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Phosphate-activated glutaminase activity is enhanced in brain, intestine and kidneys of rats following portacaval anastomosis

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World Journal of Gastroenterology 2006年第15期12卷 2406-2411页

作者： Manuel Romero-Gómez María Jover Daniel Díaz-Gómez Laura Collantes de Terán Regina Rodrigo Inés Camacho Miriam Echevarría Vicente Felipo Juan D Bautista Unit for the Clinical Management of Digestive Diseases Hospital Universitario de Valme SevillaSpain department of Biochemistry Bromatology and Toxicology Faculty of PharmacyUniversity of SevilleSpain Laboratory of Neurobiology Fundación Valenciana de investigaciones biomédicas ValenciaSpain Biochemistry Unit Hospital Universitario de Valme SevillaSpain Instituto de Investigaciones Biomédicas Departament of Physiology University of SevilleSpain Laboratory of Neurobiology Fundación Valenciana de investigaciones biomédicas ValenciaSpain

瞄准：估计在老鼠的门腔静脉吻合(PCA ) 是否在肾影响蛋白质表示或谷酰胺酶的活动，肠并且在外皮的三个大脑区域，基础轧了神经胶质和小脑并且解释在肝的脑病发现的神经病学的改变(他) 。方法：称 250-350 g 的十六只男 Wistar 老鼠被... 详细信息

瞄准：估计在老鼠的门腔静脉吻合(PCA ) 是否在肾影响蛋白质表示或谷酰胺酶的活动，肠并且在外皮的三个大脑区域，基础轧了神经胶质和小脑并且解释在肝的脑病发现的神经病学的改变(他) 。方法：称 250-350 g 的十六只男 Wistar 老鼠被组织进假冒操作的控制(n=8 ) 或 portacaval (n=8 ) 。在过程以后的 28 天，动物被牺牲。十二指肠，肾和大脑被移开， homogenised 和线粒体被孤立。氨在大脑和血被测量。激活磷酸盐的谷酰胺酶(PAG ) 活动被与 O-phthalaldehyde (OPA ) 和每蛋白质(蛋白质的 mukat/g ) 的克以单位表示的特殊活动在 37 摄氏度测量氨生产追随者孵化一个小时决定。蛋白质表示被弄污的免疫测量。结果：十二指肠并且和蛋白质内容的肾 PAG 活动比在 PCA 组是显著地更高的在控制或假冒操作老鼠(十二指肠 PAG 活动是在 PCA 老鼠对在假冒操作老鼠的蛋白质的 429.19+/-126.92mukat/g 的蛋白质的 976.95+/-268.87 mukat/g；肾 PAG 活动是在 PCA 老鼠对在控制的蛋白质的 669.67+/-400.8 mukat/g 的 1259.18+/-228.79 mukat/g 蛋白质， P<0.05；十二指肠的蛋白质内容：173% 在 PCA 对假冒操作老鼠；在肾，蛋白质的内容在 PCA 对假冒操作老鼠是 152%) 。在 PCA 老鼠的 PAG 活动和蛋白质表示在外皮是更高的并且基础在假冒操作老鼠比那些轧了神经胶质(外皮：蛋白质的 6646.6+/-1870.4 mukat/g 对在控制老鼠的蛋白质的 3573.8+/-2037.4 mukat/g， P<0.01；基础轧了神经胶质， PAG 活动是在 PCA 老鼠对在假冒的操作老鼠的蛋白质的 2271.2+/-384 mukat/g 的蛋白质的 3657.3+/-1469.6 mukat/g， P<0.05；在小脑，分别地， PAG 活动是蛋白质的 2471.6+/-701.4 mukat/g 对在 PCA 和假冒的老鼠的蛋白质的 1452.9+/-567.8 mukat/g P<0.05；蛋白质的内容：大脑皮质：162%+/-40% 对 100%+/-26% ， P<0.009；并且基础轧了神经胶质：140%+/-39% 对 100%+/-14% ， P<0.05；然而并非在里面小脑：100%+/-25% 对 100%+/-16% ， P=ns ) 。结论：在肾和十二指肠的增加的 PAG 活动能在 PCA 老鼠显著地作出贡献到 hyperammonaemia，脑病的动物模型。PAG 从外皮在 non-synaptic 线粒体被增加并且基础轧了神经胶质并且能在肝的脑病的致病被含有。因此， PAG 能是为处理的一个可能的目标他或肝机能障碍。

