Role of cell cycle regulators in adipose tissue and whole body energy homeostasis.

In the course of the last decades, metabolism research has demonstrated that adipose tissue is not an inactive tissue. Rather, adipocytes are key actors of whole body energy homeostasis. Numerous novel regulators of adipose tissue differentiation and function have been identified. With the constant increase of obesity and associated disorders, the interest in adipose tissue function alterations in the XXIst century has become of paramount importance. Recent data suggest that adipocyte differentiation, adipose tissue browning and mitochondrial function, lipogenesis and lipolysis are strongly modulated by the cell division machinery. This review will focus on the function of cell cycle regulators in adipocyte differentiation, adipose tissue function and whole body energy homeostasis; with particular attention in mouse studies.

Pharmacological modulation of LMNA SRSF1-dependent splicing abrogates diet-induced obesity in mice.

Bakground/Objectives:Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. Alternative splicing (AS) and/or polyadenylation enable the LMNA gene to express distinct protein isoforms that exert opposing effects on energy metabolism and lifespan. Here we aimed to use the splicing factor SRSF1 that contribute to the production of these different isoforms as a target to uncover new anti-obesity drug. SUBJECTS/METHODS: Small molecules modulating SR protein activity and splicing were tested for their abilities to interact with SRSF1 and to modulate LMNA (AS). Using an LMNA luciferase reporter we selected molecules that were tested in diet-induced obese (DIO) mice. Transcriptomic analyses were performed in the white adipose tissues from untreated and treated DIO mice and mice fed a chow diet. RESULTS: We identified a small molecule that specifically interacted with the RS domain of SRSF1. ABX300 abolished DIO in mice, leading to restoration of adipose tissue homeostasis. In contrast, ABX300 had no effect on mice fed a standard chow diet. A global transcriptomic analysis revealed similar profiles of white adipose tissue from DIO mice treated with ABX300 and from untreated mice fed a chow diet. Mice treated with ABX300 exhibited an increase in O2 consumption and a switch in fuel preference toward lipids. CONCLUSIONS: Targeting SRSF1 with ABX300 compensates for changes in RNA biogenesis induced by fat accumulation and consequently represents a novel unexplored approach for the treatment of obesity.

Cellulose microfluidic pH boosting on copper oxide non-enzymatic glucose sensor strip for neutral pH samples.

A cellulose microfluidic pH boosting layer adapts a non-enzymatic copper oxide glucose sensor strip for neutral pH samples. This adaptation allows the non-enzymatic technology to realize in-situ glucose measurements. A three-electrode system is constructed to test samples in a classical electrochemical cell, and in a sensing strip to test the microfluidic system. The system consists of copper oxide as working electrode, and silver and carbon paints as reference, and counter electrodes, respectively. The fabrication of the pH-boosting layer is made with natural cellulose. Within this layer are NaOH crystals, grown by a drying processes after immersion of cellulose in a concentrated solution of NaOH. The microfluidic layer is placed on top of the sensing electrodes, and while it transports the fluid sample to the sensing electrodes, the fluid dissolves the NaOH crystals, increasing the pH of the sample. This change allows the non-enzymatic mechanism to sense the glucose concentration in the fluid. Our system shows the capability to measure glucose in samples with neutral pH and human blood with a sensitivity of 70 µA/mM cm2, enough to distinguish between hypoglycemia and hyperglycemia.

Role of average speed in N2O exhaust emissions as greenhouse gas in a huge urban zone (MVMZ): would we need a cold sun?

Nowadays, the drastic pollution problems, some of them related with greenhouse gas emissions, have promoted important attempts to face and diminish the global warming effects on the Mexico Valley Metropolitan Zone (MVMZ) as well as on the huge urban zones around the world. To reduce the exhaust gas emissions, many efforts have been carried out to reformulate fuels and design new catalytic converters; however, it is well known that other variables such as socio-economic and transport structure factors also play an important role around this problem. The present study analyzes the roles played by several commonly-used three-way catalytic converters (TWC) and the average traffic speed in the emission of N(2)O as greenhouse gas. According to this study, by increasing the average traffic flow and avoiding constant decelerations (frequent stops) during common trips, remarkable environmental and economic benefits could be obtained due to the diminution of N(2)O and other contaminant emissions such as ammonia (NH(3)) and even CO(2) with the concomitant reduced fossil fuel consumption. The actions mentioned above could be highly viable to diminish, in general, the global warming effects and contamination problems.

