El ejercicio físico supervisado durante el embarazo mejora la respuesta cardiaca fetal / Supervised physical activity during pregnancy improves fetal cardiac response

Objetivo: Valorar la influencia de un programa de ejercicio físico durante la gestación en la adaptación de la frecuencia cardiaca fetal (FCF). Se espera encontrar una mejor adaptación de la FCF especialmente en cuanto a recuperaciones más rápidas. Método: 45 gestantes participantes en un ensayo clínico aleatorizado sin complicaciones ni contraindicaciones para el ejercicio fueron estudiadas durante el tercer trimestre de embarazo. Se midieron las siguientes variables: FCF en reposo, FCF post-ejercicio y tiempo de recuperación de la FCF a los niveles de reposo. Resultados: La FCF en reposo fue similar en ambos grupos. La FCF post-ejercicio fue significativamente mayor en el grupo control (GC) que en el grupo ejercicio (GE) en ambas pruebas, al 40% GE=138,5±6,4GE vs 141±7,5 GC (p=0,001), al 60% 141,6±10,8 GE vs 150,3±16,8GC. Lo mismo ocurre en los tiempos de recuperación, al 40% 78,2±95,7GE vs 328,4±315,2GC (p=0,001), al 60% 193,3±257,8 GE vs 542,6±482,9GC (p=0,003). Conclusión: El ejercicio físico desarrollado durante el embarazo tiene como consecuencia una mejor adaptación de la FCF post-ejercicio, así como recuperaciones más rápidas (AU)

Objective: To assess the influence of a physical activity program during pregnancy on the adaptation of the fetal heart rate (FHR). Greater adaptations and faster recovery are expected to find. Methods: 45 pregnant women included in a randomized control trial, all with uncomplicated pregnancies for exercise were studied in their third trimester of pregnancy. Rest FHR, post-exercise FHR and recovery time were assessed. Results: Rest FHR was similar in both groups. Post-exercise FHR were significantly higher in control group (CG) than in exercise group (EG) in both test, 40% 138,5±6,4EG vs 141±7,5CG (p=0,001), 60% 141,6±10,8EG vs 150,3±16,8CG. The same was found in recovery time, 40% 78,2±95,7EG vs 328,4±315,2CG (p=0,001), al 60% 193,3±257,8EG vs 542,6±482,9CG (p=0,003). Conclusion: Greater adaptation in post-exercise FHR and faster recovery to rest FHR have been found as a result of a physical activity program carried out during pregnancy (AU)

[Connective tissue growth factor (CTGF): a key factor in the onset and progression of kidney damage]. / El factor de crecimiento de tejido conectivo (CTGF): factor clave en el inicio y la progresión del daño renal.

Connective tissue growth factor (CTGF) is increased in several pathologies associated with fibrosis, including multiple renal diseases. CTGF is involved in biological processes such as cell cycle regulation, migration, adhesion and angiogenesis. Its expression is regulated by various factors involved in renal damage, such as transforming growth factor- , Angiotensin II, high concentrations of glucose and cellular stress. CTGF is involved in the initiation and progression of renal damage to be able to induce an inflammatory response and promote fibrosis, identified as a potential therapeutic target in the treatment of kidney diseases. In this paper we review the main actions of CTGF in renal disease, the intracellular action mechanisms and therapeutic strategies for its blocking.

El factor de crecimiento de tejido conectivo (CTGF): factor clave en el inicio y la progresión del daño renal / No disponible

El factor de crecimiento de tejido conectivo (CTGF) aparece aumentado en diferentes patologías asociadas a fibrosis, incluidas múltiples enfermedades renales. CTGF participa en procesos biológicos, como la regulación del ciclo celular, migración, adhesión y angiogénesis. Su expresión está regulada por diversos factores implicados en el daño renal, entre los que destacan el factor la angiotensina II, el factor de crecimiento transformante-beta, altas concentraciones de glucosa y situaciones de estres celular. CTGF participa en el inicio y progresión del daño renal al ser capaz de inducir una respuesta inflamatoria y promover la fibrosis, señalándole como una posible diana terapéutica en el tratamiento de patologías renales. En este trabajo revisamos las principales acciones de CTGF en la patología renal, los mecanismos intracelulares de actuación y las estrategias terapéuticas para su bloqueo (AU)

