Telómeros, telomerasa y envejecimiento. Una visita al Premio Nobel de Fisiología y Medicina de 2009 / Telomeres, telomerase and aging. A visit to the 2009 Nobel Prize in Physiology and Medicine

Introducción: En octubre de 2009, Elizabeth H. Blackburn, Carol W. Greider y Jack W. Szostak fueron galardonados por sus descubrimientos sobre los telómeros y la enzima telomerasa con el Premio Nobel de Fisiología y Medicina. Posteriormente muchas investigaciones, entre las que destacan la de científicos españoles han demostrado el papel de los telómeros en el envejecimiento y en algunas patologías relacionadas.Métodos: Para la realización de este trabajo se ha revisado tres aspectos: a) la información dada por el Comité del Nobel sobre las investigaciones de los tres galardonados; b) los mecanismos moleculares implicados en el proceso de protección de los telómeros por la acción de la telomerasa y c) la relación entre envejecimiento y sistema telómeros/telomerasa.Resultados: En las células eucariotas los telómeros constituyen el extremo terminal de los cromosomas, los cuales se acortan en cada división celular. Cuando el acortamiento es crítico, se induce daño persistente al ADN en estos extremos, senescencia, apoptosis y pérdidas de la capacidad regenerativa de los tejidos. Dada la imposibilidad de replicación completa de los telómeros por la ADN polimerasa después de cada división celular, la telomerasa, una ribonucloproteína retrotranscriptasa, actúa alargando los extremos de los cromosomas, utilizando como molde una porción de su propio ARN. Muchos factores determinan la longitud de los telómeros, sobresaliendo el acortamiento de los telómeros y la pérdida de actividad telomerásica. Además, existen multitud de factores que condicionan las diferencias entre edad fisiológica y edad cronológica.Conclusión: Entre las muchas teorías sobre el envejecimiento sobresale la que relaciona el acortamiento de los telómeros con la senescencia. No obstante se requieren más estudios en los que se determine qué mecanismos epigenéticos y de otra índole condicionan la pérdida de actividad telomerásica y la longitud de los telómeros.(AU)

Introduction: In October 2009, Elizabeth H. Blackburn, Carol W. Greider, and Jack W. Szostak were awarded the Nobel Prize in Physiology and Medicine for their discoveries about telomeres and the enzyme telomerase. Subsequently, many investigations, including that of Spanish scientists, have demonstrated the role of telomeres in aging and in some very prevalent pathologies.Methods: Three topics were reviewed to perform this article: a) the information given by the Nobel Committee on the research of the three winners of 2009 award; b) the molecular mechanisms involved in the protection process of telomeres by the telomerase enzyme; and c) the relationship between aging and the telomere/telomerase system.Results: In eukaryotic cells, telomeres constitute the terminal end of chromosomes, which are shortened within each cell division. When the shortening becomes critical, persistent DNA damage at these ends, senescence, apoptosis and loss of the tissues regenerative capacity are induced. Given the unfeasibility of telomeres complete replication by the DNA polymerase after each cell division, the telomerase, a reverse transcriptase ribonucloprotein, works by lengthening the ends of chromosomes, using as a template a portion of its own RNA. Several factors determine the length of telomeres and/or the loss of telomerase activity, with aging standing out. In addition, there are many factors that determine the differences between physiological and chronological age.Conclusion: Among aging theories, the one relating the shortening of telomeres with senescence stands out. However, more studies are required to determine which epigenetic and other mechanisms determine the loss of telomerase activity and the length of telomeres.(AU)

El algoritmo de la gasometría arterial: propuesta de un enfoque sistemático para el análisis de los trastornos del equilibrio ácido-base / The arterial blood gas algorithm: proposal of a systematic approach to analysis of acid-base disorders