Prehepatic portal hypertension worsens the enterohepatic redox balance in thioacetamide-cirrhotic rats.

BACKGROUND: Oxidative stress has been reported as a key pathogenic factor in many human liver diseases and in experimental models of cirrhosis related to hepatotoxin administration. The aim of this study was to verify the hypothesis that prehepatic portal hypertension aggravates the enterohepatic redox imbalance in thioacetamide-cirrhotic rats. MATERIALS AND METHODS: Wistar male rats were used: Control (n=9); rats with prehepatic portal hypertension by triple partial portal vein ligation (TPVL; n=9); thioacetamide-cirrhotic rats (TAA; n=9) and TPVL-rats associated to TAA administration (TPVL+TAA; n=9). Three months after the operation, portal pressure (PP), mesenteric venous vasculopathy (MVV) and portosystemic collateral circulation were studied. Liver and ileal levels of malondialdehyde (MDA), as a lipid peroxidation marker, and catalase (CAT), glutathione peroxidase (GSH-Px), glutathione transferase (GSH-t) and cytosolic and mitochondrial superoxide dismutases (cSOD and mSOD), as antioxidative enzymatic mechanisms, were measured. RESULTS: Liver and ileal MDA increased in all the experimental groups, although the higher increase occurred in the ileum of rats with portal hypertension. CAT levels decreased in the liver and the ileum in the three experimental groups. The decrease in liver and ileal GSH-Px and GSH-t was greater in rats with portal hypertension, alone or associated with TAA. mSOD activation was demonstrated in the liver when portal hypertension was added to TAA. On the contrary, this compensatory response was not activated in the ileum, where mSOD was significantly decreased. CONCLUSION: Prehepatic portal hypertension by triple partial portal vein ligation impaired the enterohepatic antioxidative activity and aggravated the intestinal oxidative stress in thioacetamide-cirrhotic rats.

CDK4, a new metabolic sensor that antagonizes AMPK.

Cyclin-dependent kinase 4 (CDK4) is a positive regulator of cell cycle progression, however, there is growing evidence demonstrating that its function exceeds the control of cell division. Here we show that CDK4 is an important regulator of cellular substrate utilization through direct inhibition of the metabolic regulator AMPK (AMP-activated protein kinase).

Peabody Picture Vocabulary Test-III: Normative data for Spanish-speaking pediatric population.

OBJECTIVE: To generate normative data for the Peabody Picture Vocabulary Test-III (PPVT-III) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Honduras, Guatemala, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the PPVT-III as part of a larger neuropsychological battery. PPVT-III scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age in all countries, such that scores increased linearly as a function of age. In addition, age2 had a significant effect in all countries, except Guatemala and Paraguay. Models showed that children whose parent(s) had a MLPE >12 years obtained higher scores compared to children whose parent(s) had a MLPE ≤12 years in all countries, except for Cuba, Peru, and Puerto Rico. Sex affected scores for Chile, Ecuador, Guatemala, Mexico, and Spain. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate interpretation of the PPVT-III when used in pediatric populations.

Modified Wisconsin Card Sorting Test (M-WCST): Normative data for Spanish-speaking pediatric population.

OBJECTIVE: To generate normative data for the Modified Wisconsin Card Sorting Test (M-WCST) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the M-WCST as part of a larger neuropsychological battery. Number of categories, perseverative errors, and total error scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models indicated main effects for age on all scores, such that the number of categories correct increased and total number of perseverative errors and total number of errors decrease linearly as a function of age. Age2 had a significant effect in Chile, Cuba, Ecuador, and Spain for numbers of categories; a significant effect for number of perseverative errors in Chile, Cuba, Mexico, and Spain; and a significant effect for number of total errors in Chile, Cuba, Peru, and Spain. Models showed an effect for MLPE in Cuba (total errors), Ecuador (categories and total errors), Mexico (all scores), Paraguay (perseverative errors and total error), and Spain (categories and total errors). Sex affected number of total errors for Ecuador. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate way to interpret the M-WCST with pediatric populations.

Stroop Color-Word Interference Test: Normative data for Spanish-speaking pediatric population.

