Endothelial dysfunction in cardiovascular and endocrine-metabolic diseases: an update

The endothelium plays a vital role in maintaining circulatory homeostasis by the release of relaxing and contracting factors. Any change in this balance may result in a process known as endothelial dysfunction that leads to impaired control of vascular tone and contributes to the pathogenesis of some cardiovascular and endocrine/metabolic diseases. Reduced endothelium-derived nitric oxide (NO) bioavailability and increased production of thromboxane A2, prostaglandin H2 and superoxide anion in conductance and resistance arteries are commonly associated with endothelial dysfunction in hypertensive, diabetic and obese animals, resulting in reduced endothelium-dependent vasodilatation and in increased vasoconstrictor responses. In addition, recent studies have demonstrated the role of enhanced overactivation ofβ-adrenergic receptors inducing vascular cytokine production and endothelial NO synthase (eNOS) uncoupling that seem to be the mechanisms underlying endothelial dysfunction in hypertension, heart failure and in endocrine-metabolic disorders. However, some adaptive mechanisms can occur in the initial stages of hypertension, such as increased NO production by eNOS. The present review focuses on the role of NO bioavailability, eNOS uncoupling, cyclooxygenase-derived products and pro-inflammatory factors on the endothelial dysfunction that occurs in hypertension, sympathetic hyperactivity, diabetes mellitus, and obesity. These are cardiovascular and endocrine-metabolic diseases of high incidence and mortality around the world, especially in developing countries and endothelial dysfunction contributes to triggering, maintenance and worsening of these pathological situations.

Hypertensive effects of the iv administration of picomoles of ouabain

Ouabain, an endogenous digitalis compound, has been detected in nanomolar concentrations in the plasma of several mammals and is associated with the development of hypertension. In addition, plasma ouabain is increased in several hypertension models, and the acute or chronic administration of ouabain increases blood pressure in rodents. These results suggest a possible association between ouabain and the genesis or development and maintenance of arterial hypertension. One explanation for this association is that ouabain binds to the α-subunit of the Na+ pump, inhibiting its activity. Inhibition of this pump increases intracellular Na+, which reduces the activity of the sarcolemmal Na+/Ca2+ exchanger and thereby reduces Ca2+ extrusion. Consequently, intracellular Ca2+ increases and is taken up by the sarcoplasmic reticulum, which, upon activation, releases more calcium and increases the vascular smooth muscle tone. In fact, acute treatment with ouabain enhances the vascular reactivity to vasopressor agents, increases the release of norepinephrine from the perivascular adrenergic nerve endings and promotes increases in the activity of endothelial angiotensin-converting enzyme and the local synthesis of angiotensin II in the tail vascular bed. Additionally, the hypertension induced by ouabain has been associated with central mechanisms that increase sympathetic tone, subsequent to the activation of the cerebral renin-angiotensin system. Thus, the association with peripheral mechanisms and central mechanisms, mainly involving the renin-angiotensin system, may contribute to the acute effects of ouabain-induced elevation of arterial blood pressure.

Estrous cycle and stress: influence of progesterone on the female brain

The female brain operates in a constantly changing chemical milieu caused by cyclical changes in gonadal hormones during the estrous cycle (menstrual cycle in women). Such hormones are highly lipophilic and pass readily from the plasma to the brain where they can influence neuronal function. It is becoming clear that the rapid reduction in peripheral circulating progesterone, which occurs during the late diestrous phase of the cycle, can trigger a withdrawal-like response, in which changes in GABA A receptor expression render hyper-responsive certain brain areas involved in processing responses to stressful stimuli. The periaqueductal gray matter (PAG) is recognised as an important region for integrating anxiety/defence responses. Withdrawal from progesterone, via actions of its neuroactive metabolite allopregnanolone, triggers up-regulation of extrasynaptic GABA A receptors on GABAergic neurons in the PAG. As a consequence, ongoing GABAergic tone on the output cells decreases, leading to an increase in functional excitability of the circuitry and enhanced responsiveness to stressful stimuli during the late diestrous phase. These changes during late diestrus could be prevented by short-term neurosteroid administration, timed to produce a more gradual fall in the peripheral concentration of allopregnanolone than the rapid decrease that occurs naturally, thus removing the trigger for the central withdrawal response.

