Alberto Maiz

Gut mucosal atrophy after a short enteral fasting period in critically ill patients.

PURPOSE The purpose of this study was to evaluate the presence of gut mucosal atrophy and changes in mucosal permeability in critically ill patients after a short fasting period. MATERIALS AND METHODS Fifteen critically ill patients underwent a period of enteral fasting of at least 4 days (mean 7.8 days). We took the following measurements the day before initiating enteral nutrition: indirect calorimetry, serum albumin, prealbumin, and lymphocyte count. We also performed a duodenal endoscopic biopsy with histopathological and mucosal morphometric analysis including villus height and crypt depth. The lactulose-mannitol test was performed to assess gut permeability. A total of 28 healthy volunteers served as controls for duodenal biopsy or lactulose-mannitol test. Clinical data, such as length of fasting, severity score, and previous parenteral nutritional support, were recorded. RESULTS We found gut mucosal atrophy, expressed as a decrease in villus height and crypt depth, in patients compared with controls. The patients also exhibited an abnormal lactulose-mannitol test. Morphometric changes did not correlate with permeability. Further, we found no correlation between the results of the lactulose-mannitol test and of mucosal morphometry with clinical data. CONCLUSIONS We found that a short period of enteral fasting was associated with significant duodenal mucosal atrophy and abnormal gut permeability in critically ill patients.

Medical and Surgical Treatments for Obesity Have Opposite Effects on Peptide YY and Appetite: A Prospective Study Controlled for Weight Loss

CONTEXT The effects of medical and surgical treatments for obesity on peptide YY (PYY) levels, in patients with similar weight loss, remain unclear. OBJECTIVE The objective of the study was to assess PYY and appetite before and after Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and medical treatment (MED). DESIGN This was a prospective, controlled, nonrandomized study. SETTING The study was conducted at the Departments of Nutrition and Digestive Surgery at a university hospital. PARTICIPANTS PARTICIPANTS included three groups of eight patients with similar body mass indexes (RYGB 37.8 +/- 0.8, SG 35.3 +/- 0.7, and MED 39.1 +/- 1.7 kg/m(2), P = NS) and eight lean controls (body mass index 21.7 +/- 0.7 kg/m(2)). MAIN OUTCOME MEASURES Total plasma PYY, hunger, and satiety visual analog scales in fasting and after ingestion of a standard test meal were measured. RESULTS At baseline there were no differences in the area under the curve (AUC) of PYY, hunger, or satiety in obese groups. Two months after the interventions, RYGB, SG, and MED groups achieved similar weight loss (17.7 +/- 3, 14.9 +/- 2.4, 16.6 +/- 4%, respectively, P = NS). PYY AUC increased in RYGB (P < 0.001) and SG (P < 0.05) and did not change in MED. PYY levels decreased at fasting, 30 min, and 180 min after a standard test meal in MED (P < 0.05). Hunger AUC decreased in RYGB (P < 0.05). Satiety AUC increased in RYGB (P < 0.05) and SG (P < 0.05). Appetite did not change in MED. PYY AUC correlated with satiety AUC (r = 0.35, P < 0.05). CONCLUSION RYGB and SG increased PYY and reduced appetite. MED failed to produce changes. Different effects occur despite similar weight loss. This suggests that the weight-loss effects of these procedures are enhanced by an increase in PYY and satiety.

