Arsenic exposure in northern Mexican women / Exposición a arsénico en mujeres del norte de México

Abstract: Objective: To describe interindividual metabolism variations and sociodemographic characteristics associated to urinary arsenic, and to estimate the arsenic contamination in water from urinary total arsenic (TAs). Materials and methods: Women (n=1 028) from northern Mexico were interviewed about their sociodemographic characteristics and their urinary concentrations of arsenic species were measured by liquid chromatography. Inorganic arsenic (iAs) in water was estimated from urinary TAs. Results: Women were 20-88 years old. TAs in urine ranged from p10=3.41 to p90=56.93 μg/L; 74% of women had levels >6.4 μg/L. iAs in water varied from p10=3.04 to p90=202.12 μg/L; 65% of women had concentrations >10 μg/L, and 41%, concentrations >25 μg/L. Large variations in iAs metabolism were observed. TAs was significantly negatively associated with age and schooling, and positively with the state of residence. Conclusion: Exposure to iAs is an environmental problem in Mexico. Individual variations in metabolism are a challenge to design prevention and control programs.

Resumen: Objetivo: Describir las variaciones interindividuales del metabolismo y las características sociodemográficas asociadas con el arsénico urinario, así como estimar su contaminación en el agua. Material y métodos. Se entrevistó a 1 028 mujeres del norte de México; por cromatografía de líquidos se midieron los metabolitos urinarios de arsénico y, a partir de ellos, se estimó la concentración en agua. Resultados: Las mujeres tuvieron 20-88 años. El arsénico urinario varió de p10=3.41 a p90=56.93 μg/L; 74% de las mujeres tuvieron niveles >6.4 μg/L. El arsénico en agua varió de p10=3.04 a p90=202.12 μg/L; 65% de las mujeres tenían concentraciones >10 μg/L, y 41%, >25 μg/L. Se observaron amplias variaciones en el metabolismo del arsénico. El arsénico urinario se asoció negativamente con la edad y escolaridad, y positivamente con el estado de residencia. Conclusión: La exposición a arsénico es un problema ambiental en México. Las variaciones individuales en su metabolismo son un desafío para diseñar programas de prevención y control.

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

BACKGROUND: Arsenic trioxide (As2O3), a drug that has been used in China for approximately two thousand years, induces cell death in a variety of cancer cell types, including neuroblastoma (NB). The tyrosine kinase receptor (Trk) family comprises three members, namely TrkA, TrkB and TrkC. Various studies have confirmed that TrkA and TrkC expression is associated with a good prognosis in NB, while TrkB overexpression can lead to tumor cell growth and invasive metastasis. Previous studies have shown that As2O3 can inhibit the growth and proliferation of a human NB cell line and can also affect the N-Myc mRNA expression. It remains unclear whether As2O3 regulates Trks for the purposes of treating NB. METHODS: The aim of the present study was to investigate the effect of As2O3 on Trk expression in NB cell lines and its potential therapeutic efficacy. SK-N-SH cells were grown with increasing doses of As2O3 at different time points. We cultured SK-N-SH cells, which were treated with increasing doses of As2O3 at different time points. Trk expression in the NB samples was quantified by immunohistochemistry, and the cell cycle was analyzed by flow cytometry. TrkA, TrkB and TrkC mRNA expression was evaluated by real-time PCR analysis. RESULTS: Immunohistochemical and real-time PCR analyses indicated that TrkA and TrkC were over-expressed in NB, and specifically during stages 1, 2 and 4S of the disease progression. TrkB expression was increased in stage 3 and 4 NB. As2O3significantly arrested SK-N-SH cells in the G2/M phase. In addition, TrkA, TrkB and TrkC expression levels were significantly upregulated by higher concentrations of As2O3 treatment, notably in the 48-h treatment period. Our findings suggested that to achieve the maximum effect and appropriate regulation of Trk expression in NB stages 1, 2 and 4S, As2O3 treatment should be at relatively higher concentrations for longer delivery times;however, for NB stages 3 and 4, an appropriate concentration and infusion time for As2O3 must be carefully determined. CONCLUSION: The present findings suggested that As2O3 induced Trk expression in SK-N-SH cells to varying degrees and may be a promising adjuvant to current treatments for NB due to its apoptotic effects.

