Serology of paracoccidioidomycosis. II. Correlation between class-specific antibodies and clinical forms of the disease

Untreated and previously treated patients with paracoccidioidomycosis were studied for: (i) serum levels of total IgG, IgM and IgA immunoglobulins, by radial immunodiffusion and Paracoccidioides brasiliensis (Pb) antibodies, by indirect immunofluorescence; (ii) correlation between their levels with the clinical forms of the disease; (iii) correlation between the serum titres obtained by tube precipitin with those of anti-Pb IgG, IgM and IgA. In the untreated group, serum IgG levels were significantly increased in patients with the more systemic forms of the disease, especially the acute progressive form. Serum IgA levels were significantly increased in all patients with no statistical difference between clinical forms. Serum IgM levels were normal in all patients. Anti-Pb IgG, IgA and IgM were detected in 97·5%, 32·5% and 45·0% of all cases, respectively. There was a sharp tendency towards higher levels of anti-Pb IgG among those with the acute progressive form (83·4%) in relation to the chronic, more localized forms, mixed form (68·0%) and isolated organic form (55·5%). In the untreated and previously treated group sera, there was positive correlation between the level of anti-Pb IgG and positivity for the tube precipitin test, suggesting that the precipitin-type antibodies are of the IgG class. Broadly, the present data demonstrate a polyclonal activation of the humoral immune system in paracoccidioidomycosis, with a positive relationship between serological results and severity of the disease. © 1984.

Correlation between cell-mediated immunity and clinical forms of paracoccidioidomycosis

Cellular immune response to specific and non-specific stimulants was investigated, both in vivo and in vitro, in 29 healthy controls and in 53 previously untreated patients with the chronic isolated organic form (CIOF), the chronic mixed form (CMF) and the acute progressive form (APF) of paracoccidioidomycosis. The study included skin tests to Paracoccidioides brasiliensis antigen (PbAg) and phytohaemagglutinin (PHA), DNCB sensitization, determination of T lymphocytes and complement rosette-forming cells, lymphocyte transformation and leucocyte migration inhibition tests using PbAg and PHA. Patients displayed staggered cutaneous response to PHA and to PbAg, with marked decrease in intensity in the APF group. DNCB sensitization test and proliferative response of lymphocytes to PHA and PbAg were severely depressed in most of the patients. Leucocyte migration inhibition indices to PbAg were highly positive, while response to PHA was slightly decreased regardless of the clinical form. The number of T lymphocytes was reduced in most of patients and in them the number of complement-rosette forming cells was normal. The distribution of patients according to a suppression index, based in the results of the tests employed, revealed a tendency towards an increased degree of cellular immunosuppression from the least severe (CIOF) to the most severe (APF) clinical form of the disease. On the whole, the present study demonstrated a gamut of immunological reactivity in paracoccidioidomycosis. © 1985.

Classical and quantal aspects of resonant normal forms

The Birkhoff-Gustavson normal form is employed to study separately chaos and resonances in a system with two degrees of freedom. In the integrable regime, tunnelling effects are appreciable when the nearest level spacings show oscillations. Tunnelling among states in the libration and rotation tori regions is also observed. The regularity of avoided crossings due to tunnelling indicates a collective effect and is associated with an isolated resonance. The spectral fluctuations also show a strong level correlation. The Husimi distribution, on the other hand, is insensitive to avoided crossings. An integrable approximation to the overlap of resonances is obtained and a theoretical description is given for an isolated cubic resonance plus a complex orbit. In the non-integrable regime chaos is stronger after overlapping and preferentially at low energies.

Severe forms of neurocysticercosis: Treatment with albeimdazole

Study of 22 patients with the severe form of neurocysticercosis treated with albendazole (ABZ) administered in 6 different schedules ranging from 15 to 30 mg/kg/day for 21 to 60 days. Dextrochloropheniramine and ketoprofen were the adjuvant drugs Multiple symptoms were observed in 90 9% of patients. Intracranial hypertension was manifested in 90.9%. Hydrocephaly occurred in 86.4%. Evolution was satisfactory in 10 patients, 8 died and 4 had sequelae. Tomographic studies showed the appearance of an isolated IVth ventricle in 9 patients, after ventriculoperitoneal shunt, before ABZ treatment in 3 of them, during in 5 and after treatment in one. Median clinical follow-up duration was 10 months for the patients who died and 3-4 years for survivors. In 3 patients there was an increase in cyst size during the administration of the 15 mg/kg/day ABZ dose, which was not observed in any patient when the 30 mg/kg/day dose was used.

