Angiotensin-(1-7) improves the post-ischemic function in isolated perfused rat hearts

We evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) on post-ischemic function in isolated hearts from adult male Wistar rats perfused according to the Langendorff technique. Local ischemia was induced by coronary ligation for 15 min. After ischemia, hearts were reperfused for 30 min. Addition of angiotensin II (Ang II) (0.20 nM, N = 10) or Ang-(1-7) (0.22 nM, N = 10) to the Krebs-Ringer perfusion solution (KRS) before the occlusion did not modify diastolic or systolic tension, heart rate or coronary flow (basal values for Ang-(1-7)-treated hearts: 0.72 ± 0.08 g, 10.50 ± 0.66 g, 216 ± 9 bpm, 5.78 ± 0.60 ml/min, respectively). During the period of occlusion, the coronary flow, heart rate and systolic tension decreased (values for Ang-(1-7)-treated hearts: 2.83 ± 0.24 ml/min, 186 ± 7 bpm, 6.95 ± 0.45 g, respectively). During reperfusion a further decrease in systolic tension was observed in control (4.95 ± 0.60 g) and Ang II-treated hearts (4.35 ± 0.62 g). However, in isolated hearts perfused with KRS containing Ang-(1-7) the further reduction of systolic tension during the reperfusion period was prevented (7.37 ± 0.68 g). The effect of Ang-(1-7) on the systolic tension was blocked by the selective Ang-(1-7) antagonist A-779 (2 nM, N = 9), by the bradykinin B2 antagonist HOE 140 (100 nM, N = 10), and by indomethacin pretreatment (5 mg/kg, ip, N = 8). Pretreatment with L-NAME (30 mg/kg, ip, N = 8) did not change the effect of Ang-(1-7) on systolic tension (6.85 ± 0.61 g). These results show that Ang-(1-7) at low concentration (0.22 nM) improves myocardial function (systolic tension) in ischemia/reperfusion through a receptor-mediated mechanism involving release of bradykinin and prostaglandins.

L- and DL-carnitine induce tetanic fade in rat neuromuscular preparation

Carnitine, a structurally choline-like metabolite, has been used to increase athletic performance, although its effects on neuromuscular transmission have not been investigated. It is present in skeletal muscle and its plasma levels are about 30 to 90 µM. Using rat phrenic nerve diaphragm preparations indirectly and directly stimulated with high rate pulses, D-carnitine (30 and 60 µM), L-carnitine (60 µM) and DL-carnitine (60 µM) were shown to induce tetanic fade (D-carnitine = 19.7 ± 3.1%, N = 6; L-carnitine = 16.6 ± 2.4%, N = 6; DL-carnitine = 14.9 ± 2.1%, N = 6) without any reduction of maximal tetanic tension. D-carnitine induced tetanic fade in neuromuscular preparations previously paralyzed with d-tubocurarine and directly stimulated. The effect was greater than that obtained by indirect muscle stimulation. Furthermore, previous addition of atropine (20 to 80 µM) to the bath did not reduce carnitine isomer-induced tetanic fade. In contrast to D-carnitine, the tetanic fade induced by L- and DL-carnitine was antagonized by choline (60 µM). The combined effect of carnitine isomers and hemicholinium-3 (0.01 nM) was similar to the effect of hemicholinium-3 alone. The data suggest that L- and DL-carnitine-induced tetanic fade seems to depend on their transport into the motor nerve terminal.

Headache complaints associated with psychiatric comorbidity in a population-based sample

The objective of the present study was to determine the frequency at which people complain of any type of headache, and its relationship with sociodemographic characteristics and psychiatric comorbidity in São Paulo, Brazil. A three-step cluster sampling method was used to select 1,464 subjects aged 18 years or older. They were mainly from families of middle and upper socioeconomic levels living in the catchment area of Instituto de Psiquiatria. However, this area also contains some slums and shantytowns. The subjects were interviewed using the Brazilian version of the Composite International Diagnostic Interview version 1.1. (CIDI 1.1) by a lay trained interviewer. Answers to CIDI 1.1 questions allowed us to classify people according to their psychiatric condition and their headaches based on their own ideas about the nature of their illness. The lifetime prevalence of "a lot of problems with" headache was 37.4% (76.2% of which were attributed to use of medicines, drugs/alcohol, physical illness or trauma, and 23.8% attributed to nervousness, tension or mental illness). The odds ratio (OR) for headache among participants with "nervousness, tension or mental illness" was elevated for depressive episodes (OR, 2.1; 95%CI, 1.4-3.4), dysthymia (OR, 3.4; 95%CI, 1.6-7.4) and generalized anxiety disorder (OR, 4.3; 95%CI, 2.1-8.6), when compared with patients without headache. For "a lot of problems with" headaches attributed to medicines, drugs/alcohol, physical illness or trauma, the risk was also increased for dysthymia but not for generalized anxiety disorder. These data show a high association between headache and chronic psychiatric disorders in this Brazilian population sample.

