Acute phase markers in obese children and adolescents with metabolic disorders

ABSTRACT Introduction. Obesity is a worldwide public health problem and the most common non-communicable chronic disease. It is associated with an increase in inflammatory acute phase proteins and proinflammatory cytokines. Objective. To assess the levels of acute phase proteins in obese children and adolescents with hepatic steatosis and metabolic syndrome. Methodology. Forty-five children with a body mass index ≥ 95th percentile aged 5.0-15.5 years were included. The following acute phase reactants were determined: C-reactive protein, haptoglobin, alpha-2-macroglobulin, and apolipoprotein A-1; besides, an ultrasound was done to assess hepatic steatosis. Results. C-reactive protein levels increased in all patients. Patients with metabolic syndrome also had high levels of apolipoprotein A-1 and haptoglobin. Patients with hepatic steatosis had a significant increase in alpha-2-macroglobulin in addition to high C-reactive protein. Key words: obesity, C-reactive protein, haptoglobins, alpha-2macroglobulins, apolipoprotein A-1

Review of plants with hepatoprotective activity evaluated in Mexico

Liver diseases represent a major health problem around the world. in Mexico these are the 5th leading cause of death in the economically active population. in Mexico, it is estimated that about 60% of the population uses some medicine from plants to treat their illnesses. The purpose of this work was to search for medicinal plants in Mexico that have been evaluated for their hepatoprotective effect in different models. in this review we found only 13 plants evaluated for hepatoprotective activity: Amole tuber, Cochlospermum vitifolium, Heterotheca inuloides, Hibiscus sabdariffa, Leucophyllum frutescens, Prostechea michuacana, Psidium Guajava, Rosmarinus officinalis, Verbena Carolin, Centaurea americana, Juglans mollis, Krameria ramossisima and Turnera diffusa. This study describes the studies conducted in Mexico for each of them and the international literature reports of pharmacological and phytochemical studies

In vitro assessment of hepatoprotective agents against damage induced by acetaminophen and CCl4

Abstract Background: In vitro bioassays are important in the evaluation of plants with possible hepatoprotective effects. The aims of this study were to evaluate the pretreatment of HepG2 cells with hepatoprotective agents against the damage induced by carbon tetrachloride (CCl4) and paracetamol (APAP). Methods: Antioxidative activity was measured using an assay to measure 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging. The in vitro hepatotoxicity of CCl4 and APAP, and the cytotoxic and hepatoprotective properties of silymarin (SLM), silybinin (SLB), and silyphos (SLP) were evaluated by measuring cell viability; activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH); total antioxidant capacity (TAOxC); and reduced glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (malondialdehyde (MDA) levels). Results: Only SLB and SLM showed strong antioxidative activity in the DPPH assay (39.71±0.85 μg/mL and 14.14±0. 65 μg/mL, respectively). CCl4 induced time- and concentration-dependent changes. CCl4 had significant effects on cell viability, enzyme activities, lipid peroxidation, TAOxC, and SOD and GSH levels. These differences remained significant up to an exposure time of 3 h. APAP induced a variety of dose- and time-dependent responses up to 72 h of exposure. SLM, SLB, and SLP were not cytotoxic. Only SLB at a concentration of 100 μg/mL or 150 μg/mL significantly decreased the enzyme activities and MDA level, and prevented depletion of total antioxidants compared with CCl4. Conclusions: CCl4 was more consistent than APAP in inducing cell injury. Only SLB provided hepatoprotection. AST, LDH, and MDA levels were good markers of liver damage. Keywords: Hepatoprotective, HepG2 cell line, Acetaminophen, Carbon tetrachloride, Silybinin, Silyphos, Silymari

Urinary protein detection by iTRAQ® associated with renal transplant complications and its modification with therapy