关键词：磷酸谷氨酰胺酶酶活性脑疾病门腔静脉吻合术

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Hypothalamic circuits and aging:keeping the circadian clock updated

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Neural Regeneration Research 2024年第9期19卷 1919-1928页

作者： Rosa Vázquez-Lizarraga Lucia Mendoza-Viveros Carolina Cid-Castro Sareni Ruiz-Montoya Erick Carreño-Vázquez Ricardo Orozco-Solis instituto Nacional de Medicina Genómica(INMEGEN) México CityMéxico Centro de Investigacíon sobre el Envejecimiento Centro de Investigacíon y de Estudios Avanzados(CIE-CINVESTAV)México CityMéxico instituto de investigaciones biomédicas Universidad Nacional Autónoma de México UNAMMéxico CityMéxico

Over the past century,age-related diseases,such as cancer,type-2 diabetes,obesity,and mental illness,have shown a significant increase,negatively impacting overall quality of life.Studies on aged animal models have unveiled a progressive discoordination at multiple regulatory levels,including transcriptional,translational,and post-translational processes,resulting from cellular stress and circadian derangements.The circadian clock emerges as a key regulator,sustaining physiological homeostasis and promoting healthy aging through timely molecular coordination of pivotal cellular processes,such as stem-cell function,cellular stress responses,and inter-tissue communication,which become disrupted during aging.Given the crucial role of hypothalamic circuits in regulating organismal physiology,metabolic control,sleep homeostasis,and circadian rhythms,and their dependence on these processes,strategies aimed at enhancing hypothalamic and circadian function,including pharmacological and non-pharmacological approaches,offer systemic benefits for healthy aging.Intranasal brain-directed drug administration represents a promising avenue for effectively targeting specific brain regions,like the hypothalamus,while reducing side effects associated with systemic drug delivery,thereby presenting new therapeutic possibilities for diverse age-related conditions.

关键词： aging astrocytes cellular stress responses circadian clock hypothalamus intranasal drug administration metabolic control nutrient sensor SIRT1 sleep homeostasis

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Hematotesticular barrier is altered from early stages of liver cirrhosis:Effect of insulin-like growth factor 1

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World Journal of Gastroenterology 2004年第17期10卷 2529-2534页

作者： Inma Castilla-Cortázar Nieves Diez María García-Fernández Juan Enrique Puche Fernando Diez-Caballero Jorge Quiroga Matías Díaz-Sánchez Alberto Castilla Amelia Díaz Casares Isabel Varela-Nieto Jesǘs Prieto Salvador González-Barón department of Human physiology University of NavarraPamplonaNavarraSpain Department of Human physiologySchool of MedicineUniversity of MlagaMalagaSpain department of Human physiology University of NavarraPamplonaNavarraSpain department of Human physiology School of MedicineUniversity of MálagaMalagaSpain instituto de investigaciones biomédicas "Alberto Sols" Consejo Superior de Investigaciones CientificasUniversidad Autónoma de Madrid (CSIC-UAM)MadridSpain Supported by the Spanish Program I+DSAF 99/0072 and SAF 2001/1672 department of Internal Medicine Hospital SierrallanaTollelavega and School of MedicineUniversity of the Basque Country-Vitoria-GasteizSpain instituto de investigaciones biomedicas"Alberto Sols"Consejo Superior de investigaciones Cientificas Universidad Autonoma de Madrid(CSIC-UAM) MadridSpain department of Internal Medicine Liver Unit University of Navarra PamplonaNavarraSpain

AIM: The pathogenesis of hypogonadism in liver cirrhosis is not well understood. Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis. The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis.The aim of this study was to establish the historical progression of the described alterations in the testes,explore testicular morphology, histopathology, cellular proliferation, integrity of testicular barrier and hypophysogonadal axis in rats with no ascitic cirrhosis.METHODS: Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride (CC14) for 11 wk,were allocated into two groups (n = 12, each) to receive recombinant IGF-1 (2 μg/100 g·d, sc) for two weeks or vehicle. Healthy rats receiving vehicle were used as control group (n = 12).RESULTS: Compared to controls, rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities.However, these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression. In addition, pituitary-gonadal axis was altered, with significant higher levels of FSH (Pder associated with compensated cirrhosis.

