Caracterização físico-química e ações farmacológicas hepatoprotetora, antiinflamatória, pró-angiogênica, antioxidante e anticoagulante da fração rica em fucana 0,8FRF 0,8 da alga marrom Lobophora variegata

This study examines the physical and chemical composition and the pharmacological effects of brown seaweed FRF 0.8 Lobophora variegata. Fractionation of the crude extract was done with the concentration of 0.8 volumes of acetone, obtaining the FRF 0.8. The physicochemical characterization showed that it was a fucana sulfated. Anti-inflammatory activity was assessed by paw edema model by the high rates of inhibition of the edema and the best results were in the fourth hour after induction (100 ± 1.4% at the dose of 75 mg / kg) and by the strong inhibitory activity of the enzyme myeloperoxidase (91.45% at the dose of 25 mg / kg). The hepataproteção was demonstrated by measurements of enzymatic and metabolic parameters indicative of liver damage, such as bilirubin (reduction in 68.81%, 70.68% and 68.21% for bilirubin total, direct and indirect, respectively at a dose of 75 mg / kg), ALT, AST and γ-GT (decrease of 76.93%, 44.58% and 50% respectively at a dose of 75 mg / kg) by analysis of histological slides of liver tissue, confirming that hepatoprotective effect the polymers of carbohydrates, showing a reduction in tissue damage caused by CCl4 and the inhibition of the enzyme complex of cytochrome P 450 (increasing sleep time in 54.6% and reducing the latency time in 71.43%). The effectiveness of the FRF 0.8 angiogenesis was examined in chorioallantoic membrane (CAM) of fertilized eggs, with the density of capillaries evaluated and scored, showing an effect proangigênico at all concentrations tested FRF (10 mg- 1000 mg). The FRF showed antioxidant activity on free radicals (by inhibiting Superoxide Radical in 55.62 ± 2.10%, Lipid Peroxidation in 100.15 ± 0.01%, Hydroxyl Radical in 41.84 ± 0.001% and 71.47 Peroxide in ± 2.69% at concentration of 0.62 mg / mL). The anticoagulant activity was observed with prolongation of activated partial thromboplastin time (aPTT) at 50 mg (> 240 s), showing that its action occurs in the intrinsic pathway of the coagulation cascade. Thus, our results indicate that these sulfated polysaccharides are an important pharmacological target

Biochemical parameters response to weight loss in patients with non-alcoholic steatohepatitis.

Background: Non-alcoholic steatohepatitis (NASH) is a chronic liver disease that is capable of progressing to end-stage liver disease, but generally has a benign course. Non-alcoholic steatohepatitis (NASH) is a growing public health problem with no approved therapy. NASH projected to be the leading cause of liver transplantation in the United States by 2020. Obesity, non-insulin-dependent diabetes mellitus and hyperlipidaemia are the most common associations of the disease. Global prevalence of NASH is 10-24% amongst general population but increases to 25-75% in obese diabetic individuals. Objective: There is an urgent need for efficient therapeutic options as there is still no approved medication. The aim of this study was to detect changes in biochemical parameters including insulin resistance, cytokines, blood lipid profile and liver enzymes following weight loss in patients with non-alcoholic steatohepatitis. Materials and methods: One hundred obese patients with NASH, their age between 35-50 years, body mass index (BMI) from 30 to 35 Kg/m2 were included in the study in two subgroups; the first group (A) received moderate aerobic exercise training in addition to diet regimen , where the second group (B) received no treatment intervention. Results: The mean values of leptin, TNF-α, IL6, IL8, Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Homeostasis Model Assessment-Insulin Resistance- index (HOMA-IR), Total Cholesterol (TC), Low Density Lipoprotein Cholesterol (LDL-c) , Triglycerides (TG) and BMI were significantly decreased in group (A), where the mean value of Adiponectin and High Density Lipoprotein Cholesterol (HDL-c) were significantly increased, while there were no significant changes in group (B). Also, there was a significant difference between both groups at the end of the study. Conclusion: Weight loss modulates insulin resistance, adiponectin, leptin, inflammatory cytokine levels and markers of hepatic function in patients with nonalcoholic steatohepatitis.

