°C) followed by 30 min in a heated environmental chamber (38°C and 60% relative humidity). Blood samples were collected before and after heat exposure. Plasma cytokine levels were measured using sandwich ELISA kits. Plasma redox status was determined by thiobarbituric acid reactive substances (TBARS) levels and ferric reducing ability of plasma (FRAP). Hypertensive subjects showed higher plasma levels of IL-10 at baseline (P<0.05), although levels of this cytokine were similar between groups after heat exposure. Moreover, after heat exposure, hypertensive individuals showed higher plasma levels of soluble TNF receptor (sTNFR1) and lower TBARS (P<0.01) and FRAP (P<0.05) levels. Controlled hypertensive subjects, who use angiotensin-converting-enzyme inhibitor (ACE inhibitors), present an anti-inflammatory status and balanced redox status. Nevertheless, exposure to a heat stress condition seems to cause an imbalance in the redox status and an unregulated inflammatory response.

Characterization and effect of clarified araçá (Psidium guineenses Sw.) juice on postprandial glycemia in healthy subjects

Brazilian native fruits are excellent sources of bioactive compounds of phenolic nature. Some of these compounds are able to inhibit carbohydrate- metabolizing enzymes (in vitro), α-amylase and α-glucosidase, delaying carbohydrate digestion. This study aimed to evaluate the effect of clarified araçá (Psidium guineenses Sw.) juice on postprandial glycemia in humans after consumption of 25 g of available carbohydrates (approximately 50 g of white bread) and characterize the phenolic compounds and in vitro antioxidant capacity of araçá juice and pulp. The results showed that the clarified juice had a positive effect on postprandial glycemia reducing the total amount of glucose absorbed, lengthening the time to reach maximum blood glucose concentration, reducing glucose incremental velocity, and decreasing glucose incremental percentage. Both frozen pulp and clarified juice had high amounts of phenolic compounds, antioxidant capacity, and proanthocyanidins, among which oligomers (monomers to tetramers), pentamers, hexamers, heptamers, octamers, nonamers, decamers, and polymers were detected, and they are probably associated with in vivo effects.

The alpha2C-adrenoceptor as a neuropsychiatric drug tar-get - PET studies in human subjects

Positron emission tomography imaging has both academic and applied uses in revealing the distribution and density of different molecular targets in the central nervous system. Following the significant progress made with the dopamine D2 receptor, advances have been made in developing PET tracers to allow analysis of receptor occupancy of many other receptor types as well as evaluating changes in endogenous synaptic transmitter concentrations of transmitters e.g. serotonin and noradrenaline. Noradrenergic receptors are divided into α1-, α2- and β-adrenoceptor subfamilies, in humans each of which is composed of three receptor subtypes. The α2-adrenoceptors have an important presynaptic auto-inhibitory function on noradrenaline release but they also have postsynaptic roles in modulating the release of other neurotransmitters, such as serotonin and dopamine. One of the subtypes, the α2C-adrenoceptor, has been detected at distinct locations in the central nervous system, most notably the dorsal striatum. Several serious neurological conditions causing dementia, Alzheimer’s disease and Parkinson’s disease have been linked to disturbed noradrenergic signaling. Furthermore, altered noradrenergic signaling has also been implicated in conditions like ADHD, depression, anxiety and schizophrenia. In order to benefit future research into these central nervous system disorders as well as being useful in the clinical development of drugs affecting brain noradrenergic neurotransmission, validation work of a novel tracer for positron emission tomography studies in humans was performed. Altogether 85 PET imaging experiments were performed during four separate clinical trials. The repeatability of [11C]ORM-13070 binding was tested in healthy individuals, followed by a study to evaluate the dose-dependent displacement of [11C]ORM-13070 from α2C-adrenoceptors by a competing ligand, and the final two studies examined the sensitivity of [11C]ORM-13070 binding to reflect changes in endogenous noradrenaline levels. The repeatability of [11C]ORM-13070 binding was very high. The binding properties of the tracer allowed for a reliable estimation of α2C-AR occupancy by using the reference tissue ratio method with low test-retest variability. [11C]ORM-13070 was dose-dependently displaced from its specific binding sites by the subtype-nonselective α2-adrenoceptor antagonist atipamezole, and thus it proved suitable for use in clinical drug development of novel α2C-adrenoceptor ligands e.g. to determine the best doses and dosing intervals for clinical trials. Convincing experimental evidence was gained to support the suitability of [11C]ORM-13070 for detecting an increase in endogenous synaptic noradrenaline in the human brain. Tracer binding in the thalamus tended to increase in accordance with reduced activity of noradrenergic projections from the locus coeruleus, although statistical significance was not reached. Thus, the investigation was unable to fully validate [11C]ORM-13070 for the detection of pharmacologically evoked reductions in noradrenaline levels.

