Marine heatwaves and the collapse of marginal North Atlantic kelp forests.

Extreme climatic events including marine heatwaves (MHWs) are becoming more frequent and severe in the Anthropocene. However, our understanding of how these events affect population dynamics of ecologically important species is limited, in part because extreme events are rare and difficult to predict. Here, we quantified the occurrence and severity of MHWs over 60 years in warm range edge kelp forests on both sides of the North Atlantic. The cumulative annual intensity of MHWs increased two- to four-fold during this period, coinciding with the disappearance of kelps. We experimentally demonstrated a relationship between strong and severe 2018 heatwaves and high kelp mortality in both regions. Patterns of kelp mortality were strongly linked to maximum temperature anomalies, which crossed lethal thresholds in both regions. Translocation and tagging experiments revealed similar kelp mortality rates on reefs dominated by healthy kelp forests and degraded sediment-laden algal 'turfs', indicating equal vulnerability to extreme events. These results suggest a mechanistic link between MHWs and broad-scale kelp loss, and highlight how warming can make ecosystem boundaries unstable, forcing shifts to undesirable ecosystem states under episodically extreme climatic conditions.

Vitamin D regulation of HAS2, hyaluronan synthesis and metabolism in triple negative breast cancer cells.

The vitamin D receptor (VDR) and its ligand 1,25(OH)2D3 (1,25D) exert anti-tumor effects, but considerable heterogeneity has been reported in different model systems. In general, cell lines derived from aggressive tumor subtypes such as Triple Negative Breast Cancer (TNBC) express low levels of VDR and are less sensitive to 1,25D than those derived from more differentiated tumor types. We have previously reported that 1,25D inhibits hyaluronic acid synthase 2 (HAS2) expression and hyaluronic acid (HA) synthesis in murine TNBC cells. Here we confirmed the inhibitory effect of 1,25D on HA synthesis in human Hs578T cells representative of the mesenchymal/stem-like (MSL) subtype of TNBC. Because HA synthesis requires the production of hexoses for incorporation into HA, we predicted that the high HA production characteristic of Hs578T cells would require sustained metabolic changes through the hexosamine biosynthetic pathway (HBP). We thus examined metabolic gene expression in Hs578T cell variants sorted for High (HAHigh) and Low (HALow) HA production, and the ability of 1,25D to reverse these adaptive changes. HAHigh populations exhibited elevated HA production, smaller size, increased proliferation and higher motility than HALow populations. Despite their more aggressive phenotype, HAHigh populations retained expression of VDR protein at levels comparable to that of parental Hs578T cells and HALow subclones. Treatment with 1,25D decreased production of HA in both HAHigh and HALow populations. We also found that multiple metabolic enzymes were aberrantly expressed in HAHigh cells, especially those involved in glutamine and glucose metabolism. Notably, Glutaminase (GLS), a known oncogene for breast cancer, was strongly upregulated in HAHigh vs. HALow cells and its expression was significantly reduced by 1,25D (100 nM, 24 h). Consistent with this finding, Seahorse extracellular flux analysis indicated that respiration in HAHigh cells was significantly more dependent on exogenous glutamine than HALow cells, however, acute 1,25D exposure did not alter metabolic flux. In contrast to GLS, the glutamate transporter SLC1A7 was significantly reduced in HAHigh cells compared to HALow cells and its expression was enhanced by 1,25D. These findings support the concept that 1,25D can reverse the metabolic gene expression changes associated with HA production in cancer cells with aggressive phenotypes.

Medición, control y conocimiento de la presión arterial: Iniciativa Mayo Mes de la Medición Colombia 2017 / Measurement, monitoring and knowledge of blood pressure: May Measurement Month, Colombia 2017

