RESUMEN
Early nutrition may have long-lasting metabolic impacts in adulthood. Even though breast milk is the gold standard, most infants are at least partly formula-fed. Despite obvious improvements, infant formulas remain perfectible to reduce the gap between breastfed and formula-fed infants. Improvements such as reducing the protein content, modulating the lipid matrix and adding prebiotics, probiotics and synbiotics, are discussed regarding metabolic health. Numerous questions remain to be answered on how impacting the infant formula composition may modulate the host metabolism and exert long-term benefits. Interactions between early nutrition (composition of human milk and infant formula) and the gut microbiota profile, as well as mechanisms connecting gut microbiota to metabolic health, are highlighted. Gut microbiota stands as a key actor in the nutritional programming but additional well-designed longitudinal human studies are needed.
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Microbioma Gastrointestinal/efectos de los fármacos , Fórmulas Infantiles/efectos adversos , Recién Nacido/metabolismo , Metabolismo/efectos de los fármacos , Leche Humana/fisiología , Alimentación con Biberón/efectos adversos , Lactancia Materna , Microbioma Gastrointestinal/fisiología , Humanos , Lactante , Fórmulas Infantiles/química , Enfermedades Metabólicas/etiología , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/prevención & control , Metabolismo/fisiologíaRESUMEN
Noble gases such as xenon and argon have been reported to provide neuroprotection against acute brain ischemic/anoxic injuries. Herein, we wished to evaluate the protective potential of these two gases under conditions relevant to the pathogenesis of chronic neurodegenerative disorders. For that, we established cultures of neurons typically affected in Alzheimer's disease (AD) pathology, that is, cortical neurons and basal forebrain cholinergic neurons and exposed them to L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) to generate sustained, low-level excitotoxic stress. Over a period of 4 days, PDC caused a progressive loss of cortical neurons which was prevented substantially when xenon replaced nitrogen in the cell culture atmosphere. Unlike xenon, argon remained inactive. Xenon acted downstream of the inhibitory and stimulatory effects elicited by PDC on glutamate uptake and efflux, respectively. Neuroprotection by xenon was mimicked by two noncompetitive antagonists of NMDA glutamate receptors, memantine and ketamine. Each of them potentiated xenon-mediated neuroprotection when used at concentrations providing suboptimal rescue to cortical neurons but most surprisingly, no rescue at all. The survival-promoting effects of xenon persisted when NMDA was used instead of PDC to trigger neuronal death, indicating that NMDA receptor antagonism was probably accountable for xenon's effects. An excess of glycine failed to reverse xenon neuroprotection, thus excluding a competitive interaction of xenon with the glycine-binding site of NMDA receptors. Noticeably, antioxidants such as Trolox and N-acetylcysteine reduced PDC-induced neuronal death but xenon itself lacked free radical-scavenging activity. Cholinergic neurons were also rescued efficaciously by xenon in basal forebrain cultures. Unexpectedly, however, xenon stimulated cholinergic traits and promoted the morphological differentiation of cholinergic neurons in these cultures. Memantine reproduced some of these neurotrophic effects, albeit with less efficacy than xenon. In conclusion, we demonstrate for the first time that xenon may have a therapeutic potential in AD.
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Fármacos Neuroprotectores/farmacología , Xenón/farmacología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Células Cultivadas , Ácidos Dicarboxílicos/farmacología , Humanos , Memantina/farmacología , Neuronas/citología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Pirrolidinas/farmacología , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Receptores de N-Metil-D-Aspartato/metabolismoRESUMEN
Herein we describe the synthesis, structure and electronic properties of an unusual redox-active ditopic ligand with a stable open-shell configuration. This stable phenoxyl radical features intense and very low energy electronic transitions in the near infrared (NIR) part of the spectrum and is structurally set up to strongly spin couple coordinated transition metal ions in [2 × 2] grid-type structures.
