Abnormalities of sodium excretion and other disorders of renal function in fulminant hepatic failure

Renal function was evaluated in 40 patients with fulminant hepatic failure, They were divided into two groups on the basis of glomerular filtration rates greater than 40 ml/min or less than 25 ml/min. A number of patients in group 1 had markedly abnormal renal retention of sodium together with a reduced free water clearance and low potassium excretion which could be explained by increased proximal tubular reabsorption of sodium. The patients in group 2 had evidence that renal tubular integrity was maintained when the glomerular filtration rate was greater than or equal ml/min (functional renal failure), but evidence of tubular damage was present when this was less than 3 ml/min (acute tubular necrosis).

Implication of Nerve Growth Factor in intestinal mucosal mast cell activity and colonic motor alterations in a model of ovalbumin-induced gut dysfunction in rats

We determined NGF involvement in MMCs and colonic motor alterations in an ovalbumin (OVA)-induced gut dysfunction model in rats. Animals received OVA (6 weeks), with/without simultaneous K252a (TrkA antagonist) treatment. MMCs, rat mast cell protease II (RMCPII) levels and colonic contractility in vitro were assessed. OVA increased MMC density and RMCPII concentration. Spontaneous contractility was similar in both groups and inhibited by K252a. Carbachol responses were increased by OVA in a K252a-independent manner. NO-synthase inhibition increased spontaneous activity in OVA-treated animals in a K252a-dependent manner. These observations support an involvement of NGF in the functional changes observed in this model.

Estudio del bypass gástrico en Y de Roux y de la gastrectomía tubular sobre el metabolismo de la glucosa y la secreción de hormonas intestinales. Estudio prospectivo y randomizado

Introducció: El bypass gàstric en Y de Roux laparoscòpic (BGYRL) és la tècnica quirúrgica d’elecció per al tractament de l’obesitat mòrbida. La gastrectomia tubular laparoscòpica (GTL) és una tècnica bariàtrica restrictiva amb resultats molt prometedors en relació a la pèrdua de pes, però se’n desconeixen els efectes metabòlics i endocrins. L’objectiu d’aquest estudi és l’avaluació de les diferències en la resposta del metabolisme de la glucosa i la secreció d’hormones intestinals entre ambdós procediments. Material i mètodes: Es va dissenyar un estudi prospectiu i aleatoritzat per la realització del BGYRL i la GTL, ambdós realitzats via laparoscòpica. Totes les pacients es varen avaluar abans, i als 3 i 12 mesos de la intervenció. Se’ls va prendre una mostra de sang venosa després d’un dejuni de 12 hores i als 10 i 60 minuts després de la ingesta d’Ensure® 420 kcal per realitzar les determinacions dels nivells plasmàtics de glucosa, insulina, grelina, leptina, pèptid relacionat amb glucagó (GLP-1), pèptid YY (PYY) i polipèptid pancreàtic (PP). Resultats: Es varen incloure 15 pacients (totes de gènere femení, edat mitja de 48±9 anys, IMC de 44±2.7 kg/m2 amlitat preoperatòria) dels quals 7 van ser aleatoritzats a BGYRL i 8 a GTL. No hi van haver diferències entre ambdós grups en edat, IMC preoperatori, classificació ASA i determinacions hormonals preoperatòries. Després de la cirurgia, s’observa un descens de la glicèmia i insulinèmia, amb una reducció de l´índex HOMA-IR en ambdós grups. Postoperatòriament, es detecta una disminución de les concentracions de la leptina en dejú i després de la ingesta, significativament menor en el grup de BGYRL. Mentre que els nivells de grelina en dejú només descendeixen de forma significativa en el grup de la GTL. Després de la ingesta es produeix una augment dels nivells de GLP-1, significativament major en el grup de BGYRL. Conclusions: Tan el BGYRL como la GTL s’associen a una significativa pèrdua de pes, encara que aquesta fou significativament superior en el BGYRL. Ambdós procediments han millorat notablement l’homeostasi de la glucosa. Només la GTL va rehuir els nivells de grelina tan en dejú com després de la ingesta, mentre que els nivells de GLP-1 i PYY s’elevaren després de la cirurgia, sense diferències estadísticament significatives entre ambdues tècniques.

