Production of 129mXe and 131mXe via neutron activation of 128Xe and 130Xe at ILL-RHF and NCBJ-MARIA high-flux reactors.

The long-lived xenon isomers 129mXe and 131mXe are of interest for the GAMMA-MRI project, which aims at developing a novel imaging modality based on magnetic resonance of polarized unstable tracers. Here, we present the steps leading to and following the production of these two isomers via neutron irradiation of highly-enriched 128Xe and 130Xe gas samples at two high-flux reactors, the High-Flux Reactor (Réacteur à haut flux, RHF) at the Institut Laue-Langevin (ILL) and the MARIA reactor at the National Centre for Nuclear Research (NCBJ). We describe the experimental setups and procedures used to prepare the stable xenon samples, to open the irradiated samples, and to transfer xenon isomers into reusable transport vials. The activity of 129mXe and 131mXe was measured to be in the range of tens of MBq per sample of 0.8(1)mg, and was proportional to thermal neutron flux density. A small activity of unstable contaminants was also visible in the samples, but their level is not limiting for the GAMMA-MRI project's objectives. In addition, the minimum thermal neutron flux density required to produce 129mXe and 131mXe sufficient for the project could be also determined.

[Cross-cultural adaptation to Spanish of the Signs of Depression Scale (SODS) to the early assessment of mood in patients admitted to a Stroke Unit]. / Adaptación transcultural al español de la Signs of Depression Scale (SODS) para la evaluación precoz del estado de ánimo en pacientes ingresados en una unidad de ictus.

INTRODUCTION: Stroke hospitalization negatively affects mood. Clinical guidelines recommend early evaluation of mood disorders. However, there is no consensus on the most appropriate scale in Spanish language. AIM: The objective of the study is the cross-cultural adaptation of the Signs of Depression Scale (SODS) in patients admitted to the stroke unit of the Hospital del Mar. MATERIALS AND METHODS: The work scheme for transcultural adaptation into Spanish was: a) direct translation; b) reconciliation and synthesis of translations; c) reverse translation into English; d) consensus of the back-translated version with original author; e) cognitive interrogation; f) revision and consensus version in Spanish; g) reading test, spelling, and grammar check; h) final version. Analysis and descriptive summary of the adaptation process was performed. RESULTS: There were no differences between direct translation versions. The back-translation version was accepted by the author of the original questionnaire. A convenience sample of patients with/without aphasia (n = 22) was included for cognitive interview from which no major problems were identified in the implementation of the questionnaire. Inclusive language was used in the final version. CONCLUSION: The transcultural adaptation of the scale allows in a simple and early way the evaluation mood in patients admitted to the stroke unit. The Spanish version is equivalent to the original instrument. This adaptation can be incorporated into care in the Stroke Unit and is extrapolated to other Spanish-speaking centres.

TITLE: Adaptación transcultural al español de la Signs of Depression Scale (SODS) para la evaluación precoz del estado de ánimo en pacientes ingresados en una unidad de ictus.Introducción. La hospitalización por ictus afecta negativamente al estado de ánimo. Las guías clínicas recomiendan evaluar precozmente el estado de ánimo. Sin embargo, no existe consenso sobre la escala más apropiada en idioma español. Objetivo. El objetivo del estudio es realizar una adaptación transcultural de la Signs of Depression Scale en pacientes ingresados en la unidad de ictus. Materiales y métodos. El esquema de trabajo de la adaptación transcultural al español fue: a) traducción directa; b) conciliación y síntesis de las traducciones; c) traducción inversa al inglés; d) consenso de la versión retrotraducida; e) interrogatorio cognitivo; f) revisión y versión consensuada en español; g) prueba de lectura, revisión ortográfica y gramatical, y h) versión final. Se realizó un análisis y un resumen descriptivo del proceso de adaptación transcultural. Resultados. Las versiones de traducción directa no presentaron diferencias. La versión de la traducción inversa fue aceptada por la autora del cuestionario original. Para el interrogatorio cognitivo se incluyó una muestra por conveniencia de 22 pacientes con/sin afasia a partir de la cual no se identificaron problemas en la aplicación del cuestionario. Se utilizó un lenguaje inclusivo en la versión final. Conclusiones. La versión española es equivalente al instrumento original. La adaptación transcultural de la escala permite, de forma sencilla y precoz, la evaluación del estado de ánimo en pacientes con ictus. Esta adaptación se puede incorporar en los cuidados en la unidad de ictus y es extrapolable a otros centros de habla hispana.