Properties of realgar bioleaching using an extremely acidophilic bacterium and its antitumor mechanism as an anticancer agent

Realgar is a naturally occurring arsenic sulfide (or Xionghuang, in Chinese). It contains over 90% tetra-arsenic tetrasulfide (As4S4). Currently, realgar has been confirmed the antitumor activities, both in vitro and in vivo, of realgar extracted using Acidithiobacillus ferrooxidans (A. ferrooxidans). Bioleaching, a new technology to greatly improve the use rate of arsenic extraction from realgar using bacteria, is a novel methodology that addressed a limitation of the traditional method for realgar preparation. The present systematic review reports on the research progress in realgar bioleaching and its antitumor mechanism as an anticancer agent. A total of 93 research articles that report on the biological activity of extracts from realgar using bacteria and its preparation were presented in this review. The realgar bioleaching solution (RBS) works by inducing apoptosis when it is used to treat tumor cells in vitro and in vivo. When it is used to treat animal model organisms in vivo, such as mice and Caenorhabditis elegans, tumor tissues grew more slowly, with mass necrosis. Meanwhile, the agent also showed obvious inhibition of tumor cell growth. Bioleaching technology greatly improves the utilization of realgar and is a novel methodology to improve the traditional method.

Genetic polymorphisms of PPAR gamma, arsenic methylation capacity and breast cancer risk in Mexican women / Polimorfismos genéticos de PPAR gamma, capacidad de metilación del arsénico y riesgo de cáncer de mama en mujeres mexicanas

Abstract Objective: To evaluate whether the presence of polymorphisms of peroxisome proliferator-activated receptor gamma PPARγ (Pro 1 2Ala) and PPARGC1B (Ala203Pro) modifies the association between the inorganic arsenic (iAs) methylation capacity and breast cancer (BC). Materials and methods: Mexican women were interviewed, and blood and urine samples were collected from them (cases/controls= 197/220). The concentration of urinary arsenic species and the polymorphisms of interest were determined by high-performance liquid chromatography with inductively coupled plasma mass spectrometry (HPLC-ICP-MS) and polymerase chain reaction (PCR), respectively. Results: In women with a high %MMA (urinary monomethyl arsenic) and high primary methylation ratio (PM = MMA/iAs), the risk of BC was increased (odds ratio [OR]%MMA T3 vs.T1= 3.60: 95% confidence interval [CI] 2.02-6.41, ORPMI T3 vs.T1= 3.47: 95%CI 1.95-6.17), which was maintained after adjusting for polymorphisms. No significant interactions were observed between the polymorphisms and the arsenic variables on the risk of BC. Conclusion: Pro 12Ala and Ala203Pro polymorphisms did not modify the association between the iAs methylation capacity and BC.

Resumen Objetivo: Evaluar si la presencia de polimorfismos de PPARγ (Pro 1 2Ala) y PPARGC1B (Ala203Pro) modifica la asociación entre la capacidad de metilación del arsénico inorgánico (Asi) y el cáncer de mama (CM). Material y métodos: Se entrevistaron mujeres mexicanas y recolectaron muestras de sangre y orina de (casos/controles=197/220). La concentración de especies de arsénico urinario y los polimorfismos de interés se determinaron mediante cromatografía líquida de alta resolución acoplada a espectrometría de masas (HPLC-ICP-MS) y reacción en cadena de la polimerasa (PCR), respectivamente. Resultados: En mujeres con %MMA (monometilarsénico urinario) y razón de primera metilación altas (PM=MMA/Asi) se incrementó el riesgo de CM (RM%MMAT3vsT1=3.60: intervalo de confianza [IC]95%2.02-6.41, RMPMT3vs.T1=3.47:IC95%1.95-6.17), que se mantuvo, respectivamente, al ajustar por polimorfismos. No se observaron interacciones significativas entre los polimorfismos y las variables arsenicales sobre el riesgo de CM. Conclusión: Los polimorfismos Pro 12Ala y Ala203Pro no modificaron la asociación entre la capacidad de metilación del Asi y el CM.

Recovery: revisão sistemática de um conceito / Recovery: systematic review of a concept

O conceito de recovery tem sido descrito em artigos como um estado de recuperação ou restabelecimento de funções psíquicas, físicas e sociais no funcionamento cotidiano. O objetivo do artigo é analisar concepções terminológicas em diferentes metodologias investigativas e a evolução paradigmática da noção de recovery. Pesquisa bibliográfica sistemática na base Pubmed com as palavras "recovery + schizophrenia", limitada a dois anos retrospectivos e a artigos completos gratuitos. Dezenove artigos foram analisados. A maioria destes busca associações entre dada característica e recovery, poucos são aqueles que discutem a sua concepção de forma que se distinga de termos comuns como "cura" e "reabilitação". Recovery como um estado em que o portador de transtorno mental grave possa sentir-se criador de seus caminhos tende a estar presente em estudos com metodologia qualitativa e em revisões bibliográficas, em que a medida de recovery deixa de relacionar-se à ausência de sintomas e passa a priorizar o quão participativa pode ser a vida de um indivíduo apesar da doença. Alguns estudos quantitativos vislumbram essa diferença conceitual. Em pesquisas qualitativas ocorre expansão na concepção de recovery e nas formas de promovê-lo.

