Survivin in Breast Cancer: A Review.

Breast cancer is the most frequently diagnosed cancer in women and ranks second among causes for cancer-related death in women. Gene technology has led to the recognition that breast cancer is a heterogeneous disease composed of different biological subtypes, and genetic profiling enables the response to chemotherapy to be predicted. This fact emphasizes the importance of selecting sensitive diagnostic and prognostic markers in the early disease stage and more efficient targeted treatments for this disease. One such prognostic marker appears to be survivin. Many studies have shown that survivin is strongly expressed in different types of cancers. Its overexpression has been demonstrated in breast cancer, and high activity of the survivin gene has been associated with a poor prognosis and worse survival rates.

Peroxisomicine A1 (toxin T-514) induces cell death of hepatocytes in vivo by triggering the intrinsic apoptotic pathway.

Karwinskia parvifolia possesses the highest concentration levels of the anthracenone T-514 (PA1). Studies have demonstrated the induction of apoptosis by PA1 in cancer cell lines. The aim was to investigate the effects of PA1 on the apoptosis of the mouse liver in vivo and its underlying pathway. Sixty CD-1 mice were divided into three groups: untreated, vehicle, and treated with PA1. The animals were euthanized at 4, 8, 12, and 24 h post-treatment. To confirm the toxic effect of PA1 we determined the activity of catalase. Liver sections were prepared for morphological examination and for immunohistochemical evaluation of anti and pro-apoptotic markers. DNA fragmentation was detected by TUNEL assay and electrophoresis. Pre-apoptotic mitochondrial alterations and cytochrome c oxidase activity were analyzed by transmission electron microscopy. PA1 induced pre-apoptotic mitochondrial alterations, a high activity of the cytochrome oxidase, and apoptosis in hepatocytes. PA1 caused p53 over-expression and down regulation of PCNA. PA1 also increased the expression levels of the pro-apoptotic markers Bax and Bak, whereas the anti-apoptotic molecule Bcl-2 was decreased. PA1 induces apoptosis by activating the intrinsic mitochondrial apoptotic pathway. These results will be useful for studies regarding the use of PA1 as an antineoplastic agent.

Toxic Effect of Cadmium, Lead, and Arsenic on the Sertoli Cell: Mechanisms of Damage Involved.

Over the past decades, an increase has been described in exposure to environmental toxins; consequently, a series of studies has been carried out with the aim of identifying problems associated with health. One of the main risk factors is exposure to heavy metals. The adverse effects that these compounds exert on health are quite complex and difficult to elucidate, in that they act at different levels and there are various signaling pathways that are implicated in the mechanisms of damage. The Sertoli cells plays a role of vital importance during the process of spermatogenesis, and it has been identified as one of the principal targets of heavy metals. In the present review, cadmium, lead, and arsenic are broached as altering the physiology of the Sertoli cells, citing mechanisms that have been cited in the literature.

In Vitro Evaluation of Damage by Heavy Metals in Tight and Gap Junctions of Sertoli Cells.

The Sertoli cell plays a vital role during the spermatogenesis process and has been identified as one of the main targets of the toxic action of heavy metals on the seminiferous epithelium. In the present work, the effect of lead (Pb), Arsenic (As), and Cadmium (Cd) in primary cultures of Sertoli cells was analyzed by measuring the expression of the genes Cldn11, Ocln, and Gja1 that participate in the tight and gap junctions, which are responsible for maintaining the blood-testis barrier. Sertoli cells were isolated from the testes of Wistar rats. Sertoli cell cultures were exposed separately and at the same concentrations of three heavy metals for 48 h. Subsequently, gene expression was measured by real-time polymerase chain reaction. In the morphological analysis of the cultures, after 24 h, the cultures exposed to Cd showed greatest detachment of the monolayer, followed by those exposed to As and Pb. As for gene expression patterns, As induced a decrease in the expression of the Cldn11 gene at 24 and 48 h (p < 0.01) and in that of Ocln at 24 (p < 0.001) and 48 h (p < 0.01), whereas Cd induced overexpression of the Gja1 gene from day 1 of exposure (p < 0.001) and subexpression of the Ocln gene (p < 0.05) at 24 h. Because each of these three metals generated different expression patterns in the three genes, we can postulate that the mechanisms of damage that they induce are different; therefore, the effect that they exert on the Sertoli cell occurs through different pathways, generating changes in structural proteins, altering Sertoli cell morphology, and compromising its function in the regulation of the spermatogenesis process.