Adaptación transcultural al español de la Signs of Depression Scale (SODS) para la evaluación precoz del estado de ánimo en pacientes ingresados en una unidad de ictus / Cross-cultural adaptation to Spanish of the Signs of Depression Scale (SODS) to the early assessment of mood in patients admitted to a Stroke Unit

Introducción: La hospitalización por ictus afecta negativamente al estado de ánimo. Las guías clínicas recomiendan evaluar precozmente el estado de ánimo. Sin embargo, no existe consenso sobre la escala más apropiada en idioma español. Objetivo: El objetivo del estudio es realizar una adaptación transcultural de la Signs of Depression Scale en pacientes ingresados en la unidad de ictus. Materiales y métodos: El esquema de trabajo de la adaptación transcultural al español fue: a) traducción directa; b) conciliación y síntesis de las traducciones; c) traducción inversa al inglés; d) consenso de la versión retrotraducida; e) interrogatorio cognitivo; f) revisión y versión consensuada en español; g) prueba de lectura, revisión ortográfica y gramatical, y h) versión final. Se realizó un análisis y un resumen descriptivo del proceso de adaptación transcultural. Resultados: Las versiones de traducción directa no presentaron diferencias. La versión de la traducción inversa fue aceptada por la autora del cuestionario original. Para el interrogatorio cognitivo se incluyó una muestra por conveniencia de 22 pacientes con/sin afasia a partir de la cual no se identificaron problemas en la aplicación del cuestionario. Se utilizó un lenguaje inclusivo en la versión final. Conclusiones: La versión española es equivalente al instrumento original. La adaptación transcultural de la escala permite, de forma sencilla y precoz, la evaluación del estado de ánimo en pacientes con ictus. Esta adaptación se puede incorporar en los cuidados en la unidad de ictus y es extrapolable a otros centros de habla hispana.(AU)

Introduction: Stroke hospitalization negatively affects mood. Clinical guidelines recommend early evaluation of mood disorders. However, there is no consensus on the most appropriate scale in Spanish language. Aim: The objective of the study is the cross-cultural adaptation of the Signs of Depression Scale (SODS) in patients admitted to the stroke unit of the Hospital del Mar. Materials and methods: The work scheme for transcultural adaptation into Spanish was: a) direct translation; b) reconciliation and synthesis of translations; c) reverse translation into English; d) consensus of the back-translated version with original author; e) cognitive interrogation; f) revision and consensus version in Spanish; g) reading test, spelling, and grammar check; h) final version. Analysis and descriptive summary of the adaptation process was performed. Results:. There were no differences between direct translation versions. The back-translation version was accepted by the author of the original questionnaire. A convenience sample of patients with/without aphasia (n = 22) was included for cognitive interview from which no major problems were identified in the implementation of the questionnaire. Inclusive language was used in the final version. Conclusion: The transcultural adaptation of the scale allows in a simple and early way the evaluation mood in patients admitted to the stroke unit. The Spanish version is equivalent to the original instrument. This adaptation can be incorporated into care in the Stroke Unit and is extrapolated to other Spanish-speaking centres.(AU)

Change in triggered EMG thresholds for thoracic pedicle screws caused by pneumothorax during surgery for adolescent idiopathic scoliosis. Report of two cases. / Alteración en los umbrales de estimulación de tornillos pediculares torácicos secundaria a neumotórax en cirugía por escoliosis idiopática del adolescente. A propósito de dos casos.

Posterior spinal instrumentation and fusion with pedicle screws inserted by free-hand technique and controlled by multimodal intraoperative monitoring is the most common technique in adolescent idiopathic scoliosis surgery. Pneumothorax is a described complication of this kind of procedure. Triggered electromyography is used to identify pedicle wall breakthrough and prevent neurological injuries. We report 2 clinical cases in which unilateral decrease in triggered electromyography values associate with ipsilateral pneumothorax. Postoperative chest radiographs need to be done in order to diagnose a pneumothorax. However, routinely performing a chest radiograph has been questioned because of the low incidence of this surgical complication. As a result of the association described in this article, we consider that when a unilateral decrease in triggered electromyography values is detected, a hidden pneumothorax should be suspected and ruled out.

