Transport: the state of affairs in landlocked developing countries of Latin America, through June 2009

This edition of the FAL Bulletin examines the state of affairs of transport in the Plurinational State of Bolivia and Paraguay, along with their transit countries. The information herein is an update of Bulletin 262 of June 2008.

Humoral immune responses against the malaria vaccine candidate antigen Plasmodium vivax AMA-1 and IL-4 gene polymorphisms in individuals living in an endemic area of the Brazilian Amazon

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Studies on the application of Myceliophthora thermophila JCP1-4 cellulases cocktail on sugarcane bagasse pretreated by different methods

The hydrolysis step for sugar production in biorefineries is crucial for the sequential processes involved and cellulases cocktails behave differently according to the pretreatment employed. In this study, the application of the cellulases cocktail produced by the fungus Myceliophthora thermophila JCP1-4 was studied on the saccharification of sugarcane bagasse pretreated by ozonolysis and thermic ferric nitrate (TFN), and the results were compared with commercial enzymes (Novozymes Celluclast 1.5L, Novozym 188). The fungal cellulases cocktail hold an activity of FPU:β-glucosidase of 1:4(U/mL); time, temperature, FPU by g of cellulose load and percentage of dry matter (DM) were studied. The analysis of central composite design of TFN pretreated showed that fungal cellulases works better in DM values of 3–3.5% (4.5% for commercial), temperatures higher than 50 °C (<45 °C for commercial) and 15FPU for both; commercial enzymes yielded 7.78 g/L of reducing sugars and the fungal enzymes 5.42 g/L. With the ozone pretreated, the fungal enzymes presented a higher thermostability with faster kinects, being able to produce 5.56 g/L of reducing sugars (60 °C, 8 h), against 5.20 g/L for commercial enzymes (50 °C, 24 h), (10FPU, 3%DM for both). The FPU derivate analysis revels better yields with 7.5FPU, and the increase of DM to 7.5% resulted 13.28 g/L of reducing sugars.

The presence of the NOS3 gene polymorphism for intron 4 mitigates the beneficial effects of exercise training on ambulatory blood pressure monitoring in adults

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Intron 4 polymorphism of the endothelial nitric oxide synthase (eNOS) gene is associated with decreased NO production in a mercury-exposed population

Nitric oxide (NO), produced by endothelial nitric oxide synthase (eNOS), is a potent vasodilator and plays a prominent role in regulating the cardiovascular system. Decreased basal NO release may predispose to cardiovascular diseases. Evidence suggests that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene may regulate eNOS expression. On the other hand, some recent reports strongly suggest an association between methylmercury (MeHg) exposures and altered NO synthesis. In the present study, we investigate the contribution of the 27-pb tandem repeat polymorphism on nitric oxide production, which could enhance susceptibility to cardiovascular disease in the MeHg-exposed study population. Two-hundred-two participants (98 men and 104 women), all chronically exposed to MeHg through fish consumption were examined. Mean blood Hg concentration and nitrite plasma concentration were 50.5 +/- 35.4 mu g/L and 251.4 +/- 106.3 nM, respectively. Mean systolic and diastolic blood pressure were 120.1 +/- 19.4 mm Hg and 72.0 +/- 10.6 mm Hg, respectively. Mean body mass index was 24.5 +/- 4.3 kg/m(2) and the mean heart rate was 69.8 +/- 11.8 bpm. There were no significant differences in age, arterial blood pressure, body mass index or cardiac frequency between genotype groups (all P>0.05). However, we observed different nitrite concentrations in the genotypes groups, with lower nitrite levels for the 4a4a genotype carriers. Age, gender and the presence of intron 4 polymorphism contributed to nitrite reduction as a result of blood Hg concentration. Taken together, our results show that the 27 nt repeat polymorphism of the intron 4 in the eNOS gene increases susceptibility to cardiovascular diseases after MeHg exposure by modulating nitric oxide levels. (C) 2011 Elsevier B.V. All rights reserved.