The concept of recovery has been described in papers as a state of psychic, physical and social recuperation of day-to-day functions. The scope of this article is to analyze the concepts of the term in different research methodologies and the paradigmatic evolution of the recovery concept. Systematic bibliographical research was conducted in the Pubmed database using the words "recovery + schizophrenia" limited to freely available full papers published in the previous two years. Nineteen papers were analyzed. The majority of the papers sought associations between characteristic data and recovery; few papers discussed the concept in a way to distinguish it from other words like cure or rehabilitation. Recovery as a state in which people with severe mental illness can feel like the creators of their own itinerary tend to be found in qualitative studies and in bibliographic reviews in which the meaning of recovery is not related to the lack of symptoms and tends to prioritize how participative the life of an individual can be despite the disease. Some quantitative studies detect this conceptual difference. In qualitative research there is an increase in the concept of recovery and in ways of promoting it.

Autocuidado do cuidador familiar de adultos ou idosos dependentes após a alta hospitalar / Self-care in family caregiver of dependent adults or elderly persons after hospital discharge / El autocuidado del cuidador familiar de adultos o ancianos dependientes tras el alta hospitalaria

Este artigo apresenta uma compreensão sobre o autocuidado do cuidador familiar segundo a teoria de Dorothea Orem. Resulta de uma pesquisa qualitativa com aporte da Teoria Fundamentada nos Dados, utilizando-se das técnicas de visita domiciliar, registro de notas de campo e entrevista semiestruturada com 11 cuidadores, após a internação de familiar em um Hospital Universitário de Minas Gerais. Foram obtidas quatro categorias, destacando uma categoria central, em torno da qual se analisaram as facilidades, dificuldades e estratégias para o autocuidado do cuidador. Entre as dificuldades, foram evidenciadas: tempo insuficiente para os cuidados com a saúde e, entre as facilidades, o apoio de outros familiares. As principais estratégias foram: apoio na fé; revezamento nos cuidados e recursos na comunidade. Concluiu-se que orientações no momento da alta e o acompanhamento de enfermagem após a alta contribuem para o autocuidado do cuidador, atuando sobre suas dificuldades e estimulando suas potencialidades.

This article presents an understanding concerning self-care in family caregivers according to Dorothea Orem's theory. Resulting from a qualitative research based on Grounded Theory, this work uses the techniques of home visiting, field notes and semistructured interviews with 11 caregivers after the hospitalization of a family member in a teaching Hospital located in Minas Gerais. Four categories were found and among them a central category is highlighted from which some facilities, difficulties and strategies for selfcare in caregiver were analyzed. Considering the difficulties, insufficient time for healthcare was noticed whereas the support from other family members appeared as a facility. The main strategies were: faith as a support; shift work in healthcare and community resources. This study demonstrated that hospital discharge guidelines and nursing follow-up after discharge were responsible for positive contributions to self-care in caregivers helping them to overcome their difficulties and enhancing their potentialities.

El artículo presenta una comprensión sobre el autocuidado del cuidador familiar, según la teoría de Dorothea Orem. Resulta de investigación cualitativa con aporte de la Teoría Fundamentada en los Datos, utilizándo se de las técnicas de visitas a domicilio; registro de apuntes de campo y entrevista semiestructurada, tras la internación de un familiar en un hospital universitario de Minas Gerais. Se llegó a cuatro categorías, señalando una categoría central, alrededor de la cual se analizaron las facilidades, dificultades y estrategias para el autocuidado del cuidador. Se evidenció, entre las dificultades, tiempo insuficiente para los cuidados con la salud y, entre las facilidades, el apoyo de otros familiares. Las principales estrategias fueron: apoyo en la fe, revezo en los cuidados y recursos en la comunidad. Se concluyó que orientaciones el momento del alta y el acompañamiento de enfermería tras el alta contribuyen para el autocuidado del cuidador, actuando sobre sus dificultades y estimulando sus potencialidades.

