ABSTRACT
Introduction: Impulsiveness and aggressiveness are characteristics of borderline personality disorders. Aggressive and impulsive behaviors are associated to a serotoninergic system dysfunction and are treated with selective serotonin reuptake inhibitors (SSRJs). The short (S) allele of the serotonin transporter promoter (5-HTTPR) gene is associated to a worse response to SSRI in major depression. The objective of this work is to study the anti-impulsive effect of fluoxetine and his relation with short and long alleles of 5-HTTPR gene in borderline personality disordered patients. Method: 59 patients with DSM-IV borderline personality disorder were treated with fluoxetine for 12 weeks. Impulsivity was evaluated with the Overt Aggression Scale Modified (OAS-M). Polymorphisms L and S of the 5-HTTPR gene were determined. Results: S carriers (LS and SS) had a significantly minor response on OAS-M and Aggression subscale than LL carriers. Conclusions: S allele of the 5-HTTPR gene predicts poor response to anti-impulsive effect of fluoxetine in borderline personality disorder. It is likely that multiple genes contribute to a SSRI response.
Introducción: Los trastornos límite de personalidad se caracterizan por una elevada impulsividad y agresividad. Las conductas agresivas e impulsivas se han asociado a disfunciones del sistema serotoninérgico y responden a los inhibidores de la recaptura de serotonina (ISRS). En depresión mayor el alelo corto (S) del promotor del gene del transportador de serotonina se asocia a pobre respuesta a los ISRS. El objetivo de este trabajo es estudiar el efecto anti-impulsivo de serotonina y su relación con los alelos LyS en pacientes con trastorno límite de personalidad. Método: 59 pacientes con trastorno límite de personalidad fueron tratados por 12 semanas confluoxetina. Se evaluó la impulsividad mediante la Overt Aggression Scale Modified (OAS-M)y se determinó los polimorfismos LyS. Resultados: Los portadores de S (LS y SS) presentaron una menor reducción en la OAS-M total y en la subescala de agresividad que los homocigotos LL. Conclusiones: En trastorno límite de personalidad el alelo S del promotor del gene del transportador de serotonina predice pobre respuesta anti-impulsiva de la fluoxetina. Probablemente múltiples genes participen en la respuesta a los ISRS.
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Antidepressive Agents, Second-Generation/therapeutic use , Fluoxetine/therapeutic use , Polymorphism, Genetic , Borderline Personality Disorder/genetics , Borderline Personality Disorder/drug therapy , Aggression , Impulsive Behavior/psychology , Selective Serotonin Reuptake Inhibitors/therapeutic use , Pharmacogenetics , Promoter Regions, Genetic , Psychiatric Status Rating Scales , Serotonin Plasma Membrane Transport Proteins , Borderline Personality Disorder/psychologyABSTRACT
A partir del año 2000 la Universidad de Chile desarrolla el Programa de Doctorado en Ciencias Médicas y Especialidad, cuyo objetivo es formar un médico especialista y doctor en Ciencias Médicas competente para realizar investigación clínica del más alto nivel, integrando conocimientos y metodologías del área de las ciencias básicas con aquellas de las ciencias clínicas. El año 2002 se abrió por primera vez la posibilidad de desarrollar simultáneamente la formación como especialista en Psiquiatría de Adultos y como Doctor en Ciencias Médicas. Dados los espectaculares avances de la Neurociencia a nivel mundial, los cuales se habían traducido en importantes progresos en el diagnóstico y tratamiento de los enfermos mentales, parecía lógico invertir recursos orientados hacia el fortalecimiento del diálogo entre los médicos clínicos y los científicos básicos en el país. En el marco de este programa se desarrolló la tesis de doctorado cuyo resumen se presenta a continuación, la cual representa la unión de esfuerzos de profesionales y estudiantes de la Unidad de Trastornos de la Personalidad de la Clínica Psiquiátrica Universitaria y de los Programas de Genética Humana y de Biología Celular y Molecular del Instituto de Ciencias Biomédicas de la Facultad de Medicina de la Universidad de Chile.