Connective tissue growth factor (CTGF) is increased in several pathologies associated with fibrosis, including multiple renal diseases. CTGF is involved in biological processes such as cell cycle regulation, migration, adhesion and angiogenesis. Its expression is regulated by various factors involved in renal damage, such as Angiotensin II, transforming growth factor-beta, high concentrations of glucose and cellular stress. CTGF is involved in the initiation and progression of renal damage to be able to induce an inflammatory response and promote fibrosis, identified as a potential therapeutic target in the treatment of kidney diseases. In this paper we review the main actions of CTGF in renal disease, the intracellular action mechanisms and therapeutic strategies for its blocking (AU)

Modelos animales de diálisis peritoneal: relevancia, dificultades y futuro / No disponible

Los estudios realizados en biopsias peritoneales de pacientes con fallo renal que son tratados mediante diálisis peritoneal (DP) han demostrado que esta terapia provoca daños en la membrana peritoneal, caracterizados por fibrosisy angiogénesis, y que culminan en la pérdida de la capacidad de ultrafiltración de la membrana peritoneal. Estos estudios son descriptivos y apenas han contribuido al conocimiento de los mecanismos implicados en el proceso patológico inducido por la exposición de la membrana peritoneal a los líquidos de diálisis. Así, es necesario el desarrollo de modelos experimentales en animales para suplirlas deficiencias presentadas por los estudios en pacientes. Aquí tratamos las ventajas y dificultades de la utilización de modelos experimentales de diálisis peritoneal y las expectativas para el futuro (AU)

The studies performed with human peritoneal biopsies of peritonealdialysis-patients have demonstrated that exposure to peritonealdialysis fluid induce peritoneal deterioration. The main alterations of peritoneal membrane are fibrosis and angiogenesis that ends with the failure of the ultrafiltration capacity of the peritonealmembrane. These studies are descriptivist and scarcely help to investigate the mechanisms and stages involved on the process. Therefore, it is necessary to supply the deficiencies presented by the studies with patients. The experimental models have strongly contributed to the knowledge of the pathologic process that is induced by the continuous exposition of the peritonealmembrane to the dialysis fluids. Most of the peritonealdialysis studies use the rat as the experimental animal. Due to the difficulty of working with small animals, few studies have been done in mice. However, models in mice offers great advantages,as long as they allow us to employ different strains and genetically modified animals. We have recently developed an experimenta lmodel in mouse of exposure of the peritoneal membrane to dialysis fluids, which resembles the process of peritonealdamage that take place during peritoneal dialysis treatment inhuman patients (AU)

[Animal models of peritoneal dialysis: relevance, difficulties, and future]. / Modelos animales de diálisis peritoneal: relevancia, dificultades y futuro.

The studies performed with human peritoneal biopsies of peritoneal dialysis -patients have demonstrated that exposure to peritoneal dialysis fluid induce peritoneal deterioration. The main alterations of peritoneal membrane are fibrosis and angiogenesis that ends with the failure of the ultrafiltration capacity of the peritoneal membrane. These studies are descriptivist and scarcely help to investigate the mechanisms and stages involved on the process. Therefore, it is necessary to supply the deficiencies presented by the studies with patients. The experimental models have strongly contributed to the knowledge of the pathologic process that is induced by the continuous exposition of the peritoneal membrane to the dialysis fluids. Most of the peritoneal dialysis studies use the rat as the experimental animal. Due to the difficulty of working with small animals, few studies have been done in mice. However, models in mice offers great advantages, as long as they allow us to employ different strains and genetically modified animals. We have recently developed an experimental model in mouse of exposure of the peritoneal membrane to dialysis fluids, which resembles the process of peritoneal damage that take place during peritoneal dialysis treatment in human patients.

Selective estrogen enzyme modulator actions of melatonin in human breast cancer cells.

Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on estrogen-dependent mammary tumors. Current knowledge about the mechanisms by which melatonin inhibits the growth of breast cancer cells point to an interaction of melatonin with estrogen-responsive pathways. The intratumoral production of estrogens in breast carcinoma tissue plays a pivotal role in the proliferation of mammary tumoral cells and its blockade is one of the main objectives of the treatment of breast cancer. The aim of the present work is centered on the study of the role of melatonin in the control of some enzymes involved in the formation and transformation of estrogens in human breast cancer cells. The present study demonstrates that melatonin, at physiologic concentrations, modulates the synthesis and transformation of biologically active estrogens in MCF-7 cells, through the inhibition of sulfatase (STS) and 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) activity and expression, enzymes involved in the estradiol formation in breast cancer cells. Physiologic concentrations of melatonin also stimulate the activity and expression of estrogen sulfotransferase (EST), the enzyme responsible for the formation of the biologically inactive estrogen sulfates. The level of EST mRNA steady-state of cells treated with melatonin was three times higher than that in control cells. These findings which document that melatonin has an inhibitory effect on STS and 17beta-HSD1 and a stimulatory effect on EST, in combination with its previously described antiaromatase effect, can open up new and interesting possibilities in clinical applications of melatonin in breast cancer.

Melatonin and estradiol effects on food intake, body weight, and leptin in ovariectomized rats.

OBJECTIVE: The study in ovariectomized (Ovx) rats, as a model of menopausal status, of the effects of melatonin (M) and/or estradiol (E), associated or not with food restriction, on body weight (BW) and serum leptin levels. METHODS: Female SD rats (200-250 g) were Ovx and treated with E, M, E+M or its diluents. Control sham-Ovx rats were treated with E-M diluents. After 7 weeks being fed ad libitum, the animals were exposed for 7 more weeks to a 30% food restriction. We measured: food intake, BW, nocturnal and diurnal urinary excretion of sulphatoxymelatonin (aMT6s), leptin in midday and midnight blood samples, glucose, total cholesterol, LDL, HDL and triglycerides. RESULTS: Day/night rhythm of aMT6s excretion was preserved in all cases. The increase of aMT6s excretion in M-treated animals basically affected the nocturnal period. In animals fed ad libitum, E fully prevented Ovx-induced increase of BW, leptin and cholesterol. Melatonin reduced food intake and partially prevented the increase of BW and cholesterol, without changing leptin levels. Under food restriction, M was the most effective treatment in reducing BW and cholesterol. Leptin levels were similar in M, E or E+M treated rats, and lower than in untreated Ovx rats. CONCLUSIONS: Our result gives a preliminary experimental basis for a post-menopausal co-treatment with estradiol and melatonin. It could combine the effectiveness of estradiol (not modified by melatonin) with the positive effects of melatonin (improvement of sleep quality, prevention of breast cancer, etc.). The possible beneficial effects of melatonin which could justify its use, need to be demonstrated in clinical trials.

Melatonin prevents the estrogenic effects of sub-chronic administration of cadmium on mice mammary glands and uterus.

Cadmium (Cd) is a heavy metal classified as a human carcinogen. Occupational exposure, dietary consumption and cigarette smoking are sources of Cd contamination. Cd-induced carcinogenicity depends on its oxidative and estrogenic actions. A possible role of Cd in breast cancer etiology has been recently suggested. Melatonin, because of its antioxidant and antiestrogenic properties could counteract the toxic effects of this metalloestrogen. Our aim was both to determine the effects of relevant doses of Cd on mice mammary glands and uterus and to test whether melatonin would counteract its effects. Female mice of different ages and estrogenic status (prepuberal, adult intact, adult ovariectomized) were treated with CdCl(2) (2-3 mg/kg, i.p.), melatonin (10 microg/mL in drinking water), CdCl(2) + melatonin, or diluents. Whereas in prepuberal animals Cd disturbs mammary ductal growth and reduces the number of terminal end buds, in adults, regardless of the steroidal milieu, Cd exerts estrogenic effects on mammary glands, increasing lobuloalveolar development and ductal branching. Uterine weight also increased as a result of Cd treatment. The effects of Cd are partially inhibited by melatonin. In adult ovariectomized mice, Cd concentration in blood of animals treated with CdCl(2) + melatonin was lower than in mice receiving only Cd; the opposite effects were found in non-castrated animals. As Cd mimics the effect of estrogens, the high incidence of breast cancer in tobacco smokers and women working in industries related with Cd could be explained because of the properties of this metal. The effects of melatonin point to a possible role of this indoleamine as a preventive agent for environmental or occupational Cd contamination.