RESUMEN
BACKGROUND: Affective dysregulation is a core feature of bipolar disorder (BD) and a significant predictor of clinical and functional outcome. Affective dysregulation can arise from abnormalities in multiple processes. This study addresses the knowledge gap regarding the precise nature of the processes that may be dysregulated in BD and their relationship to the clinical expression of the disorder. METHODS: Patients with BD (n=45) who were either in remission or in a depressive or manic state and healthy individuals (n=101) were compared in terms of the intensity, duration and physiological response (measured using inter-beat intervals and skin conductance) to affective and neutral pictures during passive viewing and during experiential suppression. RESULTS: Compared to healthy individuals, patients with BD evidenced increased affective reactivity to neutral pictures and reduced maintenance of subjective affective responses to all pictures. This pattern was present irrespective of clinical state but was more pronounced in symptomatic patients, regardless of polarity. Patients, regardless of symptomatic status, were comparable to healthy individuals in terms of physiological arousal and voluntary control of affective responses. CONCLUSION: Our study demonstrates that increased affective reactivity to neutral stimuli and decreased maintenance of affective responses are key dimensions of affective dysregulation in BD.
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Nivel de Alerta/fisiología , Trastorno Bipolar/psicología , Respuesta Galvánica de la Piel/fisiología , Reconocimiento Visual de Modelos/fisiología , Adulto , Atención/fisiología , Trastorno Bipolar/fisiopatología , Emociones/fisiología , Femenino , Fijación Ocular/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa/métodos , Tiempo de Reacción/fisiología , Valores de ReferenciaRESUMEN
We investigated the effects of the noble gas argon on the expression of locomotor sensitization to amphetamine and amphetamine-induced changes in dopamine release and mu-opioid neurotransmission in the nucleus accumbens. We found (1) argon blocked the increase in carrier-mediated dopamine release induced by amphetamine in brain slices, but, in contrast, potentiated the decrease in KCl-evoked dopamine release induced by amphetamine, thereby suggesting that argon inhibited the vesicular monoamine transporter-2; (2) argon blocked the expression of locomotor and mu-opioid neurotransmission sensitization induced by repeated amphetamine administration in a short-term model of sensitization in rats; (3) argon decreased the maximal number of binding sites and increased the dissociation constant of mu-receptors in membrane preparations, thereby indicating that argon is a mu-receptor antagonist; (4) argon blocked the expression of locomotor sensitization and context-dependent locomotor activity induced by repeated administration of amphetamine in a long-term model of sensitization. Taken together, these data indicate that argon could be of potential interest for treating drug addiction and dependence.
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Anfetamina/farmacología , Argón/farmacología , Locomoción/efectos de los fármacos , Núcleo Accumbens/efectos de los fármacos , Receptores Opioides mu/antagonistas & inhibidores , Proteínas de Transporte Vesicular de Monoaminas/antagonistas & inhibidores , Anfetamina/antagonistas & inhibidores , Animales , Sensibilización del Sistema Nervioso Central/efectos de los fármacos , Sensibilización del Sistema Nervioso Central/fisiología , Dopamina/fisiología , Masculino , Núcleo Accumbens/fisiología , Ratas , Ratas Sprague-Dawley , Proteínas de Transporte Vesicular de Monoaminas/fisiologíaRESUMEN
We describe the structural and variable temperature magnetic susceptibility properties of an unusual homoleptic bimetallic iron(III) thiocyanate tetraanion. This work represents the first structurally characterized bis(µ-1,3-thiocyanato) dimer of iron(III). A weak antiferromagnetic exchange interaction is observed between the two iron(III) ions, which is supported by broken symmetry density functional theory (DFT) calculations.