Suitability of different tooth replicas for endodontic training: perceptions and detection of common errors in the performance of postgraduate students.

AIM: To compare the perceptions of students when using five different tooth replicas and to detect common errors in the performance of students that might be attributed to a specific type of tooth replica. METHODOLOGY: Five groups (n = 10 each) of artificial first maxillary molars (DEPT, DRSK, Nissin, DENTALIKE and TrueTooth) were used. All 50 teeth were mounted individually in opaque containers, distributed in 10 packages containing a sample from each with an assigned random order for students to perform root canal treatments. Ten postgraduate students each performed a root canal treatment on the five replicas, in the assigned order, and completed a satisfaction questionnaire. Three trained and calibrated endodontic educators, each with more than 15 years of experience, evaluated their performance using a grading rubric and completed a questionnaire to detect common errors attributed to a specific tooth replica. Inter-rater reliability was calculated with the interclass correlation coefficient for both consistency and absolute agreement. A two-way related measures anova was used to assess the interaction amongst evaluators and tooth groups on the average scores of students. Post hoc T3 Dunnet was used to compare groups. The perceptions of students amongst groups were compared with chi-square and linear-by-linear association tests. RESULTS: Inter-rater reliability was very high for both consistency (ICCC = 0.939; 95% confidence interval (CI) 0.902-0.964) and absolute agreement (ICCA = 0.940; 95% CI 0.904-0.965). No significant differences were found amongst the ratings of evaluators; however, students performed differently when using the various tooth replicas (P < 0.05). Overall, 60% of students preferred the DRSK replica for root canal treatment training purposes, followed by DENTALIKE (30%). The least preferred was TrueTooth (70% responses) due to its complex anatomy and poor resistance to instruments and heat pluggers. Evaluators detected several common errors in specific tooth replicas and preferred tooth replicas manufactured based on microCT scans of natural teeth. CONCLUSIONS: Tooth replicas manufactured based on microCT scans of natural teeth (TrueTooth and DENTALIKE) had much better acceptance amongst evaluators, although students rated and performed less well in TrueTooth replicas due to their greater level of difficulty.

Tromboembolismo pulmonar (TEP) y síndrome de Klinefelter, ¿es un factor de riesgo? / No disponible

Describimos el caso clínico de un paciente de 36 años diagnosticado de síndrome de Klinefelter a la edad de 24 años, en tratamiento sustitutivo con testosterona, que ingresa con diagnóstico de tromboembolia pulmonar (TEP) aguda sintomática de bajo riesgo. En el momento del diagnóstico no se objetivó ningún factor desencadenante del evento trombótico. El paciente recibió tratamiento anticoagulante con antagonistas de la vitamina K durante 6 meses, sin complicaciones clínicas. El estudio de trombofilia fue negativo y se decidió tratamiento anticoagulante indefinido, ante un evento no provocado y bajo riesgo de hemorragia. Se desconoce si el síndrome de Klinefelter o su tratamiento se asocian a un riesgo aumentado de enfermedad tromboembólica venosa (ETEV) (AU)

A 36-year-old man who had a history of Klinefelter syndrome and was receiving treatment with testosterone, was admitted into our hospital with the diagnosis of low-risk acute symptomatic pulmonary embolism (PE). After receiving 6 months of anticoagulant therapy with vitamin K antagonists, the patient was asymptomatic and free from clinical events. He had a normal hypercoagulability workup. He was offered indefinite anticoagulation, since the risk of bleeding was low. Currently, it has not been elucidated whether there is an association between Klinefelter syndrome or its treatment and venous thromboembolism (VTE). Advising patients with Klinefelter syndrome about the optimal duration of anticoagulation following acute VTE is complex (AU)

Epistaxis in children under the age of two: possible marker of abuse/neglect? A retrospective study in North-Eastern Piedmont hospitals.

