Influence of glutathione-related genetic variants on the oxidative stress profile of Mexican patients with psychotic disorders

Objective: The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. Methods: The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. Results: GSH levels were significantly reduced and, conversely, GPx activity was higher among patients than controls. GCLC_GAG-7/9 genotype (OR = 4.3, 95%CI = 1.40-14.31, p = 0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR = 6.09, 95%CI = 1.93-22.59, p = 0.003) were found to be risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or metabolic ratio. Conclusions: GCLC variants were associated with the oxidative stress profile of patients with psychotic disorders, raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.

Intoxicación por plomo y nivel de marginación en recién nacidos de Morelos, México / Lead poisoning and marginalization in newborns of Morelos, Mexico

Resumen: Objetivo: Determinar la prevalencia de intoxicación por plomo (IPb) al nacimiento en Morelos, analizar su distribución por nivel de marginación y estimar la asociación con el uso de barro vidriado (BV). Material y métodos: Se midió plomo en sangre (PbS) en cordón umbilical de una muestra representativa de 300 nacimientos seleccionados aleatoriamente de aquéllos atendidos por los Servicios de Salud de Morelos e IMSS estatal. Resultados: La prevalencia de IPb al nacimiento (PbS>5µg/dL) fue 14.7% (IC95%: 11.1, 19.3), y 22.2% (IC95%: 14.4, 32.5) en los municipios más marginados. 57.1% (IC95%: 51.3, 62.7) de las madres usaron BV durante el embarazo y la frecuencia de uso se asoció significativamente con PbS. Conclusión: Este es el primer estudio que documenta la proporción de recién nacidos con IPb que están en riesgo de sufrir los consecuentes efectos adversos. Se recomienda monitorear PbS al nacimiento y emprender acciones para reducir esta exposición, especialmente en poblaciones marginadas.

Abstract: Objective: To determine the prevalence of lead (Pb) poisoning at birth in Morelos, analyze its distribution by social marginalization level, and estimate the association with the use of lead glazed ceramics (LGC). Materials and methods: Blood lead level (BLL) in umbilical cord was measured in a representative sample of 300 randomly selected births at the Morelos Health Services and state IMSS. Results: The prevalence of Pb poisoning at birth (BLL> 5μg/dL) was 14.7% (95%CI: 11.1, 19.3) and 22.2% (95%CI: 14.4, 32.5) in the most socially marginalized municipalities. 57.1% (95%CI: 51.3, 62.7) of the mothers used LGC during pregnancy, and the frequency of use was significantly associated with BLL. Conclusion: This is the first study to document the proportion of newborns with Pb poisoning who are at risk of experiencing the related adverse effects. It is recommended to monitor BLL at birth and take action to reduce this exposure, especially in socially marginalized populations.

Concentraciones de mercurio total en sangre y cabello por ingesta de pescado en niños, mujeres embarazadas y en edad reproductiva residentes de los municipios aledaños al lago de Chapala, Jalisco - México / Concentrations of total mercury in blood and hair and fish intake in children, residents of the municipalities bordering to the Chapala lake, Mexico

Environmental pollution (water, sediment and fish) poses serious threats to the Chapala lake, Mexico. We seek to identify the concentrations of totalMercury (Hg) in children, pregnant women and in reproductive age from the communities around the lake. We will use blood samples and hair samples as biomarkers. Exposure will be assessed by dietary habits (quantity, frequency, species and type of fish consumed).Taking in consideration that some groups may be more susceptible to Mercury (Hg). In particular, the fetus, newborn babies and infants are at high risk because their nervous system is particularly delicate. Exposure to Hg during pregnancy can affect the neuronal connection and the mielinization of the nervous system, which may result in reduced number of cells neurons " in active" at the end of life. Very limited data exists in Mexico, protection measures are difficult to support without reliable information (e.g., possible damage from fish consumption). Therefore, this investigation seeks to generate hypothesis (cross sectional study) regarding the concentrations of Hg inside the organism soon after the fish consumption. We will evaluate the possible health risk e.g., children'sneurological damages, pregnant women and those in reproductive age.

Caracterización clínica de 450 pacientes con enfermedad cerebrovascular ingresados a un hospital público durante 1997 / Retrospective analysis of 450 patients with cerebrovascular disease admitted to a public hospital during 1997

Background: In Chile, cerebrovascular diseases are the fifth cause of death among men and the third cause among women. Aim: To assess the clinical features and management of patients with cerebrovascular disease admitted to a public hospital during 1997. Patients and methods: A retrospective analysis of clinical records of patients discharged with a diagnosis of cerebrovascular disease. Those records in which there was discordance between the discharge diagnosis and the clinical picture were not considered in the analysis. Results: Of the 563 discharges from the hospital with the diagnosis of cerebrovascular disease, 487 records were located and 450 were considered in the analysis. Fifty four percent of patients were male and ages ranged from 17 to 96 years old...

