Arsenic exposure and biomarkers for oxidative stress and telomere length in indigenous populations in Bolivia.

BACKGROUND: Women living in the Bolivian Andes are environmentally exposed to arsenic, yet there is scarce information about arsenic-related effects in this region. Several biomarkers for telomere length and oxidative stress (mitochondrial DNA copy number, mtDNAcn; 8-Oxo-2'-deoxyguanosine, 8-oxo-dG; and 4-hydroxy nonenal mercapturic acid, 4-HNE-MA) have been previously linked to arsenic, and some of which are prospective biomarkers for cancer risk. OBJECTIVE AND HYPOTHESIS: To evaluate associations between arsenic exposure and telomere length, mtDNAcn, 8-oxo-dG, and 4-HNE-MA in Bolivians. Arsenic exposure was hypothesized to be positively associated with all four toxicity biomarkers, particularly in individuals with a less efficient arsenic metabolism. METHODS: The study encompassed 193 indigenous women. Arsenic exposure was assessed in urine as the sum of inorganic arsenic metabolite concentrations (U-As) measured by HPLC-HG-ICP-MS, and in whole blood as total arsenic (B-As) measured by ICP-MS. Efficiency of arsenic metabolism was evaluated by a polymorphism (rs3740393) in the main arsenic methylating gene AS3MT measured by TaqMan allelic discrimination, and by the relative fractions of urinary inorganic arsenic metabolites. Telomere length and mtDNAcn were determined in peripheral blood leukocytes by quantitative PCR, and urinary 8-oxo-dG and 4-HNE-MA by LC-MS/MS. RESULTS: U-As and B-As were associated with longer telomeres and higher mtDNAcn, particularly in women with a less efficient arsenic metabolism. Urinary 8-oxo-dG and 4-HNE-MA were positively associated with U-As, but only 4-HNE-MA was associated with B-As. Arsenic metabolism efficiency did not have a clear effect on the concentrations of either of these biomarkers. CONCLUSION: Bolivian women showed indications of arsenic toxicity, measured by four different biomarkers. Telomere length, mtDNAcn, and 4-HNE-MA were positively associated with both U-As and B-As. The association of arsenic exposure with telomere length and mtDNAcn was only present in Bolivian women with a less efficient metabolism. These findings call for additional efforts to evaluate and reduce arsenic exposure in Bolivia.

Genotoxicity in humans exposed to arsenic, lithium, and boron in drinking water in the Bolivian Andes-A cross sectional study.

Elevated concentrations of arsenic, lithium and boron in drinking water have already been reported in Bolivia. Arsenic is known to cause genotoxicity but that caused by lithium and boron is less well known. The aim of the present cross-sectional study was to evaluate potential genotoxic effects of exposure to arsenic, while considering exposure to lithium and boron and genetic susceptibility. Women (n = 230) were recruited in villages located around Lake Poopó. Exposure to arsenic was determined as the sum of concentrations of arsenic metabolites inorganic arsenic, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) in urine. Exposure to lithium and boron was determined based on their concentrations in urine. Genetic susceptibility was determined by GSTM1 (glutathione S-transferase-mu-1) and GSTT1 (glutathione S-transferase-theta-1) null genotypes and AS3MT (Arsenite Methyltransferase) rs3740393. Genotoxicity was measured in peripheral blood leukocytes using the comet assay. The geometric means of arsenic, lithium, and boron concentrations were 68, 897, and 3972 µg/L, respectively. GSTM1 and GSTT1 null carriers had more DNA strand breaks than gene carriers (p = .008, p = .005). We found no correlation between urinary arsenic and DNA strand breaks (rS = .03, p = .64), and only a weak non-significant positive association in the adjusted multivariate analysis (ß = .09 [-.03; .22], p = .14). Surprisingly, increasing concentrations of lithium in urine were negatively correlated with DNA strand breaks (rS = -.24, p = .0006), and the association persisted in multivariate analysis after adjusting for arsenic (ß = -.22 [-.36; -.08], p = .003). We found no association between boron and DNA strand breaks. The apparent protective effect of lithium merits further investigation.