Clinical and genetic markers in disease progression – a study among subjects with obstructive lung diseases

Asthma, COPD, and asthma and COPD overlap syndrome (ACOS) are chronic pulmonary diseases with an obstructive component. In COPD, the obstruction is irreversible and the disease is progressive. The aim of the study was to define and analyze factors that affected disease progression and patients’ well-being, prognosis and mortality in Chronic Airway Disease (CAD) cohort. The main focus was on COPD and ACOS patients. Retrospective data from medical records was combined with genetic and prospective follow-up data. Smoking is the biggest risk factor for COPD and even after the diagnosis of the disease, smoking plays an important role in disease development and patient’s prognosis. Sixty percent of the COPD patients had succeeded in smoking cessation. Patients who had managed to quit smoking had lower mortality rates and less psychiatric diseases and alcohol abuse although they were older and had more cardiovascular diseases than patients who continued smoking. Genetic polymorphism rs1051730 in the nicotinic acethylcholine receptor gene (CHRNA3/5) associated with heavy smoking, cancer prevalence and mortality in two Finnish independent cohorts consisting of COPD patients and male smokers. Challenges in smoking cessation and higher mortality rates may be partly due to individual patient’s genetic composition. Approximately 50% of COPD patients are physically inactive and the proportion was higher among current smokers. Physically active and inactive patients didn’t differ from each other in regard to age, gender or comorbidities. Bronchial obstruction explained inactivity only in severe disease. Subjective sensation of dyspnea, however, had very strong association to inactivity and was also associated to low health related quality of life (HRQoL). ACOS patients had a significantly lower HRQoL than either the patients with asthma or with COPD even though they were younger than COPD patients, had better lung functions and smaller tobacco exposure.

Electrophysiological analysis of the sleep onset period : a comparison between subjects with long term insomnia complaints associated with mild traumatic brain injury and matched controls /

The purpose of the current undertaking was to study the electrophysiological properties of the sleep onset period (SOP) in order to gain understanding into the persistent sleep difficulties of those who complain of insomnia following mild traumatic brain injury (MTBI). While many believe that symptoms of post concussion syndrome (PCS) following MTBI resolve within 6 to 12 months, there are a number of people who complain of persistent sleep difficulty. Two models were proposed which hypothesize alternate electrophysiological presentations of the insomnia complaints of those sustaining a MTBI: 1) Analyses of standard polysomnography (PSG) sleep parameters were conducted in order to determine if the sleep difficulties of the MTBI population were similar to that of idiopathic insomniacs (i.e. greater proportion ofREM sleep, reduced delta sleep); 2) Power spectral analysis was conducted over the SOP to determine if the sleep onset signature of those with MTBI would be similar to psychophysiological insomniacs (characterized by increased cortical arousal). Finally, exploratory analyses examined whether the sleep difficulties associated with MTBI could be explained by increases in variability of the power spectral data. Data were collected from 9 individuals who had sustained a MTBI 6 months to 5 years earlier and reported sleep difficulties that had arisen within the month subsequent to injury and persisted to the present. The control group consisted of 9 individuals who had experienced neither sleep difficulties, nor MTBI. Previous to spending 3 consecutive uninterrupted nights in the sleep lab, subjects completed questionnaires regarding sleep difficulties, adaptive functioning, and personality.

Produced subjectivities and productive subjects : locating the potential of the self-reflective blog

Blogging software has popularly been used as a mode of writing about everyday life to interact with others. This thesis examines the political potentials that are opened up by self-reflective blogging. The self-reflective blog is a synergy of self-reflective practices and computer-mediated communication. A genealogy of the history of computer-mediated communication and various public self-reflective practices is conducted to uncover affect as the utility of various economies of subject production. Efforts made to blog-like the efforts made to interact online in other CMCs-are positioned as a kind of affective labor. Adapting Hardt and Negri's (2005) theorization of the multitude, whereby affective labor-the production of social relationshipsis a kind ofbiopolitical production, affect will be determined as a kind ofbiopolitical power that exists in everyday life.

México and the United States; a study of subjects affecting their polítical, commercial and social relations, made with a view to their promotion

UANL

Longitudinal changes in HIV-specific IFN-? secretion in subjects who received Remune™ vaccination prior to treatment interruption

Affiliation: Maude Loignon, Lise Cyr & Emil Toma : Département de microbiologie et immunologie, Faculté de médecine, Université de Montréal