ABSTRACT
BACKGROUND: The relationship between lipid mediators and severe obesity remains unclear. Our study investigates the impact of severe obesity on plasma concentrations of oxylipins and fatty acids and explores the consequences of weight loss. METHODS: In the clinical trial identifier NCT05554224 study, 116 patients with severe obesity and 63 overweight/obese healthy controls matched for age and sex (≈2:1) provided plasma. To assess the effect of surgically induced weight loss, we requested paired plasma samples from 44 patients undergoing laparoscopic sleeve gastrectomy one year after the procedure. Oxylipins were measured using ultra-high-pressure liquid chromatography coupled to a triple quadrupole mass spectrometer via semi-targeted lipidomics. Cytokines and markers of interorgan crosstalk were measured using enzyme-linked immunosorbent assays. RESULTS: We observed significantly elevated levels of circulating fatty acids and oxylipins in patients with severe obesity compared to their metabolically healthier overweight/obese counterparts. Our findings indicated that sex and liver disease were not confounding factors, but we observed weak correlations in plasma with circulating adipokines, suggesting the influence of adipose tissue. Importantly, while weight loss restored the balance in circulating fatty acids, it did not fully normalize the oxylipin profile. Before surgery, oxylipins derived from lipoxygenase activity, such as 12-HETE, 11-HDoHE, 14-HDoHE, and 12-HEPE, were predominant. However, one year following laparoscopic sleeve gastrectomy, we observed a complex shift in the oxylipin profile, favoring species from the cyclooxygenase pathway, particularly proinflammatory prostanoids like TXB2, PGE2, PGD2, and 12-HHTrE. This transformation appears to be linked to a reduction in adiposity, underscoring the role of lipid turnover in the development of metabolic disorders associated with severe obesity. CONCLUSIONS: Despite the reduction in fatty acid levels associated with weight loss, the oxylipin profile shifts towards a predominance of more proinflammatory species. These observations underscore the significance of seeking mechanistic approaches to address severe obesity and emphasize the importance of closely monitoring the metabolic adaptations after weight loss.
Subject(s)
Obesity, Morbid , Oxylipins , Humans , Fatty Acids , Obesity , Obesity, Morbid/surgery , Overweight , Weight LossABSTRACT
Paraoxonase-1 (PON1) is an antioxidant enzyme associated with high-density lipoproteins (HDL). Reduced serum PON1 activity is found in diseases marked by oxidative stress and inflammation, but its role in obesity remains unclear. This study investigated PON1 activities and concentrations in morbidly obese individuals and explored the impacts of the genetic polymorphism PON1 rs662 and non-alcoholic fatty liver disease on enzymatic properties. We recruited 1349 morbidly obese patients undergoing bariatric surgery and 823 non-obese volunteers. PON1-related variables, including arylesterase, paraoxonase, and lactonase activities and PON1 concentrations, were examined. Our results showed that morbidly obese individuals exhibited higher PON1 concentrations but lower enzymatic activities than non-obese individuals. We observed inverse associations of arylesterase and paraoxonase activities with waist circumference (rho = -0.24, p < 0.001, and rho = -0.30, p < 0.001, respectively) and body mass index (rho = -0.15, p = 0.001, and rho = -0.23, p < 0.001), as well as direct associations of arylesterase, paraoxonase, and lactonase activities with HDL cholesterol (rho = 0.11, p = 0.005, rho = 0.20, p < 0.001, and rho = 0.20, p < 0.001). No significant differences were observed regarding metabolic syndrome, type 2 diabetes mellitus, hypertension, dyslipidemia, rs662 polymorphism allele frequencies, or the diagnosis of non-alcoholic steatohepatitis. Nevertheless, correlations were found between certain PON1-related variables, steatosis, and ballooning. In conclusion, changes in PON1-related variables in morbidly obese patients are dependent on the disease itself and HDL levels. The relationships between these variables and specific liver histological changes raise intriguing questions for consideration in future studies.
