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OBJECTIVE: To examine the effectiveness of splinting for reducing pain and improving function and health-related quality of life (HR-QoL) in people with thumb carpometacarpal osteoarthritis (CMC OA). DESIGN: The Cochrane Library, MEDLINE, Embase, CINAHL, ISI Web of Science, Scopus and Google Scholar, 3 trial registries and 4 conference proceedings were systematically searched for randomised and non-randomised controlled trials up to March 17th, 2018. Two reviewers independently applied the inclusion criteria to select potential studies and assess risk of methodologic bias using the Cochrane Collaboration's Risk of Bias Tool. Studies were pooled using the inverse variance method to calculate standardised mean difference (SMD). Sensitivity analyses were conducted and the quality of evidence for each outcome was judged following the Grades of Recommendation Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twelve studies were retrieved (n = 1353), 4 comparing a splint to control and 8 to another splint. In the medium-term (3-12 months), low quality evidence showed that splints cause a moderate to large reduction in pain (SMD 0.7 [95% confidence interval (CI) 1.04, 0.35], P < 0.0001) and small to moderate improvement in function (SMD 0.42 [95% CI 0.77, 0.08], P = 0.02). No significant effect was found at short-term or for different types of splints. No studies reported HR-QoL. CONCLUSIONS: Splinting demonstrated a moderate to large effect for pain and small to moderate effect for function in the medium-term but not in the short term. Quality of the evidence is low. Major challenges are the lack of diagnostic criteria and of a gold-standard outcome measure for thumb CMC OA.
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Artralgia/terapia , Articulaciones Carpometacarpianas , Procedimientos Ortopédicos/instrumentación , Osteoartritis/complicaciones , Rango del Movimiento Articular/fisiología , Férulas (Fijadores) , Artralgia/etiología , Artralgia/fisiopatología , Humanos , Osteoartritis/fisiopatología , Pulgar , Resultado del TratamientoRESUMEN
Posttransplant lymphoproliferative disorders (PTLD) represent a rare and potentially life-threatening complication after liver transplantation. Classical Hodgkin lymphoma (cHL), with an incidence of approximately 1.8-3.4% of all PTLD cases, represents a minority of PTLD, mainly presenting as a late transplant complication. The main risk factors for the development of PTLD are Epstein-Barr virus (EBV) infection and intensive immunosuppression. However, other risk factors like hepatitis C virus may, together with EBV infection, contribute to the development of PTLD. Here we present a case of late-onset EBV-positive cHL that occurred 10 years after an unrelated donor liver transplantation. To our knowledge, this is the first report of cHL occurring with such a long interval after liver transplantation. Given the low incidence of cHL PTLD, there is little information regarding pathology, clinical characteristics, and management of this disease. The development of individual, risk-adapted treatments may improve the long-term outcome of cHL PTLD.
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BACKGROUND: While DSM-5 classified pathological gambling as an addictive disorder, there is debate as to whether ICD-11 should follow suit. The debate hinges on scientific evidence such as neurobiological findings, family history of psychiatric disorders, psychiatric comorbidity, and personality variables. METHODS: In the "Baden-Württemberg Study of Pathological Gambling", we compared a group of 515 male pathological gamblers receiving treatment with 269 matched healthy controls. We studied differences in sociodemographic characteristics, gambling-related variables, psychiatric comorbidity (lifetime), family history of psychiatric conditions, as well as personality traits such as impulsivity (Barratt Impulsiveness Scale), sensation seeking (Zuckerman's Sensation Seeking Scale) and the NEO-FFI big five. Personality traits were validated in an age- and ethnicity-matched subsample of "pure" gamblers without any psychiatric comorbidity (including nicotine dependence). Data were analyzed using two-sample t-tests, Chi2 analyses, Fisher's exact test and Pearson correlation analysis, as appropriate. Bonferroni correction was applied to correct for multiple comparisons. RESULTS: Only 1% of the gamblers had been diagnosed with an impulse control disorder other than gambling (ICD-10). Notably, 88% of the gamblers in our sample had a comorbid diagnosis of substance dependence. The highest axis I comorbidity rate was for nicotine dependence (80%), followed by alcohol dependence (28%). Early age of first gambling experience was correlated with gambling severity. Compared to first-degree relatives of controls, first-degree relatives of pathological gamblers were more likely to suffer from alcohol dependence (27.0% vs. 7.4%), pathological gambling (8.3% vs. 0.7%) and suicide attempts (2.7% vs. 0.4%). Significant group differences were observed for the NEO-FFI factors neuroticism, agreeableness and conscientiousness. Gamblers were also more impulsive than controls, but did not differ from controls in terms of sensation seeking. CONCLUSIONS: Our findings support classifying pathological gambling as a behavioural addiction in the ICD-11. This decision will have a significant impact on the approaches available for prevention (e.g. age limits) and treatment.
