Melanocortin activity in the amygdala influences alcohol intake.

Melanocortins have been reported to affect alcohol intake through actions in the hypothalamus thought to be mediated by melanocortin MC4 receptors. Since these receptors are expressed in a number of amygdala regions, we have explored their role in the regulation of alcohol intake in both alcohol-preferring (P) and non-preferring (NP) rats. Injections were made at the border of the central amygdala nucleus and the basolateral amygdala. The MC3/MC4R agonist MTII reduced alcohol and food intake but increased water intake while the selective MC4R antagonist HS014 only increased food and water intake. The MC3/MC4R antagonist SHU9119 increased food and water but had little effect on alcohol intake. However, when the SHU9119 stimulation of food intake was prevented by pair-feeding, SHU9119 induced a large and prolonged decline in alcohol intake that was paralleled by an increase in water intake. These effects were only observed in P rats. We conclude that melanocortin activity in the amygdala can alter the selective preference for water and alcohol independent of effects on food intake.

Body mass influences cortical bone mass independent of leptin signaling.

Obesity in humans is associated with increased bone mass. Leptin, a hormone produced by fat cells, functions as a sentinel of energy balance, and may mediate the putative positive effects of body mass on bone. We performed studies in male C57Bl/6 wild type (WT) and leptin-deficient ob/ob mice to determine whether body mass gain induced by high fat intake increases bone mass and, if so, whether this requires central leptin signaling. The relationship between body mass and bone mass and architecture was evaluated in 9-week-old and 24-week-old WT mice fed a regular mouse diet. Femora and lumbar vertebrae were analyzed by micro computed tomography. In subsequent studies, slowly and rapidly growing ob/ob mice were injected in the hypothalamus with a recombinant adeno-associated virus containing the leptin gene (rAAV-lep) or a control vector, rAAV-GFP (green fluorescent protein). The mice were maintained on a regular control diet for 5 or 7 weeks and then subdivided into groups and either continued on the control diet or fed a high fat diet (45% of kcal from fat) for 8 weeks. In the WT mice, femoral and vertebral bone mass was positively correlated with body mass (Pearson's r=0.65-0.88 depending on endpoint). rAAV-lep therapy dramatically decreased body mass (-61%) but increased femur length. However, in the distal femur and lumbar vertebra, rAAV-lep therapy reduced cancellous bone volume/tissue volume, trabecular number and trabecular thickness, and increased trabecular spacing. The high fat diet increased body mass, irrespective of vector treatment. Total femur bone volume, length, cross-sectional volume, and cortical volume and thickness were increased in mice with increased body mass, independent of rAAV treatment. In the distal femur, increased body mass had no effect on cancellous architecture and there were no vector x body mass interactions. In WT mice, increased body mass resulted in increased (+33%) vertebral cancellous bone volume/tissue volume. Increased body mass had minimal independent effect on cancellous vertebral bone mass in ob/ob mice. Taken together, these findings suggest that increased body mass has a positive effect on femur cortical bone mass that is independent of leptin signaling.

Effect of treatment with dexamethasone on protein intake in adult and old Lou/c/jall rats.

A deleterious decrease of protein intake had been evidenced in Lou/c/jall rats during ageing. This result could be induced by an impaired regulation of feeding behaviour. Glucocorticoids inducing specific amino-acid needs for gluconeogenesis and for the synthesis of inflammatory proteins by the liver, we investigated the age-related effect of a 4-days treatment with dexamethasone (DEX) on caloric and protein intake. Males and females aged 7, 19, 25 and 31 months received 573.6 +/- 65.6 microg/(kg day) of dexamethasone via the drinking water. Body weight (BW), caloric and macronutrients intakes were monitored during treatment and during 10 days after the treatment. A strong hypophagia was seen during treatment in all groups, which was mainly due to a decrease in fat intake. In the same time, rats maintained their protein intake so that protein became the main macronutrient of the diet in most of the groups. However, older males showed a lesser efficiency in adjusting their diet. These results are in agreement with previous data obtained in a protein deprivation study. They lead to the conclusion that the loss of appetite for protein in old age probably does not reflect a loss of ability to choose the needed amount of protein. We can hypothesise that the decrease of protein intake in old rats could be due to some inadequacy of casein to the metabolic requirement of aged animals.

