Toxic Effects of Inhaled Vanadium Attached to Particulate Matter: A Literature Review.

Environmental pollution is a worldwide problem recognized by the World Health Organization as a major health risk factor that affects low-, middle- and high-income countries. Suspended particulate matter is among the most dangerous pollutants, since it contains toxicologically relevant agents, such as metals, including vanadium. Vanadium is a transition metal that is emitted into the atmosphere especially by the burning of fossil fuels to which dwellers are exposed. The objective of this literature review is to describe the toxic effects of vanadium and its compounds when they enter the body by inhalation, based especially on the results of a murine experimental model that elucidates the systemic effects that vanadium has on living organisms. To achieve this goal, we reviewed 85 articles on the relevance of vanadium as a component of particulate matter and its toxic effects. Throughout several years of research with the murine experimental model, we have shown that this element generates adverse effects in all the systems evaluated, because it causes immunotoxicity, hematotoxicity, neurotoxicity, nephrotoxicity and reprotoxicity, among other noxious effects. The results with this experimental model add evidence of the effects generated by environmental pollutants and increase the body of evidence that can lead us to make more intelligent environmental decisions for the welfare of all living beings.

A brief review of the biology of megakaryocytes and platelets and their role in thrombosis associated with particulate air pollution.

Air pollution is a worldwide public health issue and it is associated with millions of premature deaths due to cancer, thrombosis, and pulmonary and cardiovascular diseases. Thrombosis is the excessive clotting that blocks a blood vessel, and its etiology is multifactorial. In recent years, growing evidence has linked air pollution, especially particulate matter (PM) and metals, to the development of thrombosis. PM and metals induce lung and systemic inflammation and oxidative stress that are frequent mechanisms in thrombosis. Platelets are important effectors of physiological hemostasis and pathological thrombosis. They are responsible for the formation of the initial plug and are important in the cellular model of coagulation. Therefore, any changes in their morphology or function or an increase in activation could be extremely relevant in thrombosis. Megakaryocytes (MKs) in the bone marrow and in the lungs are the precursor cells of platelets, and the latter is the first organ injured by air pollution. There is substantial evidence of the effect that PM and metals have on platelets, but there is almost no research about the effect of PM and metals on MKs. It is very likely that the alterations produced by air pollution originate in these cells. In this article, we review the biology of MKs and platelets and their role in particulate air pollution-related thrombosis to emphasize the need for further research in this field.

Fisiología de la hemostasia y su alteración por la coagulopatía en COVID-19 / Physiology of Hemostasis and its Alteration by Coagulopathy in COVID-19

Resumen La pandemia de la enfermedad COVID-19, ocasionada por el virus Sars-CoV-2, ha preocupado al personal de salud, entre otras cosas, por la alta incidencia de coagulopatía asociada a aumento en la mortalidad que se presenta en los pacientes. La coagulopatía es principalmente trombótica, inicialmente en pulmón y posteriormente sistémica, macro y microvascular, asociada al daño endotelial, inflamación, trampas extracelulares de neutrófilos (NETs), activación de macrófagos y tormenta de citocinas que perpetúan el círculo vicioso de trombosis e inflamación. Se ha reportado el aumento de factores protrombóticos en los pacientes: aumento del factor tisular, factor de Von Willebrand, fibrinógeno, factor VIII, entre otros y, además, la disminución de algunos anticoagulantes naturales como la proteína S y la antitrombina. Además, se menciona la insuficiencia de la fibrinólisis, asociada con el aumento del PAI-1 (inhibidor del activador tisular de plasminógeno). Durante la enfermedad, hay depósito de fibrina intraalveolar que también es degradada. Tanto la fibrinólisis del trombo, como la degradación de fibrina intraalveolar, hacen que aumenten los dímeros D y, por esta razón, este es uno de los mejores predictores de la severidad de la enfermedad COVID-19. En este artículo se revisa la fisiología de la hemostasia, la tromboinflamación secundaria a la infección por el virus Sars-Cov-2, la evidencia clínica y lo que se sabe de la fisiopatología de la coagulopatía en COVID-19, para tratar de entenderla desde la mirada de la ciencia básica.

Abstract COVID-19 global pandemic caused by Sars-CoV-2 virus, has worried to health care providers due to the high mortality rate related to coagulopathy in many patients. COVID-19 coagulopathy is mainly thrombotic, first locally in lungs but later on it becomes micro and macrovascular systemic coagulopathy. It has been associated to endothelial damage, inflammation, neutrophil-extracellular traps, monocyte and macrophage activation, cytokines storm that induce a vicious cycle of thrombosis and inflammation. The increased levels of prothrombotic factors as tissue factor, Von Willebrand factor, fibrinogen, VIII factor and the decreased levels of antithrombotic factos, such as: antithrombin and Protein S have been reported in COVID-19 patients. Insufficiency of fibrinolysis because of the increased levels of PAI-1 (plasminogen activator inhibitor 1) have been reported also. During this disease there are intraalveolar fibrin deposits that needs to be degraded. Fibrinolysis of thrombus and fibrin intraalveolar degradation are responsible for the high increase of D-dimers levels that are an important predictor of severity of the disease. In this report, the physiology of hemostasis, thromboinflamation secondary to Sars-CoV-2 infection are reviewed, as well as the clinical evidence and the physiopathology of COVID-19 coagulopathy from the basic sciences point of view.