Objetivo: Describir los hallazgos de la implementación de la iniciativa Mayo Mes de la Medición 2017 aplicada a población colombiana adulta con el objetivo de crear conciencia sobre la importancia de la medición, conocimiento y control de la presión arterial. Materiales y métodos: Mayo Mes de la Medición es una encuesta transversal que sigue las directrices de la Sociedad Internacional de Hipertensión y la Liga Mundial de Hipertensión, que recoge información de factores de riesgo cardiovascular y mediciones de presión arterial. En Colombia su implementación fue liderada por la Fundación Oftalmológica de Santander (FOSCAL) y la Sociedad Latinoamericana de Hipertensión (LASH) con el apoyo de la Red Colombiana para la Prevención de las Enfermedades Cardiovasculares y Diabetes (RECARDI). Resultados: Se recolectaron datos en 11 departamentos de 21.797 personas, siendo el 58,7% mujeres, la edad promedio fue de 40,5±17,7 años. La prevalencia global de hipertensión arterial (HTA) fue del 20,8% (autorreporte de tratamiento antihipertensivo o toma de presión arterial sistólica [≥140mmHg]). El 46,5% del total de hipertensos tuvieron cifras de presión arterial sistólica que les clasifica como no controlados (presión arterial sistólica<140mmHg) y el 26,4% no conocían su condición de hipertensos, los cuales en el presente reporte son considerados como los casos nuevos de HTA. Conclusión: La prevalencia de presión arterial es alta en esta población adulta joven, en la cual el desconocimiento de la condición de HTA es también alta, y en aquellos que conocen su condición existe un porcentaje bajo de control de la HTA, resultados que demuestran la necesidad de implementar programas eficaces de detección de pacientes hipertensos y de establecer tratamientos estandarizados para mejorar el control de la HTA como una estrategia para la reducción de eventos cardiovasculares

Aim: To describe the findings of implementing May Measurement Month 2017 in the adult Colombian population to raise awareness of the importance of blood pressure measuring, monitoring, and awareness. Materials and methods: May Measurement Month is a cross-sectional survey that follows the directives of the International Society of Hypertension and the World Hypertension League, which gathers information on cardiovascular risk factors and blood pressure readings. Its implementation in Colombia was lead by the Santander Ophthalmological Foundation (FOSCAL) and the Latin American Society of Hypertension (LASH) with the support of the Colombian Network for the Prevention of Cardiovascular Diseases and Diabetes (RECARDI). Results: Data was collected from 11 departments on 21,797 people, 58.7% of whom were female, with an average age of 40.5±17.7 years. The overall prevalence of high blood pressure (HBP) was 20.8% (self-reported antihypertensive treatment or systolic blood pressure reading [systolic blood pressure≥140mmHg]). Of the total number of hypertensives, 46.5% had systolic blood pressure readings classified as uncontrolled (systolic blood pressure<140mmHg), and 26.4% were unaware that they were hypertensive who, in this report, we consider to be new cases of HBP. Conclusion: The prevalence of (elevated) blood pressure is high in this young adult population, whose lack of awareness of HBP is also high, and HBP in those aware of their condition is poorly controlled. These results highlight the need to implement effective detection programmes for hypertensive patients and to establish standardised treatments to improve HBP control as a strategy to reduce cardiovascular events

[Measurement, monitoring and knowledge of blood pressure: May Measurement Month, Colombia 2017]. / Medición, control y conocimiento de la presión arterial: Iniciativa Mayo Mes de la Medición Colombia 2017.

AIM: To describe the findings of implementing May Measurement Month 2017 in the adult Colombian population to raise awareness of the importance of blood pressure measuring, monitoring, and awareness. MATERIALS AND METHODS: May Measurement Month is a cross-sectional survey that follows the directives of the International Society of Hypertension and the World Hypertension League, which gathers information on cardiovascular risk factors and blood pressure readings. Its implementation in Colombia was lead by the Santander Ophthalmological Foundation (FOSCAL) and the Latin American Society of Hypertension (LASH) with the support of the Colombian Network for the Prevention of Cardiovascular Diseases and Diabetes (RECARDI). RESULTS: Data was collected from 11 departments on 21,797 people, 58.7% of whom were female, with an average age of 40.5±17.7 years. The overall prevalence of high blood pressure (HBP) was 20.8% (self-reported antihypertensive treatment or systolic blood pressure reading [systolic blood pressure≥140mmHg]). Of the total number of hypertensives, 46.5% had systolic blood pressure readings classified as uncontrolled (systolic blood pressure<140mmHg), and 26.4% were unaware that they were hypertensive who, in this report, we consider to be new cases of HBP. CONCLUSION: The prevalence of (elevated) blood pressure is high in this young adult population, whose lack of awareness of HBP is also high, and HBP in those aware of their condition is poorly controlled. These results highlight the need to implement effective detection programmes for hypertensive patients and to establish standardised treatments to improve HBP control as a strategy to reduce cardiovascular events.

Scars Matter: The Importance of Incision Decisions in Bariatric Patients.