OBJECTIVE: To generate normative data for the Stroop Word-Color Interference test in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the Stroop Word-Color Interference test as part of a larger neuropsychological battery. The Stroop Word, Stroop Color, Stroop Word-Color, and Stroop Interference scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on all scores, except on Stroop Interference for Guatemala, such that scores increased linearly as a function of age. Age2 affected Stroop Word scores for all countries, Stroop Color scores for Ecuador, Mexico, Peru, and Spain; Stroop Word-Color scores for Ecuador, Mexico, and Paraguay; and Stroop Interference scores for Cuba, Guatemala, and Spain. MLPE affected Stroop Word scores for Chile, Mexico, and Puerto Rico; Stroop Color scores for Mexico, Puerto Rico, and Spain; Stroop Word-Color scores for Ecuador, Guatemala, Mexico, Puerto Rico and Spain; and Stroop-Interference scores for Ecuador, Mexico, and Spain. Sex affected Stroop Word scores for Spain, Stroop Color scores for Mexico, and Stroop Interference for Honduras. CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the Stroop Word-Color Interference test in pediatric populations.

Concentration Endurance Test (d2): Normative data for Spanish-speaking pediatric population.

OBJECTIVE: To generate normative data for the Concentration Endurance Test (d2) in Spanish-speaking pediatric populations. METHOD: The sample consisted of 4,373 healthy children from nine countries in Latin America (Chile, Cuba, Ecuador, Guatemala, Honduras, Mexico, Paraguay, Peru, and Puerto Rico) and Spain. Each participant was administered the d2 test as part of a larger neuropsychological battery. The Total number of items processed (TN), Total number of correct responses (CR), Total performance (TP), and Concentration performance (CP) scores were normed using multiple linear regressions and standard deviations of residual values. Age, age2, sex, and mean level of parental education (MLPE) were included as predictors in the analyses. RESULTS: The final multiple linear regression models showed main effects for age on all scores, such that scores increased linearly as a function of age. TN scores were affected by age2 for Guatemala and Puerto Rico; CR scores were affected by age2 for Mexico; TP scores were affected by age2 for Chile, Mexico, Puerto Rico, and Spain; and CP scores for Mexico and Spain. Models indicated that children whose parents had a MLPE >12 years obtained higher scores compared to children whose parents had a MLPE≤12 years for Mexico and Spain in all scores, and Puerto Rico for TN, CR, and TP, and Guatemala and Paraguay for CP scores. Sex affect the scores for Ecuador and Honduras (CP scores). CONCLUSIONS: This is the largest Spanish-speaking pediatric normative study in the world, and it will allow neuropsychologists from these countries to have a more accurate approach to interpret the d2 test in pediatric populations.

Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential.

Knowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients. In 10/35 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (5/10) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.

[Spontaneous hepatic rupture during pregnancy. Report of a case. Review of the literature]. / Ruptura hepática espontánea en el embarazo. Presentación de un caso. Revisión de la literatura.

The spontaneous hepatic rupture during pregnancy or puerperium has been reported as a rare complication, with an extraordinary severity. Usually it's a pregnancy hypertensive disease complication. Since 1990 it had been reported 120 cases from this pathology in the world literature. We reported a case from a patient who presented spontaneous hepatic rupture during the immediately puerperium and a world literature revision.

Incidencia y complicaciones de cardiopatías congénitas cianosantes / Incidence and complications of cianosantes congenital cardiopathies

Comenta que en el período de ene. de 1993 a dic. 1995 en el Hospital de Niños Alejandro Mann de Guayaquil, los ingresos hospitalarios fueron de 16990 pacientes; donde 486 (2.86xciento) tuvieron diagnóstico de cardiopatia, de los cuales 429 (88.27xciento) correspondieron a cardiopatías congénitas y de éstas 125 (29.13xciento) a cardiopatías congénitas cianóticas. Se describen los datos principales de 125 pacientes de diferentes edades pediátricas portadores de cardiopatias congénicas cianóticas internados en el departamento de cardiología. La tetralogía de Fallot fue la cardiopatía congénita cianótica más frecuente 42,4xciento, seguida de la transposición de los grandes vasos 17.6xciento, pulmonar 9.6xciento, 45 pacientes (36xciento) fueron intervenidos quirúrgicamente, de los cuales 43 en forma paliativa y correctiva total...