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Conducta Adictiva/psicología , Familia/psicología , Juego de Azar/psicología , Trastornos de la Personalidad/psicología , Adulto , Alcoholismo/psicología , Conducta Adictiva/epidemiología , Comorbilidad , Femenino , Juego de Azar/epidemiología , Humanos , Conducta Impulsiva , Masculino , Persona de Mediana Edad , Personalidad , Trastornos de la Personalidad/epidemiología , Trastornos Relacionados con Sustancias/epidemiologíaRESUMEN
The number of massively multiplayer online games (MMOs) is on the rise worldwide along with the fascination that they inspire. Problems occur when the use of MMOs becomes excessive at the expense of other life domains. Although not yet formally included as disorder in common diagnostic systems, internet gaming disorder (IGD) is considered a "condition for further study" in section III of the DSM-5. The current review aims to provide an overview of cognitive and neurobiological data currently available on IGD, with a particular focus on impulsivity, compulsivity, and sensitivity to reward and punishment. Additionally, we also compare these findings on IGD with data from studies on pathological gambling (PG)-so far the only condition officially classified as a behavioral addiction in the DSM-5. Multiple similarities have been observed in the neurobiology of IGD and PG, as measured by alterations in brain function and behavior. Both patients with IGD and those with PG exhibited decreased loss sensitivity; enhanced reactivity to gaming and gambling cues, respectively; enhanced impulsive choice behavior; aberrant reward-based learning; and no changes in cognitive flexibility. In conclusion, the evidence base on the neurobiology of gaming and gambling disorders is beginning to illuminate the similarities between the two. However, as only a few studies have addressed the neurobiological basis of IGD, and some of these studies suffer from significant limitations, more research is required before IGD's inclusion as a second behavioral addiction in the next versions of the ICD and DSM can be justified.
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Conducta Adictiva/fisiopatología , Encéfalo/fisiopatología , Juego de Azar/fisiopatología , Internet , Juegos de Video , Adulto , Conducta Compulsiva , Humanos , Conducta Impulsiva , Imagen por Resonancia Magnética , RecompensaRESUMEN
Sesquiterpene lactones (STLs) are a large and structurally diverse group of plant metabolites generally found in the Asteraceae family. STLs exhibit a wide spectrum of biological activities and it is generally accepted that their major mechanism of action is the alkylation of the thiol groups of biological molecules. The guaianolides is one of various groups of STLs. Anti-tumour and anti-migraine effects, an allergenic agent, an inhibitor of smooth muscle cells and of meristematic cell proliferation are only a few of the most commonly reported activities of STLs. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under stimulus with progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. There are previous records of the inhibitory effect of dehydroleucodin (DhL), a guaianolide lactone, on the progression of meiosis. It has been also shown that DhL and its 11,13-dihydroderivative (2H-DhL; a mixture of epimers at C-11) act as blockers of the resumption of meiosis in fully grown ovarian oocytes from the amphibian Rhinella arenarum (formerly classified as Bufo arenarum). The aim of this study was to analyze the effect of four closely related guaianolides, i.e., DhL, achillin, desacetoxymatricarin and estafietin as possible inhibitors of meiosis in oocytes of amphibians in vitro and discuss some structure-activity relationships. It was found that the inhibitory effect on meiosis resumption is greater when the lactone has two potentially reactive centres, either a α,ß-α',ß'-diunsaturated cyclopentanone moiety or an epoxide group plus an exo-methylene-γ-lactone function.
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Meiosis/efectos de los fármacos , Oocitos/efectos de los fármacos , Oocitos/fisiología , Sesquiterpenos/farmacología , Animales , Bufo arenarum , Células Cultivadas , Femenino , Lactonas/química , Lactonas/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Progesterona/farmacología , Sesquiterpenos/química , Sesquiterpenos de Guayano/farmacología , Relación Estructura-ActividadRESUMEN
BACKGROUND: Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence. METHODS: Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence. RESULTS: No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value=6.63×10(-3)); 5'-adenosine monophosphate-activated protein kinase signalling (P-value=9.57×10(-3)); and apoptosis (P-value=1.75×10(-2)) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status. CONCLUSIONS: The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.