Ionic radiocontrast inhibits endothelium-dependent vasodilation of the canine renal artery in vitro: possible mechanism of renal failure following contrast medium infusion

To determine if radiocontrast impairs vascular relaxation of the renal artery, segments (4-5 mm in length) of canine renal artery were suspended in vitro in organ chambers to measure isometric force (95% O2/5% CO2, at 37ºC). Arterial segments with and without endothelium were placed at the optimal point of their length-tension relation and incubated with 10 µM indomethacin to prevent synthesis of endogenous prostanoids. The presence of nonionic radiocontrast (iohexol, Omnipaque 350, 1 ml in 25 ml control solution, 4% (v/v)) did not alter endothelium-dependent relaxation to acetylcholine in rings precontracted with both norepinephrine and prostaglandin F2alpha (N = 6). When the rings were precontracted with prostaglandin F2alpha, the presence of ionic contrast did not inhibit the relaxation of the arteries. However, in canine renal arteries contracted with norepinephrine, the presence of ionic radiocontrast (diatrizoate meglumine and diatrizoate sodium, MD-76, 1 ml in 25 ml control solution, 4% (v/v)) inhibited relaxation in response to acetylcholine, sodium nitroprusside (N = 6 in each group), and isoproterenol (N = 5; P < 0.05). Rings were relaxed less than 50% of norepinephrine contraction. Following removal of the contrast, vascular relaxation in response to the agonists returned to normal. These results indicate that ionic radiocontrast nonspecifically inhibits vasodilation (both cAMP-mediated and cGMP-mediated) of canine renal arteries contracted with norepinephrine. This reversible impairment of vasodilation could inhibit normal renal perfusion and act as a mechanism of renal failure following radiocontrast infusion. In the adopted experimental protocol the isoproterenol-induced relaxation of renal arteries precontracted with norepinephrine was more affected, suggesting a pivotal role of the cAMP system.

Eucalyptol, an essential oil, reduces contractile activity in rat cardiac muscle

Eucalyptol is an essential oil that relaxes bronchial and vascular smooth muscle although its direct actions on isolated myocardium have not been reported. We investigated a putative negative inotropic effect of the oil on left ventricular papillary muscles from male Wistar rats weighing 250 to 300 g, as well as its effects on isometric force, rate of force development, time parameters, post-rest potentiation, positive inotropic interventions produced by Ca2+ and isoproterenol, and on tetanic tension. The effects of 0.3 mM eucalyptol on myosin ATPase activity were also investigated. Eucalyptol (0.003 to 0.3 mM) reduced isometric tension, the rate of force development and time parameters. The oil reduced the force developed by steady-state contractions (50% at 0.3 mM) but did not alter sarcoplasmic reticulum function or post-rest contractions and produced a progressive increase in relative potentiation. Increased extracellular Ca2+ concentration (0.62 to 5 mM) and isoproterenol (20 nM) administration counteracted the negative inotropic effects of the oil. The activity of the contractile machinery evaluated by tetanic force development was reduced by 30 to 50% but myosin ATPase activity was not affected by eucalyptol (0.3 mM), supporting the idea of a reduction of sarcolemmal Ca2+ influx. The present results suggest that eucalyptol depresses force development, probably acting as a calcium channel blocker.

