Influencia de la gastroparesia en el logro de la meta calórica y proteica en pacientes neurocríticos / Influence of gastroparesis on achieving the caloric and protein goal in neurocritical patients

La lesión cerebral induce a la aparición de complicaciones gastrointestinales, especialmente gastroparesia, la cual es considerada uno de los pilares de la intolerancia digestiva alta. Se mide por el aumento en el residuo gástrico, reflujo gastroesofágico, vómitos, distención abdominal y/o diarrea. Como consecuencia, la nutrición enteral (NE) se inicia de manera tardía o ineficientemente, impidiendo lograr la meta calórico-proteica, aumentando el riesgo de neumonía aspirativa, prolongándose la estadía hospitalaria e incrementando la mortalidad. Se realizó una revisión bibliográfica con el objetivo de actualizar y describir el rol de la gastroparesia en el alcance de la meta calórica-proteica en el paciente neurocrítico. Se consultaron bases de datos electrónica: MEDLINE, EMBASE, LILACS, Cochrane, desde el 2007 a 2017. Se incluyeron 8 estudios, cuatro ensayos controlados y aleatorizados (ECA), dos observacionales y dos revisiones sistemáticas y metaanálisis. En tres ECA cuando la NE es postpilórica se logra un mayor aporte calórico y proteico. Dos estudios no encontraron diferencias en las calorías recibidas entre los pacientes alimentados a estómago o yeyuno. Dos revisiones y metaanálisis confirman menor riesgo de neumonía aspirativa pero no presentan diferencias en el porcentaje de adecuación a la NE por ambas vías. La mortalidad, días de asistencia respiratoria mecánica, estancia en la unidad de cuidados intensivos (UCI) y hospitalaria no fue diferente cuando la NE fue a estómago o intestino. En conclusión, la persistencia del retraso del vaciamiento gástrico favorece al déficit energético y proteico, debido a la intolerancia a la NE lo que dificulta la progresión. A la fecha, pocos estudios recomiendan la vía postpilórica para mejorar la eficiencia nutricional. Futuros estudios deberán valorar las implicancias de alcanzar la meta calórica-proteica en los resultados clínicos de acuerdo a la vía de la NE, en esta población de pacientes(AU).

The brain injury induces the appearance of gastrointestinal complications, especially gastroparesis, which is considered one of the pillars of high digestive intolerance. It is measured by the increase in gastric residue, gastroesophageal reflux, vomiting, abdominal distension and / or diarrhea. As a consequence, enteral nutrition (EN) begins late or inefficiently, preventing the caloric-protein goal from being achieved, increasing the risk of aspiration pneumonia, prolonging the hospital stay and increasing mortality. A literature review was carried out with the objective of updating and describing the role of gastroparesis in the scope of the caloric-protein goal in the neurocritical patient. Electronic databases were consulted: MEDLINE, EMBASE, LILACS, Cochrane, from 2007 to 2017. 8 studies were included, four randomized controlled trials (RCTs), two observational studies and two systematic reviews and meta-analyzes. In three RCTs when the EN is post-pyloric, a greater caloric and protein intake is achieved. Two studies found no difference in the calories received between patients fed via stomach or jejunum. Two reviews and meta-analyzes confirm a lower risk of aspiration pneumonia, but there are no differences in the percentage of adaptation to the EN by both routes. Mortality, days of mechanical ventilation, stay in the intensive care unit (ICU) and hospital stay were not different when the EN was via stomach or intestine. In conclusion, the persistence of delayed gastric emptying favors protein and energy deficit, due to intolerance to EN, which hinders progression. To date, few studies recommend the postpyloric route to improve nutritional efficiency. Future studies should evaluate the implications of reaching the caloric-protein goal in clinical results according to the EN route, in this patient population(AU).