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Anticuerpos Antiidiotipos/farmacología , Mieloma Múltiple/radioterapia , Radioinmunoterapia , Anticuerpos de Dominio Único/farmacología , Tomografía Computarizada de Emisión de Fotón Único , Microtomografía por Rayos X , Animales , Anticuerpos Antiidiotipos/administración & dosificación , Modelos Animales de Enfermedad , Humanos , Ratones , Mieloma Múltiple/patología , Radiofármacos , Anticuerpos de Dominio Único/administración & dosificación , TecnecioAsunto(s)
Apoptosis/efectos de los fármacos , Linfocitos B/patología , Médula Ósea/patología , Daño del ADN/efectos de los fármacos , Células del Estroma/patología , Tungsteno/farmacología , Animales , Linfocitos B/metabolismo , Western Blotting , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Citometría de Flujo , Humanos , Ratones , Ratones Endogámicos C57BL , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismoRESUMEN
BACKGROUND: Following kidney transplantation, ischemia-reperfusion injury contributes to adverse outcomes. The purpose of this study was to determine whether a cold-storage solution saturated with noble gas (xenon or argon) could limit ischemia-reperfusion injury following cold ischemia. METHODS: Sixty Wistar rats were randomly allocated to 4 experimental groups. Kidneys were harvested and then stored for 6 h before transplantation in cold-storage solution (Celsior®) saturated with either air, nitrogen, xenon or argon. A syngenic orthotopic transplantation was performed. Renal function was determined on days 7 and 14 after transplantation. Transplanted kidneys were removed on day 14 for histological and immunohistochemical analyses. RESULTS: Creatinine clearance was significantly higher and urinary albumin significantly lower in the argon and xenon groups than in the other groups at days 7 and 14. These effects were considerably more pronounced for argon than for xenon. In addition, kidneys stored with argon, and to a lesser extent those stored with xenon, displayed preserved renal architecture as well as higher CD-10 and little active caspase-3 expression compared to other groups. CONCLUSION: Argon- or xenon-satured cold-storage solution preserved renal architecture and function following transplantation by reducing ischemia-reperfusion injury.
RESUMEN
Multiple myeloma (MM) is a B-cell malignancy, which often remains incurable because of the development of drug resistance governed by the bone marrow (BM) microenvironment. Novel treatment strategies are therefore urgently needed. In this study, we evaluated the anti-MM activity of JNJ-26481585, a novel 'second-generation' pyrimidyl-hydroxamic acid-based histone deacetylase inhibitor, using the syngeneic murine 5TMM model of MM. In vitro, JNJ-26481585 induced caspase cascade activation and upregulation of p21, resulting in apoptosis and cell cycle arrest in the myeloma cells at low nanomolar concentrations. Similar results could be observed in BM endothelial cells using higher concentrations, indicating the selectivity of JNJ-26481585 toward cancer cells. In a prophylactic and therapeutic setting, treatment with JNJ-26481585 resulted in an almost complete reduction of the tumor load and a significant decrease in angiogenesis. 5T2MM-bearing mice also developed a MM-related bone disease, characterized by increased osteoclast number, development of osteolytic lesions and a reduction in cancellous bone. Treatment of these mice with JNJ-264815 significantly reduced the development of bone disease. These data suggest that JNJ-26481585 has a potent anti-MM activity that can overcome the stimulatory effect of the BM microenvironment in vivo making this drug a promising new anti-MM agent.
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Modelos Animales de Enfermedad , Inhibidores de Histona Desacetilasas , Ácidos Hidroxámicos/farmacología , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Enfermedades Óseas/tratamiento farmacológico , Enfermedades Óseas/etiología , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Ciclo Celular/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Mieloma Múltiple/irrigación sanguínea , Neovascularización Patológica/prevención & control , Osteólisis/tratamiento farmacológico , Osteólisis/etiologíaRESUMEN
AIMS: The ability of lactic acid bacteria (LAB) to bind fumonisins B1 and B2 (FB1, FB2) in fermented foods and feeds and in the gastrointestinal tract could contribute to decrease their bioavailability and toxic effects on farm animals and humans. The aim of this work was to identify the bacterial cell wall component(s) and the functional group(s) of FB involved in the LAB-FB interaction. METHODS AND RESULTS: The effect of physicochemical, enzymatic and genetic treatments of bacteria and the removal/inactivation of the functional groups of FB on toxin binding were evaluated. Treatments affecting the bacterial wall polysaccharides, lipids and proteins increased binding, while those degrading peptidoglycan (PG) partially decreased it. In addition, purified PG from Gram-positive bacteria bound FB in a manner analogue to that of intact LAB. For FB, tricarballylic acid (TCA) chains play a significant role in binding as hydrolysed FB had less affinity for LAB. CONCLUSIONS: Peptidoglycan and TCA are important components of LAB and FB, respectively, involved in the binding interaction. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactic acid bacteria binding efficiency seems related to the peptide moiety structure of the PG. This information can be used to select probiotics with increased FB binding efficiency.