Estudio prospectivo comparando la gastrectomía tubular laparoscópica y la gastrectomía robótica para el tratamiento de la obesidad mórbida

La cirurgia de l’obesitat suposa una eina dins de l’arsenal terapèutic dels pacients afectes d’obesitat mòrbida. La gastrectomia vertical s’ha popularitzat com a tècnica i les noves tecnologies com la laparoscòpia s’utilitzen de forma habitual. Més recentment la robòtica s’utilitza en diferents àmbits i també s’està implementant en la cirurgia de l’obesitat. A fi de compara la gastrectomia vertical realitzada mitjançant laparoscòpia o robòtica es planteja el següent estudi. S’han comparat els pacients intervinguts de gastrectomia vertical laparoscòpica i robòtica en termes de complicacions intraoperatòries, morbimortalitat i resultats en el seguiment dels pacients. Els resultats són satisfactoris en el sentit que es demostra que la tecnologia robòtica aporta els mateixos resultats en termes de complicacions intra y perioperatòries. Tanmateix es demostra que l’evolució ponderal dels pacients intervinguts de gastrectomia vertical amb tecnologia robòtica es igual a aquells intervinguts de manera tradicional. Així, es conclou que la tecnologia robòtica es una eina en ple desenvolupament que ha demostrat ser eficient, segura y eficaç per al tractament de la Obesitat Mòrbida mitjançant la Gastrectomia vertical.

Resultats a llarg termini del tractament quirúrgic de les fractures d’húmer proximal intervingudes mitjançant sutures aïllades o associades a claus d’Ender modificats

Valorem els resultats funcionals i de qualitat de vida a mig i a llarg termini de 38 fractures de l’húmer proximal, tractades en 17 casos amb fixació amb sutures transòssies i en 21 associant claus d’Ender modificats. Els pacients intervinguts amb sutures transòssies obtingueren millors resultats funcionals amb diferències significatives. Les fractures en 3 parts en valg obtingueren millors resultats funcionals que les desplaçades en var No s’observaren diferències de qualitat de vida segons tècnica quirúrgica i tipus de fractura. La fixació amb sutures associades o no a claus d’Ender modificats és una tècnica, útil, segura i amb baix índex de complicacions.

Morbi-mortalidad en fracturas de húmero proximal tratadas quirúrgicamente

L’objectiu es valorar si els pacients afectats de fractura d’húmer proximal tractats quirúrgicament tenen menys morbi-mortalitat a mig termini que els que presenten una fractura de fèmur proximal tractada quirúrgicament. Observem una menor mortalitat en les fractures d’húmer proximal amb un 14.43% respecte al 36% de les fractures de maluc als 8 anys de seguiment. El 79.5% dels pacients amb fractures d’húmer continuen essent independents per a les activitats de la vida diària. Un 26% han tingut fractures posteriors a la fractura d’húmer i un 11.3% ja estaven diagnosticats d’osteoporosis amb anterioritat.

RACE (Rapid Arterial oCclusion Evaluation): Diseño y validación prehospitalaria de una escala neurológica para la predicción de una oclusión arterial proximal en los pacientes con un ictus isquémico agudo de la circulación cerebral anterior

La Rapid Arterial oCclusion Evaluation és una escala neurològica prehospitalària que prediu la presència d’una oclusió arterial proximal (OAP) en els pacients amb un ictus isquèmic agut de la circulació cerebral anterior (IIACCA). Fou dissenyada valorant retrospectivament a 654 pacients amb un IIACCA, seleccionant la combinació dels ítems de la National Institutes of Health Stroke Scale que mostraven una major associació amb la presència d’una OAP: parèsia facial, parèsia braquial, parèsia crural, desviació oculocefàlica y agnòsia/afàsia. Fou validada valorant prospectivament a 93 activacions del Codi Ictus, mostrant una sensibilitat del 88% y una especificitat del 65% per una puntuació ≥ 4.