This study aims to determine if cosmetic outcomes play an important role for patients undergoing bariatric surgery, when considering a surgical approach. A video-animation describing open, conventional laparoscopic, and reduced incision magnetic assisted surgery was shown. The patient's perceptions of the surgical approaches were recorded using an anonymous survey. Fifty-one patients completed the survey. The median age was 45 (IQR: 36-51), and 38 (74.5%) were women. Cosmesis was found to be an important factor (77%) for selecting a surgical approach. Ninety percent of the patients believe that reduced incision magnet-assisted surgery provides superior cosmesis. Cosmetic results may play a determinant role when choosing a surgical approach.

Proteínas Totales, Fosfatasa Alcalina, Prostaglandinas E2 y Lisozima como Biomarcadores Salivales en Pacientes Adultos con Periodontitis Crónica / Total Protein, Alkaline Phosphatase, Prostaglandin E2 and Lysozyme as Salivary Biomarkers in Patients with Chronic Periodontitis

RESUMEN: La periodontitis crónica es una inflamación de los tejidos que rodean y dan soporte a los dientes. Diversos biomarcadores químicos y pro inflamatorios están aumentados durante el transcurso de la enfermedad. El objetivo del estudio fue determinar los distintos niveles salivales de proteínas totales, fosfatasa alcalina, prostaglandina E2 (PGE2) y lisozima en pacientes con periodontitis crónica. Se obtuvieron muestras de saliva de 31 pacientes con periodontitis crónica y se realizó un estudio de serie de casos para la determinación cuantitativa de los biomarcadores. La concentración de proteínas totales se encontró por sobre los rangos de referencia en 22 pacientes, la actividad de la fosfatasa alcalina se vio aumentada en 9 pacientes y la concentración de PGE2 se vio por sobre los rangos de referencia en 30 pacientes. Las proteínas totales y PGE2 son biomarcadores salivales en estos pacientes con periodontitis, no así la fosfatasa alcalina y la lisozima.

ABSTRACT: Chronic periodontitis is an inflammation of tissue that surrounds and supports the teeth; during the course of the disease there is an increase of different chemical and pro-inflammatory biomarkers. The objective of the study was to determine different levels in saliva of total protein, alkaline phosphatase, lysozyme and prostaglandin E2 (PGE2) in patients with chronic periodontitis. We used saliva samples from 31 patients who had chronic periodontitis and the study was a case of series. Our results showed 22 patients with increased concentrations of protein concentration, nine patients with increased alkaline phosphatase and PGE2 concentration was above the reference range in 30 patients: The total protein and PGE2 are good salivary biomarkers in patients with periodontitis, but not the alkaline phosphatase and lysozyme.

Integrated biomarker analysis of chlorpyrifos metabolism and toxicity in the earthworm Aporrectodea caliginosa.

To increase our understanding about the mode of toxic action of organophosphorus pesticides in earthworms, a microcosm experiment was performed with Aporrectodea caliginosa exposed to chlorpyrifos-spiked soils (0.51 and 10 mg kg(-1) dry soil) for 3 and 21 d. Acetylcholinesterase (AChE), carboxylesterase (CbE), cytochrome P450-dependent monooxygenase (CYP450), and glutathione S-transferase (GST) activities were measured in the body wall of earthworms. With short-term exposure, chlorpyrifos inhibited CbE activity (51-89%) compared with controls in both treated groups, whereas AChE activity was depressed in the 10-mg kg(-1) group (87% inhibition). With long-term exposure, chlorpyrifos strongly inhibited all esterase activities (84-97%). Native electrophoresis revealed three AChE isozymes, two of which showed a decreased staining corresponding to the level of pesticide exposure. The impact of chlorpyrifos on CbE activity was also corroborated by zymography. CYP450 activity was low in unexposed earthworms, but it increased (1.5- to 2.4-fold compared to controls) in the earthworms exposed to both chlorpyrifos concentrations for 3d. Bioactivation of chlorpyrifos was determined by incubating the muscle homogenate in the presence of chlorpyrifos and NAD(H)2. The mean (±SD, n=40) bioactivation rate in the unexposed earthworms was 0.74±0.27 nmol NAD(H)2 oxidized min(-1) mg(-1) protein, and a significant induction was detected in the low/short-term exposure group. GST activity significantly increased (33-35% of controls) in earthworms short-term exposed to both chlorpyrifos concentrations. Current data showed that CYP450 and GST activities had a prominent role in the initial exposure to the organophosphorus. With short-term exposure, CbE activity was also a key enzyme in the non-catalytic detoxification of chlorpyrifos-oxon, thereby reducing its impact on AChE activity, before it became saturated at t=21 d. Results indicate that A. caliginosa detoxify efficiently chlorpyrifos, which would explain its tolerance to relatively high exposure levels to chlorpyrifos.

