Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.

High Prevalence of bla(CTX-M) Extended Spectrum Beta-Lactamase Genes in Klebsiella pneumoniae Isolates from a Tertiary Care Hospital: First report of bla(SHV-12), bla(SHV-31), bla(SHV-38), and bla(CTX-M-15) in Brazil

The aim of this study was to investigate the presence and prevalence of bla(TEM), bla(SHV), and bla(CTX-M) and bla(GES)-like genes, responsible for extended spectrum beta-lactamases (ESBLs) production in clinical isolates of Klebsiella pneumoniae collected from a Brazilian tertiary care hospital. Sixty-five ESBL producing K. pneumoniae isolates, collected between 2005 and 2007, were screened by polymerase chain reaction (PCR). Identification of bla genes was achieved by sequencing. Genotyping of ESBL producing K. pneumoniae was performed by the enterobacterial repetitive intergenic consensus-PCR with cluster analysis by the Dice coefficient. The presence of genes encoding ESBLs was confirmed in 59/65 (90.8%) isolates, comprising 20 bla(CTX-M-2), 14 bla(CTX-M-59), 12 bla(CTX-M-15), 9 bla(SHV-12), 1 bla(SHV-2), 1 bla(SHV-2a), 1 bla(SHV-5), and 1 bla(SHV-31) genes. The ESBL genes bla(SHV-12), bla(SHV-31), and bla(CTX-M-15), and the chromosome-encoded SHV-type beta-lactamase capable of hydrolyzing imipenem were detected in Brazil for the first time. The analysis of the enterobacterial repetitive intergenic consensus-PCR band patterns revealed a high rate of multiclonal bla(CTX-M) carrying K. pneumoniae isolates (70.8%), suggesting that dissemination of encoding plasmids is likely to be the major cause of the high prevalence of these genes among the K. pneumoniae isolates considered in this study.

Hyperbaric Oxygen Prevents Early Death Caused by Experimental Cerebral Malaria

Background: Cerebral malaria (CM) is a syndrome characterized by neurological signs, seizures and coma. Despite the fact that CM presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis. Methodology/Principal Findings: C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were exposed to daily doses of HBO (100% O(2), 3.0 ATA, 1-2 h per day) in conditions well-tolerated by humans and animals, before or after parasite establishment. Cumulative survival analyses demonstrated that HBO therapy protected 50% of PbA-infected mice and delayed CM-specific neurological signs when administrated after patent parasitemia. Pressurized oxygen therapy reduced peripheral parasitemia, expression of TNF-alpha, IFN-gamma and IL-10 mRNA levels and percentage of gamma delta and alpha beta CD4(+) and CD8(+) T lymphocytes sequestered in mice brains, thus resulting in a reduction of blood-brain barrier (BBB)dysfunction and hypothermia. Conclusions/Significance: The data presented here is the first indication that HBO treatment could be used as supportive therapy, perhaps in association with neuroprotective drugs, to prevent CM clinical outcomes, including death.

beta-Hydroxy-beta-methylbutyrate (HM beta) supplementation stimulates skeletal muscle hypertrophy in rats via the mTOR pathway

beta-Hydroxy-beta-methylbutyrate (HM beta) supplementation is used to treat cancer, sepsis and exercise-induced muscle damage. However, its effects on animal and human health and the consequences of this treatment in other tissues (e. g., fat and liver) have not been examined. The purpose of this study was to evaluate the effects of HM beta supplementation on skeletal muscle hypertrophy and the expression of proteins involved in insulin signalling. Rats were treated with HM beta (320 mg/kg body weight) or saline for one month. The skeletal muscle hypertrophy and insulin signalling were evaluated by western blotting, and hormonal concentrations were evaluated using ELISAs. HM beta supplementation induced muscle hypertrophy in the extensor digitorum longus (EDL) and soleus muscles and increased serum insulin levels, the expression of the mammalian target of rapamycin (mTOR) and phosphorylation of p70S6K in the EDL muscle. Expression of the insulin receptor was increased only in liver. Thus, our results suggest that HM beta supplementation can be used to increase muscle mass without adverse health effects.

Gluon-Spin Contribution to the Proton Spin from the Double-Helicity Asymmetry in Inclusive pi(0) Production in Polarized p plus p Collisions at root s=200 GeV

The double helicity asymmetry in neutral pion production for p(T) = 1 to 12 GeV/c was measured with the PHENIX experiment to access the gluon-spin contribution, Delta G, to the proton spin. Measured asymmetries are consistent with zero, and at a theory scale of mu 2 = 4 GeV(2) a next to leading order QCD analysis gives Delta G([0.02,0.3]) = 0.2, with a constraint of -0.7 < Delta G([0.02,0.3]) < 0.5 at Delta chi(2) = 9 (similar to 3 sigma) for the sampled gluon momentum fraction (x) range, 0.02 to 0.3. The results are obtained using predictions for the measured asymmetries generated from four representative fits to polarized deep inelastic scattering data. We also consider the dependence of the Delta G constraint on the choice of the theoretical scale, a dominant uncertainty in these predictions.