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Pared Celular/metabolismo , Fumonisinas/metabolismo , Lactobacillus plantarum/metabolismo , Micotoxinas/metabolismo , Sitios de Unión , Pared Celular/química , Cromatografía Líquida de Alta Presión , Fumonisinas/química , Micotoxinas/químicaRESUMEN
Osteoporosis is a major public health problem. For the time being, the diagnosis of osteoporosis relies on densitometry (T-score < -2.5 by DXA), although the risk of fracture depends also on other factors than the bone mass. Osteoporosis diagnosis (DXA) must be distinguished from the individual risk assessment of fracture. Different risk factors complementary to bone mass have been already validated in different populations. These include an old age, a history of fracture after the age of 50, a familial history of hip fracture (father or mother), a low BMI (< 20), corticoid treatment (> 3 months), tabagism and excessive alcohol consumption. A WHO taskforce has combined these different factors in order to integrate them in a 10-years predictive risk model of fracture (FRAX**). This model should still be validated in different populations, especially in populations not included in its development, which is the case for Belgium. We are evaluating these different risk factors for fracture in a Brussels population of 5000 women (60-80 years) who will be followed each year during 10 years. We also assess the predictive value of other risk factors for fracture not included in the WHO model (tendency to fall, use of sleeping pills, early non substituted menopause, sedentarity, ...). In an interim analysis of the first 452 women included and with data yet available at the time of this writing, we could find a significant (P < 0.05) relationship between diagnosis of osteoporosis at DXA and the number of risk factors, age > 70 years, a personal history of fracture after 50 years and a BMI < 20.
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Fracturas Óseas/epidemiología , Osteoporosis/epidemiología , Accidentes por Caídas/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Bélgica/epidemiología , Índice de Masa Corporal , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Menopausia , Persona de Mediana Edad , Osteoporosis/complicaciones , Valor Predictivo de las Pruebas , Prevalencia , Factores de RiesgoRESUMEN
A patient presented with cholera and a severe degree of ECF volume contraction. Despite large losses of bicarbonate (HCO3-)-containing diarrhoeal fluid, laboratory acid-base values were remarkably close to normal. A detailed analysis emphasizing principles of physiology and a quantitative approach provided new insights and eventually better definitions of metabolic and respiratory acidosis. A shift in focus from HCO3- concentration to HCO3- content in the extracellular fluid (ECF) compartment revealed the presence of metabolic acidosis. Central to this analysis was an emphasis on the haematocrit to enable a more accurate estimate of the degree of ECF volume contraction. The latter also revealed 'contraction' metabolic alkalosis, which masked the underlying metabolic acidosis. The presence of a respiratory acidosis of the tissue type was evident from the raised venous PCO2, which was not surprising once the magnitude of the ECF contraction had been appreciated. 'Bad buffering', as defined by Professor McCance, was the immediate danger and prompted swift action to restore an effective circulation. The haematocrit and the venous PCO2 also contribute valuable information to monitor the response to therapy. Nevertheless, there were still dangers to be discovered when an in-depth analysis suggested that the administration of isotonic saline would introduce an unanticipated danger for the patient.
