Lipoic acid prevents fructose-induced changes in liver carbohydrate metabolism: Role of oxidative stress

Fructose administration rapidly induces oxidative stress that triggers compensatory hepatic metabolic changes. We evaluated the effect of an antioxidant, R/S-α-lipoic acid on fructose-induced oxidative stress and carbohydrate metabolism changes. METHODS: Wistar rats were fed a standard commercial diet, the same diet plus 10% fructose in drinking water, or injected with R/S-α-lipoic acid (35mg/kg, i.p.) (control+L and fructose+L). Three weeks thereafter, blood samples were drawn to measure glucose, triglycerides, insulin, and the homeostasis model assessment-insulin resistance (HOMA-IR) and Matsuda indices. In the liver, we measured gene expression, protein content and activity of several enzymes, and metabolite concentration. RESULTS: Comparable body weight changes and calorie intake were recorded in all groups after the treatments. Fructose fed rats had hyperinsulinemia, hypertriglyceridemia, higher HOMA-IR and lower Matsuda indices compared to control animals. Fructose fed rats showed increased fructokinase gene expression, protein content and activity, glucokinase and glucose-6-phosphatase gene expression and activity, glycogen storage, glucose-6-phosphate dehydrogenase mRNA and enzyme activity, NAD(P)H oxidase subunits (gp91phox and p22phox) gene expression and protein concentration and phosphofructokinase-2 protein content than control rats. All these changes were prevented by R/S-α-lipoic acid co-administration. CONCLUSIONS: Fructose induces hepatic metabolic changes that presumably begin with increased fructose phosphorylation by fructokinase, followed by adaptive changes that attempt to switch the substrate flow from mitochondrial metabolism to energy storage. These changes can be effectively prevented by R/S-α-lipoic acid co-administration. GENERAL SIGNIFICANCE: Control of oxidative stress could be a useful strategy to prevent the transition from impaired glucose tolerance to type 2 diabetes.Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico. Centro de Endocrinologia Experimental y Aplicada (i); Argentin

Eff ect of a community-led sanitation intervention on child diarrhoea and child growth in rural Mali: a cluster-randomised controlled trial

Background Community-led total sanitation (CLTS) uses participatory approaches to mobilise communities to build their own toilets and stop open defecation. Our aim was to undertake the fi rst randomised trial of CLTS to assess its eff ect on child health in Koulikoro, Mali. Methods We did a cluster-randomised trial to assess a CLTS programme implemented by the Government of Mali. The study population included households in rural villages (clusters) from the Koulikoro district of Mali; every household had to have at least one child aged younger than 10 years. Villages were randomly assigned (1:1) with a computergenerated sequence by a study investigator to receive CLTS or no programme. Health outcomes included diarrhoea (primary outcome), height for age, weight for age, stunting, and underweight. Outcomes were measured 1·5 years after intervention delivery (2 years after enrolment) among children younger than 5 years. Participants were not masked to intervention assignment. The trial is registered with ClinicalTrials.gov, number NCT01900912. Findings We recruited participants between April 12, and June 23, 2011. We assigned 60 villages (2365 households) to receive the CLTS intervention and 61 villages (2167 households) to the control group. No diff erences were observed in terms of diarrhoeal prevalence among children in CLTS and control villages (706 [22%] of 3140 CLTS children vs 693 [24%] of 2872 control children; prevalence ratio [PR] 0·93, 95% CI 0·76–1·14). Access to private latrines was almost twice as high in intervention villages (1373 [65%] of 2120 vs 661 [35%] of 1911 households) and reported open defecation was reduced in female (198 [9%] of 2086 vs 608 [33%] of 1869 households) and in male (195 [10%] of 2004 vs 602 [33%] of 1813 households) adults. Children in CLTS villages were taller (0·18 increase in height-for-age Z score, 95% CI 0·03–0·32; 2415 children) and less likely to be stunted (35% vs 41%, PR 0·86, 95% CI 0·74–1·0) than children in control villages. 22% of children were underweight in CLTS compared with 26% in control villages (PR 0·88, 95% CI 0·71–1·08), and the diff erence in mean weight-for-age Z score was 0·09 (95% CI –0·04 to 0·22) between groups. In CLTS villages, younger children at enrolment (<2 years) showed greater improvements in height and weight than older children. Interpretation In villages that received a behavioural sanitation intervention with no monetary subsidies, diarrhoeal prevalence remained similar to control villages. However, access to toilets substantially increased and child growth improved, particularly in children <2 years. CLTS might have prevented growth faltering through pathways other than reducing diarrhoea