Measurement of the Parity-Violating Longitudinal Single-Spin Asymmetry for W(+/-) Boson Production in Polarized Proton-Proton Collisions at root s=500 GeV

We report the first measurement of the parity-violating single-spin asymmetries for midrapidity decay positrons and electrons from W(+) and W(-) boson production in longitudinally polarized proton-proton collisions at root s = 500 GeV by the STAR experiment at RHIC. The measured asymmetries, A(L)(W+) = -0.27 +/- 0.10(stat.) +/- 0.02(syst.) +/- 0.03(norm.) and A(L)(W-) = 0.14 +/- 0.19(stat.) +/- 0.02(syst.) +/- 0.01(norm.), are consistent with theory predictions, which are large and of opposite sign. These predictions are based on polarized quark and antiquark distribution functions constrained by polarized deep-inelastic scattering measurements.

Higher Moments of Net Proton Multiplicity Distributions at RHIC

200 GeV corresponding to baryon chemical potentials (mu(B)) between 200 and 20 MeV. Our measurements of the products kappa sigma(2) and S sigma, which can be related to theoretical calculations sensitive to baryon number susceptibilities and long-range correlations, are constant as functions of collision centrality. We compare these products with results from lattice QCD and various models without a critical point and study the root s(NN) dependence of kappa sigma(2). From the measurements at the three beam energies, we find no evidence for a critical point in the QCD phase diagram for mu(B) below 200 MeV.

Near-Barrier Fusion of the (8)B+(58)Ni Proton-Halo System

Fusion cross sections were measured for the exotic proton-halo nucleus (8)B incident on a (58)Ni target at several energies near the Coulomb barrier. This is the first experiment to report on the fusion of a protonhalo nucleus. The resulting excitation function shows a striking enhancement with respect to expectations for normal projectiles. Evidence is presented that the sum of the fusion and breakup yields saturates the total reaction cross section.

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at s=200 GeV

We report a measurement of the longitudinal double-spin asymmetry A(LL) and the differential cross section for inclusive pi(0) production at midrapidity in polarized proton collisions at s=200 GeV. The cross section was measured over a transverse momentum range of 1 < p(T)< 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p(T)< 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of pi(0)'s in their parent jets was found to be around 0.7 for electromagnetically triggered events.

Longitudinal spin transfer to Lambda and Lambda hyperons in polarized proton-proton collisions at s=200 GeV

The longitudinal spin transfer, D(LL), from high energy polarized protons to Lambda and Lambda hyperons has been measured for the first time in proton-proton collisions at s=200 GeV with the STAR detector at the Relativistic Heavy Ion Collider. The measurements cover pseudorapidity, eta, in the range |eta|< 1.2 and transverse momenta, p(T), up to 4 GeV/c. The longitudinal spin transfer is found to be D(LL)=-0.03 +/- 0.13(stat)+/- 0.04(syst) for inclusive Lambda and D(LL)=-0.12 +/- 0.08(stat)+/- 0.03(syst) for inclusive Lambda hyperons with <>=0.5 and << p(T)>>=3.7 GeV/c. The dependence on eta and p(T) is presented.

Reaction cross sections for (8)B, (7)Be, and (6)Li+(58)Ni near the Coulomb barrier: Proton-halo effects

Elastic scattering of (8)B, (7)Be, and (6)Li on a (58)Ni target has been measured at energies near the Coulomb barrier. Optical-model fits were made to the experimental angular distributions, and total reaction cross sections were deduced. A comparison with other systems provides striking evidence for proton-halo effects on (8)B reactions. As opposed to the situation for the neutron-halo nucleus (6)He, for which particle transfer dominates, the ""extra"" cross section observed for (8)B appears to result entirely from projectile breakup.

Intermolecular energy transfer and photostability of luminescence-tuneable multicolour PMMA films doped with lanthanide-beta-diketonate complexes

It is reported in this work the preparation, characterisation and photoluminescence study of poly(methylmethacrylate) (PMMA) thin films co-doped with [Eu(tta)(3)(H(2)O)(2)] and [Tb(acac)(3)(H(2)O)(3)] complexes. Both the composition and excitation wavelength may be tailored to fine-tune the emission properties of these Ln(3+)-beta-diketonate doped polymer films, exhibiting green and red primary colours, as well as intermediate colours. In addition to the ligand-Ln(3+) intramolecular energy transfer, it is observed an unprecedented intermolecular energy transfer process from the (5)D(4) emitting level of the Tb(3+) ion to the excited triplet state T(1) of the tta ligand coordinated to the Eu(3+) ion. The PMMA polymer matrix acts as a co-sensitizer and enhances the overall luminescence intensity of the polymer films. Furthermore, it provides considerable UV protection for the luminescent species and improves the photostability of the doped system.