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Conducta Adictiva/genética , Juego de Azar/genética , Estudio de Asociación del Genoma Completo , Adulto , Alcoholismo/genética , Conducta Adictiva/psicología , Comorbilidad , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Juego de Azar/psicología , Alemania , Humanos , Masculino , Persona de Mediana Edad , Trastornos Relacionados con Sustancias/genéticaRESUMEN
Chinchilla lanigera, native to the Andean Mountains of Perú, Chile, Bolivia and Argentina, is a specimen of great economic importance because of its fur. In mammals, spermatozoa originate in testes and are transported to the epididymis, where they undergo morphological and biochemical modifications known as sperm maturation, a basic step in the acquisition of their fertilizing ability. The aim of this work is the macroscopic and microscopic analysis of the epididymis of Chinchilla lanigera Grey and its sectorization based on a histomorphological study. The epididymis presents a clear segmentation into four regions: initial segment, caput, corpus and cauda. The epithelium lining the seminiferous tubules is pseudostratified, with principal cells with stereocilia and basal, clear, apical, narrow and halo cells. The histological analysis showed that principal and basal cells are the prevailing populations in all regions, also revealing narrow cells and the absence of clear cells in the initial segment. Each segment presents its different histological and morphometric characteristics, which supports the idea of the specific behaviour of each region, giving a segment-specific character to the process of sperm maturation in this species. No significant differences were found in the morphometric measurements or in the histological evaluation of the epididymis of samples collected in April and October. The fact that no differences were found between the samples collected during the two periods when the reproductive ability in nature is different suggests the importance of external factors in the control of the reproductive cycle of Chinchilla lanigera.
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Chinchilla/anatomía & histología , Epidídimo/anatomía & histología , Epitelio/anatomía & histología , Testículo/anatomía & histología , Animales , Ambiente , Epidídimo/citología , Masculino , Fotoperiodo , Reproducción/fisiología , Estaciones del Año , Túbulos Seminíferos/anatomía & histología , Túbulos Seminíferos/citología , Maduración del Esperma , Temperatura , Testículo/citología , Factores de TiempoRESUMEN
Rhinella arenarum oocytes can be artificially activated, a process known as parthenogenesis, by a sesquiterpenic lactone of the guaianolide group, dehydroleucodine (DhL). Transient increases in the concentration of cytosolic Ca2+ are essential to trigger egg activation events. In this sense, the 1-4-5 inositol triphosphate receptors (IP3R) seem to be involved in the Ca2+ transient release induced by DhL in this species. We analyzed the involvement of phosphoinositide metabolism, especially the participation of phospholipase A2 (PLA2) and phospholipase C (PLC) in DhL-induced activation. Different doses of quinacrine, aristolochic acid (ATA) (PLA2 inhibitors) or neomycin, an antibiotic that binds to PIP2, thus preventing its hydrolysis, were used in mature Rhinella arenarum oocytes. In order to assay the participation of PI-PLC and PC- PLC we used U73122, a competitive inhibitor of PI-PLC dependent events and D609, an inhibitor of PC-PLC. We found that PLA2 inhibits quinacrine more effectively than ATA. This difference could be explained by the fact that quinacrine is not a specific inhibitor for PLA2 while ATA is specific for this enzyme. With respect to the participation of PLC, a higher decrease in oocyte activation was detected when cells were exposed to neomycin. Inhibition of PC-PLC with D609 and IP-PLC with U73122 indicated that the last PLC has a significant participation in the effect of DhL-induced activation. Results would indicate that DhL induces activation of in vitro matured oocytes of Rhinella arenarum by activation of IP-PLC, which in turn may induce IP3 formation which produces Ca2+ release.
