Incidence and predictors of severe liver fibrosis in HIV-infected patients with chronic hepatitis C in Brazil

The aim of this study was to examine the incidence and factors associated with the severity of liver fibrosis in 234 coinfected patients in Brazil. Patients were cared for in our clinic, from 1996 to 2004. Eligible patients were defined as patients with documented HIV and hepatitis C virus (HCV) infections and had previously undergone a liver biopsy. Patients with persistently normal alanine aminotransferase (ALT) were also included. The variables selected for study were age, gender, risk category, history of high alcohol consumption, CD4(+) T cell count, antiretroviral therapy usage, HCV genotype and duration of HCV infection. Stage of fibrosis was scored as follows: F0, no fibrosis; F1, portal fibrosis with no septa; F2, portal fibrosis with few septa; F3, bridging fibrosis with many septa; and F4, cirrhosis. The liver fibrosis stage was F3 in 39 (16.6%) and F4 in 20(8.5%) patients. Among patients with normal ALT, the liver fibrosis stage was F3-F4 in three patients (5.6%). Predictors of severe liver fibrosis (17344) by multivariate analysis were age (older patients) and genotype 3 (genotype I odds ratio [OR], 0.28; 95% confidence interval [0], 0.12 0.65). In summary, in the present study severe liver fibrosis was found in 25% of our patients and was associated with an age of more than 38 years at the time of liver biopsy as well as, HCV genotype 3. No differences were found with respect to CD4(+) T cell counts although patients with a CD4(+) T cell count greater than 50 were excluded.

BALB/c Mice Infected with Antimony Treatment Refractory Isolate of Leishmania braziliensis Present Severe Lesions due to IL-4 Production

Background: Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis-infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult. Methodology/Principal Findings: Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-gamma, TNF-alpha, IL-10 and TGF-beta were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S). Conclusion/Significance: We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens in human infection, this model could be useful to study the pathogenesis of the L. braziliensis infection, as well as to design new strategies of therapeutic intervention.

AUTOMATED DETERMINATION OF [Fe/H] AND [C/Fe] FROM LOW-RESOLUTION SPECTROSCOPY

We develop an automated spectral synthesis technique for the estimation of metallicities ([Fe/H]) and carbon abundances ([C/Fe]) for metal-poor stars, including carbon-enhanced metal-poor stars, for which other methods may prove insufficient. This technique, autoMOOG, is designed to operate on relatively strong features visible in even low- to medium-resolution spectra, yielding results comparable to much more telescope-intensive high-resolution studies. We validate this method by comparison with 913 stars which have existing high-resolution and low- to medium-resolution to medium-resolution spectra, and that cover a wide range of stellar parameters. We find that at low metallicities ([Fe/H] less than or similar to -2.0), we successfully recover both the metallicity and carbon abundance, where possible, with an accuracy of similar to 0.20 dex. At higher metallicities, due to issues of continuum placement in spectral normalization done prior to the running of autoMOOG, a general underestimate of the overall metallicity of a star is seen, although the carbon abundance is still successfully recovered. As a result, this method is only recommended for use on samples of stars of known sufficiently low metallicity. For these low- metallicity stars, however, autoMOOG performs much more consistently and quickly than similar, existing techniques, which should allow for analyses of large samples of metal-poor stars in the near future. Steps to improve and correct the continuum placement difficulties are being pursued.

A novel COL1A1 gene-splicing mutation (c. 1875+1G > C) in a Brazilian patient with osteogenesis imperfecta

Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone fragility and deformity, recurrent fractures, blue sclera, short stature, and dentinogenesis imperfecta. Most cases are caused by mutations in COL1A1 and COL1A2 genes. We present a novel splicing mutation in the COL1A1 gene (c. 1875+ 1G>C) in a 16-year-old Brazilian boy diagnosed as a type III osteogenesis imperfecta patient. This splicing mutation and its association with clinical phenotypes will be submitted to the reference database of COL1A1 mutations, which has no other description of this mutation.