ABSTRACT
This study's objective was to assess the involvement of olfactomedin 2 (OLFM2), a secreted glycoprotein related to lipid metabolism regulation, in nonalcoholic fatty liver disease (NAFLD) mediated by the adipose-tissue-liver axis. OLFM2 mRNA expression was analyzed in subcutaneous (SAT) and visceral (VAT) adipose tissue by RT-qPCR. The cohort included women with normal weight (n = 16) or morbid obesity (MO, n = 60) who were subclassified into normal liver (n = 20), simple steatosis (n = 21), and nonalcoholic steatohepatitis (NASH, n = 19) groups. The results showed that OLFM2 expression in SAT was enhanced in MO individuals and in the presence of NAFLD. Specifically, OLFM2 expression in SAT was increased in mild and moderate degrees of steatosis in comparison to the absence of it. Moreover, OLFM2 expression in SAT was negatively correlated with interleukin-6 levels. On the other hand, OLFM2 expression in VAT decreased in the presence of NASH and exhibited a positive correlation with adiponectin levels. In conclusion, OLFM2 in SAT seems to be implicated in hepatic lipid accumulation. Additionally, since we previously suggested the possible implication of hepatic OLFM2 in NAFLD progression, now we propose a possible interaction between the liver and SAT, reinforcing the potential implication of this tissue in NAFLD development.
Subject(s)
Non-alcoholic Fatty Liver Disease , Obesity, Morbid , Female , Humans , Adipose Tissue/metabolism , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , Obesity, Morbid/metabolismABSTRACT
The autophagy gene ATG7 has been shown to be essential for the induction of autophagy, a process that used to be suppressed in nonalcoholic fatty liver disease (NAFLD). However, the specific role of ATG7 in NAFLD remains unclear. The aim of this study was to analyze hepatic ATG7 mRNA and ATG7 protein expression regarding obesity-associated NAFLD. Patients included women classified into normal weight (NW, n = 6) and morbid obesity (MO, n = 72). The second group was subclassified into normal liver (NL, n = 11), simple steatosis (SS, n= 29), and nonalcoholic steatohepatitis (NASH, n = 32). mRNA expression was analyzed by RT-qPCR and protein expression was evaluated by Western blotting. Our results showed that NASH patients presented higher ATG7 mRNA and ATG7 protein levels. ATG7 mRNA expression was increased in NASH compared with SS, while ATG7 protein abundance was enhanced in NASH compared with NL. ATG7 mRNA correlated negatively with the expression of some hepatic lipid metabolism-related genes and positively with endocannabinoid receptors, adiponectin hepatic expression, and omentin levels. These results suggest that ATG7-mediated autophagy may play an important role in the pathogenesis of NAFLD, especially in NASH, perhaps playing a possible protective role. However, this is a preliminary study that needs to be further studied.
Subject(s)
Non-alcoholic Fatty Liver Disease , Humans , Female , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Autophagy-Related Protein 7/genetics , Autophagy-Related Protein 7/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Liver/metabolism , Obesity/complications , Obesity/genetics , Obesity/metabolismABSTRACT
Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipocytokine secreted by adipocytes that seems to be linked with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the role of the SFRP5-wingless-MMTV integration site family member 5a (WNT5A) pathway, closely related to adipogenesis, in subcutaneous (SAT) and visceral adipose tissues (VAT) and its relationship with obesity-related NAFLD. Our cohort was composed of 60 women with morbid obesity (MO), who underwent hypocaloric diet, subclassified according to their hepatic histopathology and 15 women with normal weight. We observed increased SFRP5 mRNA expression in VAT and lower WNT5A expression in SAT in MO compared to normal weight. We found elevated SFRP5 expression in nonalcoholic steatohepatitis (NASH) in SAT and in mild simple steatosis (SS) and NASH in VAT. We observed higher WNT5A expression in SS compared to normal liver in SAT, and a peak of WNT5A expression in mild SS. To conclude, we reported increased SFRP5 mRNA expression in SAT and VAT of NAFLD-related to obesity subjects, suggesting an implication of the SFRP5-WNT5A pathway in NAFLD pathogenesis, probably due to the adipose tissue-liver axis. Since the mechanisms by which this potential interaction takes place remain elusive, more research in this field is needed.