Time course of the hemodynamic responses to aortic depressor nerve stimulation in conscious spontaneously hypertensive rats

The time to reach the maximum response of arterial pressure, heart rate and vascular resistance (hindquarter and mesenteric) was measured in conscious male spontaneously hypertensive (SHR) and normotensive control rats (NCR; Wistar; 18-22 weeks) subjected to electrical stimulation of the aortic depressor nerve (ADN) under thiopental anesthesia. The parameters of stimulation were 1 mA intensity and 2 ms pulse length applied for 5 s, using frequencies of 10, 30, and 90 Hz. The time to reach the hemodynamic responses at different frequencies of ADN stimulation was similar for SHR (N = 15) and NCR (N = 14); hypotension = NCR (4194 ± 336 to 3695 ± 463 ms) vs SHR (3475 ± 354 to 4494 ± 300 ms); bradycardia = NCR (1618 ± 152 to 1358 ± 185 ms) vs SHR (1911 ± 323 to 1852 ± 431 ms), and the fall in hindquarter vascular resistance = NCR (6054 ± 486 to 6550 ± 847 ms) vs SHR (4849 ± 918 to 4926 ± 646 ms); mesenteric = NCR (5574 ± 790 to 5752 ± 539 ms) vs SHR (5638 ± 648 to 6777 ± 624 ms). In addition, ADN stimulation produced baroreflex responses characterized by a faster cardiac effect followed by a vascular effect, which together contributed to the decrease in arterial pressure. Therefore, the results indicate that there is no alteration in the conduction of the electrical impulse after the site of baroreceptor mechanical transduction in the baroreflex pathway (central and/or efferent) in conscious SHR compared to NCR.

Memory mood congruency phenomenon in bipolar I disorder and major depression disorder patients

The objective of the present study was to evaluate memory performance in tasks with and without affective content (to confirm the mood congruency phenomenon) in acutely admitted patients with bipolar I disorder (BD) and major depression disorder (MDD) and in healthy participants. Seventy-eight participants (24 BD, 29 MDD, and 25 healthy controls) were evaluated. Three word lists were used as the memory task with affective content (positive, negative and indifferent). Psychiatric symptoms were also evaluated with rating scales (Young Mania Rating Scale for mania and Hamilton Depression Rating Scale for depression). Patients were selected during the first week of hospitalization. BD patients showed higher scores in the word span with positive tone than MDD patients and healthy controls (P = 0.002). No other difference was observed for tests with affective tone. MDD patients presented significantly lower scores in the Mini-Mental State Exam, logical memory test, visual recognition span, and digit span, while BD patients presented lower scores in the visual recognition test and digit span. Mood congruency effect was found for word span with positive tone among BD patients but no similar effect was observed among MDD patients for negative items. MDD patients presented more memory impairment than BD patients, but BD patients also showed memory impairment

Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect

Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

Natural born weight gainers: The mechanisms of obesity in transgenic mice overexpressing neuropeptide Y