Las anomalías en el equilibrio ácido-base son problemas clínicos comunes, y pueden tener efectos perjudiciales en la función celular y ser el indicio de varios trastornos. Por lo tanto, es importante para el clínico, el hacer un diagnóstico preciso de los trastornos ácido-base presentes para un tratamiento adecuado. Se han propuesto 3 enfoques para evaluar los trastornos ácido-base: un enfoque centrado en el bicarbonato, el enfoque de Stewart y el enfoque de exceso de base. Aunque los 2 últimos tienen muchos adeptos, solo discutiremos el enfoque centrado en el bicarbonato. Este enfoque es más fácil de utilizar desde el punto de vista clínico, tiene una evaluación fisiológica del trastorno ácido-base, presenta una lógica fácilmente comprensible para evaluar la gravedad y proporciona, además, una base más sólida para el desarrollo de terapias efectivas. Por lo tanto, nuestro trabajo se limitará a un examen en profundidad de esta teoría. En esta revisión, primero se introducirán nuevos conceptos importantes; sus beneficios y discusión de sus limitaciones; y luego se mostrará su utilización para analizar casos reales. Se ha generado un algoritmo para abordar de forma sistemática el análisis que incorpora estos nuevos conceptos

Abnormalities in the acid-base balance are common clinical problems and can have deleterious effects on cellular function and be a clue to various disorders. Therefore, it is important for the clinician to make a precise diagnosis of the acid-base disorder(s) present for a proper treatment. Three approaches have been proposed to evaluate acid-base disorders: a bicarbonate-centric approach; the Stewart approach, and the base excess approach. Although the latter two have many adherents, we will only discuss the bicarbonate-centric approach. This approach is simpler to utilize at the bedside, has a physiological evaluation of the acid-base disorder, presents an easily understandable approach to assess severity, and provides a more solid foundation for the development of effective therapies. Therefore, the following discussion will be limited to an examination of this approach. In this case-centric review, important new concepts will be introduced first; their benefits and limitations discussed; and then their utilization to analyze actual cases will be shown. A systematic approach algorithm that incorporates these new concepts has been generated and will be highlighted

Hepatocitos Humanos Upcytes como modelo experimental in vitro para el estudio del daño hepático inducido por fármacos a largo plazo / Human Hepatocytes Upcytes (R) as in vitro experimental model to study long-term drug-induced liver injury

La determinación de la hepatotoxicidad a largo plazo de nuevos fármacos es esencial para el desarrollo farmacéutico pero está limitada por la falta de modelos celulares adecuados que mantengan una expresión prolongada de la funcionalidad hepática. En el presente trabajo se ha explorado la idoneidad de un nuevo modelo celular llamado Hepatocitos Humanos Upcytes (HHU) cuyas células preservan funciones hepáticas y capacidad replicativa. La caracterización exhaustiva de los principales enzimas de Fase I y II implicados en el metabolismo hepático de fármacos en HHU de tres donantes independientes a diferentes tiempos de cultivo (hasta 21 días) reveló que estas células muestran perfiles de expresión (mRNA) y niveles de actividades enzimáticas más cercanos a los hepatocitos humanos que las células HepG2. Dada la estabilidad fenotípica de los HHU, tanto a nivel transcripcional como a nivel funcional, se exploró su utilidad potencial para evaluar la hepatotoxicidad a largo plazo. Para ello las células se trataron durante diferentes periodos (hasta 21 días) con varias concentraciones de tres fármacos modelo y se evaluaron los efectos sobre la viabilidad celular, la acumulación de lípidos y fosfolípidos, el calcio intracelular y los niveles de GSH. Nuestro estudio permitió detectar efectos tóxicos crónicos, como la esteatosis o la fosfolipidosis, a concentraciones en las que la viabilidad celular no estaba comprometida, confirmando la idoneidad de este nuevo modelo celular para el estudio de la hepatotoxicidad tras tratamientos prolongados con los fármacos (AU)

Determining long-term hepatotoxicity of new drugs is essential for the pharmaceutical industry development; however, it is limited by the lack of suitable cell-based models able to maintain hepatic functions over time. In the present work we explored the suitability of a new cellular model called Human Hepatocytes Upcytes (HHU) which preserves liver functions and replicative capacity. The exhaustive characterization of the major Phase I and II enzymes involved in hepatic drug metabolism in HHU from three independent donors at different culture times (up to 21 days) revealed that these cells show expression profiles (mRNA) and activity levels enzymes that are closer to human hepatocytes than those of HepG2 cells. Given the phenotypic stability of HHU, both at the transcriptional and functional level, their potential utility to assess long-term hepatotoxicity was explored. Cells were treated for various periods (up to 21 days) with several concentrations of three model drugs and the effects on cell viability, lipid and phospholipid accumulation, intracellular calcium and GSH levels were evaluated. Our study allowed us to detect chronic toxic effects, such as steatosis or phospholipidosis, at concentrations that did not compromise celular viability, confirming the suitability of this new cellular model for the study of long-term drug-induced hepatotoxicity (AU)

