Environmental exposure to manganese and health risk assessment from personal sampling near an industrial source of airborne manganese.

Manganese (Mn), despite being a trace element necessary in small quantities for the correct functioning of the organism, at higher concentrations can induce health disorders, mainly in motor and cognitive functions, even at levels found in non-occupational environments. For this reason, US EPA guidelines define safe reference doses/concentrations (RfD/RfC) for health. In this study, the individualised health risk of exposure to Mn through different media (air, diet, soil) and routes of entry into the organism (inhalation, ingestion and dermal absorption) was assessed according to the procedure defined by the US EPA. Calculations related to Mn present in ambient air were made on the basis of data obtained from size-segregated particulate matter (PM) personal samplers carried by volunteers recruited in a cross-sectional study conducted in the Santander Bay (northern Spain), where an industrial source of airborne Mn is located. Individuals residing in the vicinity of the main Mn source (within 1.5 km) were found to have a hazard index (HI) higher than 1, indicating that there is a potential risk for these subjects to develop health alterations. Also, people living in Santander, the capital of the region, located 7-10 km from the Mn source, may have some risk (HI > 1) under some wind conditions (SW). In addition, a preliminary study of media and routes of entry into the body confirmed that inhalation of PM2.5-bound Mn is the most important route contributing to the overall non-carcinogenic health risk related to environmental Mn.

Short- and long-term exposure to trace metal(loid)s from the production of ferromanganese alloys by personal sampling and biomarkers.

The environmental exposure to trace metal(loid)s (As, Cd, Cu, Fe, Mn, Pb, and Zn) was assessed near a ferromanganese alloy plant using filters from personal particulate matter (PM) samplers (bioaccessible and non-bioaccessible fine and coarse fractions) and whole blood as short-term exposure markers, and scalp hair and fingernails as long-term biomarkers, collected from volunteers (n = 130) living in Santander Bay (northern Spain). Bioaccessible and non-bioaccessible metal(loid) concentrations in coarse and fine PM from personal samplers were determined by ICP-MS after extraction/digestion. Metal(loid) concentration in biomarkers was measured after alkaline dilution (whole blood) and acid digestion (fingernails and scalp hair) by ICP-MS as well. Results were discussed in terms of exposure, considering the distance to the main Mn source, and sex. In terms of exposure, significant differences were found for Mn in all the studied fractions of PM, As in whole blood, Mn and Cu in scalp hair and Mn and Pb in fingernails, with all concentrations being higher for those living closer to the Mn source, with the exception of Cu in scalp hair. Furthermore, the analysis of the correlation between Mn levels in the studied biomarkers and the wind-weighted distance to the main source of Mn allows us to conclude that scalp hair and mainly fingernails are appropriate biomarkers of long-term airborne Mn exposure. This was also confirmed by the significant positive correlations between scalp hair Mn and bioaccessible Mn in coarse and fine fractions, and between fingernails Mn and all PM fractions. This implies that people living closer to a ferromanganese alloy plant are exposed to higher levels of airborne metal(loid)s, mainly Mn, leading to higher levels of this metal in scalp hair and fingernails, which according to the literature, might affect some neurological outcomes. According to sex, significant differences were observed for Fe, Cu and Pb in whole blood, with higher concentrations of Fe and Pb in males, and higher levels of Cu in females; and for Mn, Cu, Zn, Cd and Pb in scalp hair, with higher concentrations in males for all metal(loid)s except Cu.

Metal(loid) bioaccessibility and inhalation risk assessment: A comparison between an urban and an industrial area.

The content of metal(loid)s in particulate matter (PM) is of special concern due to their contribution to overall (PM) toxicity. In this study, the bioaccessibility and human health risk of potentially toxic metal(loid)s associated with PM10 were investigated in two areas of the Cantabrian region (northern Spain) with different levels of exposure: an industrial area mainly influenced by a ferromanganese alloy plant; and an urban area consisting mainly of residential and commercial activities, but also affected, albeit to a lesser extent by the ferroalloy plant. Total content and bioaccessible fractions in simulated lung fluids (SLFs) of Fe, Mn, Zn, Ni, Cu, Sb, Mo, Cd and Pb were determined by ICP-MS. Gamble's solution and artificial lysosomal fluid (ALF) were used to mimic different conditions inside the human respiratory system. A health risk assessment was performed based on the United States Environmental Protection Agency's (USEPA) methodology. Most metal(loid)s showed moderate and high bioaccessibility in Gamble's solution and ALF, respectively. Despite the high variability between the samples, metal(loid) bioaccessibility was found to be higher on average at the industrial site, suggesting a greater hazard to human health in the proximity of the main metal(loid) sources. Based on the results of the risk assessment, the non-carcinogenic risk associated with Mn exposure was above the safe limit (HQ> 1) under all the studied scenarios at the industrial site and under some specific scenarios at the urban location. The estimated carcinogenic inhalation risk for Cd exposure at the industrial site was found to be within the range between 1.0 × 10-6 to 1.0 × 10-4 (uncertainty range) under some scenarios. The results obtained in this study indicate that Mn and Cd inhalation exposure occurring in the vicinities of the studied areas may pose a human health risk.