Neuropeptide Y (NPY) is a neurotransmitter promoting energy storage by activating Y-receptors and thus affecting food intake, thermogenesis and adipose tissue metabolism. NPY is expressed both in the central and sympathetic nervous system. Hypothalamic NPY is known to stimulate feeding, but the effects of noradrenergic neuron NPY are more ambiguous. Chronic stress stimulates fat accumulation via NPY release from noradrenergic neurons. Furthermore, polymorphism in the human Npy gene has been associated with metabolic disturbances and increased NPY secretion after sympathetic stimulation. The main objective of this study was to clarify the mechanisms of noradrenergic neuron NPY in the development of obesity. The metabolic phenotype of a homozygous mouse overexpressing NPY in the brain noradrenergic neurons and sympathetic nervous system (OE-NPYDβH mouse) was characterized. OE-NPYDβH mice had an increased fat mass and body weight, which caused impairments of glucose metabolism and hyperinsulinaemia with age. There were no differences in energy intake or expenditure, but the sympathetic tone was down-regulated and the endocannabinoid system activated. Furthermore, peripheral Y2-receptors in energy-rich conditions played an important role in mediating the fat-accumulating effect of NPY. These results indicate that noradrenergic neuron NPY promotes obesity via direct effects in the periphery and by modulating the sympatho-adrenal and endocannabinoid systems. Additionally, NPY in the central noradrenergic neurons is believed to possess many important roles. The phenotype of the OE-NPYDβH mouse resembles the situations of chronic stress and Npy gene polymorphism and thus these mice may be exploited in testing novel drug candidates for the treatment of obesity.

Recueil de lettres originales.