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Lactonas/farmacología , Oocitos/efectos de los fármacos , Fosfolipasas A2/metabolismo , Sesquiterpenos/farmacología , Fosfolipasas de Tipo C/metabolismo , Animales , Ácidos Aristolóquicos/farmacología , Hidrocarburos Aromáticos con Puentes/farmacología , Bufo arenarum , Estrenos/farmacología , Femenino , Técnicas de Maduración In Vitro de los Oocitos , Neomicina/farmacología , Norbornanos , Oocitos/enzimología , Oocitos/fisiología , Inhibidores de Fosfodiesterasa/farmacología , Inhibidores de la Síntesis de la Proteína/farmacología , Pirrolidinonas/farmacología , Quinacrina/farmacología , Tiocarbamatos , Tionas/farmacología , Fosfolipasas de Tipo C/antagonistas & inhibidoresRESUMEN
The mechanisms involved in fertilization are the centre of attention in order to determine the conditions required to reproduce in vitro the events that take place in vivo, with special interest in endangered species. Previous data from mouse sperm, where acrosome reaction (AR) occurs more often in the interstitium of the cumulus oophorus, contribute to strengthen the use of progesterone as a physiological inducer of this process. We studied the participation of protein kinase A (PKA), phospholipases A2 and C (PLA2 , PLC) in the AR induced by progesterone from Chinchilla epididymal spermatozoa. The addition of db-cAMP to the incubation medium caused an increase of 58% in the AR, while the use of H89 (30 µm), a PKA inhibitor, reflected a decrease of 40% in the percentage of reacted gametes. The assays conducted with arachidonic acid showed a maximum increase of 23% in the AR. When gametes were pre-incubated with PLA2 inhibitors, a dose-dependent inhibitory effect was observed. The addition of phorbol12-myristate13-acetate (10 µm) revealed higher percentages of AR induction (60%). When PLC was inhibited with neomycin and U73122, a dose-dependent decrease in AR percentages was observed. Combined inhibition of PKA, PLA2 and PLC, AR values similar to control were obtained. This work shows evidence, for the first time in Chinchilla, that progesterone activates the AC/cAMP/PKA system as well as sperm phospholipases and that these signalling pathways participate jointly and cooperatively in AR. These results contribute to the understanding of the complex regulation that is triggered in sperm after the effect of progesterone.
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Reacción Acrosómica/fisiología , Chinchilla/fisiología , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Fosfolipasas A2/metabolismo , Fosfolipasas de Tipo C/metabolismo , Reacción Acrosómica/efectos de los fármacos , Animales , Bucladesina/farmacología , Epidídimo/citología , Fertilización , Masculino , Progesterona/farmacología , Transducción de Señal/fisiología , Capacitación Espermática/fisiología , Espermatozoides/fisiologíaRESUMEN
BACKGROUND: Aggregation of functional magnetic resonance imaging (fMRI) data in regions-of-interest (ROIs) is required for complex statistical analyses not implemented in standard fMRI software. Different data-aggregation measures assess various aspects of neural activation, including spatial extent and intensity. NEW METHOD: In this study, conducted within the framework of the PREDICT study, we compared different aggregation measures for voxel-wise fMRI activations to be used as prognostic factors for relapse in 49 abstinent alcohol-dependent individuals in an outpatient setting using a cue-reactivity task. We compared the importance of the data-aggregation measures as prognostic factors for treatment outcomes by calculating the proportion of explained variation. RESULTS AND COMPARISON WITH EXISTING METHOD(S): Relapse risk was associated with cue-induced brain activation during abstinence in the ventral striatum (VS) and in the orbitofrontal cortex (OFC). While various ROI measures proved appropriate for using fMRI cue-reactivity to predict relapse, on the descriptive level the most "important" prognostic factor was a measure defined as the sum of t-values exceeding an individually defined threshold. Data collected in the VS was superior to that from other regions. CONCLUSIONS: In conclusion, it seems that fMRI cue-reactivity, especially in the VS, can be used as prognostic factor for relapse in abstinent alcohol-dependent patients. Our findings suggest that data-aggregation measures that take both spatial extent and intensity of cue-induced brain activation into account make better biomarkers for predicting relapse than measures that consider an activation's spatial extent or intensity alone.