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Non-alcoholic Fatty Liver Disease , Obesity, Morbid , Adipose Tissue/metabolism , Diet, Reducing , Female , Humans , Intracellular Signaling Peptides and Proteins , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/genetics , Non-alcoholic Fatty Liver Disease/metabolism , Obesity/complications , Obesity/genetics , Obesity/metabolism , Obesity, Morbid/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolismABSTRACT
The surgically induced remission of liver disease represents a model to investigate the signalling processes that trigger the development of nonalcoholic steatohepatitis with the aim of identifying novel therapeutic targets. We recruited patients with severe obesity with or without nonalcoholic steatohepatitis and obtained liver and plasma samples before and after laparoscopic sleeve gastrectomy for immunoblotting, immunocytochemical, metabolomic, transcriptomic and epigenetic analyses. Functional studies were performed in HepG2 cells and primary hepatocytes. Surgery was associated with a decrease in the inflammatory response and revealed the role of mitogen-activated protein kinases. Nonalcoholic steatohepatitis was associated with an increased glutaminolysis-induced production of α-ketoglutarate and the hyperactivation of mammalian target of rapamycin complex 1. These changes were crucial for adenosine monophosphate-activated protein kinase/mammalian target of rapamycin-driven pathways that modulated hepatocyte survival by coordinating apoptosis and autophagy and affected methylation-related epigenomic remodelling enzymes. Hepatic transcriptome signatures and differentially methylated genomic regions distinguished patients with and without steatohepatitis. Our results suggest that the increased glutaminolysis-induced α-ketoglutarate production and the mammalian target of rapamycin complex 1 dysregulation play a crucial role in the inefficient adaptive responses leading to steatohepatitis in obesity.
Subject(s)
Laparoscopy , Non-alcoholic Fatty Liver Disease , Obesity, Morbid , Gastrectomy/methods , Humans , Ketoglutaric Acids , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/genetics , Obesity, Morbid/surgery , TOR Serine-Threonine KinasesABSTRACT
Olfactomedins (OLFMs) are a family of glycoproteins that play a relevant role in embryonic development and in some pathological processes. Although OLFM2 is involved in the regulation of the energy metabolism and OLFM4 is an important player in inflammation, innate immunity and cancer, the role of OLFMs in NAFLD-related intestinal dysbiosis remains unknown. In this study, we analysed the hepatic mRNA expression of OLFM2 and the jejunal expression of OLFM4 in a well-established cohort of women with morbid obesity (MO), classified according to their hepatic histology into normal liver (n = 27), simple steatosis (n = 26) and nonalcoholic steatohepatitis (NASH, n = 16). Our results showed that OLFM2 hepatic mRNA was higher in NASH, in advanced degrees of steatosis and in the presence of lobular inflammation. Additionally, we obtained positive correlations between hepatic OLFM2 and glucose, cholesterol, trimethylamine N-oxide and deoxycholic acid levels and hepatic fatty acid synthase, and negative associations with weight and jejunal Toll-like receptors (TLR4) and TLR5 expression. Regarding jejunal OLFM4, we observed positive correlations with circulating interleukin (IL)-8, IL-10, IL-17 and jejunal TLR9. In conclusion, OLFM2 in the liver seems to play a relevant role in NAFLD progression, while OLFM4 in the jejunum could be involved in gut dysbiosis-related inflammatory events.