Alteraciones morfológicas del bazo de ratas (rattus norvergicus), tratadas con trióxido de arsénico / Morphological alterations of the spleen of rats (rattus norvegicus) treated with arsenic trioxide

En América Latina la presencia del arsénico en el ambiente y en las fuentes de agua para consumo humano, se debe a factores naturales de origen geológico como a actividades antropogénicas. El arsénico en las aguas naturales se encuentra principalmente como trivalente (arsenito) o pentavalente (arsenato). El objetivo de este trabajo fue determinar las alteraciones que provoca el trióxido de arsénico a nivel de la morfología del bazo de ratas (Rattus norvegicus - Sprague-Dawley). Se utilizaron 24 ratas de ambos sexos de 55 días de vida. Las ratas fueron pesadas y divididas en 3 grupos (4 hembras y 4 machos). Los grupos tratados fueron inyectados con 5 mg y 10 mg de As2O3 respectivamente, en dosis única diaria vía intraperitoneal por 15 días. Al grupo control se le aplicó agua destilada sin arsénico. Después del tratamiento los animales fueron sacrificados por eutanasia convencional y se obtuvo el bazo, los cuales fueron lavados, pesados y seccionados en cuatro partes, que fueron fijadas en formol tamponado al 10 por ciento. Mediante técnica histológica se obtuvieron 4 muestras seriadas de cada bazo, de 5 micrones de espesor con una separación de 100 micrones entre si. Posteriormente fueron teñidas con H-E. Se analizaron 30 campos (120 campos por órgano). Los datos obtenidos permiten concluir que ratas tratadas con trióxido de arsénico, presentan alteración a nivel de los compartimentos del bazo, con un aumento del compartimento de la pulpa roja, una depleción en el tamaño y número de folículos linfoides y de la zona marginal. A su vez, se observó pérdida de la celularidad de la vaina linfoide periarteriolar (PALS).

In Latin America, the presence of arsenic in the environment and water sources for human consumption is due to natural geological factors and anthropogenic activities. Arsenic in natural waters is mainly found as trivalent (arsenite) or pentavalent (arsenate). The aim of this study was to determine the alterations causing arsenic trioxide-level morphology of the spleen of rats (Rattus norvegicus - Sprague-Dawley). Were used 24 rats of both sexes of 55 days of life. The rats were weighed and divided into 3 groups (4 females and 4 males). The treated groups were injected with 5 mg and 10 mg of As2O3 respectively, intraperitoneally daily dosing for 15 days. The control group was administered arsenic-free distilled water. After treatment the animals were euthanized conventionally, and spleen was removed, which was washed, weighed and sectioned into four parts, which were fixed in 10 percent buffered formalin. Histological technique using four serial samples were obtained from each spleen of 5 microns thick with a spacing of 100 microns between them. Subsequently these were stained with H-E. We analyzed 30 fields (120 fields per organ). The data obtained indicates that rats treated with arsenic trioxide have an altered level of the compartments of the spleen, with an increased red pulp chamber, depletion in the size and number of lymphoid follicles and marginal zone. Furthermore, loss of cellularity of periarteriolar lymphoid sheath (PALS) was observed.

Tetramethylpyrazine potentiates arsenic trioxide activity against HL-60 cell lines

The objective of this study was to evaluate the effects of tetramethylpyrazine (TMP) in combination with arsenic trioxide (As2O3) on the proliferation and differentiation of HL-60 cells. The HL-60 cells were treated with 300 µg/mL TMP, 0.5 µM As2O3, and 300 µg/mL TMP combined with 0.5 µM As2O3, respectively. The proliferative inhibition rates were determined with MTT. Differentiation was detected by the nitroblue tetrazolium (NBT) reduction test, Wright’s staining and the distribution of CD11b and CD14. Flow cytometry was used to analyze cell cycle distribution. RT-PCR and Western blot assays were employed to detect the expressions of c-myc, p27, CDK2, and cyclin E1. Combination treatment had synergistic effects on the proliferative inhibition rates. The rates were increased gradually after the combination treatment, much higher than those treated with the corresponding concentration of As2O3 alone. The cells exhibited characteristics of mature granulocytes and a higher NBT-reducing ability, being a 2.6-fold increase in the rate of NBT-positive ratio of HL-60 cells within the As2O3 treatment versus almost a 13-fold increase in the TMP + As2O3 group. Cells treated with both TMP and As2O3 expressed far more CD11b antigens, almost 2-fold compared with the control group. Small doses of TMP potentiate As2O3-induced differentiation of HL-60 cells, possibly by regulating the expression and activity of G0/G1 phase-arresting molecules. Combination treatment of TMP with As2O3 has significant synergistic effects on the proliferative inhibition of HL-60 cells.