Allelic Variants of Melanocortin 3 Receptor Gene (MC3R) and Weight Loss in Obesity: A Randomised Trial of Hypo-Energetic High- versus Low-Fat Diets

Introduction The melanocortin system plays an important role in energy homeostasis. Mice genetically deficient in the melanocortin-3 receptor gene have a normal body weight with increased body fat, mild hypophagia compared to wild-type mice. In humans, Thr6Lys and Val81Ile variants of the melanocortin-3 receptor gene (MC3R) have been associated with childhood obesity, higher BMI Z-score and elevated body fat percentage compared to non-carriers. The aim of this study is to assess the association in adults between allelic variants of MC3R with weight loss induced by energy-restricted diets. Subjects and Methods This research is based on the NUGENOB study, a trial conducted to assess weight loss during a 10-week dietary intervention involving two different hypo-energetic (high-fat and low-fat) diets. A total of 760 obese patients were genotyped for 10 single nucleotide polymorphisms covering the single exon of MC3R gene and its flanking regions, including the missense variants Thr6Lys and Val81Ile. Linear mixed models and haplotype-based analysis were carried out to assess the potential association between genetic polymorphisms and differential weight loss, fat mass loss, waist change and resting energy expenditure changes. Results No differences in drop-out rate were found by MC3R genotypes. The rs6014646 polymorphism was significantly associated with weight loss using co-dominant (p = 0.04) and dominant models (p = 0.03). These p-values were not statistically significant after strict control for multiple testing. Haplotype-based multivariate analysis using permutations showed that rs3827103–rs1543873 (p = 0.06), rs6014646–rs6024730 (p = 0.05) and rs3746619–rs3827103 (p = 0.10) displayed near-statistical significant results in relation to weight loss. No other significant associations or gene*diet interactions were detected for weight loss, fat mass loss, waist change and resting energy expenditure changes. Conclusion The study provided overall sufficient evidence to support that there is no major effect of genetic variants of MC3R and differential weight loss after a 10-week dietary intervention with hypo-energetic diets in obese Europeans.

Influence of polymeric enteral nutrition supplemented with different doses of glutamine on gut permeability in critically ill patients

OBJECTIVES To evaluate the effect of glutamine-supplemented polymeric enteral formulas on the recovery of gut-permeability abnormalities in critically ill patients. METHODS Twenty-three patients were randomized to receive a conventional casein-based enteral formula (ADN), ADN plus glutamine in a dose of 0.15 g x kg(-1) x d(-1) or ADN plus 0.30 g x kg(-1) x d(-1) of glutamine for 8 d. The lactulose mannitol permeability test (L/M) was performed at baseline and at the end of the study. Nineteen healthy volunteers served as controls for the L/M test. RESULTS An increase in permeability compared with control subjects was observed in patients at baseline (mean +/- standard error of the mean; L/M ratio: 0.11 +/- 0.03 and 0.025 +/- 0.004, respectively; P < 0.02). The L/M ratio improved after the period of enteral nutrition as a whole (initial L/M: 0.11 +/- 0.03, final L/M: 0.061 +/- 0.01; P < 0.03), but no difference was found between groups. CONCLUSIONS Even though polymeric enteral nutrition was associated with a significant improvement in the L/M ratio, glutamine supplementation did not show a specific influence in improving recovery of gut permeability in critically ill patients.

Prevalence of metabolic syndrome among Chilean adults

BACKGROUND There are several diagnostic criteria for Metabolic Syndrome (MS) definition. AIM To study their application in the Chilean general adult population. MATERIAL AND METHODS We analyzed data from a random sub sample of 1.833 adults aged 17 years and older surveyed during the First Chilean National Health Survey conducted in 2003. The prevalence of MS was estimated using the update Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF 2005) criteria. The distribution of MS was analyzed according to age, gender, educational level, geographic area, obesity and sedentary lifestyle. RESULTS The overall prevalence of MS was 31.6% (95% CI 28.5-34.9) and 36.8% (95% CI 33.5-40.3), according to update ATPIII-NCEP and IDF criteria respectively. Both criteria had a 90% concordance. Demographic and socioeconomic distribution was similar for both criteria. The prevalence of high blood pressure, high fasting glucose, and low HDL cholesterol (MS components) were: 46, 22 and 53% respectively. The prevalence of abnormal waist circumference was 30 and 59% according to update ATPIII-NCEP and IDF criteria, respectively. Using update ATPIII-NCEP criteria, the gender, age and educational level adjusted odds ratio (OR) for having MS was 9.59 (95% IC 6.8-13.6) for obese subjects compared with normal weight subjects and 2.14 (95% IC 1.3-3.7) for sedentary subjects compared with non sedentary. CONCLUSIONS There was a 90% agreement between update ATPIII-NCEP and IDF criteria for the diagnosis of MS. The overall prevalence of MS in this population was 32% usuing update ATPIII-NCEP criteria, with higher prevalence among obese and sedentary subjects.