Induction of STEAP4 correlates with 1,25-dihydroxyvitamin D3 stimulation of adipogenesis in mesenchymal progenitor cells derived from human adipose tissue.

The vitamin D receptor (VDR) is expressed in human adipocytes and is transiently induced during early adipogenesis in mesenchymal progenitor cell models. VDR null mice exhibit enhanced energy expenditure and reduced adiposity even when fed high fat diets. Adipocyte-specific transgenic-expression of human VDR in mice enhances adipose tissue mass, indicating that VDR activation in adipocytes enhances lipid storage in vivo. In these studies, we conducted genomic profiling and differentiation assays in primary cultures of human adipose-derived mesenchymal progenitor cells to define the role of the VDR and its ligand 1,25-dihydroxyvitamin D3 (1,25D) in adipogenesis. In the presence of adipogenic media, 1,25D promoted lipid accumulation and enhanced the expression of FABP4, FASN, and PPARγ. Mesenchymal cells derived from 6-month old VDR null mice exhibited impaired adipogenesis ex vivo but differentiation was restored by stable expression of human VDR. STEAP4, a gene that encodes a metalloreductase linked to obesity, insulin sensitivity, metabolic homeostasis and inflammation, was highly induced in human adipose cells differentiated in the presence of 1,25D but was minimally affected by 1,25D in undifferentiated precursors. These studies provide a molecular basis for recent epidemiological associations between vitamin D status, body weight and insulin resistance which may have relevance for prevention or treatment of metabolic syndrome and obesity.

Resultados en cirugía mayor ambulatoria en otorrinolaringología realizada en un hospital de baja complejidad / Results in major ambulatory surgery in otorhinolaryngology performed in ahospital of low complexity

Introducción: La cirugía mayor ambulatoria confiere al sistema sanitario un modelo de gestión eficiente y de alta calidad. Objetivo: Conocer los resultados de la cirugía mayor ambulatoria en otorrinolaringología (ORL) en un hospital de baja complejidad. Material y método: Estudio descriptivo retrospectivo realizado en el Hospital Santo Tomás de Limache entre los años 2004 y 2009. La inclusión de pacientes sometidos a cirugía otorrinolaringológica bajo la modalidad de cirugía mayor ambulatoria. Se realizó análisis descriptivo en base a promedios, desviación estándar y proporciones. En análisis bivariado, se emplearon las pruebas de chi cuadrado y t-student. Resultados: Se incorporó 815 pacientes. El 58% fue de sexo masculino, con edad promedio de 8,4±6,2 años. La adenoamigdalectomía sola o asociada a otras cirugías se efectuó en 54,2%% de los casos. La tasa de complicaciones posoperatorias fue de 1,22%%, la mitad de ella, la hemorragia. No hubo mortalidad. No se encontró asociación estadística entre la presencia de complicaciones y alguna variable en particular. Conclusiones: En pacientes de otorrinolaringología seleccionados, la cirugía mayor ambulatoria efectuada en un hospital de baja complejidad tiene buenos resultados, con una baja tasa de complicaciones.

Introduction: Major ambulatory surgery provide to public health and efficient and high quality model. Aim: To know the results in patient underwent Otorrinolaringologic surgery in a low complexity hospital. Material and methods: Retrospective descritive study. Date from 815 who underwent Otorrinolaringologic surgery carried on a major ambulatory surgery basis in Hospital Santo Tomás de Limache, between 2004 and 2009 where retrospectively reviewed. Analysed date included sex, age, type of conducted surgery, type of complications and the period of time in which patients were discharged. Averages, standard deviation and proportions were used. In bivariate analysis, chi square and t-student were used. Results: 58% of enrolled patients were males with age average of 8.4±6.2 years. Adenotonsillectomy single or associated to other surgeries took place in 54.2% of the cases. The rate of postoperation side effects was 1.22%, And half of these patient presented postoperatory bleeding. There was no mortality. There was not statistical association between the presence of complications and some variable in particular. Conclusions: Major ambulatory surgery In selected patients who need otorrinolaringologic surgery in a low complexity hospital is safe with low rate of complication.

