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Biomedical subjects

C M Pereira

Publications and source records attributed to C M Pereira.

At least 19 recordsLinked to original sources

Primary intraosseous fibrosarcoma of jaw.

This paper reports one case of primary fibrosarcoma affecting the mandible in a 41-year-old woman. Microscopically, the tumor was cellularized with an intense mitotic activity, and areas of necrosis and hemorrhage, and the cells showed immunoreactivity only for vimentin, establishing the diagnosis of primary intraosseous fibrosarcoma. The patient underwent tumor surgical resection, supraomohyoid neck dissection and mandible reconstruction with fibula flap and titanium bar. She also received post-surgical radiotherapy and is in follow up for 36 months without signs of recurrence or metastases.

Adult↗

Peutz-Jeghers syndrome in a 14-year-old boy: case report and review of the literature.

Peutz-Jeghers syndrome (PSJ) is a relatively rare but well-recognized condition, with a prevalence of approximately one in 120,000 births in the USA. It is generally inherited as an autosomal dominant trait, although 35% of cases are new mutations. This disorder is characterized by melanocytic macules on the hands, feet, peri-oral skin and oral mucosa, and multiple gastrointestinal hamartomatous polyps. People with PSJ have an increased risk for developing a variety of malignant tumours. The aim of the present study was to report one case of PSJ in a 14-year-old boy with mucocutaneous pigmentation associated with duodenal hamartomatous polyps.

Adolescent↗

Mouth metastasis of peripheral primitive neuroectodermal tumor.

We describe a case of oral metastasis of peripheral primitive neuroectodermal tumor (pPNET) in a 68-year-old man, who presented the primary lesion in the chest. Oral metastasis of pPNETs is very rare and we have not found any similar case reported in the English literature. Clinical examination showed an extensive and ulcerated fleshy mass measuring 3.0 x 3.5 cm in the right lower gingivae. Microscopic examination showed sheets of proliferating small, hyperchromatic, round cells. Tumor cells were reactive to neuron-specific enolase (NSE), vimentin and MIC-2 gene by immunohistochemistry, consistent with PNET. The patient died 3 weeks later because of respiratory insufficiency.

Aged↗

Oral avascular bone necrosis associated with chemotherapy and biphosphonate therapy.

BACKGROUND: Oral avascular bone necrosis is an important adverse effect of chemotherapy and biphosphate therapy. OBJECTIVE: To report our experience in oral avascular bone necrosis in cancer patients assigned to undergo chemotherapy. PATIENTS AND METHODS: Fourteen patients presenting oral avascular bone necrosis were selected from the clinical files of five Stomatological Clinics in Brazil. Clinical data as well as treatment and prognosis information were obtained from all 14 patients. RESULTS: Twelve patients (86%) were submitted to biphosphonate therapy. The most important symptom was pain, present in all cases, and the mandible was the most common involved site. Most patients (79%) had their conditions managed by antibiotic therapy and surgical debridation; however complete response was achieved in only three cases (21%). CONCLUSION: Avascular bone necrosis is a serious oral side-effect of cancer chemotherapy, particularly in patients using biphosphonates, and antibiotic therapy and surgical debridation were not able to promote complete response in most cases.

Adult↗

Development of Zn(II) sensors based on the assisted transfer of metal ions by hydrophobic ligands through gel-supported microinterfaces.

Square-wave voltammetry (SWV) has been used to study the transfer of zinc(II) ion under static conditions, assisted by 5,6-diphenyl-3-(2-pyridyl)-1,2,4-triazine (DPT), through gel-supported microinterfaces. Microhole arrays created by laser photoablation of thin polyester films were used to support an organic gel phase prepared by addition of 1,3:2,4-dibenzylidenesorbitol (DBS) to a solution of o-nitrophenyloctyl ether (o-NPOE) with the appropriate supporting electrolyte. The results show that SWV can be used with the gel-supported microinterfaces if a gelified aqueous reference is used for the organic phase. Under such conditions a preliminary estimate of the detection limit for the determination of Zn2+ is 5 x 10(-8) mol L(-1).

Electrochemistry↗

Pulse amperometric detection of salt concentrations by flow injection analysis using ionodes.

