Thermal analysis and compatibility studies of prednicarbate with excipients used in semi solid pharmaceutical form

Differential Scanning Calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TG/DTG) and infrared spectroscopy (IR) techniques were used to investigate the compatibility between prednicarbate and several excipients commonly used in semi solid pharmaceutical form. The thermoanalytical studies of 1:1 (m/m) drug/excipient physical mixtures showed that the beginning of the first thermal decomposition stage of the prednicarbate (T (onset) value) was decreased in the presence of stearyl alcohol and glyceryl stearate compared to the drug alone. For the binary mixture of drug/sodium pirrolidone carboxilate the first thermal decomposition stage was not changed, however the DTG peak temperature (T (peak DTG)) decreased. The comparison of the IR spectra of the drug, the physical mixtures and of the thermally treated samples confirmed the thermal decomposition of prednicarbate. By the comparison of the thermal profiles of 1:1 prednicarbate:excipients mixtures (methylparaben, propylparaben, carbomer 940, acrylate crosspolymer, lactic acid, light liquid paraffin, isopropyl palmitate, myristyl lactate and cetyl alcohol) no interaction was observed.

Thixocasting of an A356 alloy: Fluidity, porosity distribution and thermomechanical fatigue behavior

An extensive set of experiments was performed on a semi-solid A356 alloy in order to assess its flow behavior, mechanical properties, microstructural evolution and porosity level. Three different microstructural conditioning techniques (raw material preparation) were employed: deformation recrystallization, magnetohydrodynamic stirring and low temperature pouring. Measurement of microstructural parameters such as Al-alpha particle size, shape factor, contiguity and entrapped liquid showed a relative equivalency among the various conditioning techniques. It was found that the strongest influence on semi-solid slurry fluidity is exerted by the mould temperature. Tensile properties and porosity levels were measured on a demonstration part produced with different slurry ingate velocities. Results showed similar strength levels among all thixocast samples, a strong correlation between elongation and pore volume fraction and porosity levels much lower than the typical figure for permanent mould or die cast Al-Si alloys. Finally, thermomechanical fatigue tests results were much more favorable to the semi-solid material when compared with the conventionally cast alloy, a result attributed to lower porosity, spheroidal shape of the Al-alpha phase, and refined Si eutectic particles. alpha 2007 Elsevier B.V. All rights reserved.

Comparison of Humanized IgG and FvFc Anti-CD3 Monoclonal Antibodies Expressed in CHO Cells

Two humanized monoclonal antibody constructs bearing the same variable regions of an anti-CD3 monoclonal antibody, whole IgG and FvFc, were expressed in CHO cells. Random and site-specific integration were used resulting in similar expression levels. The transfectants were selected with appropriate selection agent, and the surviving cells were plated in semi-solid medium for capture with FITC-conjugated anti-human IG antibody and picked with the robotic ClonePix FL. Conditioned media from selected clones were purified by affinity chromatography and characterized by SDS-PAGE, Western-blot, SEC-HPLC, and isoelectric focusing. Binding to the target present in healthy human mononuclear cells was assessed by flow cytometry, as well as by competition between the two constructs and the original murine monoclonal antibody. The humanized constructs were not able to dislodge the murine antibody while the murine anti-CD3 antibody could dislodge around 20% of the FvFc or IgG humanized versions. Further in vitro and in vivo pre-clinical analyses will be carried out to verify the ability of the humanized versions to demonstrate the immunoregulatory profile required for a humanized anti-CD3 monoclonal antibody.