关键词：血睾肝硬化胰岛素生长因子1 消化系统

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Microbial phenolic metabolites are associated with better frontal lobe cognition

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Food Science and Human Wellness 2024年

作者： Inés Domínguez-López Isabella Parilli-Moser Anna Vallverdú-Queralt Anna Tresserra-Rimbau Cinta Valls-Pedret Zenaida Vázquez-Ruiz Olga Casta?er Ramon Estruch Emili Ros Rosa M.Lamuela-Raventós Lipid Clinic Endocrinology and Nutrition Service Institut d'Investigacions biomèdiques August Pi i Sunyer Hospital Clínic 08036 Barcelona Spain Unit of Cardiovascular Risk and Nutrition Institut Hospital del Mar de investigaciones Médicas (IMIM) department of Preventive Medicine and Public Health University of Navarra departament de Nutrició Ciències de l'Alimentació i Gastronomía Facultat de Farmacia Universitat de Barcelon (UB) Av.de Joan XXII department of Endocrinology Hospital Clinic IDIBAPS Barcelona Spain department of Internal Medicine Hospital Clinic Institut d'Investigació biomèdica August Pi i Sunyer (IDIBAPS) University of Barcelona CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) instituto de Salud Carlos III Institut de Nutrició i Seguretat Alimentària (INSA) Universitat de Barcelona (UB)

With increasing life expectancy， neurodegenerative diseases have become one of the leading causes of ill-health in the elderly. Preventive strategies include following healthy diets， such as the Mediterranean diet， which is particularly rich in polyphenols， bioactive compounds with neuroprotective properties. The aim of this study was to assess the association of microbial phenolic metabolites (MPM) with cognition. This cross-sectional analysis was performed with 200 participants of the PREDIMED trial (Barcelona-Clinic recruitment center). A novel method based on liquid chromatography coupled to mass spectrometry was used to identify urinary MPM (protocatechuic acid， enterodiol glucuronide， enterolactone glucuronide， urolithin B glucuronide， and vanillic acid glucuronide)， and cognitive function was evaluated with neuropsychological tests. Multivariable-adjusted ordinary least squares regression was used to assess the associations between cognitive function and MPM， and a score was calculated as the weighted sum of MPM. A higher MPM score was associated with better frontal lobe function. Among individual metabolites， vanillic acid glucuronide was correlated with frontal cognitive performance. Participants with higher concentrations of vanillic acid glucuronide and urolithin B glucuronide obtained better scores in the Color Trail Test part 2. A higher score for urinary multi-MPM was associated with better frontal cognitive performance in an older Mediterranean population.

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Selective and constructive mechanisms contribute to neural circuit formation in the barrel cortex of the developing rat

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Advances in Bioscience and Biotechnology 2013年第7期4卷 785-797页

作者： Eileen Uribe-Querol Eduardo Martínez-Martínez Luis Rodrigo Hernández Patricia Padilla Cortés Horacio Merchant-Larios Gabriel Gutiérrez-Ospinac Cell Biology and physiology department Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México Mexico City Mexico División de Estudios de Posgrado e Investigación Facultad de Odontología Universidad Nacional Autónoma de México Mexico City Mexico Unidad de HPLC Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México Mexico City Mexico

The cellular strategy leading to formation of neuronal circuits in the rodent barrel cortex is still a matter of controversy. Both selective and constructive mechanisms have been proposed. The selective mechanism involves an overproduction of neuronal processes and synapses followed by activity dependent pruning. Conversely, a constructive mechanism would increase the number of axons, dendrites, and synapses during development to match functionality. In order to discern the contributions of these two mechanisms in establishing a neuronal circuit in the somatosensory cortex, morphometric analysis of dendritic and axonal arbor growth was performed. Also, the number of synapses was followed by electron microscopy during the first month of life. We observed that axonal and dendritic arbors retracted distal branches, and elongated proximal branches, resulting in increased arbor complexity. This neuronal remodeling was accompanied by the steady increase in the number of synapses within barrel hollows. Similarly, the content of molecular markers for dendrites, axons and synapses also increased during this period. Finally, cytochrome oxidase activity rose with age in barrels indicating that the arbors became more complex while synapse density and metabolic demands increased. Our results support the simultaneous use of both selective and constructive mechanisms in establishing the barrel cortex circuitry.

