New Perspectives on Circulating Ferritin: Its Role in Health and Disease.

The diagnosis of iron disturbances usually includes the evaluation of serum parameters. Serum iron is assumed to be entirely bound to transferrin, and transferrin saturation-the ratio between the serum iron concentration and serum transferrin-usually reflects iron availability. Additionally, serum ferritin is commonly used as a surrogate of tissue iron levels. Low serum ferritin values are interpreted as a sign of iron deficiency, and high values are the main indicator of pathological iron overload. However, in situations of inflammation, serum ferritin levels may be very high, independently of tissue iron levels. This presents a particularly puzzling challenge for the clinician evaluating the overall iron status of the patient in the presence of an inflammatory condition. The increase in serum ferritin during inflammation is one of the enigmas regarding iron metabolism. Neither the origin, the mechanism of release, nor the effects of serum ferritin are known. The use of serum ferritin as a biomarker of disease has been rising, and it has become increasingly diverse, but whether or not it contributes to controlling the disease or host pathology, and how it would do it, are important, open questions. These will be discussed here, where we spotlight circulating ferritin and revise the recent clinical and preclinical data regarding its role in health and disease.

Serum amyloid A proteins reduce bone mass during mycobacterial infections.

Introduction: Osteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required. Methods: Genetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis. Results and discussion: We found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.

Cystic Fibrosis Bone Disease: The Interplay between CFTR Dysfunction and Chronic Inflammation.

Cystic fibrosis is a monogenic disease with a multisystemic phenotype, ranging from predisposition to chronic lung infection and inflammation to reduced bone mass. The exact mechanisms unbalancing the maintenance of an optimal bone mass in cystic fibrosis patients remain unknown. Multiple factors may contribute to severe bone mass reduction that, in turn, have devastating consequences in the patients' quality of life and longevity. Here, we will review the existing evidence linking the CFTR dysfunction and cell-intrinsic bone defects. Additionally, we will also address how the proinflammatory environment due to CFTR dysfunction in immune cells and chronic infection impairs the maintenance of an adequate bone mass in CF patients.

Prevalence and associated factors for asthma in adults in Quito: a cross-sectional study.

Background: Although several epidemiological studies of asthma have been carried out in Ecuador in the last two decades, none of these has estimated the prevalence of asthma in adult populations. Objective: To estimate the prevalence of asthma symptoms in adults in the city of Quito and to identify possible associated factors. Methods: A cross-sectional study was conducted on subjects older than 18 years residing in the Metropolitan District of Quito. The Global Asthma Network (GAN) questionnaire was applied to collect information on asthma symptoms and sociodemographic and lifestyle data. Bivariate and multivariate analyses with logistic regression were used to identify asthma-related factors. Results: 2,476 subjects answered the questionnaire (80.9% women, mean age 40 years). The prevalence of wheezing in the last 12 months, asthma ever, and asthma diagnosed by a doctor were 6.3%, 1.9% and 1.6%, respectively. The prevalence of rhinitis ever and eczema ever was 13.7% and 5.5%. The presence of mould at home (OR: 2.13; 95% CI: 1.48 -3.06; p <0.001), cat at home (OR: 1.06; 95% CI: 1.06 -2.13; p <0.022) and rhinitis at some time (OR: 3.65; 95% CI: 2.53 - 5.29; p <0.022) were associated with the presence of wheezing in the last 12 months. Conclusions: Our study shows that, compared to other cities in Latin America, the prevalence of asthma in adults in Quito is relatively low. Along with the presence of rhinitis, factors related to housing quality are closely linked to the occurrence of asthma in adult populations.