Evaluación de riesgo genotóxico por exposición laboral al betún en lustracalzados. La Paz-Bolivia / Evaluation of genotoxic risk due to shoe polish exposurein shoeshine boys. La Paz-Bolivia

OBJETIVO: Evaluar el riesgo genotóxico en los lustracalzados expuestos laboralmente al betún y sus componentes. MATERIAL Y MÉTODOS: Estudio de casos-controles y autocontroles. Se estudiaron 53 lustracalzados y 24 controles. Se determinó el daño genotóxico mediante la técnica de micronúcleos y otras alteraciones metanucleadas en mucosa bucal. RESULTADOS: Las edades promedio del grupo de expuestos y controles fue de 35.0±8.8 y 27.8±1.5 respectivamente. El grupo de expuestos estuvo conformado varones (83%) y mujeres (17%), con un promedio de años de trabajo de 13.4±7.6, de los cuales la mayoría no usa medidas de protección laboral (73.6%). No se observó diferencias significativas en la frecuencia de alteraciones metanucleadas entre el grupo de expuesto y controles: binucleadas (BN) (p=0.273), broken egg (BE) (p=0.635), carriorexis (CR) (p=0.677), cariolisis (CL) (p=0.770), índice de reparación celular (p=0.201). El análisis de asociación entre exposición y genotoxicidad demostró que el uso del betún no es un factor de riesgo. La evaluación pre y post exposición al betún del grupo de lustracalzados no obtuvo diferencias significativas luego del periodo ventana para BN (p=0.804), BE (p=1.274), CR (p=0.503), CL (p= 1.000) e IR (p=0.424). CONCLUSIÓN: El uso del betún en la población estudiada, no es un factor de riesgo genotóxico. Sin embargo, es necesario continuar estudios de cohorte con una población más numerosa.

OBJECTIVE: To asses the genotoxic risk in shoeshine boys who are constantly exposed to shoe polish and its components. MATERIAL AND METHODS: The study was cross-sectional (exposed and controls) and of cross over trials. It was studied 53 shoe shiners (exposed group) and 24 controls. The buccal cytome technique was applied on children for determining genotoxic damage. RESULTS: The average age of the exposed group and controls was 35.0 ± 8.8 and 27.8 ± 1.5 respectively. The exposed group consisted males (83%) and women (17%), with an average of 13.4 years of work ± 7.6, most of which do not use labor protection measures (73.6%). No significant differences were observed in frequency of metanucleadas alterations from the group of exposed and controls: binucleate (BN) (p = 0.273), broken egg (BE) (p = 0.635), karyorrhexis (KR) (p = 0.677), karyolysis (KL) (p = 0.770), cellular repair rate (RR) (p = 0.201). The analysis of association between exposure and genotoxicity showed that the use of shoe polish and its components is not a risk factor. The assessment pre and post-exposure to shoe polish in the exposed group showed no significant differences after the window period for BN (p = 0.804), BE (p = 1.274), CR (p = 0.503), CL (p = 1.000) and RR (p = 0.424). CONCLUSION: The use of shoe polish by shoeshine boy population is not a genotoxic risk factor. However it is necessary to continue cohort studies with a larger population.

Terapia celular para el tratamiento de úlceras crónicas / Cell therapy in chronic ulcers treatment

INTRODUCCIÓN: las úlceras por presión son producto de una necrosis isquémica en la piel y tejido subcutáneo, se presentan en pacientes inmovilizados por etiología diversa, y en estadios avanzados incrementan la mortalidad. La terapia celular con Células Madre Somáticas, que se diferencian y proliferan a células maduras funcionalmente normales, tiene la finalidad de reparar la función de tejidos lesionados. OBJETIVO: Evidenciar la eficacia de las Células Madre Somáticas de médula ósea en la reparación de úlceras crónicas por presión, como una posibilidad terapéutica en los tratamientos convencionales no exitosos. MÉTODO: Se estudió 4 pacientes con úlceras crónicas por presión en estadios avanzados y refractarias a tratamiento convencional. Se obtuvo Células Madre Somáticas de la médula ósea del esternón, y se procedió al sembrado de las mismas una vez por semana. Resultados.- Las Células Madre Somáticas sembradas en las úlceras crónicas se diferenciaron en tejido muscular, conjuntivo, subcutáneo y epitelial en un periodo comprendido entre 30 a 69 días. CONCLUSIÓN: la terapia celular con Células Madre Somáticas de médula ósea se constituye en una posibilidad terapéutica en úlceras crónicas de estadios avanzados y refractarias a tratamiento convencional.