Biología y mecanobiología del disco intervertebral / Biology and mechanobiology of the intervertebral disc

El disco intervertebral (DIV) se caracteriza por su escasa celularidad y por constituir la estructura avascular más grande del cuerpo humano. Las escasas células del disco tienen que adaptarse a un metabolismo anaerobio con baja tensión de O2 y pH ácido. Además de sobrevivir a un microambiente adverso, están expuestas a un elevado estrés mecánico. La adaptación biológica de las células a las condiciones de acidosis e hiperosmolaridad está regulada por mecanoproteínas responsables de convertir una señal mecánica en respuesta celular, modificando su expresión génica. La mecanobiología nos ayuda a entender mejor la biopatología del DIV y su potencial reparación biológica

The intervertebral disc (IVD) is noted for its low cell content, and being the largest avascular structure of human body. The low amount of cells in the disc have to adapt to an anaerobic metabolism with low oxygen pressure and acidic pH. Apart from surviving in an adverse microenvironment, they are exposed to a high level of mechanical stress. The biological adaptation of cells to acidosis and hyperosmolarity conditions are regulated by mechanoproteins, which are responsible for converting a mechanical signal into a cellular response, thus modifying its gene expression. Mechanobiology helps us to better understand the pathophysiology of IVD and its potential biological repair

Anti-proliferative effects of paeonol on human prostate cancer cell lines DU145 and PC-3

Paeonol (Pae) is the main active ingredient from the root bark of Paeonia moutan and the grass of Radix Cynanchi Paniculati. Numerous reports indicate that Pae effectively inhibits several types of cancer lines. In this study, we report that Pae hinders prostate cancer growth both in vivo and in vitro. Human prostate cancer lines DU145 and PC-3 were cultured in the presence of Pae. The xenograft tumor in mice was established by subcutaneous injection of DU145 cells. Cell growth was measured by MTT, and the apoptosis was detected by the flow cytometry. Expression of Bcl-2, Bax, Akt, and mTOR were tested by western blotting assay. DU145 and PC-3 showed remarkable sensitivity to Pae, and exposure to Pae induced dose-and time-dependent growth inhibitory responses. Moreover, treatment of Pae promoted apoptosis and enhanced activities of caspase-3, caspase-8, and caspase-9 in DU145. Further work demonstrated Pae reduced expression of Bcl-2 and increased expression of Bax in DU145. Interestingly, we observed that Pae significantly decreased phosphorylated status of Akt and mTOR, and inhibitory effects of Pae and PI3K/Akt inhibitor on DU145 proliferation were synergistic. Finally, we confirmed that oral administration of Pae to the DU145 tumor-bearing mice significantly lowered tumor cell proliferation and led to tumor regression. Pae possesses inhibitory effects on prostate cancer cell growth both in vitro and in vivo, and the anti-proliferative effect may be closely related to its activation of extrinsic and intrinsic apoptotic pathway and inhibition of the PI3K/Akt pathway (AU)

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M3 cholinoreceptors alter electrical activity of rat left atrium via suppression of L-type Ca2+ current without affecting K+ conductance

Electrophysiological effects produced by selective activation of M3 cholinoreceptors were studied in isolated left atrium preparations from rat using the standard sharp glass microelectrode technique. The stimulation of M3 receptors was obtained by application of muscarinic agonist pilocarpine (10-5 M) in the presence of selective M2 antagonist methoctramine (10-7 M). Stimulation of M3 receptors induced marked reduction of action potential duration by 14.4 ± 2.4% and 16.1 ± 2.5% of control duration measured at 50 and 90% of repolarization, respectively. This effect was completely abolished by selective M3 blocker 4-DAMP (10-8 M). In isolated myocytes obtained from the rat left atrium, similar pharmacological stimulation of M3 receptors led to suppression of peak L-type calcium current by 13.9 ± 2.6% of control amplitude (measured at +10 mV), but failed to affect K+ currents Ito, IKur, and IKir. In the absence of M2 blocker methoctramine, pilocarpine (10-5 M) produced stronger attenuation of ICaL and induced an increase in IKir. This additive inward rectifier current could be abolished by highly selective blocker of Kir3.1/3.4 channels tertiapin-Q (10-6 M) and therefore was identified as IKACh. Thus, in the rat atrial myocardium activation of M3 receptors leads to shortening of action potentials via suppression of ICaL, but does not enhance the major potassium currents involved in repolarization. Joint stimulation of M2 and M3 receptors produces stronger action potential shortening due to M2-mediated activation of IKACh (AU)