Cysteinyl-leukotriene type 1 receptors transduce a critical signal for the up-regulation of eosinophilopoiesis by interleukin-13 and eotaxin in murine bone marrow

IL-13 and eotaxin play important, inter-related roles in asthma models. In the lungs, CysLT, produced by the 5-LO-LTC4S pathway, mediate some local responses to IL-13 and eotaxin; in bone marrow, CysLT enhance IL-5-dependent eosinophil differentiation. We examined the effects of IL-13 and eotaxin on eosinophil differentiation. Semi-solid or liquid cultures were established from murine bone marrow with GM-CSF or IL-5, respectively, and the effects of IL-13, eotaxin, or CysLT on eosinophil colony formation and on eosinophil differentiation in liquid culture were evaluated, in the absence or presence of: a) the 5-LO inhibitor zileuton, the FLAP inhibitor MK886, or the CysLT1R antagonists, montelukast and MK571; b) mutations that inactivate 5-LO, LTC4S, or CysLT1R; and c) neutralizing mAb against eotaxin and its CCR3 receptor. Both cytokines enhanced GM-CSF-dependent eosinophil colony formation and IL-5-stimulated eosinophil differentiation. Although IL-13 did not induce eotaxin production, its effects were abolished by anti-eotaxin and anti-CCR3 antibodies, suggesting up-regulation by IL-13 of responses to endogenous eotaxin. Anti-CCR3 blocked eotaxin completely. The effects of both cytokines were prevented by zileuton, MK886, montelukast, and MK571, as well as by inactivation of the genes coding for 5-LO, LTC4S, and CysLT1R. In the absence of either cytokine, these treatments or mutations had no effect. These findings provide evidence for: a) a novel role of eotaxin and IL-13 in regulating eosinophilopoiesis; and b) a role for CysLTRs in bone marrow cells in transducing cytokine regulatory signals. J. Leukoc. Biol. 87: 885-893; 2010.

An Alternative Section Method for Casting and Posterior Laser Welding of Metallic Frameworks for an Implant-Supported Prosthesis

Purpose: The aim of this study was to compare the accuracy of fit of three types of implant-supported frameworks cast in Ni-Cr alloy: specifically, a framework cast as one piece compared to frameworks cast separately in sections to the transverse or the diagonal axis, and later laser welded. Materials and Methods: Three sets of similar implant-supported frameworks were constructed. The first group of six 3-unit implant-supported frameworks were cast as one piece, the second group of six were sectioned in the transverse axis of the pontic region prior to casting, and the last group of six were sectioned in the diagonal axis of the pontic region prior to casting. The sectioned frameworks were positioned in the matrix (10 N(.)cm torque) and laser welded. To evaluate passive fit, readings were made with an optical microscope with both screws tightened and with only one-screw tightened. Data were submitted to ANOVA and Tukey-Kramer`s test (p < 0.05). Results: When both screws were tightened, no differences were found between the three groups (p > 0.05). In the single-screw-tightened test, with readings made opposite to the tightened side, the group cast as one piece (57.02 +/- 33.48 mu m) was significantly different (p < 0.05) from the group sectioned diagonally (18.92 +/- 4.75 mu m) but no different (p > 0.05) from the group transversally sectioned (31.42 +/- 20.68 mu m). On the tightened side, no significant differences were found between the groups (p > 0.05). Conclusions: Results of this study showed that casting diagonally sectioned frameworks lowers misfit levels of prosthetic implant-supported frameworks and also improves the levels of passivity to the same frameworks when compared to structures cast as one piece.

Topological instability and electronegativity effects on the glass-forming ability of metallic alloys

The glass-forming ability (GFA) of metallic alloys is associated with a topological instability criterion combined with a new parameter based on the average electronegativity difference of an element and its surrounding neighbours. In this model, we assume that during solidification the glassy phase competes directly with the supersaturated solid solution having the lowest topological instability factor for a given composition. This criterion is combined with the average electronegativity difference among the elements in the alloy, which reflects the strength of the liquid. The GFA is successfully correlated with this combined criterion in several binary glass-forming systems.