Contient : 1 Lettre du roi « CHARLES » IX aux « ducz de Nemours et d'Aumalle,... A Verdun, le XXIIe jour d'avril 1569 » ; 2 Lettre du roi « CHARLES » IX au « duc de Nemours,... A Reyns, le XIIe jour de may 1569 » ; 3 Lettre du roi « CHARLES » IX au « duc de Nemoux,... De Verdun, ce XXe jour d'avril 1569 » ; 4 Lettre du roi « CHARLES » IX au « duc de Nemours,... A Verdun, le XXIIIIe jour d'avril 1569 » ; 5 Lettre de « CATERINE » DE MEDICIS au « duc de Nemours,... De Verdun, cet XXIIIme d'avril 1569 » ; 6 Lettre du roi « CHARLES » IX au « duc de Nemours,... De Soully, le XXIXe jour d'avril 1569 » ; 7 Lettre de « CATERINE [DE MEDICIS]... à... monsieur le duc de Nemours,... De Penney, cet XIIIIme de may 1569 » ; 8 Lettre du roi « CHARLES » IX au « duc de Nemours,... A Montceaulx, le XIXe jour de may 1569 » ; 9 Lettre du roi « CHARLES » IX au « duc de Nemours,... A Montceaulx, le XIXe jour de may 1569 » ; 10 Lettre de « CATERINE [DE MEDICIS]... à... madame de Nemours,... De Chenonseaulx, cet XXIme jour de may 157II » ; 11 Lettre d'ALFONSE II, « duca DI FERRARA », au « duca di Nemours,... Di Ferrara, a XX di maggio M.D.LXIX » ; 12 Lettre d'« E[MMANUEL] PHILIBERT [duc DE SAVOIE]... à... monseigneur [le duc de] Genevoys et de Nemours,... De Thurin, le XXIe may 1569 » ; 13 Lettre de « HENRIETTE DE CLEVES [duchesse DE NEVERS]... à monsieur le duc de Nemours,... De Nevers, ce XXIe may 1569 » ; 14 Lettre de « ALFONSO D'ORNANO,... all' illustrissimo... duca di Namors,... Da Cuers in Provenza, il XXII magio 1569 » ; 15 Lettre de « GUILLAUME DE MONTMORENCY,... à monsieur le duc de Nemoux,... Au camp de Ste Gemes, ce XXIIe may 1569 » ; 16 Lettre de « MARGUERITE DE FRANCE,... à... monseigneur le duc de Nemours,... De Thurin, ce XXIIIIe jour de may 1569 » ; 17 Lettre de « CLAUDE DE LORRAINE,... à monsieur le duc de Nemoux,... De camp pres Bourges, ce XXVe may 1569 » ; 18 Lettre de « BELLIEVRE,... à monseigneur le duc de Genevois et de Nemours,... De Solleurre, le XXVe jour de may 1569 » ; 19 Lettre de « HENRIETTE DE CLEVES,... à monsieur le duc de Nemours,... De Nevers, ce XXVe may 1569 » ; 20 Lettre de « FRANÇOYS [duc D'ALENÇON]... à madame... de Ferrare,... De Paris, ce XXIIIIme juing 1569 » ; 21 Lettre de « CATERINE [DE MEDICIS]... à... madame de Nemours,... D'Orleans, cet premier jour de joulet 1569 » ; 22 Lettre de « CATERINE [DE MEDICIS]... D'Orleans, cet VIIIme de joulet 1569 » ; 23 Lettre de « JAQUELINE DE ROHAN,... à madame de Nemours,... De Blandi, ce 27e juillet 1569 » ; 24 Lettre de « LEONOR D'ORLEANS [duc DE LONGUEVILLE]... à monsieur le duc de Nemours,... De Gallon, ce IIe d'aoust 1569 » ; 25 Lettre de « Don FRANCES DE ALAVA,... à madame la duchesse de Ferrare,... De Paris, le IIIe d'aoust 1569 » ; 26 Lettre d'« ENTRAIGUES,... à madame la duchesse de Ferrare,... D'Orleans, le XVIe jour d'aoust 1569 » ; 27 Lettre de FRANÇOIS DE « MONTMORENCY,... à monsieur... le duc de Nemoux,... D'Amboize, le XIIIIme jour d'aoust 1569 » ; 28 Lettre de « FRANÇOYS », duc D'ALENÇON, au « duc de Nemours,... De Paris, le XXe jour d'aoust 1569 » ; 29 Lettre de « FRANÇOYS [duc D'ALENÇON]... à... madame de Ferrare,... A Paris, le XXIIIIe jour d'aoust 1569 » ; 30 Lettre de « FRANÇOYS [duc D'ALENÇON]... à... monsieur le duc de Nemours,... De Paris, ce XXVIme jour d'aoust 1569 » ; 31 Lettre de « BASTIEN DE LUXAMBOURG,... à monsieur... le duc d'Annemours,... Au camp de Chynon, ce XXIe jour de septembre 1569 » ; 32 Lettre de « ROGIER DE BELLEGARDE,... à monseigneur... le duc de Nemours... 1569 » ; 33 Lettre de « CATERINE [DE MEDICIS]... à... madame de Nemours,... Du Plesis, cet Xme d'octobre 1569 » ; 34 Lettre d'« E[MMANUEL] PHILIBERT [duc DE SAVOIE]... à madame... la duchesse de Genevoys et d'Anemours,... De Chambery, ce 26 octobre 1569 » ; 35 Lettre de « CATERINE [DE MEDICIS]... à... madame de Nemours,... De Tone Botone, cet VIme de novembre 1569 » ; 36 Lettre de « CLAUDE DE LORRAINE,... à monsieur... le duc de Nemours,... De Tonne et Boutonne pres St Jehan d'Angely, le XVe novembre 1569 » ; 37 Lettre du roi « CHARLES » IX au « duc de Nemoux,... Au camp de Tonne Boutonne, le XVIIe jour de novembre 1569 » ; 38 Lettre de « BASTIEN DE LUXAMBOURG,... à monsieur... le duc de Nemours et de Gennevoys,... Au camp de Tonné Boutonne, ce XVIIme jour de novembre 1569 » ; 39 Lettre de « CHARLES, e[vêque] du Mans... à monseigneur... le duc de Genevoys et de Nemours,... De Romme, ce XXIme de novembre 1569 » ; 40 Lettre, en espagnol, de « Don FRANCES DE ALAVA,... al illmo... duque de Nevers,... Metz, 8 decembris 1569 » ; 41 Lettre de « MARGUERITE DE FRANCE,... à... monsieur le duc de Nemours,... De Thurin, ce VIe jour de decembre 1569 » ; 42 Lettre de « C., conte DE ROGENDORFF,... à monseigneur... le duc de Nemours,... De Montereau Faut Yone, le VIIIe de decembre 1569 » ; 43 Lettre de « CATERINE [DE MEDICIS]... à... monsieur de Nemours,... De Tonay Botone, cet XI de decembre 1569 » ; 44 Lettre de « CATERINE [DE MEDICIS]... à... madame de Nemours,... De Colonge La Reau, cete nuit de Noel 1569 » ; 45 Lettre de « LEONOR D'ORLEANS [duc DE LONGUEVILLE]... à monsieur... de Nemoux,... De Blandy, ce XXIIIIe jour de decembre 1569 » ; 46 Lettre, en italien, de « FRANCESCO MARIA, principeD'URBINO », à Renée de France, duchesse de Ferrare. « Di Pesaro, alli XXVIII Xbre M.D.LXIX » ; 47 Lettre de « JAQUES DE SAVOYE [duc DE NEMOURS]... à madame... la duchesse de Ferrare » ; 48 Lettre, en italien, de l'évêque de Sinigaglia « a... madama la duchessa di Ferrara,... Da Sinigaglia, il XV di genaro 1570 » ; 49 Lettre, en italien, d'« ALESSANDRO RANGONE,... a... madama Rhenea di Franza,... Di Modena, li XXI di genaro M.D.LXX » ; 50 Lettre, en italien, de FRANÇOIS MARIE, « principe D'URBINO,... a... madama Renea di Francia, duchessa di Ferrara,... Di Pesaro, a XXII di genaro del LXX » ; 51 Lettre, en italien, du « duca D'URBINO,... a... madama Renea di Francia, duchessa di Ferrara,... Di Pesaro, il di III di genaro del LXX »