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Alcoholismo/diagnóstico , Alcoholismo/fisiopatología , Encéfalo/fisiopatología , Imagen por Resonancia Magnética/métodos , Adulto , Alcoholismo/terapia , Mapeo Encefálico/métodos , Señales (Psicología) , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Pacientes Ambulatorios , Pronóstico , Recurrencia , Riesgo , Procesamiento de Señales Asistido por Computador , Análisis de Supervivencia , Resultado del Tratamiento , Percepción Visual/fisiologíaRESUMEN
Human brain anatomy is strikingly diverse and highly inheritable: genetic factors may explain up to 80% of its variability. Prior studies have tried to detect genetic variants with a large effect on neuroanatomical diversity, but those currently identified account for <5% of the variance. Here, based on our analyses of neuroimaging and whole-genome genotyping data from 1765 subjects, we show that up to 54% of this heritability is captured by large numbers of single-nucleotide polymorphisms of small-effect spread throughout the genome, especially within genes and close regulatory regions. The genetic bases of neuroanatomical diversity appear to be relatively independent of those of body size (height), but shared with those of verbal intelligence scores. The study of this genomic architecture should help us better understand brain evolution and disease.
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Encéfalo/anatomía & histología , Genoma , Fenotipo , Adolescente , Estudios de Cohortes , Simulación por Computador , Femenino , Estudio de Asociación del Genoma Completo , Técnicas de Genotipaje , Humanos , Imagen por Resonancia Magnética , Masculino , Modelos Genéticos , Tamaño de los Órganos , Polimorfismo de Nucleótido SimpleRESUMEN
Mature oocytes are arrested in metaphase II due to the presence of high levels of active maturation promoting factor (MPF). After fertilization, active MPF levels decline abruptly, enabling oocytes to complete meiosis II. One of the first and universal events of oocyte activation is an increase in cytosolic Ca2+ that would be responsible for MPF inactivation. Mature oocytes can also be activated by parthenogenetic activation. The aims of this work are to test the ability of dehydroleucodine (DhL) and its hydrogenated derivative 11,13-dihydro-dehydroleucodine (2H-DhL) to induce chemical activation in amphibian oocytes and to study the participation of calcium in the process. Results indicated that DhL and 2H-DhL induced oocyte activation in a dose-dependent manner. After 90 min of treatment, DhL 36 µM was able to induce 95% activation, while 2H-DhL 36 µM was less active, with only 40% activation. Our results suggest that DhL induced the inhibition of MPF activity, probably by an increase in intracellular Ca2+ concentration. Extracellular Ca2+ would not be significant, although Ca2+ release from intracellular stores is critical. In this sense, IP3Rs and RyRs were involved in the Ca2+ transient induced by lactones. In this species, RyRs appears to be the largest contributor to Ca2+ release in DhL-induced activation. Although more studies are needed on the mechanism of action through which these lactones induce oocyte activation in Rhinella arenarum, the results of this research provide interesting perspectives for the use of these lactones as chemical activators in in vitro fertilization and cloning.
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Bufo arenarum , Lactonas/farmacología , Oocitos/efectos de los fármacos , Oocitos/fisiología , Sesquiterpenos/farmacología , Animales , Calcio/metabolismo , Células Cultivadas , Relación Dosis-Respuesta a Droga , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Femenino , Técnicas de Maduración In Vitro de los Oocitos , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Factor Promotor de Maduración/antagonistas & inhibidores , Factor Promotor de Maduración/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/metabolismoRESUMEN
Despite the recognition that cortical thickness is heritable and correlates with intellectual ability in children and adolescents, the genes contributing to individual differences in these traits remain unknown. We conducted a large-scale association study in 1583 adolescents to identify genes affecting cortical thickness. Single-nucleotide polymorphisms (SNPs; n=54,837) within genes whose expression changed between stages of growth and differentiation of a human neural stem cell line were selected for association analyses with average cortical thickness. We identified a variant, rs7171755, associating with thinner cortex in the left hemisphere (P=1.12 × 10(-)(7)), particularly in the frontal and temporal lobes. Localized effects of this SNP on cortical thickness differently affected verbal and nonverbal intellectual abilities. The rs7171755 polymorphism acted in cis to affect expression in the human brain of the synaptic cell adhesion glycoprotein-encoding gene NPTN. We also found that cortical thickness and NPTN expression were on average higher in the right hemisphere, suggesting that asymmetric NPTN expression may render the left hemisphere more sensitive to the effects of NPTN mutations, accounting for the lateralized effect of rs7171755 found in our study. Altogether, our findings support a potential role for regional synaptic dysfunctions in forms of intellectual deficits.