Effects of MT1 melatonin receptor overexpression on the aromatase-suppressive effect of melatonin in MCF-7 human breast cancer cells.

A major mechanism through which melatonin reduces the development of breast cancer is based on its anti-estrogenic actions by interfering at different levels with the estrogen-signalling pathways. Melatonin inhibits both aromatase activity and expression in vitro (MCF-7 cells) as well as in vivo, thus behaving as a selective estrogen enzyme modulator. The objective of this study was to study the effect of MT1 melatonin receptor overexpression in MCF-7 breast cancer cells on the aromatase-suppressive effects of melatonin. Transfection of the MT1 melatonin receptor in MCF-7 cells significantly decreased aromatase activity of the cells and MT1-transfected cells showed a level of aromatase activity that was 50% of vector-transfected MCF-7 cells. The proliferation of estrogen-sensitive MCF-7 cells in an estradiol-free media but in the presence of testosterone (an indirect measure of aromatase activity) was strongly inhibited by melatonin in those cells overexpressing the MT1 receptor. This inhibitory effect of melatonin on cell growth was higher on MT1 transfected cells than in vector transfected ones. In MT1-transfected cells, aromatase activity (measured by the tritiated water release assay) was inhibited by melatonin (20% at 1 nM; 40% at 10 microM concentrations). The same concentrations of melatonin did not significantly influence the aromatase activity of vector-transfected cells. MT1 melatonin receptor transfection also induced a significant 55% inhibition of aromatase steady-state mRNA expression in comparison to vector-transfected MCF-7 cells (p<0.001). In addition, in MT1-transfected cells melatonin treatment inhibited aromatase mRNA expression and 1 nM melatonin induced a higher and significant down-regulation of aromatase mRNA expression (p<0.05) than in vector-transfected cells. The findings presented herein point to the importance of MT1 melatonin receptor in mediating the oncostatic action of melatonin in MCF-7 human breast cancer cells and confirm MT1 melatonin receptor as a major mediator in the melatonin signalling pathway in breast cancer.

Stable expression of intracellular Notch suppresses v-Src-induced transformation in avian neural cells.

Understanding how disruption of differentiation contributes to the cancer cell phenotype is required to identify alterations essential for malignant transformation and provide experimental basis for their correction. We investigated whether primary quail neuroretina cells, transformed by a conditional v-Src mutant (QNR/v-src(ts)), could revert to a normal phenotype, in response to the stable expression of constitutively active Notch1 intracellular domain (ICN). This model system was chosen because Notch signaling plays an instructive role in cell fate determination during NR development, and because the intrinsic capacity of QNR cultures to differentiate is blocked by v-Src. We report that stable ICN expression results in suppression of QNR/v-src(ts) cell transformation in the presence of an active oncoprotein. This phenotypic reversion coincides with a major switch in cell identity, as these undifferentiated cells acquire glial differentiation traits. Both changes appear to be mediated by CBF, a transcription factor that binds to ICN and activates target genes. Cells restored to a normal and differentiated phenotype have undergone changes in the functioning of signaling effectors, essentially regulating cell morphology and cytoskeleton organization. This dominant interference may be partially mediated by an autocrine/paracrine mechanism, as revertant cells secrete a factor(s), which inhibits transformation properties of QNR/v-src(ts) cells.

Topoisomerase II inhibition and high yield of endoreduplication induced by the flavonoids luteolin and quercetin.