Evaluating the biological risk of functionalized multiwalled carbon nanotubes and functionalized oxygen-doped multiwalled carbon nanotubes as possible toxic, carcinogenic, and embryotoxic agents.

Carbon nanotubes (CNTs) have been a focus of attention due to their possible applications in medicine, by serving as scaffolds for cell growth and proliferation and improving mesenchymal cell transplantation and engraftment. The emphasis on the benefits of CNTs has been offset by the ample debate on the safety of nanotechnologies. In this study, we determine whether functionalized multiwalled CNTs (fMWCNTs) and functionalized oxygen-doped multiwalled CNTs (fCOxs) have toxic effects on rat mesenchymal stem cells (MSCs) in vitro by analyzing morphology and cell proliferation and, using in vivo models, whether they are able to transform MSCs in cancer cells or induce embryotoxicity. Our results demonstrate that there are statistically significant differences in cell proliferation and the cell cycle of MSCs in culture. We identified dramatic changes in cells that were treated with fMWCNTs. Our evaluation of the transformation to cancer cells and cytotoxicity process showed little effect. However, we found a severe embryotoxicity in chicken embryos that were treated with fMWCNTs, while fCOxs seem to exert cardioembryotoxicity and a discrete teratogenicity. Furthermore, it seems that the time of contact plays an important role during cell transformation and embryotoxicity. A single contact with fMWCNTs is not sufficient to transform cells in a short time; an exposure of fMWCNTs for 2 weeks led to cell transformation risk and cardioembryotoxicity effects.

Thymic cytoarchitecture changes in mice exposed to vanadium.

The thymus is a vital immune system organ wherein selection of T-lymphocytes occurs in a process regulated by dendritic and epithelial thymic cells. Previously, we have reported that in a mouse model of vanadium inhalation, a decrease in CD11c dendritic cells was observed. In the present study, we report on a thymic cortex-medulla distribution distortion in these hosts due to apparent effects of the inhaled vanadium on cytokeratin-5 (K5+) epithelial cells in the same mouse model - after 1, 2, and 4 weeks of exposure - by immunohistochemistry. These cells - together with dendritic cells - eliminate autoreactive T-cell clones and regulate the production of regulatory T-cells in situ. Because both cell types are involved in the negative selection of autoreactive clones, a potential for an increase in development of autoimmune conditions could be a possible consequence among individuals who might be exposed often to vanadium in air pollution, including dwellers of highly polluted cities with elevated levels of particulate matter onto which vanadium is often adsorbed.

Pollution by metals: Is there a relationship in glycemic control?

There are evidences of environmental pollution and health effects. Metals are pollutants implicated in systemic toxicity. One of the least studied effects, but which is currently becoming more important, is the effect of metals on glycemic control. Metals have been implicated as causes of chronic inflammation and oxidative stress and are associated to obesity, hyperglycemia and even diabetes. Arsenic, iron, mercury, lead, cadmium and nickel have been studied as a risk factor for hyperglycemia and diabetes. There is another group of metals that causes hypoglycemia such as vanadium, chromium, zinc and magnesium by different mechanisms. Zinc, magnesium and chromium deficiency is associated with increased risk of diabetes. This review summarizes some metals involved in glycemic control and pretends to alert health professionals about considering environmental metals as an important factor that could explain the poor glycemic control in patients. Further studies are needed to understand this poorly assessed problem.

Unilateral injection of Aß25-35 in the hippocampus reduces the number of dendritic spines in hyperglycemic rats.

Alzheimer's disease (AD) is a neurodegenerative process exacerbated by several risk factors including impaired glucose metabolism in the brain that could cause molecular and neurochemical alterations in cognitive regions such as the hippocampus (Hp). Consequently, this process could cause neuronal morphological changes; however, the mechanism remains elusive. We induced chronic hyperglycemia after streptozotocin (STZ) administration. Then, we examined spatial learning and memory using the Morris water maze test and evaluated neuronal morphological changes using the Golgi-Cox stain procedure in hyperglycemic rats that received a Aß25-35 unilateral injection into the Hp. Our results demonstrate that STZ combined with Aß25-35 induced significant deficits in the spatial memory. In addition, we observed a significant reduction in the number of dendritic spines of pyramidal neurons in the dorsal Hp of rats with STZ plus Aß25-35 . In conclusion, the reduced spine density of pyramidal neurons in the CA1 dorsal Hp could produce the spatial memory deficit observed in these animals. These results suggest that hyperglycemia can trigger Aß-induced neurodegeneration and thus the appearance of AD symptoms would be accelerated. Synapse 68:585-594, 2014. © 2014 Wiley Periodicals, Inc.

