ABSTRACT
Preterm neonates are at high risk of infectious and inflammatory diseases which require antibiotic treatment. Antibiotics influence neonatal gut microbiome development, and intestinal dysbiosis has been associated with delayed gastrointestinal transit. Neonates who take less time to pass meconium have a better tolerance to enteral feeding. We analyzed the effect of neonatal antibiotic treatment on the stool pattern and oral tolerance in 106 preterm infants < 33 weeks gestational age. Neonates were classified in 3 groups according to neonatal antibiotic (ABT) treatment days: no antibiotics, 3−7 d ABT, and ≥8 d ABT. Preterm infants from the ≥8 d ABT group took longer to pass meconium and to start green and yellow stools, took longer to reach 100 and 150 mL/kg/day, and reached reduced volumes in enteral feeds at day of life 14 and 28 than infants from no ABT and 3−7 d ABT groups. Multiple linear regression models showed that neonatal antibiotic treatment, birth weight, invasive mechanical ventilation, surfactant, enteral feeding start day, neonatal parenteral nutrition, and neonatal fasting days are associated with the stool pattern and oral tolerance in preterm infants.
ABSTRACT
During pregnancy, prolactin (PRL) is a neuro-immuno-cytokine that contributes actively to the crosstalk between the immune and endocrine systems and, thus, to the creation of an immune-privileged milieu. This work aims to analyze the capacity of PRL to modulate the synthesis and secretion of pro-inflammatory markers associated with labor. Studies were conducted using human fetal membranes at term mounted in a model of two independent chambers. The choriodecidual region was stimulated with 500-ng/mL lipopolysaccharide (LPS), and the amnion and choriodecidual region were co-simulated with different concentrations of PRL that can arise during pregnancy: 250, 500, 1000, and 4000ng/mL. Following these co-treatments, the tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, and IL-10 levels were measured in both compartments. As expected, treatment with LPS induced all cytokines to increase. Co-stimulation with the highest tested concentration of PRL induced significant decreases in TNF-α in the choriodecidual region and IL-1ß in both regions of the fetal membranes. PRL did not modified the IL-6 and IL-10 secretion profile. These findings, coupled with clinical evidence, suggest that the high level of PRL in the amniotic cavity is involved the mechanism by which the fetal-placental unit regulates the equilibrium between pro- and anti-inflammatory modulators.
Subject(s)
Amnion/immunology , Anti-Inflammatory Agents/metabolism , Decidua/immunology , Prolactin/metabolism , Cells, Cultured , Female , Humans , Immunomodulation , Inflammation Mediators/metabolism , Interleukin-10/metabolism , Lipopolysaccharides/immunology , Neuroimmunomodulation , Organ Culture Techniques , Placental Circulation , PregnancyABSTRACT
BACKGROUND & AIM: Adiponectin and ghrelin are hormones that participate in hepatic lipid metabolism, and their expression in liver tissue could have important implications for nonalcoholic fatty liver disease (NAFLD). The aim of this study was to evaluate the hepatic expression of ghrelin, adiponectin, AdipoR, and IL-6 in patients with NAFLD and normal liver. METHODS: We studied patients with clinical-pathological diagnosis of NAFLD or a normal liver. Patients were classified according to their diagnosis into three groups: normal liver, nonalcoholic hepatic steatosis, and nonalcoholic steatohepatitis (NASH). Adiponectin, AdipoR1, AdipoR2, IL-6, and ghrelin mRNA levels were assessed in biopsies by reverse transcriptase-polymerase chain reaction. RESULTS: Of the 21 patients, three had a normal liver biopsy, 14 had nonalcoholic steatosis, and four had NASH. Patients with NAFLD exhibited significantly higher HOMA-IR and triglyceride concentration (both P<0.05). There was a nonsignificant trend towards higher ghrelin expression in patients with NASH > nonalcoholic steatosis > normal liver. Patients with NASH had significantly higher mRNA adiponectin levels and lower IL-6 levels than did those with a normal liver (P<0.05). AdipoR expression did not differ significantly between groups. CONCLUSION: Adiponectin overexpression was observed in patients with NASH. The role of hepatic ghrelin in NAFLD requires further research.