Investigating the peculiar emission from the new VHE gamma-ray source H1722+119

The MAGIC (Major Atmospheric Gamma-ray Imaging Cherenkov) telescopes observed the BL Lac object H1722+119 (redshift unknown) for six consecutive nights between 2013 May 17 and 22, for a total of 12.5 h. The observations were triggered by high activity in the optical band measured by the KVA (Kungliga Vetenskapsakademien) telescope. The source was for the first time detected in the very high energy (VHE, E > 100 GeV) γ-ray band with a statistical significance of 5.9 σ. The integral flux above 150 GeV is estimated to be (2.0 ± 0.5) per cent of the Crab Nebula flux. We used contemporaneous high energy (HE, 100MeV < E < 100 GeV) γ-ray observations from Fermi-LAT (Large Area Telescope) to estimate the redshift of the source. Within the framework of the current extragalactic background light models, we estimate the redshift to be z = 0.34±0.15. Additionally, we used contemporaneous X-ray to radio data collected by the instruments on board the Swift satellite, the KVA, and the OVRO (Owens Valley Radio Observatory) telescope to study multifrequency characteristics of the source. We found no significant temporal variability of the flux in the HE and VHE bands. The flux in the optical and radio wavebands, on the other hand, did vary with different patterns. The spectral energy distribution (SED) of H1722+119 shows surprising behaviour in the ∼ 3×1014 −1018 Hz frequency range. It can be modelled using an inhomogeneous helical jet synchrotron self-Compton model.

Co-infecção pelo vírus da hepatite G em pacientes infectados pelo Leihsmania chagasi

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Does Epoetin Beta Still Have a Place in Peginterferon Alpha-2a Plus Ribavirin Treatment Strategies for Chronic Hepatitis C?

International audience

Ferrous iron sensing and responding in Pseudomonas aeruginosa

Controlling iron distribution is important for all organisms, and is key in bacterial pathogenesis. It has long been understood that cystic fibrosis (CF) patient sputum contains elevated iron concentrations. However, anaerobic bacteria have been isolated from CF sputum and hypoxic zones in sputum have been measured. Because ferrous iron [Fe(II)] is stable in reducing, acidic conditions, it could exist in the CF lung. I show that a two-component system, BqsRS, specifically responds to Fe(II) in the CF pathogen, Pseudomonas aeruginosa. Concurrently, a clinical study found that Fe(II) is present in CF sputum at all stages of lung function decline. Fe(II), not Fe(III) correlates with patients in the most severe disease state. Furthermore, transcripts of the newly identified BqsRS were detected in sputum. Two component systems are the main method bacteria interact with their extracellular environment. A typical two-component system contains a sensor histidine kinase, which upon activation phosphorylates a response regulator that then acts as a transcription factor to elicit a cellular response to stimuli. To explore the mechanism of BqsRS, I describe the Fe(II)-sensing RExxE motif in the sensor BqsS and determine the consensus DNA sequence BqsR binds. With the BqsR binding sequence, I identify novel regulon members through bioinformatic and molecular biology techniques. From the predicted function of new BqsR regulon members, I find that Fe(II) elicits a response that globally protects the cells against cationic stressors, including clinically relevant antibiotics. Subsequently, I use BqsR as a case study to determine if promoter outputs can accurately be predicted based only on a deep understanding of a transcriptional activator’s operator or if a broader regulatory context is required for accurate predictions at all genomic loci. This work highlights the importance of Fe(II) as a (micro)environmental factor, even in conditions typically thought of as aerobic. Since the presence of Fe(II) can alter P. aeruginosa’s antibiotic susceptibility, combining the current strategy of targeting Fe(III) with a new approach targeting Fe(II) may help eradicate infections in the CF lung in the future.

Estimativa de estádios ninfais do Psilídeo-de-concha em função dos tamanhos das conchas.