Subject(s)
Extracellular Matrix Proteins , Glycoproteins , Granulocyte Colony-Stimulating Factor , Non-alcoholic Fatty Liver Disease , Dysbiosis/pathology , Extracellular Matrix Proteins/metabolism , Female , Glycoproteins/metabolism , Granulocyte Colony-Stimulating Factor/metabolism , Humans , Inflammation/metabolism , Inflammation/pathology , Liver/metabolism , Non-alcoholic Fatty Liver Disease/metabolism , RNA, Messenger/metabolismABSTRACT
Non-alcoholic fatty liver disease (NAFLD) extends from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Peripheral serotonin (5-HT) has become as an important regulator of different metabolic pathways. 5-HT has been related to obesity and lipid accumulation in the liver. The objective of this study was to assess the relationship between the 5-HT signaling pathway and the degree of NAFLD, as well as to investigate whether peripheral 5-HT levels are related to the hepatic and jejunal mRNA abundance of serotonin receptors (HTR) in a cohort of women with morbid obesity (MO) and NAFLD. ELISA was used to quantify the serum 5-HT from normal-weight subjects (n = 26) and patients with MO (n = 58). We used RTq-PCR analysis to evaluate the relative expression of HTR in women with MO with normal liver (n = 22), SS (n = 21), and NASH (n = 15). The 5-HT was diminished in women with MO under a hypocaloric diet, regardless of the presence of NAFLD. Additionally, we report a negative correlation of 5-HT levels with metabolic syndrome criteria, suggesting that serotonin may have a protective role in obesity. Additionally, the hepatic expression of HTR2A and HTR2B were decreased in women with MO and NAFLD, but no significant differences in the HTR jejunal expression according to the presence of NAFLD were found.
ABSTRACT
BACKGROUND & AIMS: Hepatic alterations, such as in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are frequently associated with obesity. To investigate the molecular mechanisms of these alterations and to identify molecules that could be used as potential therapeutic targets, we investigated the modulation of hepatic indices of oxidative stress and inflammation in obese patients undergoing laparoscopic sleeve gastrectomy (LSG). METHODS: Patients (nâ¯=â¯436) attending our obesity clinic underwent LSG for weight loss. We obtained a diagnostic intraoperative liver biopsy, and a sub-cohort (nâ¯=â¯120) agreed to a 1-year follow-up that included donation of blood samples and additional liver biopsies. Selected key molecules in blood and liver tissue were used to investigate the hepatic alterations in obesity, and their response to LSG. RESULTS: One year post-surgery, the prevalence of diabetes, dyslipidemia and hypertension decreased significantly. LSG improved liver histology features in all patients. Improvement was greater in severe cases of NAFLD including those with steatohepatitis, bridging fibrosis or cirrhosis. Significant pre-surgery differences in plasma, and liver markers of oxidative stress and inflammation (including chemokine C-C motif ligand 2, paraoxonase-1, galectin-3, and sonic hedgehog) were observed between patients with, and those without, NASH; post-surgery indicated consistent improvements in these parameters. CONCLUSION: Our study shows that the histology and liver function of patients with morbid obesity are significantly improved after LSG via mechanisms that involve the reduction of oxidative stress and inflammatory processes. These data encourage the use of LSG as a therapeutic option to improve, or resolve, NAFLD.
Subject(s)
Gastrectomy/methods , Inflammation/therapy , Non-alcoholic Fatty Liver Disease/surgery , Oxidative Stress , Adult , Biomarkers , Biopsy , Female , Humans , Inflammation/surgery , Laparoscopy , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/therapy , Obesity, Morbid/surgery , Treatment OutcomeABSTRACT