Chronic glucocorticoid-rich milieu and liver dysfunction

We investigated the impact of chronic hypercorticosteronemia (due to neonatal monosodium L-glutamate, MSG, and treatment) on liver oxidative stress (OS), inflammation, and carbohydrate/lipid metabolism in adult male rats. We evaluated the peripheral concentrations of several metabolic and OS markers and insulin resistance indexes. In liver we assessed (a) OS (GSH and protein carbonyl groups) and inflammatory (IL-1b, TNFa, and PAI-1) biomarkers and (b) carbohydrate and lipid metabolisms. MSG rats displayed degenerated optic nerves, hypophagia, low body and liver weights, and enlarged adipose tissue mass; higher peripheral levels of glucose, triglycerides, insulin, uric acid, leptin, corticosterone, transaminases and TBARS, and peripheral and liver insulin resistance; elevated liver OS, inflammation markers, and glucokinase (mRNA/activity) and fructokinase (mRNA). Additionally, MSG liver phosphofructokinase-2, glucose-6-phosphatase (mRNA and activity) and glucose-6-phosphate dehydrogenase, Chrebp, Srebp1c, fatty acid synthase, and glycerol-3-phosphate (mRNAs) were increased. In conclusion adult MSG rats developed an insulin-resistant state and increased OS and serious hepatic dysfunction characterized by inflammation and metabolic signs suggesting increased lipogenesis. These features, shared by both metabolic and Cushing?s syndrome human phenotypes, support that a chronic glucocorticoid-rich endogenous environment mainly impacts on hepatic glucose cycle, displacing local metabolism to lipogenesis. Whether correcting the glucocorticoid-rich environment ameliorates such dysfunctions requires further investigation.Fil: Villagarcía, Hernán Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Sabugo, Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Schinella, Guillermo Raúl. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Castrogiovanni, Daniel Cayetano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentin

Chronological appearance of endocrine and metabolic dysfunctions induced by an unhealthy diet in rats

Background and Objectives: The work was aimed to determine the chronological sequence of events triggered by a fructose-rich diet (FRD) (10% w/v in the drinking water) in normal rats. Material and Methods: Serum parameters, liver and islet markers of metabolism, inflammation and oxidative stress were determined weekly for 21 days. Results: At the end of the first week, rats fed with a FRD showed an early increase in circulating triglycerides, fat liver deposit, and enzymatic activity of liver glucokinase and glucose-6-phosphate dehydrogenase (G6P-DH). After two weeks of such a diet, liver glucose-6-phosphatase (G6Pase) activity and liver oxidative stress markers were significantly increased. Liver sterol regulatory element-binding protein 1c (SREBP1c) mRNA also increased in the second week while their target genes fatty acid synthase (FAS) and glycerol-3-phosphate dehydrogenase (GPAT) enhanced their expression at the third week. Liver and pancreatic inflammation markers also enhanced their gene expression in the last week of treatment. Whereas both control and FRD rats remained normoglycemic throughout the entire period of treatment, blood insulin levels were significantly higher in FRD animals at the third week, thereby evidencing an insulin-resistant state (higher HOMA-IR, HOMA-B and HIS indexes). Pancreatic islets isolated from rats fed with a FRD for 3 weeks also increased glucose-induced insulin secretion (8.3 and 16.7 mM). Conclusions: FRD induces asynchronous changes involving early hypertriglyceridemia together with intrahepatic lipid deposit and metabolic disturbances from week one, followed by enhanced liver oxidative stress, liver and pancreas inflammation, pancreatic β-cell dysfunction, and peripheral insulin-resistance registered at the third week. Knowledge of time-course adaptation mechanisms involved in our rat model could be helpful in developing appropriate strategies to prevent the progression from prediabetes to Type 2 diabetes (T2D) triggered by unhealthy diets.Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Villagarcía, Hernán Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Román, Carolina Lisi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Maiztegui, Barbara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Flores, Luis Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Schinella, Guillermo Raúl. Universidad Nacional de La Plata; Argentina. Universidad Nacional Arturo Jauretche; ArgentinaFil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; ArgentinaFil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentin

New perspectives in diagnosis and risk stratification of non-ischaemic dilated cardiomyopathy

Dilated cardiomyopathy is a primitive heart muscle condition, characterized by structural and functional abnormalities, in the absence of a specific cause sufficient to determine the disease. It is, though, an 'umbrella' term that describes the final common pathway of different pathogenic processes and gene-environment interactions. Performing an accurate diagnostic workup and appropriate characterization of the patient has a direct impact on the patient's outcome. The physician should adapt a multiparametric approach, including a careful anamnesis and physical examination and integrating imaging data and genetic testing. Aetiological characterization should be pursued, and appropriate arrhythmic risk stratification should be performed. Evaluations should be repeated thoroughly at follow-up, as the disease is dynamical over time and individual risk might evolve. The goal is an all-around characterization of the patient, a personalized medicine approach, in order to establish a diagnosis and therapy tailored for the individual patient

