RESUMEN
Tardive dyskinesia (TD) is associated with polymorphisms of the dopamine D(3), serotonin 2A and 2C receptors (DRD3, HTR2A and HTR2C, respectively). This study investigated the possible relationship between TD and the polymorphisms Ser9Gly (DRD3), 102T>C (HTR2A), -1438G>A(HTR2A) and Cys23Ser (HTR2C) in African-Caribbean inpatients. One hundred and twenty-six patients under chronic antipsychotic treatment were genotyped. The assessment of TD was carried out with the abnormal involuntary movement scale (AIMS). The relationships between the carriership of the least frequent alleles and the respective orofaciolingual dyskinesia (TDof) (sum of the items 1-4 of the AIMS), limb-truncal dyskinesia (TDlt) (sum of items 5-7 of the AIMS) and TD (sum of items 1-7 of the AIMS) were analyzed with ANCOVA, comparing means with age as a covariate and stratification for carriers and non-carriers of the mutations. In addition, we conducted pre-planned t-tests to compare AIMS values of carriers of the combinations of alleles versus the corresponding non-carriers. In the study population, females with 9Ser carriership exhibited higher AIMS values than non-carriers. Male subjects with 9Ser carriership in combination with 23Ser or -1438A carriership exhibited higher AIMS values. In male patients also, the combination of 23Ser and -1438A carriership increased TD. The study clearly shows that the African-Caribbean population differs from the Caucasian population with regard to the association of TD with the polymorphisms studied and suggests that the association of TD with the studied polymorphisms of the 5-HT(2C) and probably of the 5-HT(2A) receptor are the result of a changed susceptibility of the patients, independent of the action of the antipsychotics on these receptors.
Asunto(s)
Antipsicóticos/efectos adversos , Discinesia Inducida por Medicamentos/genética , Discinesia Inducida por Medicamentos/psicología , Receptor de Serotonina 5-HT2A/efectos de los fármacos , Receptor de Serotonina 5-HT2A/genética , Receptor de Serotonina 5-HT2C/efectos de los fármacos , Receptor de Serotonina 5-HT2C/genética , Receptores de Dopamina D3/efectos de los fármacos , Receptores de Dopamina D3/genética , Adulto , Anciano , Envejecimiento/fisiología , Alelos , Población Negra , ADN/genética , Femenino , Frecuencia de los Genes , Variación Genética , Genotipo , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Antillas Holandesas/epidemiologíaRESUMEN
In this study we used a new method to detect reactive oxygen species (ROS) induced damage at the level of the sperm plasma membrane in fresh and frozen-thawed stallion sperm. Lipid peroxidation (LPO) in sperm cells was assessed by a fluorescent assay involving the labeling of stallion sperm with the LPO reporter probe C11-BODIPY(581/591). The peroxidation dependent spectral emission shift of this membrane probe could be localized using inverted spectral confocal microscopy and quantified on living and deteriorated sperm cells using flow cytometry. Mass spectrometric analysis of the main endogenous lipid class, phosphatidylcholine (PC), was carried out to determine the formation of hydroxy- and hydroperoxyphosphatidylcholine in fresh sperm cells. Peroxidation as reported by the fluorescent probe corresponded with the presence of hydroxy- and hydroperoxyphosphatidylcholine in the sperm membranes, which are early stage products of LPO. This allowed us to correlate endogenous LPO with localization of this process in the living sperm cells. In absence of peroxidation inducers, only relatively little peroxidation was noted in fresh sperm cells whereas some mid-piece specific probe oxidation was noted for frozen-thawed sperm cells. After induction of peroxidation in fresh and frozen-thawed sperm cells with the 0.1 mM of lipid soluble ROS tert-butylhydrogen peroxide (t-BUT) intense probe oxidation was produced in the mid-piece, whereas the probe remained intact in the sperm head, demonstrating antioxidant activity in the head of fresh sperm cells. At higher levels of t-BUT, probe peroxidation was also noted for the sperm head followed by a loss of membranes there. Frozen-thawed sperm were more vulnerable to t-BUT than fresh sperm. The potential importance of the new assays for sperm assessments is discussed.