Cardiotoxicidade por cocaína e disfunção ventricular em paciente jovem

The use of psychoactive substances can induce cardiovascular complications. The purpose of this report is to describe the case of a young patient with dilated cardiomyopathy secondary to cocaine use. Patient with dyspnea for six months, with progressive worsening, paroxysmal nocturnal dyspnea, orthopnea, and lower limb edema. Physical examination showed tachycardia (110 bpm), with other vital signs without alterations, presence of crackling rales in the bases and middle fields, moderate volume ascites, and significant lower limb edema. Electrocardiogram showed sinus rhythm with left chamber overload; chest X-ray only marked cardiomegaly. The echocardiogram showed reduced left ventricular (LV) ejection fraction (7%), enlarged left atrium, and right ventricle (RV), with eccentric hypertrophy and severe left ventricular systolic dysfunction, with moderate RV dysfunction and pulmonary hypertension (39 mmHg). Resonance presented mild right atrial dilatation, RV with significant dilatation, significant biventricular systolic dysfunction, with diffuse hypokinesia, and myocardial fibrosis of non-coronary pattern. The reported case shows a diagnosis whose pathophysiological mechanism of dilated cardiomyopathy is not clear. The most coherent association of dilated cardiomyopathy presented by the patient is related to cocaine abuse, due to the long-term recurrent stimulus that excess catecholamines caused in the myocardium. Given the spectrum of cardiomyopathy, infarction, and arrhythmias that may potentially occur associated with cocaine use, the hypothesis of cardiotoxicity should be considered in the evaluation of a patient with a history of cocaine abuse.O uso de substâncias psicoativas pode induzir complicações cardiovasculares. O objetivo deste relato é descrever o caso de um paciente jovem com cardiomiopatia dilatada secundária ao uso de cocaína. Paciente com dispneia há seis meses, com piora progressiva, dispneia paroxística noturna, ortopneia e edema de membros inferiores. Ao exame físico apresentava taquicardia (110 bpm), com demais sinais vitais sem alterações, presença de estertores crepitantes em bases e campos médios, ascite de moderado volume e edema importante de membros inferiores. No eletrocardiograma, apresentava ritmo sinusal com sobrecarga de câmaras esquerdas; na radiografia de tórax, apenas cardiomegalia acentuada. O ecocardiograma evidenciou fração de ejeção (FE) do ventrículo esquerdo (VE) reduzida (7%), aumento de átrio esquerdo e ventrículo direito (VD), com hipertrofia excêntrica e disfunção sistólica acentuada do VE, com disfunção moderada do VD e hipertensão pulmonar (39 mmHg). Na ressonância, apresentou dilatação discreta do átrio direito, VD com dilatação importante, disfunção sistólica biventricular importante, com hipocinesia difusa (FE 8% de VD), além de fibrose miocárdica de padrão não coronariano inferosseptal. O caso relatado evidencia um diagnóstico cujo mecanismo fisiopatológico da cardiomiopatia dilatada não está claro. A associação mais coerente da cardiomiopatia dilatada apresentada pelo paciente está relacionada ao uso abusivo de cocaína, devido ao estímulo recorrente e de longa duração que o excesso de catecolaminas provocou no miocárdio. Tendo em vista o espectro de cardiomiopatia, infarto e arritmias que potencialmente podem ocorrer associados ao uso de cocaína, deve-se considerar a hipótese de cardiotoxicidade na avaliação de paciente com história de abuso de cocaína.  

Optostimulation of striatonigral terminals in substantia nigra induces dyskinesia that increases after L‐DOPA in a mouse model of Parkinson's disease

Background and Purpose: L-DOPA-induced dyskinesia (LID) remains a major complication of L-DOPA therapy in Parkinson's disease. LID is believed to result from inhibition of substantia nigra reticulata (SNr) neurons by GABAergic striatal projection neurons that become supersensitive to dopamine receptor stimulation after severe nigrostriatal degeneration. Here, we asked if stimulation of direct medium spiny neuron (dMSN) GABAergic terminals at the SNr can produce a full dyskinetic state similar to that induced by L-DOPA. Experimental Approach: Adult C57BL6 mice were lesioned with 6-hydroxydopamine in the medial forebrain bundle. Channel rhodopsin was expressed in striatonigral terminals by ipsilateral striatal injection of adeno-associated viral particles under the CaMKII promoter. Optic fibres were implanted on the ipsilateral SNr. Optical stimulation was performed before and 24 hr after three daily doses of L-DOPA at subthreshold and suprathreshold dyskinetic doses. We also examined the combined effect of light stimulation and an acute L-DOPA challenge. Key Results: Optostimulation of striatonigral terminals inhibited SNr neurons and induced all dyskinesia subtypes (optostimulation-induced dyskinesia [OID]) in 6-hydroxydopamine animals, but not in sham-lesioned animals. Additionally, chronic L-DOPA administration sensitised dyskinetic responses to striatonigral terminal optostimulation, as OIDs were more severe 24 hr after L-DOPA administration. Furthermore, L-DOPA combined with light stimulation did not result in higher dyskinesia scores than OID alone, suggesting that optostimulation has a masking effect on LID. Conclusion and Implications: This work suggests that striatonigral inhibition of basal ganglia output (SNr) is a decisive mechanism mediating LID and identifies the SNr as a target for managing LID.Fil: Keifman, Ettel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina. Consejo Superior de Investigaciones Científicas; EspañaFil: Ruiz De Diego, Irene. Consejo Superior de Investigaciones Científicas; EspañaFil: Pafundo, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Paz, Rodrigo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Solís, Oscar. Consejo Superior de Investigaciones Científicas; EspañaFil: Murer, Mario Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Moratalla, Rosario. Consejo Superior de Investigaciones Científicas; Españ