Mental Health of Long Term Survivors of Childhood and Young Adult Cancer

Background/Objectives Leukemic cells produce higher amounts of ROS than healthy cells and express low levels of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). Recently, it was demonstrated that rMnSOD, a recombinant new isoform of MnSOD, recently isolated from human liposarcoma cell line, is able to trigger apoptosis of human T-ALL cells (99%) without toxic effects on healthy cells. The present study was aimed to verify if rMnSOD is able to induce apoptosis and to stop in G0/G1 stage of the cell cycle in pediatric patients with B-cell acute lymphoblastic leukaemia (ALL) and if it displays synergic action with daunorubicin. Design and Methods Cells were collected from three patients diagnosed for B-cell ALL at the Pediatric Oncology of University “Luigi Vanvitelli”. Cell viability, apoptosis and cell cycle of lymphoblasts and SUP-B15 cell line (ATCC) were analyzed through “ Muse Kit” after rMnSOD treatment. ROS analysis was detected with NAC. Apoptotic fragmentations of SUP-B15 were demonstrated by confocal imaging. Results We observed that low concentrations of rMnSOD are able to trigger apoptosis of SUP-B15 cell line and B-ALL cells from pediatric patients. In detail, we observed an apoptosis rate from 30% to 46% in B-ALL pediatric patient cells and of 45% in SUP-B15 cell line. Instead, cell cycle analysis showed a cell fraction decrease in G0/G1 phase. Moreover, the synergic activity of rMnSOD and Daunorubicin induces apoptosis in 92% of cells, by comparing the treatment with the single substances, rMnSOD (64,7%) and Daunorubicin (23,9%). Confocal microscopy analysis revealed internalization of rMnSOD in SUP-B15 cells and evident apoptotic alterations, such as nuclear fragmentations and apoptotic-bodies. In conclusion, rMnSOD exerts toxic activity only against cancer cells, by enhancing drug effect, thus allowing to utilize lower concentration of standard chemotherapy to increase the apoptosis level

Gestión de contenidos en la era de las TIC

La línea de investigación presentada propone desde una mirada interdisciplinaria determinar y sistematizar aspectos determinantes en el desarrollo de materiales didácticos digitales a fin de constituir un Manual de Buenas Prácticas para su producción, administración y almacenamiento. Se consideran materiales digitales aquellos desarrollados para su utilización en los EVA (Entorno Virtual de Enseñanza y Aprendizaje), PLE (Entornos personales de aprendizaje), televisión digital, etc. A la hora de desarrollar materiales digitales se cuenta con la posibilidad de utilizar diferentes medios y sistemas simbólicos para presentar, concretar y estructurar la información. Ello nos permitirá desde poder ofrecer una redundancia de la información más significativa, hasta concretarla o especificarla de manera más clara posible. Los medios con los que podemos contar, fundamentalmente, para la realización del contenido son la ilustración, el audio, el vídeo, la animación, la tecnología web, los hipertextos, entre otros. Es importante, respecto de los diferentes medios, no perder de vista los comentarios que realiza Kilian (2001), cuando nos llama la atención respecto al diseño de la información para la red”… exige una clase de escritura muy diferente a las de otros medios, ni mejor ni peor, sólo diferente.” Es por ello que a la hora de producir materiales digitales debemos tener en cuenta aspectos que van desde el tipo de utilización educativa que realizaremos de la red, hasta la dimensión conceptual en la cual nos apoyemos para la realización de los materiales que transmitiremos a través de ella. Desde este proyecto se plantea el desarrollo de un Manual de Buenas Prácticas para la producción, administración y almacenamiento de contenido digital. El cual contendrá entre otras cosas la sistematización de aspectos que facilitan la producción de materiales didácticos digitales, aspectos que favorezcan a la gestión y administración de dichos materiales.Eje: Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI

Clinical-Genetic Features Influencing Disability in Spastic Paraplegia Type 4: A Cross-sectional Study by the Italian DAISY Network