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Encéfalo/anatomía & histología , Cognición/fisiología , Inteligencia/fisiología , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Animales , Células Cultivadas , Femenino , Estudios de Asociación Genética , Humanos , Procesamiento de Imagen Asistido por Computador , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Metaanálisis como Asunto , Ratones , Ratones Transgénicos , Análisis por Micromatrices , Células-Madre Neurales/fisiología , Pruebas NeuropsicológicasRESUMEN
The sesquiterpene lactones (STLs) are a large class of plant secondary metabolites that are generally found in the Asteraceae family and that have high diversity with respect to chemical structure as well as biological activity. STLs have been classified into different groups, such as guaianolides, germacranolides, and melampolides etc., based on their carboxylic skeleton. In amphibians, fully grown ovarian oocytes are arrested at the beginning of meiosis I. Under the stimulus of progesterone, this meiotic arrest is released and meiosis progresses to metaphase II, a process known as oocyte maturation. The purpose of this work was to determine whether sesquiterpene lactones from the germacranolide and melampolide groups act as inhibitor agents on the meiosis of amphibian oocytes in vitro. Results for germacranolides indicated that the addition of deoxyelephantopins caused a high degree of inhibition and that minimolide showed a moderate inhibitory effect, whereas glaucolide A was inactive. Furthermore, the addition of melampolides (uvedalin, enhydrin, polymatin A and polymatin B) showed inhibitory effects. For enhydrin and uvedalin, inhibitory effects were observed at the higher concentrations assayed. The results of this study suggest that the inhibitory activity of the tested sesquiterpene lactones on the meiosis of Rhinella arenarum oocytes is not dependent on the group to which they belong, i.e. not on the carboxylic skeleton, but probably due to the arrangement and type of function groups present in the molecules. All assayed lactones in the germacranolide group showed low toxicity. In contrast, important differences in toxicity were observed for lactones from the melampolide group: enhydrin and uvedalin showed low toxicity, but polymatin A and B were highly toxic.
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Bufo arenarum , Técnicas de Maduración In Vitro de los Oocitos/métodos , Lactonas/farmacología , Oocitos/efectos de los fármacos , Oocitos/fisiología , Sesquiterpenos/farmacología , Animales , Femenino , Progesterona/farmacología , Sesquiterpenos de Germacrano/farmacologíaRESUMEN
Preeclampsia is a severe pregnancy-related disorder and a leading cause of maternal and fetal mortality worldwide. Early identification of patients with an increased risk for preeclampsia is thus one of the most important goals in obstetrics. Here we identify two related human microRNAs as potential biomarkers to detect at-risk pregnancies. We demonstrate that miR455-3P and miR455-5P are significantly downregulated in placentas from preeclampsia patients, whereas other placenta-specific microRNAs remain unaffected. microRNA target prediction and validation revealed a potential link of miR455-3P to hypoxia signaling. Together with our observation that expression levels of miR455-3P and miR455-5P are upregulated during trophoblast differentiation, our results suggest a model in which miR455-3P represses a hypoxia response that might otherwise prevent cytotrophoblasts from syncytiotrophoblast differentiation. In summary, our work reveals aberrant hypoxia signaling in preeclampsia that can be explained by deregulated expression of miR455. As miR455 has been found in circulating blood, the development of noninvasive prenatal tests enabling early diagnosis of preeclampsia may be possible.