Efectividad del uso tópico de Salvia officinalis en la disminución del índice gingival en sujetos con gingivitis / Effectiveness of topical use of Salvia officinalis in the gingival index decrease in subjects with gingivitis

Introducción: La gingivitis es el problema periodontal de mayor prevalencia en la población, por lo que deben buscarse más alternativas de tratamiento y prevención. Objetivo: Evaluar efecto del uso de Salvia officinalis en disminución del índice gingival modificado (IG) en alumnos de Odontología de la Universidad del Desarrollo diagnosticados con gingivitis, año 2010. Sujetos y Método: Fue realizado un estudio cuantitativo, ciego, experimental del tipo ensayo clínico controlado con placebo, sobre la acción de extracto de S. officinalis en dentífrico y colutorios para gingivitis inducida por placa bacteriana, en 33 alumnos de odontología de la Universidad del Desarrollo, Concepción; 13 mujeres y 20 hombres entre 21 y 29 años. Fueron divididos en tres grupos; placebo, colutorio y dentífrico. Luego del inicio del tratamiento fueron citados a los 7, 14 y 28 días, finalizando el tratamiento el día 14. Resultados: En el control no se encontró diferencias significativas (p=0.061) la primera semana, mientras que en los grupos con colutorio o dentífrico si hubo diferencias significativas (p=0.000 y p=0.002). La última semana al retirar el placebo, el IG se mantuvo, por otro lado en los grupos con S. officinalis no continuó el descenso. La disminución del IG fue mayor para los grupos colutorio y dentífrico que para el control. Discusión: El uso de S. officinalis es efectivo en la disminución del IG. El colutorio y dentífrico logran disminuir con mayor rapidez el IG. El colutorio logró la mayor disminución del IG.

Background: Gingivitis is the most prevalent periodontal problem in people, so we need to find new alternatives for treatment and prevention. Aim: To evaluate the effects of Salvia officinalis in the declining modified gingival index (GI) in dentistry students of the Universidad del Desarrollo diagnosed with gingivitis, year 2010. Subjects and Methods: This was a quantitative study, blinded, experimental type of placebo-controlled clinical trials on the action of extract of S. officinalis in toothpaste and mouthwash for plaque-induced gingivitis in 33 dental students from Universidad del Desarrollo, Concepción; 13 women and 20 men between 21 and 29 years old, were divided into three groups: placebo, mouthwash and toothpaste. After the first appointment we call the patients every 7, 14 and 28 days, we ended the treatment at day 14. Results: In the control group there was no significant difference (p=0.061) the first week, while groups with mouthwash and toothpaste, there were significant differences (p=0.00). The last week, as we remove the placebo, the GI was maintained. On the other hand, in groups with S. officinalis the drop did not continue. The decrease of GI was higher in groups with mouthwash and toothpaste than in the control group. Discussion: The use of S. officinalis is effective in reducing the GI. The mouthwash and toothpaste decrease more rapidly the IG. The mouthwash achieved the greatest reduction of IG.

Complicaciones del catéter central subclavio guiado por doppler o reparos anatómicos Hospital de San José, Bogotá D.C. Colombia / Complications of doppler-guided or anatomic landmark central subclavian catheter insertion San José Hospital, Bogotá DC. Colombia

El paso de catéteres venosos centrales ya sea bajo la técnica de reparos anatómicos (convencional) o la guiada por doppler dúplex, es una práctica común en el medio hospitalario. La evidencia sugiere ventajas para el doppler y los accesos a la vena subclavia o la innominada son los más comunes. El grupo desconoce estudios que comparen los dos abordajes. El presente análisis evalúa la frecuencia de complicaciones tempranas y tardías derivadas del paso de catéter con las dos técnicas, mediante un diseño descriptivo longitudinal. Se seleccionaron 50 pacientes, 22 bajo guía doppler y 28 por reparos anatómicos. La frecuencia total de complicaciones fue del 20%, y de éstas 20% tempranas y el 80% tardías. Usando reparos anatómicos ocurrieron todas las complicaciones tempranas (neumotórax y hematoma del sitio de punción) y 37% de las tardías, mientras que con doppler fueron 63% de las tardías (infección). Las limitantes del diseño escogido y el número de pacientes impiden la generalización de las observaciones obtenidas pero son de utilidad para futuros estudios.