Old as mature LOU/c/jall rats enhance protein selection in response to a protein deprivation.

Previous experiments have shown a strong decrease in protein consumption as rats grow old. This result could be induced by an impaired regulation of feeding behaviour. Present study investigated the ability of ageing rats to adapt their protein intake to protein requirements. Four groups of self-selecting LOU/c/jall male and female rats (4, 16, 22, 28 months at the beginning of the experiments) were submitted to 4-days of protein deprivation periods while their macronutrient intakes were monitored. Moreover, they were submitted to a 4-day fasting period. After reintroduction of proteins, old and senescent rats were able to increase their protein intake in response to the specific protein need created by the protein deprivation. They were also able to increase caloric intake after the fasting period. These results led to the conclusion that the loss of appetite for protein observed with ageing reflects rather an adaptation than an impairment of the regulation of macronutrient choice. Another important observation was that older animals did not recover initial body weight after a body weight loss even if they ate as many calories as younger animals. This data supports a decrease in the efficacious utilization of body fuels in old and senescent rats.

Effect of morphine on caloric intake and macronutrient selection in male and female Lou/c/jall rats during ageing.

Previous studies have showed a shift of preferences from carbohydrate to fat in the Lou/c/jall rat with advancing age when they are submitted to a self-selection procedure. Protein intake also decreased according to the age, earlier for males (after 16 months) than for females (29 months). The present study aimed at investigating the mechanism underlying these modifications. We analysed the effect of the reference mu agonist, morphine (5 mg/kg subcutaneous), on the caloric intake, body weight and macronutrient intake of 30 male and 30 female rats divided in four age groups: young adults (10), mature (17), old (24) and senescent rats (29 months). During the experiment, animals had the choice between separate sources of the three pure macronutrients. Morphine injection reduced total daily caloric intake and induced a decrease in body weight. The weight loss was age- and sex-related (males and old rats were more affected by the drugs). The injection of morphine evoked a triphasic influence on the chronology of the intake. A brief (1 h) hypophagia was followed by an hyperphagia (3 h) and a persistent hypophagia (8 h). No modification in the diet composition was observed. These results did not support a clear involvement of the opioid system concerning the modifications in macronutrient rates in diet previously observed across ageing.

The frequency analysis of signal-averaged ECG of P wave as predictor of efficacy of class III antiarrhythmic drugs to maintain sinus rhythm in recurrent idiopathic atrial fibrillation.

BACKGROUND: The use of class III antiarrhythmic drugs (ADIII) has been considered a good predictor of sinus rhythm in patients post-cardioversion from atrial fibrillation (AF). Several studies using frequency domain analysis of signal-averaged ECG (FDSAECG) of the P wave were able to identify patients at risk for AF. The aim of this study was to assess the FDSAECG in predicting recurrence of idiopathic persistent AF (IPAF) in patients under ADIII therapy. METHODS: In 33 patients with two or more previous symptomatic episodes of IPAF, despite classes I and II therapy, the FDSAECG of the P wave was performed during sinus rhythm and free-drug state. The parameters were the mean and standard deviation of the frequency intersegmentar spectral correlation and the standard deviation of the signal frequency edge track. During the follow-up of 30 +/- 18 months, all patients received either amiodarone or sotalol. RESULTS: During the follow-up, the patients were divided into two groups: Group I-frequent recurrence (>or= three events/year; 16 patients), and Group II-infrequent recurrence (< three events/year; 17 patients). With appropriate cutoff points for each parameter analyzed, intense fragmented electrical activity defined by the presence of at least two abnormal criteria were observed in 13 of 16 patients group I and in 3 of 17 patients group II (P = 0.0003). Sensitivity, specificity, positive and negative predictive values for frequent recurrence were 81.3, 82.4, 81.3, and 82.4, respectively. CONCLUSIONS: The results suggested that FDSAECG analysis of the P wave accurately predicted patients whose ADIII therapy will be effective in maintaining the sinus rhythm without frequent recurrence of IPAF.