E3 ubiquitin ligase Cbl-b potentiates the apoptotic action of arsenic trioxide by inhibiting the PI3K/Akt pathway

Arsenic trioxide (ATO) is a strong inducer of apoptosis in malignant hematological cells. Inducible phosphatidyl inositol 3 kinase (PI3K)-Akt activation promotes resistance to ATO. In the present study, we evaluated whether E3 ubiquitin ligase Cbl-b, a negative regulator of PI3K activation, is involved in the action of ATO. The effect of ATO on cell viability was measured by the Trypan blue exclusion assay or by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was determined by flow cytometry and protein expression was assayed by Western blotting. ATO decreased the viability of HL60 cells and induced cellular apoptosis, which was accompanied by transient activation of Akt. The PI3K/Akt inhibitor, LY294002, significantly increased ATO-induced apoptosis (P < 0.05). In addition, ATO up-regulated the expression of Cbl-b proteins. Furthermore, ATO inhibited cell viability with an IC50 of 18.54 μM at 24 h in rat basophilic leukemia-2H3 cells. ATO induced cellular apoptosis with transient activation of Akt and Cbl-b was also up-regulated. Rat basophilic leukemia-2H3 cells transfected with a dominant negative (DN) Cbl-b mutation showed overexpression of Cbl-b (DN) and enhanced Akt activation. Compared with cells transfected with vector, ATO-induced apoptosis was decreased and G2/M phase cells were increased at the same concentration (P < 0.05). The PI3K/Akt inhibitor, LY294002, re-sensitized Cbl-b (DN) overexpressing cells to ATO and reversed G2/M arrest (P < 0.05). Taken together, these results suggest that Cbl-b potentiates the apoptotic action of ATO by inhibition of the PI3K/Akt pathway.

Optimización y validación metodológica de la cuantificación de arsénico por inyección en flujo -generación de hidruros- espectrometría de absorción atómica (IF-GH-EAA) previa derivatización con L-cisteína / Optimization and validation method for arsenic quantification by flow injection-hydride generation - atomic absorption spectrometry (FI-HG-AAS) after L-cysteine derivatization

El arsénico (As) es un contaminante natural que afecta una amplia zona de Argentina. El nivel de As en agua de consumo es utilizado para evaluar la fuente de exposición y en orina para evaluar exposición a este tóxico. El presente trabajo tuvo como objetivo la optimización y validación metodológica de una técnica para la cuantificación de As [As suma = As inorgánico (AsI) + especies metiladas: ácido monometilarsónico (MMA) y ácido dimetilarsónico (DMA)], producto del metabolismo del AsI, por inyección en flujo- generación de hidruros- espectrometría de absorción atómica (IF-GH-EAA), previa derivatización con L-cisteína. La recuperación de las especies estudiadas: AsI (AsIII y AsV), MMA y DMA fue cercana al 100% en todos los casos. Los límites de detección y cuantificación encontrados fueron para agua y orina: 2 y 3 µg/L; 5 y 8 µg/L respectivamente y el rango dinámico de trabajo establecido fue desde 5 a 75 µg/L, permitiendo cuantificar As en muestras de agua cercanos a los estándares internacionales vigentes para valores máximos de As en agua de consumo y en orina en niveles comparables con los establecidos en población laboralmente no expuesta. Esta propuesta metodológica es una alternativa para evaluar la exposición al As en muestras de agua y orina, sin necesidad de utilizar prolongados pre-tratamientos de muestra, de forma más rápida y económica.

Arsenic (As) is a natural contaminant that affects a large area of Argentina. Quantification of As in drinking water has been used to evaluate the source of exposure and As in urine to assess exposure to this toxic. This study aimed to optimize and validate a methodological technique for the quantification of As [As sum = inorganic As (AsI) + methylated species: monometilarsonic acid (MMA) and dimetilarsinic acid (DMA)], product of AsI metabolism by flow injection hydridegeneration-atomic absorption spectrometry (FI-GH-AAS), after derivatization with L-cysteine. The recovery of the studied species: AsI (AsIII and AsV), MMA and DMA was close to 100% in all cases. The limits of detection and quantitation were foundfor water and urine: 2 and 3 µg/L; 5 and 8 µg/L respectively and a linear working range from 5 to 75 µg/L, allowing quantify As in water close to international standards of maximum As values for drinking water and urine samples with levels comparables with those found in people non exposed ocupacionally . This methodology is a valid alternative for assessing exposure to As in water and urine samples without the need of prolonged pre-treatment sample, more quickly and inexpensively.