AIM: Epistaxis is an extremely common event at all ages; however, under two years of age epistaxis is a very rare event and recent studies carried out in Great Britain concern this event as related to possible non-accidental trauma. To date, no other studies carried out in Italy are available on this topic. METHODS: A file review of all cases of epistaxis occurred in children under the age of 2 who were admitted into the ED in our area over a period of two years was carried out. RESULTS: We have collected data concerning 10 cases of epistaxis occurred in children under 2 years of age with an incidence of 10.4 cases per 10000 accessions to the ED of children under the age of 2. Four of the cases had attendances for head injury or facial trauma. CONCLUSION: The results obtained are higher than the results of the British studies adopting the same methodology, but comparable to their surveillance data on the general population. Through the analysis of the collected data, two correlated assumptions have been made: a possible relationship between epistaxis and neglect, and a relation between epistaxis and domestic accidents.

Correlación de resultados clínicos y perfil sagital en escoliosis del adulto. Valor del ángulo espinosacro y del ángulo de inclinación del raquis / Relationship between clinical results and sagittal profile in adult scoliosis. Value of the spinal-sacral angle and the spinal inclination angle

Objetivos. Evaluar la validez clínica en EA de 2 nuevos parámetros (ASS y ST) descritos recientemente para la evaluación del perfil sagital espinopélvicos, y cuyo papel en EA no está aún definido. Material y método. Análisis prospectivo (no concurrente) radiográfico y clínico de 59 cirugías primarias de EA (Cobb > 40°), mínimo 2 años de seguimiento. Para este trabajo dispusimos de radiografías y cuestionarios de salud de 49 pacientes. Se evaluó el cambio de los parámetros radiográficos tras cirugía (test Wilcoxon) y la correlación resultados clínicos-radiográficos-edad (test de Spearman y regresión lineal múltiple). Resultados. Mediana de seguimiento postoperatorio 8,5 años. Mediana edad 49,5 años. Hubo cambio estadísticamente significativo con la cirugía en ASS y ST (en ambos inferior a 5°), cifosis torácica (CT), lordosis lumbar (LL), rotación pélvica (RP), balance sagital (BS) y Cobb frontal. No hubo correlación entre dolor y ASS-ST. Hubo correlación significativa entre actividad y ASS, ST, LL, BS) y edad. Tras análisis multivariante solo la edad (ni ASS ni ST) persistió como posible predictor de menor actividad. Discusión. Cuando predomina la deformidad frontal, los parámetros radiográficos sagitales, incluidos los más novedosos ángulos, si bien sí influyen en la actividad del paciente cuando se analizan de forma aislada, pierden esta influencia cuando se analizan en conjunto y junto a otros parámetros clínicos. Conclusiones. Los valores de SSA y ST varían escasamente con la cirugía. Solo se correlacionan con la actividad pero no pueden considerarse predictores de la misma. No parecen pues medidas de utilidad en EA (AU)

Objectives. To assess the clinical validity of two new recently described parameters (spinal-sacral angle (SSA) and spinal inclination angle (SIA) in adult scoliosis (AS) for evaluating the spinal-pelvic sagittal profile, as well as their still undefined role in AS. Material and method. A non-concurrent prospective radiographic and clinical study was conducted on 59 primary surgeries of AS (Cobb>40°), with a minimum of 2 years follow-up. The available X-rays and health questionnaires of 49 patients were used in the study. The changes in X-ray parameters after surgery were evaluated (Wilcoxon test), as well as the correlations as regards the clinical-radiography-age parameters (Spearman test and multiple linear regression). Results. The median post-surgical follow-up was 8.5 years, and the median age of the patients was 49.5 years. There was a statistically significant change with the surgery in the SSA and SIA (less than 5° in both), thoracic kyphosis, lumbar lordosis (LL), pelvic rotation, sagittal balance (SB) and frontal Cobb. There was no correlation between pain and SSA-ST. There was a significant relationship between activity and SSA, ST, LL, SB, and age. After the multivariate analysis only age (not SSA or SIA) remained as a possible predictor of lower activity. Discussion. When frontal deformity predominates, the sagittal radiographic parameters, including the newest angles, although they have an influence patient activity when analysed individually, they lose this influence when they are analysed together and with other clinical parameters. Conclusions. The SSA and SIA hardly change with surgery. They only correlate with activity, but cannot be considered predictors of this. Thus they do seem to be useful measurements in AS (AU)

[Relationship between clinical results and sagittal profile in adult scoliosis. Value of the spinal-sacral angle and the spinal inclination angle]. / Correlación de resultados clínicos y perfil sagital en escoliosis del adulto. Valor del ángulo espinosacro y del ángulo de inclinación del raquis.