Effects of peripheral and central administration of GHRH on feeding in aging LOU rats.

In aging LOU rats, a decreased protein intake is restored by GH administration. To study the contribution of GHRH to macronutrient selection, hGHRH NH(2) was administered sc. (1 mg/kg B.W./day/14 days) or icv. (4 and 40 pmol/rat) to 11-, 19-, 24- and 28-month-old rats. Sc. administration induced a decreased food and lipid intakes from 24 months of age and a transient stimulation of protein intake in 19-month-old and older low protein eaters (<10% protein/total intake). Icv. administration induced decreased food and lipid intakes in all age groups. These results suggest that GHRH may regulate feeding through pituitary and/or hypothalamic GHRH receptor mechanisms.

A moderate swimming exercise regularly performed throughout the life induces age and sex-related modifications in adaptive macronutrients choice.

The ability of laboratory rats to adapt food intake to needs is well-known. The present study investigates changes in this adaptive behavior when animals grow old. A cohort of male and female Lou/c/jall rats was regularly submitted to an exercise throughout their life (6 consecutive days of moderate intensity training (3x15 min/day)). Caloric intake and macronutrients selection during exercise and post-exercise periods were compared to the pre-training period. During swimming, a decrease in both caloric intake and fat selection was observed and an increase in protein intake was specifically seen in female groups. However, males were unable to modify the diet composition (macronutrient rate) from 16 months of age, whereas females were able to do it until 24 months of age. The present results suggest a sex-dependent loss of capacity of adjusting feeding behavior to metabolic needs when animals grow old, may be due to a deterioration of the central control of food intake.

Arrhythmogenic cardiomyopathy of the right ventricle. Predictive value of QT interval dispersion to assess arrhythmogenic risk and sudden death.

OBJECTIVE: To determine in arrhythmogenic right ventricular cardiomyopathy the value of QT interval dispersion for identifying the induction of sustained ventricular tachycardia in the electrophysiological study or the risk of sudden cardiac death. METHODS: We assessed QT interval dispersion in the 12-lead electrocardiogram of 26 patients with arrhythmogenic right ventricular cardiomyopathy. We analyzed its association with sustained ventricular tachycardia and sudden cardiac death, and in 16 controls similar in age and sex. RESULTS: (mean +/- SD). QT interval dispersion: patients = 53.8+/-14.1 ms; control group = 35.0+/-10.6 ms, p = 0.001. Patients with induction of ventricular tachycardia: 52.5+/-13.8 ms; without induction of ventricular tachycardia: 57.5+/-12.8 ms, p =0.420. In a mean follow-up period of 41+/-11 months, five sudden cardiac deaths occurred. QT interval dispersion in this group was 62.0+/-17.8, and in the others it was 51.9+/-12.8 ms, p = 0.852. Using a cutoff > or =60 ms to define an increase in the degree of the QT interval dispersion, we were able to identify patients at risk of sudden cardiac death with a sensitivity of 60%, a specificity of 57%, and positive and negative predictive values of 25% and 85%, respectively. CONCLUSION: Patients with arrhythmogenic right ventricular cardiomyopathy have a significant increase in the degree of QT interval dispersion when compared with the healthy population. However it, did not identify patients with induction of ventricular tachycardia in the electrophysiological study, showing a very low predictive value for defining the risk of sudden cardiac death in the population studied.

Age-related changes in nociception and effect of morphine in the Lou rat.