Dissecting the Relation between a Nuclear Receptor and GATA: Binding Affinity Studies of Thyroid Hormone Receptor and GATA2 on TSH beta Promoter

Background: Much is known about how genes regulated by nuclear receptors (NRs) are switched on in the presence of a ligand. However, the molecular mechanism for gene down-regulation by liganded NRs remains a conundrum. The interaction between two zinc-finger transcription factors, Nuclear Receptor and GATA, was described almost a decade ago as a strategy adopted by the cell to up-or down-regulate gene expression. More recently, cell-based assays have shown that the Zn-finger region of GATA2 (GATA2-Zf) has an important role in down-regulation of the thyrotropin gene (TSH beta) by liganded thyroid hormone receptor (TR). Methodology/Principal Findings: In an effort to better understand the mechanism that drives TSH beta down-regulation by a liganded TR and GATA2, we have carried out equilibrium binding assays using fluorescence anisotropy to study the interaction of recombinant TR and GATA2-Zf with regulatory elements present in the TSH beta promoter. Surprisingly, we observed that ligand (T3) weakens TR binding to a negative regulatory element (NRE) present in the TSH beta promoter. We also show that TR may interact with GATA2-Zf in the absence of ligand, but T3 is crucial for increasing the affinity of this complex for different GATA response elements (GATA-REs). Importantly, these results indicate that TR complex formation enhances DNA binding of the TR-GATA2 in a ligand-dependent manner. Conclusions: Our findings extend previous results obtained in vivo, further improving our understanding of how liganded nuclear receptors down-regulate gene transcription, with the cooperative binding of transcription factors to DNA forming the core of this process.

Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly in patients with heart failure

Background -: Beta-2 adrenergic receptor gene polymorphisms Gln27Glu, Arg16Gly and Thr164Ile were suggested to have an effect in heart failure. We evaluated these polymorphisms relative to clinical characteristics and prognosis of alarge cohort of patients with heart failure of different etiologies. Methods -: We studied 501 patients with heart failure of different etiologies. Mean age was 58 years (standard deviation 14.4 years), 298 (60%) were men. Polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism. Results -: During the mean follow-up of 12.6 months (standard deviation 10.3 months), 188 (38%) patients died. Distribution of genotypes of polymorphism Arg16Gly was different relative to body mass index (chi(2) = 9.797; p = 0.04). Overall the probability of survival was not significantly predicted by genotypes of Gln27Glu, Arg16Gly, or Thr164Ile. Allele and haplotype analysis also did not disclose any significant difference regarding mortality. Exploratory analysis through classification trees pointed towards a potential association between the Gln27Glu polymorphism and mortality in older individuals. Conclusion -: In this study sample, we were not able to demonstrate an overall influence of polymorphisms Gln27Glu and Arg16Gly of beta-2 receptor gene on prognosis. Nevertheless, Gln27Glu polymorphism may have a potential predictive value in older individuals.

Ionic mobility of the solvated proton and acid-base titration in a four-compartment capillary electrophoresis system

Although H(+) and OH(-) are the most common ions in aqueous media, they are not usually observable in capillary electrophoresis (CE) experiments, because of the extensive use of buffer solutions as the background electrolyte. In the present work, we introduce CE equipment designed to allow the determination of such ions in a similar fashion as any other ion. Basically, it consists of a four-compartment piece of equipment for electrolysis-separated experiments (D. P. de Jesus et at, Anal. Chem., 2005, 77, 607). In such a system, the ends of the capillary are placed in two reservoirs, which are connected to two other reservoirs through electrolyte-filled tubes. The electrodes of the high-voltage power source are positioned in these reservoirs. Thus, the electrolysis products are kept away from the inputs of the capillary. The detection was provided by two capacitively coupled contactless conductivity detectors (CD), each one positioned about 11 cm from the end of the capillary. Two applications were demonstrated: titration-like procedures for nanolitre samples and mobility measurements. Strong and weak acids (pK(a) < 5), pure or mixtures, could be titrated. The analytical curve is linear from 50 mu M up to 10 mM of total dissociable hydrogen (r = 0.99899 for n =10) in 10-nL samples. By including D(2)O in the running electrolyte, we could demonstrate how to measure the mixed proton/deuteron mobility. When H(2)O/D(2)O (9 : 1 v/v) was used as the solvent, the mobility was 289.6 +/- 0.5 x 10(-5) cm(2) V(-1) s(-1). Due to the fast conversion of the species, this value is related to the overall behaviour of all isotopologues and isotopomers of the Zundel and Eigen structures, as well as the Stokesian mobility of proton and deuteron. The effect of neutral (o-phenanthroline) and negatively charged (chloroacetate) bases and aprotic solvent (DMSO) over the H(+) mobility was also demonstrated.