Procesos de plasticidad sináptica en gyrus dentado hipocampal durante la administración crónica y el síndrome de abstinencia a cocaína. Synaptic plasticity in hippocampal dentate gyrus during chronic administration and withdrawal from cocaine.

Los procesos neuronales adaptativos que se observan como consecuencia de la administración crónica de drogas de abuso, son similares a los procesos plásticos que subyacen al aprendizaje y la memoria. Por otra parte, el hipocampo forma parte del circuito neuronal responsable de los cambios conductuales observados como consecuencia de la administración crónica de diferentes drogas de abuso. De acuerdo con esto, resultados previos de nuestro laboratorio demostraron que la plasticidad sináptica en el hipocampo y las claves contextuales relacionadas con la administración de la droga, son relevantes para el incremento de la plasticidad hipocampal por la administración crónica de diazepam. Específicamente en el gyrus dentado hipocampal se han descripto fenómenos plásticos relacionados con la exposición crónica a psicofármacos, tales como facilitación en la transmisión sináptica, disminución de la proliferación celular y el aumento del factor de transcripción ?Fos B. Debido a la correlación existente entre los mecanismos de plasticidad neuronal, los aprendizaje asociativos y formación de memorias y aquellos responsables de la adicción, el objetivo general de este trabajo es caracterizar los cambios inducidos por la exposición repetida de cocaína y durante el periodo de abstinencia, en la excitabilidad neuronal de las células del gyrus dentado hipocampal, los canales iónicos afectados y los posibles mecanismos bioquímicos involucrados en dichos cambios, que podrían explicar las alteraciones conductuales observadas después de dicho tratamiento. Con este propósito, se estudiará: 1) la plasticidad sináptica (potenciación a largo plazo, LTP y depotenciación a largo plazo, LTD) en el gyrus dentado, mediante registros electrofisiológios multiunitarios; 2)la excitabilidad de las células granulares del gyrus dentado y la actividad de los canales iónicos, utilizando la técnica de patch clamp; 3) las alteraciones en la neurotransmisión glutamatergica, midiendo los niveles del neurotransmisor in vivo, utilizando la técnica de microdiálisis; el tráfico de receptores glutamatérgicos, utilizando la técnica de western-blott, 4) la participación del óxido nítrico en los cambios adaptativos observados como consecuencia de la sensibilización a cocaína. Además, mediante la utilización de técnicas comportamentales (avoidance inhibitorio), se estudiarán las posibles alteraciones de conductas que se sabe dependen de la integridad funcional del hipocampo.En relación a los resultados del presente proyecto se espera obtener un incremento en la plasticidad sináptica, en la excitabilidad neuronal de las células granulares del gyrus dentado de la formación hipocámpica, en la liberación extracelular de glutamato in vivo, como así también en el tráfico de receptores glutamatérgicos. Además se espera obtener un aumento de las vías de señalización activadas por la acción de glutamato, como la de óxido nítrico/GMPc, como consecuencia de la administración crónica de cocaína. Con este aumento global de la plasticidad sináptica hipocampal, las conductas dependientes de esta estructura debieran estar facilitadas, demostrando así una participación activa del hipocampo en los procesos de sensibilización y posiblemente en la adicción a psicoestimulantes. La caracterización del impacto del desarrollo de sensibilización a cocaína en la excitabilidad neuronal en el hipocampo, sobre los sistemas de neurotransmisión y las vías de señalización involucradas contribuirían a dilucidar los mecanismos que contribuyen al desarrollo de sensibilización a cocaína, los cuales podrían representar potenciales blancos terapéuticos para el tratamiento de la adicción, considerando principalmente aspectos específicos de la actividad eléctrica neuronal y la plasticidad sináptica asociada con las diferentes fases del ciclo de la adicción.

Effects of Yoga in Patients with Chronic Heart Failure: A Meta-Analysis

The use of yoga as an effective cardiac rehabilitation in patients with chronic heart failure (CHF) remains controversial. We performed a meta-analysis to examine the effects of yoga on exercise capacity and health-related quality of life (HRQOL) in patients with CHF. Methods: We searched MEDLINE, Cochrane Central Register of Controlled Trials, Excerpta Medica database, LILACS, Physiotherapy Evidence Database, The Scientific Electronic Library Online, and Cumulative Index to Nursing and Allied Health (from the earliest date available to December 2013) for randomized controlled trials (RCTs) examining the effects of yoga versus exercise and/or of yoga versus control on exercise capacity (peakVO2) and quality-of-life (HRQOL) in CHF. Two reviewers selected studies independently. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated, and heterogeneity was assessed using the I2 test. Two studies met the selection criteria (total: 30 yoga and 29 control patients). The results suggested that yoga compared with control had a positive impact on peak VO2 and HRQOL. Peak VO2, WMD (3.87 95% CI: 1.95 to 5.80), and global HRQOL standardized mean differences (-12.46 95% CI: -22.49 to -2.43) improved in the yoga group compared to the control group. Yoga enhances peak VO2 and HRQOL in patients with CHF and could be considered for inclusion in cardiac rehabilitation programs. Larger RCTs are required to further investigate the effects of yoga in patients with CHF.

Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)

Left Atrial Function in Patients with Chronic Chagasic Cardiomyopathy

Background:Chagas disease is a cause of dilated cardiomyopathy, and information about left atrial (LA) function in this disease still lacks.Objective:To assess the different LA functions (reservoir, conduit and pump functions) and their correlation with the echocardiographic parameters of left ventricular (LV) systolic and diastolic functions.Methods:10 control subjects (CG), and patients with Chagas disease as follows: 26 with the indeterminate form (GI); 30 with ECG alterations (GII); and 19 with LV dysfunction (GIII). All patients underwent M-mode and two-dimensional echocardiography, pulsed-wave Doppler and tissue Doppler imaging.Results:Reservoir function (Total Emptying Fraction: TEF): (p <0.0001), lower in GIII as compared to CG (p = 0.003), GI (p <0.001) and GII (p <0.001). Conduit function (Passive Emptying Fraction: PEF): (p = 0.004), lower in GIII (GIII and CG, p = 0.06; GI and GII, p = 0.06; and GII and GIII, p = 0.07). Pump function (Active Emptying Fraction: AEF): (p = 0.0001), lower in GIII as compared to CG (p = 0.05), GI (p<0.0001) and GII (p = 0.002). There was a negative correlation of E/e’average with the reservoir and pump functions (TEF and AEF), and a positive correlation of e’average with s’ wave (both septal and lateral walls) and the reservoir, conduit and pump LA functions.Conclusion:An impairment of LA functions in Chagas cardiomyopathy was observed.

Human Tissue Kallikrein Activity in Angiographically Documented Chronic Stable Coronary Artery Disease

AbstractBackground:Human tissue kallikrein (hK1) is a key enzyme in the kallikrein–kinin system (KKS). hK1-specific amidase activity is reduced in urine samples from hypertensive and heart failure (HF) patients. The pathophysiologic role of hK1 in coronary artery disease (CAD) remains unclear.Objective:To evaluate hK1-specific amidase activity in the urine of CAD patientsMethods:Sixty-five individuals (18–75 years) who underwent cardiac catheterism (CATH) were included. Random midstream urine samples were collected immediately before CATH. Patients were classified in two groups according to the presence of coronary lesions: CAD (43 patients) and non-CAD (22 patients). hK1 amidase activity was estimated using the chromogenic substrate D-Val-Leu-Arg-Nan. Creatinine was determined using Jaffé’s method. Urinary hK1-specific amidase activity was expressed as µM/(min · mg creatinine) to correct for differences in urine flow rates.Results:Urinary hK1-specific amidase activity levels were similar between CAD [0.146 µM/(min ·mg creatinine)] and non-CAD [0.189 µM/(min . mg creatinine)] patients (p = 0.803) and remained similar to values previously reported for hypertensive patients [0.210 µM/(min . mg creatinine)] and HF patients [0.104 µM/(min . mg creatinine)]. CAD severity and hypertension were not observed to significantly affect urinary hK1-specific amidase activity.Conclusion:CAD patients had low levels of urinary hK1-specific amidase activity, suggesting that renal KKS activity may be reduced in patients with this disease.

Assessment of Galectin-3 Polymorphism in Subjects with Chronic Chagas Disease

AbstractBackground:Galectin-3, a β-galactoside binding lectin, has been described as a mediator of cardiac fibrosis in experimental studies and as a risk factor associated with cardiovascular events in subjects with heart failure. Previous studies have evaluated the genetic susceptibility to Chagas disease in humans, including the polymorphisms of cytokine genes, demonstrating correlations between the genetic polymorphism and cardiomyopathy development in the chronic phase. However, the relationship between the galectin-3 single nucleotide polymorphism (SNP) and phenotypic variations in Chagas disease has not been evaluated.Objective:The present study aimed to determine whether genetic polymorphisms of galectin-3 may predispose to the development of cardiac forms of Chagas disease.Methods:Fifty-five subjects with Chagas disease were enrolled in this observational study. Real-time polymerase chain reaction (PCR) was used for genotyping the variants rs4644 and rs4652 of the galectin-3 gene.Results:For the SNP rs4644, the relative risk for the cardiac form was not associated with the genotypes AA (OR = 0.79, p = 0.759), AC (OR = 4.38, p = 0.058), or CC (OR = 0.39, p = 0.127). Similarly, for the SNP rs4652, no association was found between the genotypes AA (OR = 0.64, p = 0.571), AC (OR = 2.85, p = 0.105), or CC (OR = 0.49, p = 0.227) and the cardiac form of the disease.Conclusion:Our results showed no association between the different genotypes for both SNPs of the galectin-3 gene and the cardiac form of Chagas disease. (Arq Bras Cardiol. 2015; [online].ahead print, PP.0-0)