Multicellular spheroids of bone marrow stromal cells: a three-dimensional in vitro culture system for the study of hematopoietic cell migration

Cell fate decisions are governed by a complex interplay between cell-autonomous signals and stimuli from the surrounding tissue. In vivo cells are connected to their neighbors and to the extracellular matrix forming a complex three-dimensional (3-D) microenvironment that is not reproduced in conventional in vitro systems. A large body of evidence indicates that mechanical tension applied to the cytoskeleton controls cell proliferation, differentiation and migration, suggesting that 3-D in vitro culture systems that mimic the in vivo situation would reveal biological subtleties. In hematopoietic tissues, the microenvironment plays a crucial role in stem and progenitor cell survival, differentiation, proliferation, and migration. In adults, hematopoiesis takes place inside the bone marrow cavity where hematopoietic cells are intimately associated with a specialized three 3-D scaffold of stromal cell surfaces and extracellular matrix that comprise specific niches. The relationship between hematopoietic cells and their niches is highly dynamic. Under steady-state conditions, hematopoietic cells migrate within the marrow cavity and circulate in the bloodstream. The mechanisms underlying hematopoietic stem/progenitor cell homing and mobilization have been studied in animal models, since conventional two-dimensional (2-D) bone marrow cell cultures do not reproduce the complex 3-D environment. In this review, we will highlight some of the mechanisms controlling hematopoietic cell migration and 3-D culture systems.

Effect of age on upper and lower eyelid saccades

To study the effect of age on the metrics of upper and lower eyelid saccades, eyelid movement of two groups of 30 subjects each were measured using computed image analysis. The patients were divided on the basis of age into a younger group (20-30 years) and an older group (60-91 years). Eyelid saccade functions were fitted by the damped harmonic oscillator model. Amplitude and peak velocity were used to compare the effect of age on the saccades of the upper and lower eyelid. There was no statistically significant difference in saccade amplitude between groups for the upper eyelid (mean ± SEM; upward, young = 9.18 ± 0.32 mm, older = 8.93 ± 0.31 mm, t = 0.56, P = 0.58; downward, young = 9.11 ± 0.27 mm, older = 8.86 ± 0.32 mm, t = 0.58, P = 0.56) However, there was a clear decline in the peak velocity of the upper eyelid saccades of older subjects (upward, young = 59.06 ± 2.34 mm/s, older = 50.12 ± 1.95 mm/s, t = 2.93, P = 0.005; downward, young = 71.78 ± 1.78 mm/s, older = 60.29 ± 2.62 mm/s, t = 3.63, P = 0.0006). In contrast, for the lower eyelid there was a clear increase of saccade amplitude in the elderly group (upward, young = 2.27 ± 0.09 mm, older = 2.98 ± 0.15 mm, t = 4.33, P < 0.0001; downward, young = 2.21 ± 0.10 mm, older = 2.96 ± 0.17 mm, t = 3.85, P < 0.001). These data suggest that the aging process affects the metrics of the lid saccades in a different manner according to the eyelid. In the upper eyelid the lower tension exerted by a weak aponeurosis is reflected only on the peak velocity of the saccades. In the lower eyelid, age is accompanied by an increase in saccade amplitude which indicates that the force transmission to the lid is not affected in the elderly.

Gadolinium increases the vascular reactivity of rat aortic rings

Gadolinium (Gd) blocks intra- and extracellular ATP hydrolysis. We determined whether Gd affects vascular reactivity to contractile responses to phenylephrine (PHE) by blocking aortic ectonucleoside triphosphate diphosphohydrolase (E-NTPDase). Wistar rats of both sexes (260-300 g, 23 females, 7 males) were used. Experiments were performed before and after incubation of aortic rings with 3 µM Gd. Concentration-response curves to PHE (0.1 nM to 0.1 mM) were obtained in the presence and absence of endothelium, after incubation with 100 µM L-NAME, 10 µM losartan, or 10 µM enalaprilat. Gd significantly increased the maximum response (control: 72.3 ± 3.5; Gd: 101.3 ± 6.4%) and sensitivity (control: 6.6 ± 0.1; Gd: 10.5 ± 2.8%) to PHE. To investigate the blockade of E-NTDase activity by Gd, we added 1 mM ATP to the bath. ATP reduced smooth muscle tension and Gd increased its relaxing effect (control: -33.5 ± 4.1; Gd: -47.4 ± 4.1%). Endothelial damage abolished the effect of Gd on the contractile responses to PHE (control: 132.6 ± 8.6; Gd: 122.4 ± 7.1%). L-NAME + Gd in the presence of endothelium reduced PHE contractile responses (control/L-NAME: 151.1 ± 28.8; L-NAME + Gd: 67.9 ± 19% AUC). ATP hydrolysis was reduced after Gd administration, which led to ATP accumulation in the nutrient solution and reduced ADP concentration, while adenosine levels remained the same. Incubation with Gd plus losartan and enalaprilat eliminated the pressor effects of Gd. Gd increased vascular reactivity to PHE regardless of the reduction of E-NTPDase activity and adenosine production. Moreover, the increased reactivity to PHE promoted by Gd was endothelium-dependent, reducing NO bioavailability and involving an increased stimulation of angiotensin-converting enzyme and angiotensin II AT1 receptors.