O psilídeo-de-concha, Glycaspis brimblecombei, é considerado praga quarentenária de elevada importância econômica para o setor forestal no Brasil pela preferência a Eucaliptus camaldulensis ? espécie mais plantada no país. A insufciência de métodos químicos, aceitáveis pelas empresas certifcadas internacionalmente, para o controle da praga vem tornando a estratégia de controle biológico pelo parasitóide Psyllaephagus bliteus a opção mais apropriada no momento. Por esta razão, a disponibilidade de métodos que ajudem a detectar fases de desenvolvimento da praga mais apropriadas ao parasitismo é de grande importância tanto para a identifcação precisa do seu ciclo de vida quanto à proposição de estratégias de seu controle biológico. O objetivo deste trabalho foi identificar faixas de tamanhos de concha de G. brimblecombei, de modo a utilizá-las como padrão de referencia para um método inédito de estimativas de estádios ninfais de desenvolvimento da praga em função do seu respectivo tamanho de concha amostrado. Essas faixas (ou classes de tamanhos) foram obtidas através de minucioso trabalho entomológico realizado em laboratório, onde os diâmetros das conchas e seus respectivos insetos foram medidos com auxílio de lupa e avaliados quanto aos estádios de desenvolvimento. Posteriormente, foram realizadas análises estatísticas e de tendências. As seguintes classes de tamanhos de concha foram determinadas como resultado: Ninfa 1 ? de 0,7 mm a 0,9 mm; Ninfa 2 ? de 0,8mm a 1,1 mm; Ninfa 3 ? de 1,1 mm a 1,7 mm; Ninfa 4 ? de 1,6 mm a 2,2 mm;e Ninfa 5 ? de 2,2 mm a 2,8 mm.

Serum Aminotransferases in Thai Children With Dengue Infection

Background: Hepatic manifestations are one of the unusual manifestations of dengue infection. Objectives: We conducted this study in order to study the pattern of serum aminotransferases and sequential changes before and after shock in Thai children with dengue infection. Patients and Methods: Children who were clinically and serologically diagnosed as dengue infection and were admitted to King Chulalongkorn Memorial Hospital during a peroid of one year were enrolled. They were clinically classified into a non-shock group and a shock group. The majority of serum aminotransferases including aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were obtained within a week after the onset of fever and until 3 days after shock in the shock group. Student t-test and median in boxplot form were used for statistical analysis. Results: We enrolled 127 children with a mean age of 7.6 ± 3.6 years. The incidence of abnormal AST and ALT levels was 97.4% and 50.0% in the shock group, and 91.8% and 44.9% in the non-shock group respectively. 29% and 15.4% of the patients in shock group and only 10.2% and 4.1% in non-shock group had the respective AST and ALT levels > 200 U/L. Serum aminotransferase levels were significantly higher in the shock group when compared to the non-shock group. AST tended to increase starting from one day before shock and continued to increase within a few days whereas ALT was less likely to be affected. Conclusions: Elevated serum aminotransferases are a common finding in children with dengue infection and the levels of AST are higher than those of ALT. Patients with shock have significantly higher aminotransferase levels that increase up to 3 days after shock.

Liver injury from ampicillin-induced intestinal microbiota distresses in rats fed carbohydrate- and protein-rich diets

Purpose: To investigate the effect of ampicillin on rat intestinal microflora and liver in the presence of high carbohydrate and protein diets. Methods: Male Wistar albino rats were divided into four groups. The first group served as the control, the second group was treated with ampicillin (50 mg/kg for 3 weeks) and fed with a standard diet, while the third and fourth groups were treated with the same dose of ampicillin and fed with acarbohydrateand protein-rich diets, respectively, to observe the effect of diet on gut flora and liver. Fecal specimens were collected and used for qualitative determination of gut microbiota composition. Serum hepatospecific markers (AST, ALT and ALP) were estimated. The antioxidant status of liver tissues was estimated for GSH, MDA, GST, LDH and vitamin C l, in addition to sodium and potassium. Results: Administration of orogastric dose of ampicillin for 3 weeks induced inhibition of E.coli, yeasts, total anaerobes, and anaerobic lactobacilli with new growth of P. vulgaris and K. pneumonia. The levels of serum AST, ALT and ALP showed significant (p ˂ 0.05) increase to 163, 112.38 and 115.35 %, respectively in ampicillin-treated animals, compared to control. Also significant (p ˂ 0.05) increase in lipid peroxidation (120 %) and LDH (111 %) coupled with significant (p ˂ 0.05) decrease in glutathione (74.57 %), vitamin C (63.49 %) and glutathione S-transferase (41.51 %) were observed in ampicillintreated groups. No significant variation (p ˂ 0.05) in sodium and potassium levels were found between control and the treated group after 3 weeks of treatment. Conclusion: These results confirm that extended ampicillin therapy disrupts gut flora, which results in liver injury; hence, overuse of antibiotics should be avoid.