Alternatives to Aerobic Exercise Prescription in Patients with Chronic Heart Failure

Background: Exercise is essential for patients with heart failure as it leads to a reduction in morbidity and mortality as well as improved functional capacity and oxygen uptake (v̇O2). However, the need for an experienced physiologist and the cost of the exam may render the cardiopulmonary exercise test (CPET) unfeasible. Thus, the six-minute walk test (6MWT) and step test (ST) may be alternatives for exercise prescription. Objective: The aim was to correlate heart rate (HR) during the 6MWT and ST with HR at the anaerobic threshold (HRAT) and peak HR (HRP) obtained on the CPET. Methods: Eighty-three patients (58 ± 11 years) with heart failure (NYHA class II) were included and all subjects had optimized medication for at least 3 months. Evaluations involved CPET (v̇O2, HRAT, HRP), 6MWT (HR6MWT) and ST (HRST). Results: The participants exhibited severe ventricular dysfunction (ejection fraction: 31 ± 7%) and low peak v̇O2 (15.2 ± 3.1 mL.kg-1.min-1). HRP (113 ± 19 bpm) was higher than HRAT (92 ± 14 bpm; p < 0.05) and HR6MWT (94 ± 13 bpm; p < 0.05). No significant difference was found between HRP and HRST. Moreover, a strong correlation was found between HRAT and HR6MWT (r = 0.81; p < 0.0001), and between HRP and HRST (r = 0.89; p < 0.0001). Conclusion: These findings suggest that, in the absence of CPET, exercise prescription can be performed by use of 6MWT and ST, based on HR6MWT and HRST

Carlos Chagas Discoveries as a Drop Back to Scientific Construction of Chronic Chagas Heart Disease

Abstract The scientific construction of chronic Chagas heart disease (CCHD) started in 1910 when Carlos Chagas highlighted the presence of cardiac arrhythmia during physical examination of patients with chronic Chagas disease, and described a case of heart failure associated with myocardial inflammation and nests of parasites at autopsy. He described sudden cardiac death associated with arrhythmias in 1911, and its association with complete AV block detected by Jacquet's polygraph as Chagas reported in 1912. Chagas showed the presence of myocardial fibrosis underlying the clinical picture of CCHD in 1916, he presented a full characterization of the clinical aspects of CCHD in 1922. In 1928, Chagas detected fibrosis of the conductive system, and pointed out the presence of marked cardiomegaly at the chest X-Ray associated with minimal symptomatology. The use of serological reaction to diagnose CCHD was put into clinical practice in 1936, after Chagas' death, which along with the 12-lead ECG, revealed the epidemiological importance of CCHD in 1945. In 1953, the long period between initial infection and appearance of CCHD was established, whereas the annual incidence of CCHD from patients with the indeterminate form of the disease was established in 1956. The use of heart catheterization in 1965, exercise stress testing in 1973, Holter monitoring in 1975, Electrophysiologic testing in 1973, echocardiography in 1975, endomyocardial biopsy in 1981, and Magnetic Resonance Imaging in 1995, added to the fundamental clinical aspects of CCHD as described by Carlos Chagas.

"Eczema in psoriatico" : closing the gap between palmoplantar psoriasis and palmoplantar chronic contact dermatitis : a clinical, histological and immunohistological study

