Effects of smoking and physical exercise on platelet free cytosolic calcium in healthy normotensive volunteers.

Platelet free cytosolic calcium (PFCC) was measured in 21 healthy volunteers before and after cigarette smoking or physical exercise. The aim was to investigate whether acute blood pressure changes and increases in circulating levels of catecholamines and vasopressin modify PFCC. PFCC was determined using the Quin-2 method. Following cigarette smoking, significant increases in blood pressure, heart rate, plasma epinephrine (35 +/- 18 pg/ml before versus 51 +/- 31 pg/ml after smoking, P less than 0.05, mean +/- s.d.) and vasopressin levels (0.8 +/- 0.3 pg/ml before and 4.2 +/- 4.1 pg/ml after smoking, P less than 0.001) were observed. However, despite these acute hormonal and hemodynamic changes, PFCC remained stable at 156 +/- 55 nmol/l prior to the study and 157 +/- 29 nmol/l and 156 +/- 38 nmol/l at 20 and 80 min post-smoking, respectively. Acute physical exercise led to an increase in heart rate and systolic blood pressure but to a decrease in diastolic pressure. Moreover, a marked increase in plasma norepinephrine levels was observed after exercise (213 +/- 71 pg/ml before versus 747 +/- 501 pg/ml after exercise, P +/- 0.001). Again, PFCC was stable at 185 +/- 56 nmol/l at baseline versus 188 +/- 51 nmol/l at 20 min and 155 +/- 26 nmol/l at 80 min after exercise. These results therefore demonstrate that PFCC is not influenced acutely either by blood pressure increases, or by elevations in circulating catecholamine and vasopressin concentrations.

Enhanced diastolic reflections on arterial pressure pulse during exercise recovery

RESUMEDurant la phase de récupération d'un exercice de course à pied d'intensité maximale ou submaximale, une augmentation de la pression artérielle systolique centrale (aortique) résultant de la réflexion des ondes de pouls sur l'arbre vasculaire est constatée chez l'individu en bonne santé. En diastole cependant, l'impact de la réflexion de ces ondes de pouls sur la pression centrale demeure inconnu durant la récupération d'un exercice.Nous avons évalué les ondes de pouls centrales systolique et diastolique chez onze athlètes d'endurance durant la phase de récupération d'un exercice de course à pied dans des conditions d'effort maximal (sur tapis de course) et lors d'un effort submaximal lors d'une course à pied de 4000 mètres en plein air sur terrain mixte.Pour chaque sujet et lors des deux exercices, l'onde de pouls a été mesurée au niveau radial par tonométrie d'aplanation durant une phase de repos précédant l'exercice, puis à 5, 15, 25, 35 et 45 minutes après la fin de l'exercice. En utilisant une fonction mathématique de transfert, l'onde de pouls centrale a été extrapolée à partir de l'onde de pouls radiale. En compilant la forme de l'onde de pouls centrale avec une mesure simultanée de la pression artérielle brachiale, un index d'augmentation de l'onde de pouls en systole (Alx) et en diastole (Als) peut être calculé, reflétant l'augmentation des pressions résultant de la réflexion des ondes sur l'arbre vasculaire périphérique.A 5 minutes de la fin de l'exercice, les deux index ont été mesurés moindres que ceux mesurés lors de la phase précédant celui-ci. Lors des mesures suivantes, Alx est resté bas, alors que Aid a progressivement augmenté pour finalement dépasser la valeur de repos après 45 minutes de récupération. Le même phénomène a été constaté pour les deux modalités d'exercice (maximal ou submaximal). Ainsi, au-delà de quelques minutes de récupération après un exercice de course d'intensité maximale ou submaximale, nous avons montré par ces investigations que les ondes de pouls réfléchies en périphérie augmentent de façon sélective la pression centrale en diastole chez l'athlète d'endurance.ABSTRACTDuring recovery from a maximal or submaximal aerobic exercise, augmentation of central (aortic) systolic pressure by reflected pressure waves is blunted in healthy humans. However, the extent to which reflected pressure waves modify the central pulse in diastole in these conditions remains unknown. We evaluated systolic and diastolic central reflected waves in 11 endurance-trained athletes on recovery from a maximal running test on a treadmill (treadmill-max) and a 4000m run in field conditions. On both occasions in each subject, the radial pulse was recorded with applanation tonometry in the resting preexercise state and then 5, 15, 25, 35, and 45 minutes after exercise termination. From the central waveform, as reconstructed by application of a generalized transfer function, we computed a systolic (Alx) and a diastolic index (Aid) of pressure augmentation by reflections. At 5 minutes, both indices were below preexercise. At further time-points, Alx remained low, while Aid progressively increased, to overshoot above preexercise at 45 minutes. The same behavior was observed with both exercise types. Beyond the first few minutes of recovery following either maximal or submaximal aerobic exercise, reflected waves selectively augment the central pressure pulse in diastole, at least in endurance- trained athletes.