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Hipoxia de la Célula , MicroARNs/metabolismo , Preeclampsia/patología , Regiones no Traducidas 3' , Adulto , Secuencia de Bases , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/antagonistas & inhibidores , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Estudios de Casos y Controles , Diferenciación Celular/efectos de los fármacos , Línea Celular , Gonadotropina Coriónica/genética , Gonadotropina Coriónica/metabolismo , Colforsina/farmacología , Regulación hacia Abajo/efectos de los fármacos , Femenino , Colágenos Fibrilares/genética , Colágenos Fibrilares/metabolismo , Humanos , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Mucina-1/química , Mucina-1/genética , Mucina-1/metabolismo , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/metabolismo , Placenta/metabolismo , Preeclampsia/metabolismo , Embarazo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal/efectos de los fármacos , Trofoblastos/citología , Trofoblastos/metabolismoRESUMEN
A classification of osteomyelitis must reflect the complexity of the disease and, moreover, provide conclusions for the treatment. The classification is based on the following eight parameters: source of infection (OM [osteomyelitis]/OT [post-traumatic OM]), anatomic region, stability of affected bone (continuity of bone), foreign material (internal fixation, prosthesis), range of infection (involved structures), activity of infection (acute, chronic, quiescent), causative microbes (unspecific and specific bacteria, fungi) and comorbidity (immunosuppressive diseases, general and local). In the long version of the classification, which was designed for scientific studies, the parameters are named by capital letters and specified by Arabic numbers, e.g., an acute, haematogenous osteomyelitis of a femur in an adolescent with diabetes mellitus, caused by Staphylococcus aureus, multi-sensible is coded as: OM2 Lo33 S1a M1 In1d Aa1 Ba2a K2a. The letters and numbers can be found in clearly arranged tables or calculated by a freely available grouper on the internet (www.osteomyelitis.exquit.net). An equally composed compact version of the classification for clinical use includes all eight parameters, but without further specification. The above-mentioned example in the compact version is: OM 3 S a Ba2 K2. The short version of the classification uses only the first six parameters and excludes causative microbes and comorbidity. The above mentioned example in the short version is: OM 3 S a. The long version of the classification describes an osteomyelitis in every detail. The complexity of the patient's disease is clearly reproducible and can be used for scientific comparisons. The for clinical use suggested compact and short versions of the classification include all important characteristics of an osteomyelitis, can be composed quickly and distinctly with the help of tables and provide conclusions for the individual treatment. The freely available grouper (www.osteomyelitis.exquit.net) creates all three versions of the classification in one step.
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Bacteriemia/clasificación , Bacteriemia/complicaciones , Fracturas Óseas/clasificación , Fracturas Óseas/complicaciones , Fungemia/clasificación , Fungemia/complicaciones , Osteítis/clasificación , Osteítis/etiología , Osteomielitis/clasificación , Osteomielitis/etiología , Infección de Heridas/clasificación , Infección de Heridas/complicaciones , HumanosRESUMEN
Chinchilla, the lanigera variety in particular, is one of the most valuable rodents in the fur industry. The chinchilla ovary is morphologically similar to that of other South American hystricognath rodents, especially as regards its anatomy and, to a lesser degree, its histology. The presence of numerous primary follicles throughout the annual cycle suggests that a few of them are recruited to initiate growth and differentiation during folliculogenesis. Primary follicles with two or more oocytes are common; this is not the case with follicles at more advanced stages, suggesting that they do not develop. Only one or two large corpora lutea (CL) and three to five small or accessories CL were observed but no corpora albicans. The presence of accessory CL may reflect the importance of continuous hormonal production to support prolonged gestation. Atretic CL were also present, showing signs of degeneration in luteal cells. The interstitial cells distributed throughout the cortex were the main histological feature shared with other species, as stated in previous reports. Antral atresia was observed in all sizes of antral follicles while basal atresia was confined exclusively to smaller follicles.
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Chinchilla , Ovario/citología , Animales , Animales Domésticos , Chinchilla/anatomía & histología , Chinchilla/fisiología , Cuerpo Lúteo/citología , Femenino , Atresia Folicular , Fase Folicular , Folículo Ovárico/citología , Ovario/ultraestructura , Ovulación/fisiología , Maduración Sexual/fisiologíaRESUMEN