Role of transient receptor potential vanilloid 4 in rat joint inflammation

Objective To determine whether activation of transient receptor potential vanilloid 4 (TRPV-4) induces inflammation in the rat temporomandibular joint (TMJ), and to assess the effects of TRPV-4 agonists and proinflammatory mediators, such as a protease-activated receptor 2 (PAR-2) agonist, on TRPV-4 responses. Methods Four hours after intraarticular injection of carrageenan into the rat joints, expression of TRPV-4 and PAR-2 in trigeminal ganglion (TG) neurons and in the TMJs were evaluated by real-time reverse transcriptionpolymerase chain reaction and immunofluorescence, followed by confocal microscopy. The functionality of TRPV-4 and its sensitization by a PAR-2activating peptide (PAR-2AP) were analyzed by measuring the intracellular Ca2+ concentration in TMJ fibroblast-like synovial cells or TG neurons. Plasma extravasation, myeloperoxidase activity, and the head-withdrawal threshold (index of mechanical allodynia) were evaluated after intraarticular injection of selective TRPV-4 agonists, either injected alone or coinjected with PAR-2AP. Results In the rat TMJs, TRPV-4 and PAR-2 expression levels were up-regulated after the induction of inflammation. Two TRPV-4 agonists specifically activated calcium influx in TMJ fibroblast-like synovial cells or TG neurons. In vivo, the agonists triggered dose-dependent increases in plasma extravasation, myeloperoxidase activity, and mechanical allodynia. In synovial cells or TG neurons, pretreatment with PAR-2AP potentiated a TRPV-4 agonistinduced increase in [Ca2+]i. In addition, TRPV-4 agonistinduced inflammation was potentiated by PAR-2AP in vivo. Conclusion In this rat model, TRPV-4 is expressed and functional in TG neurons and synovial cells, and activation of TRPV-4 in vivo causes inflammation in the TMJ. Proinflammatory mediators, such as PAR-2 agonists, sensitize the activity of TRPV-4. These results identify TRPV-4 as an important signal of inflammation in the joint.

Gastrin-Releasing Peptide Receptor Antagonism Induces Protection from Lethal Sepsis: Involvement of Toll-like Receptor 4 Signaling

In sepsis, toll-like receptor (TLR)-4 modulates the migration of neutrophils to infectious foci, favoring bacteremia and mortality. In experimental sepsis, organ dysfunction and cytokines released by activated macrophages can be reduced by gastrin-releasing peptide (GRP) receptor (GRPR) antagonist RC-3095. Here we report a link between GRPR and TLR-4 in experimental models and in sepsis patients. RAW 264.7 culture cells were exposed to lipopolysaccharide (LPS) or tumor necrosis factor (TNF)-alpha and RC-3095 (10 ng/mL), Male Wistar rats were subjected to cecal ligation and puncture (CLP), and RC-3095 was administered (3 mg/kg, subcutaneously); after 6 h, we removed the blood, bronchoalveolar lavage, peritoneal lavage and lung. Human patients with a clinical diagnosis of sepsis received a continuous infusion with RC-3095 (3 mg/kg, intravenous) over a period of 12 h, and plasma was collected before and after RC-3095 administration and, in a different set of patients with systemic inflammatory response syndrome (SIRS) or sepsis. GRP plasma levels were determined. RC-3095 inhibited TLR-4, extracellular-signal-related kinase (ERK)-1/2, Jun NH2-terminal kinase (JNK) and Akt and decreased activation of activator protein 1 (AP-1), nuclear factor (NF)-kappa B and interleukin (IL)-6 in macrophages stimulated by LPS. It also decreased IL-6 release from macrophages stimulated by TNF-alpha. RC-3095 treatment in CLP rats decreased lung TLR-4, reduced the migration of cells to the lung and reduced systemic cytokines and bacterial dissemination. Patients with sepsis and systemic inflammatory response syndrome have elevated plasma levels of GRP which associates with clinical outcome in the sepsis patients. These findings highlight the role of GRPR signaling in sepsis outcome and the beneficial action of GRPR antagonists in controlling the inflammatory response in sepsis through a mechanism involving at least inhibition of TLR-4 signaling. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00083

Lack of signaling by IL-4 or by IL-4/IL-13 has more attenuating effects on Leishmania amazonensis dorsal skin - than on footpad-infected mice