Luteolin and quercetin are widely distributed plant flavonoids that possess a variety of chemical and biological activities, including free-radical scavenging and antioxidant activity. Recently, both flavonoids have been reported to inhibit DNA topoisomerases I and II (topo I and topo II), a property that, together with their ability to induce DNA and chromosome damage, has made them candidate anticancer compounds. In the present study, we confirmed that both compounds are topo II inhibitors by conducting a comparative study of their effect on topo II activity from Chinese hamster ovary AA8 cells. Because interference with the function of topo II to resolve DNA entanglement at the end of replication results in chromosome malsegregation at mitosis, we investigated whether luteolin and quercetin are effective in inducing endoreduplication in AA8 cells. Concentrations of luteolin and quercetin that inhibited topo II catalytic activity resulted in extraordinarily high yields of metaphases showing diplochromosomes. Given the established relationship of polyploidy with tumor development via aneuploidy and genetic instability, these results question the usefulness of luteolin and quercetin in cancer therapy.

Genotyping of Uruguayan Human adenovirus isolates collected between 1994 and 1998.

Adenoviruses are one of the most frequent causative agents of acute lower respiratory infections in infants and young children. Twenty-three adenovirus isolates from nasopharyngeal aspirates of children hospitalized for acute lower respiratory infections in Uruguay between 1994 and 1998 were studied by restriction enzyme analysis. The genomic analysis showed that 60.9% (n = 14) of isolates belonged to the species Human adenovirus C (HAdV-C) and 31.9% (n = 9) to the species Human adenovirus B (HAdV-B). Whereas some isolates could be classified according to the published profiles into genotype or genomic variant, others displayed migration patterns not allowing classification. Eight isolates (89%) of HAdV-B corresponded to the Ad7h genotype that has been associated with severe and fatal pneumonia and necrotizing bronchiolitis in children in South America. The isolates of HAdV-C showed a great variability in accordance with the data published earlier.

Induction of genotoxic and cytotoxic damage by aclarubicin, a dual topoisomerase inhibitor.

The anthracycline aclarubicin (ACLA) is an intercalative antibiotic and antineoplastic agent that efficiently binds to DNA, leading to a secondary inhibition of the catalytic activity of topoisomerase II (topo II) on DNA. Besides this activity, ACLA has been reported to exert a concomitant poisoning effect on topo I, in a fashion similar to that of the antitumor drug camptothecin and its derivatives. As a consequence of this dual (topo II catalytic inhibiting/topo I poisoning) activity of ACLA, the picture is somewhat confusing with regards to DNA damage and cytotoxicity. We studied the capacity of ACLA to induce catalytic inhibition of topo II as well as cytotoxic effects and DNA damage in cultured Chinese hamster V79 cells and their radiosensitive counterparts irs-2. The ultimate purpose was to find out whether differences could be observed between the two cell lines in their response to ACLA, as has been widely reported for radiosensitive cells treated with topo poisons. Our results seem to agree with the view that the radiosensitive irs-2 cells appear as hypersensitive ACLA as compared with radiation repair-proficient V79 cells. The recovery after ACLA treatment was also followed-up, and the irs-2 mutant was found to be less proficient than V79 to repair DNA strand breaks induced by ACLA.

Placenta percreta, rotura uterina e histerectomía obstétrica / Placenta percreta. Uterine perforation and obstetric hysterectomy

La placenta percreta es aquella cuya inserción alcanza la serosa o incluso penetra en la cavidad abdominal. Es una entidad poco frecuente, aunque su incidencia aumenta en los casos que se asocian a placenta previa y con el antecedente de cesárea. En nuestro caso clínico, presentamos a una paciente diagnosticada de placenta previa, con antecedentes de cesárea y útero bicorne a la que indicamos una cesárea urgente por riesgo de pérdida de bienestar fetal y en la cual se objetivó hemoperitoneo, placenta percreta y rotura uterina, por lo que se realizó una histerectomía abdominal total simple. La evolución materna y fetal fue satisfactoria (AU)

Metástasis tiroidea del carcinoma de mama. Descripción de un caso clínico / Thyroid metastases from breast cancer. A case report

Las metástasis tiroideas son raras (3 por ciento) y pueden proceder de cualquier neoplasia que metastatice por vía hemática, como el cáncer de mama.Cualquier nódulo tiroideo en pacientes con tumor primario conocido no tiroideo, se debe estudiar. Lo recomendable es combinar la citología-aspiración con aguja fina y el ultrasonido, que permite diferenciar nódulos únicos o múltiples, unilaterales o bilaterales, y detecta afectación linfática del cuello. El tratamiento suele considerarse paliativo porque es habitual que la masa tiroidea aparezca en el contexto de otras metástasis. El diagnóstico precoz y un tratamiento agresivo con quimioterapia y radioterapia, pueden contribuir a prolongar la supervivencia (AU)

DNA strand breaks induced by the anti-topoisomerase II bis-dioxopiperazine ICRF-193.