关键词： Barrel Cortex Synaptogenesis Axonal Growth dendritic Growth Thalamocortical Pathway

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Adverse effects induced by chromium Ⅵ, cadmium and arsenic exposure on hypothalamus-pituitary physiology

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BIOCELL 2016年第1期40卷 15-18页

作者： JIMENA P.CABILLA SONIA A.RONCHETTI BEATRIZ H.DUVILANSKI instituto de investigaciones biomédicas(INbiomED)UBA-CONICET Facultad de MedicinaUniversidad de Buenos AiresParaguay 215510°pisoCiudad Autónoma de Buenos AiresC1121ABGArgentina

Environmental contamination with some metalloids and heavy metals(M/HM)raises concern due to well known adverse effects on health.Among these pollutants,chromium VI(Cr VI),cadmium(Cd)and arse-nic(As)are frequently present as a result of natural sources or due to industrial activities.They are able to easily enter the organism and negatively affect many organs and systems.In vivo(exposure to Cr VI,Cd or As through drinking water)and in vitro experiments(primary pituitary cell cultures)were performed in male Wistar rats to address their actions on hypothalamus-pituitary axis.All the M/HM accumulated in hypothalamus and pi-tuitary gland and decreased pituitary cell viability and prolactin release mostly by generation of reactive oxygen species,since it was partially prevented by antioxidant treatment.In the pituitary,they increased lipid peroxy-dation and the expression of several oxidative stress markers.Cell death was mainly due to caspase-dependent apoptosis.Lactotrophs(prolactin-secreting cells)were the most affected pituitary population.Cd-driven cell death was also partially calcium-and calpain-dependent.Parallely,Cd stimulated the production of low levels of nitric oxide which exerted cytoprotective actions.These results showed that these M/HM display deleterious actions in hypothalamic-pituitary physiology by altering hormone release and promoting cell death.

关键词： metalloid heavy metals cell death oxidative stress hormone release

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Anaplerosis in cancer: Another step beyond the warburg effect

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American Journal of Molecular Biology 2012年第4期2卷 291-303页

作者： Estefania Ochoa-Ruiz Rodrigo Diaz-Ruiz Facultad de Medicina Programa de Posgrado en Ciencias Médicas Odontológicas y de la Salud Universidad Nacional Autónoma de México Mexico City Mexico Unidad de Genética de la Nutrición Instituto de Investigaciones Biomédicas Universidad Nacional Autónoma de México Mexico City Mexico

Biosynthesis is up-regulated in tumors and thus the demand for anabolic intermediates is increased. The metabolic routes providing the building blocks for macromolecules are thus a very attractive target as they are not normally up-regulated in a normal quiescent cell. Some routes for glycolysis-derived intermediates production have been identified, but these do not constitute the whole pool of biosynthetic molecules in the cell, as many of these derive from mitochondria in the Krebs cycle. Indeed, this metabolic pathway is considered a “biosynthetic hub” from which anabolism is fed. If a metabolite efflux is indeed occurring, anaplerotic reactions must keep a steady supply of substrates. In spite of this obvious relevance of anaplerosis, it has been poorly characterized in the malignant cell context. Glutaminolysis and and pyruvate carboxylation are two pathways that function in an anaplerotic fashion. In spite of the increasing evidence implicating these two processes in cancer metabolism their role as intermediate providers is overlooked. In this review we analyze the implications of an active anaplerosis in cancer and we discuss experimental evidence showing the relevance of these metabolic routes in tumor physiology.

关键词： Anaplerosis Biosynthesis Cancer Glutaminase Krebs Cycle Metabolism Mitochondria Pyruvate Carboxylase Warburg Effect

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How to protect liver graft with nitric oxide

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World Journal of Gastroenterology 2011年第24期17卷 2879-2889页

作者： Hassen Ben Abdennebi Mohamed Amine Zaoualí Izabel Alfany-Fernandez Donia Tabka Joan Roselló-Catafau Laboratory of Human physiology Faculty of PharmacyUniversity of Monastir Unit of Experimental Hepatic IschemiaReperfusion Institut of d'Investigacions Biomèdiques de BarcelonaConsejo Superior de Investigaciones Científicas Unitat de Transplantament de Fetge i Viabilitat de l'Empelt Institut d'Investigacions Biomèdiques August Pi i Sunyer