OBJECTIVES: To assess the clinical validity of two new recently described parameters (spinal-sacral angle (SSA) and spinal inclination angle (SIA) in adult scoliosis (AS) for evaluating the spinal-pelvic sagittal profile, as well as their still undefined role in AS. MATERIAL AND METHOD: A non-concurrent prospective radiographic and clinical study was conducted on 59 primary surgeries of AS (Cobb>40°), with a minimum of 2 years follow-up. The available X-rays and health questionnaires of 49 patients were used in the study. The changes in X-ray parameters after surgery were evaluated (Wilcoxon test), as well as the correlations as regards the clinical-radiography-age parameters (Spearman test and multiple linear regression). RESULTS: The median post-surgical follow-up was 8.5 years, and the median age of the patients was 49.5 years. There was a statistically significant change with the surgery in the SSA and SIA (less than 5° in both), thoracic kyphosis, lumbar lordosis (LL), pelvic rotation, sagittal balance (SB) and frontal Cobb. There was no correlation between pain and SSA-ST. There was a significant relationship between activity and SSA, ST, LL, SB, and age. After the multivariate analysis only age (not SSA or SIA) remained as a possible predictor of lower activity. DISCUSSION: When frontal deformity predominates, the sagittal radiographic parameters, including the newest angles, although they have an influence patient activity when analysed individually, they lose this influence when they are analysed together and with other clinical parameters. CONCLUSIONS: The SSA and SIA hardly change with surgery. They only correlate with activity, but cannot be considered predictors of this. Thus they do seem to be useful measurements in AS.

Biofilm. Un Nuevo concepto de infección en Endodoncia / Biofilm. A new infection concept in endodintics

Distintos estudios concluyen que el porcentaje de éxito del tratamiento de conductos en dientes necróticos es menor que en dientes vitales. Hoy día, se postula que la verdadera causa de fracaso de muchos tratamientos de conductos aparentemente correctos es la entidad infecciosa conocida como biofilm. Además, se ha mostrado como un tipo de infección doble. Por un lado, conocer el papel del biofilm en Endodoncia: morfología, metabolismo, formación, evolución y localización. Por otro, actualizar los métodos que propone la Endodoncia para controlarlo y eliminarlo, poniendo especial atención EN la técnica de irrigación. Elegida por muchos autores como la clave para su tratamiento (AU)

Different studies have concluded that the success rate of root canal treatment in necreotic teeth is lower than in vita l teeth. Nowadays, the real cause of failure in many root canal treatment that have apparently been correctly carried out is considered to be the infectious matter know as biofilm. Elimination form the canal of this type of infection has proved to be very difficult and has become one of the great challenges in modern endodontics. The aim of this review article is twofold: firstly, to understand the role of bifilm in endodontics, with respect to its morphology, metabolism, formation, evolution and localization, and, secondly to update endodontic procedures for controlling and eliminating it, paying particular attention to the technique of irrigation which is the preferred key to treatment of many authors (AU)

Importancia de la irrigación en el éxito del tratamiento de conductos radiculares necróticos. Parte 2 / No disponible

La primera parte de este trabajo actualizaba el conocimiento de la necrosis pulpar y analizaba el tipo de bacterias características, así como su relación con el sistema de conductos radiculares. A continuación, se exponía el tratamiento, priorizando la acción de los irrigantes, así como distintas secuencias de irrigación y asociaciones de irrigantes recomendadas por la literatura. En esta segunda parte, nos ocuparemos de la relevancia de los instrumentos de endodoncia y de su relación con la irrigación. Además, se revisarán otros métodos de desinfección intraconducto alternativos a los instrumentos e irrigante so que los complementen y se expondrán los nuevos irrigantes que nos aporta bibliografía actual. Por último. Se expone lo más relevante conocido hasta el momento de biofilm, entidad infecciosa de reciente conocimiento en Endodoncia, y sus posibilidades de tratamiento (AU)