AbstractBackgroundAfter renal transplant, surgical, infection complications, as well as graft rejection may occur; early detection through non-invasive markers is the key to change therapy and avoid biopsy.ObjectiveThe aim of the study is to determine urine protein profiles in patients undergoing renal transplant with complications and detect its variation when therapy is modified.Material and methodsUrine samples were collected from patients prior the transplant and various postoperative stages. Urinary protein profiles were obtained by peptide labelling using isobaric isotopes for relative quantification (iTRAQ®).ResultsA total of 22 patients were included, of whom 12 developed post-transplant complication: 2 with graft rejection (1 male and 1 female) and 10 (6 males and 4 females) in the group of post-transplant infections. Using iTRAQ® 15/345 and 28/113 proteins were identified and fulfilled the acceptance criteria, in graft rejection and post-transplant infections group, respectively.ConclusionsAlbumin was the only protein found in both groups, the remaining proteins were different. The five proteins with higher scores in graft rejection were: alpha-1-microglobulin, 5′-nucleotidase cytosolic III, retinol-binding protein 4, membrane protein palmitoylated 4, and serine carboxypeptidase, while post-transplant infections were: mitochondrial acetyl-coenzyme A synthetase, putative adenosyl homocysteinase 2, zinc finger protein GLIS1, putative protein FAM157B, and zinc finger protein 615. It remains to elucidate the involvement of each of these in patients with renal transplantation

Low dose of sublingual immunotherapy in patients with allergic rhinitis in a randomized double-blind placebocontrolled study

Background: Few placebo controlled studies for sublingual immunotherapy (SLIT) have been performed so far in Latin America, and some issues like treatment scheme and doses remain uncertain Objective: to asses improvement in nasal, pharyngeal and ocular symptoms with low doses of SLIT to Dermatophagoides pteronyssinus comparing it with a placebo, in a Mexican population with allergic rhinitis (AR). Methods: a prospective, double-blind placebo-controlled, randomized study, with 32, patients with chronic, moderate to severe AR; 16 patients were treated with SLIT and 16 with placebo for 6 months with a total dose of D. pteronyssinus (Der p1) of 50.4 mcg. Nasal, pharyngeal and ocular symptoms were monitored using a symptoms diary to evaluate the degree of improvement and reduction in the use of medication. Results: Significant lower symptom and drug scores were found in SLIT group where 85% of patients showed clinical improvement. On the placebo group, 24% of patients improved and 76% had no response or worsened; 94% of patients on SLIT required less symptomatic medication compared with the placebo group. There was a reduction in positivity to cutaneous test to D. pteronyssinus in 50% of the patients on SLIT, whereas placebo patients remained all positiv

Cytokine inflammation state in non-alcoholic steatohepatitis surpasses that of chronic hepatits C and alcoholic liver disease

Increased serum levels of cytokines were reported in persistent inflammatory conditions such as non-alcoholic steatohepatitis (NASH), chronic hepatitis C (CHC) and alcoholic liver disease (ALD). The aim of this study was to compare cytokines IL-6, TNF-α, VEGF, EG-VEGF, BB-PDGF and ICAM-1 levels in these patients. Ninety patients seen in two Mexican outpatient clinics (Liver Unit, UANL and HIPAM and UNAM) were included: NASH (30), CHC (30) and ALD (30). Serum cytokines IL-6, TNF-α, VEGF, EG-VEGF, BB-PDGF and ICAM-1 were measured by ELISA. A statistically significant difference was found in 5/6 mediators studied in NASH patients vs. CHC and ALD. Regarding ICAM-1 (5.482±613 vs. 2.145±1011 vs. 1.830±1224 pg/mL; P<0.05; respectively), IL-6 (2.430±1506 vs. 726±735 vs. 516±603 pg/mL; P<0.05, respectively), TNF-α (3686±1409 vs. 677±747 vs. 437±70 pg/mL; P<0.05; respectively), VEFG (2.267±486 vs. 421±557 vs. 554±619 pg/mL; P<0.05; respectively) and EG-VEGF (2.146±1914 vs. 1.225±1388 vs. 799±1046 pg/mL; P<0.05; respectively). VEGF positively correlated with TNF-α(r+0.51 and P=0.004) in NASH and negatively in CHC (r-0.44 and P=0.01). The only positive correlation for BB-PDGF was with EG-VEGF levels (r=+0.41 and P=0.02). IL-6 exhibited a positive correlation vs. ICAM-1 in ALD (r+0.42 and P=0.02). We demonstrated a significant increase in pro-inflammatory cytokines (TNF-α, IL-6, VEGF and EG-VEGF) and ICAM-1 in patients with NASH. Correlations showed differential cytokine and adhesion molecule patterns on the basis of the liver disease etiology. These abnormalities in cytokine profile can influence the pathophysiology of liver injury

Subclinical abnormal glucose tolerance is a predictor of death in liver cirrhosis