SHORT-TERM FORELIMB MOTOR CORTEX (FM1) PLASTICITY AFTER INACTIVATION OF THE CORRESPONDING CORTEX IN THE OPPOSITE HEMISPHERE

Aim: In the primary motor cortex (M1) of adult mammals, electrophysiological changes which are behind the interhemispheric diaschisis remain unclear. In the present study we aimed to demonstrate rapid changes in the M1 forelimb movement representation as the effect of inactivation of the homotopic cortical region. Methods: Five adult rats underwent three injections of Lidocaine (L-group) within the FM1 of one hemisphere (10μL delivered through a Hamilton syringe at a depth of 1mm from the pial surface). After injections, rats underwent intracortical microstimulation (ICMS) for M1 mapping in both hemispheres. Under ketamine anaesthesia (50mg\Kg i.p.), ICMS (30ms trains of 0.2ms cathodal pulses at 300Hz, stimulation current ≤ 60μA ) was delivered at a depth of 1.5mm from the pial surface using glass-insulated tungsten microelettrodes (impedance:0.6-1.2 ΩM). Other 5 rats were used as Sham-group and 5 rats were used as Control-group. Results: The cortical area that elicits forelimb movement was analyzed in the hemisphere contralateral to lidocaine injections. We observed significant increase in the forelimb area in the L-group as compared to Sham and Control- group (P<0.005, ANOVA). The forelimb area in L-group expanded in the medial direction overlapping the lateral portion of the vibrissa representation. In this part of M1, the ICMS evoked forelimb and vibrissa movement at the same current threshold. These dual movement sites increase significantly in L-group rats relative to Control and Sham- group of rats (P<0.001, ANOVA). Conclusions: Our results suggest that FM1 inactivation leads to shaping and size changes of forelimb movement representation in the contralateral hemisphere. We conclude that the loss of the inhibitory interhemispheric input induces the loss of the sharp border between vibrissa and forelimb representation

Suppression of activity in the forelimb motor cortex temporarily enlarges forelimb representation in the homotopic cortex in adult rats.

After forelimb motor cortex (FMC) damage, the unaffected homotopic motor cortex showed plastic changes. The present experiments were designed to clarify the electrophysiological nature of these interhemispheric effects. To this end the output reorganization of the forelimb motor cortex (FMC) was investigated after homotopic area activity was suppressed in adult rats. FMC output was compared after Lidocaine-induced inactivation (L group) or Quinolinic acid-induced lesion (Q-group) of the contralateral homotopic cortex. In the Q-group of animals, FMC mapping was performed, respectively, three days (Q3D group) and two weeks (Q2W group) after cortical lesion. In each animal, FMC output was assessed by mapping movements induced by intracortical microstimulation (ICMS) in both hemispheres (hemisphere Ipsilateral and Contralateral to injections). Findings demonstrated that in the L-group, the size of forelimb representation was 42.2% higher than in the Control group (P<0.0001). The percentage of dual forelimb-vibrissa movement sites significantly increased over the Controls (P<0.0005). The dual-movement sites occupied a strip of the map along the rostro-caudal border between the forelimb and vibrissa representation. This form of interhemispheric diaschisis had completely reversed, with the recovery of the baseline map, 3 days after the lesion in the contalatreral FMC. This restored forelimb map showed no ICMS-induced changes 2 weeks after the lesion in the contralateral FMC. The present results suggest that the FMCs in the two hemispheres interact continuously through predominantly inhibitory influences that preserve the forelimb representation and the border vs. vibrissa representation

The root locus approach to the analysis of zero-location procedures

The general two-term scattering-type recursive form (1) of the usual s-domain stability-test procedures is considered. The Hurwiti property of its right-hand side is studied with reference to suitable root loci. Along these lines, three interesting particular cases and the related locus shapes are analysed in order to motivate the structure of the left-hand side of the recurrence relation. Finally, mention is made of the corresponding z-domain relations and of the root locus associated with the two-term scattering-type form of the Bistritz algorithm

Identification of trigger factors in migraine and tensione-type headache: data from a retrospective and prospective study with two types of questionnaire.

none4noneMampreso E; Maggioni F; Viaro F; G. ZANCHINMampreso, E; Maggioni, Ferdinando; Viaro, F; Zanchin, Giorgi