Use of BARD scoring system in non-alcoholic fatty liver disease patients and its correlation with ultrasonographic grading in Gizan, Saudi Arabia

Purpose: To assess the efficacy of the BARD scoring system in Saudi non‐alcoholic fatty liver disease (NAFLD) patients attending Gizan General Hospital and to identify the clinical variables associated with advanced fibrosis. . Methods: The cross-sectional study involved 120 patients aged ≥ 18 years who attended the Ultrasound Department of Gizan General Hospital, Gizan, Saudi Arabia, during January – June 2013. BARD scoring system comprised the following variables: body mass index (BMI) ≥ 28 = 1 point, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio ≥ 0.8 = 2 points, and type 2 diabetes mellitus = 1 point. Results: Patients with advanced fibrosis were older (55.0 years) than patients with no/mild fibrosis (48.6 years), albeit not significantly so. A higher BMI was associated with advanced fibrosis in males, females and all study participants (p = 0.013, 0.016 and 0.001, respectively). Advanced fibrosis was more common in older patients with a higher weight to height ratio. Logistic regression suggested that age ≥ 50 years was associated with a 2.52-fold increase in the risk of advanced fibrosis, but this did not have a significant clinical impact (p = 0.087). BMI > 28 was associated with a 26.73-fold increased risk of advanced fibrosis, while AST/ALT ≥ 0.8 was associated with an 18.46-fold increased risk of advanced liver fibrosis (p = 0.002 and 0.006, respectively). Conclusion: The major risk factors for advanced fibrosis using BARD scoring system in patients with NAFLD were old age, BMI > 28, and AST/ALT ≥ 0.8. In addition, grade 3 ultrasonographic fatty liver significantly correlated with advanced fibrosis.

Protective effect of rhamnopyranosyl vanilloyl isolated from Scrophularia ningpoensis Hemsl (Scrophulariaceae) root against acute liver injury in mice

Purpose: To investigate the protective effect of rhamnopyranosyl vanilloyl (RV) from Scrophularia ningpoensis root against tetrachloromethane (CCl4)-induced acute liver injury (ALI) in mice. Methods: RV was isolated from S. ningpoensis by column chromatography. ALI model of mice was established by intraperitoneal injection of CCl4. Liver index, liver function indices, as well as serum alanine transaminase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) were evaluated. Lipid peroxidation (LPO)-related indices, including malonaldehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Apoptotic proteins (Bcl-2, Bax and caspase-3) in liver tissue were determined by enzyme-linked immunosorbent assay (ELISA) and Western blot. Results: After treatment with RV (10, 20 or 40 mg/kg), liver index (5.65 - 5.21 vs. 6.68 %), ALT (90.18 - 79.68 vs. 112.47 U/L), AST (64.44 - 57.63 vs. 75.41 U/L) and TBIL (2.68 - 1.95 vs. 3.21 U/L) activities, as well as MDA (3.58 - 2.88 vs. 4.13 μmol/g), Bax and caspase-3 levels significantly (p < 0.05 or 0.01) decreased, compared with those in control group. After treatment with RV (10, 20 or 40 mg/kg), GSH (16.58 - 22.14 vs. 12.34 μmol/g), Bcl-2, SOD (86.45 - 107.61 vs. 68.43 U/mg) and GSH-Px (295.64 - 329.47 vs. 268.49 U/mg) levels or activities significantly (p < 0.05 or 0.01) increased, compared with those in control group. Conclusion: RV has protective effect against CCl4-induced ALI in mice, and the mechanisms involve the inhibition of LPO and apoptosis in liver cells. Thus, RV is a potential drug for the treatment of liver injury

Flow around a hemisphere-cylinder at high angle of attack and low Reynolds number. Part II: POD and DMD applied to reduced domains