Melatonin treatment decreases c-fos expression in a headache model induced by capsaicin

The aim of the present work was to analyze c-fos response within the trigeminal nucleus caudalis (TNC) of pinealectomized rats and animals that received intraperitoneal melatonin, after intracisternal infusion of capsaicin, used to induce intracranial trigeminovascular stimulation. Experimental groups consisted of animals that received vehicle solution (saline-ethanol-Tween 80, 8:1:1, diluted 1:50) only (VEI, n = 5); animals that received capsaicin solution (200 nM) only (CAP, n = 6); animals submitted to pinealectomy (PX, n = 5); sham-operated animals (SH, n = 5); animals submitted to pinealectomy followed by capsaicin stimulation (200 nM) after 15 days (PX + CAP, n = 7); and animals that received capsaicin solution (200 nM) and intraperitoneal melatonin (10 mg/kg) (CAP + MEL, n = 5). Control rats, receiving vehicle in the cisterna magna, showed a small number of c-fos-positive cells in the TNC (layer I/II) as well as the sham-operated and pinealectomized rats, when compared to animals stimulated by capsaicin. On the other hand, pinealectomized rats, which received capsaicin, presented the highest number of c-fos-positive cells. Animals receiving capsaicin and melatonin treatment had similar expression of the vehicle group. Our data provide experimental evidence to support the role of melatonin and pineal gland in the pathophysiology of neurovascular headaches.

Social Networks Shape the Transmission Dynamics of Hepatitis C Virus

Hepatitis C virus (HCV) infects 170 million people worldwide, and is a major public health problem in Brazil, where over 1% of the population may be infected and where multiple viral genotypes co-circulate. Chronically infected individuals are both the source of transmission to others and are at risk for HCV-related diseases, such as liver cancer and cirrhosis. Before the adoption of anti-HCV control measures in blood banks, this virus was mainly transmitted via blood transfusion. Today, needle sharing among injecting drug users is the most common form of HCV transmission. Of particular importance is that HCV prevalence is growing in non-risk groups. Since there is no vaccine against HCV, it is important to determine the factors that control viral transmission in order to develop more efficient control measures. However, despite the health costs associated with HCV, the factors that determine the spread of virus at the epidemiological scale are often poorly understood. Here, we sequenced partial NS5b gene sequences sampled from blood samples collected from 591 patients in Sao Paulo state, Brazil. We show that different viral genotypes entered Sao Paulo at different times, grew at different rates, and are associated with different age groups and risk behaviors. In particular, subtype 1b is older and grew more slowly than subtypes 1a and 3a, and is associated with multiple age classes. In contrast, subtypes 1a and 3b are associated with younger people infected more recently, possibly with higher rates of sexual transmission. The transmission dynamics of HCV in Sao Paulo therefore vary by subtype and are determined by a combination of age, risk exposure and underlying social network. We conclude that social factors may play a key role in determining the rate and pattern of HCV spread, and should influence future intervention policies.

Naturally-acquired humoral immune responses against the N- and C-termini of the Plasmodium vivax MSP1 protein in endemic regions of Brazil and Papua New Guinea using a multiplex assay

Background: Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. Methods: Glutathione S-transferase (GST) and GST-fusion proteins representing the N-terminus of the merozoite surface protein 1 of P. vivax, PvMSP1-N, and the C-terminus, PvMSP1-C, were covalently coupled to BioPlex carboxylated beads. Recombinant proteins and coupled beads were used, respectively, in ELISA and Bioplex assays using immune sera of P. vivax patients from Brazil and PNG to determine IgG and subclass responses. Concordances between the two methods in the seropositivity responses were evaluated using the Kappa statistic and the Spearman's rank correlation. Results: The results using this methodology were compared with the classical microtitre enzyme-linked immnosorbent assay ( ELISA), showing that the assay was sensitive, reproducible and had good concordance with ELISA; yet, further research into different statistical analyses seems desirable before claiming conclusive results exclusively based on multiplex assays. As expected, results demonstrated that PvMSP1 was immunogenic in natural infections of patients from different endemic regions of Brazil and Papua New Guinea ( PNG), and that age correlated only with antibodies against the C-terminus part of the molecule. Furthermore, the IgG subclass profiles were different in these endemic regions having IgG3 predominantly recognizing PvMSP1 in Brazil and IgG1 predominantly recognizing PvMSP1 in PNG. Conclusions: This study validates the use of the multiplex assay to measure naturally-acquired IgG antibodies against the merozoite surface protein 1 of P. vivax.