Organ preservation and ischemia reperfusion injury as- sociated with liver transplantation play an important role in the induction of graft injury. One of the earliest events associated with the reperfusion injury is en- dothelial cell dysfunction. It is generally accepted that endothelial nitric oxide synthase (e-NOS) is cell-pro- tective by mediating vasodilatation, whereas inducible nitric oxide synthase mediates liver graft injury after transplantation. We conducted a critical review of the literature evaluating the potential applications of regu- lating and promoting e-NOS activity in liver preservation and transplantation, showing the most current evidenceto support the concept that enhanced bioavailability of NO derived from e-NOS is detrimental to ameliorate graft liver preservation, as well as preventing subse- quent graft reperfusion injury. This review deals mainly with the beneficial effects of promoting "endogenous" pathways for NO generation, via e-NOS inducer drugs in cold preservation solution, surgical strategies such as ischemic preconditioning, and alternative "exogenous" pathways that focus on the enrichment of cold storage liquid with NO donors. Finally, we also provide a basic bench-to-bed side summary of the liver physiology and cell signalling mechanisms that account for explaining the e-NOS protective effects in liver preservation and transplantation. ? 2011 Baishideng. All rights reserved.

关键词：一氧化氮合成酶保护作用肝移植缺血再灌注损伤 NOS活性内皮细胞一氧化氮合酶生物利用度

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Toll-like receptor 4 polymorphisms and bacterial infections in patients with cirrhosis and ascites

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World Journal of Hepatology 2018年第1期10卷 124-133页

作者： Edilmar Alvarado-Tapias Carlos Guarner-Argente Elida Oblitas Elisabet Sánchez Silvia Vidal Eva Román Mar Concepción Maria Poca Cristina Gely Oana Pavel Juan Camilo Nieto Cándido Juárez Carlos Guarner Germán Soriano department of Gastroenterology Hospital de la Santa Creu i Sant PauBarcelona 08025Spain instituto de Salud Carlos III Institut de Recerca IIBSant PauUniversitat Autònoma de BarcelonaBellaterra(Cerdanyola del Vallès)08193Spain Centro de Investigación biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain department of Immunology Hospital de la Santa Creu i Sant PauBarcelona 08025Spain Escola Universitària d’Infermeria EUI-Sant Pau Hospital de la Santa Creu i Sant PauBarcelona 08025Spain

AIM To assess the relationship between the presence of toll-like receptor 4(TLR4) polymorphisms and bacterial infections in cirrhotic patients with ascites. METHODS We prospectively included consecutive patients with cirrhosis and ascites hospitalized during a 6-year period. Patients with human immunodeficiency virus(HIV) infection or any other immunodeficiency, patients with advanced hepatocellular carcinoma(beyond Milan's criteria) or any other condition determining poor short-term prognosis, and patients with a permanent urinary catheter were excluded. The presence of D299 G and/or T399 I TLR4 polymorphisms was determined by sequencing and related to the incidence and probability of bacterial infections, other complications of cirrhosis, hepatocellular carcinoma, and mortality during follow-up. A multivariate analysis to identify predictive variables of mortality in the whole series was performed. RESULTS We included 258 patients: 28(10.8%) were carriers of D299G and/or T399I TLR4 polymorphisms(polymorphism group) and 230 patients were not(wildtype group). The probability of developing any bacterial infection at one-year follow-up was 78% in the polymorphism group and 69% in the wild-type group(P = 0.54). The one-year probability of presenting infections caused by gram-negative bacilli(51% vs 44%, P = 0.68), infections caused by gram-positive cocci(49% vs 40%, P = 0.53), and spontaneous bacterial peritonitis(29% vs 34%, respectively, P = 0.99) did not differ between the two groups. The oneyear probability of transplant-free survival was 55% in the polymorphism group and 66% in the wild-type group(P = 0.15). Multivariate analysis confirmed that age, Child-Pugh score, active alcohol intake, previous hepatic encephalopathy, hepatocellular carcinoma and serum creatinine were associated with a higher risk of death during follow-up. CONCLUSION Genetic polymorphisms D299 G and/or T399 I of TLR4 do not seem to play a relevant role in the predisposition of cirrhotic patients with ascites to bacterial infections.

关键词： Cirrhosis Genetic polymorphisms Toll-like receptor 4 Bacterial infections Ascites

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