Antecedentes: Aunque en el Ecuador se han realizado varios estudios epidemiológicos de asma en las dos últimas décadas, ninguno de estos ha estimado la prevalencia de asma en poblaciones adultas. Objetivo: Estimar la prevalencia de síntomas de asma en adultos en Quito e identificar posibles factores asociados. Métodos: Se realizó un estudio transversal en sujetos mayores a 18 años residentes en la ciudad de Quito-Ecuador. Se aplicó el cuestionario Global Asthma Network para recolectar información sobre síntomas de asma y datos sociodemográficas y de estilo de vida. Para la identificación de factores asociados con asma se utilizó análisis bivariados y multivariados con regresión logística. Resultados: Un total de 2,476 sujetos respondieron el cuestionario (80.9% mujeres, edad media 40 años). La prevalencia de sibilancias en los últimos 12 meses, asma alguna vez y asma diagnosticado por un médico fue de 6.3%; 1.9% y 1.6%, respectivamente. La prevalencia de rinitis y eczema alguna vez fue de 13.7% y 5.5%. La presencia de moho en el hogar (OR: 2.13; 95% IC: 1.48-3.06; p <0.001), gato en casa (OR: 1.06; 95% IC: 1.06-2.13; p <0.022) y rinitis alguna vez (OR: 3.65; 95% IC: 2.53-5.29; p <0.022) estaban asociados con la presencia de sibilancias en los últimos 12 meses. Conclusiones: Nuestro estudio muestra que, en comparación con otras ciudades de América Latina, la prevalencia de asma en adultos en Quito es relativamente baja. Junto con la presencia de rinitis, factores relacionados con la calidad de la vivienda están estrechamente ligados con la ocurrencia de asma en poblaciones adultas.

Prevalence and associated factors for asthma in adults in Quito: a cross-sectional study / Prevalencia y factores asociados para asma en adultos en Quito: un estudio transversal

Abstract Background: Although several epidemiological studies of asthma have been carried out in Ecuador in the last two decades, none of these has estimated the prevalence of asthma in adult populations. Objective: To estimate the prevalence of asthma symptoms in adults in the city of Quito and to identify possible associated factors. Methods: A cross-sectional study was conducted on subjects older than 18 years residing in the Metropolitan District of Quito. The Global Asthma Network (GAN) questionnaire was applied to collect information on asthma symptoms and sociodemographic and lifestyle data. Bivariate and multivariate analyses with logistic regression were used to identify asthma-related factors. Results: 2,476 subjects answered the questionnaire (80.9% women, mean age 40 years). The prevalence of wheezing in the last 12 months, asthma ever, and asthma diagnosed by a doctor were 6.3%, 1.9% and 1.6%, respectively. The prevalence of rhinitis ever and eczema ever was 13.7% and 5.5%. The presence of mould at home (OR: 2.13; 95% CI: 1.48 -3.06; p <0.001), cat at home (OR: 1.06; 95% CI: 1.06 -2.13; p <0.022) and rhinitis at some time (OR: 3.65; 95% CI: 2.53 - 5.29; p <0.022) were associated with the presence of wheezing in the last 12 months. Conclusions: Our study shows that, compared to other cities in Latin America, the prevalence of asthma in adults in Quito is relatively low. Along with the presence of rhinitis, factors related to housing quality are closely linked to the occurrence of asthma in adult populations.

Resumen Antecedentes: Aunque en el Ecuador se han realizado varios estudios epidemiológicos de asma en las dos últimas décadas, ninguno de estos ha estimado la prevalencia de asma en poblaciones adultas. Objetivo: Estimar la prevalencia de síntomas de asma en adultos en Quito e identificar posibles factores asociados. Métodos: Se realizó un estudio transversal en sujetos mayores a 18 años residentes en la ciudad de Quito-Ecuador. Se aplicó el cuestionario Global Asthma Network para recolectar información sobre síntomas de asma y datos sociodemográficas y de estilo de vida. Para la identificación de factores asociados con asma se utilizó análisis bivariados y multivariados con regresión logística. Resultados: Un total de 2,476 sujetos respondieron el cuestionario (80.9% mujeres, edad media 40 años). La prevalencia de sibilancias en los últimos 12 meses, asma alguna vez y asma diagnosticado por un médico fue de 6.3%; 1.9% y 1.6%, respectivamente. La prevalencia de rinitis y eczema alguna vez fue de 13.7% y 5.5%. La presencia de moho en el hogar (OR: 2.13; 95% IC: 1.48-3.06; p <0.001), gato en casa (OR: 1.06; 95% IC: 1.06-2.13; p <0.022) y rinitis alguna vez (OR: 3.65; 95% IC: 2.53-5.29; p <0.022) estaban asociados con la presencia de sibilancias en los últimos 12 meses. Conclusiones: Nuestro estudio muestra que, en comparación con otras ciudades de América Latina, la prevalencia de asma en adultos en Quito es relativamente baja. Junto con la presencia de rinitis, factores relacionados con la calidad de la vivienda están estrechamente ligados con la ocurrencia de asma en poblaciones adultas.