Little is known about how the ageing process affects pain sensitivity and a relevant animal model is therefore required. The effect of age on pain reactivity in animals has been investigated by several experimenters but the results are conflicting. Four groups of male and female Lou/C/Jall rats (4-29 months old) were used for our study. Four pain tests based on evaluation of reflex or more integrated behaviours after a thermal (tail immersion test) or mechanical (paw pressure test and von Frey test) stimulation were used. With mechanical stimulus, a significant decrease in the pain threshold across age was observed, females were more sensitive than males. This increase in nociceptive sensitivity to mechanical stimulation was more pronounced on integrated behaviours (struggle reaction) than on withdrawal reflex. An age-related increase in sensitivity was found on von Frey test. No effect on the latency of reflex induced by thermal stimulation was observed. In addition, a decrease in the spontaneous motor activity during exploration was observed across ageing; this effect was more marked for the females. The effect of morphine at doses of 1, 3 and 9 mg/kg (s.c.) decreased in intensity across ageing. These data demonstrate the need to use (1) various noxious stimuli because differences were observed in the modification of pain reactivity according to the nature of the stimulus; (2) various pain parameters and particularly integrated behaviours; (3) several age groups. In addition, Lou/C/Jall rat could be a useful model for studying of effect of age on pain.

The Brugada syndrome. Outcome of one case.

The Brugada syndrome is a rare condition, and due to its mutating manner of presentation it may be difficult to diagnose. We report one case and discuss the diagnostic aspects and the clinical outcome of one patient with characteristic findings of this syndrome. These findings are especially defined by J-ST elevation in the right leads of serial electrocardiographic records, wide oscillations of J points and ST segments during 24-hour Holter monitoring, and nocturnal sudden death. We stress the importance of the Holter monitor findings for diagnostic complementation. Through this method it is possible to establish a correlation between vigil activities and sleep and the variability of the degree of impairment in ventricular repolarization.

Electrical behavior of T-wave polarity alternans in patients with congenital long QT syndrome.

OBJECTIVES: This study was designed to evaluate the incidence and characteristics of onset of T-wave polarity alternans (TWPA) in patients with long QT syndrome. BACKGROUND: The T-wave alternans is a phenomenon that consists of beat-to-beat variability in the amplitude, morphology, and sometimes polarity of the T-wave, and it may trigger life-threatening arrhythmias. METHODS: The 24-h Holter recordings of 11 patients with congenital long QT syndrome were studied. Episodes of TWPA with 10 or more consecutive cycles were selected and analyzed as follows: 1) mean cycle length (MCL) and QTc interval duration (QTcI) of the episodes of TWPA and the 10 cycles preceding and succeeding the TWPA; 2) MCL and QTcI of the third, second, and first minute before onset (Mn_3, Mn_2, Mn_1); 3) MCL and QTcI from the tenth to the first cycle immediately preceding the onset of TWPA (R_10 to R_1); 4) MCL and QTcI from the first to the fourteenth cycle during alternans (R0 to R14); 5) MCL and QTcI from the first to the tenth cycle immediately succeeding TWPA (R+1 to R+10); 6) linear correlation (Lnc) between QT interval and cycle length (CL) (LncQT/CL) during alternans and for the 10 preceding cycles; 7) Lnc between the first three alternans cycles and episode duration (Lnc 3CL/EpD); and 8) difference between the longest and shortest QTc interval. We also selected episodes consisting of four or more consecutive cycles in order to analyze daily rhythms of the phenomenon. RESULTS: The TWPA was observed in 5 (45%) out of the 11 patients studied. The alternans process is initiated by a sudden shortening of the first alternans cycle without previous heart rate changes and ends at the moment when prolongation of the cycle tends to occur. LncQT/ CL-alternans: r = 0.38 +/- 0.2 (p = 0.20); without alternans: r = 0.81 +/- 0.06 (p = 0.01). Lnc 3CL/EpD: r = 0.002 (p = 0.992). The QTc difference during alternans: 312.0 +/- 52.1 ms; without alternans: 86.0 +/- 36.4 ms (p = 0.001). Daily rhythm: 71% of the episodes occurred between 8 AM and 8 PM, with higher incidence during the morning. CONCLUSIONS: The TWPA was dependent on the cardiac CL; there was loss of the LncQT/CL and an increase in the QT interval variability. Like other biological variables, T-wave polarity alternans has a higher density during the morning.