Sensate lateral arm flap for defects of the lower leg.

Ideally, reconstruction of lower extremity soft tissue defects includes not only an esthetically pleasing 3-dimensional shape and solid anchoring to the underlying structures to resist shear forces, but should also address the restoration of sensation. Therefore, we present a prospective study on defect reconstruction of the lower leg and ankle to evaluate the role of sensate free fasciocutaneous lateral arm flap and the impact of sensory nerve reconstruction. Thirty patients were allocated randomly to the study group (n = 15) that obtained end-to-side sensate coaptation using the lower lateral cutaneous brachial nerve to the tibial nerve using the epineural window technique, or to the control group reconstructed without nerve coaptation. At 1-year follow-up the patients were evaluated for pain sensation, thermal sensibility, static and moving 2-point discrimination, and Semmes-Weinstein monofilament tests. Data from both groups were compared and statistically analyzed with the Mann-Whitney U test and the Fisher exact test. Flaps of the study group reached a static and moving 2-point discrimination and Semmes-Weinstein monofilament tests nearly equal to the contralateral leg area and significantly better than flaps of the control group. Donor damage morbidity of the tibial nerve did not occur. To our point of view resensation should be carried out by end-to-side neurorrhaphy to the tibial nerve because of the superior restoration of sensibility.

Integration of olfactory information in a spatial representation enabling accurate arm choice in the radial arm maze

The aim of the present study was to determine whether and how rats can use local olfactory cues for spatial orientation. Rats were trained in an eight-arm radial maze under different conditions as defined by the presence or absence of supplementary olfactory cues marking each arm, the availability of distant visuospatial information, and the illumination of the maze (light or darkness). The different visual conditions were designed to dissociate among the effects of light per se and those of visuospatial cues, on the use of olfactory cues for accurate arm choice. Different procedures with modifications of the arrangement of olfactory cues were used to determine if rats formed a representation of the spatial configuration of the olfactory cues and if they could rely on such a representation for accurate arm choice in the radial maze. The present study demonstrated that the use of olfactory cues to direct arm choice in the radial arm maze was critically dependent on the illumination conditions and implied two different modes of processing of olfactory information according to the presence or the absence of light. Olfactory cues were used in an explicit manner and enabled accurate arm choice only in the absence of light. Rats, however, had an implicit memory of the location of the olfactory cues and formed a representation of the spatial position of these cues, whatever the lighting conditions. They did not memorize the spatial configuration of the olfactory cues per se but needed these cues to be linked to the external spatial frame of reference.

Islands of euchromatin-like sequence and expressed polymorphic sequences within the short arm of human chromosome 21

The goals of the human genome project did not include sequencing of the heterochromatic regions. We describe here an initial sequence of 1.1 Mb of the short arm of human chromosome 21 (HSA21p), estimated to be 10% of 21p. This region contains extensive euchromatic-like sequence and includes on average one transcript every 100 kb. These transcripts show multiple inter- and intrachromosomal copies, and extensive copy number and sequence variability. The sequencing of the "heterochromatic" regions of the human genome is likely to reveal many additional functional elements and provide important evolutionary information.