Morbilidad materna extrema y mortalidad en un hospital regional de Sudáfrica / Extreme maternal morbidity and mortality in a regional hospital in South Africa

Introducción La vigilancia de la morbilidad materna severa y la mortalidad contribuye a evaluar el estado de la salud materna en los diferentes países. Objetivo Caracterizar la morbilidad materna extrema y la mortalidad materna en un hospital regional de Sudáfrica. Método Estudio descriptivo transversal en el Hospital Tshilidzini de Sudáfrica durante 3 años con un universo de 145 casos de morbilidad y 21 muertes maternas que también constituyó la muestra de manera intencional. Los datos se recolectaron mediante un formulario y se calcularon indicadores de salud materna empleando medidas descriptivas y pruebas inferenciales para el análisis estadístico. Resultados Hubo mayor morbilidad en adolescentes (30,3%) y mortalidad en añosas (28,6%), sin diferencias en cuanto al lugar de procedencia; la eclampsia (35,9%), preeclampsia severa (23,4%) y la hemorragia postparto (19,3%) fueron las causas principales de morbilidad; así, la hemorragia postparto (42,9%) y las infecciones severas (28,6%) de mortalidad, y el shock hipovolémico (23,8%), síndrome de dificultad respiratoria aguda (19%) y coagulación intravascular diseminada (14,3%) las causas finales más frecuentes. La razón de morbilidad materna extrema y resultado materno adverso fue 8,4 y 9,6 por cada 1000 nacidos vivos respectivamente; la razón de mortalidad materna 121,1 por cada 100 000 nacidos vivos, la razón morbilidad / mortalidad 6,9:1 y el índice de mortalidad 12,7%. Conclusiones La preeclamsia-eclampsia, hemorragia obstétrica e infecciones severas constituyeron las principales causas de morbilidad y mortalidad, todas mayormente prevenibles y que llevan a indicadores desfavorables de salud materna.

ABSTRACT Introduction Surveillance of severe maternal morbidity and mortality helps to assess the state of maternal health in different countries. Objective To characterize extreme maternal morbidity and maternal mortality in a regional hospital in South Africa. Method Cross-sectional descriptive study at Tshilidzini Hospital in South Africa for 3 years with a universe of 145 cases of morbidity and 21 maternal deaths that also intentionally constituted the sample. Data were collected using a form and maternal health indicators were calculated using descriptive measures and inferential tests for statistical analysis. Results There was greater morbidity in adolescents (30,3%) and mortality in elderly women (28,6%), without differences in the place of origin; eclampsia (35,9%), severe preeclampsia (23,4%) and postpartum hemorrhage (19,3%) were the main causes of morbidity; thus, postpartum hemorrhage (42,9%) and severe infections (28,6%) of mortality, and hypovolemic shock (23,8%), acute respiratory distress syndrome (19%) and disseminated intravascular coagulation (14,3%) the most frequent final causes. Extreme maternal morbidity ratio and adverse maternal outcome was 8,4 and 9,6 per 1000 live births respectively; the maternal mortality ratio 121,1 per 100,000 live births, the morbidity / mortality ratio 6,9: 1 and the mortality index 12,7%. Conclusions The preeclampsia-eclampsia, obstetric hemorrhage and severe infections were the main causes of morbidity and mortality, all mostly preventable and leading to unfavorable indicators of maternal health.