Kinetics of ascorbate and dithiothreitol oxidation by soluble copper, iron, and manganese, and 1,4-naphthoquinone: Influence of the species concentration and the type of fluid.

An alternative metric to account for particulate matter (PM) composition-based toxicity is the ability of PM-species to generate reactive oxygen species (ROS) and deplete antioxidants, the so-called oxidative potential (OP). Acellular OP assays are the most used worldwide, mainly those based on ascorbic acid (AA) and dithiothreitol (DTT) depletion; OP values are calculated from AA/DTT concentration over time kinetic curves. Since a great variability in OP-DTT and OP-AA values can be found in the literature, the understanding of those factors affecting the kinetic rate of AA and DTT oxidation in the presence of PM-bound species will improve the interpretation of OP values. In this work, a kinetic study of the oxidation rate of AA and DTT driven by species usually found in PM (transition metals and naphthoquinone (NQ)) was carried out. In particular, the influence of the concentration of Cu(II), Fe(II), Fe(III), Mn(II), Mn(III), and 1,4-NQ, and the type of fluid used in the assay (phosphate buffer (PB), phosphate buffer saline (PBS) and artificial lysosomal fluid (ALF)) is analysed and discussed. The reaction orders with respect to the AA/DTT and the active compound, and the kinetic rate constants were also determined. The results show great variability in OP values among the studied species depending on the fluid used; the OP values were mostly higher in PB0.05 M, followed by PBS1x and ALF. Moreover, different species concentration-responses for OP-DTT/OP-AA were obtained. These differences were explained by the different reaction orders and kinetic rate constants obtained for each active compound in each fluid.

Assessment of regional metal levels in ambient air by statistical regression models.

The assessment of the particulate matter (PM) levels and its constituents presented in the atmosphere is an important requirement of the air quality management and air pollution abatement. The heavy metal levels in PM10 are commonly evaluated by experimental measurements; nevertheless, the EC Directives also allow the Regional Governments to estimate the regulated metal levels (Pb in Directive 2008/50/EC and As, Ni and Cd in Directive 2004/107/EC) by objective estimation and modelling techniques. These techniques are proper alternatives to the experimental determination because the required analysis and/or the number of required sampling sites are reduced. The present work aims to estimate the annual levels of regulated heavy metals by means of multivariate linear regression (MLR) and principal component regression (PCR) at four sites in the Cantabria region (Northern Spain). Since the objective estimation techniques may only be applied when the regulated metal concentrations are below to the lower assessment threshold, a previous evaluation of the determined annual levels of heavy metals is conducted to test the fulfilment of the EC Directives requirements. At the four studied sites, the results show that the objective estimations are allowed alternatives to the experimental determination. The annual average metal concentrations are well estimated by the MLR technique in all the studied sites; furthermore, the EC quality requirements for the objective estimations are fulfilled by the developed statistical MLR models. Hence these estimations may be used by Regional Governments as a proper alternative to the experimental measurements for the regulated metal levels assessment.

Understanding how methodological aspects affect the release of trace metal(loid)s from urban dust in inhalation bioaccessibility tests.