Lesion development in tegumentary leishmaniasis is markedly influenced by the inoculation site and the type and number of injected infective forms. This and the yet unclear contribution of Th2 cytokines as susceptibility factors to Leishmania amazonensis infection prompted us to investigate the roles of IL-4, IL-13 and IL-10 on C57BL/6 and BALB/c mice infected in the footpad (paw) or rump with low-dose L. amazonensis purified-metacyclics. Wild-type (WT) mice of either strain developed, in the rump, a single large ulcerated lesion whereas paw lesions never ulcerated and were much smaller in C57BL/6 than in BALB/c mice. However, rump-inoculated IL-4-deficient (IL-4(-/-))C57BL/6 mice did not develop any visible lesions although parasites remained in the dermis and lymph nodes, even after systemic IL-10-receptor blocking. By comparison, all IL-4(-/-) BALB/c mice developed rump ulcers. Strikingly, only 30% of rump-infected IL-4R alpha(-/-) BALB/c mice developed lesions. IL-4(-/-) mice had higher IFN-gamma and lower IL-10 and IL-13 levels than WT mice. Paw-infected IL-4R alpha(-/-) BALB/c mice developed minimal paw lesions. While other factors contributing to L amazonensis susceptibility cannot be discounted, our results indicate that absent signalling by IL-4 or by IL-4/IL-13 have more intense attenuating effects on rump than on paw lesions but do not eradicate parasitism. (C) 2011 Elsevier Inc. All rights reserved.

Pseudopolymorphism in hydroxybenzophenones: the dihydrate of 2,2 ',4,4 '-tetrahydroxybenzophenone

A dihydrate pseudopolymorph of bis(2,4-dihydroxyphenyl)methanone, C13H10O5 center dot 2H2O, (I), was obtained during polymorphism screening of hydroxybenzophenone derivatives. This structure, in which the molecule sits on a twofold axis, was compared with the known anhydrous form of (I) [Schlemper (1982). Acta Cryst. B38, 554559]. The role of water in the crystal assembly was established on the basis of the known monohydrate pseudopolymorph of 3,4-dihydroxybenzophenone [Landre, Souza, Correa, Martins & Doriguetto (2010). Acta Cryst. C66, o463o465].

Gas-phase reactivity of 2-hydroxy-1,4-naphthoquinones: a computational and mass spectrometry study of lapachol congeners

In order to understand the influence of alkyl side chains on the gas-phase reactivity of 1,4-naphthoquinone derivatives, some 2-hydroxy-1,4-naphthoquinone derivatives have been prepared and studied by electrospray ionization tandem mass spectrometry in combination with computational quantum chemistry calculations. Protonation and deprotonation sites were suggested on the basis of gas-phase basicity, proton affinity, gas-phase acidity (?Gacid), atomic charges and frontier orbital analyses. The nature of the intramolecular interaction as well as of the hydrogen bond in the systems was investigated by the atoms-in-molecules theory and the natural bond orbital analysis. The results were compared with data published for lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone). For the protonated molecules, water elimination was verified to occur at lower proportion when compared with side chain elimination, as evidenced in earlier studies on lapachol. The side chain at position C(3) was found to play important roles in the fragmentation mechanisms of these compounds. Copyright (c) 2012 John Wiley & Sons, Ltd.

Assessment of the role of transcript for GATA-4 as a marker of unfavorable outcome in human adrenocortical neoplasms