Physiological and pathological implications of cholesterol.

Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review.

Influencia de la obesidad en los costos en salud y en el ausentismo laboral de causa médica en una cohorte de trabajadores

Background: The health associated costs of obesity can represent between 2% and 9% of the total health costs of a given country. Aim: To assess the impact of obesity on health care costs and absenteeism in a cohort of mine workers. Patients and wethods: Prospective study of 4.673 men, employees of a mining company, aged 49 ± 7 years that were followed for 24 ± 11 months. Total health care cost and days of sick leave were recordedfor each individual. The association between obesity and these variables was analyzed by logistic regression adjusting for co-morbidities, age and other variables. Results: Mean annual health care costs for obese workers were 17% higher (p CI 1.2 to 2.0), hypertension (OR 1,34, 95%> CI 1.2 to 1.6) and severe and morbid obesity (OR 1.50, 95%o CI 1.1 to 2.1). Conclusions: Obesity increases significantly health care costs and absenteeism

Retracted: Advances in the physiological and pathological implications of cholesterol

Cholesterol has evolved to fulfill sophisticated biophysical, cell signalling, and endocrine functions in animal systems. At the cellular level, cholesterol is found in membranes where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid‐protein membrane microdomains with critical topographical and signalling functions. At the organismal level, cholesterol is the precursor of all steroid hormones, including gluco‐ and mineralo‐corticoids, sex hormones, and vitamin D, which regulate carbohydrate, sodium, reproductive, and bone homeostasis, respectively. This sterol is also the immediate precursor of bile acids, which are important for intestinal absorption of dietary lipids as well as energy homeostasis and glucose regulation. Complex mechanisms maintain cholesterol within physiological ranges and the dysregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these conditions has been demonstrated by genetic and pharmacological manipulations in animal models of human disease that are discussed herein. Importantly, the understanding of basic aspects of cholesterol biology has led to the development of high‐impact pharmaceutical therapies during the past century. The continuing effort to offer successful treatments for prevalent cholesterol‐related diseases, such as atherosclerosis and neurodegenerative disorders, warrants further interdisciplinary research in the coming decades.

Tratamiento y prevención de la mucositis oral asociada al tratamiento del cáncer

One of the most common and troublesome complications of modern intensive anticancer treatments is oral mucositis. The purpose of this review is to summarize current evidence and clinical guidelines regarding its prevention and therapy. The use of keratinocyte growth factor-1, supplementary glutamine and other recently developed treatment modalities are discussed. The injury of the oral mucosa caused by antineoplastic agents promotes the local expression of multiple pro-inflammatory and pro-apoptotic molecules and eventually leads to the development of ulcers. Such lesions predispose patients to several infectious and nutritional complications. Also, they lead to modification of treatment schedules, potentially affecting overall prognosis. Local cryotherapy with ice chips and phototherapy with low energy laser may be useful as preventive measures. Mouthwashes with allopurinol and phototherapy with low energy laser can be used as treatment. In radiotherapy, special radiation administration techniques should be used to minimize mucosal injury. Pain control should always be optimized, with the use of patient controlled analgesia and topical use of morphine. Supplemental glutamine should not be used outside of research protocols. Lastly, thorough attention should be paid to general care and hygiene measures.

APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family

BackgroundSevere hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family.MethodsWe carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives.ResultsA large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls.ConclusionThe Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.