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Acidosis/complicaciones , Cólera/complicaciones , Acidosis/fisiopatología , Acidosis/terapia , Acidosis Respiratoria/complicaciones , Acidosis Respiratoria/fisiopatología , Bicarbonatos/metabolismo , Dióxido de Carbono/análisis , Cólera/fisiopatología , Líquido Extracelular/metabolismo , Hematócrito/métodos , HumanosRESUMEN
In Kluyveromyces lactis, the casein kinase I (Rag8p) regulates the transcription of glycolytic genes and the expression of the low-affinity glucose transporter gene RAG1. This control involves the transcription factor Sck1p, a homologue of Sgc1p of Saccharomyces cerevisiae. SGC1 is known to interact genetically with ScGCR1 and ScGCR2, which code for regulators of glycolytic gene expression. Therefore, we studied the role of KlGCR1 and KlGCR2 genes in K. lactis. The Klgcr1 null mutant could not grow on glucose when respiration was blocked by antimycin A (Rag(- )phenotype). In contrast, the Klgcr2 null mutant could grow under the same conditions, although at a reduced rate. In both mutants, the transcription of glycolytic genes was affected, while that of ribosomal protein genes was not modified. Furthermore, the transcription of the glucose permease genes was also found to be affected in the two mutants, although dissimilarly. While RAG1 transcription decreased at high glucose concentrations, the expression of the high-affinity glucose permease gene HGT1 was unexpectedly impaired under gluconeogenic conditions, in the absence of glucose. Gel mobility shift assays performed with purified maltose-binding protein-KlGcr1p showed that KlGcr1p could interact directly with the promoters of the glycolytic genes, but not with the promoters of the glucose permease genes. Thus, the control exerted by KlGcr1p and KlGcr2p upon glucose transporter genes is probably indirect.
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Glucosa/metabolismo , Glucólisis/fisiología , Kluyveromyces/metabolismo , Proteínas de Transporte de Monosacáridos/fisiología , Secuencia de Aminoácidos , Northern Blotting , Proteínas Portadoras/análisis , Quinasa de la Caseína I/metabolismo , Dactinomicina/farmacología , Ensayo de Cambio de Movilidad Electroforética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica/genética , Genes RAG-1/genética , Gluconeogénesis/fisiología , Kluyveromyces/genética , Proteínas de Unión a Maltosa , Datos de Secuencia Molecular , Proteínas de Transporte de Monosacáridos/metabolismo , Inhibidores de la Síntesis del Ácido Nucleico/farmacología , Sistema de Fosfotransferasa de Azúcar del Fosfoenolpiruvato/genética , Inhibidores de la Síntesis de la Proteína/farmacología , Proteínas Ribosómicas/metabolismo , Transcripción Genética/genéticaRESUMEN
During a field trial to evaluate the efficacy of repeated vaccinations with bovine herpesvirus type 1 (BHV-1) marker vaccines, a glycoprotein E (gE)-negative BHV-1 strain was isolated from the nasal secretions of two cows, eight months after vaccination with a gE-negative live-attenuated vaccine, initially given intranasally, then intramuscularly. The strain isolated was characterised using immunofluorescence, restriction analysis and PCR. All the techniques used identified the isolated virus as a gE-negative BHV-1 phenotypically and genotypically identical to the Za strain used as a control.
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Enfermedades de los Bovinos/virología , Eliminación de Gen , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/virología , Herpesvirus Bovino 1/genética , Herpesvirus Bovino 1/aislamiento & purificación , Proteínas del Envoltorio Viral/genética , Animales , Bovinos , Enfermedades de los Bovinos/inmunología , Genotipo , Infecciones por Herpesviridae/inmunología , Herpesvirus Bovino 1/clasificación , Herpesvirus Bovino 1/inmunología , Fenotipo , Proteínas Virales , Vacunas Virales/inmunología , Esparcimiento de VirusRESUMEN
We investigate the distribution of sizes of fragments obtained from the amplified fragment length polymorphism (AFLP) marker technique. We find that empirical distributions obtained in two plant species, Phaseolus lunatus and Lolium perenne, are consistent with the expected distributions obtained from analytical theory and from numerical simulations. Our results indicate that the size distribution is strongly asymmetrical, with a much higher proportion of small than large fragments, that it is not influenced by the number of selective nucleotides nor by genome size but that it may vary with genome-wide GC-content, with a higher proportion of small fragments in cases of lower GC-content when considering the standard AFLP protocol with the enzyme MseI. Results from population samples of the two plant species show that there is a negative relationship between AFLP fragment size and fragment population frequency. Monte Carlo simulations reveal that size homoplasy, arising from pulling together nonhomologous fragments of the same size, generates patterns similar to those observed in P. lunatus and L. perenne because of the asymmetry of the size distribution. We discuss the implications of these results in the context of estimating genetic diversity with AFLP markers.