Teratogenic effect of ethylene glycol-methyl cellosolve mixture in rats: I: reproductive damage / Teratogénesis por etilenglicol-metilcelosolve en ratas: I: daño reproductivo

We investigated the reproductive damage and teratogenic effect of an ethylene glycol-methyl cellosolve mixture on gestating Wistar rats, which received a daily intraperitoneal dose of different concentration of the mixture on day 8 of gestation until day 20. In rats treated with the mixture the number of live fetuses decreased and reabsorptions increased with increasing concentrations of the mixture, as well as the number of abnormal fetuses. We conclude that the ethylene glycol-methyl cellosolve mixture possesses a higher teratogenic potential than each of its constituents separately, producing reproductive damage, external fetal abnormalities, growth delay, and increased fetal death.

Se investigó el daño reproductivo y efecto teratogénico de una mezcla de etilenglicol y metilcelosolve en ratas gestantes, las cuales recibieron por vía intraperitoneal una dosis diaria, a diferentes concentraciones de la mezcla, del día 8 al día 20 de gestación. En las ratas tratadas con la mezcla el número de fetos vivos disminuyó y las reabsorciones y el número de fetos anormales aumentaron a mayor concentración de los solventes. Concluimos que la mezcla de etilenglicol-metilcelosolve tiene mayor efecto teratogénico que cuando actúan cada uno de los solventes por separado, produciendo daño reproductivo, anormalidades fetales externas, retraso del crecimiento y aumento de muerte fetal.

Teratogenic effect of ethylene glycol-methyl cellosolve mixture in rats: II: craniofacial and limb abnormalities / Teratogénesis por etilenglicol-metilcelosolve en ratas: II: anormalidades craneofaciales y de miembros

We investigated the teratogenic effect of an ethylene glycol-methyl cellosolve mixture on gestating Wistar rats, that received a daily intraperitoneal dose of different concentration of the mixture on day 8 of gestation until day 20. Multivariate analysis and Post-Hoc Bonferroni tests were used and relative risk and attributable fraction were calculated. In rats treated with the mixture the number of live fetuses decreased and reabsorptions increased with increasing concentrations of the mixture, as well as the number of abnormal fetuses. Abnormalities consisted mainly in atypical craniofacial morphology, protruding tongue, edema, signs of growth delay and shorter limbs, their frequency and severity increased at higher concentrations of the mixture. We conclude that the ethylene glycol-methyl cellosolve mixture possesses a higher teratogenic potential than each of its constituents separately, producing external fetal abnormalities, growth delay, and increased fetal death.

Se investigó el efecto teratogénicos de una mezcla de etilenglicol y metilcelosolve en ratas gestantes, las cuales recibieron por vía intraperitoneal una dosis diaria, a diferentes concentraciones de la mezcla, del día 8 al día 20 de gestación. Se utilizaron las pruebas de análisis multivariado y Post-Hoc de Bonferroni, y se calcularon el riesgo relativo y la fracción atribuible. En las ratas tratadas con la mezcla el número de fetos vivos disminuyó y las reabsorciones y el número de fetos anormales aumentaron a mayor concentración de los solventes. Las anormalidades fetales consistieron principalmente en morfología atípica craneofacial, protrusión de la lengua, edema, signos de retraso de crecimiento y acortamiento de extremidades, y su frecuencia y severidad se incrementó a mayor concentración de la mezcla. Concluimos que la mezcla de etilenglicol-metilcelosolve tiene mayor efecto teratogénico que cuando actúan cada uno de los solventes por separado, produciendo anormalidades fetales externas, retraso del crecimiento y aumento de muerte fetal.

Morphometric study of the ventricular segment of the human fetal heart between 13 and 20 weeks' gestation.

UNLABELLED: Our objective was to determine the normal dimensions of the ventricular segment of the human fetal heart between 13 and 20 weeks' gestation. STUDY DESIGN: 103 hearts obtained by necropsy were dissected and measurements of different portions of ventricles were determined under stereoscopic magnification. In each ventricle were measured anteroposterior and lateral diameters, inlet and outlet length, and thickness of walls at different levels. Our results showed the cardiac apex was constituted by the left ventricle in 68.9% of the hearts. Both ventricles showed linear growth during this period of fetal development. Ranges in median values of external and internal ventricular measurements were determined. The left ventricular wall was thicker than the right, and the right ventricular cavity was larger. This study provides morphometric reference information concerning the dimensions and growth of both ventricles of the fetal heart, which may be useful in pediatric cardiac surgery and echocardiography.