Men's Basketball Team (1988-89)

Coach: Garney Henley Team (Alphabetically): Bruce Adams, Frank Capretta, Kevin Farrow, David Dennis, Rob Demott, Brian Hayden, Peter Kaija, Steve Kolenko, Leacoft Panton, Kevin Rome, Kevin Stevinson, Glen Tone, Moe Willoughby

ERP and cardiovascular correlates of source memory discrimination in older and younger adults /

There is much evidence to support an age-related decline in source memory ability. However, the underlying mechanisms responsible for this decline are not well understood. The current study was carried out to determine the electrophysiological correlates of source memory discrimination in younger and older adults. Event-related potentials (ERPs) and continuous electrocardiographic (ECG) data were collected from younger (M= 21 years) and older (M= 71 years) adults during a source memory task. Older adults were more likely to make source memory errors for recently repeated, non-target words than were younger adults. Moreover, their ERP records for correct trials showed an increased amplitude in the late positive (LP) component (400-800 msec) for the most recently presented, non-target stimuli relative to the LP noted for target items. Younger adults showed an opposite pattern, with a large LP component for target items, and a much smaller LP component for the recently repeated non-target items. Computation of parasympathetic activity in the vagus nerve was performed on the ECG data (Porges, 1985). The resulting measure, vagal tone, was used as an index of physiological responsivity. The vagal tone index of physiological responsivity was negatively related to the LP amplitude for the most recently repeated, non-target words in both groups, after accounting for age effects. The ERP data support the hypothesis that the tendency to make source memory errors on the part of older adults is related to the ability to selectively control attentional processes during task performance. Furthermore, the relationship between vagal tone and ERP reactivity suggests that there is a physiological basis to the heightened reactivity measured in the LP response to recently repeated non-target items such that, under decreased physiological resources, there is an impairment in the ability to selectively inhibit bottom-up, stimulus based properties in favour of task-related goals in older adults. The inconsistency of these results with other explanatory models of source memory deficits is discussed. It is concluded that the data are consistent with a physiological reactivity model requiring inhibition of reactivity to irrelevant, but perceptually-fluent, stimuli.