The bioaccessibility of metal(loid)s in ambient particulate matter (PM) has been recently used to represent the risk of inhalation exposure. Nevertheless, different methodological factors affect the bioaccessibility values; among these, the type and composition of surrogate biological fluids and the liquid to solid ratio have been revealed to be the most important. To better understand how these methodological aspects affect the bioaccessibility, a reference material corresponding to urban dust (SRM1648a) was contacted with synthetic biological fluids commonly used in the literature representing surrogate fluids that may interact with fine (Gamble's solutions, artificial lysosomal fluid (ALF)) and coarse particles (gastric fluid), for liquid to solid (L/S) ratios ranging from 500 to 20,000. Visual MINTEQ 3.1. was used to enhance the discussion on how the solubility of metals in the leaching solution depends on the composition of the simulated fluids and the speciation of metals. The results obtained indicate that a small change in the composition of Gamble's solution (the presence of glycine) may increase significantly the bioaccessibility at a L/S ratio of 5,000. The highest bioaccessibility of most of the studied metal(loid)s at a L/S ratio of 5,000 was found for ALF fluid. The study of the effect of the L/S ratio showed that metal(loid)s bioaccessibility in Gamble's fluid increased logarithmically with increasing L/S ratio, while it remained practically constant in ALF and gastric fluid. This different behavior is explained assuming that the leaching of metal(loid)s in Gamble's solution is solubility-controlled, while in ALF and gastric fluid is availability-controlled.

Using multi-site data to apportion PM-bound metal(loid)s: Impact of a manganese alloy plant in an urban area.

The identification and quantification of the PM emission sources influencing a specific area is vital to better assess the potential health effects related to the PM exposure of the local population. In this work, a multi-site PM10 sampling campaign was performed in seven sites located in the southern part of the Santander Bay (northern Spain), an urban area characterized by the proximity of some metal(loid) industrial sources (mainly a manganese alloy plant). The total content of V, Mn, Fe, Ni, Cu, Zn, As, Mo, Cd, Sb and Pb was determined by ICP-MS. This multi-site dataset was evaluated by positive matrix factorization (PMF) in order to identify the main anthropogenic metal(loid) sources impacting the studied area, and to quantify their contribution to the measured metal(loid) levels. The attribution of the sources was done by comparing the factor profiles obtained by the PMF analysis with representative profiles from known metal(loid) sources in the area, included in both the European database SPECIEUROPE (V2.0) and the US database EPA-SPECIATE (V4.5) or calculated from literature data. In addition, conditional bivariate probability functions (CBPF)s were used to assist in the identification of the sources. Four metal(loid) sources were identified: Fugitive and point source emissions from the manganese alloy plant (49.9% and 9.9%, respectively), non-exhaust traffic emissions (38.3%) and a minor source of mixed origin (1.8%). The PMF analysis was able to make a clear separation between two different sources from the manganese alloy plant, which represented almost 60% of the total measured metal(loid) levels, >80% of these emissions being assigned to fugitive emissions. These results will be useful for the assessment of the health risk associated with PM10-bound metal(loid) exposure and for the design of efficient abatement strategies in areas impacted by similar industries.

A comparative study between the fluxes of trace elements in bulk atmospheric deposition at industrial, urban, traffic, and rural sites.

The input of trace elements via atmospheric deposition towards industrial, urban, traffic, and rural areas is quite different and depends on the intensity of the anthropogenic activity. A comparative study between the element deposition fluxes in four sampling sites (industrial, urban, traffic, and rural) of the Cantabria region (northern Spain) has been performed. Sampling was carried out monthly using a bulk (funnel bottle) sampler. The trace elements, As, Cd, Cr, Cu, Mn, Mo, Ni, Pb, Ti, Zn, and V, were determined in the water soluble and insoluble fractions of bulk deposition samples. The element deposition fluxes at the rural, urban, and traffic sites followed a similar order (Zn > Mn> > Cu ≈ Ti > Pb > V ≈ Cr > Ni> > As ≈ Mo > Cd). The most enriched elements were Cd, Zn, and Cu, while V, Ni, and Cr were less enriched. An extremely high deposition of Mn was found at the industrial site, leading to high enrichment factor values, resulting from the presence of a ferro-manganese/silico-manganese production plant in the vicinity of the sampling site. Important differences were found in the element solubilities in the studied sites; the element solubilities were higher at the traffic and rural sites, and lower at the urban and industrial sites. For all sites, Zn and Cd were the most soluble elements, whereas Cr and Ti were less soluble. The inter-site correlation coefficients for each element were calculated to assess the differences between the sites. The rural and traffic sites showed some similarities in the sources of trace elements; however, the sources of these elements at the industrial and rural sites were quite different. Additionally, the element fluxes measured in the insoluble fraction of the bulk atmospheric deposition exhibited a good correlation with the daily traffic volume at the traffic site.