Part one of this article updated the knowledge about pulp necrosis and analyzed the type of bacteria as well as its relationship with the root canal system. After, the treatment was exposed, prioritizaing irrigants action as well as different irrigation sequences. We showed associations of irrigants recommended in the literature too. In part two, we will deal with relevance of endodontic instruments and its relationship with irrigation. Furthermore, other ways of canal disinfection, alternative to the instruments and irrigation, will be reviewed, and we will show the new irrigants contributed by current bibliography. Last, the most relevant aspects of biofilm, emerging infectious entity in endodontics, are exposed as well as the different treatment options (AU)

Importancia de la irrigación en el éxito del tratamiento de conductos radiculares necróticos. Parte 1 / No disponible

El objetivo del tratamiento de conductos es la limpieza y conformación de sistema de conductos radiculares. Una de las principales patología que trata es la periodontitis apical crónica, que sería la consecuencia en los tejidos periapicales de la necrosis del tejido pulpar. Diversos estudios científicos muestran un índice mayor de fracasos en dientes con esta patología que con otras. Además, muchos autores coinciden en que la irrigación es actualmente el arma terapéutica más eficaz ante esta patología. El objetivo de esta primera parte de la revisión es actualizar los conocimientos sobre la periodontitis apical crónica y su tratamiento, especialmente desde el punto de vista de la irrigación (AU)

The objective of the intracanal treatment procedures is cleaning and shaping the root canal system in such a way that the filling will be facilitated in order to seal the apical foramen. One of the most important diseases this therapy treats is apical periodontitis which is a sequel to endodontic infection and manifests as the host defense response to microbial challenge. Many studies demonstrate a higher failure rate with apical periodontitis than others pathologies. Furthermore many authors agree that irrigation is the most powerful weapon against this pathology. The aim of this first part of the review study is to update the knowledge about chronic apical periodontitis and its treatment, specially form the point of view of irrigation (AU)

Bile secretion by the rat liver during synchronized regeneration.

Simultaneous coexistence of differentiated, proliferating and redifferentiated hepatocytes occurs during normal liver regeneration (LR). The aim of the present work was to study the time course of the capacity of the liver to form bile during synchronized LR. Following two-thirds partial hepatectomy (PH) in rats, i.v. administration of the ribonucleotide reductase reversible inhibitor hydroxyurea (HU) was used to transiently block liver cells at G1/S boundary. Experiments were performed at 0 and 4 hours, and 1, 3 or 7 days after releasing HU-induced inhibition. Bile acid pool size was determined by collecting bile samples over 24 hours. Initial (first hour) bile flow and bile acid output were increased early on during synchronized LR as compared with the values found in non-hepatectomized control animals. These values were thereafter (1 day) reduced, but increased again at 3 days after halting HU infusion. The time course of bile acid depletion and changes in bile flow were very similar in control and synchronized LR, except that in the latter a more important early reduction in bile flow and bile acid output was found. Shortly after PH, part of the bile acid pool was lost, but this was quickly restored, soon (1 day) reaching a net bile acid pool size very similar to that found in control rats. The highest pool size relative to liver weight was found on day 1, when bile acid output and bile flow reached their lowest values. Additional experiments were performed using in situ perfused regenerating rat livers in which stepwise infusion of taurocholate (TC) was carried out. PH alone modified neither the bile acid-independent (BAIF) nor the bile acid-dependent fraction of bile flow (BADF). However, in normal LR, the BAIF decreased on day 1 and recovered at 7 days, while in synchronized LR it remained depressed up to 7 days. The BADF was only reduced during the early phase of normal LR and did not change significantly in synchronized LR. The maximal secretion rate (SRmax) for TC, as expressed per gram of remaining liver tissue, was not affected immediately after PH, but a marked reduction was observed on day 1 in both normal and synchronized LR. Afterwards, SRmax was quickly restored in both synchronized LR and, although in a slower way, normal LR. These results suggest that synchronization of LR involves changes in the time required to the recovery of specific liver functions such as bile formation.

Role of rate-limiting enzymes of nucleotide metabolism in taurocholate-induced DNA synthesis inhibition.

