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Biomedical subjects

A G Oliveira

Publications and source records attributed to A G Oliveira.

At least 19 recordsLinked to original sources
PubMed2006

Doxorubicin biocompatible O/W microemulsion stabilized by mixed surfactant containing soya phosphatidylcholine.

Microemulsions (ME) containing soya phosphatidylcholine (SPC)/polyoxyethylenglycerol trihydroxystearate 40 (EU)/sodium oleate (SO) as surfactant cholesterol (CHO) as oil phase and aqueous buffer were studied. Pseudo-ternary phase diagrams of the investigated systems were obtained at constant SPC/EU/SO weight ratio 3.5:3.5:3.0 by titration, in order to characterize the proportions between the components to form clear systems. The dynamic light scattering results showed that the size of the oil droplets decreases significantly with the ratio of surfactant/oil phase added to system. Depending on the composition ME system could exhibit a thixotropic behavior. The apparent viscosity increased 25- and 13-folds with cholesterol concentration for drug-free and drug-load ME, respectively. It was also verified that the octanol/aqueous buffer partition coefficient (KO/B) of doxorubicin (DOX) was pH dependent increasing abruptly above pH 6.0. It was possible to incorporate 2.24 mg/ml of DOX into ME. The incorporation of DOX in the ME systems increased the droplets size for all surfactant concentrations used in the system. The results suggest that DOX interacts with the microstructure of the ME at the studied pH increasing significantly the drug solubility. It was possible to conclude that the investigated ME can be a very promising vehicle as drug-carrier for administration of doxorubicin.

Antibiotics, Antineoplastic↗
PubMed2005

On the incorporation of the non-steroidal anti-inflammatory naproxen into cationic O/W microemulsions.

Microemulsions (ME) containing hexadecyltrimethylammonium bromide (HTAB)/ethanol as surfactant, isopropylmyristate (IM) or butylstearate (BS) as oil phase and aqueous buffer were studied. Pseudo-ternary phase diagrams of the investigated systems were obtained at constant surfactant/cosurfactant molar ratio (1:5) by titration in order to characterize the proportions between the components to obtain clear systems. Oil in water microemulsions were prepared in a wide range of phase volume (phi). UV-vis absorption spectra of naproxen at pH 5.5 showed that the solubility of Np increases significantly in the presence of O/W ME in high phase volumes. For both, IM and BS microemulsions, the dynamic light scattering experiments showed that the size of the oil droplets remains constant in low values of phi, increasing abruptly in high phi values. Phase solubility study revealed that for both IM and BS microemulsions, the drug incorporation followed a straight-line profile in all range of phi. The data could be analyzed through the phase-separation model and the association constants (K) calculated varied from 27 to 90 M(-1), depending on the pH and on the microemulsion oil phase.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Studies on the encapsulation of diclofenac in small unilamellar liposomes of soya phosphatidylcholine.

The encapsulation of acid (AD) and sodium diclofenac (SD) in small unilamellar liposomes (SUV) as well as the interactions of the drug with the bilayer was studied. SUV was prepared by sonication from multilamellar liposomes containing soya phosphatidylcholine and diclofenac at various proportions. The size distribution obtained from dynamic light scattering showed that the incorporation of SD decreases significantly the size of the liposomes suggesting that the drug interacts with the bilayer of the liposomes. This size decrease is related with the phase transition of liposomes to mixed micelar solution. The encapsulation of the hydrophilic dye indocyanine green in the aqueous compartment of liposomes showed that the rate of captured dye decreases with SD concentration suggesting the transition of liposomes to mixed micelles. The (31)P NMR analysis indicates that SD interacts with the phosphate of phosphatidylcholine head groups. A schematic model for interaction of SD with phosphatidylcholine of the liposomes in which the diclofenac anion interacts with the ammonium group of the phospholipid and the dichlorophenyl ring occupies a more internal site of bilayer near phosphate group was proposed.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Study of the diclofenac/phospholipid interactions with liposomes and monolayers.