Abstract Background Malignant neoplasia of the adrenal cortex is usually associated with very poor prognosis. When adrenocortical neoplasms are diagnosed in the early stages, distinction between carcinoma and adenoma can be very difficult to accomplish, since there is yet no reliable marker to predict tumor recurrence or dissemination. GATA transcription factors play an essential role in the developmental control of cell fate, cell proliferation and differentiation, organ morphogenesis, and tissue-specific gene expression. Normal mouse adrenal cortex expresses GATA-6 while its malignant counterpart only expresses GATA-4. The goal of the present study was to assess whether this reciprocal change in the expression of GATA factors might be relevant for predicting the prognosis of human adrenocortical neoplasms. Since human adrenal cortices express luteinizing hormone (LH/hCG) receptor and the gonadotropins are known to up-regulate GATA-4 in gonadal tumor cell lines, we also studied the expression of LH/hCG receptor. Methods We conducted a study on 13 non-metastasizing (NM) and 10 metastasizing/recurrent (MR) tumors obtained from a group of twenty-two adult and pediatric patients. The expression of GATA-4, GATA-6, and LH/hCG receptor (LHR) in normal and tumoral human adrenal cortices was analysed using reverse transcriptase-polymerase chain reaction (RT-PCR) complemented by dot blot hybridization. Results Messenger RNA for GATA-6 was detected in normal adrenal tissue, as well as in the totality of NM and MR tumors. GATA-4, by its turn, was detected in normal adrenal tissue, in 11 out of 13 NM tumors, and in 9 of the 10 MR tumors, with larger amounts of mRNA found among those presenting aggressive clinical behavior. Transcripts for LH receptor were observed both in normal tissue and neoplasms. A more intense LHR transcript accumulation was observed on those tumors with better clinical outcome. Conclusion Our data suggest that the expression of GATA-6 in human adrenal cortex is not affected by tumorigenesis. GATA-4 expression is more abundant in MR tumors, while NM tumors express more intensely LHR. Further studies with larger cohorts are needed to test whether relative expression levels of LHR or GATA-4 might be used as prognosis predictors.

Ecology of an uncultured heterotrophic flagellate lineage: MAST-4

Programa de oceanografía

The Council of Ministers of the European Union After the Lisbon Treaty

The Treaty of Lisbon has brought remarkable changes and innovations to the European Union. As far as the Council of Ministers of the European Union (“the Council” hereinafter) is concerned, there are two significant innovations: double qualified majority voting and new rotating Presidency scheme, which are considered to make the working of the Council more efficiently, stably and consistently. With the modification relating to other key institutions, the Commission and the European Parliament, and with certain procedures being re-codified, the power of the Council varies accordingly, where the inter-institutional balance counts for more research. As the Council is one of the co-legislatures of the Union, the legislative function of it would be probably influenced, positively or negatively, by the internal innovations and the inter-institutional re-balance. Has the legislative function of the Council been reinforced or not? How could the Council better reach its functional goal designed by the Treaties’ drafter? How to evaluate the Council’s evolution after Lisbon Treaty in the light of European integration? This thesis is attempting to find the answers by analyzing two main internal innovations and inter-institutional re-balance thereinafter.

Increased IL-4 and decreased regulatory cytokine production following relocation of Icelandic horses from a high to low endoparasite environment

Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides spp. IBH does not occur in Iceland where Culicoides are absent. However, following importation into continental Europe where Culicoides are present, >or=50% of Icelandic horses (1st generation) develop IBH but

Complicated intra-abdominal infections in Europe: preliminary data from the first three months of the CIAO Study

The CIAO Study is a multicenter observational study currently underway in 66 European medical institutions over the course of a six-month study period (January-June 2012).This preliminary report overviews the findings of the first half of the study, which includes all data from the first three months of the six-month study period.Patients with either community-acquired or healthcare-associated complicated intra-abdominal infections (IAIs) were included in the study.912 patients with a mean age of 54.4 years (range 4-98) were enrolled in the study during the first three-month period. 47.7% of the patients were women and 52.3% were men. Among these patients, 83.3% were affected by community-acquired IAIs while the remaining 16.7% presented with healthcare-associated infections. Intraperitoneal specimens were collected from 64.2% of the enrolled patients, and from these samples, 825 microorganisms were collectively identified.The overall mortality rate was 6.4% (58/912). According to univariate statistical analysis of the data, critical clinical condition of the patient upon hospital admission (defined by severe sepsis and septic shock) as well as healthcare-associated infections, non-appendicular origin, generalized peritonitis, and serious comorbidities such as malignancy and severe cardiovascular disease were all significant risk factors for patient mortality.White Blood Cell counts (WBCs) greater than 12,000 or less than 4,000 and core body temperatures exceeding 38°C or less than 36°C by the third post-operative day were statistically significant indicators of patient mortality.