Subject(s)
Fatty Liver/physiopathology , Ghrelin/genetics , Receptors, Adiponectin/genetics , Receptors, Ghrelin/genetics , Adiponectin/genetics , Adult , Biopsy , Cross-Sectional Studies , Fatty Liver/pathology , Female , Gene Expression , Humans , Interleukin-6/genetics , Liver/pathology , Liver/physiology , Male , Middle Aged , RNA, Messenger/metabolismABSTRACT
BACKGROUND AND OBJECTIVE: Iron overload has been associated with HFE mutations (C282Y and H63D). We investigated the association between these mutations and high serum ferritin in a sample of healthy adult men. DESIGN AND METHODS: We enrolled unrelated blood donors from three hospitals in Mexico City in a crosssectional study. Serum ferritin (SF) was determined to define iron overload, and HFE gene mutations were identified by PCR-RFLP. RESULTS: We evaluated 2524 male blood donors and included 246 individuals for each group. We identified 108 individuals with HFE gene mutation, 20.5 % were heterozygote (wt/H63D or wt/C282Y) and the remaining homozygote (H63D/ H63D). The genotype wt/C282Y was observed in two cases, none cases with C282Y/C282Y. The allelic frequency of H63D and C282Y was 0.115 and 0.002, respectively. We observed different association for H63D allele with iron overload (OR 1.54, CI 95 %1.16-2.03) and none in allele C282Y. Although values averages were different, the extreme dispersion of serum ferritin not showed statistically significant differences between H63D and C282Y alleles and ferritin concentrations. CONCLUSIONS: The male unrelated blood donors from Mexico City with iron overload prevalence of 13.8% hold similarities with other populations from Europe o America continent, respecting the allele frequency H63D. Nevertheless, allele frequency C282Y is lower than that observed in descendents from northern Europe. We have not observed statistic difference of SF or iron overload frequency by effect of both alleles.
Subject(s)
Blood Donors , DNA/genetics , Histocompatibility Antigens Class I/genetics , Iron Overload/genetics , Membrane Proteins/genetics , Mutation , Urban Population , Adolescent , Adult , Cross-Sectional Studies , Gene Frequency , Genetic Predisposition to Disease , Genotype , Hemochromatosis Protein , Humans , Iron Overload/blood , Iron Overload/epidemiology , Male , Mexico/epidemiology , Middle Aged , Polymerase Chain Reaction , Prevalence , Retrospective StudiesABSTRACT
OBJECTIVE: Investigate the association between polymorphisms in the leptin receptor gene associated with obesity and gallstone disease. DESIGN: We conducted a cross-sectional study, carried out at a tertiary setting. SUBJECTS: We enrolled 97 subjects, comprising 54 subjects with gallstones (cases) and 43 controls (without gallstones). MEASUREMENTS: Diet was assessed using a validated questionnaire for the Mexican population. Body mass index, waist circumference, serum glucose,insulin, leptin, lipids and lipoproteins levels were measured. Insulin resistance was calculated by HOMA-IR. Genomic DNA was isolated from lymphoblastoid cells, and Q223R and K656N polymorphisms in the leptin receptor gene were typed using polymerase chain reaction. Unconditional univariate logistic regression analysis was conducted to estimate the probability of gallstone disease associated with the polymorphisms as main effect. RESULTS: Cases were different in gender(40.74% males in cases vs 74.41% in controls; p < 0.001), older (49.74 vs 44.83 years; p < 0.05), and had more body fat (32.34% vs 28.14%; p = 0.01). Individuals carrying the polymorphism Q223R exhibited a higher BMI (28.44 +/- 6.6 kg/m2 vs 25.94 +/- 3.67 kg/m2, p < 0.05) and waist circumference (96.7 +/- 16.39 cm vs 89.2 +/- 11.05 cm, p < 0.05). In univariate analysis, we did not observe a relation between the presence of a R223 or N656 genotype and gallstone disease in our population (OR = 0.78, 95% CI 0.35-1.73). CONCLUSION: Obesity-related leptin receptor polymorphisms are not associated with gallstones disease.