Information processing in sleep-onset insomnia : a test of the neurocognitive model /

The present thesis study is a systematic investigation of information processing at sleep onset, using auditory event-related potentials (ERPs) as a test of the neurocognitive model of insomnia. Insomnia is an extremely prevalent disorder in society resulting in problems with daytime functioning (e.g., memory, concentration, job performance, mood, job and driving safety). Various models have been put forth in an effort to better understand the etiology and pathophysiology of this disorder. One of the newer models, the neurocognitive model of insomnia, suggests that chronic insomnia occurs through conditioned central nervous system arousal. This arousal is reflected through increased information processing which may interfere with sleep initiation or maintenance. The present thesis employed event-related potentials as a direct method to test information processing during the sleep-onset period. Thirteen poor sleepers with sleep-onset insomnia and 1 2 good sleepers participated in the present study. All poor sleepers met the diagnostic criteria for psychophysiological insomnia and had a complaint of problems with sleep initiation. All good sleepers reported no trouble sleeping and no excessive daytime sleepiness. Good and poor sleepers spent two nights at the Brock University Sleep Research Laboratory. The first night was used to screen for sleep disorders; the second night was used to investigate information processing during the sleep-onset period. Both groups underwent a repeated sleep-onsets task during which an auditory oddball paradigm was delivered. Participants signalled detection of a higher pitch target tone with a button press as they fell asleep. In addition, waking alert ERPs were recorded 1 hour before and after sleep on both Nights 1 and 2.As predicted by the neurocognitive model of insomnia, increased CNS activity was found in the poor sleepers; this was reflected by their smaller amplitude P2 component seen during wake of the sleep-onset period. Unlike the P2 component, the Nl, N350, and P300 did not vary between the groups. The smaller P2 seen in our poor sleepers indicates that they have a deficit in the sleep initiation processes. Specifically, poor sleepers do not disengage their attention from the outside environment to the same extent as good sleepers during the sleep-onset period. The lack of findings for the N350 suggest that this sleep component may be intact in those with insomnia and that it is the waking components (i.e., Nl, P2) that may be leading to the deficit in sleep initiation. Further, it may be that the mechanism responsible for the disruption of sleep initiation in the poor sleepers is most reflected by the P2 component. Future research investigating ERPs in insomnia should focus on the identification of the components most sensitive to sleep disruption. As well, methods should be developed in order to more clearly identify the various types of insomnia populations in research contexts (e.g., psychophysiological vs. sleep-state misperception) and the various individual (personality characteristics, motivation) and environmental factors (arousal-related variables) that influence particular ERP components. Insomnia has serious consequences for health, safety, and daytime functioning, thus research efforts should continue in order to help alleviate this highly prevalent condition.

Moral reasoning and ethics in educational leadership /

School leaders face difficult decisions regarding discipline matters. Often, such decisions play an important role in determining the moral tone of the school and the health of the school community. Many stakeholders are affected by the outcome of such decisions. Codes of conduct, board and school policies, and discipline meetings are often shrouded under secrecy, making the discipline process mysterious. .; In this study I examined the process of moral reasoning. I sought to determine the extent to which school leaders were aware that they were involved in a process of moral reasoning, and ftirthermore, what kind of moral reasoning they practiced. As well, I investigated the ethical grounds and foundations underlying moral reasoning. Thus, in this study I probed the awareness of the process of moral reasoning and sought to find the ethical grounding of decision making. This qualitative study featured short field research. The process involved individual interviews with three different participants: school leaders of a public. Catholic, and an independent school. It found that each school leader practiced moral reasoning to varying degrees through the discipline process. It also explored the possible democratization of moral reasoning by linking to concepts such as fairness, due process, public accountability, and greater participation in the administering of discipline. This study has implications for practice, theory, and future research. The examination of school leaders as the primary focus for discipline matters opens the door to future research that could explore differences between the school systems and possibly other parties affected by moral reasoning in discipline cases.

