Arsenic exposure is associated with alterations to multiple red blood cell parameters among adults in rural Bangladesh.

Chronic arsenic exposures are associated with multiple hematologic disturbances, including anemia. The goal of this study was to evaluate associations between arsenic exposures and hematological parameters among men and women who are chronically exposed to elevated levels of arsenic from drinking water. Hematologic analyses were performed on blood collected from 755 participants (45% male and 54% female) in the Health Effects of Arsenic Longitudinal Study (HEALS) cohort, Bangladesh. Herein, we used linear regression models to estimate associations between red blood cell (RBC) parameters (i.e., RBC counts, hematocrit (HCT), hemoglobin (Hgb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC)) and measurements of arsenic exposure (urinary arsenic and urinary arsenic metabolites). Arsenic exposures showed trending associations with decreased RBC counts in both men and women, a positive association with MCV in males, and an inverse association with MCHC among males, but not among non-smoking females. Among men, those who smoked had stronger associations between arsenic exposures and MCHC than non-smoking males. Collectively, our results show that arsenic exposures affect multiple RBC parameters and highlight potentially important sex differences in arsenic-induced hematotoxicity.

Experiencia en cirugía colorrectal resectiva laparoscópica en pacientes mayores de 75 años

Objetivo: Describir la experiencia en cirugía colorrectal resectiva laparoscópica en mayores de 75 años durante los años 2004 a 2019 en Clínica INDISA. Material y Método: Estudio transversal de las cirugías electivas por vía laparoscópica en mayores de 75 años, en los que se realizó anastomosis colorrectal, basado en el registro clínico electrónico. Resultados: Un total de 48 cirugías completamente laparoscópicas, la mayoría por cáncer colorrectal (CCR) (89,6%), mostraron indicadores de calidad óptima en la cosecha ganglionar en el 73,2%. Con una mediana de estadía de 6 días y una mortalidad a 30 días de 2,1% (un caso), comparable a las series internacionales. Discusión: El abordaje laparoscópico en pacientes ancianos tiene beneficios por sobre la vía abierta y presenta morbimortalidad aceptable. El balance intraoperatorio entre riesgo/seguridad quirúrgica y pronóstico oncológico es un factor a tener en cuenta en la toma de decisiones, junto con las patologías inherentes al grupo etario y la reserva funcional de cada paciente en particular. Conclusión: Se trata de la primera serie nacional de pacientes sobre 75 años sometidos a cirugía colorrectal resectiva electiva vía laparoscópica. Es factible y seguro en estos pacientes realizar cirugía mínimamente invasiva con morbimortalidad aceptable. La edad por sí sola no representa una contraindicación para la cirugía colorrectal laparoscópica. Es necesario contar con estudios de mayor volumen para conocer mejor la realidad nacional y los resultados a largo plazo.

Objective: To describe the experience in laparoscopic resective colorectal surgery in older than 75 years old, during 2004 to 2019 in INDISA Clinic. Material and Methods: It's a transversal study about all the elective laparoscopic surgeries with colorectal anastomosis in elderly people, based on electronic clinical records. Results: 48 full laparoscopic surgeries, the majority by colorectal cancer (89.6%) shows optimal quality indicators about nodal harvest in 73.2%. The median duration of hospital stay after surgery was 6 days with 30 days mortality of 2.1%. These results are comparable to the international reports. Discussion: The laparoscopic approach in elderly patients has benefits over the open approach with acceptable morbility and mortality. The intraoperatory balance between surgical risk/security and oncologic prognostic it's a factor to consider in the decision-making process besides the morbility by the age and the own functional reserve. Conclusion. It's the first series in Chile about over 75 years patients with laparoscopic resective colorectal surgery. Is feasible and secure to do minimal invasive surgery with acceptable morbility and mortality. Only the age isn't a contraindication to laparoscopic colorectal surgery. It's necessary more studies with mayor number of patients to known better the national results and long-term results.