The interaction of diclofenac sodium (SD) with soya phosphatidylcholine (SPC) has been studied with floating Langmuir monolayers and liposomes. SD was either introduced into the subphase of SPC monolayers or co-spread with SPC on an aqueous subphase. In both cases, SD caused the surface pressure isotherm to become more expanded, thus demonstrating the affinity between SD and SPC. The incorporation of SD caused SPC liposomes to have a decreased diameter according to light scattering experiments. When SPC liposomes were injected into an aqueous subphase, their destruction yielding surface-active monomers could be monitored by changes in surface pressure. SD-loaded liposomes displayed a much faster kinetics when the surface density of surface-active monomers was plotted against time, with rate constants increasing significantly with the SD concentration. The kinetic profile can be quantitatively analyzed by plotting ln[1 - (gamma/gamma infinity)] versus t1/2.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2004

Defining 3D residue environment in protein structures using SCORPION and FORMIGA.

SUMMARY: Two web-based applications to analyze amino acids three-dimensional (3D) local environment within protein structures-SCORPION and FORMIGA-are presented. SCORPION and FORMIGA produce a graphical presentation for simple statistical data showing the frequency of residue occurrence within a given sphere (defined here as the 3D contacts). The center of that sphere is placed at the Calpha and at the last heavy atom in the side chain of the selected amino acid. Further depth of detail is given in terms of a secondary structure to which the profiled amino acid belongs. Results obtained with those two applications are relevant for estimating the importance of the amino acid 3D local environment for protein folding and stability. Effectively, SCORPION and FORMIGA construct knowledge-based force fields. The difference between SCORPION and FORMIGA is in that the latter operates on protein interfaces, while the former only functions for a single protein chain. Both applications are implemented as stand-alone components of STING Millennium Suite. AVAILABILITY: http://sms.cbi.cnptia.embrapa.br/SMS, http://trantor.bioc.columbia.edu/SMS, http://mirrors.rcsb.org/SMS, http://www.es.embnet.org/SMS and http://www.ar.embnet.org/SMS. [options: Scorpion, Formiga]

Algorithms↗
PubMed2003

Transcriptome characterization of the dimorphic and pathogenic fungus Paracoccidioides brasiliensis by EST analysis.

Paracoccidioides brasiliensis is a pathogenic fungus that undergoes a temperature-dependent cell morphology change from mycelium (22 degrees C) to yeast (36 degrees C). It is assumed that this morphological transition correlates with the infection of the human host. Our goal was to identify genes expressed in the mycelium (M) and yeast (Y) forms by EST sequencing in order to generate a partial map of the fungus transcriptome. Individual EST sequences were clustered by the CAP3 program and annotated using Blastx similarity analysis and InterPro Scan. Three different databases, GenBank nr, COG (clusters of orthologous groups) and GO (gene ontology) were used for annotation. A total of 3,938 (Y = 1,654 and M = 2,274) ESTs were sequenced and clustered into 597 contigs and 1,563 singlets, making up a total of 2,160 genes, which possibly represent one-quarter of the complete gene repertoire in P. brasiliensis. From this total, 1,040 were successfully annotated and 894 could be classified in 18 functional COG categories as follows: cellular metabolism (44%); information storage and processing (25%); cellular processes-cell division, posttranslational modifications, among others (19%); and genes of unknown functions (12%). Computer analysis enabled us to identify some genes potentially involved in the dimorphic transition and drug resistance. Furthermore, computer subtraction analysis revealed several genes possibly expressed in stage-specific forms of P. brasiliensis. Further analysis of these genes may provide new insights into the pathology and differentiation of P. brasiliensis.

Base Sequence↗
PubMed2002

Tissue tolerance of diclofenac sodium encapsulated in liposomes after intramuscular administration.

In this work the effect of the encapsulation of diclofenac sodium within liposomes on the reduction of the myotoxicity after intramuscular administration in rats was studied. Diclofenac sodium was encapsulated in small unilamellar liposomes obtained from phosphatidylcholine, cholesterol, and alpha-tocopherol (40:10:0.04 mM), and administered by intramuscular injection in the quadriceps femoral muscle of male Wistar rats. After a single dose of 0.2 mg diclofenac formulations the local tissue damage was assessed by plasma creatine kinase (CPK) activity and histological analysis. It was demonstrated that formulations containing free diclofenac produced a higher increase in CPK activity, while those encapsulated in liposomes exhibited CPK activity similar to the control groups. Histopathological analysis of local muscle tissue performed on the third and seventh days following the injection showed intense cellular damage when free drug solution was used, while encapsulation in liposome protected the tissue against the local tissue inflammation.