Factores asociados a lesiones músculo-esqueléticas por carga en trabajadores hospitalarios de la ciudad de Torreón, Coahuila, México / Musculoskeletal lesions while lifting-related factors in workers at 3 hospitals in Torreon, Coahuila, Mexico

OBJETIVO. Identificar factores asociados en la aparición de lesiones músculo-esqueléticas por carga en trabajadores hospitalarios. MÉTODOS. Se aplicó el cuestionario estandarizado nórdico de sintomatologías músculo-esqueléticas con corte transversal que evaluó la frecuencia y factores asociados para las lesiones músculo-esqueléticas en 48 trabajadores. RESULTADOS. La media de edad en hombres fue de 29,1+6,7 y en mujeres 26,5+6,9. El turno matutino tiene mayor actividad laboral. El 43,75% eran paramédicos y el 22,92% enfermeras. La espalda fue la región más afectada en los camilleros y paramédicos; mientras que enfermería reportó más dolor en pies y piernas. Se presentaron correlaciones significativas entre la antigüedad y los días que se presenta el dolor en la región anatómica. El 81,9% no usa equipo de protección contra lesiones en espalda. El 91,67% refirió capacitación previa para desarrollar actividades de cargas dentro del hospital. CONCLUSIONES. Consideramos la importancia de la higiene ocupacional en las actividades hospitalarias y la capacitación del uso del equipo de protección personal en las actividades laborales que se realizan, la falta de uso puede ser uno de los factores determinantes para el incremento en los días con dolor en alguna región anatómica cuando incrementan los años laborables, principalmente lo que corresponde a espalda alta y baja.

OBJECTIVE: To identify musculoskeletal lesions while lifting-related factors in hospital workers and lifting. METHODS: A transversal study was carried out evaluating the prevalence and associated factors to musculoskeletal lesions in 48 workers, using the Nordic Standardized Questionnaire of musculoskeletal symptoms. RESULTS: The mean age was 29.1+6.7 for males and 26.5+6.9 for females. The morning shift had greater activity, Paramedics accounted for the 43.75% and nurses for the 22.92%. Back pain was the most reported symptom among paramedics and auxiliary personnel; nurses reported feet and legs pain. Significant correlations were observed between seniority and the days with pain in the different anatomical regions. 81.9% of the workers do not use safety equipment against back injuries, and 91.67% stated receiving previous training course on lifting activities within the hospital. CONCLUSIONS: We evaluated the importance of occupational hygiene within the hospital activities, as well as training of personal safety equipment. The lack of such may be a determining factor that increases days in pain in specific anatomic regions as the working years go by, particularly those pertaining to both upper and lower back.

El extracto acuoso de ruta graveolens del norte de méxico causa apoptosis y muestra efecto antiproliferativo sobre el hígado de rata wistar: evidencia morfológica / Aqueous extract of ruta graveolens from the north of mexico causes apoptosis and shows antiproliferative effect on the liver of wistar rat: morphological evidence

