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1.
Dis Esophagus ; 28(8): 705-10, 2015.
Article in English | MEDLINE | ID: mdl-25164712

ABSTRACT

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized pathologically by eosinophil infiltration. In addition to loss of barrier integrity, a dominant T Helper 2-associated immune response and strong allergic connection, the esophagus tissue undergoes dramatic changes, with frequent presence of mucosal rings, strictures, linear furrows, and trachealization. Although the inflammatory mechanisms behind this disease are being increasingly well understood, the structural features remain unexplained. We examined the expression of key members of the Wnt-signaling pathway in biopsies from patients with EoE. This pathway has been shown to be critically important in regulating cellular homeostasis, growth, and differentiation and to be dysregulated in several disease conditions. Biopsies from adult EoE patients were collected by endoscopy and mRNA extracted. After cDNA synthesis, the relative gene expression from key upstream (secreted frizzled-related protein 1) and downstream (c-myc and Cyclin D1) molecules in the Wnt pathway, as well as several Wnt pathway members (Wnt1, Axin1, low-density lipoprotein receptor-related protein 6, glycogen synthase kinase 3 beta, and ß-catenin), were determined. Biopsies from patients with EoE displayed significantly higher expression of secreted frizzed-related protein 1 than controls, as well as reductions in Cyclin D1 and c-myc. In contrast, there were no differences in the Wnt pathway molecules. The levels of expression of Cyclin D1 and c-myc, as well as ß-catenin, in EoE patients showed strong correlations with the frequency of esophageal eosinophils. Our findings suggest that although there are no changes in the overall levels of key Wnt pathway genes in adult EoE, there is evidence for dysregulation of upstream and downstream regulators of Wnt signaling. Importantly, the associations with eosinophilia suggest that these may participate in the pathogenesis of this disease and be markers of disease severity.


Subject(s)
Eosinophilic Esophagitis/genetics , Wnt Signaling Pathway/genetics , Adult , Axin Protein/genetics , Biopsy , Cyclin D1/genetics , Eosinophilic Esophagitis/pathology , Eosinophils/pathology , Esophagoscopy , Esophagus/pathology , Female , Genes, myc/genetics , Genetic Markers/genetics , Glycogen Synthase Kinase 3/genetics , Glycogen Synthase Kinase 3 beta , Glycoproteins , Humans , Intracellular Signaling Peptides and Proteins , Low Density Lipoprotein Receptor-Related Protein-6/genetics , Male , Prospective Studies , RNA, Messenger/analysis , Wnt1 Protein/genetics , beta Catenin/genetics
2.
Int J Obes (Lond) ; 36(3): 336-41, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22143620

ABSTRACT

BACKGROUND: Nonalcoholic fatty liver disease is a common finding in obese subjects. Increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome. OBJECTIVE: Aim of this longitudinal study was to evaluate the relationships between several anthropometric measures, including the hepatic left lobe volume (HLLV), and various indicators of the metabolic syndrome in a cohort of severely obese women before and after laparoscopic adjustable gastric banding (LAGB). STUDY DESIGN AND RESULTS: Seventy-five obese women (mean age 45 ± 10 years and body mass index (BMI) 42.5 ± 4.8 kg m(-2)) underwent LAGB and completed an average (± s.d.) post-surgical follow-up of 24 ± 6 months. Determination of HLLV, subcutaneous and intra-abdominal fat (IAF) was based on ultrasound. The principal component statistical analysis applied to pre-operative measurements, highlighted HLLV as a parameter that clustered with serum insulin, IAF, serum glucose and uric acid, along with triglycerides (TGs), alkaline phosphatase and high-density lipoprotein cholesterol. After LAGB, the average reduction of BMI was 23%, 12% for subcutaneous fat (SCF), 42% for HLLV and 40% for visceral fat. Among body weight, BMI, SCF, IAF and HLLV, reduction of the latter was an independent predictor of reduction of serum transaminases and γ-Glutamyltransferase, glucose, insulin and TGs. CONCLUSIONS: In severely obese women: (i) HLLV is a sensitive indicator of ectopic fat deposition, clustering with parameters defining the metabolic syndrome; (ii) weight loss achieved by LAGB is associated with a reduction of liver volume as estimated by HLLV; (iii) among various anthropometric parameters measured, reduction of HLLV that follows LAGB represents the best single predictor of improvement of various cardiometabolic risk factors.