INTRODUCTION: chronic pressure ulcers result from an ischemic necrosis of the skin and subcutaneous tissue. This type of ulcers occurs in patients physically restrained by different etiology and in advanced stages increase mortality. Cell therapy allows to regenerate the function of injured tissues by using somatic stem cells that differentiate and proliferate into mature cells on order to repair injured tissues. OBJECTIVE: to demonstrate the effectiveness ofusing Somatic Stem Cells obtained from bone marrow in chronic pressure ulcers treatment, as a likely therapeutic option to unsuccessful conventional treatments. METHOD: it was studied 4 patients with chronic pressure ulcers in advanced stages and refractory to conventional treatment. It was obtained Somatic Stem Cells from the bone marrow and followed a process of seeding on a weekly basis. RESULTS: somatic Stem Cells seeded in chronic pressure ulcers differentiated into muscle, connective, epithelial and subcutaneous tissues. The repair of injured tissues lasted between 30 to 69 days. CONCLUSION: cell therapy by using Somatic Stem Cells from bone marrow constitutes a therapeutic option in chronic ulcers of advanced stages and refractory to conventional treatment.

Leucemia bifenotípica aguda B/T: presentación de caso clínico / Biphenotypic acute leukemia: case report

La leucemia bifenotípica aguda (LBA) es una enfermedad poco frecuente que comprende alrededor de 2 al 5% del total de casos de todas las leucemias. La LBA se caracteriza por la expresión asociada de 2 o más marcadores de diferentes líneas celulares en la población celular de blastos. Al respecto, la clasificación de neoplasias hematológicas y linfoides realizada por la OMS el 2008, incorporó los criterios de EGIL para el diagnóstico de este tipo de leucemia. La leucemia bifenotípica, que muestra fenotipos B y T es extremadamente rara y de mal pronóstico por lo que existe poca información respecto al manejo clínico de estos pacientes. Actualmente no existe un tratamiento estándar para estos casos, ya que no se pueden realizar estudios clínicos aleatorizados debido a la baja incidencia de la LBA. Sin embargo, el uso del protocolo Hiper CVAD (hiperfraccionamiento de ciclofosfamida, vincristina, adriamicina y dexametasona; y altas dosis de citarabina y metotrexato) ha logrado un 78% de remisión completa y una media de duración de sobrevivencia de 27 meses. Recientemente la incorporación de inhibidores de la tirosina kinasa (imatinib, nilotinib o dasatinib) en combinación con el protocolo hiperCVAD ha mejorado la tasa de remisión completa durante la inducción. En este trabajo reportamos el caso de un paciente diagnosticado con leucemia bifenotípica B/T cuya población clonal presentó positividad para marcadores linfoides, obteniéndose una puntuación de 6,5 para el linaje B y 4,5 para el linaje T según los criterios de EGIL.

Biphenotypic acute leukemia (BAL) is an uncommon disease comprising approximately from 2 to 5% of all leukemia cases. BAL is characterized by the associated expression of two or more markers of different cell lines in a single blasts population. In this regard, 2008 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues included EGIL score system for diagnosing this type of leukemia. The biphenotypic leukemia that expresses B and T phenotypes is extremely unusual and it has poor prognosis. Due to low incidence of BAL, it is not possible to conduct randomized trials and consequently little is known about the clinical management of this kind of patients. Currently, there is no a standard treatment for these cases. However, the use of Hyper-CVAD regimen (hyperfractionated of cyclophosphamide, vincristine, adriamycin, and dexamethasone; and high dose of methotrexate and cytarabine) has achieved a 78% of complete remission with an average survival of 27 months; and the incorporation of tyrosine kinase inhibitors (imatinib, nilotinib or dasatinib) has improved the remission rate during induction. We report the case of a patient whose clones gave positive for B and T lymphoid markers and according to EGIL score system, it was obtained 6.5 for B lineage and 4.5 for Tlineage