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Gamma-Tocotrienol prevents cell cycle arrest in aged human fibroblast cells through p16INK4a pathway

Human diploid fibroblasts (HDFs) proliferation in culture has been used as a model of aging at the cellular level. Growth arrest is one of the most important mechanisms responsible for replicative senescence. Recent researches have been focusing on the function of vitamin E in modulating cellular signaling and gene expression. Therefore, the aim of this study was to elucidate the effect of palm γ-tocotrienol (vitamin E) in modulating cellular aging through p16INK4a pathway in HDF cells. Primary culture of senescent HDFs was incubated with 70 μM of palm γ-tocotrienol for 24 hours. Silencing of p16INK4a was carried out by siRNA transfection. RNA was extracted from the different treatment groups and gene expression analysis was carried out by real-time reverse transcription polymerase chain reaction. Proteins that were regulated by p16INK4a were determined by western blot technique. The finding of this study showed that p16INK4a mRNA was overexpressed in senescent HDFs, and hypophosphorylated-pRb and cyclin D1 protein expressions were increased (p < 0.05). However, downregulation of p16INK4a and hypophosphorylated-pRb and cyclin D1 protein expressions (p < 0.05) by γ-tocotrienol led to modulation of the cell cycle regulation during cellular aging. In conclusion, senescent HDFs showed change in biological process specifically in cell cycle regulation with elevated expression of genes and proteins which may contribute to cell cycle arrest. Palm γ-tocotrienol may delay cellular senescence of HDFs by regulating cell cycle through downregulation of p16INK4a and hypophosphorylated-pRb and cyclin D1 protein expressions (AU)

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Inhibition of microRNA-181a may suppress proliferation and invasion and promote apoptosis of cervical cancer cells through the PTEN/Akt/FOXO1 pathway

MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs, which play a critical role in regulating varieties of the biological and pathologic processes. miR-181a has been reported to participate in tumorigenic progression. However, the roles of miR-181a in cervical cancer (CC) are still unknown. The aim of this research was to explore the effects and molecular mechanism of miR-181a in CC cells. In this paper, the levels of miR-181a in CC cell lines were determined by real-time PCR. We found that the levels of miR-181a were evidently enhanced in CC cell lines compared with normal cervical epithelium cells. Then, the miR-181a inhibitor was transiently transfected into HeLa and CaSKi cells using Lipofectamine 2000 reagent. Subsequently, the Cell Counting Kit-8 (CCK-8) and BrdU-ELISA results showed that down-regulation of miR-181a inhibited the cell viability and proliferation. Our data also demonstrated that miR-181a inhibitor arrested cell cycle progression of HeLa and CaSKi cells by up-regulation of p21 and p27 expressions. In addition, inhibition of miR-181a promoted apoptosis of HeLa and CaSKi cells due to increasing Bax expression and decreasing Bcl-2 expression. Ultimately, the effect of miR-181a inhibitor on the PTEN/Akt/FOXO1 signaling pathway was investigated by Western blot. From our results, down-regulation of miR-181a increased the expression of PTEN and decreased phosphorylation of Akt and FOXO1. Altogether, miR-181a might be an oncogene in CC cells. The potential mechanism was that inhibition of miR-181a might suppress proliferation and invasion and promote apoptosis of HeLa and CaSKi cells by modulating the PTEN/Akt/FOXO1 signaling pathway (AU)

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Let-7b inhibits the malignant behavior of glioma cells and glioma stem-like cells via downregulation of E2F2

