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

Comparative Effects of Triflusal, S-Adenosylmethionine, and Dextromethorphan over Intestinal Ischemia/Reperfusion Injury

Ischemia/reperfusion (I/R) is a condition that stimulates an intense inflammatory response. No ideal treatment exists. Triflusal is an antiplatelet salicylate derivative with anti-inflammatory effects. S-adenosylmethionine is a metabolic precursor for glutathione, an endogenous antioxidant. Dextromethorphan is a low-affinity N-methyl-D-aspartate receptor inhibitor. There is evidence that these agents modulate some of the pathways involved in I/R physiopathology. Intestinal I/R was induced in rats by clamping the superior mesenteric artery for 60 minutes, followed by 60 minutes of reperfusion. Rats either received saline or the drugs studied. At the end of the procedure, serum concentrations of tumor necrosis factor-alpha (TNF-alpha), malonaldehyde (MDA), and total antioxidant capacity (TAC) were determined and intestinal morphology analyzed. I/R resulted in tissue damage, serum TNF-alpha and MDA elevations, and depletion of TAC. All drugs showed tissue protection. Only triflusal reduced TNF-alpha levels. All drugs lowered MDA levels, but only triflusal and S-adenosylmethionine maintained the serum TAC

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

A Multicenter, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Saroglitazar in Patients With Primary Biliary Cholangitis

Introduction: Patients with primary biliary cholangitis (PBC) without biochemical response to ursodeoxycholic acid (UDCA) are at increased risk of liver-related mortality. Saroglitazar is a novel peroxisome proliferator-activated receptor (PPAR) agonist with dual PPAR agonistic properties (α/γ). There is a strong mechanistic rationale for studying saroglitazar in PBC because PPARα is a molecular target of fibrates that showed improvements in liver tests in patients with PBC. Methods: In this 16-week, open-label, phase 3 study, 37 patients were screened across 3 clinical centers to enroll 7 patients. All patients received daily dose of saroglitazar 4 mg for 16 weeks in addition to their ongoing treatment with UDCA. The primary efficacy endpoint was the reduction in alkaline phosphatase (ALP) level at week 16 as compared to baseline. Results: Mean age of the study population was 51.1 ± 10.0 years, all patients were female of Mexican descent, and mean body mass index was 25.5± = 4.8 kg/m2. Six (85.7%) patients reported taking ursodiol at baseline and continued throughout the study with a mean daily dosage of 417 mg. Among these, the daily dosage of UDCA 500 mg in 4 and 250 mg in 2 subjects, respectively. The mean baseline ALP level was 230 ± 103 U/L. The primary efficacy endpoint, mean change (reduction) from baseline in ALP concentration at week 16 based on the modified intent-to-treat population was -94 ± 53 U/L (P = 0.003), corresponding to a reduction of 48 ± 23%. Treatment with saroglitazar 4 mg resulted in a rapid and sustained decrease of ALP levels at week 4 (-84 ± 47 U/L, P = 0.003). Six patients who completed the study achieved mean ALP reduction of at least 40% at week 4 and all subsequent visits. Discussion: Although the study was terminated because of lack of enrollment, saroglitazar daily for 16 weeks resulted in rapid and sustained improvements in ALP with an acceptable safety profile in patients with PBC

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

Noninvasive Biomarkers for the Diagnosis of Liver Fibrosis and Cirrhosis

The clinical importance of monitoring liver fibrosis lies in the morbidity and mortality of the chronic liver diseases in relation to the stage and progression of fibrosis. Whether the fibrosis stabilizes or regresses depends on the specific treatment. Liver biopsy, the current standard for the diagnosis, has implicit limitations due to sampling heterogeneity. There are noninvasive imaging methods, such as transient elastography that measures the stiffness of the liver, but it has some limitations (feasibility and unreliability), particularly in obese patients. FibroTest is the most widely used noninvasive serological method worldwide which is efficacious in the extreme stages of fibrosis, but these methods cannot discern intermediate stages. Liver fibrosis is a dynamic response that involves multiple cellular and molecular events with an excessive deposit of extracellular matrix. Even though there is much information on the pathophysiology of fibrosis, that knowledge is still incomplete, greatly hindering the development of both an accurate treatment and a noninvasive diagnostic method with adequate sensitivity for all the stages of fibrosis. It is known that IGFBP participates in liver homeostasis, and thus these proteins can be used as serum biomarkers during the progression of liver fibrosis in chronic hepatitis C