Subject(s)
Fatty Liver/pathology , Gastroplasty , Intra-Abdominal Fat/pathology , Liver/pathology , Obesity, Morbid/metabolism , Obesity, Morbid/pathology , Adult , Aged , Analysis of Variance , Fatty Liver/metabolism , Female , Follow-Up Studies , Gastroplasty/methods , Humans , Liver/metabolism , Longitudinal Studies , Metabolic Syndrome/etiology , Metabolic Syndrome/prevention & control , Middle Aged , Non-alcoholic Fatty Liver Disease , Obesity, Morbid/complications , Obesity, Morbid/surgery , Organ Size , Postoperative Period , Preoperative Period , Weight Loss
3.
Obes Surg ; 19(4): 467-74, 2009 Apr.
Article in English | MEDLINE | ID: mdl-18923878

ABSTRACT

BACKGROUND: Adiponectin has antisteatosis-anti-inflammatory properties and its circulating levels are reduced in nonalcoholic steatohepatitis (NASH). METHODS: To assess the role of adiponectin in NASH, we measured expression of adiponectin gene (APM1) and receptors (AdipoR1/AdipoR2) in liver and subcutaneous and visceral fat in subjects with biopsy-proven NASH or pure steatosis (PS). In 103 subjects undergoing gastric bypass or elective abdominal surgery (17 with normal liver histology (C), 52 with PS, and 34 with NASH), RNA was extracted from tissue samples, and quantification of APM1, AdipoR1, and AdipoR2 was carried out by real-time polymerase chain reaction. RESULTS: In NASH vs C, circulating adiponectin levels (3.6[2.4] vs 5.3[4.3] microg/ml, median[interquartile range], p < 0.05) and adiponectin concentrations, APM1, AdipoR1, and AdipoR2 expression in visceral fat were all reduced (p < or = 0.03). These differences disappeared when adjusting for obesity. In contrast, liver AdipoR1 (1.40 [0.46] vs 1.00 [0.32] of controls) and AdipoR2 expression (1.20 [0.41] vs 0.78 [0.43]) were increased in NASH, and group differences were statistically significant (p < 0.0001 for AdipoR1 and p = 0.0001 for AdipoR2). Results for PS were generally intermediate between NASH and C. Liver receptor expression was reciprocally related to circulating adiponectin (rho = -0.42, p < 0.003 for AdipoR1 and rho = -0.26, p < 0.009 for AdipoR2). In multivariate models adjusting for sex, age, fasting plasma glucose, and obesity, liver enzymes levels were directly related to both AdipoR1 and AdipoR2 expression in liver. CONCLUSION: In obese patients with NASH, adiponectin receptors are underexpressed in visceral fat-as a likely correlate of obesity-but overexpressed in liver, possibly as a compensatory response to hypoadiponectinemia, and positively associated with liver damage.


Subject(s)
Fatty Liver/metabolism , Liver/metabolism , Receptors, Adiponectin/metabolism , Adiponectin/metabolism , Adult , Diabetes Mellitus, Type 2/metabolism , Female , Humans , Intra-Abdominal Fat/metabolism , Male , Middle Aged , Obesity/metabolism
4.
J Endocrinol Invest ; 30(2): 104-10, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17392599

ABSTRACT

Non-alcoholic fatty liver disease is a common finding in obese subjects, and increasing evidence has been provided suggesting that it represents the hepatic component of the metabolic syndrome. The aim of this study was to evaluate whether the extent of liver enlargement is related to the severity of the metabolic syndrome in obese women. The relationship between ultrasound- measured hepatic left lobe volume (HLLV) and various features of the metabolic syndrome was evaluated in 85 obese women. The mean+/-SD value of HLLV in obese women was 431+/-214 ml (range 46-1019 ml) while it was 187+/-31 ml (range 143-258 ml) in lean subjects. In a multiple logistic regression analysis, ultrasound-measured intra-abdominal fat was the only anthropometric measure independently associated with HLLV. A strong positive association was found between HLLV and serum liver enzymes, triglycerides, glucose, insulin, uric acid, C reactive protein, systolic and diastolic blood pressure, while a negative correlation was observed between HLLV and HDL cholesterol. The values of HLLV corresponding to the cut-off values of various risk factors for the diagnosis of the metabolic syndrome were calculated, yielding a mean value of 465 ml. In conclusion, ultrasound measurement of HLLV represents a simple, reliable and low-cost tool for the evaluation of liver involvement in the metabolic syndrome. The strong association between liver enlargement and various cardiovascular risk factors associated with insulin resistance supports the role of liver steatosis as an important link among the many facets of the metabolic syndrome in human obesity.


Subject(s)
Liver/anatomy & histology , Liver/diagnostic imaging , Metabolic Syndrome/diagnostic imaging , Obesity/diagnostic imaging , Adult , Aged , Body Mass Index , Fatty Liver/complications , Fatty Liver/diagnostic imaging , Fatty Liver/pathology , Female , Humans , Intra-Abdominal Fat/diagnostic imaging , Intra-Abdominal Fat/pathology , Liver/pathology , Metabolic Syndrome/complications , Metabolic Syndrome/pathology , Middle Aged , Obesity/complications , Ultrasonography
5.
Int J Obes (Lond) ; 30(6): 948-56, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16446750