(7,9,10)Be elastic scattering and total reaction cross sections on a (12)C target

Elastic scattering angular distributions for (7)Be, (9)Be, and (10)Be isotopes on (12)C target were measured at laboratory energies of 18.8, 26.0, and 23.2 MeV, respectively. The analysis was performed in terms of optical model potentials using Woods-Saxon and double-folding form factors. Also, continuum discretized coupled-channels calculations were performed for (7)Be and (9)Be + (12)C systems to infer the role of breakup in the elastic scattering. For the (10)Be + (12)C system, bound states coupled-channels calculations were considered. Moreover, total reaction cross sections were deduced from the elastic scattering analysis and compared with published data on other weakly and tightly bound projectiles elastically scattered on the (12)C target, as a function of energy.

Elastic scattering and total reaction cross sections for the (8)Li+(12)C system

The elastic-scattering angular distribution for (8)Li on (12)C has been measured at E(LAB) = 23.9 MeV with (8)Li radioactive nuclear beam produced by the Radioactive Ion Beams in Brazil facility. This angular distribution was analyzed in terms of optical-model with Woods-Saxon and double-folding Sao Paulo potential. The roles of the breakup and inelastic channels were also investigated with cluster folding and deformed potentials, respectively, through coupled-channels calculations. The angular distribution for the proton-transfer (12)C((8)Li, (9)Be)(11)B reaction was also measured at the same energy. The spectroscopic factor for the <(9)Be|(8)Li + p > bound system was obtained and compared with shell-model calculations and with other experimental values. Total reaction cross sections for the present system were also extracted from the elastic-scattering analysis. A systematic of the reduced reaction cross sections obtained from the present and published data on (6,7,8)Li isotopes on (12)C was performed as a function of energy.

Possible hyperdeformed band in (36)Ar observed in (12)C+(24)Mg elastic scattering

Fifteen strongly oscillating angular distributions of the elastic scattering of (12)C + (24)Mg at energies around the Coulomb barrier (E(c.m). = 10.67-16.00 MeV) are reproduced by adding five Breit-Wigner resonance terms to the l = 2, 4, 6, 7, and 8 elastic S matrix. The nonresonant, background elastic scattering S matrix S(l)(0) is calculated using the Sao Paulo potential. The J = 2, 4, 6, 7, and 8 (h) over bar molecular resonances fit well into a rotational molecular band, together with other higher lying resonances observed in the (16)O + (20)Ne elastic scattering. We propose that the presently observed, largely deformed molecular band corresponds to the hyperdeformed band, which has been found previously in alpha-cluster calculations, as well as in a new Nilsson model calculation. Systematic study of its possible clusterizations predicts the preference of the (12)C + (24)Mg and (16)O + (20)Ne molecular structure, in accordance with our present results.

Elastic scattering and total reaction cross sections for the (8)B, (7)Be, and (6)Li+(12)C systems

Angular distributions for the elastic scattering of (8)B, (7)Be, and (6)Li on a (12)C target have been measured at E(lab) = 25.8, 18.8, and 12.3 MeV, respectively. The analyses of these angular distributions have been performed in terms of the optical model using Woods-Saxon and double-folding type potentials. The effect of breakup in the elastic scattering of (8)B + (12)C is investigated by performing coupled-channels calculations with the continuum discretized coupled-channel method and cluster-model folding potentials. Total reaction cross sections were deduced from the elastic-scattering analysis and compared with published data on elastic scattering of other weakly and tightly bound projectiles on (12)C, as a function of energy. With the exception of (4)He and (16)O, the data can be described using a universal function for the reduced cross sections.