Microstructure and texture assessment of Al-Mn-Fe-Si (3003) aluminum alloy produced by continuous and semicontinuous casting processes

Aluminum sheets are currently produced by the direct-chill process (DC). The need for low-cost aluminum sheets is a challenge for the development of new materials produced by the twin roll caster (TRC) process. It is expected that sheets produced from these different casting procedures will differ in their microstructure. These differences in microstructure and in the crystallographic texture have great impact on sheet mechanical properties and formability. The present study investigated microstructure and evaluated texture of two strips of Al-Mn-Fe-Si (3003) aluminum alloy produced by TRC and by hot-rolling processes. It was possible to notice that the microstructure, morphology, and grain size of the TRC sample were more homogenous than those found in hot-rolled samples. Both strips, obtained by the two processes, showed strong texture gradient across the thickness.

Evaluation of flow regimes in a semi-cylindrical spouted bed through statistical, mutual information, spectral and Hurst`s analysis

Hydrodynamic studies were conducted in a semi-cylindrical spouted bed column of diameter 150 mm, height 1000 mm, conical base included angle of 60 degrees and inlet orifice diameter 25 mm. Pressure transducers at several axial positions were used to obtain pressure fluctuation time series with 1.2 and 2.4 mm glass beads at U/U-ms from 0.3 to 1.6, and static bed depths from 150 to 600 mm. The conditions covered several flow regimes (fixed bed, incipient spouting, stable spouting, pulsating spouting, slugging, bubble spouting and fluidization). Images of the system dynamics were also acquired through the transparent walls with a digital camera. The data were analyzed via statistical, mutual information theory, spectral and Hurst`s Rescaled Range methods to assess the potential of these methods to characterize the spouting quality. The results indicate that these methods have potential for monitoring spouted bed operation.

Growth and Melting of Metallic Nanoclusters in Glass: A Review of Recent Investigations

The mechanisms of nucleation and growth and the solid-to-liquid transition of metallic nanoclusters embedded in sodium borate glass were recently studied in situ via small-angle X-ray scattering (SAXS) and wide-an-le X-ray scattering (WAXS). SAXS results indicate that, under isothermal annealing conditions, the formation and growth of Bi or Ag nanoclusters embedded in sodium borate glass occurs through two successive stages after a short incubation period. The first stage is characterized by the nucleation and growth of spherical metal clusters promoted by the diffusion of Bi or Ag atoms through the initially supersaturated glass phase. The second stage is named the coarsening stage and occurs when the (Bi- or Ag-) doping level of the vitreous matrix is close to the equilibrium value. The experimental results demonstrated that, at advanced stages of the growth process, the time dependence of the average radius and density number of the clusters is in agreement with the classical Lifshitz-Slyozov-Waoner (LSW) theory. However, the radius distribution function is better described by a lognormal function than by the function derived from the theoretical LSW model. From the results of SAXS measurements at different temperatures, the activation energies for the diffusion of Ag and Bi through sodium borate glass were determined. In addition, via combination of the results of simultaneous WAXS and SAXS measurements at different temperatures, the crystallographic structure and the dependence of melting temperature T(m) on crystal radius R of Bi nanocrystals were established. The experimental results indicate that T(m) is a linear and decreasing function of nanocrystal reciprocal radius 1/R, in agreement with the Couchman and Jesser theoretical model. Finally, a weak contraction in the lattice parameters of Bi nanocrystals with respect to bulk crystals was established.

Effect of casting atmosphere on the shear bond strength of a ceramic to Ni-Cr and Ni-Cr-Be alloys

The success of metal-ceramic restorations depends on an optimal bond between metal and ceramic. This study evaluated the effect of 3 casting atmospheres on the metal-ceramic bond strength (MCBS) of 2 Ni-Cr alloys, with beryllium (Fit Cast V) and without beryllium (Fit Cast SB). Sixty acrylic resin patterns (8 mm long and 5 mm diameter) were obtained using a fluorocarbon resin matrix. Wax was used to refine the surface of acrylic resin patterns that were invested and cast in an induction casting machine under normal, vacuum, and argon atmospheres at a temperature of 1340ºC. The castings were divested manually and airborne-particle abraded with 100-µm aluminum-oxide. Ten castings were obtained for each group. The IPS Classic V ceramic was applied (2 mm high and 5 mm diameter). The shear bond strength was tested in a mechanical testing machine with a crosshead speed of 2.0 mm/min. The MCBS data (MPa) were subjected to 2-way analysis of variance (α=0.05). There was no statistically significant difference (p>0.05) between the alloys or among the casting atmospheres. Within the limitations of this study, it may be concluded that the presence of beryllium and the casting atmosphere did not interfere in the MCBS of the evaluated metal-ceramic combinations