Effects of short-term administration of estradiol on reperfusion arrhythmias in rats of different ages

Little is known about age-related differences in short-term effects of estradiol on ischemia-reperfusion (I/R) insults. The present study was designed to evaluate the effects of short-term treatment with estradiol on reperfusion arrhythmias in isolated hearts of 6-7-week-old and 12-14-month-old female rats. Wistar rats were sham-operated, ovariectomized and treated with vehicle or ovariectomized and treated with 17β-estradiol (E2; 5 µg·100 g-1·day-1) for 4 days. Hearts were perfused by the Langendorff technique. Reperfusion arrhythmias, i.e., ventricular tachycardia and/or ventricular fibrillation, were induced by 15 min of left coronary artery ligation and 30 min of reperfusion. The duration and incidence of I/R arrhythmias were significantly higher in young rats compared to middle-aged rats (arrhythmia severity index: 9.4 ± 1.0 vs 3.0 ± 0.3 arbitrary units, respectively, P < 0.05). In addition, middle-aged rats showed lower heart rate, systolic tension and coronary flow. Four-day E2 treatment caused an increase in uterine weight. Although E2 administration had no significant effect on the duration of I/R arrhythmias in middle-aged rats, it induced a marked reduction in the rhythm disturbances of young rats accompanied by a decrease in heart rate of isolated hearts. Also, this reduction was associated with an increase in QT interval. No significant changes were observed in the QT interval of middle-aged E2-treated rats. These data demonstrate that short-term estradiol treatment protects against I/R arrhythmias in hearts of young female rats. The anti-arrhythmogenic effect of estradiol might be related to a lengthening of the QT interval.

Acute exposure to lead increases myocardial contractility independent of hypertension development

We studied the effects of the acute administration of small doses of lead over time on hemodynamic parameters in anesthetized rats to determine if myocardial contractility changes are dependent or not on the development of hypertension. Male Wistar rats received 320 µg/kg lead acetateiv once, and their hemodynamic parameters were measured for 2 h. Cardiac contractility was evaluated in vitro using left ventricular papillary muscles as were Na+,K+-ATPase and myosin Ca2+-ATPase activities. Lead increased left- (control: 112 ± 3.7 vs lead: 129 ± 3.2 mmHg) and right-ventricular systolic pressures (control: 28 ± 1.2vs lead: 34 ± 1.2 mmHg) significantly without modifying heart rate. Papillary muscles were exposed to 8 µM lead acetate and evaluated 60 min later. Isometric contractions increased (control: 0.546 ± 0.07 vs lead: 0.608 ± 0.06 g/mg) and time to peak tension decreased (control: 268 ± 13vs lead: 227 ± 5.58 ms), but relaxation time was unchanged. Post-pause potentiation was similar between groups (n = 6 per group), suggesting no change in sarcoplasmic reticulum activity, evaluated indirectly by this protocol. After 1-h exposure to lead acetate, the papillary muscles became hyperactive in response to a β-adrenergic agonist (10 µM isoproterenol). In addition, post-rest contractions decreased, suggesting a reduction in sarcolemmal calcium influx. The heart samples treated with 8 µM lead acetate presented increased Na+,K+-ATPase (approximately 140%, P < 0.05 for control vs lead) and myosin ATPase (approximately 30%, P < 0.05 for control vs lead) activity. Our results indicated that acute exposure to low lead concentrations produces direct positive inotropic and lusitropic effects on myocardial contractility and increases the right and left ventricular systolic pressure, thus potentially contributing to the early development of hypertension.