Evaluación comparativa de la efectividad en el manejo del dolor posthemorroidectomia con tres estrategias farmacológicas diferentes

Introducción: La hemorroidectomía produce un intenso dolor postoperatorio recomendándose la analgesia multimodal para su manejo, manteniéndose como problema no resuelto. El objetivo fue evaluar la efectividad analgésica de tres combinaciones farmacológicas para el dolor post-hemorroidectomía. Materiales y Método: Estudio clínico prospectivo, aleatorizado, realizado en Clínica INDISA, entre diciembre 2019 y diciembre 2021, incluyendo pacientes con indicación de hemorroidectomía electiva. Se excluyeron hemorroidectomías asociadas a otro procedimiento quirúrgico, embarazadas/lactancia, reacciones adversas a medicamentos (RAM) a los fármacos en estudio, enfermedades hepáticas, renales o alteraciones/discapacidades mentales. Grupo I (control): Ketorolaco, Tramadol, Paracetamol. Grupo II: Grupo I y Nifedipino 0,2% tópico. Grupo III: Buprenorfina en parche 10 mcg/hora, Paracetamol y Ketorolaco. Asociado a régimen rico en fibra, polietilenglicol, baños de asiento y omeprazol. Se utilizó estadística descriptiva y analítica usando Chi-cuadrado, ANOVA-Bonferroni, Test de Kruskal Wallis, Wilcoxon y Fisher. Software R, utilizando un alfa del 5%. Resultados: De 117 pacientes, se enrolaron 39 = Grupo I, 41 = Grupo II y 37 = Grupo III. No hubo diferencias en la efectividad analgésica (p = 0,45). Para las RAM se observó que los pacientes con Buprenorfina tuvieron más náuseas (p = 0,08), vómitos (p = 0,04), dermatitis (p < 0,001) y prurito (p = 0,006). Discusión y Conclusiones: No hubo diferencias significativas para la efectividad analgésica post-hemorroidectomía al comparar los grupos de estudio. El uso de nifedipino tópico se recomienda como complemento a la terapia multimodal al mejorar los resultados sin aumentar las RAM. El uso de buprenorfina presentó más RAM sin mejores resultados como analgésico. El principal determinante para el alivio del dolor fue el tiempo transcurrido desde la cirugía.

Introduction: Hemorrhoidectomy produces intense postoperative pain, recommending multimodal analgesia for its management, remaining as an unresolved problem. The aim of this study was to evaluate the analgesic effectiveness of three pharmacological combinations for post-hemorrhoidectomy pain. Material and Method: A prospective, randomized clinical study, conducted at the INDISA Clinic, between December 2019 and December 2021, including patients with an indication for elective hemorrhoidectomy. Hemorrhoidectomies associated with another surgical procedure, pregnant/lactating women, adverse drug reactions (ADRs) to the study drugs, liver and kidney diseases, or mental disorders/disabilities were excluded. Group I (control): Ketorolac, Tramadol, Paracetamol. Group II: Group I and Nifedipine 0.2% topical. Group III: Buprenorphine patch 10 mcg/hour, Paracetamol and Ketorolac. Associated with a diet rich in fiber, polyethylene glycol, sitz baths, and omeprazole. Descriptive and analytical statistics were used using Chi-square, ANOVA-Bonferroni, Kruskal Wallis, Wilcoxon and Fisher test. Software R, using an alpha of 5%. Of 117 patients, 39 = Group I, 41 = Group II and 37 = Group III were enrolled. Results: There were no differences in analgesic effectiveness (p = 0.45). For the ADRs, it was observed that the patients with Buprenorphine had more nausea (p = 0.08), vomiting (p = 0.04), dermatitis (p < 0.001) and itching (p = 0.006). Discussion and Conclusion: There were no significant differences for post-hemorrhoidectomy analgesic effectiveness when comparing the study groups. The use of topical nifedipine is recommended as a complement to multimodal therapy as it improves results without increasing adverse drugs reaction (ADR).The use of buprenorphine presented more ADR without better results as an analgesic.The main determinant for pain relief was the time elapsed since surgery.

Arsenic impairs the lineage commitment of hematopoietic progenitor cells through the attenuation of GATA-2 DNA binding activity.