Three-dimensional direct numerical simulations (DNS) have been performed on a finite-size hemispherecylinder model at angle of attack AoA = 20◦ and Reynolds numbers Re = 350 and 1000. Under these conditions, massive separation exists on the nose and lee-side of the cylinder, and at both Reynolds numbers the flow is found to be unsteady. Proper orthogonal decomposition (POD) and dynamic mode decomposition (DMD) are employed in order to study the primary instability that triggers unsteadiness at Re = 350. The dominant coherent flow structures identified at the lower Reynolds number are also found to exist at Re = 1000; the question is then posed whether the flow oscillations and structures found at the two Reynolds numbers are related. POD and DMD computations are performed using different subdomains of the DNS computational domain. Besides reducing the computational cost of the analyses, this also permits to isolate spatially localized oscillatory structures from other, more energetic structures present in the flow. It is found that POD and DMD are in general sensitive to domain truncation and noneducated choices of the subdomain may lead to inconsistent results. Analyses at Re = 350 show that the primary instability is related to the counter rotating vortex pair conforming the three-dimensional afterbody wake, and characterized by the frequency St ≈ 0.11, in line with results in the literature. At Re = 1000, vortex-shedding is present in the wake with an associated broadband spectrum centered around the same frequency. The horn/leeward vortices at the cylinder lee-side, upstream of the cylinder base, also present finite amplitude oscillations at the higher Reynolds number. The spatial structure of these oscillations, described by the POD modes, is easily differentiated from that of the wake oscillations. Additionally, the frequency spectra associated with the lee-side vortices presents well defined peaks, corresponding to St ≈ 0.11 and its few harmonics, as opposed to the broadband spectrum found at the wake.

Flow around a hemisphere-cylinder at high angle of attack and low Reynolds number. Part I: Experimental and numerical investigation

Three-dimensional Direct Numerical Simulations combined with Particle Image Velocimetry experiments have been performed on a hemisphere-cylinder at Reynolds number 1000 and angle of attack 20◦. At these flow conditions, a pair of vortices, so-called “horn” vortices, are found to be associated with flow separation. In order to understand the highly complex phenomena associated with this fully threedimensional massively separated flow, different structural analysis techniques have been employed: Proper Orthogonal and Dynamic Mode Decompositions, POD and DMD, respectively, as well as criticalpoint theory. A single dominant frequency associated with the von Karman vortex shedding has been identified in both the experimental and the numerical results. POD and DMD modes associated with this frequency were recovered in the analysis. Flow separation was also found to be intrinsically linked to the observed modes. On the other hand, critical-point theory has been applied in order to highlight possible links of the topology patterns over the surface of the body with the computed modes. Critical points and separation lines on the body surface show in detail the presence of different flow patterns in the base flow: a three-dimensional separation bubble and two pairs of unsteady vortices systems, the horn vortices, mentioned before, and the so-called “leeward” vortices. The horn vortices emerge perpendicularly from the body surface at the separation region. On the other hand, the leeward vortices are originated downstream of the separation bubble, as a result of the boundary layer separation. The frequencies associated with these vortical structures have been quantified.

Comparative fixed gear studies in the Cyclades (Aegean Sea): size selectivity of small-hook longlines and monofilament gill nets

Fishing trials with monofilament gill nets and longlines using small hooks were carried out at the same fishing grounds in Cyclades (Aegean Sea) over 1 year. Four sizes of MUSTAD brand, round bent, flatted sea hooks (Quality 2316 DT, numbers 15, 13, 12 and 11) and four mesh sizes of 22, 24, 26 and 28 turn nominal bar length monofilament gill nets were used. Significant differences in the catch size frequency distributions of the two gears were found for four out of five of the most important species caught by both the gears (Diplodus annularis, Diplodus vulgaris, Pagellus erythrinus, Scorpaena porcus and Serranus cabrilla), with longlines catching larger fish and a wider size range than gill nets. Whereas longline catch size frequency distributions for most species for the different hook sizes were generally highly overlapped, suggesting little or no differences in size selectivity, gill net catch size frequency distributions clearly showed size selection, with larger mesh sizes catching larger fish. A variety of models were fitted to the gill net data, with the lognormal providing the best fit in most cases. A maximum likelihood method was also used to estimate the parameters of the logistic model for the longline data. Because of the highly overlapped longline catch size frequency distributions parameters could only be estimated for two species. This study shows that the two static gears have different impacts in terms of size selection. This information will be useful for the more effective management of these small-scale, multi-species and multi-gear fisheries. (C) 2002 Elsevier Science B.V. All rights reserved.

Estudio molecular en dos hermanas afectadas por ictiosis congénita autosómica recesiva : descripción de una nueva mutación causal en TGM1

Se describe la variante homocigota c.320-2A>G de TGM1 en dos hermanas con ictiosis congénita autosómica recesiva. El clonaje de los transcritos generados por esta variante permitió identificar tres mecanismos moleculares de splicing alternativos.