Efficacy of cognitive behavioral therapy in reducing psychiatric symptoms in patients with implantable cardioverter defibrillator: an integrative review

This article is a systematic review of the available literature on the benefits that cognitive behavioral therapy (CBT) offers patients with implanted cardioverter defibrillators (ICDs) and confirms its effectiveness. After receiving the device, some patients fear that it will malfunction, or they remain in a constant state of tension due to sudden electrical discharges and develop symptoms of anxiety and depression. A search with the key words “anxiety”, “depression”, “implantable cardioverter”, “cognitive behavioral therapy” and “psychotherapy” was carried out. The search was conducted in early January 2013. Sources for the search were ISI Web of Knowledge, PubMed, and PsycINFO. A total of 224 articles were retrieved: 155 from PubMed, 69 from ISI Web of Knowledge. Of these, 16 were written in a foreign language and 47 were duplicates, leaving 161 references for analysis of the abstracts. A total of 19 articles were eliminated after analysis of the abstracts, 13 were eliminated after full-text reading, and 11 articles were selected for the review. The collection of articles for literature review covered studies conducted over a period of 13 years (1998-2011), and, according to methodological design, there were 1 cross-sectional study, 1 prospective observational study, 2 clinical trials, 4 case-control studies, and 3 case studies. The criterion used for selection of the 11 articles was the effectiveness of the intervention of CBT to decrease anxiety and depression in patients with ICD, expressed as a ratio. The research indicated that CBT has been effective in the treatment of ICD patients with depressive and anxiety symptoms. Research also showed that young women represented a risk group, for which further study is needed. Because the number of references on this theme was small, further studies should be carried out.

Immobilization and therapeutic passive stretching generate thickening and increase the expression of laminin and dystrophin in skeletal muscle

Extracellular matrix and costamere proteins transmit the concentric, isometric, and eccentric forces produced by active muscle contraction. The expression of these proteins after application of passive tension stimuli to muscle remains unknown. This study investigated the expression of laminin and dystrophin in the soleus muscle of rats immobilized with the right ankle in plantar flexion for 10 days and subsequent remobilization, either by isolated free movement in a cage or associated with passive stretching for up to 10 days. The intensity of the macrophage response was also evaluated. One hundred and twenty-eight female Wistar rats were divided into 8 groups: free for 10 days; immobilized for 10 days; immobilized/free for 1, 3, or 10 days; or immobilized/stretched/free for 1, 3, or 10 days. After the experimental procedures, muscle tissue was processed for immunofluorescence (dystrophin/laminin/CD68) and Western blot analysis (dystrophin/laminin). Immobilization increased the expression of dystrophin and laminin but did not alter the number of macrophages in the muscle. In the stretched muscle groups, there was an increase in dystrophin and the number of macrophages after 3 days compared with the other groups; dystrophin showed a discontinuous labeling pattern, and laminin was found in the intracellular space. The amount of laminin was increased in the muscles treated by immobilization followed by free movement for 10 days. In the initial stages of postimmobilization (1 and 3 days), an exacerbated macrophage response and an increase of dystrophin suggested that the therapeutic stretching technique induced additional stress in the muscle fibers and costameres.

Regulação de indústrias de rede: entre flexibilidade e estabilidade

This paper explores the problems of an unstable regulatory regime in network industries and addresses the tension between the necessary flexibility in the long-term regulatory commitment and the need for institutional stability. A draft statute that substantively changes the initial terms under which fixed telecommunications services have been transferred to private companies - currently under discussion in the Brazilian Congress - is presented as an example of that tension. Some alternative proposals to tackle with universal service challenges - the underlying problem behind the mentioned draft statute - are presented in the end.

Institutions, credibility and crisis: the inconsistencies of Argentine exchange rate policy (1991-2006)

The purpose of this article is twofold. The first is to explain the time inconsistencies of the convertibility regime that led to the 2001 crisis. The argument suggests that the credibility requirements for convertibility induced a dynamic of legal, fiscal, financial and external commitments that increased exit costs and time inconsistencies. The second objective is to explain the tensions of the floating regime that replaced convertibility in 2002. We describe the effects of a floating exchange rate on macroeconomic imbalance and the growing tension between competitiveness and inflation.

Chronic macro-economic and financial imbalances in the world economy: a meta-economic view

Global finance, combining offshore banking and universal banks to drive a broader globalization process, has transformed the modus operandi of the world economy. This requires a new "meta-economic" framework in which short-term portfolio-investment flows are treated as the dominant phenomenon they have become. Organized by global finance, these layered bi-directional flows between center and periphery manage a tension between financial concentration and monetary fragmentation. The resulting imbalances express the asymmetries built into that tension and render the exchange rate a more strategic policy variable than ever.