RESUMEN
Thimerosal (THI, ethyl-mercury thiosalicylate) is added to vaccines as a preservative; as a consequence, infants may have been exposed to bolus doses of Hg that collectively added up to nominally 200 µg Hg during the first 6 months of life. While several studies report an association between THI-containing vaccines and neurological disorders, other studies do not support the causal relation between THI and autism. With the purpose to understand the molecular mechanisms of the toxic effect of THI it was assayed on human red cells and in bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), classes of phospholipids found in the outer and inner monolayers of the human erythrocyte membrane, respectively. The capacity of THI to interact with DMPC and DMPE was determined by X-ray diffraction and differential scanning calorimetry, whereas intact human erythrocytes were observed by optical, defocusing and scanning electron microscopy. The experimental findings of this study demonstrated that THI interacted in a concentration-dependent manner with DMPC and DMPE bilayers, and in vitro interacted with erythrocytes inducing morphological changes. However, concentrations were considerable higher than those present in vaccines.
Asunto(s)
Eritrocitos/efectos de los fármacos , Membrana Dobles de Lípidos , Timerosal/farmacología , Rastreo Diferencial de Calorimetría , Células Cultivadas , Dimiristoilfosfatidilcolina/química , Membrana Eritrocítica/química , Membrana Eritrocítica/efectos de los fármacos , Eritrocitos/ultraestructura , Humanos , Membrana Dobles de Lípidos/química , Liposomas , Estructura Molecular , Fosfatidiletanolaminas/química , Conservadores Farmacéuticos/farmacología , Termodinámica , Timerosal/química , Difracción de Rayos XRESUMEN
Chilean legislators have voted to ban vaccines preserved with thiomersal, an initiative that the Executive has vetoed. Most scientific evidence has dismissed the alleged toxicity of this substance, in accordance with the formal and publicly expressed opinion of local experts, and yet, medical authorities have issued contradictory statements. Some have argued that the principle of precaution suggests eliminating thiomersal preserved vaccines; others have declared that current vaccines should be maintained to protect the population. From the perspective of bioethics, this polemic is another example of the shortcoming of the deliberation process leading to controversial laws in lieu of including citizens in the discussion of regulations that harbor uncertainties, and respect for individual autonomy to accept or reject public immunization programs. The Chilean legal system has been unwilling to implement participatory democratic procedures like plebiscites or institutions such as the ombudsman. In 2006 a law was enacted that creates a National Commission of Bioethics, but successive governments have failed to create such a commission, which is an efficient social instrument to conduct deliberation on bioethical issues that require a balanced participation of the public, experts, and politicians.
El Poder Legislativo chileno propone una ley que elimine el timerosal como preservante de las vacunas parenterales del Programa Nacional de Inmunizaciones, proyecto que el Poder Ejecutivo se ha propuesto vetar. El mundo científico informa mayoritariamente que la sospecha de neurotoxicidad atribuida al timerosal es infundada. Pese a ello, las autoridades médicas han oscilado entre sostener que la precaución sugiere apoyar la ley y en otros momentos han manifestando que es más precautorio mantener los programas de vacunación actualmente vigentes. Estas contradicciones y oposiciones ilustran que materias que conciernen a la ciudadanía, requieren una reflexión bioética acabada sobre las políticas públicas sanitarias. Han quedado claro las deficiencias de la deliberación política y la falta de participación social en decisiones que, dado el grado de incertidumbre involucrada en temas como inmunización, requieren no sólo la inclusión de la ciudadanía sino el respeto de la autonomía individual para aceptar o rechazar la inclusión en los programas de vacunación propuestos por las políticas sanitarias. La participación ciudadana en nuestro país se ve severamente limitada por la falta de instrumentos sociales como el plebiscito, el ombudsman y, especialmente, la desidia en crear la Comisión Nacional de Bioética exigida por la Ley 20.120 de 2006, una de cuyas funciones más importantes es mediar deliberativamente entre legos, expertos y políticos en la generación de políticas sanitarias legitimadas por la participación ciudadana.
Asunto(s)
Legislación de Medicamentos , Conservadores Farmacéuticos/efectos adversos , Timerosal/efectos adversos , Vacunas/efectos adversos , Discusiones Bioéticas , Chile , Humanos , Conservadores Farmacéuticos/química , Timerosal/química , Vacunas/administración & dosificación , Vacunas/químicaRESUMEN
This article analyzes the recent controversy regarding the introduction of a bill to Chilean Congress that aims to ban thiomersal and/or any trace of organomercurial compounds from vaccines in the country. Rather than providing a formal overview of all available evidence, this analysis focuses on the reasons behind the controversy, the scientific evidence invoked by both sides in the debate, and the anomalies in the healthcare decision-making process.