Animals↗
PubMed2001

Inclusion complex of piroxicam with beta-cyclodextrin and incorporation in cationic microemulsion. In vitro drug release and in vivo topical anti-inflammatory effect.

Topical formulations of piroxicam were evaluated by determination of their in vitro release and in vivo anti-inflammatory effect. The in vitro release assay demonstrated that the microemulsion (ME) systems provided a reservoir effect for piroxicam release. However, the incorporation of the ME into carboxyvinilic gel provoked a greater reduction in the release of piroxicam than the ME system alone. Anti-inflammatory activity was carried out by the cotton pellet granuloma inhibition bioassay. Topical anti-inflammatory effect of the piroxicam inclusion complex/ME contained in carboxyvinilic gel showed significant inhibition of the inflammation process (36.9%, P<0.05). Subcutaneous administration of the drug formulations showed a significant effect on the inhibition of inflammation, 68.8 and 70.5%, P<0.05, when the piroxicam was incorporated in ME and in the combined system beta-cyclodextrin (beta-CD)/ME, respectively, relative to the buffered piroxicam (42.2%). These results demonstrated that the ME induced prolonged effects, providing inhibition of the inflammation for 9 days after a single dose administration.

Administration, Topical↗
PubMed2001

Alpha-interferon improves liver fibrosis in chronic hepatitis C: clinical significance of the serum N-terminal propeptide of procollagen type III.

Our objective was to estimate the effect of interferon (IFN) on the evolution of fibrosis in chronic hepatitis C and the significance of the N-terminal propeptide of procollagen type III (PIIIP) as a marker of fibrogenesis. One hundred seventeen patients, 72 male (61%) and 45 female (39%), with a mean age of 40.7+/-11.9 years were treated with a2b-IFN, 3 to 5 MU, for 12 months: sustained responders (SR = 44), relapsers (RR = 35), and nonresponders (NR = 38). Liver biopsies were performed before treatment and 1 year after cessation of IFN for evaluation of the histological activity index (HAI). Serum PIIIP was obtained at the time of liver biopsy, at the beginning, during, and end of therapy and during the follow-up. The normal value in 29 healthy individuals was 0.37+/-0.18 U/L. Staging was reduced in 58% of SR, 12.5% of RR, and 11.5% of NR. There was a correlation between PIIIP and the HAI before (n = 71, r(s) = 0.41, P < 0.0004) and after IFN (n = 71, r(s) = 0.58, P < 0.0001). The SR had a better improvement in grading (90.3%; P < 0.05) and staging (58%; P < 0.001). The correlation of the HAI parameters with the variation of PIIIP showed significance only for fibrosis (r(s) = 0.36, P < 0.002) and portal inflammation (r(s) = 0.35, P < 0.01). PIIIP normalized only in patients whose fibrosis improved (P < 0.01). At the end of therapy, PIIIP had a predictive value in the distinction of SR from RR (PPV, 64; PNV, 55.6). During the follow-up, PIIIP remained lower in SR compared with RR and NR (P < 0.002). The response to a-IFN improved liver inflammation and fibrosis. Serum PIIIP is a useful noninvasive method to evaluate serially fibrogenesis in chronic hepatitis C treated with IFN.

Adult↗
PubMed2001

Parenteral nutrition and cyclosporine: do lipids make a difference? A prospective randomized crossover trial.