The bis-dioxopiperazine ICRF-193 has long time been considered as a pure topoisomerase II catalytic inhibitor able to exert its inhibitory effect on the enzyme without stabilization of the so-called cleavable complex formed by DNA covalently bound to topoisomerase II. In recent years, however, this concept has been challenged, as a number of reports have shown that ICRF-193 really "poisons" the enzyme, most likely through a different mechanism from that shown by the classical topoisomerase II poisons used in cancer chemotherapy. In the present investigation, we have carried out a study of the capacity of ICRF-193 to induce DNA strand breaks, as classical poisons do, in cultured V79 and irs-2 Chinese hamster lung fibroblasts using the comet assay and pulsed-field gel electrophoresis (PFGE). Our results clearly show that ICRF-193 readily induces breakage in DNA through a mechanism as yet poorly understood.

The contribution of the CEA marker to CA 15.3 in the follow-up of breast cancer.

PURPOSE OF INVESTIGATION: The clinical use of tumor markers during breast cancer follow-up is still surrounded by controversy. The objective of this study consisted of determining the contribution of the CEA marker to CA 15.3 in the follow-up of breast cancer patients as applied to clinical practice. METHODS: Three hundred and eighteen cases of women with breast cancer were analyzed retrospectively as far as the sensitivity, the specificity and the positive and negative predictable values of the CA 15.3 and CEA markers. RESULTS: Of the 318 patients, 59 suffered a relapse during the study. After evaluation of both markers the sensitivity was 56.8% (CA 15.3: 47.4%), the specificity 85.3% (CA 15.3: 88.4%), the positive predictable value was 46.4% (CA 15.3: 48.2%) and the negative predictable value was 89.41% (CA 15.3: 88%). CONCLUSIONS: The low sensitivity of studied tumor markers proved of limited use on a clinical scale.

Carcinoma de mama bilateralsincrónico / Synchronous bilateral breast carcinoma

El carcinoma de mama bilateral sincrónico se define por la aparición de dos tumores de forma simultánea en ambas mamas. Según otros autores, es aquel que se diagnostica en los primeros 3, 6 o 12 meses tras el descubrimiento del primer tumor. De forma habitual, el cáncer de mama contralateral se diagnostica mediante mamografía, y suele encontrarse en un estadio más temprano que el primero. Presentamos el caso de una mujer de 35 años que, sin antecedentes personales de interés, fue diagnosticada de carcinoma de mama bilateral sincrónico (AU)

Seguimiento de las mujeres postmenopáusicas asintomáticas tratadas con tamoxifeno en el cáncer de mama / Follow-up in asymptomatic postmenopausal women treated with tamoxifen for breast cancer

El tamoxifeno es un fármaco utilizado en el tratamiento de mujeres postmenopáusicas con cáncer de mama. Sus beneficios en estas pacientes está ampliamente demostrado; sin embargo, tiene efectos secundarios, siendo el más preocupante el aumento de la patología endometrial. Debido a esto se han utilizado diferentes pruebas diagnósticas para la monitorización del grosor endometrial de estas mujeres como la ultrasonografía transvaginal, la histerosonografía, la histeroscopia y la biopsia endometrial, habiendose demostrado en los distintos estudios revisados que efectivamente existe un incremento de patología endometrial. Todo esto ha llevado a un incremento del coste, de la morbilidad y, no menos importante, de la ansiedad de las pacientes, sin que ningún trabajo demuestre claramente que la vigilancia endometrial dismunuye la mortalidad secundaria a carcinoma de endometrio en mujeres con cáncer de mama tratadas con tamoxifeno (AU)