Adriana González-Villalva

Thrombocytosis induced in mice after subacute and subchronic V2O5 inhalation.

Reports about vanadium (V) inhalation toxicity on the hematopoietic system, specifically about coagulation are limited. Therefore, we decided to evaluate the effects of V with a complete blood count and morphologic analysis of platelets on blood smears. CD-1 male mice inhaled V2O5 0.02 M 1 h twice weekly over 12 weeks. Blood samples were obtained by direct heart puncture; Wright stained smears were used for platelet quantification. An increase in platelet count from the third week of exposure was observed, as well as the presence of megaplatelets. Our results demonstrate, for the first time, that V induces thrombocytosis and it might correlate with some thromboembolic diseases. Further analysis is needed to evaluate the functionality of these platelets as well as the cause of its increase.

Vanadium Pentoxide Inhalation Provokes Germinal Center Hyperplasia and Suppressed Humoral Immune Responses

Vanadium, an important air pollutant derived from fuel product combustion, aggravates respiratory diseases and impairs cardiovascular function. In contrast, its effects on immune response are conflicting. The aim of our work was to determine if spleens of vanadium-exposed CD1 mice showed histological lesions that might result in immune response malfunction. One hundred and twelve CD-1 male mice were placed in an acrylic box and inhaled 0.02 M vanadium pentoxide (V2O5); actual concentration in chamber ≈1.4 mg V2O5/m3) for 1 hr/d, twice a week, for 12 wk. Control mice inhaled only vehicle. Eight mice were sacrificed prior to the exposures. Eight control and eight V2O5-exposed mice were sacrificed 24 hr after the second exposure of each week until the 12-wk study was over. Another 8 mice that completed the 12-wk regimen were immunized with recombinant Hepatitis B surface antigen (HBsAg; three times over an 8-wk period) before sacrifice and analyses of their levels of anti-HBsAg antibody (HBSAb) using ELISA. In all studies, at sacrifice, blood samples were obtained by direct heart puncture and the spleen was removed, weighed and processed for H-E staining and quantitation of CD19 cells. The results indicated that the spleen weight of V2O5-exposed animals peaked at 9 wk (546 ± 45 vs. 274 ± 27 mg, p < 0.0001) and thereafter progressively decreased (321 ± 39 mg at 12 wk, p < 0.001; control spleen = 298 ± 35 mg). Spleens of V2O5-exposed animals showed an increased number of very large and non-clearly delimited germinal centers (that contained more lymphocytes and megakaryocytes) compared to those of control mice. In addition, their red pulp was poorly delimited and had an increase in CD19+ cells within hyperplasic germinal nodes. The mean HBsAb levels in immunized control mice were greater than that in the exposed hosts (i.e., OD = 0.39 ± 0.03 vs. 0.11 ± 0.05, p < 0.01). HBsAb avidity dropped to a value of 40 in V2O5-exposed animals vs. 86 in controls (p < 0.0001). We conclude that the chronic inhalation of V2O5, a frequent particle (PM2.5) component, induces histological changes and functional damage to the spleen, each of which appear to result in severe effects on the humoral immune response.

Overview of environmental and occupational vanadium exposure and associated health outcomes: an article based on a presentation at the 8th International Symposium on Vanadium Chemistry, Biological Chemistry, and Toxicology, Washington DC, August 15-18, 2012.

Abstract Vanadium (V) has a variety of applications that make it suitable for use in ceramic production and decoration, production of pigments for a variety of products, an accelerator for drying paint, production of aniline black dye, and as a mordant in coloring textiles. Taking advantage of its hardness, resilience, ability to form alloys, and its resistance to corrosion, V is also used in the production of tools, steel, machinery, and surgical implants. V is employed in producing photographic developers, batteries, and semi-conductors, and in catalyst-based recycling processes. As technologies have evolved, the use of V has increased in jet aircraft and space technology, as well as in manufacture of ultraviolet filter glass to prevent radiation injury. Due to these myriad uses, the potential for occupational exposure to V is ever-evident. Similarly, there is an increased risk for environmental contamination by V agents themselves or as components of by-products released into the environment. For example, the use of V in sulfuric acid production results in the release of soot and/or fly ash rich in vanadium pentoxide. Petroleum refinery, smelting, welding, and cutting of V-rich steel alloy, the cleaning and repair of oil-fired boilers, and catalysis of chemical productions are other sources of increased airborne V-bearing particles in local/distant environments. Exposure of non-workers to V is an increasing health concern. Studies have demonstrated associations between exposure to airborne V-bearing particles (as part of air pollution) and increased risks of a variety of pathologies like hypertension, dysrhythmia, systemic inflammation, hyper-coagulation, cancers, and bronchial hyper-reactivity. This paper will provide a review of the history of V usage in occupational settings, documented exposure levels, environmental levels of V associated with pollution, epidemiologic data relating V exposure(s) to adverse health outcomes, and governmental responses to protect both workers and non-workers from exposure to this metal.