Fracturas de escafoides carpiano: estudio retrospectivo en fracturas de polo proximal

Con el objetivo de evaluar los resultados obtenidos en nuestra experiencia con las fracturas de polo proximal de escafoides carpiano nos dispusimos a analizar una serie de variables para constatar los resultados finales en estas fracturas, detectar fallos en nuestros protocolos de actuación y plantear puntos de mejora en su diagnóstico y tratamiento. Para ello se recogieron todos los pacientes diagnosticados de fractura de polo proximal de escafoides entre 2001 y 2007 y de entre ellos analizamos los resultados de aquellos que se intervinieron quirúrgicamente (n=20). Esto incluía tanto aquellos pacientes que presentaban fracturas agudas, así como las pseudoartrosis y los retrasos de consolidación.

Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in utero

BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been described in a number of cell types in adult rat and humans. These changes can play a key part in the impairment of nutrient assimilation and postnatal growth retardation after prenatal damage of the intestinal epithelium produced by ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal proteins are affected by longterm ethanol exposure in utero and to what extent. ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and control group receiving water as drinking fluid. METHODS: Single and double electron microscopy immunolocalisation and label density estimation of cytoskeletal proteins on sections of proximal small intestine incubated with monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1, 5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4-galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker, or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions from small intestine. Western blotting analysis was carried out by incubation with the same antibodies used for immunolocalisation. RESULTS: Intestinal epithelium of newborn rats from the ethanol treated group showed an overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related polypeptide of 28-29 kDa was identified together with an increase in free ubiquitin in the same group. It was noteworthy that actin and cytokeratin were abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure to ethanol in utero causes severe dysfunction in the cytoskeleton of the developing intestinal epithelium. Actin and cytokeratins, which are involved in cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly affected, showing overexpression, impaired proteolysis, and mislocalisation.

Conditional BDNF release under pathological conditions improves Huntington's disease pathology by delaying neuronal dysfunction

Background Brain-Derived Neurotrophic Factor (BDNF) is the main candidate for neuroprotective therapy for Huntington's disease (HD), but its conditional administration is one of its most challenging problems. Results Here we used transgenic mice that over-express BDNF under the control of the Glial Fibrillary Acidic Protein (GFAP) promoter (pGFAP-BDNF mice) to test whether up-regulation and release of BDNF, dependent on astrogliosis, could be protective in HD. Thus, we cross-mated pGFAP-BDNF mice with R6/2 mice to generate a double-mutant mouse with mutant huntingtin protein and with a conditional over-expression of BDNF, only under pathological conditions. In these R6/2:pGFAP-BDNF animals, the decrease in striatal BDNF levels induced by mutant huntingtin was prevented in comparison to R6/2 animals at 12 weeks of age. The recovery of the neurotrophin levels in R6/2:pGFAP-BDNF mice correlated with an improvement in several motor coordination tasks and with a significant delay in anxiety and clasping alterations. Therefore, we next examined a possible improvement in cortico-striatal connectivity in R62:pGFAP-BDNF mice. Interestingly, we found that the over-expression of BDNF prevented the decrease of cortico-striatal presynaptic (VGLUT1) and postsynaptic (PSD-95) markers in the R6/2:pGFAP-BDNF striatum. Electrophysiological studies also showed that basal synaptic transmission and synaptic fatigue both improved in R6/2:pGAP-BDNF mice. Conclusions These results indicate that the conditional administration of BDNF under the GFAP promoter could become a therapeutic strategy for HD due to its positive effects on synaptic plasticity.