Stages of change, barriers, benefits, and preferences for exercise in RA patients: a cross-sectional study

OBJECTIVES: To determine the distribution of exercise stages of change in a rheumatoid arthritis (RA) cohort, and to examine patients' perceptions of exercise benefits, barriers, and their preferences for exercise. METHODS: One hundred and twenty RA patients who attended the Rheumatology Unit of a University Hospital were asked to participate in the study. Those who agreed were administered a questionnaire to determine their exercise stage of change, their perceived benefits and barriers to exercise, and their preferences for various features of exercise. RESULTS: Eighty-nine (74%) patients were finally included in the analyses. Their mean age was 58.4 years, mean RA duration 10.1 years, and mean disease activity score 2.8. The distribution of exercise stages of change was as follows: precontemplation (n = 30, 34%), contemplation (n = 11, 13%), preparation (n = 5, 6%), action (n = 2, 2%), and maintenance (n = 39, 45%). Compared to patients in the maintenance stage of change, precontemplators exhibited different demographic and functional characteristics and reported less exercise benefits and more barriers to exercise. Most participants preferred exercising alone (40%), at home (29%), at a moderate intensity (64%), with advice provided by a rheumatologist (34%) or a specialist in exercise and RA (34%). Walking was by far the preferred type of exercise, in both the summer (86%) and the winter (51%). CONCLUSIONS: Our cohort of patients with RA was essentially distributed across the precontemplation and maintenance exercise stages of change. These subgroups of patients exhibit psychological and functional differences that make their needs different in terms of exercise counselling.

Exercise and postprandial thermogenesis in obese women before and after weight loss.

The magnitude of thermogenesis induced by a test meal (17% protein, 54% CHO, and 29% fat) was assessed using indirect calorimetry in six obese women before and after weight loss (mean loss: 11.2 kg) and compared with six nonobese matched controls at rest for 5 h and during and following graded moderate exercise on a bicycle ergometer at three workloads. The test meal contained 60% of the energy expended in basal state over 24 h (736-1020 kcal/meal according to the group). In obese subjects the net absolute increase in energy expenditure (delta EE) in response to the meal was similar between exercising and resting conditions (delta EE = 0.27 vs 0.32 kcal/min, respectively) but tended to be lower in obese women after weight loss (delta EE = 0.19 kcal/min while exercising and 0.25 kcal/min while resting, p less than 0.05) and in control subjects (delta EE = 0.16 vs. 0.25 kcal/min, respectively: p less than 0.05). These results show that the thermogenic response to a meal is not potentiated by moderate exercise.

Effect of hypoxia on cerebral blood flow regulation during rest and exercise : role of cerebral oxygen delivery on performance