Comparative study of two commercially pure titanium casting methods

The interest in using titanium to fabricate removable partial denture (RPD) frameworks has increased, but there are few studies evaluating the effects of casting methods on clasp behavior. OBJECTIVE: This study compared the occurrence of porosities and the retentive force of commercially pure titanium (CP Ti) and cobalt-chromium (Co-Cr) removable partial denture circumferential clasps cast by induction/centrifugation and plasma/vacuum-pressure. MATERIAL AND METHODS: 72 frameworks were cast from CP Ti (n=36) and Co-Cr alloy (n=36; control group). For each material, 18 frameworks were casted by electromagnetic induction and injected by centrifugation, whereas the other 18 were casted by plasma and injected by vacuum-pressure. For each casting method, three subgroups (n=6) were formed: 0.25 mm, 0.50 mm, and 0.75 mm undercuts. The specimens were radiographed and subjected to an insertion/removal test simulating 5 years of framework use. Data were analyzed by ANOVA and Tukey's to compare materials and cast methods (α=0.05). RESULTS: Three of 18 specimens of the induction/centrifugation group and 9 of 18 specimens of plasma/vacuum-pressure cast presented porosities, but only 1 and 7 specimens, respectively, were rejected for simulation test. For Co-Cr alloy, no defects were found. Comparing the casting methods, statistically significant differences (p<0.05) were observed only for the Co-Cr alloy with 0.25 mm and 0.50 mm undercuts. Significant differences were found for the 0.25 mm and 0.75 mm undercuts dependent on the material used. For the 0.50 mm undercut, significant differences were found when the materials were induction casted. CONCLUSION: Although both casting methods produced satisfactory CP Ti RPD frameworks, the occurrence of porosities was greater in the plasma/vacuum-pressure than in the induction/centrifugation method, the latter resulting in higher clasp rigidity, generating higher retention force values.

Influence of dental metallic artifact from multislice CT in the assessment of simulated mandibular lesions

OBJECTIVE: This study evaluated the influence of metallic dental artifacts on the accuracy of simulated mandibular lesion detection by using multislice technology. MATERIAL AND METHODS: Fifteen macerated mandibles were used. Perforations were done simulating bone lesions and the mandibles were subjected to axial 16 rows multislice CT images using 0.5 mm of slice thickness with 0.3 mm interval of reconstruction. Metallic dental restorations were done and the mandibles were subjected again to CT in the same protocol. The images were analyzed to detect simulated lesions in the mandibles, verifying the loci number and if there was any cortical perforation exposing medullar bone. The analysis was performed by two independent examiners using e-film software. RESULTS: The samples without artifacts presented better results compared to the gold standard (dried mandible with perforations). In the samples without artifacts, all cortical perforation were identified and 46 loci were detected (of 51) in loci number analysis. Among the samples with artifacts, 12 lesions out of 14 were recognized regarding medullar invasion, and 40 out of 51 concerning loci number. The sensitivity in samples without artifacts was 90% and 100% regarding loci number and medullar invasion, respectively. In samples with artifacts, these values dropped to 78% and 86%, respectively. The presence of metallic restorations affected the sensitivity values of the method, but the difference was not significant (p>0.05). CONCLUSIONS: Although there were differences in the results of samples with and without artifacts, the presence of metallic restoration did not lead to misinterpretation of the final diagnosis. However, the validity of multislice CT imaging in this study was established for detection of simulated mandibular bone lesions.