Arsenic exposure produces significant hematotoxicity in vitro and in vivo. Our previous work shows that arsenic (in the form of arsenite, AsIII) interacts with the zinc finger domains of GATA-1, inhibiting the function of this critical transcription factor, and resulting in the suppression of erythropoiesis. In addition to GATA-1, GATA-2 also plays a key role in the regulation of hematopoiesis. GATA-1 and GATA-2 have similar zinc finger domains (C4-type) that are structurally favorable for AsIII interactions. Taking this into consideration, we hypothesized that early stages of hematopoietic differentiation that are dependent on the function of GATA-2 may also be disrupted by AsIII exposure. We found that in vitro AsIII exposures disrupt the erythromegakaryocytic lineage commitment and differentiation of erythropoietin-stimulated primary mouse bone marrow hematopoietic progenitor cells (HPCs), producing an aberrant accumulation of cells in early stages of hematopoiesis and subsequent reduction of committed erythro-megakaryocyte progenitor cells. Arsenic significantly accumulated in the GATA-2 protein, causing the loss of zinc, and disruption of GATA-2 function, as measured by chromatin immunoprecipitation and the expression of GATA-2 responsive genes. Our results show that the attenuation of GATA-2 function is an important mechanism contributing to the aberrant lineage commitment and differentiation of early HPCs. Collectively, findings from the present study suggest that the AsIII-induced disruption of erythro-megakaryopoiesis may contribute to the onset and/or exacerbation of hematological disorders, such as anemia.

Arsenite exposure inhibits the erythroid differentiation of human hematopoietic progenitor CD34+ cells and causes decreased levels of hemoglobin.

Arsenic exposure poses numerous threats to human health. Our previous work in mice has shown that arsenic causes anemia by inhibiting erythropoiesis. However, the impacts of arsenic exposure on human erythropoiesis remain largely unclear. We report here that low-dose arsenic exposure inhibits the erythroid differentiation of human hematopoietic progenitor cells (HPCs). The impacts of arsenic (in the form of arsenite; As3+) on red blood cell (RBC) development was evaluated using a long-term culture of normal human bone marrow CD34+-HPCs stimulated in vitro to undergo erythropoiesis. Over the time course studied, we analyzed the expression of the cell surface antigens CD34, CD71 and CD235a, which are markers commonly used to monitor the progression of HPCs through the stages of erythropoiesis. Simultaneously, we measured hemoglobin content, which is an important criterion used clinically for diagnosing anemia. As compared to control, low-dose As3+ exposure (100 nM and 500 nM) inhibited the expansion of CD34+-HPCs over the time course investigated; decreased the number of committed erythroid progenitors (BFU-E and CFU-E) and erythroblast differentiation in the subsequent stages; and caused a reduction of hemoglobin content. These findings demonstrate that low-dose arsenic exposure impairs human erythropoiesis, likely by combined effects on various stages of RBC formation.

Inhalation of Tungsten Metal Particulates Alters the Lung and Bone Microenvironments Following Acute Exposure.

Inhalation of tungsten particulates is a relevant route of exposure in occupational and military settings. Exposure to tungsten alloys is associated with increased incidence of lung pathologies, including interstitial lung disease and cancer. We have demonstrated, oral exposure to soluble tungsten enhances breast cancer metastasis to the lungs through changes in the surrounding microenvironment. However, more research is required to investigate if changes in the lung microenvironment, following tungsten particulate exposure, can drive tumorigenesis or metastasis to the lung niche. This study examined if inhalation to environmentally relevant concentrations of tungsten particulates caused acute damage to the microenvironment in the lungs and/or systemically using a whole-body inhalation system. Twenty-four female BALB/c mice were exposed to Filtered Air, 0.60 mg/m3, or 1.7 mg/m3 tungsten particulates (<1 µm) for 4 h. Tissue samples were collected at days 1 and 7 post-exposure. Tungsten accumulation in the lungs persisted up to 7 days post-exposure and produced acute changes to the lung microenvironment including increased macrophage and neutrophil infiltration, increased levels of proinflammatory cytokines interleukin 1 beta and C-X-C motif chemokine ligand 1, and an increased percentage of activated fibroblasts (alpha-smooth muscle actin+). Exposure to tungsten also resulted in systemic effects on the bone, including tungsten deposition and transient increases in gene expression of proinflammatory cytokines. Taken together, acute whole-body inhalation of tungsten particulates, at levels commonly observed in occupational and military settings, resulted in changes to the lung and bone microenvironments that may promote tumorigenesis or metastasis and be important molecular drivers of other tungsten-associated lung pathologies such as interstitial lung disease.

Uranium directly interacts with the DNA repair protein poly (ADP-ribose) polymerase 1.