Involvement of Potassium Channels, Nitric Oxide Synthase, and Guanylate Cyclase in the Spasmolytic Effect of Simaba ferruginea A.St.-Hil on Rat Isolated Ileum.

BACKGROUND AND AIM: Simaba ferruginea A.St.-Hil. Popularly known as "calunga," is a typical Brazilian cerrado plant whose rhizomes are popular for treating diarrhea. AIMS: The aim of this study was to evaluate the spasmolytic activity and the antidiarrheal effect of the ethanolic extract obtained from S. ferruginea (Sf-EtOH). METHODS: Ileal segments (1-2 cm) from male Wistar rats were mounted in isolated organ baths and connected to a force transducer, and then to an amplifier which was connected to a computer (AVS Projetos/São Paulo-SP). After stabilization for 60 min, under tension (1 gf), two submaximal contractions were induced with KCl 40 mM or carbachol 10-6 M on ileal segments. During the third tonic and sustained contraction, Sf-EtOH was added in cumulative concentrations to the organ bath. Incubations with L-NAME (10-4 M), ODQ (10-5 M), TEA+ (5 or 1 mM), glibenclamide (10-5 M), or apamine (100 nM) were prepared (n = 5), separately and used to verify the involvement of the nitric oxide synthase, guanylate cyclase, and potassium channels in the relaxing effect. The results were expressed as mean ± standard error of the mean and were statistically evaluated using one-way ANOVA followed by Bonferroni test, when necessary *p < 0.05. RESULTS: Sf-EtOH promotes relaxation on rat isolated ileum pre-contracted with CCh and KCl in a concentration-dependent manner. Sf-EtOH also inhibited ileum contractions against cumulative concentrations of carbachol (CCh), KCl, and CaCl2, shifting the curves to the right in a non-parallel manner with an Emax reduction. In the presence of potassium channel blockers, Sf-EtOH shifted the curves to the right with a reduction of Emax, suggesting the involvement of BKCa, KATP, and SKCa in its spasmolytic effect. In the presence of L-NAME or ODQ, the relaxation curves were shifted to the right, suggesting the involvement of this pathway in Sf-EtOH spasmolytic effect. CONCLUSIONS: Sf-EtOH acts in a concentration-dependent manner, involving the positive modulation of K+ channels and NO pathway.

Evaluación de la exposición de ciclistas a la contaminación del aire: una revisión de la literatura / Evaluation of cyclists exposure to air pollution: a literature review

RESUMEN Objetivos Describir e interpretar las metodologías y resultados de los principales estudios relacionados con el monitoreo de contaminación atmosférica en ciclistas. Métodos Se buscaron y analizaron las investigaciones a nivel nacional e internacional de los últimos diez años en las bases de datos Cochrane, Scopus, Embase, Science Direct y Pubmed. La búsqueda se realizó de Agosto a Septiembre del año 2017 usando los siguientes descriptores de búsqueda para MeSH: air pollution, bicycling, environmental exposure, enviromental health, inhalation exposure, environmental pollutants, transportation, public health y toxicology, y para DeCS: contaminación del aire, ciclismo, exposición a riesgos ambientales, contaminantes ambientales, inhalación, transportes, salud pública y toxicología. Resultados Se identificaron diecinueve artículos publicados elegibles. La mayoría de los estudios se realizaron en Europa y Estados Unidos. En Latinoamérica se han reportado cuatro estudios. Otros estudios buscaban comparar la exposición en distintas rutas en bicicleta, comparar trayectos de una misma ruta, y otros determinar la relación distancia vs exposición. De igual manera, variables como el tráfico vehicular, la distancia a las fuentes de emisión y el tipo de ciclorruta, juegan un papel fundamental en la exposición a contaminantes en ciclistas. Conclusiones Se encontraron diversas variables que influyen de forma directa o indirectamente en la exposición a la contaminación del aire de los usuarios de bicicleta, así como algunos factores que pueden reducir la exposición a estos contaminantes.(AU)