A sensitive novel approach of using an amperometric ion detector for the flow injection analysis of salts has been developed. The detection methodology is based on measuring the current associated with the transfer of ions across polarized microinterfaces between the aqueous sample solution and a 2-nitrophenyloctyl ether-poly(vinyl chloride) gel phase, referred to as ionodes. Different sodium salts of fluoride, chloride, bromide, nitrate, and sulfate were investigated. It was found that by employing an amperometric pulse detection mode and pure water as eluent, the detection limit of the ionode detector could be lowered to ppt level of salt concentrations under flowing conditions.

Journal Article↗

In vitro models to predict the in vivo mechanism, rate, and extent of placental transfer of dideoxynucleoside drugs against human immunodeficiency virus.

OBJECTIVE: We tested the hypothesis that the mechanism, rate, and extent of in vivo placental transfer of dideoxynucleoside drugs against human immunodeficiency virus can be predicted by the in vitro perfused human placenta and the drug octanol-water partition coefficient. STUDY DESIGN: Near-term pregnant macaques (Macaca nemestrina ) underwent long-term catheterization for the administration of 4 dideoxynucleosides against human immunodeficiency virus: zidovudine, didanosine, zalcitabine, and stavudine. Maternal plasma, fetal plasma, and amniotic fluid concentrations were determined frequently after intravenous bolus and/or infusion of the drugs administered into the maternal or fetal circulation on separate occasions. Antipyrine was included in all experiments as a marker of placental blood flow. The mechanism, rate, and extent of placental transfer of the 4 dideoxynucleosides in perfused human placenta were determined and compared with the findings obtained by others. RESULTS: The mechanism and rate of the antipyrine-normalized placental transfer of the 4 dideoxynucleosides in perfused human placenta were highly correlated with those observed in vivo. The extent of placental transfer (fetal/maternal steady-state plasma concentration ratio) was also highly correlated with both the antipyrine-normalized placental transfer clearance (clearance index) determined in the in vitro perfused human placenta model (r 2 = 0.95, in vitro clearance-index model) and the drug octanol-water partition coefficient (r 2 = 0.99, in vitro partition-coefficient model). To determine the predictive capacity of these correlative models, we predicted the fetal/maternal steady-state plasma concentration ratio of each drug after excluding the data on that drug from the model fit. Both in vitro models to predict in vivo placental transfer of drug models resulted in good predictions of the observed fetal/maternal steady-state plasma concentration ratio (mean error: in vitro clearance-index model = -1. 2%; in vitro partition-coefficient model = 3.9%). CONCLUSIONS: We propose that our models will accurately predict the extent of placental transfer of dideoxynucleoside drugs against human immunodeficiency virus. The models may also be applicable to other classes of drugs, regardless of therapeutic category, provided that these drugs passively diffuse across the placenta. Such a result will expedite phase 1 clinical trials of drugs in pregnant women.

Animals↗

Adhesion of Escherichia coli to HeLa cells mediated by Trypanosoma cruzi surface glycoprotein-derived peptides inserted in the outer membrane protein LamB.

Peptides derived from the surface glycoprotein gp82 of Trypanosoma cruzi, previously implicated in the parasite's invasion of host cells, were expressed as fusions to the protein LamB of Escherichia coli in a region known to be exposed on the cell surface. Bacteria expressing these proteins adhered to HeLa cells in a manner that mimics the pattern of parasite invasion of mammalian cells. Purified LamB fusion proteins were shown to bind to HeLa cells and to inhibit infection by T. cruzi, supporting the notion that these gp82-derived peptides can mediate interaction of the parasite with its host.

Amino Acid Sequence↗

Mapping of B cell epitopes in an immunodominant antigen of Trypanosoma cruzi using fusions to the Escherichia coli LamB protein.

The JL8 protein antigen from Trypanosoma cruzi, a dominant immunogen in man, has been characterized as containing tandem amino acid repeats. Here, we describe the use of the LamB protein of Escherichia coli as a carrier of JL8 derived sequences in order to map the immunodominant B cell epitopes in this antigen. Five different sequences of JL8 were inserted in the LamB protein and the JL8-LamB fusion proteins were tested by ELISA with human chronic chagasic sera. The fusion carrying the sequence AEKQKAAEATKVAE was recognized by most sera. This protein was also capable of inhibiting the binding of human chagasic antibodies to GST-JL8 in competitive ELISA suggesting that it contains an immunodominant B cell epitope of JL8.

