Leptin regulates sugar and amino acids transport in the human intestinal cell line Caco-2.

AIM: Studies in rodents have shown that leptin controls sugars and glutamine entry in the enterocytes by regulating membrane transporters. Here, we have examined the effect of leptin on sugar and amino acids absorption in the human model of intestinal cells Caco-2 and investigated the transporters involved. METHODS: Substrate uptake experiments were performed in Caco-2 cells, grown on plates, in the presence and the absence of leptin, and the expression of the different transporters in brush border membrane vesicles was analysed by Western blot. RESULTS: Leptin inhibited 0.1 mm α-methyl-D-glucoside uptake after 5 or 30 min treatment and decreased SGLT1 protein abundance in the apical membrane. Uptake of 20 µm glutamine and 0.1 mm phenylalanine was also inhibited by leptin, indicating sensitivity to the hormone of the Na(+) -dependent neutral amino acid transporters ASCT2 and B(0) AT1. This inhibition was accompanied by a reduction in the transporters expression at the brush border membrane. Leptin also inhibited 1 mm proline and ß-alanine uptake in Na(+) medium at pH 6, conditions for optimal activity of the H(+) -dependent neutral amino acid transporter PAT1. In this case, abundance of PAT1 in the brush border membrane after leptin treatment was not modified. Interestingly, leptin inhibitory effect on ß-alanine uptake was reversed by the PKA inhibitor H-89 suggesting involvement of PKA pathway in leptin's regulation of PAT1 activity. CONCLUSION: These data show in human intestinal cells that leptin can rapidly control the activity of physiologically relevant transporters for rich-energy molecules, that is, D-glucose (SGLT1) and amino acids (ASCT2, B(0) AT1 and PAT1).

DNA copy number variation and gene expression analyses reveal the implication of specific oncogenes and genes in GBM.

To understand the pathogenesis of glioblastoma multiforme (GBM) we used high-resolution comparative genomic hybridization arrays and gene expression microarrays to identify DNA copy number alterations and gene expression changes in comparable sets of GBM samples. Gains were detected at chromosomes 1, 2, 7, 9, 12, 19, and 20 and losses at 6, 9, and 10. Gene expression analyses identified specific genes overexpressed in GBM mapping at amplified chromosomal regions. Among these genes we found genes involved in angiogenesis, extracellular matrix remodeling and several oncogenes. DNA copy number analysis along with gene expression profiles provides a powerful strategy to understand tumor progression and identification of genes involved in GBM pathogenesis.

Luminal leptin inhibits intestinal sugar absorption in vivo.

AIM: We have previously demonstrated that leptin inhibits galactose absorption in rat intestinal everted rings and that leptin receptors are present in the apical membrane of the enterocytes. This adipocyte-derived hormone is also secreted by gastric mucosal cells and is able to reach the intestinal lumen. The goal of the present study was to prove whether luminal leptin acts on intestinal sugar absorption in vivo both at low (basal state) and high sugar concentration (post-prandial state). METHODS: In vivo intestinal sugar absorption in rat was measured with recirculating and single-pass perfusion systems. Sugar disappearance in the perfusate was measured by radioactivity and biochemical methods. Luminal leptin effect on intestinal absorption mediated by sodium-dependent glucose transporter 1 (SGLT1) and glucose transporter 2 (GLUT2) as well as intestinal permeability (mannitol absorption) was determined. RESULTS: Luminal leptin inhibited intestinal sugar absorption at low galactose concentrations, which indicates that leptin regulates SGLT1 activity in vivo. The inhibition was reversed in the absence of hormone in the intestinal lumen, suggesting that it was produced by post-translational regulation processes. At high luminal glucose concentrations, leptin also inhibited the phloretin-insensitive component of sugar absorption mediated by SGLT1. There was no significant effect on the apical GLUT2 component of absorption. Leptin did not modify in vivo intestinal permeability determined with (14)C-mannitol. CONCLUSION: These observations support the view that gastric leptin exerts a regulatory role on intestinal sugar absorption in the postprandial state by modifying the active component of absorption.

Na+ and pH dependence of proline and beta-alanine absorption in rat small intestine.

AIMS: Early characterization of intestinal absorption of imino acids in mammals has demonstrated the existence of a Na+-dependent, Cl- -independent transport system in rat small intestine, which is the only carrier for beta-alanine. Based on the substrate selectivity, it was proposed that the Proton Amino Acid Transporter 1 (PAT1) could be the same as this imino acid carrier. The present study characterizes the pH and Na+ dependence of proline and beta-alanine uptake in rat small intestine. METHODS: Intestinal uptake of radiolabelled l-proline or beta-alanine was measured in brush border membrane vesicles and everted intestinal rings, in the presence and absence of Na+ and at different pH values. RESULTS: The existence of an inwardly directed H+ gradient in the absence of Na+ enhanced the initial entry of proline and beta-alanine in brush border membrane vesicles, that reached a transient overshoot with maximal value around 30 s. In the absence of pH gradient, no overshoot was shown. In entire tissue, there was an increase of proline and beta-alanine uptake at acidic pH that was higher in the presence of Na+ than in its absence. This ion dependence and pH effect of the amino acids uptake also increased with the incubation period. Substrate inhibition studies confirmed that intestinal proline absorption in rat occurs mainly by system B and PAT1-like transporter. CONCLUSIONS: There is a Na+ -independent, H+ -dependent transporter of amino acids at the apical membrane of the rat enterocytes.