Evaluación de dos técnicas analíticas para la especiación de arsénico en aguas superficiales del sur del Perú / Evaluation of two analytical techniques for speciation of arsenic in surface waters from southern Perú

El arsénico es altamente tóxico, la exposición crónica a este elemento causa diversos daños en la salud de las personas, en el Perú se han reportado niveles elevados, sobre todo en ríos de la costa sur. Objetivo. Evaluar dos técnicas analíticas de especiación de las dos formas de arsénico inorgánico en agua fluvial de Tacna, en el sur del Perú. Materiales y métodos. Se desarrolló un estudio comparativo entre la técnica de separación por resina de intercambio aniónico y la cromatografía iónica para la especiación del arsénico (V) y arsénico (III) en muestras de agua de cuatro ríos de la vertiente del Pacífico en dos distritos de la región Tacna. La cantidad de arsénico total se determinó con el sistema de inyección de flujo asistido con absorción atómica. Resultados. Se obtuvo un buen grado de separación en ambos procedimientos, sin embargo, la técnica de resinas de intercambio aniónico tiene un límite de detección inferior que la cromatografía iónica, 2,0 μg/L y 32 μg/L, respectivamente. En cuatro de las seis muestras se obtuvieron valores superiores a los recomendados por la Agencia de Protección Ambiental de los Estados Unidos, y en ellas se logró determinar las cantidades de arsénico (III) y arsénico (V). Conclusiones. La técnica de separación por resina de intercambio aniónico tiene mayor sensibilidad de detección de arsénico que la cromatografía iónica y permite un alto grado de especiación del arsénico inórganico en muestras de agua fluvial.

It is widely known that arsenic is highly toxic to humans, and the chronic exposure to this element produces various damages to the health of people. In Peru have been reported particularly high levels in rivers of the south coast. Objective. Evaluate two analytical techniques of speciation of the two forms of inorganic arsenic in river water of Tacna, in southern Peru. Material and methods. Developed a comparative study of the technique of separation by anion-exchange resin and ion chromatography for the speciation of arsenic (V) and arsenic (III) in water samples from four rivers of the Pacific slope in two districts of the region Tacna. The total amount of arsenic was determined with flow injection system with atomic absorption attended. Results. We obtained a good degree of separation in both procedures, however, the technique of anionic exchange resins have a lower detection limit of ion chromatography, 2.0 mg/L and 32 mg/L, respectively. In four of the six samples were higher than those recommended by the Environmental Protection Agency of the United States, and they succeeded in determining the amounts of arsenic (III) and arsenic (V). Conclusions. Both techniques can be considered applicable for different types of water; nevertheless, the technique of separation by anion-exchange resin has higher detection sensitivity than the technique of separation by arsenic ion chromatography; and allows a high degree of speciation of inorganic arsenic in samples of river water.

Historia del tratamiento de la Sífilis / The history of Syphilis´ treatment

El nombre sífilis proviene del griego siph: cerdo y philus: amor. Recuerda al personaje de una obra, llamado Syphilo, que fue castigado por los dioses a sufrir una terrible enfermedad. Se analizan los datos sobre la sífilis en la antigüedad (que difieren según su fuente). Su mención en la Edad Media, su controversial origen, la ayuda de los paleopatólogos para encontrarlo. Luego de la Revolución Francesa y el inicio de la Edad Contemporánea, el porcentaje de enfermos fue creciendo y se acentuó la segregación de los mismos por la sociedad. Desde el año 1500 hasta principios del siglo XX el tratamiento de la sífilis dependía del mercurio. Tenía una gran variedad de formas de aplicación. La vía tópica: el ungüento gris, en calomelano o tabletas, en inyecciones, en fricciones y fumigaciones en donde el mercurio se introducía en el cuerpo por lo pulmones. Se adjudicó a la madera del guayaco pretendidas características curativas, que no poseía. Los ioduros se utilizaron para el terciarismo. Ehrlich en 1907, patentó el compuesto 606 o Salvarsan y en 1910, el Neo-Salvarsan o Arsfenamina (compuesto 914). Por estos descubrimientos recibió el Premio Nobel. En 1887, Julios Wagner Jauregg sugirió que la fiebre terapéuticamente inducida era útil en el tratamiento de enfermos psicóticos. En 1912 publicó sus satisfactorios resultados al tratar la paresias con una combinación de mercurio-iodo y tuberculina de Koch. En 1917 ingresó a su servicio un enfermo de malaria, con cuya sangre escarificaron la piel palúdica de tres paréticos, en lugar de darle inmediatamente quinina. Por ello fue galardona con el Premio Nobel. Se utilizó luego el bismuto, a partir de 1922, pero posteriormente fue sustituido por las sulfamidas, de aplicación dificultosa. El avance terapéutico más importante ocurrió en 1943, año en que se comenzó a utilizar la penicilina por Mahoney y colaboradores. Luego se confirmó la eficacia de la tetraciclina para los alérgicos a la penicilina. Últimamente se confirmó la eficacia de la azitromicina en dosis de 500mg cada día, durante los 10 días o el régimen de 500mg en días alternos.