Since 2000, University of Chile develops the Doctorate in Medical Sciences Program which is associated to a medical specialty. Its objective is to prepare a specialist MD and PhD capable of developing high quality clinical research, by integrating knowledge and methodologies of basic and clinical sciences. On 2002 the Program considered for the first time Psychiatry as the associated specialty. Given the spectacular progress of Neurosciences around the world, which have determined significant changes in the diagnosis and treatment of mental disorders, it seemed rational to invest resources destined to strengthen the dialog between clinical and basic scientists in Chile. The doctoral thesis that is hereby presented as a summary was developed in the context of this program. It was made possible by the joint efforts of professionals and students of the Personality Disorders Unit of the University Psychiatric Clinic and of the Programs of Human Genetics and of Cell and Molecular Biology of the Biomedical Sciences Institute of the Faculty of Medicine of University of Chile.
Subject(s)
Humans , Male , Female , Polymorphism, Genetic , Borderline Personality Disorder/geneticsABSTRACT
Genetic studies on depression have focused on the polimorphisms of the serotonin system genes. It has been investigated the tryptophan hydroxylase and the serotonin receptor genes, specifically the serotonin transporter. Two alleles of the promoter for the serotonin transporter gene have been described: a long allele (L) and a short allele (S). Studies suggest that the presence of the short allele (S) is associated to a higher vulnerability for depression in the presence of adverse environmental factors. By the other hand, the presence of the long allele (L) gives resilience for stressful situations. It is believed that the acquisition of higher vulnerability for stress must occur during early stages of neurodevelopment.
Los estudios genéticos en depresión se han enfocado especialmente en los polimorfismos de los genes asociados al sistema serotoninérgico. Se han investigado los genes de la triptofano hidroxilasa, de algunos receptores de serotonina y particularmente del transportador de serotonina. Se han descrito dos alelos en la región promotora del transportador de serotonina: uno largo (L) y otro corto (S). Los estudios sugieren que la presencia del alelo corto (S) se asocia a una mayor vulnerabilidad a la depresión en presencia de factores ambientales adversos. A la inversa, la presencia del alelo largo (L) parece conferir resiliencia frente a las situaciones de estrés. Se cree que la adquisición de la mayor vulnerabilidad al estrés debe ocurrir en etapas tempranas del neurodesarrollo.
Subject(s)
Humans , Depression/genetics , Polymorphism, Genetic , Dopamine Plasma Membrane Transport ProteinsABSTRACT
Background: International studies show a low compliance with norms for the management of cardiovascular risk factors. Aim: To assess the prevalence of risk factors in patients admitted for a coronary or vascular event and to evaluate the proportion of patients that normalize these factors after one year of follow up. Material and Methods: Three hundred and fifty seven patients aged 64±13 years (264 males), admitted to a University Clinical Hospital for a coronary or vascular event were studied. They were educated about cardiovascular risk factors and followed by their treating physicians for a mean of 11.9±2 months. During this period, smoking habits, body mass index. blood pressure, serum lipid levels, blood glucose and the appearance of new cardiovascular events were registered. Results: One year survival was 96% (all 13 deaths were of cardiac origin). Eighty seven percent of patients were free of major cardiovascular events. At discharge from hospital and at the end of follow up 49% and 44% had a total cholesterol over 200 mg/dl respectively, 9,6% and 20,8% had systolic pressure over 140 mmHg. There was no diastolic hypertension in these patients, 27% and 31% had a body mass index over 25 kg/m2 and 2% smoked (versus 32% before the event). Conclusions: After one year of follow up, the prevalence of risk factors in patients that had suffered a cardiovascular event, continues to be high.