Impact of the global economic crisis on metal levels in particulate matter (PM) at an urban area in the Cantabria Region (Northern Spain).

Air pollution by particulate matter is well linked with anthropogenic activities; the global economic crisis that broke out in the last year may be a proper indicator of this close relationship. Some economic indicators show the regional effects of the crisis on the Cantabria Region. The present work aims to evaluate the impact of the economic crisis on PM10 levels and composition at the major city of the region, Santander. Some metals linked to anthropogenic activities were measured at Santander and studied by Positive Matrix Factorization; this statistical analysis allowed to identify three main factors: urban background, industrial and molybdenum-related factor. The main results show that the temporal trend of the levels of the industrial tracers found in the present study are well agree with the evolution of the studied economic indicators; nevertheless, the urban background tracers and PM10 concentration levels are not well correlated with the studied economic indicators.

[Amicrobial pustulosis of the folds: report of a new case and review of literature]. / Pustulosis amicrobiana de las flexuras. Descripción de un nuevo caso y revisión de la literatura.

Amicrobial pustulosis of the folds is a rare disorder characterized by a recurrent sterile pustular rash mainly affecting the skinfolds, scalp, and periorificial regions such as around the external auditory meatus. Few cases have been reported in the literature, most of them occurring women and all of them associated with some immunological disorder, the most common being lupus erythematosus. We present a new case of amicrobial pustulosis of the folds in a woman; the only immunologic abnormality detected was an elevation of immunoglobulin E. We have also reviewed the 35 cases reported in the literature.

Opciones terapéuticas en quistes odontogénicos. Revisión / Therapeutic options in odontogenic cyst. Review

Los huesos maxilares constituyen asiento de una gran variedad de quistes y neoplasias que pueden ser de difícil diagnóstico. De entre todos los procesos tumorales que se dan en el territorio maxilofacial, los quistes son de gran importancia debido a la frecuencia de su presentación. Los quistes maxilares tienen distinto origen y comportamiento clínico. A partir de la clasificación de la OMS de 1992, esta revisión estudia las características clínicas, radiográficas y epidemiológicas de los quistes del desarrollo odontógenos. Una adecuada exploración clínica y radiográfica por parte del odontólogo es suficiente para alcanzar un diagnóstico de presunción. Las consideraciones clínicas y terapéuticas de cada uno de estos quistes son variables, por lo que es necesario conocer el comportamiento epidemiológico de ellos. El diagnóstico de presunción, el tamaño de la lesión y la relación de esta con estructuras anatómicas vecinas condicionará el tipo de tratamiento. El diagnóstico definitivo lo dictaminará el análisis anatomopatológico (AU)

The maxillary bones constitute the base of a big variety of cyst and tumours that can be difficult to diagnose. Among all the tumor processes that can occur in the maxillofacial area, cysts are of the utmost importance due to their frequency. Jaw cysts have different origins and clinical behaviour. After the OMS classification in 1992,this review examines the clinical, radiographic and epidemiological characteristics of the cyst of the odontogenic development. An appropriate clinical and radiographic exploration on the part of the dentist is enough to reach a presumptive diagnosis. The clinical and therapeutic considerations of each of these cysts are variable, so it is necessary to know their epidemiological behaviour. The presumptive diagnosis, the size of the cyst and its relationship with neighbouring anatomical structures will determine the type of treatment. The definitive diagnosis will be determined by the anatomical and pathological diagnosis (AU)

Evaluation of two dextrose-based directly compressible excipients.

The objectives of this research were to evaluate the physical properties and compaction behavior of two dextrose-based directly compressed excipients. Anhydrous theophylline (10% w/w) was used as a drug model, Emdex and or Maltrin M510 (89.5% w/w) were used as diluent, and magnesium stearate (0.5% w/w) was used as lubricant. Direct compression and wet granulation methods were used for preparing the compacts. In general, the wet granulation method reduced the density of the mixture and consequently its flow rate compared to the mixture prepared only by solid-solid mixing. All formulations were compressed at four different compressional forces and at a target weight of 450 mg +/- 5%. Tablets obtained were different in physical properties and mechanical strength based on type of excipient used and methods of tablet preparation (direct compression versus wet granulation). Compacts prepared from Maltrin M510 had a longer disintegration time and slower drug release than compacts of the same composition but prepared with Emdex. Disintegration time and drug dissolution from tablets containing Maltrin M510 as diluent and prepared by wet granulation appeared to be controlled by a "gel" layer formation around the tablets and not by the tablets porosity. This study demonstrates that full characterization of excipients is needed because a different manufacturing process for the same excipients may produce differences in the pharmaceutical products.