People living in southwest part of United States are exposed to uranium (U) through drinking water, air, and soil. U is radioactive, but independent of this radioactivity also has important toxicological considerations as an environmental metal. At environmentally relevant concentrations, U is both mutagenic and carcinogenic. Emerging evidence shows that U inhibits DNA repair activity, but how U interacts with DNA repair proteins is still largely unknown. Herein, we report that U directly interacts with the DNA repair protein, Protein Poly (ADP-ribose) Polymerase 1 (PARP-1) through direct binding with the zinc finger motif, resulting in zinc release from zinc finger and DNA binding activity loss of the protein. At the peptide level, instead of direct competition with zinc ion in the zinc finger motif, U does not show thermodynamic advantages over zinc. Furthermore, zinc pre-occupied PARP-1 zinc finger is insensitive to U treatment, but U bound to PARP-1 zinc finger can be partially replaced by zinc. These results provide mechanistic basis on molecular level to U inhibition of DNA repair.

Inhibition of red blood cell development by arsenic-induced disruption of GATA-1.

Anemia is a hematological disorder that adversely affects the health of millions of people worldwide. Although many variables influence the development and exacerbation of anemia, one major contributing factor is the impairment of erythropoiesis. Normal erythropoiesis is highly regulated by the zinc finger transcription factor GATA-1. Disruption of the zinc finger motifs in GATA-1, such as produced by germline mutations, compromises the function of this critical transcription factor and causes dyserythropoietic anemia. Herein, we utilize a combination of in vitro and in vivo studies to provide evidence that arsenic, a widespread environmental toxicant, inhibits erythropoiesis likely through replacing zinc within the zinc fingers of the critical transcription factor GATA-1. We found that arsenic interacts with the N- and C-terminal zinc finger motifs of GATA-1, causing zinc loss and inhibition of DNA and protein binding activities, leading to dyserythropoiesis and an imbalance of hematopoietic differentiation. For the first time, we show that exposures to a prevalent environmental contaminant compromises the function of a key regulatory factor in erythropoiesis, producing effects functionally similar to inherited GATA-1 mutations. These findings highlight a novel molecular mechanism by which arsenic exposure may cause anemia and provide critical insights into potential prevention and intervention for arsenic-related anemias.

Minimal uranium immunotoxicity following a 60-day drinking water exposure to uranyl acetate in male and female C57BL/6J mice.

Historical uranium (U) mining in the Southwestern United States resulted in significant environmental contamination throughout this region and presents a significant risk of chronic metal exposure and toxicity for communities living in close proximity to mine waste sites. Uranium exposure is associated with numerous deleterious health effects including immune dysfunction; however, its effects on the immune system have yet to be fully characterized. We recently published that drinking water exposure to U, in the form of uranyl acetate (UA), results in low overall tissue retention of U (<0.01%), with very little accumulation in immune organs (blood, bone marrow, spleen, and thymus) of male and female mice. In the present study we characterized the immunotoxicity of U, in the form of UA, following a 60-day drinking water exposure to 5 and 50 ppm in male and female C57BL/6J mice. The following immunotoxicity endpoints were evaluated: hematology, immune tissue weights and total cell recoveries, immunophenotying of the spleen and thymus, and immune cell function (lymphocyte mitogenesis and T-dependent antibody response). Uranium exposure had subtle impacts on the immune endpoints evaluated, likely due to low U accumulation at these sites. The only significant alterations were a slight decrease in the percentages of splenic natural killer T-cells and macrophages in exposed male mice. Despite minimal immunological effects, this study highlights the importance of investigating toxicological endpoints in both sexes and developing accurate animal models that model epidemiological exposures in the future.

Minimal uranium accumulation in lymphoid tissues following an oral 60-day uranyl acetate exposure in male and female C57BL/6J mice.

High levels of uranium (U) exist in soil, water, and air in the Southwestern United States due, in part, to waste generated from more than 160,000 abandoned hard rock mines located in this region. As a result, many people living in this region are chronically exposed to U at levels that have been linked to detrimental health outcomes. In an effort to establish a relevant in vivo mouse model for future U immunotoxicity studies, we evaluated the tissue distribution of U in immune organs; blood, bone marrow, spleen, and thymus, as well as femur bones, kidneys, and liver, following a 60-d drinking water exposure to uranyl acetate (UA) in male and female C57BL/6J mice. Following the 60-d exposure, there was low overall tissue retention of U (<0.01%) at both the 5 and the 50 ppm (mg/L) oral concentrations. In both male and female mice, there was limited U accumulation in immune organs. U only accumulated at low concentrations in the blood and bone marrow of male mice (0.6 and 16.8 ng/g, respectively). Consistent with previous reports, the predominant sites of U accumulation were the femur bones (350.1 and 399.0 ng/g, respectively) and kidneys (134.0 and 361.3 ng/g, respectively) of male and female mice. Findings from this study provide critical insights into the distribution and retention of U in lymphoid tissues following chronic drinking water exposure to U. This information will serve as a foundation for immunotoxicological assessments of U, alone and in combination with other metals.