The objective of this study is to explore the longitudinal progression of atherosclerosis and the correlation between methods to measure the lesion in apolipoprotein E-deficient mice. Atherosclerosis progression was assessed by measurements of foam cell-rich depositions in their proximal aortas, and/or in surgically excised arteries, to assess the histological luminal narrowing. A longitudinal study was performed by comparing the values for carotid, aorta, and femoral and iliac arteries using common histological techniques. There were no significant differences in progression between different arteries, but correlation with the classical measurement of atherosclerosis in the aortic root was poor. Each laboratory requires specific standardization. Carotid arteries were sensitive to atherosclerosis in these mice, and progression was exponential. In conclusion, morphometric data show the importance of the choice of the duration of treatment, the appropriate controls, and the age at which to begin the experiments
El objetivo de este estudio es explorar la progresión longitudinal de la aterosclerosis y la correlación entre los métodos para medir la lesión en los ratones deficientes en apolipoproteína E. La progresión de la aterosclerosis se evaluó mediante mediciones de deposiciones ricas en células espumosas en las aortas proximales y/o en las arterias extirpadas quirúrgicamente para evaluar histológicamente el estrechamiento luminal. Se realizó un estudio longitudinal, y los valores para la carótida, la aorta, las arterias femorales e ilíacas se compararon mediante técnicas histológicas comunes. No hubo diferencias significativas en la progresión entre las diferentes arterias, pero la correlación con la medición clásica de la aterosclerosis en la raíz aórtica era pobre. Cada laboratorio requiere su normalización específica. Las arterias carótidas fueron sensibles a la aterosclerosis en estos ratones y la progresión fue exponencial. En conclusión, los datos morfométricos muestran la importancia en la elección de la duración del tratamiento, los controles apropiados y la edad a la cual comenzar los experimentos
Subject(s)
Animals , Rats , Atherosclerosis/physiopathology , Hypolipoproteinemias/physiopathology , Apolipoproteins E/deficiency , Disease Progression , Disease Models, Animal , Carotid Artery Diseases/physiopathologyABSTRACT
Introduction. Aspergillus tracheobronchitis is an uncommon manifestation of Aspergillus infection. This study retrospectively analysed patients presenting tracheobronchitis among non-neutropenic/non-transplant adult patients with at least two valuable cultures of respiratory samples yielding Aspergillus spp. in Spanish hospitals. Methods. Clinical records were retrospectively reviewed. Simple tracheobronchitis was considered when the bronchoscopy report described mucosal inflammation and mucus secretions and invasive tracheobronchitis when ulceration and pseudomembrane formation was reported. Cases were considered "proven" (histopathological confirmation) or probable aspergillar tracheobronchitis. Results. A total of 38 cases of tracheobronchitis (26 simple, 12 invasive) were identified, all considered probable aspergillar tracheobronchitis. Patients were elderly (89.5% patients were ≥65 years), males (76.3%), presented advanced COPD (GOLD III+IV in 81.3%) and heart insufficiency (55.3%), with higher APACHE II score in those with invasive tracheobronchitis (10.17±7.38 vs. 4.32±4.39, p=0.019). Up to 50% patients were taking steroids (accumulated doses >100 mg in 89.5% of them) and 34.2% antibiotics pre-admission. Antifungals were administered to 60.5% patients (57.7% with simple and 66.6% with invasive tracheobronchitis). Voriconazole was the most frequent antifungal (alone or in combination): 69.6% in the 23 treated patients (60.0% simple and 87.5% invasive tracheobronchitis). Mortality was 23.7% (15.4% in simple and 41.7% in invasive tracheobronchitis). Conclusions. The results of the present studty suggest that aspergillar tacheobronchitis should be considered in the differential diagnosis of non-immunocompromised patients with deteriorating chronic airway limitation (AU)