Glioblastoma multiforme (GBM), the most common and lethal primary brain tumor in adults characterized by high proliferative ability and mortality rate, contains a small subpopulation of cancer stem-like cells (CSCs), which is responsible for GBM progression and therapeutic resistance. Numerous microRNAs are strongly implicated in the malignancy of glioma. However, their specific functions and roles have yet to be fully demonstrated. In the present study, we revealed that the upregulation of Let-7b, a member of the Let-7 microRNA family, inhibited proliferation, migration, and invasion in glioma cell lines. Using bioinformatics, expression analysis, and luciferase assay, E2F2 was confirmed as a candidate target of Let-7b. Moreover, we also observed that elevated levels of Let-7b resulted in a reduction of tumor sphere growth and stemness of glioma stem-like cells. Furthermore, we found that knockdown of E2F2 expression could reduce the proliferation of glioma and GSCs, while overexpression of E2F2 partially abrogated the inhibitory effect of Let-7b on the proliferation of glioma and GSCs. In conclusion, we suggest that Let-7b could be developed into a promising anticancer target in glioma (AU)

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A common effect of angiotensin II and relaxin 2 on the PNT1A normal prostate epithelial cell line

The prostate gland is a part of the male reproductive tract which produces both angiotensin II (Ang II) and relaxin 2 (RLN2). The present study analyzes the effect of both these peptide hormones at concentration 10−8M on viability, proliferation, adhesion, migration, and invasion of normal prostate epithelial cells (PNT1A). Improved survival in two- and three-dimensional cell cultures was noted as well as visual changes in colony size and structure in Geltrex™. Stimulatory influence on cell viability of each peptide applied single was lower than in combination. Enhanced survival of PNT1A cells appears to be associated with increased BCL2/BAX messenger RNA (mRNA) expression ratio. Modulation of cell spreading and cell-extracellular matrix adhesion dynamics were also altered as an influence of tested hormone application. However, long-term Ang II and RLN2 effects may lead to an increase of normal prostate cell migration and invasion abilities. Moreover, gelatin zymography revealed that both gelatinases A and B were augmented by Ang II treatment, whereas RLN2 significantly stimulated only MMP-9 secretion. These results support the hypothesis that deregulation of locally secreted peptide hormones such as Ang II and RLN2 may take part in the development of certain cancers, including prostate cancer. Moreover, the observed ability of relaxin 2 to act as a regulator of mRNA expression levels not only LGR7 but also classic angiotensin receptors suggested that renin-angiotensin system and relaxin family peptide system are functionally linked (AU)

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Chain elongation analog of resveratrol as potent cancer chemoprevention agent

Resveratrol is identified as a natural cancer chemoprevention agent. There has been a lot of interest in designing and developing resveratrol analogs with cancer chemoprevention activity superior to that of parent molecule and exploring their action mechanism in the past several decades. In this study, we have synthesized resveratrol analogs of compounds A-C via conjugated chain elongation based on isoprene unit retention strategy. Remarkably, cytotoxic activity analysis results indicated that compound B possesses the best proliferation inhibition activity for NCI-H460 cells in all the test compounds. Intriguingly, compound B displayed a higher cytotoxicity against human non-small cell lung cancer cells (NCI-H460) compared to normal human embryonic lung fibroblasts (MRC-5). Afterward, flow cytometry analysis showed that compound B would induce cell apoptosis. We further researched the action mechanism. When NCI-H460 cells were incubated by compound B for 6 or 9 h, respectively, the intracellular reactive oxygen species (ROS) level was enhanced obviously. With elevation of intracellular ROS level, flow cytometry measurement verified mitochondrial transmembrane potential collapse, which was accompanied by the up-regulation of Bax and down-regulation of Bcl-2. More interestingly, compound B increased the expression of caspase-9 and caspase-3, which induced cell apoptosis. Moreover, compound B arrested cell cycle in G0/G1 phase. These are all to provide useful information for designing resveratrol-based chemoprevention agent and understanding the action mechanism (AU)

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Cinnamtannin B-1, a natural antioxidant that reduces the effects of H2O2 on CCK-8-evoked responses in mouse pancreatic acinar cells