The effect of vanadium on platelet function

Vanadium pentoxide (V(2)O(5)) inhalation effect on platelet function in mice was explored, as well as the in vitro effect on human platelets. Mouse blood samples were collected and processed for aggregometry and flow cytometry to assess the presence of P-selectin and monocyte-platelet conjugates. Simultaneously, human platelets were processed for aggregometry(.) The mouse results showed platelet aggregation inhibition in platelet-rich-plasma (PRP) at four-week exposure time, and normality returned at eight weeks of exposure, remaining unchanged after the exposure was discontinued after four weeks. This platelet aggregation inhibition effect was reinforced with the in vitro assay. In addition, P-selectin preserved their values during the exposure, until the exposure was discontinued during four weeks, when this activation marker increased. We conclude that vanadium affects platelet function, but further studies are required to evaluate its effect on other components of the hemostatic system.

Ultrastructural megakaryocyte modifications after vanadium inhalation in spleen and bone marrow

Previous reports from our laboratory informed in mice an increase in platelets in blood, and megakaryocytes in spleen and bone marrow after vanadium inhalation. This element has become important in recent years because of its increased presence as an air pollutant. With this precedent, we evaluate the ultrastructural modifications in MKs from the spleen and bone marrow in our mouse experimental model. Mice inhaled 0.02 M V(2)O(5) 1 h twice a week for 12 weeks. Tissues were processed for transmission electron microscopy. Results indicate an increase in the size and cytoplasmic granular content, as well as nuclear changes in MKs of exposed mice, changes which correlate with the time of exposure. Modifications in MKs described here suggest that inhaled vanadium induce megakaryocytic maturation, a raise in its granules content and demarcation membrane systems, which may lead to a rise in circulating platelet production and an increased risk for thromboembolic events.

Características clínicas y anticuerpos antifosfolipídicos (anticardiolipina-β2GP-1) en líquido cefalorraquídeo y suero en una muestra de pacientes con esclerosis múltiple en México

Resumen Introduccion El diagnostico diferencial de la esclerosis multiple (EM) incluye una gran variedad de enfermedades autoinmunitarias (lupus eritematoso sistemico, sindrome de Sjogren, sindrome antifosfolipidico, etc.). Los anticuerpos antifosfolipidicos (AAFL) en el suero de pacientes con EM se encuentran en cifras tan bajas como en el 10% y tan altas como en el 88% de los casos, pero su significacion en la patogenia de la enfermedad o su utilidad diagnostica aun no se han establecido. El objetivo fue conocer las caracteristicas clinicas y demograficas de una muestra de pacientes con EM del Hospital General de Mexico (HGM), y determinar presencia y frecuencia de anticuerpos antifosfolipidicos en liquido cefalorraquideo y suero de estos pacientes. Pacientes y metodos Se realizo un estudio prospectivo con pacientes captados en la consulta externa de neurologia del HGM, con diagnostico definido de EM a lo largo de 1 ano. Se analizaron sus caracteristicas clinicodemograficas y se determino VDRL y anticuerpos anticomplejo cardiolipina-β2GP-1 en LCR y suero. Resultados Se incluyo a 12 pacientes, con predominio del sexo femenino (58%). El cuadro clinico predominante fue la neuritis optica (66,6%) seguida de la afeccion medular (58%). La mayoria de los pacientes fueron ambulatorios ( Conclusiones Las caracteristicas clinicodemograficas en la muestra de este estudio son semejantes a las comunicadas con anterioridad y las concentraciones de anticardiolipina-β2GP-1 fueron negativas, lo cual puede indicar que hay diversas variables clinicas y demograficas que influyen en su deteccion.

Functional and morphological olfactory bulb modifications in mice after vanadium inhalation.

Neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases, have olfaction impairment. These pathologies have also been linked to environmental pollutants. Vanadium is a pollutant, and its toxic mechanisms are related to the production of oxidative stress. In this study, we evaluated the effects of inhaled vanadium on olfaction, the olfactory bulb antioxidant, through histological and ultrastructural changes in granule cells. Mice in control group were made to inhale saline; the experimental group inhaled 0.02-M vanadium pentoxide (V2O5) for 1 hr twice a week for 4 weeks. Animals were sacrificed at 1, 2, 3, and 4 weeks after inhalation. Olfactory function was evaluated by the odorant test. The activity of glutathione peroxidase (GPx) and glutathione reductase (GR) was assayed in olfactory bulbs and processed for rapid Golgi method and ultrastructural analysis. Results show that olfactory function decreased at 4-week vanadium exposure; granule cells showed a decrease in dendritic spine density and increased lipofuscin, Golgi apparatus vacuolation, apoptosis, and necrosis. The activity of GPx and GR in the olfactory bulb was increased compared to that of the controls. Our results demonstrate that vanadium inhalation disturbs olfaction, histology, and the ultrastructure of the granule cells that might be associated with oxidative stress, a risk factor in neurodegenerative diseases.

Clinical characteristics and presence of antiphospholipid antibodies (anticardiolipin-β2GP-1) cerebrospinal fluid and serum of in a series of patients with multiple sclerosis in Mexico

INTRODUCTION The differential diagnosis of multiple sclerosis (MS) includes a wide variety of autoimmune diseases (systemic lupus erythematosus, Sjögren syndrome, antiphospholipid syndrome, etc.). The presence of antiphospholipid antibodies (APLA) in serum of MS patients has been reported to be as low as 10%, or sometimes as high as 88% of the cases, although its significance in the pathogenesis of the disease, or its diagnostic usefulness is still unknown. The goal of this study was to describe the clinic and demographic characteristics of a sample of patients with MS from the Hospital General de México (HGM), as well as to determine the presence and frequency of APLA in cerebrospinal fluid (CSF) and serum samples of these patients. PATIENTS AND METHODS A prospective study with patients from the Neurology Department at the HGM was performed. These patients were diagnosed with MS over a one-year period. Clinical and demographic characteristics were compiled. VDRL and anti-cardiolipin-beta2GP-1 complex antibodies were analyzed in CSF and serum samples. RESULTS Twelve patients were included in the study, the majority females (58%). The predominant clinic feature was optic neuritis (66.6%) followed by medullary involvement (58%). Most of patients were ambulatory (< 4 EDSS points). Auto-antibody levels were found in negative ranges in all cases, both in CSF and serum. CONCLUSIONS The clinical-demographic characteristics in patients studied in this work were similar to those previously reported, and the levels of anti-cardiolipin-beta2GP-1 were negative, thus indicating the existence of different clinical and demographic variables influencing their detection.

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.

Activation of Janus kinase/signal transducers and activators of transcription pathway involved in megakaryocyte proliferation induced by vanadium resembles some aspects of essential thrombocythemia.

Vanadium (V) is an air pollutant released into the atmosphere by burning fossil fuels. Also, it has been recently evaluated for their carcinogenic potential to establish permissible limits of exposure at workplaces. We previously reported an increase in the number and size of platelets and their precursor cells and megakaryocytes in bone marrow and spleen. The aim of this study was to identify the involvement of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway and thrombopoietin (TPO) receptor, and myeloproliferative leukemia virus oncogene (Mpl), in megakaryocyte proliferation induced by this compound. Mice were exposed twice a week to vanadium pentoxide inhalation (0.02 M) and were killed at 4th, 6th, and 8th week of exposure. Phosphorylated JAK2 (JAK2 ph), STAT3 (STAT3 ph), STAT5, and Mpl were identified in mice spleen megakaryocytes by cytofluorometry and immunohistochemistry. An increase in JAK2 ph and STAT3 ph, but a decrease in Mpl at 8-week exposure was identified in our findings. Taking together, we propose that the morphological findings, JAK/STAT activation, and decreased Mpl receptor induced by V leads to a condition comparable to essential thrombocythemia, so the effect on megakaryocytes caused by different mechanisms is similar. We also suggest that the decrease in Mpl is a negative feedback mechanism after the JAK/STAT activation. Since megakaryocytes are platelet precursors, their alteration affects platelet morphology and function, which might have implications in hemostasis as demonstrated previously, so it is important to continue evaluating the effects of toxics and pollutants on megakaryocytes and platelets.