Central venous catheter insertion by anatomic landmarks (conventional) or doppler-guided is a common practice at the hospital setting. Evidence suggests advantages of the doppler-assisted technique and access to the subclavia or innominate veins is the most common. The group is not aware of other comparative studies on this topic. This paper evaluates the frequency of early and late complications derived from catheter insertion with the two techniques using a descriptive longitudinal design study. Fifty (50) patients were selected, 22 underwent doppler-assisted catheter insertion and 28 were conducted using anatomic landmarks. The total complication rate was 20%, of which 20% were early complications and 80% were late complications. All early complications (e.g. neumothorax and hematoma at the site of puncture) and 37% of late complications occured using anatomic landmarks, whereas, 63% of patients presented late complications (infection) with the doppler technique. Obtained observations could not be generalized because of selected study design and number of patient limitations but they are useful for further study.

Restricción en pacientes agitados atendidos en unidades de cuidado médico primario / Restriction in agitated patients attendend in units of primary medical care

El manejo inicial de pacientes agresivos es frecuente en la práctica clínica, sin embargo, tanto el diagnóstico como el tratamiento iniciales tienden a ser imprecisos. La restricción física es una práctica muy usada por el personal de la salud, pero poco se sabe sobre su metodología, indicaciones, contraindicaciones y efectos adversos. Con el interés de aportar pautas, al personal de salud, encargado de la atención médica primaria de los pacientes agresivos en Colombia; realizamos una búsqueda en la literatura de los últimos cinco años en MEDLINE, HINARI, PROQUEST y OVID mediante combinación de la siguientes palabras clave: restraint, physical, aggression; emergency services, psychiatric; tranquilizing agents, con especial atención a los artículos de revisión y metaanálisis. Se seleccionaron 28 de 202 artículos de mayor relevancia para su aplicación en nuestro medio. Las indicaciones más importantes de restricción son: el riesgo de hetero o auto agresividad y el daño a la planta física. Existen claras contraindicaciones e implicaciones éticas, médicas y legales de los procedimientos de restricción que se deben acatar juiciosamente para realizar una adecuada práctica clínica. El adecuado uso de la restricción física del paciente agitado o agresivo, en unidades de atención primaria, es vital para su adecuado tratamiento y pronóstico. Es muy importante identificar la patología médica general subyacente

Functions of 1alpha,25-dihydroxyvitamin D(3) in mammary gland: from normal development to breast cancer.

This review examines the role of 1alpha,25(OH)(2)D(3) (1,25D) and the vitamin D(3) receptor in growth regulation of normal and transformed mammary epithelial cells. 1,25D exerts both anti-proliferative and pro-apoptotic functions in transformed mammary cells such as MCF-7. The anti-proliferative effects of 1,25D have been linked to suppression of growth stimulatory signals and potentiation of growth inhibitory signals, which lead to changes in cell cycle regulators such as p21, p27, cyclins and Rb. The pro-apoptotic effects of 1,25D involve alterations in the relative ratios of the bcl-2 family members which regulate mitochondrial integrity. In MCF-7 human breast cancer cells, 1,25D mediated apoptosis is associated with translocation of the pro-apoptotic protein Bax to the mitochondria, generation of reactive oxygen species, dissipation of the mitochondrial membrane potential and release of cytochrome c. These mitochondrial events trigger apoptosis in a caspase-independent manner, since caspase inhibitors do not rescue 1,25D treated cells from death. The potential role of 1,25D in growth and differentiation of normal mammary epithelial cells has been examined in VDR null mice. Initial data indicates a significant decrease in ductal differentiation in VDR null mice compared to age matched wild type mice, reflected as an increased number of undifferentiated terminal end buds in the VDR null mouse. These data suggest that 1,25D promotes differentiation during early mammary gland development. In summary, our studies suggest an expanding role for the vitamin D(3) endocrine system in control of proliferation, differentiation and apoptosis of mammary epithelial cells.

Role of mitochondria and caspases in vitamin D-mediated apoptosis of MCF-7 breast cancer cells.