Changes in the enterocyte cytoskeleton in newborn rats exposed to ethanol in utero

BACKGROUND: Cytoskeletal changes after longterm exposure to ethanol have been described in a number of cell types in adult rat and humans. These changes can play a key part in the impairment of nutrient assimilation and postnatal growth retardation after prenatal damage of the intestinal epithelium produced by ethanol intake. AIMS: To determine, in the newborn rat, which cytoskeletal proteins are affected by longterm ethanol exposure in utero and to what extent. ANIMALS: The offspring of two experimental groups of female Wistar rats: ethanol treated group receiving up to 25% (w/v) of ethanol in the drinking fluid and control group receiving water as drinking fluid. METHODS: Single and double electron microscopy immunolocalisation and label density estimation of cytoskeletal proteins on sections of proximal small intestine incubated with monoclonal antibodies against actin, alpha-tubulin, cytokeratin (polypeptides 1, 5, 6, 7, 8, 10, 11, and 18), and with a polyclonal antibody anti-beta 1,4-galactosyl transferase as trans golgi (TG) or trans golgi network (TGN) marker, or both. SDS-PAGE technique was also performed on cytoskeletal enriched fractions from small intestine. Western blotting analysis was carried out by incubation with the same antibodies used for immunolocalisation. RESULTS: Intestinal epithelium of newborn rats from the ethanol treated group showed an overexpression of cytoskeletal polypeptides ranging from 39 to 54 kDa, affecting actin and some cytokeratins, but not tubulin. Furthermore, a cytokeratin related polypeptide of 28-29 kDa was identified together with an increase in free ubiquitin in the same group. It was noteworthy that actin and cytokeratin were abnormally located in the TG or the TGN, or both. CONCLUSIONS: Longterm exposure to ethanol in utero causes severe dysfunction in the cytoskeleton of the developing intestinal epithelium. Actin and cytokeratins, which are involved in cytoskeleton anchoring to plasma membrane and cell adhesion, are particularly affected, showing overexpression, impaired proteolysis, and mislocalisation.

Respiratory chain dysfunction associated with multiple mitochondrial DNA deletions in antiretroviral therapy-related lipodystrophy.

Highly-active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome characterized by peripheral fat wasting and central adiposity, usually associated with hyperlipidaemia and insulin resistance [1,2]. Indirect data have led some authors to propose that mitochondrial dysfunction could play a role in this syndrome [3,4].To date, as recently outlined by Kakuda et al. [5] in this journal, HIV-infected patients developing lipodystrophy have not been studied for mitochondrial changes or respiratory chain capacity...

Respiratory chain dysfunction associated with multiple mitochondrial DNA deletions in antiretroviral therapy-related lipodystrophy.

Highly-active antiretroviral therapy (HAART) can induce a characteristic lipodystrophy syndrome characterized by peripheral fat wasting and central adiposity, usually associated with hyperlipidaemia and insulin resistance [1,2]. Indirect data have led some authors to propose that mitochondrial dysfunction could play a role in this syndrome [3,4].To date, as recently outlined by Kakuda et al. [5] in this journal, HIV-infected patients developing lipodystrophy have not been studied for mitochondrial changes or respiratory chain capacity...

Mitochondrial dysfunction increases oxidative stress and decreases chronological life span in fission yeast

Background: Oxidative stress is a probable cause of aging and associated diseases. Reactive oxygen species (ROS) originate mainly from endogenous sources, namely the mitochondria. Methodology/Principal Findings: We analyzed the effect of aerobic metabolism on oxidative damage in Schizosaccharomyces pombe by global mapping of those genes that are required for growth on both respiratory-proficient media and hydrogen-peroxide-containing fermentable media. Out of a collection of approximately 2700 haploid yeast deletion mutants, 51 were sensitive to both conditions and 19 of these were related to mitochondrial function. Twelve deletion mutants lacked components of the electron transport chain. The growth defects of these mutants can be alleviated by the addition of antioxidants, which points to intrinsic oxidative stress as the origin of the phenotypes observed. These respiration-deficient mutants display elevated steady-state levels of ROS, probably due to enhanced electron leakage from their defective transport chains, which compromises the viability of chronologically-aged cells. Conclusion/Significance: Individual mitochondrial dysfunctions have often been described as the cause of diseases or aging, and our global characterization emphasizes the primacy of oxidative stress in the etiology of such processes.