Introducción. La traqueobronquitis aspergilar es una manifestación poco frecuente de la infección por Aspergillus. Este estudio analiza de forma retrospectiva los pacientes que presentaron traqueobronquitis entre pacientes adultos no neutropénicos y sin trasplante con al menos dos cultivos de muestras respiratorias del tracto inferior mostrando crecimiento de Aspergillus spp. en hospitales españoles. Métodos. Se revisó retrospectivamente las historias clínicas y se consideró traqueobronquitis simple cuando el informe de la broncoscopia describía inflamación de la mucosa y secreción mucosa y traqueobronquitis invasiva ante la presencia de ulceraciones y pseudomembranas. Los casos se consideraron "probados" (confirmación histopatológica) o "probable traqueobronquitis aspergilar". Resultados. Se identificó un total de 38 casos de traqueobronquitis (26 simples, 12 invasivas), todos ellos considerados probable traqueobronquitis aspergilar. Los pacientes presentaban edad avanzada (89,5% de los pacientes con ≥65 años), eran varones en la mayoría de casos (76,3%), y presentaban enfermedad pulmonar obstructiva crónica avanzada (GOLD III+IV en el 81,3% de los casos) e insuficiencia cardiaca (55,3%), con una mayor puntuación en el APACHE II en aquellos pacientes con traqueobronquitis invasiva (10,17±7,38 vs. 4,32±4,39, p=0,019). Un 50% de los pacientes recibía esteroides (con dosis acumuladas >100 mg en el 89,5% de ellos) y un 34,2% antibióticos previos al ingreso. Se administró antifúngicos al 60,5% de los pacientes (al 57,7% de aquellos con traqueobronquitis simple y al 66,6% de los pacientes con traqueobronquitis invasiva). Voriconazol fue el antifúngico más utilizado (solo o en combinación): 69,6% de los 23 pacientes tratados (60,0% de los pacientes con traqueobronquitis simple que recibieron tratamiento y 87,5% de aquellos con traqueobronquitis invasiva que fueron tratados con antifúngicos). La mortalidad fue del 23,7% (15,4% en traqueobronquitis simple y 41,7% en traqueobronquitis invasiva). Conclusiones. Los resultados del presente estudio sugieren que la traqueobronquitis aspergilar debe considerarse en el diagnóstico diferencial en pacientes no inmunocomprometidos con deterioro crónico de la función respiratoria (AU)
Subject(s)
Humans , Tracheitis/epidemiology , Bronchitis/epidemiology , Pulmonary Aspergillosis/epidemiology , Aspergillus/isolation & purification , Retrospective Studies , Pulmonary Disease, Chronic Obstructive/epidemiology , Anti-Bacterial Agents/therapeutic use , Diagnosis, DifferentialABSTRACT
OBJECTIVE: Recent studies report the effect of bariatric surgery on glycaemia control and prevention of type-2-diabetes in obese patients. This study is about the pathophysiological mechanisms associated to these changes. DESIGN AND METHODS: Circulating levels of receptors of tumor necrosis factor (TNF-RI, TNF-RII), visfatin, high molecular weight (HMW) adiponectin, and C reactive protein (CRP) in 30 morbidly obese women (body mass index, BMI>40 kg/m(2) ) and 60 normal-weight controls (BMI>25 kg/m(2) ) were analyzed. Morbidly obese were studied at three time-points: before surgery (baseline), and 6 and 12 months after. RESULTS: After surgery, the levels of TNF-RI, TNF-RII, visfatin, and CRP were significantly lower than its baseline levels, whereas HMW adiponectin was higher. Fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA2-IR) levels were markedly lower postoperatively. High density lipoproteins (HDL) moderately increased, and triglyceride levels had sharply decreased. The study of the predictive value of variables indicated that preoperative levels of TNF-RI and visfatin correlated positively with levels of glucose, insulin, glycosylated hemoglobin A1c, and HOMA2-IR postoperatively, whereas adiponectin levels correlated negatively. Baseline CRP levels negatively linked to HDL and TNF-RII positively to triglyceride. CONCLUSIONS: The preoperative profile with high levels of proinflammatory adipocytokines is linked to smaller improvements in glucose homeostasis and lipid factors. The use of a range of biomarkers may predict the level of metabolic changes following bariatric surgery.