Vitamin D(3) compounds are currently in clinical trials for human breast cancer and offer an alternative approach to anti-hormonal therapies for this disease. 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), the active form of vitamin D(3), induces apoptosis in breast cancer cells and tumors, but the underlying mechanisms are poorly characterized. In these studies, we focused on the role of caspase activation and mitochondrial disruption in 1alpha,25(OH)(2)D(3)-mediated apoptosis in breast cancer cells (MCF-7) in vitro. The effect of 1alpha,25(OH)(2)D(3) on MCF-7 cells was compared with that of tumor necrosis factor alpha, which induces apoptosis via a caspase-dependent pathway. Our major findings are that 1alpha,25(OH)(2)D(3) induces apoptosis in MCF-7 cells by disruption of mitochondrial function, which is associated with Bax translocation to mitochondria, cytochrome c release, and production of reactive oxygen species. Moreover, we show that Bax translocation and mitochondrial disruption do not occur after 1alpha,25(OH)(2)D(3) treatment of a MCF-7 cell clone selected for resistance to 1alpha,25(OH)(2)D(3)-mediated apoptosis. These mitochondrial effects of 1alpha,25(OH)(2)D(3) do not require caspase activation, since they are not blocked by the cell-permeable caspase inhibitor z-Val-Ala-Asp-fluoromethylketone. Although caspase inhibition blocks 1alpha,25(OH)(2)D(3)-mediated events downstream of mitochondria such as poly(ADP-ribose) polymerase cleavage, external display of phosphatidylserine, and DNA fragmentation, MCF-7 cells still execute apoptosis in the presence of z-Val-Ala-Asp-fluoromethylketone, indicating that the commitment to 1alpha,25(OH)(2)D(3)-mediated cell death is caspase-independent.

Assessment of insecticide resistance in five insect pests attacking field and vegetable crops in Nicaragua.

Field populations of Hypothenemus hampei (Ferrari), Plutella xylostella (L.), Spodoptera exigua (Hübner), Helicoverpa zea (Boddie) and Bemisia tabaci (Gennadius) were tested for resistance to several insecticides commonly used in Nicariagua. Assays were conducted to estimate the LD50s or LC50s and the corresponding resistance ratios. A diagnostic concentration was used to discriminate between susceptible and resistant strains of H. hampei. The tests with >6,000 H. hampei adults collected from six different sites indicate the absence of resistance to endosulfan. Resistance to cypermethrin, deltamethrin, chlorfluazuron, thiocyclam, and methamidophos was documented in six field populations of P. xylostella. High levels of resistance to cypermethrin and deltamethrin, but moderate levels of resistance to chlorpyriphos and methomyl, were also documented in two field populations of S. exigua. Moderate levels of resistance to cypermethrin, deltamethrin and chlorpyriphos were also documented in three field populations of H. zea. Moderate to high levels of resistance to bifenthrin, methamidophos and endosulfan were documented in four field populations of B. tabaci. The presence of significant correlations between LD50s or LC50s suggests the occurrence of cross-resistance or simultaneous selection for resistance by different insecticides with different modes of action. Our data could not differentiate between these two possibilities. Because insecticides will continue being used in Nicaragua, a resistance management program is urgently needed. The implementation of integrated pest management tactics must be accompanied by specific regulations for pesticide registration. In the future, pesticide registration regulations in Nicaragua should include periodic resistance monitoring. The mechanisms to cover the costs of resistance monitoring and resistance management should also be established.

Differential effects of 1,25-dihydroxyvitamin D3 and tetradecanoylphorbol acetate on cell cycle and apoptosis of MCF-7 cells and a vitamin D3-resistant variant.

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3), the active form of vitamin D3, and tetradecanoylphorbol acetate (TPA) are potent negative growth regulators of breast cancer cells. In this study, we compared the mechanism of action of these two compounds in MCF-7 cells and a vitamin D3-resistant variant (MCF-7D3Res). In parental MCF-7 cells, 1,25-(OH)2D3 induced morphological and biochemical markers of apoptosis (chromatin and nuclear matrix condensation and DNA fragmentation), whereas TPA induced growth arrest without apoptosis. Both 1,25-(OH)2D3 and TPA independently up-regulated the vitamin D receptor, p21, and the hypophosphorylated form of retinoblastoma (Rb) protein. The growth regulatory effects of 1,25-(OH)2D3 and TPA did not correlate with induction of p53 protein expression. When both compounds were added simultaneously, synergistic effects on MCF-7 cell number were observed, and cell cycle regulatory proteins were down-regulated. The MCF-7D3Res cells, which are not sensitive to 1,25-(OH)2D3, were growth inhibited by TPA, and TPA partially sensitized MCF-7D3Res cells to the growth inhibitory effects of 1,25-(OH)2D3. In MCF-7D3Res cells, 1,25-(OH)2D3 treatment had minimal effects on p21 or Rb protein expression, whereas TPA down-regulated Rb protein and transiently up-regulated p21. These studies indicate dissociation between the pathways triggered by 1,25-(OH)2D3 and TPA, which mediate growth regulation in MCF-7 cells. Because both compounds induce growth arrest, but only 1,25-(OH)2D3 mediates apoptosis, we conclude that cell cycle arrest is not sufficient to trigger cell death of MCF-7 cells, and that 1,25-(OH)2D3 generates distinct signals which lead to induction of apoptosis in breast cancer cells.