Neuroplasticidad y ácidos grasos omega 3 en adultos mayores / Neuroplasticity and omega-3 fatty acids in older adults

El aumento en la expectativa de vida ha llevado a que las enfermedades neurodegenerativas relacionadas con la vejez sean más investigadas. Las diversas intervenciones no farmacológicas en el campo de las demencias tienen su punto de partida en el concepto de neuroplasticidad o capacidad plástica del cerebro. Se conoce como neuroplasticidad a la capacidad cerebral para minimizar los efectos de las lesiones a través de cambios estructurales y funcionales, lo que permite al cerebro reaccionar o ajustarse a cambios ambientales internos y externos bajo condiciones fisiológicas y patológicas, a través modificaciones morfológicas extensas, como las que se observan en la regeneración de axones, formación de nuevas sinapsis, promoción de la neurogénesis, hasta sutiles cambios moleculares que alteran la respuesta celular a los neurotransmisores. Se ha propuesto como una de las estrategias en el tratamiento de la Enfermedad de Alzheimer, el deterioro cognitivo leve y las intervenciones post ACV la suplementación con ácidos grasos poliinsaturados (AGPI). Los AGPI omega 3 (AGPI ω-3) poseen múltiples mecanismos de acción en el cerebro y en el sistema vascular que podrían generar cierta protección contra el declive cognitivo y la demencia. Los estudios encontrados que fueron realizados en humanos corresponden a pacientes con deterioro cognitivo leve y enfermedad de Alzheimer (EA) leve a moderada y en un solo trabajo se evaluó la suplementación con omega 3 en pacientes post ACV. Aunque la evidencia clínica es algo contradictoria, probablemente en gran parte debido a cuestiones metodológicas, diversos estudios han demostrado que los AGPI ω-3 pueden mejorar la función cognitiva en los individuos adultos sanos y atenuar el deterioro cognitivo en el envejecimiento y EA leve. En los pacientes con EA moderada no se observaron cambios significativos. Hasta hoy no existen resultados concluyentes para incluir a los AGPI omega 3 como parte de un protocolo de tratamiento en enfermedades neurodegenerativas. Se necesitan más estudios aleatorizados controlados para definir el tiempo, dosis y momento adecuado para la prescripción de estos ácidos grasos.

The increase in life expectancy has led to the fact that the neurodegenerative diseases related to old age are being more and more researched. The various non-pharmacological interventions in the field of dementias have their starting point in the concept of neuroplasticity or plastic capacity of the brain. Neuroplasticity is known as the brain capacity to minimize the effects of injuries through structural and functional changes, allowing the brain to react or adjust to internal and external environmental changes under physiological and pathological conditions, through extensive morphological modifications, as the ones observed in the regeneration of axons, formation of new synapses, promotion of neurogenesis, to subtle molecular changes that alter the cellular response to neurotransmitters. It has been proposed as one of the strategies in the treatment of Alzheimer's Disease (AD), mild cognitive impairment (MCI) and poststroke interventions with polyunsaturated fatty acid (PUFA) supplementation. The omega-3 PUFAs (ω-3PUFA) have multiple mechanisms of action in the brain and vascular system that could provide some protection against cognitive decline and dementia. The studies found that were performed in humans correspond to patients with mild cognitive impairment and mild to moderate AD and in only one study, supplementation with omega-3 in poststroke patients was evaluated. Although clinical evidence is somehow contradictory, probably largely due to methodological issues, several studies have shown that ω-3 PUFAs may improve cognitive function in healthy adult individuals and attenuate cognitive impairment in aging and mild AD. No significant changes were observed in patients with moderate AD. Until today, there are no conclusive results to include omega-3 PUFAs as part of a treatment protocol in neurodegenerative diseases. Further randomized controlled studies are needed to define the time, dose and appropriate timing for the prescription of these fatty acids.

Impacto de la sedación en el gasto energético del paciente neurocrítico / Impact of sedation on the energy expenditure of neurocritical patient

La sedoanalgesia en el paciente neurocrítico permite la reducción del dolor, el control de la temperatura corporal, favorece la adaptación a la asistencia respiratoria mecánica y evita el aumento de la presión intracraneal. Además, disminuye la actividad cerebral mediante la reducción del consumo de oxígeno y la frecuencia cardiaca, repercutiendo directamente en el gasto energético en reposo. Se realizó una revisión bibliográfica con el objetivo de actualizar y describir el efecto de la sedación en el gasto energético de pacientes críticos con injuria cerebral, para lo cual fueron consultadas 4 bases de datos electrónicas: MEDLINE, EMBASE, LILACS, Cochrane, desde el año 2006 a 2016. Se observó que el gasto energético en el paciente neurocrítico es altamente variable debido a la utilización de sedoanalgesia, relajantes musculares y barbitúricos que lo reducen en un 12 a 32%, siendo menores los descensos con el uso de propanolol o morfina, atenuando el hipermetabolismo característico de estos pacientes. En conclusión, debe tenerse en cuenta el uso de sedación al momento de estimar los requerimientos energéticos a fin de evitar las consecuencias adversas derivadas de la hipo e hiperalimentación, siendo necesarios a la fecha disponer de más estudios al respecto.