Ruta graveolens es una planta nativa del Mediterráneo Oriental y del área Sur Occidental de Asia, de esta planta se han aislado más de 120 compuestos químicos. En un estudio previo en nuestro laboratorio se observó que un extracto acuoso de R. graveolens causó necrosis y alteraciones morfológicas sugestivas de apoptosis sobre el hígado de rata Wistar. El objetivo del presente estudio, fue evaluar la inducción de apoptosis y el posible efecto antiproliferativo in vivo de un extracto acuso de R. graveolens del norte de México, mediante métodos inmunohistoquímicos. Se utilizaron 25 ratas Wistar y se dividieron en 5 grupos (n=5). El grupo 1 correspondió al grupo control negativo, el grupo 2 o control positivo se trató con 100 mg de dexametasona/kg/día. Los grupos 3 y 4 se trataron con 30 y 100 mg de extracto de R. graveolens/kg/día respectivamente. Al grupo 5 se le administraron 100 mg de dexametasona/kg/día combinados con 100 mg de extracto de R. graveolens/kg/día. Las administraciones se realizaron vía intraperitoneal por tres días. Los animales se sacrificaron por dislocación cervical, y se tomaron muestras de hígado que se fijaron en formalina, posteriormente se incluyeron en bloques de parafina. Se obtuvieron cortes histológicos que se tiñeron con el método tricrómico de Masson. También se realizaron pruebas inmunohistoquímicas de TUNEL, anti-bcl-2 y anti-PCNA; además de un estudio morfométrico. Los resultados demuestran por primera vez el potencial apoptósico y antiproliferativo del extracto acuoso de R. graveolens del norte de México, sobre el hígado de rata Wistar. Se sugiere la posibilidad de emplear dosis menores a las administradas en este estudio del extracto acuoso de R. graveolens, para investigar su potencial uso como agente antineoplásico en estudios in vitro con líneas celulares tumorales e/o implantadas en modelos murinos de cáncer.

Ruta graveolens, is a native plant of the Eastern Mediterranean and the South Western area of Asia. From this plant, more than 120 chemical compounds have been isolated. In a previous study in our laboratory, we observed that an aqueous extract of R. graveolens, caused necrosis and morphological alterations suggestive of apoptosis on the liver of Wistar rats. The objective of this study, was to evaluate the induction of apoptosis and a possible antiproliferative effect in vivo of an aqueous extract of R. graveolens from the north of Mexico, by immunohistochemical methods. 25 Wistar rats were used and divided into 5 groups (n= 5). Group 1 corresponded to negative control group, group 2 or positive control was treated with 100 mg of dexamethasone/kg/day. Groups 3 and 4 were treated with 30 and 100 mg of extract of R. graveolens/kg/day respectively. Group 5 received the administration of 100 mg of dexamethasone/kg/day combined with 100 mg of extract of R. graveolens/kg/day. The administrations were by intraperitoneal via for three days. The animals were sacrificed by cervical dislocation, liver samples were taken, fixed in formalin and then samples were embedded in paraffin blocks. Histological sections were obtained and stained with Masson trichrome method. Immunohistochemical assays of TUNEL, anti-bcl-2, and anti-PCNA were performed. Also a morphometric study was carried out. Results show for the first time the potential apoptotic and antiproliferative effect of an aqueous extract of R. graveolens from the north of Mexico on the liver of Wistar rats. This suggests the use of lower doses of the extract of R. graveolens, to investigate its potential use as an antineoplastic agent, in studies in vitro with tumor cell lines and/or implanted in murine models of cancer.

Efecto tóxico del extracto acuoso de ruta graveolens del norte de mexico sobre el hígado de rata wistar / Toxic effect of aqueous extract of ruta graveolens from the north of mexico on the liver of wistar rat