Metáforas biomédicas e interpretación social: ausencias y emergencias dentro de la esfera pública contemporánea / Metáforas biomédicas e interpretação social: ausências e emergências na esfera pública contemporânea / Biomedical metaphors and social interpretation: absences and emergencies within the contemporary public sphere

Resumen El trabajo problematiza sobre el uso de metáforas biomédicas para interpretar fenómenos del mundo social contemporáneo. A partir de la Teoría Lingüística Cognitiva y la Crítica Postcolonial se analizan las metáforas del "Cuerpo Social" y la "Semántica Inmunitaria" como productos históricos de transformaciones tecnológicas y socio-políticas cuyo carácter es altamente conflictivo. Este tipo de metáforas evocarían una secuencia unilineal de examen/diagnóstico/terapia social que facilitaría cierto manejo centralizado y racional del poder. Se concluye que ciencias biomédicas, ciencias sociales y esfera pública del Norte Global compartirían una matriz metafórica asociada a una racionalidad moderna (capitalista/colonial/patriarcal) plegada sobre sí misma, que comienza, sin embargo, a ser progresivamente fisurada por "otras metáforas" producidas en el Sur Global.

Resumo O artigo discute o uso de metáforas biomédicas para interpretar os fenômenos do mundo social contemporâneo. Utilizam-se a Teoria Linguística-Cognitiva e a Crítica Pós-Colonial das Ciências para analisar as metáforas do "Corpo Social" e a "Semântica Imune" da bibliografia selecionada como produtos históricos de transformações tecnológicas e sociopolíticas, cujo caráter é altamente controverso. Este tipo de metáforas evoca uma sequência unilinear de exame/diagnóstico/terapia que socialmente facilitaria uma gestão centralizada e racional do poder. Conclui-se que Ciências Biomédicas, Ciências Sociais e esfera pública do Norte Global compartilham uma matriz metafórica comum associada com a racionalidade moderna (capitalista /colonial/patriarcal) dobrada sobre si mesma, mas que começa gradualmente a ser fissurada por "outras metáforas" produzidas no Sul global.

Abstract This paper problematizes the use of biomedical metaphors to interpret the contemporary social world. Using the Cognitive Linguistic Theory and the Postcolonial Studies of Sciences, it analyzes the metaphors of the "Social Body" and the "Immunitarian Semantics" from a selected bibliography as historical products of technological and socio-political transformations of conflicting characteristics. This kind of metaphors evokes a sequence of examination/diagnosis/social-therapy that facilitates a centralized and rational management of power. Finally, the text suggests that Biomedical Sciences, Social Sciences, and the public sphere of the Global North share a common metaphoric matrix associated with the modern (capitalist/colonial/ patriarchal) rationality, folded over itself, which progressively begins to be fissured by "other metaphors" produced in Global South.

El Sistema Informático de la reforma GES en Chile: una etnografía de dispositivos de gobierno sanitario / The computer system of the GES reform in Chile: ethnography of health governance devices / O sistema de informática na reforma do GES no Chile: uma etnografia dos dispositivos de governança em saúde

Resumen En las últimas décadas las Tecnologías Informáticas han sido incorporadas a los sistemas de atención sanitaria, de la mano de la conformación de "redes asistenciales" que deben integrar distintos niveles, instituciones y agentes. En Chile, el régimen de "Garantías Explicitas en Salud" (GES) se vincula a estas reformas modernizadoras del Estado, cuya meta es mejorar la eficiencia del gasto público. El presente trabajo analiza críticamente el desarrollo e implementación del "Sistema de Información para la Gestión de Garantías en Salud" (SIGGES) incorporando metodologías propias de los Estudios Sociales de la Ciencia y Tecnología, y se propone un diseño de "etnografía del dispositivo". Como principales resultados, se evidencia que esta tecnología informática tiene un rol central en la estabilización de la política modernizadora en salud, que pone la gestión administrativa por sobre la integralidad de los cuidados. El SIGGES actúa como mediador entre múltiples niveles y agentes en salud para medir la productividad del sistema, vinculado al financiamiento, con lo cual modifica actividades clínicas y procesos de subjetivación, haciendo que se privilegien prestaciones curativas sobre preventivas y de promoción, patologías GES sobre No-GES, y conglomerados urbanos sobre zonas rurales.