El presente artículo tiene por objetivo analizar la controversia ocurrida en Chile, especialmente durante los últimos meses, en relación a un proyecto de ley que busca prohibir la fabricación, importación, comercialización o distribución de vacunas que contengan dentro de sus compuestos, en cualquier nivel de concentración, timerosal o compuestos organomercúricos. Sin constituir una síntesis formal de toda la investigación existente, se analiza la evidencia científica que los distintos actores han utilizado, las razones de la controversia y las anomalías en el proceso de toma de decisión sanitaria.
Asunto(s)
Legislación de Medicamentos , Conservadores Farmacéuticos/efectos adversos , Timerosal/efectos adversos , Vacunas/efectos adversos , Chile , Toma de Decisiones , Humanos , Conservadores Farmacéuticos/química , Timerosal/química , Vacunas/administración & dosificación , Vacunas/químicaRESUMEN
A simplified thiourea-based chromatography method, originally developed for methyl and inorganic mercury, was adapted to separate methylmercury (MeHg), ethylmercury (EtHg), and inorganic mercury (Hg(II)) in infants' hair. Samples were weighed and leached with an acidic thiourea solution. Leachates were concentrated on a polymeric resin prior to analysis by Hg-thiourea liquid chromatography/cold vapor atomic fluorescence spectrometry. All but one sample showed small amounts of EtHg, and four of the six analyzed samples had proportionally higher Hg(II) as a percent of total Hg. Breastfed infants from riverine Amazonian communities are exposed to mercury in breast milk (from high levels of maternal sources that include both fish consumption and dental amalgam) and to EtHg in vaccines (from thimerosal). The method proved sensitive enough to detect and quantify acute EtHg exposure after shots of thimerosal-containing vaccines. Based on work with MeHg and Hg(II), estimated detection limits for this method are 0.050, 0.10, and 0.10 ng g⻹ for MeHg, Hg(II), and EtHg, respectively, for a 20-mg sample. Specific limits depend on the amount of sample extracted and the amount of extract injected.
Asunto(s)
Compuestos de Etilmercurio/análisis , Cabello/química , Mercurio/análisis , Compuestos de Metilmercurio/análisis , Timerosal/química , Vacunas/efectos adversos , Vacunas/química , Preescolar , Humanos , Tiourea/químicaRESUMEN
Breastfeeding is the best natural protection infants have against morbidity and mortality, and the development of safe and effective vaccines has made it possible to immunize children against infectious disease. Both of these mechanisms for ensuring good health in children may be compromised by contact with mercury (Hg). Maternal exposure to environmental Hg during pregnancy can predispose nursing children to neurodevelopmental disorders. Despite the World Health Organization assurance that thimerosal-preserved vaccines are safe to use in infants, the United States, the European Union, and dozens of other countries have eliminated thimerosal as a vaccine preservative and stopped the immunization of children with such vaccines. Because of the increase in environmental pollution and the need to produce cheap and safe vaccines, there is a need to address the uncertainty of vaccine-ethylmercury risk of toxicity and Hg exposure during breastfeeding.
Asunto(s)
Lactancia Materna , Exposición Materna , Mercurio/análisis , Leche Humana/química , Vacunas/análisis , Sistema Nervioso Central/crecimiento & desarrollo , Relación Dosis-Respuesta a Droga , Compuestos de Etilmercurio/química , Femenino , Humanos , Lactante , Recién Nacido , Recien Nacido Prematuro , Mercurio/metabolismo , Conservadores Farmacéuticos/química , Factores de Riesgo , Timerosal/químicaRESUMEN
Children are exposed to Hg from mothers (via placenta and lactation), environment (food), and in many parts of the world by thimerosal-containing vaccines (TCV) during immunization. Neurodevelopment studies based on infant hair-Hg (HHg) have been designed without explicit attention to the factors associated with changes in infant physiology and Hg sources of exposure. A longitudinal study of changes in HHg concentrations from birth to 5 years was done in a sample of children from Porto Velho (Rondonia), Brazilian Amazonia. The study extracted information from the asymmetry associated with maternal and infant HHg changes at specified sampling: birth (fetal exposure), 6 months of exclusive breastfeeding, 36 months (weaning) and 60 months (pre-school). The distribution of HHg in breastfed infants followed a pattern different from their mothers. While mothers had the highest HHg concentrations at childbirth, infants showed the highest HHg values at 6 months after the recommended full schedule (six shots) of immunization with TCV; after that, the downward trend in HHg shown by children coincided with both weaning and less frequent vaccination period (5 years). Extended lactation (up to 36 months) was not significantly associated with HHg of infants or mothers; however, significant association (Spearman's r) between maternal and infant HHg concentration was seen at birth (r=0.3534; P=0.001), 6 months (r=0.4793; P<0.0001), 3 years (r=0.0122; P=0.012) and 5 years (r=0.0357; P=0.005). Maternal postpartum metabolic changes, infant development and transitional diets and possibly Hg from TCV contribute to the asymmetry of HHg changes between mothers and children.