Adequate supply of oxygen to the brain is critical for maintaining normal brain function. Severe hypoxia, such as that experienced during high altitude ascent, presents a unique challenge to brain oxygen (O2) supply. During high-intensity exercise, hyperventilation-induced hypocapnia leads to cerebral vasoconstriction, followed by reductions in cerebral blood flow (CBF), oxygen delivery (DO2), and tissue oxygenation. This reduced O2 supply to the brain could potentially account for the reduced performance typically observed during exercise in severe hypoxic conditions. The aims of this thesis were to document the effect of acute and chronic exposure to hypoxia on CBF control, and to determine the role of cerebral DO2 and tissue oxygenation in limiting performance during exercise in severe hypoxia. We assessed CBF, arterial O2 content (CaO2), haemoglobin concentration ([Hb]), partial pressure of arterial O2 (PaO2), cerebrovascular CO2 reactivity, ventilatory response to CO2, cerebral autoregulation (CA), and estimated cerebral DO2 (CBF ⨉ CaO2) at sea level (SL), upon ascent to 5,260 m (ALT1), and following 16 days of acclimatisation to 5,260 m (ALT16). We found an increase in CBF despite an elevated cerebrovascular CO2 reactivity at ALT1, which coincided with a reduced CA. Meanwhile, PaO2 was greatly decreased despite increased ventilatory drive at ALT1, resulting in a concomitant decrease in CaO2. At ALT16, CBF decreased towards SL values, while cerebrovascular CO2 reactivity and ventilatory drive were further elevated. Acclimatisation increased PaO2, [Hb], and therefore CaO2 at ALT16, but these changes did not improve CA compared to ALT1. No differences were observed in cerebral DO2 across SL, ALT1, and ALT16. Our findings demonstrate that cerebral DO2 is maintained during both acute and chronic exposure to 5,260 m, due to the reciprocal changes in CBF and CaO2. We measured middle cerebral artery velocity (MCAv: index of CBF), cerebral DO2, ventilation (VE), and performance during incremental cycling to exhaustion and 15km time trial cycling in both normoxia and severe hypoxia (11% O2, normobaric), with and without added CO2 to the inspirate (CO2 breathing). We found MCAv was higher during exercise in severe hypoxia compared in normoxia, while cerebral tissue oxygenation and DO2 were reduced. CO2 breathing was effective in preventing the development of hyperventilation-induced hypocapnia during intense exercise in both normoxia and hypoxia. As a result, we were able to increase both MCAv and cerebral DO2 during exercise in hypoxia with our CO2 breathing setup. However, we concomitantly increased VE and PaO2 (and presumably respiratory work) due to the increased hypercapnic stimuli with CO2 breathing, which subsequently contributed to the cerebral DO2 increase during hypoxic exercise. While we effectively restored cerebral DO2 during exercise in hypoxia to normoxic values with CO2 breathing, we did not observe any improvement in cerebral tissue oxygenation or exercise performance. Accordingly, our findings do not support the role of reduced cerebral DO2 in limiting exercise performance in severe hypoxia. -- Un apport adéquat en oxygène au niveau du cerveau est primordial pour le maintien des fonctions cérébrales normales. L'hypoxie sévère, telle qu'expérimentée au cours d'ascensions en haute altitude, présente un défi unique pour l'apport cérébral en oxygène (O2). Lors d'exercices à haute intensité, l'hypocapnie induite par l'hyperventilation entraîne une vasoconstriction cérébrale suivie par une réduction du flux sanguin cérébral (CBF), de l'apport en oxygène (DO2), ainsi que de l'oxygénation tissulaire. Cette réduction de l'apport en O2 au cerveau pourrait potentiellement être responsable de la diminution de performance observée au cours d'exercices en condition d'hypoxie sévère. Les buts de cette thèse étaient de documenter l'effet de l'exposition aiguë et chronique à l'hypoxie sur le contrôle du CBF, ainsi que de déterminer le rôle du DO2 cérébral et de l'oxygénation tissulaire comme facteurs limitant la performance lors d'exercices en hypoxie sévère. Nous avons mesuré CBF, le contenu artériel en oxygène (CaO2), la concentration en hémoglobine ([Hb]), la pression partielle artérielle en O2 (PaO2), la réactivité cérébrovasculaire au CO2, la réponse ventilatoire au CO2, et l'autorégulation cérébrale sanguine (CA), et estimé DO2 cérébral (CBF x CaO2), au niveau de la mer (SL), au premier jour à 5.260 m (ALT1) et après seize jours d'acclimatation à 5.260 m (ALT16). Nous avons trouvé des augmentations du CBF et de la réactivité cérébrovasculaire au CO2 après une ascension à 5.260 m. Ces augmentations coïncidaient avec une réduction de l'autorégulation cérébrale. Simultanément, la PaO2 était grandement réduite, malgré l'augmentation de la ventilation (VE), résultant en une diminution de la CaO2. Après seize jours d'acclimatation à 5.260 m, le CBF revenait autour des valeurs observées au niveau de la mer, alors que la réactivité cérébrovasculaire au CO2 et la VE augmentaient par rapport à ALT1. L'acclimatation augmentait la PaO2, la concentration en hémoglobine, et donc la CaO2, mais n'améliorait pas l'autorégulation cérébrale, comparé à ALT1. Aucune différence n'était observée au niveau du DO2 cérébral entre SL, ALT1 et ALT16. Nos résultats montrent que le DO2 cérébral est maintenu constant lors d'expositions aiguë et chronique à 5.260m, ce qui s'explique par la réciprocité des variations du CBF et de la CaO2. Nous avons mesuré la vitesse d'écoulement du sang dans l'artère cérébrale moyenne (MCAv : un indice du CBF), le DO2 cérébral, la VE et la performance lors d'exercice incrémentaux jusqu'à épuisement sur cycloergomètre, ainsi que des contre-la-montres de 15 km en normoxie et en hypoxie sévère (11% O2, normobarique) ; avec ajout ou non de CO2 dans le mélange gazeux inspiré. Nous avons trouvé que MCAv était plus haute pendant l'exercice hypoxique, comparé à la normoxie alors que le DO2 cérébral était réduit. L'ajout de CO2 dans le gaz inspiré était efficace pour prévenir l'hypocapnie induite par l'hyperventilation, qui se développe à l'exercice intense, à la fois en normoxie et en hypoxie. Nous avons pu augmenter MCAv et le DO2 cérébral pendant l'exercice hypoxique, grâce à l'ajout de CO2. Cependant, nous avons augmenté la VE et la PaO2 (et probablement le travail respiratoire) à cause de l'augmentation du stimulus hypercapnique. Alors que nous avons, grâce à l'ajout de CO2, efficacement restauré le DO2 cérébral au cours de l'exercice en hypoxie à des valeurs obtenues en normoxie, nous n'avons observé aucune amélioration dans l'oxygénation du tissu cérébral ou de la performance. En conséquence, nos résultats ne soutiennent pas le rôle d'un DO2 cérébral réduit comme facteur limitant de la performance en hypoxie sévère.