AIMS: This prospective, controlled, randomized crossover trial was conducted to assess the effects of parenteral nutrition, with or without lipids, in cyclosporine (CyA) pharmacokinetics. METHODS: 10 adult patients were randomized on the day of allogeneic bone marrow transplantation to receive isocaloric and isonitrogenous parenteral nutrition admixtures without (regimen A) or with lipids (regimen B). Admixtures were started on average by day + 7.4; 5 patients received regimen A followed by B, 5 in reverse order. Blood samples were collected at day 4 after transplantation, under oral diet, and 4 days after the initiation of each regimen as the sole nutrition support. At each time point, 8 whole blood samples were analysed for CyA to evaluate: area under the curve (AUC), trough concentration and systemic clearance. Clinical/laboratory events were recorded until 31 months of follow-up. RESULTS: There was no evidence of a period or treatment-by period interaction, thus results were combined for further analysis. There were no statistically significant differences between regimens in any CyA pharmacokinetic parameters; there were no significant differences from baseline values, except for a higher systemic clearance of CyA with regimen A (0.40+/-0.09 vs 0.29+/-0.06 L/Kg/h, p=0.03). CONCLUSIONS: The provision of 0.8 g/Kg/d of a 50:50 mixture of medium and long chain triglycerides did not affect CyA parameters, which were closer to baseline. In the short or long term there were no attributable side effects.

Adult↗
PubMed1999

Inclusion complex of piroxicam with beta-cyclodextrin and incorporation in hexadecyltrimethylammonium bromide based microemulsion.

The interaction of piroxicam with beta-cyclodextrin (beta-CD), hexadecyltrimethylammonium bromide-based microemulsion (ME), and ME in the presence of beta-CD aimed at the optimization of topical drug delivery was studied. UV-VIS absorption spectra at pH 5.5 were obtained with and without beta-CD and ME. The stability constant (K) values for the piroxicam/beta-CD complex in the pH range 4.5-6.0 varied from 87 to 29 M-1. The cationic microemulsion was characterized by pseudo-ternary phase diagram. The association constant (Ks) of piroxicam/ME was determined using the framework of the pseudophase model. The value of Ks obtained for piroxicam at pH 5.5 was 132 M-1. At the same pH, the value of Ks for the incorporation of piroxicam/beta-CD complex in the ME was 150 M-1.

Administration, Topical↗
PubMed1999

Piroxicam encapsulated in liposomes: characterization and in vivo evaluation of topical anti-inflammatory effect.

Liposomes of soya phosphatidylcholine, cholesterol, and stearylamine (molar ratio 6/3/1) and 0.1% alpha-tocopherol were prepared by the extrusion of multilamellar vesicles through 0.2-micron polycarbonate membrane. Liposomes were characterized by electron transmission microscopy, and the mean structure diameter was 278 nm. The encapsulation efficiency obtained was 12.73%. The topical anti-inflammatory effect was evaluated in vivo by the cotton pellet granuloma method. We analyzed free piroxicam at 4 mg/kg, piroxicam encapsulated in liposomes added to 1.5% hydroxyethylcellulose (HEC) gel at 1.6 mg/kg, and piroxicam encapsulated in liposomes added to HEC gel at 4 mg/kg; the inhibition of inflammation obtained was 21.1%, 32.8%, and 47.4%, respectively. These results showed that the encapsulation of piroxicam produced an increase of topical anti-inflammatory effect, suggesting that the inhibition of inflammation can be obtained with lower drug concentrations.

Administration, Topical↗
PubMed1997

p53 protein immunoexpression in esophageal squamous cell carcinoma and adjacent epithelium.

BACKGROUND: Immunoreactivity for p53 tumor suppressor gene product is commonly found in human malignancies and some premalignant lesions, but its role in cancer development and its value as a marker of tumor biologic behavior is still unclear. OBJECTIVES: This study was undertaken to assess p53 immunoexpression in esophageal squamous cell carcinoma and attempts to determine its correlation with morphological features associated with tumor behavior. METHODS: Immunohistochemical study was performed on archival paraffin-embedded tissue of 37 esophageal squamous cell carcinomas and respective adjacent mucosa. RESULTS: Twenty-one tumors (56.8%) demonstrated specific staining for p53. Sixteen areas of dysplasia were present in 14 out of the 35 cases. p53 positivity was found in one low-grade dysplasia and in six high-grade dysplasias. By univariate analysis, p53 immunoexpression correlated positively with local invasion (P = 0.01) and perineural spread (P = 0.04). Multivariate analysis with logistic regression showed that tumor invasion was the only factor that discriminated between p53 positive and p53 negative cases (OR: 15.6, P < 0.02). No relationship was found between p53 expression and tumor grade, DNA nuclear ploidy, and S-phase fraction. CONCLUSIONS: These data suggest that p53 dysfunction may be implicated in early, preinvasive, stages of esophageal cancer as well as in the tumor progression related to a more invasive phenotype.