The roles of ERK1/2 and PI3K in abnormal vascular functions in angiotensin II-infused hypertensive rats

Background: Ang II plays a major role in cardiovascular regulation. Recently, it has become apparent that vascular superoxide anion may play an important role in hypertension development. Treatment with antisense NAD(P)H oxidase or SOD decreased BP in Ang II-infused rats. Wang et al recently reported mice which lack one of the subunits of NAD(P)H oxidase developed hypertension at a much lower extent when compared to the wild type animals infused with Ang II, indicating that superoxide anion contributes to elevation in BP in the Ang II-infused hypertensive model. In the Ang II-infused hypertensive model, altered reactivity of blood vessels is often associated with the elevation of systolic blood pressure. We have observed abnormal tension development and impaired endothelium-dependent relaxation in the isolated aorta of Ang II-infused and DOCA-salt hypertensive rats. Recently, several other cellular signal molecules, including ERK1I2 and PI3K, have been determined to play important roles in the regulation of smooth muscle contraction and relaxation. ERKl/2 and PI3K pathways are also reported to contribute to Ang II induced cell growth, hypertrophy, remodeling and contraction. Moreover, these signaling pathways have shown ROS-sensitive properties. Therefore, the aim of the present study is to investigate the roles of ERKl12 and PI3K in vascular oxidative stress, spontaneous tone and impaired endothelium relaxation in Ang II-infused hypertensive model. Hypothesis: We hypothesize that the activation of ERKl12 and PI3K are elevated in response to an Ang II infusion for 6 days. The elevated activation of phospho-ERKl/2 and PI3K mediated the increased level of vascular superoxide anion, the abnormal vascular contraction and impaired endothelium-dependent vascular relaxation in Ang II-infused hypertensive rats. Methods: Vascular superoxide anion level is measured by lucigenin chemiluminescence. Spontaneous tone and ACh-induced endothelium-dependent relaxation was measured by isometric tension recording in organ chamber. The activity of ERK pathway will be measured by its Western blot of phosphorylation of ERK. PI3K activity was evaluated indirectly by Western blot of the phosphorylation of PDKl, a downstream protein of PI3K signaling pathway. The role of each pathway was also addressed via comparing the responses to the specific inhibitors. Results: Superoxide anion was markedly increased in the isolated thoracic aorta from Ang II-infused rats. There was spontaneous tone developed in rings from Ang II-induced hypertensive but not sham-operated normotensive rats. ACh-induced endothelium-dependent relaxation function is impaired in Ang II-infused hypertensive rats. Superoxide dismutase and NAD(P)H oxidase inhibitor, apocynin, inhibited the abnormal spontaneous tone and ameliorated impaired endothelium-dependent relaxation. The expression of phopho-ERKII2 was enhanced in Ang II-infused rats, indicating the activity of ERK1I2 could be increased. MEK1I2 inhibitors, PD98059 and U126, but not their inactive analogues, SB203580 and U124, significantly reduced the vascular superoxide anion in aortas from Ang II-infused rats. The MEK1I2 inhibitors reduced the spontaneous tone and improved the impaired endothelium-dependent relaxation in aorta of hypertension. These findings supported the role of ERKII2 signaling pathway in vascular oxidative stress, spontaneous tone and impaired endothelium-dependent relaxation in Ang II-infused hypertensive rats. The amount of phospho-PDK, a downstream protein of PI3K was increased in Ang II rats indicating the activity of PI3K activity was elevated. Strikingly, PI3K significantly inhibited the increase of superoxide anion level, abnormal spontaneous tone and restored endothelium-dependent relaxation in Ang II-infused hypertensive rats. These findings indicated the important role of PI3K in Ang II-infused hypertensive rats. Conclusion: ERKII2 and PI3K signaling pathways are sustained activated in Ang II-infused hypertensive rats. The activated ERKII2 and PI3K mediate the increase of vascular superoxide anion level, vascular abnormal spontaneous tone and impaired endothelium-dependent relaxation.