Distribution of exoantigens and a 43-kDa glycoprotein (gp43) in the yeast and mycelial forms of Paracoccidioides brasiliensis

Objective. Paracoccidioides brasiliensis antigens (strain 113) were located at ultrastructural level in both yeast and mycelial forms of the fungus. The reactivity of the sera employed was analysed. Materials and methods. Immunofluorescence and ultrastructural protein A-gold immunolabelling techniques were performed using two polyclonal antisera: one against P. brasiliensis exoantigens and the other against a 43-kDa glycoprotein (gp43). Immunoblotting assays were employed to define reactivity of these antisera with somatic and metabolic antigens of both forms of the fungus. Results. The techniques employed revealed in both yeast and mycelial forms of P. brasiliensis a similar antigenic distribution. The antigens deposits were seen within the cytoplasm, and over the cell wall of the fungus. The anti-exoantigen serum recognized several bands in both forms of the fungus. The anti-gp43 serum reacted strongly with the 43-kDa fraction and weakly with few other fractions. Conclusions. Immunocytochemical techniques suggest a protein synthesis within the cytoplasm followed by excretion through the cell wall. Similar results employing both polyclonal antisera were obtained.

Morphometry of the sexual forms of Acromyrmex subterraneus brunneus Forel, 1911 (Hym., Formicidae) in queenright and queenless laboratory colonies

A morphometric study was performed on the sexual forms of Acromyrmex subterraneus brunneus in colonies kept under laboratory conditions. The males studied were obtained from queenright and queenless colonies, i.e. they were produced by either the queen or the workers. Cluster analysis revealed a wide distribution in the size of the sexual forms produced in queenless colonies compared with queenright colonies, and that some of the worker-produced males were significantly smaller than those produced in queenright colonies. However, we found no indication that the males produced in queenless colonies are unable to mate, as smaller and larger males had identical genitalia that varied only in size, and therefore probably represent an alternative route of reproduction in this species. © 2005 Blackwell Verlag.

Magnetic images of pharmaceutical dosage forms in the human gastrointestinal tract

Oral administration with solid dosage forms is a common route in the drug therapy widely used. The drug release by the disintegration process occurs in several gastrointestinal tract (GIT) regions. AC Biosusceptometry (ACB) was originally proposal to characterize the disintegration process of tablets in vitro and in the human stomach, through changes in magnetic signals. The aim of this work was to employ a multisensor ACB system to monitoring magnetic tablets and capsules in the human GIT and to obtain the magnetic images of the disintegration process. The ACB showed accuracy to quantify the gastric residence time, the intestinal transit time and the magnetic images allowed to visualize the disintegration of magnetic formulations in the GIT. The ACB is a non-invasive, radiation free technique, completely safe and harmless to the volunteers and had demonstrated potential to evaluate pharmaceutical dosage forms in the human gastrointestinal tract. © 2005 IEEE.

Ex vivo biocompatibility tests of regular and white forms of mineral trioxide aggregate

Aim: To examine the genotoxicity and cytotoxicity of regular and white mineral trioxide aggregate (MTA) ex vivo by the single-cell gel (comet) assay and trypan blue exclusion test, respectively. Methodology: Aliquots of 1 × 10 4 Chinese hamster ovary cells were incubated at 37°C for 3 h with grey and white forms of MTA at final concentrations ranging from 1 to 1000 μg mL -1. The negative control group was treated with vehicle control phosphate buffer solution for 3 h at 37°C and the positive control group was treated with methyl metasulfonate (at 1 μg mL -1) for 1 h at 37°C. After incubation, the cells were centrifuged at 180 g for 5 min and washed twice with fresh medium and resuspended with fresh medium. Each individual treatment was repeated three times consecutively to ensure reproducibility. Parameters from single-cell gel (comet) and cytotoxicity assays were assessed by the Kruskal-Wallis nonparametric test. Results: Neither compounds produced genotoxic effects with respect to the single-cell gel (comet) assay in all concentrations evaluated. In the same way, the dose-response relationships of all compounds tested at concentrations ranging from 1 to 1000 μg mL -1 on cell viability assessed by the trypan blue assay displayed no statistically significant differences (P > 0.05) for either endodontic material. Conclusions: Regular (grey) and white MTA are not genotoxins and do not induce cellular death. © 2006 International Endodontic Journal.

A new insight about pharmaceutical dosage forms for benzathine penicillin G

In this work, a micellar system of benzathine penicillin G (BPG) in sodium deoxycholate (NaDC) was developed and evaluated physicochemically. The solubility profile of the drug in water and buffer solutions at various pH was determined, as well as its n-octanol/water partition coefficient. The Critical Micellar Concentration of NaDC and its ability to incorporate BPG were also assessed. The study was carried out at low and high ionic strength which was adjusted by the addition of sodium chloride. The results demonstrated the ability of the micellar system to incorporate BPG, as well as to increase its apparent solubility in water. The enhancement of the solubility of BPG by the presence of NaDC micelles could be analyzed quantitatively within the framework of the pseudo-phase model. Concentration analysis showed that the micellar system could attain up to 90% incorporation of BPG. The incorporated drug is expected to exhibit improved stability, since the antibiotic enclosed in the hydrophobic core of micelles is rather shielded from the aqueous external environment.