Background and objectives: Hereditary spastic paraplegias (HSPs) are a group of inherited rare neurologic disorders characterized by length-dependent degeneration of the corticospinal tracts and dorsal columns, whose prominent clinical feature is represented by spastic gait. Spastic paraplegia type 4 (SPG4, SPAST-HSP) is the most common form. We present both clinical and molecular findings of a large cohort of patients, with the aim of (1) defining the clinical spectrum of SPAST-HSP in Italy; (2) describing their molecular features; and (3) assessing genotype-phenotype correlations to identify features associated with worse disability. Methods: A cross-sectional retrospective study with molecular and clinical data collected in an anonymized database was performed. Results: A total of 723 Italian patients with SPAST-HSP (58% men) from 316 families, with a median age at onset of 35 years, were included. Penetrance was 97.8%, with men showing higher Spastic Paraplegia Rating Scale (SPRS) scores (19.67 ± 12.58 vs 16.15 ± 12.61, p = 0.009). In 26.6% of patients with SPAST-HSP, we observed a complicated phenotype, mainly including intellectual disability (8%), polyneuropathy (6.7%), and cognitive decline (6.5%). Late-onset cases seemed to progress more rapidly, and patients with a longer disease course displayed a more severe neurologic disability, with higher SPATAX (3.61 ± 1.46 vs 2.71 ± 1.20, p &lt; 0.001) and SPRS scores (22.63 ± 11.81 vs 12.40 ± 8.83, p &lt; 0.001). Overall, 186 different variants in the SPAST gene were recorded, of which 48 were novel. Patients with SPAST-HSP harboring missense variants displayed intellectual disability (14.5% vs 4.4%, p &lt; 0.001) more frequently, whereas patients with truncating variants presented more commonly cognitive decline (9.7% vs 2.6%, p = 0.001), cerebral atrophy (11.2% vs 3.4%, p = 0.003), lower limb spasticity (61.5% vs 44.5%), urinary symptoms (50.0% vs 31.3%, p &lt; 0.001), and sensorimotor polyneuropathy (11.1% vs 1.1%, p &lt; 0.001). Increasing disease duration (DD) and abnormal motor evoked potentials (MEPs) were also associated with increased likelihood of worse disability (SPATAX score&gt;3). Discussion: The SPAST-HSP phenotypic spectrum in Italian patients confirms a predominantly pure form of HSP with mild-to-moderate disability in 75% of cases, and slight prevalence of men, who appeared more severely affected. Early-onset cases with intellectual disability were more frequent among patients carrying missense SPAST variants, whereas patients with truncating variants showed a more complicated disease. Both longer DD and altered MEPs are associated with worse disability

Generación de contenidos educativos digitales

La presente línea de investigación propone desde una mirada interdisciplinaria determinar y sistematizar aspectos determinantes en el desarrollo de materiales didácticos digitales a fin de generar un manual de buenas prácticas para la producción, administración y almacenamiento. Se consideran materiales digitales aquellos desarrollados para su utilización en los EVEA (Entornos Virtuales de Enseñanza y Aprendizaje), PLE (Entornos Personales de Aprendizaje), televisión digital, etc. A la hora de desarrollar materiales digitales se cuenta con la posibilidad de utilizar diferentes medios y sistemas simbólicos para presentar, concretar y estructurar la información. Ello nos permitirá poder ofrecer redundancia de la información más significativa y especificarla de manera clara. Los medios con los que podemos contar, para la realización del contenido son: la ilustración, el audio, el vídeo, la animación, la tecnología web, los hipertextos, entre otros. Desde esta línea de investigación se plantea el desarrollo de un manual de buenas prácticas para la producción, administración y almacenamiento de contenido digital. El cual contendrá la sistematización de aspectos que facilitan la producción de materiales didácticos digitales, aspectos que favorezcan a la gestión y administración de dichos materiales.Eje: Tecnología informática aplicada en educaciónRed de Universidades con Carreras en Informática (RedUNCI

Generación de contenidos educativos digitales

La presente línea de investigación propone desde una mirada interdisciplinaria determinar y sistematizar aspectos determinantes en el desarrollo de materiales didácticos digitales a fin de generar un manual de buenas prácticas para la producción, administración y almacenamiento. Se consideran materiales digitales aquellos desarrollados para su utilización en los EVEA (Entornos Virtuales de Enseñanza y Aprendizaje), PLE (Entornos Personales de Aprendizaje), televisión digital, etc. A la hora de desarrollar materiales digitales se cuenta con la posibilidad de utilizar diferentes medios y sistemas simbólicos para presentar, concretar y estructurar la información. Ello nos permitirá poder ofrecer redundancia de la información más significativa y especificarla de manera clara. Los medios con los que podemos contar, para la realización del contenido son: la ilustración, el audio, el vídeo, la animación, la tecnología web, los hipertextos, entre otros. Desde esta línea de investigación se plantea el desarrollo de un manual de buenas prácticas para la producción, administración y almacenamiento de contenido digital. El cual contendrá la sistematización de aspectos que facilitan la producción de materiales didácticos digitales, aspectos que favorezcan a la gestión y administración de dichos materiales.Eje: Tecnología informática aplicada en educaciónRed de Universidades con Carreras en Informática (RedUNCI