Subject(s)
Adipokines/blood , Bariatric Surgery , Obesity, Morbid/blood , Obesity, Morbid/surgery , Adult , Animals , Biomarkers/blood , Blood Glucose/metabolism , Body Mass Index , C-Reactive Protein/metabolism , Case-Control Studies , Cholesterol, HDL/blood , Diabetes Mellitus, Type 2/prevention & control , Female , Glycated Hemoglobin/metabolism , Humans , Insulin/blood , Insulin Resistance , Middle Aged , Nicotinamide Phosphoribosyltransferase/blood , Postoperative Period , Receptors, Tumor Necrosis Factor, Type I/blood , Receptors, Tumor Necrosis Factor, Type II/blood , Triglycerides/bloodABSTRACT
Se lleva a cabo un estudio de la evolución de la cirugía bariátrica experimental en animales de laboratorio y se determinan las necesidades actuales en este campo para el seguimiento de nuevas líneas de investigación.Se hace una revisión de los trabajos experimentales sobre cirugía de la obesidad mórbida desde la última mitad del siglo xx, según las diferentes técnicas existentes (malbsortivas, restrictivas, mixtas y experimentales). Las fuentes de información utilizadas han sido las búsquedas en la National Library of Medicine (PubMed).Se observa una clara tendencia a la utilización de animales de gran tamaño (cerdos) para el perfeccionamiento técnico, en especial de la laparoscopia.Una segunda dirección en la experimentación animal se centra en determinar un nexo metabolicoquirúrgico, que determinaría una mejoría de las comorbilidades. Por último, una tercera línea de investigación estaría centrada en la manipulación de la ingesta a partir de control central y vagal.Se necesitan estudios en que se combine la cirugía experimental en animales de laboratorio con los mecanismos que determinan su fisiopatología, su metabolismo y los que regulan su ingesta, tanto en las técnicas que están aplicadas a la práctica clínica como en las que están en fase experimental. Es necesario que los trabajos se realicen con animales obesos para conocer con exactitud los patrones metabólicos y evitar conclusiones erróneas sobre los mecanismos de la pérdida de peso (AU)
Subject(s)
Animals , Obesity, Morbid/surgery , Gastric Balloon , Gastroplasty/methods , Biliopancreatic Diversion/methods , Gastric Bypass/methods , Vagotomy/methodsABSTRACT
FUNDAMENTO Y OBJETIVO: En pacientes con enfermedad pulmonar obstructiva crónica (EPOC) en insuficiencia respiratoria aguda hipercápnica se ha demostrado que la ventilación mecánica no invasiva (VMNI) con soporte de presión (mediante el dispositivo BiPAP) puede mejorar los parámetros clínicos y fisiológicos. El objetivo de nuestro estudio ha sido evaluar, en un trabajo prospectivo y aleatorizado, los beneficios del tratamiento con VMNI aplicada a los pacientes ingresados en una planta de neumología por descompensación hipercápnica de su EPOC frente al tratamiento estándar en un hospital de tercer nivel. PACIENTES Y MÉTODO: Se incluyó en el estudio a 41 pacientes que se asignaron de forma aleatoria al grupo de tratamiento médico convencional (grupo control) o la VMNI con soporte de presión (BiPAP ST, Respironics Inc., Murrysville, PA, EE.UU.) además del tratamiento estándar. No hubo diferencias entre los dos grupos en los parámetros clínicos o fisiológicos en el momento del ingreso. RESULTADOS: En el grupo de tratamiento con VMNI se observó una reducción de la frecuencia respiratoria y mejoría del nivel de conciencia en las primeras 2 h respecto al grupo control (p < 0,001).Hubo también una mejoría significativa en las cifras de presión parcial de CO2 en sangre arterial (PaCO2) y pH a las 6 h de tratamiento (p < 0,05). En el grupo control tres pacientes (14 por ciento) requirieron soporte ventilatorio, mientras que sólo uno (5 por ciento) del grupo VMNI precisó intubación. La estancia hospitalaria fue significativamente menor en el grupo VMNI (7 frente a 10 días; p < 0,01). Hubo escasas complicaciones debidas al tratamiento con VMNI, que en general fue bien tolerada. CONCLUSIONES: La aplicación temprana de VMNI en los pacientes con descompensación hipercápnica de su EPOC consigue una mejoría clínica y fisiológica más rápida frente al tratamiento estándar. El uso de esta modalidad terapéutica en una planta convencional de neumología es factible (AU)
Subject(s)
Aged , Male , Female , Humans , Treatment Outcome , Prospective Studies , Respiratory Insufficiency , Pulmonary Disease, Chronic Obstructive , Blood Gas Analysis , Length of Stay , Intubation, Intratracheal , Intermittent Positive-Pressure Ventilation , Respiratory Function TestsABSTRACT
Diagnostica las deficiencias de la escuela peruana acrecentadas por la violencia y propone al magisterio nacional y a la sociedad civil soluciones democráticas, participativas, opuestas al autoritarismo ideológico, al centralismo esterilizante y a todo intento a vender adoctrinamiento por educación. Propone recobrar no sólo el espacio educativo sino usarlo para el desarrollo humano