Orphan nuclear receptor NGFI-B forms dimers with nonclassical interface

The orphan receptor nerve growth factor-induced B (NGFI-B) is a member of the nuclear receptor's subfamily 4A (Nr4a). NGFI-B was shown to be capable of binding both as a monomer to an extended half-site containing a single AAAGGTCA motif and also as a homodimer to a widely separated everted repeat, as opposed to a large number of nuclear receptors that recognize and bind specific DNA sequences predominantly as homo- and/or heterodimers. To unveil the structural organization of NGFI-B in solution, we determined the quaternary structure of the NGFI-B LBD by a combination of ab initio procedures from small-angle X-ray scattering (SAXS) data and hydrogen-deuterium exchange followed by mass spectrometry. Here we report that the protein forms dimers in solution with a radius of gyration of 2.9 nm and maximum dimension of 9.0 nm. We also show that the NGFI-B LBD dimer is V-shaped, with the opening angle significantly larger than that of classical dimer's exemplified by estrogen receptor (ER) or retinoid X receptor (RXR). Surprisingly, NGFI-B dimers formation does not occur via the classical nuclear receptor dimerization interface exemplified by ER and RXR, but instead, involves an extended surface area composed of the loop between helices 3 and 4 and C-terminal fraction of the helix 3. Remarkably, the NGFI-B dimer interface is similar to the dimerization interface earlier revealed for glucocorticoid nuclear receptor (GR), which might be relevant to the recognition of cognate DNA response elements by NGFI-B and to antagonism of NGFI-B-dependent transcription exercised by GR in cells. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 The Protein Society.

Non-conventional applications of computerized tomography: Analysis of solid dosage forms produced by pharmaceutical industry

X-ray computed tomography (CT) refers to the cross-sectional imaging of an object measuring the transmitted radiation at different directions. In this work, we describe a non-conventional application of computerized tomography: visualization and improvements in the understanding of some internal structural features of solid dosage forms. A micro-CT X-ray scanner, with a minimum resolution of 30 μm was used to characterize some pharmaceutical tablets, granules, controlled-release osmotic tablet and liquid-filled soft-gelatin capsules. The analysis presented in this work are essentially qualitative, but quantitative parameters, such as porosity, density distribution, tablets dimensions, etc. could also be obtained using the related CT techniques. © 2010 American Institute of Physics.

Cellular decomposition of quaternionic spherical space forms

We obtain an explicit cellular decomposition of the quaternionic spherical space forms, manifolds of positive constant curvature that are factors of an odd sphere by a free orthogonal action of a generalized quaternionic group. The cellular structure gives and explicit description of the associated cellular chain complex of modules over the integral group ring of the fundamental group. As an application we compute the Whitehead torsion of these spaces for any representation of the fundamental group. © 2012 Springer Science+Business Media B.V.

Urea-induced unfolding of Glossoscolex paulistus hemoglobin, in oxy- and cyanomet-forms: A dissociation model

The urea effect on the giant extracellular hemoglobin of Glossoscolex paulistus (HbGp) stability was studied by analytical ultracentrifugation (AUC) and small angle X-ray scattering (SAXS). AUC data show that the sedimentation coefficient distributions curves c (S), at 1.0mol/L of urea, display a single peak at 57 S, associated to the undissociated protein. The increase in urea concentration, up to 4.0mol/L, induces the appearance of smaller species, due to oligomeric dissociation. The sedimentation coefficients and molecular masses are 9.2S and 204kDa for the dodecamer (abcd)3, 5.5S and 69kDa for the tetramer (abcd), 4.1S and 52kDa for the trimer (abc) and 2.0 S and 17kDa for the monomer d, respectively. SAXS data show initially a decrease in the I(0) values due to the oligomeric dissociation, and then, above 4.0mol/L of denaturant, for oxy-HbGp, and above 6.0mol/L for cyanomet-HbGp, an increase in the maximum dimension and gyration radius is observed, due to the unfolding process. According to AUC and SAXS data the HbGp unfolding is described by two phases: the first one, at low urea concentration, below 4.0mol/L, characterizes the oligomeric dissociation, while the second one, at higher urea concentration, is associated to the unfolding of dissociated species. Our results are complementary to a recent report based on spectroscopic observations. © 2012 Elsevier B.V.

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