Compressional characterization of two dextrose-based directly compressible excipients using an instrumented tablet press.

The main objective of this work was to evaluate the compaction behavior and record the work and the force involved in the compaction of blends and granules of two dextrose-based directly compressed excipients using a single-punch instrumented tablet press. The second objective was to identify the predominant form of deformation for the two different directly compressible excipients. Anhydrous theophylline (10% w/w) was used as a drug model, Emdex and/or Maltrin M 510 (89.5% w/w) were used as diluent, and magnesium stearate (0.5% w/w) was used as lubricant. All formulations were compressed at four different compressional forces and at a target tablet weight of 450 mg +/- 5%. Results show that compacts prepared from Emdex using the direct compression method produced the lowest elastic work and die wall friction, and the best degree of lubrication. Wet granulation for Maltrin M 510 decreased elastic work, frictional work, and ejection force, and enhanced both net work and degree of lubrication. In general, wet granulation for both Emdex and Maltrin M 510 decreased the crushing strength of the tablets and enhanced the degree of lubrication, compared to direct compression formulations. All formulations showed similar shape pattern for plastic deformation, suggesting that the predominant mechanism of deformation is plastic deformation type a Heckel plots.

Eritema nodoso inducido por anillo vaginal / Vaginal ring inducing erythema nodosum

El eritema nodoso (EN) es la forma de paniculitis más común, y a su vez es considerado el prototipo de paniculitis septal. Este trastorno representauna reacción de hipersensibilidad frente a diferentes antígenos, así como múltiples enfermedades sistémicas y fármacos. Aunque en la mayoríade casos se desconoce la causa. Nuevos fármacos se añaden a la lista involucrados en la etiopatogenia del EN. Reportamos dos casos de EN en relacióncon el uso del anillo vaginal (AU)

Erythema nodosum (EN) represents the commonest form of nodular panniculitis and is the prototype of septal panniculitis. This disorder representsa hypersensitivity reaction in front of different antigens, such as several systemic diseases and drug therapies. In the majority of cases, the causeremains unknown. New drugs are being added to the list of drugs implicated in the etiopathogenesis of EN. We report two cases of EN in relationto the use of the vaginal ring (AU)

Pustulosis amicrobiana de las flexuras. Descripción de un nuevo caso y revisión de la literatura / Amicrobial Pustulosis of the Folds: Report of a New Case and Review of Literature

La pustulosis amicrobiana de las flexuras es una entidad poco frecuente, caracterizada por erupciones formadas por pústulas estériles, de curso recidivante, que afectan a los grandes pliegues cutáneos, cuero cabelludo y áreas periorificiales como el conducto auditivo externo, mayormente. Se han descrito pocos casos en la literatura, la mayoría de ellos en mujeres, y todos ellos asociados a alguna alteración inmunológica, siendo el lupus eritematoso el más frecuente. Presentamos un nuevo caso de esta enfermedad, en una mujer que como única alteración inmunológica presentaba una elevación de la IgE, revisando también los casos descritos en la literatura por el momento (AU)

Amicrobial pustulosis of the folds is a rare disorder characterized by a recurrent sterile pustular rash mainly affecting the skinfolds, scalp, and periorificial regions such as around the external auditory meatus. Few cases have been reported in the literature, most of them occurring women and all of them associated with some immunological disorder, the most common being lupus erythematosus. We present a new case of amicrobial pustulosis of the folds in a woman; the only immunologic abnormality detected was an elevation of immunoglobulin E. We have also reviewed the 35 cases reported in the literature (AU)

Erupción acneiforme secundaria a cetuximab con cambios histopatológicos pseudomalignos / Acneiform eruption secondary to cetuximab with pseudomalignant histopathological changes

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Leiomiomatosis intravenosa / Intravenous leiomyomatosis

La leiomiomatosis intravenosa es una neoplasia benigna rara, que crece en el interior de los vasos pélvicos y vena cava inferior y que, raramente, alcanza cavidades derechas del corazón. Nosotros presentamos un caso de leiomiomatosis intravenosa sin afectación cardíaca, con diagnóstico casual durante el estudio histológico. El tratamiento de elección es la resección quirúrgica de útero y ovarios (AU)