Age-related changes in adaptive macronutrient intake in swimming male and female Lou rats.

To evaluate the age-related changes in capacity to adjust the nutrient intake to needs, self-selecting male and female Lou/C/jall rats of 4, 6, 12, 16 and 23 months of age were submitted to a swimming exercise. They were given 6 consecutive days of moderate intensity training (3 x 15 minutes per day). Exercise and postexercise periods were compared with results from the pretraining period. During swimming, a body weight loss and a decrease in both caloric intake and fat selection were observed. This effect was more marked in older groups compared to 4 month-old groups. An increase in protein intake was observed in females, specially in older groups, whereas no effect was seen in males. The ability to increase caloric ingestion and regain weight during the postexercise period decreased with advancing age and was better in females than in males. We also showed an age-related effect on the recovery of initial nutrient intake rate that was more pronounced and more precocious for males. Moreover, males tended to decrease their protein intake, whereas females significantly increased it. The present findings suggest a decrease of capacity of adjusting feeding behavior to metabolic needs in aged rats, may be due to a deterioration of the central control of food intake.

Age-related changes in adaptive mechanisms of macronutrient self-selection: evidence for a sexual dimorphism.

The effect of aging on patterns of food intake and nutrient selection was investigated using a longitudinal study. Male (n = 10) and female (n = 10) Wistar-Lou rats from 4 to 28 months of age were repeatedly submitted to a macronutrient self-selection (S-S) regimen while controls were maintained under a standard chow diet (Std). An age-related shift of preferences from CHO to fat diets, and a decrease in protein intake for both males and females were evident. Nevertheless, all these modifications were more pronounced and precocious for males. Physical exercise (45 min/day of swimming, on 6 days) induced a body weight loss and an hypophagia more pronounced for males than for females. S-S regimen results revealed that hypophagia concerned exclusively fat intake and that females significantly increased protein intake during and after the exercise period. Study of longevity curves showed a decrease of the mortality in S-S submitted male rats compared to control rats. This study shows that aging induces a sex-difference in feeding patterns which undoubtedly reveals a sex-difference metabolic requirements. Moreover, these results suggest that allowing rats to select macronutrient intakes could delay the process of senescence.

[Sinus node modification by catheter using radiofrequency current in a patient with inappropriate sinus tachycardia. Evaluation of early and late results]. / Modificação do nódulo sinusal via cateter por energia de radiofreqüência em paciente com taquicardia sinusal inapropriada. Avaliação dos resultados imediatos e tardios.

This article reports the early and late results of a patient in whom radiofrequency current was used to ablate an incessant inappropriate sinus tachycardia. During successful radiofrequency application there was a sudden change of rate and subsequent emergence of a stable rhythm with the same sinus node P wave characteristics. During follow-up, normal cardiac cycles were still present after six months of the procedure, although the patient still complained of palpitations, suggesting no correlation with the heart rate.

Dispersäo temporal da repolarizaçäo ventricular, alternância elétrica da onda T e variabilidade dos intervalos Qt: metodologia de aquisiçäo, análise dos dados, importância clínica / Temporal dispersion of the ventricular repolarization, T wave eletrical alternans and Q-T intervals variability. Methodology analysis of data and clinical importance