Comparative effects of 1,25(OH)2D3 and EB1089 on cell cycle kinetics and apoptosis in MCF-7 breast cancer cells.

1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the active metabolite of vitamin D2 inhibits breast cancer cell growth both in vivo and in vitro. In addition to its anti-proliferative effects, 1,25(OH)2D3 induces morphological and biochemical markers of apoptosis in MCF-7 cells. In the studies reported here, we compared the effects of 1,25(OH)2D3 and EB1089, a low calcemic vitamin D analog, on cell cycle kinetics and apoptosis in MCF-7 cells. Both vitamin D compounds reduced viable MCF-7 cell number in a time and dose dependent manner, with EB1089 approximately 50 fold more potent than 1,25(OH)2D3. Flow cytometric analysis indicated that both agents induced cell cycle arrest in G, G1 which was associated with accumulation of the hypophosphorylated form of the retinoblastoma (Rb) protein. MCF-7 cells treated with either 1,25(OH)2D3 or EB1089 for 48 h exhibited characteristics of apoptosis, including cytoplasmic condensation, pyknotic nuclei, condensed chromatin and DNA fragmentation. Cells treated with either agent exhibited up regulation of proteins associated with mammary gland regression (clusterin and cathepsin B) and down regulation of the anti-apoptotic protein bcl-2. These studies demonstrate that, despite its lower calcemic activity in vivo, the vitamin D analog EB1089 induces effects that are indistinguishable from those of 1,25(OH)2D3 on cell number, cell cycle and indices of apoptosis in MCF-7 cells in vitro. In addition, since both agents rapidly down regulate estrogen receptor, disruption of estrogen dependent signalling may play a role in the induction of apoptosis by vitamin D compounds in MCF-7 cells.

1,25-Dihydroxyvitamin D3 induces morphological and biochemical markers of apoptosis in MCF-7 breast cancer cells.

1,25-Dihydroxyvitamin D3 [1,25(OH)2(D)3], the active metabolite of vitamin D, is a potent inhibitor of breast cancer cell growth both in vivo and in vitro. To complement data which documents the anti-proliferative effects of 1,25(OH)2(D)3, we assessed the role of apoptosis in vitamin D-mediated growth arrest of MCF-7 cells. Time course studies indicated that 100 nM 1,25(OH)2(D)3 significantly reduces MCF-7 cell numbers within 48 h of treatment. Morphological assessment demonstrated that MCF-7 cells treated with 1,25(OH)2(D)3 for 48 h exhibit characteristic apoptotic features, including cytoplasmic condensation, pyknotic nuclei, condensed chromatin and nuclear matrix re-organization. In situ end labelling with terminal transferase indicated that cells exhibiting apoptotic morphology in 1,25(OH)2(D)3-treated cultures were positive for DNA strand breaks. These morphological features of apoptosis were accompanied by an increase in the cell death rate assessed as soluble DNA-histone complexes indicative of DNA fragmentation. To complement the morphological data, we assessed the temporal expression of two proteins which have been associated with apoptosis in mammary cells and tumors. The steady state mRNA levels for TRPM-2/clusterin and cathepsin B mRNA were significantly up-regulated in MCF-7 cells treated with 1,25(OH)2(D)3 compared to control cells. Time-dependent increases in the expression of TRPM-2/clusterin and cathepsin B proteins were detected by Western blotting in 1,25(OH)2(D)3-treated cells. These findings indicate that, in addition to its anti-proliferative effects, 1,25(OH)2(D)3 activates the apoptotic cell death pathway in MCF-7 breast cancer cells.

Infección por papiloma virus humano (HPV) cervico-uterino: citomorfología-grupo I-II-III servicio de citología-Solca núcleo de Quito

Los autores hacen un estudio de los caracteres estructurales y bioevolutivos del HPV cervicouterino. Sobre esta base formulan 3 agrupaciones con la esperanza de sistematizar la dificil y heterogenea patología producida por el HPV. Enfatizan que las mujeres portadoras del HPV de alto riesgo serán cuidadosamente manejados por el oncologo y, por el contrario, las mujeres portadoras del HPV de bajo riesgo no deberían ser alarmadas, pues el 95 por ciento de los casos regresionan a la normalidad espontaneamente. Indican además que estudios posteriores comparativos de los tres grupos con técnicas de hibridación serían recomendables.