A comparative solid state (13)C NMR and thermal study of CO(2) capture by amidines PMDBD and DBN

The present work shows study of the CO(2) capture by amidines DBN and PMDBD using (13)C solid-state NMR and thermal techniques. The solid state (13)C NMR analyses demonstrate the formation of a single PMDBD-CO(2) product which was assigned to stable bicarbonate. In the case of DBN, it is shown that two DBN-CO(2) products are formed, which are suggested to be stable bicarbonate and unstable carbamate. The role of water in the DBN-CO(2) capture as well as the stability of the products to environmental moisture was also investigated. The results suggest that the carbamate formation is favored in dry DBN, but in the presence of water it decompose to form bicarbonate. Thermal analysis shows a good gravimetric CO(2) absorption of DBN. Release of CO(2) was found to be almost quantitative from the PMDBDH(+) bicarbonate about 110 degrees C.

Pseudodifferential operators with C*-algebra-valued symbols: Abstract characterizations

Given a separable unital C*-algebra C with norm parallel to center dot parallel to, let E-n denote the Banach-space completion of the C-valued Schwartz space on R-n with norm parallel to f parallel to(2)=parallel to < f, f >parallel to(1/2), < f, g >=integral f(x)* g(x)dx. The assignment of the pseudodifferential operator A=a(x,D) with C-valued symbol a(x,xi) to each smooth function with bounded derivatives a is an element of B-C(R-2n) defines an injective mapping O, from B-C(R-2n) to the set H of all operators with smooth orbit under the canonical action of the Heisenberg group on the algebra of all adjointable operators on the Hilbert module E-n. In this paper, we construct a left-inverse S for O and prove that S is injective if C is commutative. This generalizes Cordes' description of H in the scalar case. Combined with previous results of the second author, our main theorem implies that, given a skew-symmetric n x n matrix J and if C is commutative, then any A is an element of H which commutes with every pseudodifferential operator with symbol F(x+J xi), F is an element of B-C(R-n), is a pseudodifferential operator with symbol G(x - J xi), for some G is an element of B-C(R-n). That was conjectured by Rieffel.

ON SPACES OF COMPACT OPERATORS ON C(K, X) SPACES

This paper concerns the spaces of compact operators kappa(E,F), where E and F are Banach spaces C([1, xi], X) of all continuous X-valued functions defined on the interval of ordinals [1, xi] and equipped with the supremun norm. We provide sufficient conditions on X, Y, alpha, beta, xi and eta, with omega <= alpha <= beta < omega 1 for the following equivalence: (a) kappa(C([1, xi], X), C([1, alpha], Y)) is isomorphic to kappa(C([1,eta], X), C([1, beta], Y)), (b) beta < alpha(omega). In this way, we unify and extend results due to Bessaga and Pelczynski (1960) and C. Samuel (2009). Our result covers the case of the classical spaces X = l(p) and Y = l(q) with 1 < p, q < infinity.

Spectroscopic, structural, and functional characterization of the alternative low-spin state of horse heart cytochrome c

The alternative low-spin states of Fe3+ and Fe2+ cytochrome c induced by SDS or AOT/hexane reverse micelles exhibited the heme group in a less rhombic symmetry and were characterized by electron paramagnetic resonance, UV-visible, CD, magnetic CD, fluorescence, and Raman resonance. Consistent with the replacement of Met 80 by another strong field ligand at the sixth heme iron coordination position, Fe3+ ALSScytc exhibited 1-nm Soret band blue shift and e enhancement accompanied by disappearance of the 695-nm charge transfer band. The Raman resonance, CD, and magnetic CD spectra of Fe3+ and Fe2+ ALSScytc exhibited significant changes suggestive of alterations in the heme iron microenvironment and conformation and should not be assigned to unfold because the Trp(59) fluorescence remained quenched by the neighboring heme group. ALSScytc was obtained with His(33) and His(26) carboxyethoxylated horse cytochrome c and with tuna cytochrome c (His(33) replaced by Asn) pointing out Lys(79) as the probable heme iron ligand. Fe3+ ALSScytc retained the capacity to cleave tert-butylhydroperoxide and to be reduced by dithiothreitol and diphenylacetaldehyde but not by ascorbate. Compatible with a more open heme crevice, ALSScytc exhibited a redox potential similar to 200 mV lower than the wild-type protein (1220 mV) and was more susceptible to the attack of free radicals.