AIM: To determine if subclinical abnormal glucose tolerance (SAGT) has influence on survival of non-diabetic patients with liver cirrhosis. METHODS: In total, 100 patients with compensated liver cirrhosis and normal fasting plasma glucose were included. Fasting plasma insulin (FPI) levels were measured, and oral glucose tolerance test (OGTT) was performed. According to OGTT results two groups of patients were formed: those with normal glucose tolerance (NGT) and those with SAGT. Patients were followed every three months. The mean follow-up was 932 d (range of 180-1925). Survival was analyzed by the Kaplan-Meyer method, and predictive factors of death were analyzed using the Cox proportional hazard regression model. RESULTS: Of the included patients, 30 showed NGT and 70 SAGT. Groups were significantly different only in age, INR, FPI and HOMA2-IR. Patients with SAGT showed lower 5-year cumulated survival than NGT patients (31.7% vs 71.6%, P = 0.02). Differences in survival were significant only after 3 years of follow-up. SAGT, Child-Pugh B, and high Child-Pugh and Model for EndStage Liver Disease (MELD) scores were independent predictors of death. The causes of death in 90.3% of cases were due to complications related to liver disease. CONCLUSION: SAGT was associated with lower survival. SAGT, Child-Pugh B, and high Child-Pugh and MELD scores were independent negative predictors of survival

Spironolactone Effect in Hepatic Ischemia/Reperfusion Injury in Wistar Rats

Introduction. Ischemia/reperfusion (IR) injury, often associated with liver surgery, is an unresolved problem in the clinical practice. Spironolactone is an antagonist of aldosterone that has shown benefits over IR injury in several tissues, but its effects in hepatic IR are unknown. Objective. To evaluate the effect of spironolactone on IR-induced damage in liver. Materials and Methods. Total hepatic ischemia was induced in rats for 20 min followed by 60 min of reperfusion. Spironolactone was administered and hepatic injury, cytokine production, and oxidative stress were assessed. Results. After IR, increased transaminases levels and widespread acute inflammatory infiltrate, disorganization of hepatic hemorrhage trabeculae, and presence of apoptotic bodies were observed. Administration of SPI reduced biochemical and histological parameters of liver injury. SPI treatment increased IL-6 levels when compared with IR group but did not modify either IL-1β or TNF-α with respect to IR group. Regarding oxidative stress, increased levels of catalase activity were recorded in IR + SPI group in comparison with group without treatment, whereas MDA levels were similar in IR + SPI and IR groups. Conclusions. Spironolactone reduced the liver damage induced by IR, and this was associated with an increase in IL-6 production and catalase activity

Advantages of adipose tissue stem cells over CD34+ mobilization to decrease hepatic fibrosis in Wistar rats

Introduction and Objectives: Chronic liver inflammation may lead to hepatic cirrhosis, limiting its regenerative capacity. The clinical standard of care is transplantation, although stem cell therapy may be an alternative option. The study aim was to induce endogenous hematopoietic stem cells (HSCs) with granulocyte colony stimulating factor (G-CSF) and/or intravenous administration of adipose tissue-derived mesenchymal stem cells (MSCs) to decrease hepatic fibrosis in an experimental model. Material and methods: A liver fibrosis model was developed with femaleWistar rats via multiple intraperitoneal doses of carbon tetrachloride. Three rats were selected to confirm cirrhosis, and the rest were set into experimental groups to evaluate single and combined therapies of G-CSF-stimulated HSC mobilization and intravenous MSC administration. Results: Treatment with MSCs and G-CSF significantly improved alanine amino transferase levels, while treatment with G-CSF, MSCs, and G-CSF + MSCs decreased aspartate amino transferase levels. Hepatocyte growth factor (HGF) and interleukin 10 levels increased with MSC treatment. Transforming growth factor levels were lower with MSC treatment. Interleukin 1 and tumor necrosis factor alpha levels decreased in all treated groups. Histopathology showed that MSCs and G-CSF reduced liver fibrosis from F4 to F2. Conclusions: MSC treatment improves liver function, decreases hepatic fibrosis, and plays an antiinflammatory role;it promotes HGF levels and increased proliferating cell nuclear antigen when followed by MSC treatment mobilization using G-CSF. When these therapies were combined, however, fibrosis improvement was less evident