Abstract In the last decades, computer technologies have been incorporated into health care systems, through the conformation of "healthcare networks" that must integrate different levels, institutions and agents. In Chile, the system of "Explicit Guarantees in Health" (GES) is linked to these modernizing reforms of the State, whose goal is to improve the efficiency of public spending. This work critically analyzes the development and implementation of the "Information System for the Management of Guarantees in Health" (SIGGES) incorporating methodologies from the Social Studies of Science and Technology, and proposing a "device ethnography" design. As main results, the evidence shows that this information technology has a central role in the stabilization of modernizing health policy, which places administrative management over the integrality of care: SIGGES acts as a mediator between multiple levels and agents in health to measure the productivity of the system, linked to financing, with which modifies clinical activities and processes of subjectivation, privileging curative benefits on preventive and promotion, pathologies GES on No-GES, and urban conglomerates on rural areas.

Resumo Nas últimas décadas, as tecnologias da informação foram incorporadas aos sistemas de saúde por meio da criação de "redes assistenciais", que devem integrar diferentes níveis, instituições e agentes. No Chile, o regime de "garantias explícitas em saúde" (GES) liga-se a essas reformas modernizadoras do Estado, cujo objetivo é melhorar a eficiência dos gastos públicos. Este trabalho analisa criticamente o desenvolvimento e implementação do "Sistema de Informação para a Gestão de Garantias em Saúde" (SIGGES), incorporando metodologias dos Estudos Sociais de Ciência e Tecnologia, e propõe um desenho de "etnografia do dispositivo". Como principais resultados, fica evidente que esta tecnologia da informação tem papel central na estabilização da política de saúde modernizadora, que deixa a gestão administrativa acima da integralidade do cuidado: o SIGGES atua como um mediador entre vários níveis e agentes em saúde para medir a produtividade do sistema, vinculada ao financiamento, com o qual modifica atividades clínicas e processos de subjetivação, privilegiando serviços curativos em vez de preventivos e de promoção; patologías GES em vez de No-GES, e centros urbanos em detrimento de áreas rurais.

Arsenic exposures alter clinical indicators of anemia in a male population of smokers and non-smokers in Bangladesh.

Drinking water arsenic (WAs) exposure has been linked to a number of detrimental health outcomes including anemia, primarily among pregnant women. Little is known about the effects of arsenic (As) on hematological disorders among men. We have examined the role of As exposure on hematological indicators of anemia in a group of men exposed to a wide range of As in their drinking water. We conducted a cross-sectional investigation among 119 healthy men in the Health Effects of As Longitudinal Study (HEALS) cohort, in rural Bangladesh. The participants are part of an ongoing study focused on evaluating the influence of As and smoking on immune function. Samples were collected at recruitment and analyzed for water As, urinary As (UAs) and UAs metabolites to assess As exposure. Blood samples were also collected at recruitment and assayed immediately for hematological parameters. We found that increased WAs levels were associated with decreased red blood cell counts [ß=-0.13, p<0.0001] as well as hematocrit packed cell volumes [ß=-0.68, p=0.008] following adjustment for age, smoking, body mass index and polycyclic aromatic hydrocarbon-DNA adducts. Other measures of As exposure (UAs and its metabolites) demonstrated similar associations. Slightly stronger effects were observed among smokers. We also observed an effect of As on hemoglobin among smokers in relation to UAs [ß=-0.54, p<0.05]. Our analysis revealed effects of As exposure on hematological indicators of anemia in a group of healthy male smokers and non-smokers.

Low level arsenite exposures suppress the development of bone marrow erythroid progenitors and result in anemia in adult male mice.