Subject(s)
Gallstones/complications , Gallstones/genetics , Obesity/complications , Obesity/genetics , Receptors, Cell Surface/genetics , Adult , Female , Genetic Predisposition to Disease , Genotype , Humans , Insulin Resistance/genetics , Logistic Models , Male , Mexico , Middle Aged , Polymerase Chain Reaction , Polymorphism, Genetic , Receptors, LeptinABSTRACT
AIM: To explore the role of ghrelin in gallstone disease. METHODS: We carried out a cross-sectional study in 150 subjects, 38 with gallstones (cases) and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index (BMI), serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses (univariate and multivariate) were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations. RESULTS: Cases were statistically different from controls in gender distribution (P = 0.01), age (53 vs 44 yr, P = 0.002), BMI (28 vs 25; P = 0.004), and glucose (5.26 vs 4.98 mmol/L; P = 0.05). The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome (P < 0.05). In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value (OR = 0.27, 95%CI 0.09-0.82, P = 0.02). Twenty (20%) gallbladder specimens expressed ghrelin mRNA. CONCLUSION: Serum ghrelin concentrations are associated with a protective effect of GD.
Subject(s)
Gallbladder/physiopathology , Gallstones/blood , Gallstones/physiopathology , Peptide Hormones/blood , Adolescent , Adult , Aged , Aged, 80 and over , Body Mass Index , Case-Control Studies , Child , Cross-Sectional Studies , Female , Gallbladder/chemistry , Gallstones/prevention & control , Ghrelin , Humans , Insulin/blood , Lipids/blood , Male , Middle Aged , Peptide Hormones/analysis , Peptide Hormones/genetics , Peptide Hormones/physiology , RNA, Messenger/analysis , Regression Analysis , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
AIM: To establish an association between the serum leptin levels and the development of gallstone disease (GD). METHODS: We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two hundred and eighty-seven subjects were included: 97 cases with gallstones and 190 controls. Body mass index (BMI), fasting plasma leptin, insulin, serum lipid, and lipoprotein levels were measured. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Unconditional logistic regression analysis (univariate and multivariate) stratified by BMI was used to calculate the risk of GD. RESULTS: The multivariate conditional regression analysis revealed a model for those patients with BMI <30. The selected variables in the model were HOMA-IR index with OR = 1.31, P = 0.02 and leptin higher than median with OR = 2.11, P = 0.05. In the stratum of BMI >=30, we did not find a useful model. CONCLUSION: We concluded that insulin resistance and the development of GD appears to be associated with serum leptin levels in subjects with overweight, but not in obese subjects with similar metabolic profiles.