This work was designed in order to gain an insight on the mechanisms by which antioxidants prevent pancreatic disorders. We have examined the properties of cinnamtannin B-1, which belongs to the class of polyphenols, against the effect of hydrogen peroxide (H2O2) in mouse pancreatic acinar cells. We have studied Ca2+ mobilization, oxidative state, amylase secretion, and cell viability of cells treated with cinnamtannin B-1 in the presence of various concentrations of H2O2. We found that H2O2 (0.1-100 ìM) increased CM-H2DCFDA-derived fluorescence, reflecting an increase in oxidation. Cinnamtannin B-1 (10 ìM) reduced H2O2-induced oxidation of CM-H2DCFDA. CCK-8 induced oxidation of CM-H2DCFDA in a similar way to low micromolar concentrations of H2O2, and cinnamtannin B-1 reduced the oxidant effect of CCK-8. In addition, H2O2 induced a slow and progressive increase in intracellular free Ca2+ concentration ([Ca2+]c). Cinnamtannin B-1 reduced the effect of H2O2 on [Ca2+]c, but only at the lower concentrations of the oxidant. H2O2 inhibited amylase secretion in response to cholecystokinin, and cinnamtannin B-1 reduced the inhibitory action of H2O2 on enzyme secretion. Finally, H2O2 reduced cell viability, and the antioxidant protected acinar cells against H2O2. In conclusion, the beneficial effects of cinnamtannin B-1 appear to be mediated by reducing the intracellular Ca2+ overload and intracellular accumulation of digestive enzymes evoked by ROS, which is a common pathological precursor that mediates pancreatitis. Our results support the beneficial effect of natural antioxidants in the therapy against oxidative stress-derived deleterious effects on cellular physiology (AU)

Una aproximación farmacológica al tratamiento de la acondroplasia / A pharmacological appoach to achondroplasia treatment

La acondroplasia es una patología caracterizada por una mutación en el receptorpara el factor de crecimiento de fibroblastos de tipo 3 (FGFR3). Esta alteracióncausa la patología que conocemos habitualmente con el nombre de enanismo congénitoy que se manifiesta con individuos de talla baja con diversos problemasmúsculo-esqueléticos. La aplicación de nucleótidos y dinucleótidos ha permitidoobservar que las células acondroplásicas pueden fenomenológicamente comportarsecomo células normales, en especial cuando son tratadas con el dinucleótidoAp4A. Este compuesto reestablece los niveles de calcio en los condrocitos acondroplásicos,permitiendo que se comporten como células absolutamente normales enlo que respecta a este ion. Por otro lado, también este dinucleótido permite que elreceptor de FGFR3, que no se internaliza y degrada con normalidad, pueda pasara ser degradado por las vías proteosomales y lisosomales, como sucede en lascélulas normales, haciendo que el receptor motivo de la patología desaparezca de las membranas de los condrocitos acondroplásicos. Por último, hemos podidocomprobar cómo el derivado del piridoxalfosfato, el PPADS, presenta propiedadesextraordinarias al reducir prácticamente a cero los niveles de fosforilación de lasproteínas ERK, que son anormalmente elevadas por el receptor FGFR3 acondroplásicoy que originan la patología. En resumen, se plantean una serie de nuevasestrategias encaminadas al tratamiento de la acondroplasia por medio de estrategiasde tipo farmacológico en claro contrate con las estrategias actuales de tipoquirúrgico

Achondroplasia is a pathology due to a mutation in the receptor for thefibroblast growth factor type 3 (FGFR3). This alteration produces problems inindividuals’ stature as well as other muscle-skeletal problems. The application ofnucleotides and dinucleotides permit achondroplasic cells (chondrocytes) torecover, aparently, from this pathology. In particular, the application of thedinucleotide Ap4A, permits to restore the correct calcium levels in achondroplasiccell. Moreover, this dinucleotide permits the right degradation of the FGFR3receptor, which does not downregulate properly in achondropasic chondrocytes,by facilitating the proteosomal and lysosomal pathways alter the dinucleotideapplication. Also we have discovered that the pyridoxal phosphate derivative PPADScan dramatically reduce the activation of ERK casacade which is abnormalyelevated by the achondroplasic FGFR3 receptor raising the pathology. In summary,we wish to introduce a series of new pharmacological strategies for the treatmentof achondroplasia in clear contrast with the current surgery ones

Carcinoma oral de células escamosas. Parámetros citométricos de interés pronóstico / Oral squamous cell carcinoma. Cytometric parameters of prognostic interest