Asunto(s)
Exposición a Riesgos Ambientales/análisis , Cabello/química , Mercurio/análisis , Efectos Tardíos de la Exposición Prenatal , Conservadores Farmacéuticos/farmacocinética , Timerosal/farmacocinética , Adolescente , Adulto , Brasil , Niño , Preescolar , Monitoreo del Ambiente , Femenino , Humanos , Lactante , Recién Nacido , Exposición Materna , Mercurio/sangre , Persona de Mediana Edad , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Conservadores Farmacéuticos/química , Timerosal/químicaRESUMEN
Montenegro skin test (MST) represents the main complementary diagnostic test for tegumentary leishmaniases (TL) in endemic regions. Most antigen formulations used for the MST contain thimerosal as preservative. The Food and Drug Administration (FDA), however, recommended reducing or eliminating thimerosal from vaccines and other biological reagents and the Agência Nacional de Vigilância Sanitária (ANVISA) in Brazil, prohibited the use of mercurial compounds in immunobiologicals. In the search for an alternative stabilizer, phenol and thimerosal were tested as antigen preservatives in MST. Formulations were tested when fresh and after a 12-month storage at 4 degrees C in TL confirmed mice and human patients, and were evaluated for protein constitution by SDS-PAGE, Western blot and anti-gp63 ELISA. In mice, a decrease in the diagnostic effectiveness in merthiolate formulation was observed after a 12-month storage. SDS-PAGE, Western blot and anti-gp63 ELISA analyses showed a degradation of antigen proteins in both formulations after 12-month storage and that phenol-preserved antigen was quantitatively and qualitatively better than the merthiolate-preserved one. In patients, the average of induration diameter was larger in fresh antigens (p<0.05). However, storage time did not jeopardize their diagnostic capacity. No non-specific reactions produced by phenol or merthiolate were observed neither in humans nor in mice. Phenol could be a good alternative to replace the merthiolate in MST, and despite the proteolytic activity, antigens remain viable for at least 12 months.
Asunto(s)
Antígenos de Protozoos/química , Antígenos de Protozoos/inmunología , Leishmaniasis Cutánea/diagnóstico , Fenol/química , Conservadores Farmacéuticos/química , Pruebas Cutáneas/métodos , Timerosal/química , Animales , Almacenaje de Medicamentos , Femenino , Humanos , Leishmaniasis Cutánea/inmunología , Ratones , Fenol/farmacología , Conservadores Farmacéuticos/farmacología , Timerosal/farmacologíaRESUMEN
Microspheres of polymers like poly(lactic-co-glycolic acid) (PLGA) have been studied as a vehicle for controlled release vaccines. They require materials and processes that might change the protein antigenicity. Lactic acid is produced during microsphere degradation that occurs in tandem with protein liberation. In addition, most of the proteins that have been used in microencapsulation studies contain Thimerosal((R))(TM) and this can introduce another undesirable effect for their stability. We demonstrated in vitro that the thiosalycilic acid (TSA), produced after the reduction of TM by lactic acid, reduces the S-S bridge of the previously incubated diphtheric toxoid (Dtxd). This reduction is immediately followed by blocking the two -SH formed by the same TSA molecules. In the light of these conclusions it is necessary now, to reinterpret the in vitro protein degradation-stabilization data in the presence of PLGA microspheres, mainly for those proteins which contain S-S. We propose that all the PLGA microspheres microencapsulation studies and protein structural considerations should be done in the absence of TM as preservative.