Subject(s)
Gallstones/blood , Gallstones/complications , Insulin Resistance , Leptin/blood , Obesity/blood , Obesity/complications , Adult , Body Weight , Case-Control Studies , Female , Humans , Male , Middle Aged , Regression AnalysisABSTRACT
Las metaloprotesas de matriz extracelular (MMP) son las mediadoras fisiológicas de la degradación de la colágena y su participación en la fisiopatogenia de la ruptura prematura de membranas ha sido sugerida por nuestro grupo. Con objeto de definir si algunas MMP se activan de manera coordinada con el trabajo de parto en las membranas fetales, analizamos la actividad enzimática y proteína inmunorreactiva presente en extractos de membranas obtenidas durante cesáreas, sin trabajo de parto, aunque su actividad/cantidad fue apenas detectable. En cambio los extractos de membranas fetales obtenidas durante el trabajo de parto activo, mostraron gran actividad/cantidad de ésta MMP. Con ayuda de un anticuerpo monoclonal, fue posible demostrar que la forma activa de la MMP-9 se podía encontrar sólo en las muestras con trabajo de parto. La MMP-9 y su ARN mensajero correspondiente fueron localizados por inmunohistoquímica e hibridación in situ en el epitelio amniótico, en algunos fibroblastos de la capa compacta y en células con características de trofoblasto en el corion. Se concluye que: 1. La actividad y la cantidad de la MMP-9 se incrementa de manera selectiva asociada al trabajo de parto y 2. que esta enzima es expresada por diferentes poblaciones celulares de la membrana fetal
Subject(s)
Collagen/physiology , Collagen/chemistry , Extracellular Matrix/enzymology , Extracellular Matrix/physiology , Extraembryonic Membranes/chemistry , Extraembryonic Membranes/enzymology , Extraembryonic Membranes/ultrastructure , Fetal Membranes, Premature Rupture/enzymology , Immunohistochemistry/instrumentation , Labor, Obstetric/physiology , Metalloproteases/biosynthesis , Metalloproteases/isolation & purification , Metalloproteases/physiologyABSTRACT
La ruptura de membranas corioamnióticas (RPM) está asociada a complicaciones perinatales y es la causa identificada más frecuente de parto pretérmino. A pesar de que la RPM se ha estudiado desde hace tiempo, en las actualidad hay controversia entre los mecanismos que la median y su etiopatogenia no ha sido bien comprendida. Actualmente se reconoce que el rompimiento de las membranas se asocia al aumento de presión intrauterina, siendo una diferencia que las membranas que se rompen en forma prematura son más débiles que las normales, sin embargo, la pura explicación mecánica parece incompleta, por lo que se han estudiado otros factores que podrían estar relacionados con la RPM entre los que se encuentran el infeccioso, el dietético y otros como pueden ser maniobras quirúrgicas, incompetencia ítsmico-cervical y polihidramnios. Por otro lado se han analizado aspectos moleculares relacionados con la RPM, estas comprenden studios sobre el metabolismo de la colégena que es principal constituyente de las membranas corioamnióticas, como resultado de ellos, se han propuesto diferentes niveles de daño que adectan tanto a la síntesis como a la degradación de la colágena
Subject(s)
Humans , Female , Pregnancy , Ascorbic Acid/supply & distribution , Fetal Membranes, Premature Rupture/etiology , Fetal Membranes, Premature Rupture/physiopathology , Amniotic Fluid/enzymology , Amniotic Fluid/physiology , Microbial Collagenase/biosynthesis , Microbial Collagenase/metabolism , Pregnancy Complications/etiologyABSTRACT
Antecedentes: Los mecanismos moleculares que median la ruptura prematura de membranas (RPM) son hasta el momento poco comprendidos. Recientemente se ha propuesto que la actividad de degradación aumentada de elementos del tejido conectivo en la membrana fetal, podría explicar el sedarrollo de la RPM. Objetivo: En este trabajo se analiza la modulación ejercida por la interleucina 1-alfa (IL-1-alfa) y la prostaglandina E2 (PGE2), que han sido propuestos como mediadores del trabajo de parto, en la expresión de metaloproteasas de matriz extracelular (MMP) por células del epitelio amniótico en cultivos primarios. Material y métodos: Las células fueron estimuladas con estos dos compuestos y se midió la actividad gelatinolítica presente en los medios, utilizando la técnica de geles-sustrato y de manera simultánea se extrajeron los ARNm, que se cuantificaron mediante la técnica de northern blot utilizando sondas de cDNA para MMp-1, MMP-2 y MMP-9. Resultados: La estimulación de las células epiteliales con IL-1-alfa y PGE2 resultó en aumento de la expresión del ARNm de MMP-1 y MMP-9, así como, disminución del correspondiente a MMP-2. Este patrón fue equivalente al encontrado en la actividad enzimática presente en los medios de cultivo, cuando se utilizó la técnica de geles sustrato. Discusión: La modulación ejercida por IL-1-alfa y PGE2 permite establecer una evidencia experimental que podría ligar la existencia de infección y el posterior desarrollo de RPM