Objetivos: el presente estudio se realizó para encontrar posiblesfactores pronósticos del Carcinoma oral de células escamosaspuesto que es una enfermedad frecuente ( 3 – 4 % de los tumoresmalignos ) que origina una gran morbilidad y mortalidad y quejustifica cualquier intento que trate de aportar algo para conocermejor esta patología. Diseño del estudio: hemos realizadoun estudio sobre 81 carcinomas orales de células escamosasextraídos del archivo del Hospital Universitario Marqués deValdecilla ( Santander ) , tratados con el mismo procedimiento, de los cuales en 67 de ellos se realizó citometría de flujo.Resultados: No hemos encontrado diferencias estadísticamentesignificativas entre el índice de proliferación celular y el índicemitótico , la ploidía y la fase S. Así mismo ninguna de lasvariables citométricas estudiadas ha presentado relación conla aparición de recidiva loco-regional , metástasis a distanciani con la supervivencia.Conclusiones: no podemos utilizar éstas variables como factor pronósticoen el carcinoma de células escamosas de la cavidad oral

Objectives: the present study was made in order to find possibleprognostic factors in oral squamous cell carcinoma, given thatit is a frequent disease (3-4% of all malignant tumors) and isthe cause of a high morbidity and mortality which justifies anyattempt to contribute something towards the understanding ofthis pathology.Study design: 81 oral squamous cell carcinomas, treated with thesame procedure, and retrieved from the archive of the HospitalUniversitario Marqués de Valdecilla (Santander) were studied.Flow cytometry was carried out on 67 of the samples.Results: no statistically significant differences were foundbetween the cellular proliferative index and the mitotic index,ploidy and the S-phase factor. Likewise, none of the cytometricvariables studied presented any association with the appearanceof local relapse, distant metastases or survival.Conclusions: these variables cannot be used as a prognosticfactors in squamous cell carcinomas of the oral cavity

Líneas celulares adenohipofisarias alfaT3-1, LBetaT2, RC-4B/C y MtTW-10: regulación y fisiología celular / Anterior pituitary cell lines alphaT3-1, LBetaT2, RC-4B/C and MtTW-10: regulation and cellular physiology

La adenohipófisis es un órgano bien estructurado y con una función claramente definida, que ofrece la posibilidad de estudiar los mecanismos que intervienen en la organogenia y el mantenimiento de funciones celulares específicas. Debido a la gran diversidad celular de esta glándula endocrina, la obtención de cultivos primarios altamente purificados de tipos celulares concretos a partir de este órgano es una tarea difícil. El desarrollo reciente de técnicas de oncogenia dirigida ha permitido la obtención de líneas celulares que mantienen fenotipos diferenciados específicos y que son una herramienta valiosa para el estudio de su biología celular. Estos sistemas permiten la investigación detallada de mecanismos celulares y moleculares que, de otra manera, resultarían difícilmente accesibles tanto in vivo como en cultivos primarios de células adenohipofisarias. De esta forma, líneas celulares, como alfaT3-1 y LBetaT2, representan estadios discretos del desarrollo y se caracterizan básicamente por la expresión de funciones diferenciadas del linaje de células gonadotropas. Junto con estos sistemas experimentales existen otros que muestran una población celular tan diversa como la observada en glándulas adenohipofisarias adultas, como ocurre en las líneas celulares RC-4B/C y MtTW-10. En este artículo presentamos una descripción resumida de cada una de las líneas mencionadas anteriormente (AU)

Las principales etapas de la evolución del metabolismo celular. Una aproximación evolucionista al estuido del metabolismo

Todos los fenómenos biológicos son el resultado de un proceso evolutivo. El metabolismo celular no es una excepción y en las células actuales se pueden encontrar huellas de ese proceso. En este trabajo ponemos de manifiesto, a través del análisis comparado, rasgos metabólicos suficientemente significativos como para permitirnos proponer un modelo filogenético de despliegue del metabolismo celular e identificar las principales etapas del mismo. El primer modelo de este tipo fue desarrollado por F. Cordón (1990), en el contexto de su teoría de unidades de niveles de integración, y forma parte del desarrollo de la misma. El que presentamos aquí coincide plenamente con el de Cordón, pero está razonado a partir de argumentos que no son privativos de su teoría; con ello perseguimos independizar la discusión del primero de la argumentación de la segunda, de manera que la verosimilitud del modelo que proponemos, en el que se llega a las mismas conclusiones, refuerce los argumentos propios de la teoría y, como consecuencia, a ésta. (AU)