BACKGROUND/AIMS: In previous studies we have shown the ability of bile acids to reduce the rate of thymidine incorporation into DNA by the regenerating rodent liver. The aim of the present work was to investigate the sensitivity of the key pathways involved in thymidine metabolism to taurocholate. METHODS/RESULTS: Incubation of [14C]-thymidine with mouse liver extracts revealed that addition of taurocholate to the reaction medium induced significant dose-dependent inhibition in the activity of the salvage nucleotide pathway rate-limiting enzyme, thymidine kinase, while other steps of nucleotide metabolism machinery, such as the rate-limiting enzyme of de novo deoxyribonucleotide synthesis, ribonucleotide reductase and the rate-limiting enzyme of thymidine catabolism, dihydropyrimidine dehydrogenase were found to be insensitive to inhibition by taurocholate. Additional experiments were carried out on isolated perfused rat livers whose regeneration was induced by two-thirds hepatectomy and synchronized by intravenous administration of reversible ribonucleic reductase inhibitor hydroxyurea (bolus: 170 mumol/100 g body weight, plus 10 h infusion: 2.0 mumol/min per 100 g body weight, from 14 to 24 h after hepatectomy). Hydroxyurea treatment was interrupted and liver perfusions were carried out 0, 2, 4 or 8 h later. Thymidine incorporation into DNA over 30 min perfusion with media containing [14C]-thymidine was measured after separating DNA from acid-soluble fraction. A marked increase in DNA synthesis was observed up to 4 h after stopping ribonucleotide reductase inhibition. At this time, reduced relevance of the salvage pathway can be expected as compared with the de novo released pathway. In contrast with the inhibitory effect observed when taurocholate was added to the perfusate of untreated regenerating livers, taurocholate was found to have no effect on DNA synthesis, at the peak of synchronized DNA synthesis, although taurocholate-induced alteration in thymidine metabolism was suggested from h.p.l.c. analysis of acid-soluble fraction. CONCLUSIONS: These results suggest that effects on the nucleotide metabolism machinery, and hence changes in deoxyribonucleotide phosphate pools may underlie the ability of taurocholate to affect DNA synthesis by the regenerating rodent liver.

Evidence for dual effect of bile acids on thymidine anabolism and catabolism by the regenerating rat liver.

Bile acids have been reported to modify DNA synthesis by rodent livers in regeneration, which may be due in part to their ability to interact with the machinery responsible for deoxyribonucleotide synthesis. The aim of this work was to gain information on the effect of taurocholate (TC) on both anabolic and catabolic pathways accounting for the fate of [methyl-14C]thymidine in the liver of two-third hepatectomized rats. Using high-pressure liquid chromatography, the soluble fraction of liver homogenate was used to measure the ability of TC to modify both the rate of thymidine monophosphate formation from thymidine - i.e., thymidine kinase (TK) activity - and the rate of thymidine release from thymidine, which is the result of at least three different reactions catalyzed by thymidine phosphorylase, nucleosidase and nucleoside deoxyribosyl transferase. TC was found to induce a dose-dependent inhibition of both processes. The nature of this inhibition seems to be in part competitive. Apparent Ki values were 1.5 mM for TK and 4 mM for thymidine release. These inhibitory effects were mimicked by glycocholate but not by taurine. To investigate the relevance of the TC-induced modification of anabolism and catabolism in the whole organ, experiments on regenerating perfused rat livers were carried out. The donors underwent two-third hepatectomy 24 h before liver isolation. They were either fasted during this period (F) or allowed free access to food (NF). DNA synthesis, as measured by [methyl-14C]thymidine incorporation into DNA, was significantly increased in both groups, as compared with control non-hepatectomized animals. However, enhancement in DNA synthesis in group F was only 50% of the value found in the NF group. Intravenous TC administration before and/or during liver perfusions induced a dose-dependent recovery of DNA synthesis in the F group. This effect was accompanied by opposed modifications in the amount of radiolabelled metabolites contained in the non-DNA fraction of liver homogenate, consistent with a marked inhibition of thymidine catabolism. These results suggest that, in addition to the previously reported effects of TC on thymidine anabolism, bile acids are also able to affect the thymidine catabolism. The overall results of this dual effect on the fate of thymidine in the regenerating rat liver depend on the metabolic situation. Under circumstances of no nutrient restriction, the effect of TC is characterized by inhibition of thymidine incorporation into DNA. By contrast, under depressed DNA synthesis due to fasting, the overall effect of TC is a partial recovery of this process.