Eliminación del plomo por curado casero / Lead elimination by traditional acidic curing

Objetivo. Evaluar el curado ácido como medida preventiva para reducir el contenido de plomo en vasijas de barro vidriadas. Material y métodos. En 27 vasijas de barro procedentes de cuatro estados de México se determinó, mediante espectrofotometría de absorción atómica, el nivel de plomo residual, después de cuatro lavados con ácido acético al 3 por ciento. Resultados. El contenido de plomo en el ácido acético utilizado para lavar las vasijas disminuyó proporcionalmente con el número de lavados, aunque se conservo por arriba de los niveles permisibles (2.5-7.0 p.p.m.). Conclusiones. El curado ácido de piezas de barro no es una medida preventiva útil para reducir la exposición a plomo

Changes in transition metal contents in rat brain regions after in vivo quinolinate intrastriatal administration

Total copper and manganese contents were measured in five rat brain regions 7 days after a unilateral striatal injection of quinolinic acid (QUIN, 240 nmol/1µl), an endogenous N-methyl-D-aspartate (NMDA) receptor agonist. Concentrations of both transition metals were evaluated in tissue of brain cortex, hippocampus, corpus striatum, midbrain and cerebellum of saline- and QUIN-treated rats using graphite furnace atomic absorption spectrophotometry. Increases in copper content were observad after QUIN striatal injection in cerebellum, hippocampus, midbrain and corpus striatum (37, 55, 71 and 152 percent as compared against control values, respectively) but not in brain cortex. Manganese levels were found enhanced only in corpus striatum of QUIN-treated rats by 35 percent vs. control values, but not in all other brain regions analyzed. QUIN-induced increases in regional copper content were partially prevented in hippocampus, midbrain and striatum (17, 57, and 23 percent vs. control, respectively) by pretreatment of rats with an NMDA receptor antagonist, dizocilpine (MK-801, 10 mg/kg, i.p.), administered 60 min before QUIN microinjection. The same protective effect of fizocilpine was observed against QUIN-induced enhancement of striatal manganese content (-0.45 percent vs. control). These findings resemble those changes observed in postmortem Huntington's disease brain and suggest that alterations in regional content of copper, but not in manganese, may be a consequence of the spreading of QUIN-induced neurotoxic events into the striatal tissue to the neighboring regions of the brain, by action of QUIN on NMDA receptors

Humoral and cellular immune response within the subarachnoid space of patients with neurocysticercosis

To study the immune response within the subarachnoid space in patients with neurocysticercosis, we measured the cerebrospinal fluid contents of immunoglobulins A, E, G, and M in 38 patients and the contents of the proinflammatory cytokines TNF-alpha, IL-1b, IL-6 and IFN-gamma in 17 patients. The same measurements were made in 30 neurological patients without inflammatory or immune-mediated disorders. Each immunoglobulin and cytokine, including the gender and age of the patient, was compared by multiple regression analysis with the CSF contents of cells, protein and ELISA for cysticercal antigens. A direct correlation was found of IgM with cell content (p<0.058) and with ELISA values (p<0.027); of age with protein content (p<0.006); of IL-6 with protein content (p<0.018) and of IL-1b with ELISA values (p<0.004). An inverse correlation was found of glucose with ELISA values (p<0.008). A complex function of the immune response within the subarachonid space was observed: mean values of IgG, IgM, IgE and interleukins 1b and 6 were increased, whereas values of IgA, TNF-alpha and IFN-gamma were similar to those of controls

Mecanismos de neurotoxicidad de la 1-Metil-4-Fenil-1,2,3, 6-Tetrahidropiridina (MPTP) / Mechanisms of the neurotoxicity of 1 Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

La neurotoxina 1-metil-4-fenil-1,2,3,6-tetrahidropiridina (MPTP) produce toxicidad de las neuronas dopaminérgicas de la vía nigroestriatal, como en la enfermedad de Parkinson idiopática. El mecanismo de daño celular causado por esta toxina se desconoce, sin embargo, se han propuesto una serie de hipótesis: el daño a la mitocondria y la fuerza oxidativa. El 1-metil-4-fenilpiridino (MPP+), el mayor metabolito activo de la MPTP es captado por la mitocondria, en donde se acumula e inhibe la oxidación de sustratos unidos al NADH de la mitocondria causando una disminución del ATP. Esto sugiere que la toxicidad del MPP+ puede atribuirse a la inhibición de las funciones de la mitocondria. Sin embargo, esta disminución ha sido observada durante pocas horas. Esto sugiere un segundo mecanismo de daño a las neuronas que pueda explicar los efectos a largo plazo del MPP+. La MPTP genera la formación de radicales libres del oxígeno así como también reduce las defensas antioxidantes endógenas y el glutatión para combatir los radicales libres. La toxicidad de la MPTP es disminuida por una variedad de antioxidantes y por el ácido ascórbico que pueden reducir los cambios bioquímicos producidos por el tratamiento con la MPTP. Esos resultados sugieren que la fuerza oxidativa puede producir daño a las neuronas después de la administración de la MPTP.