Early-onset liver mtDNA depletion and late-onset proteinuric nephropathy in Mpv17 knockout mice.

In humans, MPV17 mutations are responsible for severe mitochondrial depletion syndrome, mainly affecting the liver and the nervous system. To gain insight into physiopathology of MPV17-related disease, we investigated an available Mpv17 knockout animal model. We found severe mtDNA depletion in liver and, albeit to a lesser extent, in skeletal muscle, whereas hardly any depletion was detected in brain and kidney, up to 1 year after birth. Mouse embryonic fibroblasts did show mtDNA depletion, but only after several culturing passages, or in a serumless culturing medium. In spite of severe mtDNA depletion, only moderate decrease in respiratory chain enzymatic activities, and mild cytoarchitectural alterations, were observed in the Mpv17(-/-) livers, but neither cirrhosis nor failure ever occurred in this organ at any age. The mtDNA transcription rate was markedly increased in liver, which could contribute to compensate the severe mtDNA depletion. This phenomenon was associated with specific downregulation of Mterf1, a negative modulator of mtDNA transcription. The most relevant clinical features involved skin, inner ear and kidney. The coat of the Mpv17(-/-) mice turned gray early in adulthood, and 18-month or older mice developed focal segmental glomerulosclerosis (FSGS) with massive proteinuria. Concomitant degeneration of cochlear sensory epithelia was reported as well. These symptoms were associated with significantly shorter lifespan. Coincidental with the onset of FSGS, there was hardly any mtDNA left in the glomerular tufts. These results demonstrate that Mpv17 controls mtDNA copy number by a highly tissue- and possibly cytotype-specific mechanism.

Severe infantile encephalomyopathy caused by a mutation in COX6B1, a nucleus-encoded subunit of cytochrome c oxidase.

Cytochrome c oxidase (COX) deficiency, one of the most common respiratory-chain defects in humans, has been associated with mutations in either mitochondrial DNA genes or nucleus-encoded proteins that are not part in but promote the biogenesis of COX. Mutations of nucleus-encoded structural subunits were sought for but never found in COX-defective patients, leading to the conjecture that they may be incompatible with extra-uterine survival. We report a disease-associated mutation in one such subunit, COX6B1. Nuclear-encoded COX genes should be reconsidered and included in the diagnostic mutational screening of human disorders related to COX deficiency.

Lack of founder effect for an identical mtDNA depletion syndrome (MDS)-associated MPV17 mutation shared by Navajos and Italians.

Navajo neurohepatopathy is a hepato-cerebral variant of mitochondrial DNA depletion syndrome due to a specific mutation in MPV17, a gene located on human chromosome 2p. The same mutation was reported in an Italian family. To understand whether the MPV17 mutation was transmitted by descent from a common ancestor to Navajos and Italians we constructed a dense haplotype of the MPV17 locus using suitable single nucleotide polymorphisms. Complete discordance between Italian and Navajo haplotypes rules out the former hypothesis, suggesting that the mutation occurred independently in the two populations.

Evidence for a role of glycosphingolipids in CXCR4-dependent cell migration.

Chemotaxis induction is a major effect evoked by stimulation of the chemokine receptor CXCR4 with its sole ligand CXCL12. We now report that treatment of CHP-100 human neuroepithelioma cells with the glucosylceramide synthase (GCS) inhibitor DL-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol inhibits CXCR4-dependent chemotaxis. We provide evidence that the phenomenon is not due to unspecific effects of the inhibitor employed and that inhibition of GCS neither affects total or plasmamembrane CXCR4 expression, nor CXCL12-induced Ca(2+) mobilization. The effects of the GCS inhibitor on impairment of CXCL12-induced cell migration temporally correlated with a pronounced downregulation of neutral glycosphingolipids, particularly glucosylceramide, and with a delayed and more moderate downregulation of gangliosides; moreover, exogenously administered glycosphingolipids allowed resumption of CXCR4-dependent chemotaxis. Altogether our results provide evidence, for the first time, for a role glycosphingolipids in sustaining CXCL12-induced cell migration.