The name Syphilis comes from greek language: Siph: Pig and Philus: Love, meaning, in honor of the Sheppard of a story where the Character, Named Syphilo, is punished by the gods to suffer a terrible disease. Data about Syphilis was analized in ancient times (which differ according to the source). Its mention in the middle age, its controversial origin, the help provided from paleopathologists to find it. When the French revolution and the beginning of the contemporary age began, the percentage of sick people grew. The segregation of these is proved by the society. From the year 1500 to the beginnings of the XX century, the treatment of Syphilis depended on mercury. There were a great variety of application methods: topical: the grey ointment, in «calomelanos or tabs¼, in injections, in frictions and fumigations where the mercury was introduced in the body by the lungs. Guayacos wood was named with curative features which it did not posses. The iodides were used for tertiary syphilis. In 1907, Ehrlich formulates the 606 compound or Salvarsan and in 1910 the Neo-Salvarsan or Arsfenamina or compound 914.Due to these discoveries he received the nobel prize. In 1887, Julius Wagner of Jauregg suggested that: the inducted therapeutic fiber was useful in the treatment of the psychosis. In 1912 he published his satisfactory results in treating the paresis with a combination of mercury and iodides and tuberculin of Koch. In 1917 he treated a patient who had malaria and instead of giving him immediately quinine, he made a scarification with his paludic blood the skin of 3 paretic patients. Because of this he was awarded with the nobel prize. Since 1922 bismuth was used, but then it was substituted by the sulphamidas of difficult application. The most important therapeutical advance happened in 1943, year in which penicillin was put in use by Mahoney and col. Later it was confirmed the efficiency of the tetracycline for the penicillin-allergic patients. Lately it has been confirmed the efficiency of the azithromizine in 500 mg dosis each day during 10 days or the regimen of 500 mg in alternate days.

Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 æM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 ± 3.9 percent in HNE1-LMP1 cells vs 37.89 ± 4.9 percent in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9 percent), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1 percent), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27 percent) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.

Evaluación de la citotoxidad del trióxido de arsénico en líneas celulares tumorales humanas con la técnica colorimétrica de la sulforhodamina B / Evaluation of the cytotoxicity of arsenic trioxide in human tumoral cellular lines by the sulforhodamine B colorimetric technique

El trióxido de arsénico ha demostrado ser un inductor de apoptosis en líneas celulares de leucemia promielocítica aguda. Estudios clínicos han demostrado su efectividad en el tratamiento de esta enfermedad en pacientes refractarios al tratamiento con ácido retinoico. En este trabajo se determinó la actividad citotóxica de este producto frente a un panel de 3 líneas celulares tumorales humanas de tumores sólidos (M14, MCF7, HT-29) y una línea de leucemia promielocítica aguda, utilizando la técnica de la sulforhodamina B. Se realizaron 2 experimentos en los cuales las células fueron incubadas durante 48 h en presencia del producto. Las IC50 s obtenidas en ambos experimentos fueron: M14 (0,471 y 0,450 µg/mL), MCF7 (0,122 µg/mL), HT-29 (0,543 y 0,659 µ g/mL) y HL60 (0,487 y 0,351 µg/mL). Se concluyó que el trióxido de arsénico posee una marcada actividad citotóxica, no solo en la línea de leucemia promielocítica aguda, sino también, en las líneas de tumores sólidos humanos estudiadas por lo que se recomendó realizar un estudio de actividad antitumoral de este producto

Estudio de los niveles de contaminaciónpor Arsénico en trabajadores metalúrgicos del departamento de Oruro / Study of the levels of contamination for Arsenic in metallurgical workers of the departament of Oruro