ABSTRACT

BACKGROUND: The aim of this study was to evaluate the relationship between insulin resistance and preclinical abnormalities of the left ventricular structure and function detected in severe obesity by Color Doppler Myocardial Imaging (CDMI). Forty-eight consecutive severely obese patients (Group O) (11 males, 37 females, mean age 32.8+/-7 years) were enrolled. Forty-eight sex- and age-matched non-obese healthy subjects were also recruited as controls (Group C). All subjects underwent conventional 2D-Color Doppler echocardiography and CDMI. The homeostasis model assessment insulin resistance index (HOMA-IR) was used to assess insulin resistance results. Obese subjects had a greater left ventricular mass index (by height) (58.8+/-14 g/m(2.7)) than controls (37+/-8 g/m(2.7)) (P<0.0001), owing to compensation response to volume overload caused by a greater cardiac output (P<0.02). Preload reserve was increased in obese subjects, as demonstrated by a significant increase in left atrial dimension (P<0.0001). Obese patients had a slightly reduced LV diastolic function (transmitral E/A ratio: Group O, 1.1+/-0.8 vs Group C, 1.5 +/-0.5; P<0.002). Cardiac deformation assessed by regional myocardial systolic strain and strain rate (SR) values was significantly lower (abnormal) in obese patients than in controls, both at the septum and lateral wall level. These strain and SR abnormalities were significantly related to body mass index. In addition, the early phase of diastolic function, evaluated using SR, was compromised in obese patients (P<0.001). The HOMA-IR values in obese patients were significantly higher (3.09+/-1.6) than those determined in the control group (0.92+/-0.5) (P<0.0001). The HOMA-IR values, in the obese group, were significantly related to systolic strain and SR values sampled at the septum level (P<0.0001). CONCLUSION: In conclusion, this study has demonstrated that obese patients pointed out systolic structural and functional abnormalities at a preclinical stage, in particular through strain and SR analysis; on the other hand, those altered CDMI parameters well distinguish obese subjects as compared with the control group. Furthermore, another main finding of the study was that myocardial deformation (systolic strain) could have a correlation with insulin resistance level.


Subject(s)
Insulin Resistance , Obesity, Morbid/complications , Ventricular Dysfunction, Left/etiology , Adult , Anthropometry , Blood Flow Velocity , Body Mass Index , Echocardiography, Doppler, Color , Exercise Test , Female , Humans , Male , Middle Aged , Mitral Valve/diagnostic imaging , Mitral Valve/physiopathology , Obesity, Morbid/diagnostic imaging , Obesity, Morbid/physiopathology , Sensitivity and Specificity , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology
6.
J Endocrinol Invest ; 27(2): RC5-7, 2004 Feb.
Article in English | MEDLINE | ID: mdl-15129802

ABSTRACT

Thyroid dysfunction is associated with metabolic changes that affect mass and adipocyte function, as well as lipid and carbohydrate metabolism. Adipose tissue performs complex metabolic and endocrine functions. Leptin and adiponectin are two of the most important adipocytokines, both involved in the regulation of intermediate metabolism. The aim of this study was to evaluate the relationships between thyroid status and circulating levels of the two adipose tissue hormones. We studied 15 patients with hyperthyroidism, 15 patients with hypothyroidism and 15 euthyroid subjects, all matched by sex, age and body mass index (BMI). Serum concentrations of free thyroxine, free tri-iodothyronine, thyrotropin, leptin and adiponectin and anthropometric parameters (weight, height, BMI) were assessed. No significant difference was found among the 3 groups, as assessed by Student's t-test, both for adiponectin and leptin. We conclude that metabolic changes associated with thyroid dysfunction are not related to variations in serum levels of adiponectin or leptin.


Subject(s)
Adipose Tissue/metabolism , Intercellular Signaling Peptides and Proteins , Leptin/blood , Proteins/metabolism , Thyroid Gland/metabolism , Adiponectin , Adult , Anthropometry , Case-Control Studies , Female , Humans , Hyperthyroidism/metabolism , Hypothyroidism/metabolism , Male , Middle Aged , Thyrotropin/blood , Thyroxine/blood , Triiodothyronine/blood
8.
11.
Rev. bras. saúde ocup ; 10(38): 58-62, 1982.
Article in Portuguese | LILACS | ID: lil-8286

ABSTRACT

Os autores constatam a falta de esclarecimento e de conscientizacao acerca dos direitos trabalhistas concedidos a gestante e ao seu produto conceptual, tanto no periodo pre como no pos-parto. Destacam as possibilidades previstas por legislacao como, a alteracao funcional, a transferencia de locais insalubres ou impregnados de agentes patologicos prejudiciais, para locais salubres e, ainda, a existencia de local apropriado e tempo necessario a amamentacao. A proposito do desenvolvimento tecnologico, consideram que o dispendio de forca fisica prejudicial no periodo gestacional e puerperal tenha diminuido sensivelmente, fato esse que possibilita a mulher desempenhar suas funcoes profissionais, principalmente nos paises desenvolvidos e em vias de desenvolvimento


Subject(s)
Pregnancy , Women's Rights , Work
13.
Science ; 209(4460): 1028-9, 1980 Aug 29.
Article in English | MEDLINE | ID: mdl-7403865

ABSTRACT

When tsetse flies are fed on human blood, the hemolymph of the flies contains human albumin. If the flies then ingest antibodies to human albumin, they die within a short time. The albumin fraction in their hemolymph disappears and osmoregulation is severely disturbed.


Subject(s)
Antibodies , Insect Control/methods , Serum Albumin/immunology , Tsetse Flies/immunology , Animals , Hemolymph/metabolism , Tsetse Flies/metabolism , Water-Electrolyte Balance
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