The short arm of the law: judicial institutions and local governance in Brazil

This paper estimates the effect of judicial institutions on governance at the local level in Brazil. Our estimation strategy exploits a unique institutional feature of state judiciary branches which assigns prosecutors and judges to the most populous among contiguous counties forming a judiciary district. As a result of this assignment mechanism there are counties with nearly identical populations, some with and some without local judicial presence, which we exploit to impute counterfactual outcomes. Conditional on observable county characteristics, offenses per civil servant are about 35% lower in counties that have a local seat of the state judiciary. The lower incidence of infractions stems mostly from fewer violations of financial management regulations by local administrators, fewer instances of problems in project execution and project managment, fewer cases of non-existent or ineffective civil society oversight and fewer cases of improper handling of remittances to local residents.

Impaired musculoskeletal response to age and exercise in PPARβ(-/-) diabetic mice.

Fragility fractures are recognized complication of diabetes, but yet the underlying mechanisms remain poorly understood. This is particularly pronounced in type 2 diabetes in which the propensity to fall is increased but bone mass is not necessarily low. Thus, whether factors implicated in the development of insulin resistance and diabetes directly impact on the musculoskeletal system remains to be investigated. PPARβ(-/-) mice have reduced metabolic activity and are glucose intolerant. We examined changes in bone and muscle in PPARβ(-/-) mice and investigated both the mechanism behind those changes with age as well as their response to exercise. Compared with their wild type, PPARβ(-/-) mice had an accelerated and parallel decline in both muscle and bone strength with age. These changes were accompanied by increased myostatin expression, low bone formation, and increased resorption. In addition, mesenchymal cells from PPARβ(-/-) had a reduced proliferation capacity and appeared to differentiate into more of an adipogenic phenotype. Concomitantly we observed an increased expression of PPARγ, characteristic of adipocytes. The anabolic responses of muscle and bone to exercise were also diminished in PPARβ(-/-) mice. The periosteal bone formation response to direct bone compression was, however, maintained, indicating that PPARβ controls periosteal bone formation through muscle contraction and/or metabolism. Taken together, these data indicate that PPARβ deficiency leads to glucose intolerance, decreased muscle function, and reduced bone strength. On a molecular level, PPARβ appears to regulate myostatin and PPARγ expression in muscle and bone, thereby providing potential new targets to reverse bone fragility in patients with metabolic disturbances.