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Lolium/genética , Modelos Genéticos , Phaseolus/genética , Polimorfismo Genético , Alelos , Simulación por Computador , Cruzamientos Genéticos , ADN de Plantas/química , ADN de Plantas/genética , Desoxirribonucleasas de Localización Especificada Tipo II/química , Electroforesis en Gel de Poliacrilamida , Variación Genética , Lolium/química , Método de Montecarlo , Phaseolus/química , Reacción en Cadena de la PolimerasaRESUMEN
Although a number of studies have implicated the hippocampal formation in social recognition memory in the rat, a recent study in this laboratory has demonstrated that selective cytotoxic lesions, confined to the hippocampus proper (encompassing the four CA subfields and the dentate gyrus), are without effect on this behaviour. This finding suggests that the hippocampus proper does not subserve social recognition memory in the rat, but does not preclude the possibility that other areas of the hippocampal formation, such as the entorhinal cortex or subiculum, could support this form of learning. The present study addressed this issue by examining the effects of selective cytotoxic retrohippocampal (RHR) lesions (including both the entorhinal cortex and subiculum) on social recognition memory in the rat. RHR lesions produced a mild social recognition memory impairment, although lesioned animals still displayed a reduction in investigation time between the first and second exposure to the juvenile. This result is consistent with other studies which have implicated the retrohippocampal or parahippocampal area in olfactory recognition memory processes. It also suggests, however, that other areas, out with the retrohippocampal region, are also likely to play an important role in social recognition memory.
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Corteza Entorrinal/fisiopatología , Hipocampo/fisiopatología , Trastornos de la Memoria/patología , Trastornos de la Memoria/fisiopatología , Reconocimiento en Psicología/fisiología , Conducta Social , Factores de Edad , Animales , Aprendizaje Discriminativo/fisiología , Corteza Entorrinal/lesiones , Corteza Entorrinal/patología , Hipocampo/lesiones , Hipocampo/patología , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/fisiología , Neurotoxinas/farmacología , Ratas , Ratas Endogámicas , Tiempo de Reacción/fisiología , Olfato/fisiologíaRESUMEN
It is generally acknowledged that the rodent hippocampus plays an important role in spatial learning and memory. The importance of the entorhinal cortex (ERC), an area that is closely interconnected anatomically with the hippocampus, in these forms of learning is less clear cut. Recent studies using selective, fibre-sparing cytotoxic lesions have generated conflicting results, with some studies showing that spatial learning can proceed normally without the ERC, suggesting that this area is not required for normal hippocampal function. The present study compared cytotoxic and aspiration ERC lesions with both fimbria fornix (FFX) lesions and sham-operated controls on two spatial learning tasks which have repeatedly been shown to depend on the hippocampus. Both groups of ERC lesions were impaired during non-matching-to-place testing (rewarded alternation) on the elevated T-maze. However, neither of these lesions subsequently had any effect on the acquisition of a standard spatial reference memory task in the water maze. FFX lesions produced a robust and reliable impairment on both of these tasks. A second experiment confirmed that cytotoxic ERC lesions spared water maze learning but disrupted rewarded alternation on the T-maze, when the order of behavioural testing was reversed. These results confirm previous reports that ERC-lesioned animals are capable of spatial navigation in the water maze, suggesting that the ERC is not a prerequisite for normal hippocampal function in this task. The present demonstration that ERC lesions disrupt non-matching-to-place performance may, however, be consistent with the possibility that ERC lesions affect attentional mechanisms, for example, by increasing the sensitivity to recent reward history.