Análise de um ciclone semi-estacionário na costa sul do Brasil associado a bloqueio atmosférico

Na primeira semana de maio de 2008, durante quatro dias, um ciclone em superfície permaneceu semi-estacionário na costa da região sul do Brasil. Este sistema foi responsável por chuvas e ventos fortes no Rio Grande do Sul e Santa Catarina, os quais causaram muitos danos (queda de árvores, enchentes e desabamentos). O objetivo deste trabalho é avaliar o processo de formação e entender os mecanismos responsáveis pelo lento deslocamento do ciclone, já que a maioria dos ciclones nesta região possui deslocamento mais rápido. A equação de desenvolvimento de Sutcliffe mostrou que a advecção de vorticidade absoluta ciclônica na média troposfera e a advecção de ar quente na camada entre 1000-500 hPa foram mecanismos importantes para a ciclogênese. Neste período, o intenso aquecimento diabático também contribuiu para a ciclogênese, à medida que se contrapôs ao intenso resfriamento adiabático devido aos movimentos verticais ascendentes. A advecção de vorticidade absoluta ciclônica que favoreceu a ciclogênese esteve associada a um Vórtice Ciclônico em Altos Níveis (VCAN), que se formou numa região de anomalia de vorticidade potencial. O VCAN se manteve semi-estacionário e compôs o setor norte de um bloqueio do tipo dipolo. Tal bloqueio intensificou um anticiclone em superfície, situado a sul/leste do ciclone, o que contribuiu para o ciclone se manter semi-estacionário. O movimento atípico e lento do ciclone para sul, e em alguns períodos para sudoeste, esteve associado com advecções de vorticidade absoluta ciclônica na média troposfera e de ar quente no seu setor sul. Somente quando o bloqueio em níveis médios e a anomalia de vorticidade potencial em níveis médios/altos se enfraqueceram, o ciclone em superfície se afastou da costa sul do Brasil.

Convecção linearmente organizada na área de Petrolina, semi-árido do Nordeste do Brasil: aspectos em meso e grande escala

É apresentado um estudo sobre sistemas convectivos linearmente organizados e observados por um radar meteorológico banda-C na região semi-árida do Nordeste do Brasil. São analisados três dias (27 a 29) de março de 1985, com ênfase na investigação do papel desempenhado por fatores locais e de grande escala no desenvolvimento dos sistemas. No cenário de grande escala, a área de cobertura do radar foi influenciada por um cavado de ar superior austral no dia 27 e por um vórtice ciclônico de altos níveis no dia 29. A convergência de umidade próxima à superfície favoreceu a atividade convectiva nos dias 27 e 29, enquanto que divergência de umidade próxima à superfície inibiu a atividade convectiva no dia 28. No cenário de mesoescala, foi observado que o aquecimento diurno é um fator importante para a formação de células convectivas, somando-se a ele o papel determinante da orografia na localização dos ecos. De maneira geral, as imagens de radar mostram os sistemas convectivos linearmente organizados em áreas elevadas e núcleos convectivos intensos envolvidos por uma área de precipitação estratiforme. Os resultados indicam que convergência do fluxo de umidade em grande escala e aquecimento radiativo, são fatores determinantes na evolução e desenvolvimento dos ecos na área de estudo.

Evaluation of a simple hyphenated system for flow injection solid-phase pre-concentration and capillary electrophoresis

In this work, the development and evaluation of a hyphenated flow injection-capillary electrophoresis system with on-line pre-concentration is described. Preliminary tests were performed to investigate the influence of flow rates over the analytical signals. Results revealed losses in terms of sensitivity of the FIA-CE system when compared to the conventional CE system. To overcome signal decrease and to make the system more efficient, a lower flow rate was set and an anionic resin column was added to the flow manifold in order to pre-concentrate the analyte. The pre-concentration FIA-CE system presented a sensitivity improvement of about 660% and there was only a small increase of 8% in total peak dispersion. These results have confirmed the great potential of the proposed system for many analytical tasks especially for low concentration samples.