Epidemiological studies report an association between chronic arsenic (As) exposure and anemia in men, and women who are predisposed to anemia. The purpose of these studies was to determine whether a 60 d drinking water exposure of adult male C57BL/6J mice to 0, 100, and 500ppb arsenite (As+3) results in anemia due to alterations in erythroid progenitor cell development in the bone marrow. Exposure to 500ppb As+3 for 60 d resulted in a reduction of mean corpuscular hemoglobin (MCH) levels, but did not significantly alter red blood cell (RBC) counts, hemoglobin (Hgb) levels, mean corpuscular Hgb concentrations (MCHC), or mean corpuscular volumes (MCV). Attenuation of burst-forming unit-erythroid (BFU-E) colony formation was observed in bone marrow cells of mice exposed to 500ppb As+3. The differentiation of late-stage bone marrow erythroblasts as defined by CD71 and Ter119 surface marker expression was reduced with the 500ppb As+3 exposure. Mice exposed to 500ppb As+3 also had elevated serum levels of erythropoietin (EPO). Collectively, these results show that exposure to low levels of As+3 attenuate the development of early BFU-E cells and reduce the differentiation of late-stage erythroblasts. This suppression of bone marrow erythropoiesis may be a contributing factor to the mild hypochromic anemia observed in 500ppb As+3 exposed mice.

Differential sensitivities of bone marrow, spleen and thymus to genotoxicity induced by environmentally relevant concentrations of arsenite.

It is known in humans and mouse models, that drinking water exposures to arsenite (As+3) leads to immunotoxicity. Previously, our group showed that certain types of immune cells are extremely sensitive to arsenic induced genotoxicity. In order to see if cells from different immune organs have differential sensitivities to As+3, and if the sensitivities correlate with the intracellular concentrations of arsenic species, male C57BL/6J mice were dosed with 0, 100 and 500ppb As+3via drinking water for 30d. Oxidation State Specific Hydride Generation- Cryotrapping- Inductively Coupled Plasma- Mass Spectrometry (HG- CT- ICP- MS) was applied to analyze the intracellular arsenic species and concentrations in bone marrow, spleen and thymus cells isolated from the exposed mice. A dose-dependent increase in intracellular monomethylarsonous acid (MMA+3) was observed in both bone marrow and thymus cells, but not spleen cells. The total arsenic and MMA+3 levels were correlated with an increase in DNA damage in bone marrow and thymus cells. An in vitro treatment of 5, 50 and 500nM As+3 and MMA+3 revealed that bone marrow cells are most sensitive to As+3 treatment, and MMA+3 is more genotoxic than As+3. These results suggest that the differential sensitivities of the three immune organs to As+3 exposure are due to the different intracellular arsenic species and concentrations, and that MMA+3 may play a critical role in immunotoxicity.

Evaluation of Toxicity in Mouse Bone Marrow Progenitor Cells.

Development of blood cells through hematopoiesis occurs in the bone marrow (BM), and can be adversely impacted by various substances and/or conditions ranging from known therapeutic, intentionally administered xenobiotics to unintentional food additives and exposure to environmental chemicals. The principles underlying the techniques for evaluating toxicity to BM progenitors (erythroid, myeloid, and lymphoid) exploit changes in the normal hematopoietic process, biochemical cell surface and intracellular markers, as well as components of the BM microenvironment. Toxicological investigations following in vivo exposures of mice or in vitro exposures of mouse primary BM cell cultures allow the assessment of the developmental and functional integrity of BM cells, cell population shifts, and adverse biochemical effects due to toxicity. Colony forming unit (CFU) assays and flow cytometry are indispensable techniques in these toxicity studies.

Comportamiento in vitro del colágeno de la unión amelo-dentinaria en premolares humanos sometidos a altas temperaturas / In vitro behavior of the dentin-enamel junction collagen in human premolars subjected to high temperatures

Objetivo: Determinar el comportamiento in vitro del colágeno de la unión amelo-dentinaria en premolares humanos sometidos a altas temperaturas. Materiales y métodos:Estudio descriptivo pseudo-experimental in vitro de corte transversal que determinó, a través de microscopía electrónica de barrido, el comportamiento físico del colágeno de la unión amelodentinaria en 60 premolares humanos sometidos a altas temperaturas (200°C, 400°C, 600°C, 800°C y 1.000°C), para proporcionar evidencia científica que permita emplear la separación del esmalte y la dentina como un marcador fehaciente repetitivo de utilidad en los procesos de identificación odontológica y documentación de la necropsia médico-legal para el caso de cadáveres o restos humanos que resulten quemados, carbonizados o incinerados. Resultados:Se observa que el diseño micro-estructural del patrón reticular de colágeno de la dentina en relación con los cristales de hidroxiapatita resulto afectado conforme aumentaba la temperatura. Conclusiones: En conjunto, la alteración del patrón reticular del colágeno y los cambios micro-estructurales de la hidroxiapatita de calcio (fusión y sinterización de las nano-esferas de fosfato octa-cálcico) de la dentina y del esmalte, explican la separación gradual y progresiva de estos dos tejidos a nivel de la unión amelo-dentinaria.