Utilizando el método de digestión ácida yEspectrofotometría de Absorción Atómica con Horno de Grafito, se determinó la concentración de As, en 390 muestras de orina y 384 muestras de cabellos de trabajadores de una empresa fundidora en Oruro. El promedio de As en orina fue 7,826 mg/L (DE=3,548mg/ L con 95% de confianza), mayor al Límite de Tolerancia Biológico (LTB) de 0,1mg/L sugerido por el Instituto Nacional para Salud y Seguridad en el Trabajo (NIOSH). El promedio de As en cabello fue 0,557mg/g (DE=3,741 con 95% de confianza), mucho mayor al LTB de0,001mg/g. El análisis de promedios de concentración en relación a la edad no determinó diferencias representativas. No se encontraron diferencias significativas tanto por la prueba t student (p>0.05)como por el método de Levene’s (F=2.232; p=0.136), en las áreas de trabajo consideradas de exposición directa e indirecta.

Tratamiento de liquen plano con griseofulvina / Treatment of lichen planus with griseofulvin

Presentamos un paciente de sexo masculino, de 15 años de edad, con diagnóstico clínico e histopatológico de liquen plano. Fue tratado con griseofulvina 500 mg/día y fenoxifenadina 120 mg/día con mejoría tanto subjetiva como objetiva al cabo del mes de tratamiento. Se confirma la griseofulvina como alternativa terapéutica para el liquen plano

The application of single cell gel electrophoresis or comet assay to human monitoring studies

Objetivo. En la búsqueda de nuevos marcadores genotóxicos aplicables a estudios de poblaciones humanas expuestos a xenobióticos, la utilización del ensayo de electroforesis en una sola célula se ha propuesto como un método sensible y una buena alternativa. Material y métodos. Esta técnica detecta rompimientos en el ADN de cadena sencilla, así como sitios álcali lábiles y sitios retardados de reparación. Resultados. En este trabajo, presentamos nuestra experiencia utilizando este ensayo en poblaciones humanas expuestas ocupacionalmente o ambientalmente a diferentes xenobióticos. Conclusiones. Se discute la posible utilidad de este ensayo como un biomarcador de efecto genotóxico

Eosinofilia pulmonar tropical filariotica e o seu diagnostico diferencial / Tropical pulmonary eosinophilia its differential diagnosis

Os autores fazem uma ampla revisao sobre a eosinofilia pulmonar tropical (EPT) de origem filarial e o seu diagnostico diferencial com relacao a outras sindromes afins. Abordaram os aspectos epidemiologicos, clinicos, diagnosticos, terapeuticos e fisiopatogenicos, enfatizando os novos avancos ocorridos no conhecimento da doenca filarial e sua repercussao para um melhor entendimento da EPT. Tambem destacaram a ocorrencia de uma forma denominada EPT-LIKE, causada por helmintos intestinais, de dificil diagnostico diferencial com relacao a EPT e que pode ocorrer tambem em areas nao endemicas de filariose. No final do artigo, os autores sugerem um roteiro para a interpretacao dos dados epidemiologicos, clinicos, laboratoriais, radiologicos (e ultra-sonograficos) e terapeuticos na orientacao para a suspeicao diagnostica do paciente portador de EPT...

Intoxicación aguda por arsina: aspecto médico laboral / Sharp intoxication due to arsine: medico legal aspect

La intoxicación aguda por arsina está descripta como una entidad rara de origen accidental en la industria. La acción de los ácidos sobre metales que tienen impureza de arsénico forman el gas arsina. Se describe una triada compuesta por ictericia, hemoglobinuria y dolor abdominal como consecuencia de anemia hemolítica (el gas arsénico es un potente agente hemolítico), insuficiencia renal aguda y hepatopatía tóxica. Como tratamiento se encuentra indicado la diuresis alcalina forzada, transfusión de sangre, la diálisis peritoneal o hemodiálisis e incluso la exanguinotransfusion

Poroqueratosis de Mibelli diseminada y carcinoma espinocelular con metástasis / Disseminated Mibelli's porokeratosis and metastatic squamous cell carcinoma

En la literatura se reportaron hasta el presente dos casos de pacientes con poroqueratosis de Mibelli diseminada, que desarrollaron carcinoma espinocelular con matástasis y evolución fatal. Se presenta el tercer caso de poroqueratosis de Mibelli, con carcinoma espinocelular y adenopatía metastásica y se comparan las características clínico-evolutivas de los tres casos. Asimismo se destaca la importancia del control de pacientes con lesiones ulcerosas persistentes, que deben ser estudiadas histopatológicamente, más aún cuando están asociadas a enfermedades con potencial neoplásico como la poroqueratosis de Mibelli y la queratosis arsenical