Variables cualitativas del desarrollo humano normal de la 9ª a 20ª semanas de gestación / Cualitative variables in normal human development betwen 9º to 20º weeks of gestation

Introducción. La etapa fetal del desarrollo prenatal se caracteriza por el rápido incremento de la masa corporal mas que por los cambios culitativos que son muy sutiles. No existe en la literatura información precisa sobre estos cambios cualitativos ni del momento en que ocurren, lo cual frecuentemente dificulta la valoración de productos con retardo del crecimineto o malformaciones del tipo de las displasias óseas. Objetivo. Describir los cambios morfológicos cualitativos mas relevantes que ocurren en el desarrollo prenatal humano entre la 9a. y la 20a. semanas de gestación. Material y métodos. Se estudiaron 215 fetos obtenidos de abortos espontáneos con edades comprendidas entre 9 y 20 semanas de gestación, normales y en excelente estado de conservación. A cada uno de los casos se les valoró el desarrollo de los párpados, la presencia de surco medio nasal, la ubicación y desarrollo de los pabellones auriculares, la presencia de lanugo, el desarrollo de las uñas de los dedos y de los ortejos, las características de los genitales externos, la perforación del orificio anal y la presencia de cola. Resultados. Las características mas constantes fueron el desarrollo de los párpados y de los pabellones auriculares, así como la presencia de lanugo y aparición de las uñas. Los genitales externos fueron identificables en todos los casos a partir de la semana 11. La presencia de surco medio nasal y perforación del orificio anal fue una característica muy variable. Conclusiones: Las características cualitativas son parámetros útiles, auxiliares de la somatometría fetal, para evaluar aquellos casos con retardo del crecimiento o trastornos esqueléticos que afectan la proporción de los segmentos corporales

Antropometría fetal normal de la 9 a 20 semanas del desarrollo / Fetal antrophometry between 9 to 20 weeks of development

Introducción. Es bien sabido que las diversas variables antropométricas son la base para caracterizar a los diferentes grupos poblacionales ya que dependen de la diversidad genética propia de cada grupo étnico. Estas características se han establecido en individuos adultos y, algunas de ellas, en niños de diversas edades y en diferentes poblaciones, incluyendo la mexicana, pero no así en la etapa prenatal, la que se desconoce en nuestra población. Objetivo. Elaborar tablas somatométricas del desarrollo prenatal en la población mexicana y compararlas con las de otros grupos poblacionales. Material y métodos. Se estudiaron 215 fetos obtenidos de abortos espontáneos en el Hospital General "Dr. Manuel Gea Gonzáles" con edades comprendidas entre 9 y 20 semanas de gestación, normales y en excelente estado de conservación. Cada uno de los casos pesó y midió la longitud coronilla-rabadilla, diámetros cefálicos, perímetros fetales y longitud de los segementos de las extremidades superiores e inferiores. Todas las mediciones fueron analizadas estadísticamente. Resultados. Se elaboraron las tablas somatométricas por semana de edad gestacional. Se pudo apreciar que todas las medidas guardan una alta correlación entre sí, por lo que junta o por separado pueden ser un indicador confiable del grado del desarrollo fetal. El mayor incremento somatométrico ocurrió entre la 9ª y la 13ª semanas de gestación en casi todas las variables estudiadas. Se compararon las mediciones obtenidas con aquéllas referidas en otras poblaciones, no encontrando diferencias significativas en ninguna de las variables analizadas. Conclusiones. Nuestros resultados nos permiten sugerir una alta confiabilidad para la predicción de la edad morfológica real del feto entre la 9ª yla 20ª semanas de gestación, en todas las variables estudiadas, sólas o combinadas entre sí. De igual manera nos permiten concluir que en la somatometría externa fetal temprana no hay diferencias significativas en la población mexicana con respecto a otras poblaciones informadas en la literatura.

Atresia pulmonar con tabique interventricular íntegro: presentación del caso de una paciente de siete años de edad / Pulmonary atresia with intact ventricular septum: presentation of the case of a seven year old patient

Se presenta el caso de un paciente femenino de siete años, quien fue atendido por primera vez en el Instituto Nacional de Pediatría a los 13 meses de edad por meningoencefalitis bacteriana. Se halló que tenía una cardiopatía congénita. Se efectuó cateterismo cardiaco y se encontro artresia pulmonar con tabique interventricular a la neuroinfección, por ello no se consideró conveniente realizar una intervención quirúrgica. Vivó hasta los siete, cuando en forma accidental falaleció por broncoaspiración