Estudio sobre el uso de antibióticos en infecciones respiratorias en el Medio Penitenciario / Study of the antibiotic treatments used for respiratory infections in prison’s settings

Se ha realizado un estudio descriptivo de los tratamientos antibióticos prescritos en las infecciones respiratorias en el medio penitenciario, así como de los medios diagnósticos que se usan y la evolución de estas infecciones. Se solicitó a 14 médicos de distintos centros penitenciarios distribuidos por toda España y cubriendo los diversos tipos de centros existentes siguiendo el modelo de médicos centinela, que cumplimentasen una encuesta diseñada para este estudio.Los resultados indican que los grupos farmacológicos de penicilinas y macrólidos suponen el 98,5% de las prescripciones en las infecciones respiratorias de vías altas tratadas, el 84,0% de las prescripciones en infecciones de las de vías bajas y el 33,3% en las neumonías típicas. Por otra parte las pautas de prescripción se acomodan notablemente a las recomendadas por guías de prescripción de atención primaria

A descriptive study of the antibiotic treatments used for respiratory infections in prison’s settings was done. The evolution of these infections and diagnostic techniques were also investigated. 14 doctors of the same number of prisons from all over Spain aswered a questionnaire specifically designed for this study. The selection of doctors was done following the methodologyof sentinel netwoks.Our results show that peniciles and macrolids are used in 98,5% of treated high respiratory tract infections, 84% of treated low respiratory tract infections and 33,3% treated pneumonias. Finally we observed that the used of antibiotics agree with the published guidelines for primary health care

Leptin effect on intestinal galactose absorption in ob/ob and db/db mice.

Our previous works demonstrated that leptin inhibits galactose absorption in rat and mice intestinal rings. Here, we have studied the effect of exogenous leptin on intestinal galactose absorption in the genetically obese db/db (leptin-resistant) and ob/ob (leptin-deficient) mice. Assays were performed by incubating the intestinal rings in saline solution containing 5 mM galactose in the absence or presence of 0.2 or 0.4 nM leptin. Basal galactose uptake was similar in the wild-type and the two obese groups. Contrarily to what happens in wild-type mice, leptin increased galactose uptake in db/db animals; since these mice lack the functional long leptin receptor, the measured effect may be due to the short receptor signaling. In the ob/ob mice, 0.2 nM leptin also increased galactose absorption whereas 0.4 nM did not have any effect, suggesting that in the genetically obese animals the expression and regulation of leptin receptors may be altered.

Mortality in maximum security psychiatric hospital patients.

Numerous studies have mentioned to the high percentage of violent deaths in prison psychiatric hospitals, with suicide being the principal cause. The aim of this study was to analyze the circumstances related with the deaths recorded in a high security institution. Postmortem reports on all the deaths at the Alicante Psychiatric Prison between 1984 and 1997 were studied (36 cases of unnatural death and 28 of natural death). Of the violent deaths recorded 34 (94.4%) were suicides. Demographic, clinical and interpersonal variables factors were registered. In the cases of suicides, the method used, the place of death, season, month and time of suicide were analyzed. In our study, 64.7% of suicides were schizophrenic and 32.4% had inflicted self-harm previously. We found a statistically significant association between the cause of death (natural, suicide or homicide) and age, 47.1% of suicides being between the ages of 18 and 30 and 29.4% between the ages of 30 and 45. Natural causes predominated in older subjects. The prison population studied showed grave negative traits, mental illness and criminal behavior having forced them to the very edge of society. Our results were compared with the death and suicide rates of the general Spanish population.

[Progressive subaortic stenosis caused by accessory mitral valve tissue]. / Estenosis subaórtica progresiva causada por tejido mitral accesorio.

Accessory mitral valve tissue is a rare cause of subaortic obstruction. The reported case correspond to a two days old patient diagnosed by 2D-Echocardiography. Serial doppler flow analysis showed progressive left ventricular outflow obstruction. A cardiac catheterization at the age of 9 months confirmed the obstruction without defining the cause. Five months later, transesophageal echocardiography clearly defined the intraventricular connections of the accessory mitral tissue. At the age of 18 months the patient suffered from cardiac failure and underwent surgery for removing the accessory tissue, assisted by intraoperative transesophageal echocardiography pre and post by-pass. Follow-up echocardiography at 25 months showed no left ventricle outflow obstruction and the patient is now asymptomatic.