Magdeburg, Univ., Med. Fak., Diss., 2014

Neuronal alterations in chronic cerebral Toxoplasma gondii infection

Magdeburg, Univ., Fak. für Naturwiss., Diss., 2015

Investigações sobre doenças de Psittacideos

The present paper colligates the notions acquired in previous investigations, already published, and new observations upon diseases of the psittacidae, liable to be confused with psittacosis of parrots. The author calls attention to the indifference with regard to this question shown by investigators, even by those who dealt with the study of this disease on the occasion of the latest outbreak of psittacosis, in flagrant contrast with the researches upon the alterations induced by pathogenic agents of other diseases transmissible to man, when these agents pass through animals or when the latter are depositaries of the virus. This remark considerably enhances the importance of the presence paper from a hygienic and epidemiologic point of view, representing moreover a contribution to general knowledge and to veterinary medicine. The researches carried out since the appearance of the latest outbreak of psittacosis,-which occurred simultaneously with an epizooty in parrots lodged in aviary of the park of Agua Branca (Directory of Animal Industry of the State São Paulo)-led to the verification of the frequent existence in these animals of various diseases liable to be confused with psittacosis. These diseases are due to two kinds of pathogenic agents: virus and bacteria. In the first group there are to be found the diseases occasioned by the virus of human psittacosis, discovered by Western, Bedson and Simpson, and the disease me with in parrots coming from traders in S. Paulo. The infections by bacteria of the genus Salmonella and by those of other genera belong to the second group. As differential characters of the two infections due to virus, delineated on the strength of notions drawn from a detailed experimental study and from the literature on this subject, the following are given: ¹ Samples of our virus were sent, for comparison, to various investigators of psittacosis. Amongst them, Prof. M. Rivers acceded to our request; he found its nature to be different from that of the virus of psittacosis studiedby him. We are very much obliged to him for the attention he paid to this verification. Virus of psittacosis - Infectiousness: man, monkey, rabbit, mouse, hen, canary. Neurotropic affinity. Inclusions: small, protoplasmic. Exsiccation: the virus has good power of preservation. Symptoms: inactivity, drowsiness, frequent diarrhoea, oculo-nasal discharge and cough, coma. Duration: 4 to 5 days. Bodily lesions: congestion of intestines, splenomegaly. Virus of S. Paulo - Infects only psittacidae, particularly those of the genus Amazona. No localization in the nervous system. Large, nuclear. Is rapidly destroyed. Inactivity, inappetency, adynamia (drooping of the wings, indifference, leaning its beak against the bars of the cage in order not to fall down); profuse diarrhoea, of whitish stools, at times enterorrhagia; prolonged coma. 2 to 8 days. Foci of yellowish necrosis in liver, spleen and lung. At times, congestion of intestines. Characteristic features common to the two viruses.-They act in great dilutions, filter through tight candles though being partly retained, are preserved under glycerine or Bedson's solution, are stable at 55°C. heat and are destroyed by physical and chemical agents. Both virus diseases are very seldom met with in psittacidae: only once, amongst numberless sick parrots, the author met with a disease of the virus differring from that of psittacosis. This disease, greatly transmissible to man, ought to be more frequent, if it were common in parrots. On the contrary, bacteria cause diseases in these animals with great frequency, presenting variable characters, from a severe epizootic form, rapidly mortal, to ambulatory or silent forms, for the most part developing towards a cure or assuming a chronic character. Amongst the bacteria which cause the infection of this group the salmonellae predominate and amongst them the bacterium discovered by Nocard, as well as a species which in the course of this study is characterized under the name of Salmonella nocardi. The author believes that in the epizooty from which Nocard isolated his bacterium there was association of the virus-disease inducing the epizooty of that epoch in Paris with the bacterial disease, as must have happened in Argentina, where the disease was transmitted to man, and Santillan, according to Barros, isolated from the sick parrots bacteria of the genus Salmonella. The diseases of the two groups, that due to virus and that due to bacteria, are differentiated: Virus-diseases - Evolution: rapid, nearly always followed by death. Symptoms: sadness, profuse diarrhoea, of whitish stools, at times enterorrhagia, complete inappetency, adynamia, indifference, prolonged coma. Clinical forms: acute and subacute. Lesions: Foci of necrosis in liver and spleen without cellular reaction around the focus, yellow liver, multiple serositis. Presence of protoplasmic or nuclear granulations. Bacteriology: Complete lack or inconstant presence of bacteria in the organs and blood. Infectiousness of the organs and blood after filtration: positive. Bacterial diseases - Varies from one week to a month or more, not always fatal. Sadness, partial inappetency, tremblings, intensive thirst, mucous or mucosanguineous diarrhoea, lack of adynamia (reacts to stimulations and moves well at any time of the disease, though showing little disposition to locomotion), soiling of feathers. Frustrate, acute, subacute and chronic. Hepatic and intestinal cogestion, foci of necrosis in liver, spleen and lung with cellular reaction around the focus. Lack of granulations. Constant presence of bacteria in the organs and blood. Negative. The analysis of the litterature shows that the characteristic features of the diseases in parrots referred to parrot psittacosis, more frequently approach the bacterial diseases here described of these animals, a hypothesis which is reinforced by the observation of the greater frequency of infections...