ABSTRACT Objectives To describe and interpret the methodologies and results of the main studies related to the monitoring of exposure of cyclists to air pollution. Methods Research and analysis of national and international research of the last ten years in the Cochrane, Scopus, Embase, Science Direct and Pubmed databases. The search was conducted in August and September 2017 using the following search descriptors for MeSH: air pollution, bicycle riding, environmental exposure, environmental health, exposure by inhalation, environmental pollutants, transportation, public health and toxicology. For DeCS: air Pollution, cycling, exposure to environmental risks, environmental pollutants, inhalation, transportation, public health and toxicology. Results Nineteen eligible published articles were identified. Most studies were conducted in Europe and the United States. Four studies have been reported in South America. Other studies seek comparisons on different bicycle routes, compare exposure during variations of the same route, and others determine the distance-exposure relationship. In the same way, variables such as vehicular traffic, distance to the emission sources and the type of bike path, play a fundamental role in the exposure to pollutants in cyclists. Conclusions Several variables were found that influence, directly or indirectly, the cyclists exposure to air pollution, as well as some factors that can reduce this exposure.(AU)

[Evaluation of cyclists exposure to air pollution: a literature review]. / Evaluación de la exposición de ciclistas a la contaminación del aire: una revisión de la literatura.

OBJECTIVES: To describe and interpret the methodologies and results of the main studies related to the monitoring of exposure of cyclists to air pollution. METHODS: Research and analysis of national and international research of the last ten years in the Cochrane, Scopus, Embase, Science Direct and Pubmed databases. The search was conducted in August and September 2017 using the following search descriptors for MeSH: air pollution, bicycle riding, environmental exposure, environmental health, exposure by inhalation, environmental pollutants, transportation, public health and toxicology. For DeCS: air Pollution, cycling, exposure to environmental risks, environmental pollutants, inhalation, transportation, public health and toxicology. RESULTS: Nineteen eligible published articles were identified. Most studies were conducted in Europe and the United States. Four studies have been reported in South America. Other studies seek comparisons on different bicycle routes, compare exposure during variations of the same route, and others determine the distance-exposure relationship. In the same way, variables such as vehicular traffic, distance to the emission sources and the type of bike path, play a fundamental role in the exposure to pollutants in cyclists. CONCLUSIONS: Several variables were found that influence, directly or indirectly, the cyclists exposure to air pollution, as well as some factors that can reduce this exposure.

OBJETIVOS: Describir e interpretar las metodologías y resultados de los principales estudios relacionados con el monitoreo de contaminación atmosférica en ciclistas. MÉTODOS: Se buscaron y analizaron las investigaciones a nivel nacional e internacional de los últimos diez años en las bases de datos Cochrane, Scopus, Embase, Science Direct y Pubmed. La búsqueda se realizó de Agosto a Septiembre del año 2017 usando los siguientes descriptores de búsqueda para MeSH: air pollution, bicycling, environmental exposure, enviromental health, inhalation exposure, environmental pollutants, transportation, public health y toxicology, y para DeCS: contaminación del aire, ciclismo, exposición a riesgos ambientales, contaminantes ambientales, inhalación, transportes, salud pública y toxicología. RESULTADOS: Se identificaron diecinueve artículos publicados elegibles. La mayoría de los estudios se realizaron en Europa y Estados Unidos. En Latinoamérica se han reportado cuatro estudios. Otros estudios buscaban comparar la exposición en distintas rutas en bicicleta, comparar trayectos de una misma ruta, y otros determinar la relación distancia vs exposición. De igual manera, variables como el tráfico vehicular, la distancia a las fuentes de emisión y el tipo de ciclorruta, juegan un papel fundamental en la exposición a contaminantes en ciclistas. CONCLUSIONES: Se encontraron diversas variables que influyen de forma directa o indirectamente en la exposición a la contaminación del aire de los usuarios de bicicleta, así como algunos factores que pueden reducir la exposición a estos contaminantes.