Autonomic prediction of error-related ERP components in perceptual and conceptual tasks in older and younger adults

In studies of cognitive processing, the allocation of attention has been consistently linked to subtle, phasic adjustments in autonomic control. Both autonomic control of heart rate and control of the allocation of attention are known to decline with age. It is not known, however, whether characteristic individual differences in autonomic control and the ability to control attention are closely linked. To test this, a measure of parasympathetic function, vagal tone (VT) was computed from cardiac recordings from older and younger adults taken before and during performance of two attentiondemanding tasks - the Eriksen visual flanker task and the source memory task. Both tasks elicited event-related potentials (ERPs) that accompany errors, i.e., error-related negativities (ERNs) and error positivities (Pe's). The ERN is a negative deflection in the ERP signal, time-locked to responses made on incorrect trials, likely generated in the anterior cingulate. It is followed immediately by the Pe, a broad, positive deflection which may reflect conscious awareness of having committed an error. Age-attenuation ofERN amplitude has previously been found in paradigms with simple stimulus-response mappings, such as the flanker task, but has rarely been examined in more complex, conceptual tasks. Until now, there have been no reports of its being investigated in a source monitoring task. Age-attenuation of the ERN component was observed in both tasks. Results also indicated that the ERNs generated in these two tasks were generally comparable for young adults. For older adults, however, the ERN from the source monitoring task was not only shallower, but incorporated more frontal processing, apparently reflecting task demands. The error positivities elicited by 3 the two tasks were not comparable, however, and age-attenuation of the Pe was seen only in the more perceptual flanker task. For younger adults, it was Pe scalp topography that seemed to reflect task demands, being maximal over central parietal areas in the flanker task, but over very frontal areas in the source monitoring task. With respect to vagal tone, in the flanker task, neither the number of errors nor ERP amplitudes were predicted by baseline or on-task vagal tone measures. However, in the more difficult source memory task, lower VT was marginally associated with greater numbers of source memory errors in the older group. Thus, for older adults, relatively low levels of parasympathetic control over cardiac response coincided with poorer source memory discrimination. In both groups, lower levels of baseline VT were associated with larger amplitude ERNs, and smaller amplitude Pe's. Thus, low VT was associated in a conceptual task with a greater "emergency response" to errors, and at the same time, reduced awareness of having made them. The efficiency of an individual's complex cognitive processing was therefore associated with the flexibility of parasympathetic control of heart rate, in response to a cognitively challenging task.

Experiential learning instruments : an examination of the concept of the instrumental approach in experiential learning

Experiential Learning Instruments (ELls) are employed to modify the leamer's apprehension and / or comprehension in experiential learning situations, thereby improving the efficiency and effectiveness of those modalities in the learning process. They involve the learner in reciprocally interactive and determining transactions with his/her environment. Experiential Learning Instruments are used to keep experiential learning a process rather than an object. Their use is aimed at the continual refinement of the learner's knowledge and skill. Learning happens as the leamer's awareness, directed by the use of Ells, comes to experience, monitor and then use experiential feedback from living situations in a way that facilitates knmvledge/skill acquisition, self-correction and refinement. The thesis examined the literature relevant to the establishing of a theoretical experiential learning framework within which ELls can be understood. This framework included the concept that some learnings have intrinsic value-knowledge of necessary information-while others have instrumental value-knowledge of how to learn. The Kolb Learning Cycle and Kolb's six characteristics of experiential learning were used in analyzing three ELls from different fields of learning-saxophone tone production, body building and interpersonal communications. The ELls were examined to determine their learning objectives and how they work using experiential learning situations. It was noted that ELls do not transmit information but assist the learner in attending to and comprehending aspects of personal experience. Their function is to telescope the experiential learning process.