During meiosis resumption, oocytes undergo a series of nuclear and cytosolic changes that prepare them for fertilization and that are referred to as oocyte maturation. These events are characterized by germinal vesicle breakdown (GVBD), chromatin condensation and spindle formation and, among cytosolic changes, organelle redistribution and maturation of Ca2+-release mechanisms. The progression of the meiotic cell cycle is regulated by M phase/maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK). Changes in the levels of intracellular free Ca2+ ion have also been implicated strongly in the triggering of the initiation of the M phase. Ca2+ signals can be generated by Ca2+ release from intracellular Ca2+ stores (endoplasmic reticulum; ER) or by Ca2+ influx from the extracellular space. In this sense, the L-type Ca2+ channel plays an important role in the incorporation of Ca2+ from the extracellular space. Two types of intracellular Ca2+ receptor/channels are known to mediate the intracellular Ca2+ release from the ER lumen. The most abundant, the inositol 1,4,5-trisphosphate receptor (IP3R), and the other Ca2+ channel, the ryanodine receptor (RyR), have also been reported to mediate Ca2+ release in several oocytes. In amphibians, MPF and MAPK play a central role during oocyte maturation, controlling several events. However, no definitive relationships have been identified between Ca2+ and MPF or MAPK. We investigated the participation of Ca2+ in the spontaneous and progesterone-induced nuclear maturation in Rhinella arenarum oocytes and the effect of different pharmacological agents known to produce modifications in the Ca2+ channels. We demonstrated that loading competent and incompetent oocytes with the intracellular calcium chelator BAPTA/AM produced suppression of spontaneous and progesterone-induced GVBD. In our results, the capacity of progesterone to trigger meiosis reinitiation in Rhinella in the presence of L-type Ca2+ channel blockers (nifedipine and lanthane) indicated that spontaneous and progesterone-induced maturation would be independent of extracellular calcium influx, but would be sensitive to intracellular Ca2+ deprivation. As demonstrated by the effect of thimerosal and heparin in Rhinella arenarum, the intracellular increase in Ca2+ during maturation is also mediated mainly by IP3R. In addition, our results using caffeine, an agonist of the RyR, could suggest that Ca2+ release from ryanodine-sensitive stores is not essential for oocyte maturation in Rhinella. The decrease in MPF activity with NaVO3 negatively affected the percentage of thimerosal-induced GVBD. This finding suggests that Ca2+ release through the IP3R could be involved in the signalling pathway that induces MPF activation. However, the inhibition of MAP/ERK kinase (MEK) by PD98128 or P90 by geldanamycin produced a significant decrease in the percentages of GVBD induced by thimerosal. This finding suggests that Ca2+ release per se cannot bypass the inhibition of the MAPK activity.
Asunto(s)
Canales de Calcio Tipo L/metabolismo , Núcleo Celular/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Oocitos/fisiología , Oogénesis/fisiología , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Animales , Bufo arenarum , Calcio/metabolismo , Núcleo Celular/efectos de los fármacos , Células Cultivadas , Femenino , Oocitos/citología , Oocitos/efectos de los fármacos , Oogénesis/efectos de los fármacos , Progesterona/farmacología , Transducción de SeñalRESUMEN
REASONS FOR PERFORMING STUDY: Computed tomographic (CT) studies evaluating the relevance of individual CT features of apical infection in maxillary cheek teeth are lacking. OBJECTIVES: To study the prevalence and relationship of single CT features in horses with and without clinical evidence of apical infection in maxillary cheek teeth. STUDY DESIGN: Retrospective case-control study. METHODS: Multislice CT scans of the head of 49 horses were evaluated retrospectively. Changes of the infundibulum, pulp, root, lamina dura, periodontal space and alveolar bone in maxillary cheek teeth were recorded. RESULTS: Single CT changes were much more prevalent in the 28 horses with clinical signs. However, infundibular changes and a nondetectable lamina dura were also common in the 21 horses without clinical evidence of apical infection. Computed tomographic abnormalities of the pulp, root, periapical bone and periodontal space and the presence of a tooth fracture were significantly related. Infundibular changes were not associated with other CT signs of apical infection. Although nondetectable lamina dura was the most frequent CT change in all teeth in both studied groups, it was most commonly a solitary feature in otherwise normal teeth. Apical infections, defined as ≥3 CT changes, occurred mainly in the 108/208, 109/209 and 110/210 (Triadan numbers) and were found only in horses with clinical evidence of apical infection, except in one horse without clinical signs that had one affected root. CONCLUSIONS: Combined CT changes of the pulp, root, lamina dura, periapical bone and periodontal space and the presence of a tooth fracture appear to be reliable features to diagnose apical infection in maxillary cheek teeth. As a solitary feature, a nondetectable lamina dura should be interpreted cautiously and may even be considered normal due to its minor thickness and/or too low resolution of the imaging modality.
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Enfermedades de los Caballos/diagnóstico por imagen , Diente Molar/patología , Absceso Periapical/veterinaria , Tomografía Computarizada por Rayos X/veterinaria , Animales , Estudios de Casos y Controles , Enfermedades de los Caballos/patología , Caballos , Diente Molar/diagnóstico por imagen , Absceso Periapical/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
Reward learning represents a crucial mechanism in the acquisition and maintenance of addictive behavior. The underlying neurobiological foundations and associated neurobiological pathways are identified in this review and similarities between substance abuse and behavioral addictions will be discussed. In the second section current neuroimaging findings on neurobiological mechanisms of pathological gambling and computer and internet addiction are discussed. The main focuses are on changes in neurocognitive processes, such as cue reactivity, reward and punishment processing and behavioral control.