Subject(s)
Adolescent , Adult , Animals , Child , Female , Humans , Male , Middle Aged , Antiprotozoal Agents/therapeutic use , Chagas Disease , Electrocardiography , Trypanosoma cruzi/drug effects , Allopurinol/therapeutic use , Chagas Disease/diagnosis , Chagas Disease/drug therapy , Chagas Disease/parasitology , Follow-Up Studies , Itraconazole/therapeutic use , Polymerase Chain Reaction , Retrospective Studies , Treatment Outcome , XenodiagnosisABSTRACT
Background:The great variability in the clinical presentation of Chagas disease may depend in part in the genetic variability of Trypanosoma cruzi populations. Aim: To compare prepatent period, parasitemia, mortality and histological lesions in mice infected with two populations of Trypanosoma cruzi isolated in Chile. Material and methods: Two Trypanosoma cruzi populations, isolated from Chilean Triatomides and genetically characterized by kinetoplast restriction fragment DNA profiles, were compared. Two groups of 40 Balb/c mice were studied. Each mouse was inoculated with 104 trypomastigotes, of the V-121 and sp COMB 2 Trypanosoma cruzi populations. The prepatent period, parasitemia, mortality and histopathological lesions, at different evolutionary stages of infection were registered during 32 days. Results: Prepatency and mortality were similar in both groups of mice. However, parasitemia was significantly greater in mice inoculated with V-121 than those inoculated with sp COMB 2. Amastigote pseudocysts and inflammation were present only in skeletal muscle and myocardium in both groups of mice. The intensity of tissue involvement was associated to the level of parasitemia, therefore it was greater in mice inoculated with V-121 population. Conclusions: V-121 population of Trypanosoma cruzi caused a greater parasitemia than COMB 2, in inoculated mice.
Subject(s)
Animals , Mice , Chagas Disease/mortality , Chagas Disease/parasitology , Chagas Disease/pathology , Trypanosoma cruzi/isolation & purification , Trypanosoma cruzi/growth & development , Chile , Disease Models, AnimalABSTRACT
Trypanosoma cruzi from 23 chronic and acute cases of Chagas dosease were isolated and further characterized. They displayed a remarkable similarity, after typification by schizodeme analysis using restriction endonuclease Eco Ri. All trypanosoma cruzi isolates belonged to the isoenzymatic Zymodeme 2 Bol. These findings were corroborated analyzing cases from families with demonstrated congenital transmission. The acute cases were newborns or offspring of infected mothers or patients with AIDS. All trypanosoma cruzi strains isolated in theses cases were very similar with almost identical schizodemes. Patients with AIDS had severe clinical manifestations whereas children with congenital infections had a great variety of clinical symptoms. In chronic cases, little clinical differences were observated for the different trypanosoma cruzi strains. It is concluded that there is a low correlation between the trypanosoma cruzi strain and the clinical prognosis of Chagas disease, being of greater relevance the host's genetic background and inmune response
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Adolescent , Adult , Trypanosoma cruzi/genetics , Chagas Disease/epidemiology , Trypanosoma cruzi/isolation & purification , Trypanosoma cruzi/pathogenicity , Chagas Disease/congenital , Chronic Disease , Nucleic Acid Hybridization/methodsABSTRACT
705 inhabitants of rural towns in northern Chile were surveyed to study chagasic infection and cardiac involvement. Clinical evaluation, electrocardiogram, indirect hemagglutination test and senodiagnosis for reactores were employed. culture of positive xendoiagnsis was done to identify different zymodemes and schizodemes of T cruzi, T spinolai was not found in this area implying the absence of a wild cycle. Triotomines were not found over 3000 m high. Four cases of Z2b T. cruzi strains were found. Simultaneous infection by Z1 and Z2b strains was found in the same bug obtained from houses. Overall human infection rate was 10%, and 69% of then showed altered electrocardiograms. Therefore, a lower infection rate but greater evidence of cardiac involvement is found in northern Chile compared to other areas in the country