A Ruta graveolens se le atribuyen propiedades benéficas en medicina tradicional, sin embargo se ha demostrado que también puede producir efectos adversos. A la fecha no existe evidencia que ratifique que R. graveolens es totalmente inofensiva, por este motivo el objetivo de este estudio fue determinar el efecto tóxico del extracto acuoso de las hojas de esta especie vegetal en hígado de rata. Se utilizaron 25 ratas Wistar y se dividieron en 5 grupos (n=5). El grupo 1 correspondió al grupo control negativo, el grupo 2 o control positivo se trató con 100 mg de dexametasona/kg/día. Los grupos 3 y 4 se trataron con 30 y 100 mg de extracto de R. graveolens respectivamente. Al grupo 5 se le administraron 100 mg de dexametasona/kg/día combinado con 100 mg de extracto de R. graveolens/kg/día. Las administraciones se realizaron vía intraperitoneal por tres días. Los animales se sacrificaron por dislocación cervical. Las muestras de hígado se fijaron en formalina y posteriormente se incluyeron en parafina. Se obtuvieron cortes histológicos de 5 micras de grosor que se tiñeron con Hematoxilina-Eosina para la evaluación histológica con microscopia de luz. Los resultados demuestran por primera vez que la exposición al extracto acuoso de R. graveolens induce alteraciones morfológicas en el hígado de ratas Wistar. Estas alteraciones se observaron de manera leve en el grupo 3 y se incrementaron en el grupo 4. Destacó que el mayor daño se observó en el grupo 5. Se concluye que el extracto acuoso de R. graveolens resultó tóxico, sin embargo es necesario realizar estudios adicionales con el fin de caracterizar otros efectos toxicológicos que soporten el riesgo del uso de R. graveolens en medicina tradicional a largo plazo.

In traditional medicine, beneficial properties are attributed to Ruta graveolens, but it has been shown that it can also cause side effects. Because there is no evidence that ratifies that R. graveolens is totally harmless. The aim of this study was to determine the toxic effect of aqueous extract of the leaves of this plant in rat liver. 25 Wistar rats were used and divided into 5 groups (n = 5). Group 1 corresponded to the negative control group; group 2 or positive control was treated with 100 mg of dexamethasone/kg/day. Groups 3 and 4 were treated with 30 and 100 mg of extract of R. graveolens respectively. Group 5 was treated with 100 mg dexamethasone/kg/ day in combination with 100 mg of extract of R. graveolens/kg/day. Administrations were performed intraperitoneally for three days. All animals were sacrificed by cervical dislocation. Liver samples were fixed in formalin and then embedded in paraffin. Histological sections were obtained from 5 microns thick and stained with hematoxylin-eosin for histological evaluation by light microscopy. The results demonstrate for the first time that exposure to aqueous extract of R. graveolens induces morphological changes in the liver of Wistar rats. These alterations were observed slightly in group 3. Alterations increased in group 4. Highest damage was observed in group 5. The aqueous extract of R. graveolens was toxic; furthermore additional studies are needed to characterize other toxicological effects that support the risk of use of R. graveolens in traditional medicine in a long term.

Lead-, cadmium-, and arsenic-induced DNA damage in rat germinal cells.

Toxic agents can interfere with the male reproductive system at many targets. One of the major unresolved questions concerning male infertility is identification of its molecular origins. Clinical and animal studies indicate that abnormalities of spermatogenesis result from exposure to three toxic metals (lead acetate, cadmium chloride, and arsenic trioxide), but the effects on primary spermatocyte DNA of the male rat after chronic exposure to these metals have not been identified. The aims of this study were to analyze, in three independent experiments, the DNA damage induced by lead (Pb), cadmium (Cd), and arsenic (As) in rat germinal cells during three time periods, and to determine the relationship between DNA damage and blood Pb, blood Cd, and urine As levels. For lead acetate and cadmium chloride experiments, blood was collected by cardiac puncture, while for arsenic trioxide a 24-h urine sample was collected. Afterward, the animals were sacrificed by decapitation. Pachytene spermatocytes from rat testes were purified by trypsin digestion followed by centrifugal elutriation. After establishment of cell purity and viability, DNA damage (tail length) was measured employing a single cell gel/comet assay. Significant DNA damage was found in primary spermatocytes from rats with chronic exposure (13 weeks) to toxic metals. In conclusion, these findings indicate that exposure to toxic metals affects primary spermatocyte DNA and are suggestive of possible direct testicular toxicity.