No presente artigo, os autores fazem uma revisäo da metodologia e da importância clínica de alguns novos métodos de análise da repolarizaçäo ventricular pelo eletrocardiograma de superfície ou utilizando a eletrocardiograma de superfície ou utilizando a eletrocardiografia dinâmica pelo sistema Holter. Incluem,no estudo, a análise da dispersäo temporal da repolarizaçäo ventricular, a variabilidade dos intervalos Qt e a alternância elétrica da onda T. Acentuam a importância e as limitaçöes desses métodos na estratificaçäo de risco arritmogênico em algumas cardiopatias e as perspectivas dos mesmos com os estudos em andamento que tentam desenvolver programas e algoritmos que permitam uma correta determinaçäo automática das variáveis envolvidas

Fibrilação e flutter atriais / Atrial fibrillation and flutter

No presente artigo os autores fazem uma breve revisão da clínica dos mecanismos eletrofisiológicos do Flutter e Fibrilação atriais. Procuram de forma sucinta fazer uma atualização terapêutica, uma vez que o grande avanço ocorrido na última década na área de eletrofisiologia clínica possibilitou não apenas um melhor conhecimento dos mecanismos das arritmias cardíacas e o mecanismo de ação das drogas antiarrítmicas, como também o tratamento não farmacológico das mesmas. Nesta revisão, os autores procuram abranger o tratamento farmacológico das arritmias, a indicação atual para a anticoagulação na prevenção dos fenômenos tromboembólicos e avaliar as indicaçöes atuais, sucessos e limitaçöes da terapia não farmacológica dos distúrbios do ritmo em questão.

[Significance of alcohol abstinence in alcoholic cardiomyopathy with moderate left ventricular dysfunction]. / O significado da abstinência do alcool na cardiomiopatia alcoólica com disfunção ventricular moderada.

PURPOSE: To evaluate the role of a 12 month alcohol abstinence period in patients with moderate left ventricular dysfunction treated with anticongestive therapy. METHODS: Prospective observational study with 20 patients with alcoholic cardiomyopathy (ACM), 9 (45%) in functional class (FC) II and 11 (55%) in FC III, 16 (80%) men, mostly black (55%), from 35 to 56 (x = 45) years old, heavy alcohol users (> 80 g ethanol for 51 to 112 (x = 88) months. At the beginning, all agreed to participate with psychotherapy and clinical evaluation. After 12 months, they were divided in G-I, formed by those who remained abstemious and G-II of non-abstemious. RESULTS: After 12 months, among the 11 (55%) who remained in psychotherapy, 8 were in G-I, among those who did not 9 (45%), only 2 (22.22%) remained abstemious (G-I). At the end of the evaluation period, both groups had the same number of patients. Comparing them, we observed: a) lower mean systolic and diastolic left ventricular diameters in G-I; b) more hospitalizations in G-II (3); c) more patients with stable or better clinical evaluation in G-I. CONCLUSION: Despite the initial will, only 50% reached abstinence. When it was reached, patients had a better evolution in left ventricular systolic diameter and abstinence should always be tried even in the presence of moderate left ventricular dysfunction.

[Evaluation of fragmented potentials in right bundle branch block without structural myocardium abnormalities. Study made by signal-averaged electrocardiogram on time and frequency domain]. / Avaliação de potenciais fragmentados em presença de bloqueio de ramo direito sem alterações estruturais miocárdicas ventriculares. Estudo pelo eletrocardiograma de alta resolução no domínio da freqüência.

PURPOSE: To evaluate if the presence of right bundle branch block (RBBB), without structural myocardial abnormalities (SMA) can generate fragmented potentials (FP) and spectral turbulence on signal-averaged electrocardiogram (SAECG). METHODS: Twelve children with atrial septal defect (ASD) and incomplete right bundle branch block (IRBBB without SMA (group I) were compared to 17 children with post-operative tetralogy of Fallot (TF) with CRBBB, all with SMA, 5 with ventricular premature beats and 2 with sustained ventricular tachycardia (group II). All had SAECG on time (TD) and frequency domain (FD) with 5 variables analysed. RESULTS: All patients of group I had normal variables, in contrast with group II which presented abnormal variables suggesting FP and ST. CONCLUSION: In ASD without SMA, the isolated IRBBB did not generate FP and ST.