Objective: To determine the behavior in vitro of collagen at the dentine-enamel junction of human premolars subjected to high temperatures. Materials and methods: Pseudo-experimental descrip-tive study, in vitro, cross-sectional, that determined by Scanning Electron Microscopy (SEM), the physical behavior of collagen at the dentine-enamel junction in 60 human premolars subjected to high temperatures (200°C, 400°C, 600°C, 800°C and 1000°C) to provide scientific evidence that allows to employ the separation of enamel and dentin as a reliable repetitive marker, useful in dental identification processes and documentation of medical-legal autopsy for bodies or human remains that were burned, charred or incinerated. Results: It was observed that the micro-structural design of reticular collagen pattern of the dentin in relation to hydroxyapatite crystals, was affected with increasing temperature. Conclusions: In general, alteration of reticular collagen pattern and the micro-structural changes of calcium hydroxyapatite (melting and sintering of the nano-spheres of octa-calcium phosphate) of dentin and enamel, explains the gradual and progressive separation of both tissues in dentine-enamel junction level.

Análisis mediante radiografía convencional de los tejidos dentales y periodontales de cerdo (Sus domesticus) sometidos a altas temperaturas / Conventional X-ray analysis of porcine (Sus domesticus) periodontal and dental tissue subjected to high temperature

Introducción: La implementación de modelos animales para el estudio de los tejidos dentales y periodontales de dientes articulados en sus alvéolos sometidos a altas temperaturas permite el establecimiento de parámetros repetitivos que contribuyen con los procesos de identificación. Objetivo: Describir los cambios radiográficos de los tejidos dentales y periodontales de cerdo (Sus domesticus) sometidos a altas temperaturas. Material y métodos: Se realizó un estudio observacional descriptivo de naturaleza pseudo-experimental in vitro para observar los cambios radiográficos de los tejidos dentales y periodontales en 60 dientes de cerdo doméstico sometidos a altas temperaturas (200, 400, 600, 800 y 1,000 ºC). Resultados: Los tejidos dentales y periodontales estudiados presentan gran resistencia a las altas temperaturas sin variar considerablemente su microestructura, de tal manera que los cambios físicos (estabilidad dimensional, fisuras, grietas y fracturas) que ocurren en la medida que aumenta la temperatura pueden describirse a través de radiografía convencional. Conclusiones: El análisis radiográfico de los dientes articulados en sus respectivos alvéolos se constituye en un mecanismo para determinar la temperatura a la cual estuvo sometido un diente, lo que puede ser empleado durante el proceso de identificación odontológica y documentación de la necropsia médico-legal para el caso de cadáveres o restos humanos quemados, carbonizados e incinerados. El cerdo doméstico (Sus domesticus) se constituye en un modelo animal experimental adecuado para estudiar dichos cambios; sin embargo, se recomienda realizar un estudio en dientes humanos articulados en su respectiva unidad alveolar, para determinar si los hallazgos radiográficos descritos se repiten y son extrapolables.

Introduction: The implementation of animal models for the study of periodontal and dental tissues of teeth articulated into their sockets and subjected to high temperatures allows the establishment of repetitive parameters which might contribute to identification processes. Aim: To describe radiographic changes of pig's (Sus domesticus) periodontal and dental tissues subjected to high temperatures. Material and methods: An in vitro pseudo-experimental, descriptive and observational study was undertaken in order to assess radiological changes of periodontal and dental tissues of 60 domestic pig's teeth which had been subjected to high temperatures (200, 400, 600, 800 and 1,000 ºC). Results: The dental and periodontal tissues subject of this research article presented strong resistance to high temperatures without considerable variation of their micro-structure. Thus, physical changes (dimensional stability, fissures, cracks and fractures) which took place as temperature increased, could be described using a conventional X-ray. Conclusions: Radiographic examination of teeth articulated in their sockets can be established as a mechanism to determine the temperature at which the tooth was subjected. This could be used in processes of dental identification and medical-legal autopsy documentation in cases of burned, carbonized or incinerated human remains. Domestic pigs (Sus domesticus) can be regarded as a suitable experimental animal models to study the aforementioned changes. Nevertheless, a study involving human teeth articulated in their own socket is recommended in order to determine whether the radiographic findings herein described are replicated and can be extrapolated.