Adult↗
PubMed1997

Flow cytometric DNA ploidy and S-phase fraction correlate with histopathologic indicators of tumor behavior in colorectal carcinoma.

BACKGROUND: The clinical behavior of colorectal carcinoma is highly variable without reliable predictive biomarkers. Previous reports have shown that flow cytometric DNA analysis may provide valuable prognostic information in these tumors. PURPOSE AND METHODS: This study evaluates the DNA ploidy and the S-phase fraction (SPF) on frozen samples obtained from 61 patients with colorectal carcinoma by using flow cytometry, and it correlates the data with histopathologic features known to affect disease prognosis. Tumors were classified using the World Health Organization's histologic criteria and were staged according the American Joint Committee on Cancer's classification system. Grade of the neoplasm, vascular invasion, and perineural tumor spread were evaluated in every case. RESULTS: Fifty-nine percent of tumors were aneuploid and showed statistically significant higher S-phase values than diploid tumors (22.5 vs. 11.2 percent; P < 0.00001). Mean SPF of the whole series was 17.9 (range, 4.2-44.2) percent. A statistically significant association was found between SPF values and histologic grade (P < 0.0016), nodal status (P < 0.0007), distant metastasis (P < 0.0001), tumor stage (P < 0.0001), venous invasion (P < 0.0002), and lymphatic permeation (P < 0.01) but not with perineural growth and infiltration of the neoplasm through the bowel wall (T). DNA ploidy correlated positively with tumor stage (P < 0.03), and the association between aneuploidy and advanced stages of the disease was statistically significant. CONCLUSIONS: These findings showed that flow cytometric DNA ploidy and SPF, evaluated in fresh samples, are potentially useful parameters to estimate colorectal carcinoma biopathology. Aneuploidy and high replicative neoplastic activity correlated with histopathologic features that are commonly associated with the prognosis of colorectal carcinoma, being SPF-related to disease dissemination and, therefore, an indicator of clinical relevance.

Adult↗
PubMed1997

Nutritional deficiencies in chronic alcoholics: relation to dietary intake and alcohol consumption.

OBJECTIVES: Relationships of nutritional status with ethanol consumption and diet were studied in 33 chronic alcoholics with no clinical or laboratory evidence of liver disease. METHODS: Nutritional assessment included subjective global assessment, weight-height index, body mass index, and serum albumin measurements. Dietary intake included estimates of daily intake of substrates, folic acid, vitamins B1, B5, B6, and B12. Circulating concentrations of folate, pyridoxal-phosphate and vitamin B12 were evaluated as well. RESULTS: Only 18.1% of patients were considered malnourished, with body mass indices lower than those with an average or good nutritional status (p < 0.0001). Body weight was under 90% of the ideal in 8/33 (24%) patients. Serum albumin values were within normal range in all patients. In terms of calories provided by nonalcoholic substrates, protein, or vitamin intake, we observed no differences between well and poorly nourished individuals. However, malnourished alcoholics consumed significantly more ethanol (p = 0.01) and an inverse correlation was found between ethanol intake and weight-height index (r = -0.35; p = 0.03). Low circulating concentrations of pyridoxal-phosphate and red blood cell folate were found in 51.5% and 60.6% of alcoholics, respectively. These were not correlated with vitamin dietary intake or ethanol consumption, but there was a trend toward malnourished patients to present lower concentrations of red blood cell folate (p = 0.13). CONCLUSIONS: Although over malnutrition is infrequent in this group of chronic alcoholics, specific vitamin deficiencies are present in a substantial proportion of patients and are more likely related to alcohol consumption.

Adult↗