Animals↗

Glutamate toxicity on a PC12 cell line involves glutathione (GSH) depletion and oxidative stress.

The effect of antioxidants and reducing agents on glutamate-induced cytotoxicity was examined using PC12 cells. The antioxidants vitamin E, idebenone, and selegiline protected cells against the cytotoxicity observed 24 h after exposure to 0.5 or 10 mM glutamate, as determined by lactate dehydrogenase leakage, even when added 3 h after glutamate. The reducing agents, glutathione (GSH) and dithiothreitol (DTT), also provided protection against the cytotoxicity of glutamate. Preincubation of PC12 cells with the antioxidants mentioned above, or the incubation with those antioxidants after exposure to glutamate for 3 h, prevented the reduction of viability caused by glutamate. Cystine uptake was inhibited by exposure of cells to glutamate, as determined by L-[35S]-cystine uptake. Incubation of cells with 0.5 or 10 mM glutamate caused a marked decrease in cellular GSH levels, not prevented by antioxidants. The activity of GSSG reductase was decreased by glutamate and this inhibition was reverted in the presence of the reducing agents GSH and DTT. These results indicate that glutamate toxicity on PC12 cells results from the inhibition of cystine uptake with consequent GSH depletion and oxidative stress, suggesting that antioxidants may reduce the cellular damage in pathologic conditions associated with excessive glutamate release.

Animals↗

Pharmacokinetic-pharmacodynamic modelling for captopril in healthy anaesthetized piglets.

The use of the angiotensin converting enzyme inhibitor, captopril, specially in children, has been empirical. This is because the relationship between the pharmacokinetics and pharmacodynamics of captopril has not been clearly defined. It is not usually feasible to obtain the serial kinetic-dynamic data necessary to study this relationship in infants. The piglet was therefore investigated as an animal model in which to study the relationship between the kinetics and dynamics of captopril. The standard pharmacokinetic parameters for captopril in healthy anaesthetized piglets were found to be within the range reported for humans. ClTB was estimated to be 1.42 +/- 0.33 L h-1 kg(-1); t1/2 was 0.44 +/- 0.08 h; Vdss was calculated to be 0.64 +/- 0.13 L kg(-1); t1/2 and AUC0-infinity was estimated to be 145 +/- 27 ng h mL(-1). The observed haemodynamic response was qualitatively similar to that in humans. Aortic pressure was reduced by 42 +/- 18%; heart rate was reduced by 21 +/- 11%. A parametric pharmacokinetic (two-compartment)-pharmacodynamic (linear) model has been established to describe plasma captopril concentration and aortic pressure relationship. Based on the observed results, the piglet was considered to be a viable model for our purpose.

Angiotensin-Converting Enzyme Inhibitors↗

Effect of zidovudine on transplacental pharmacokinetics of ddI in the pigtailed macaque (Macaca nemestrina).

Since zidovudine and ddI may be used in combination in the future to treat pregnant women who are human immunodeficiency virus positive, we conducted a study to determine whether zidovudine affects the transfer of ddI across the placenta. Zidovudine and ddI were infused simultaneously to three near-term pregnant macaques (Macaca nemestrina) at 156 +/- 1.5 days of gestation. Samples of maternal and fetal blood and amniotic fluid were drawn at intervals for 30 h. The steady-state dideoxyinosine concentrations in the plasma of the dam (Cssd), the fetus (Cssf), and the amniotic fluid (Cssa) and the ratios Cssf/Cssd and Cssa/Cssf were found to be not significantly different from the values previously determined after the administration of ddI alone during the same pregnancy. We conclude that concurrent zidovudine administration does not affect the transfer of ddI across the placenta in near-term Macaca nemestrina.

Animals↗

Transplacental pharmacokinetics of dideoxyinosine in pigtailed macaques.

To determine whether dideoxyinosine is actively transported across the placenta, four pregnant macques (Macaca nemestrina) near term and their fetuses were infused intravenously in random order with simultaneous doses of dideoxyinosine (42.5 micrograms/min/kg of body weight) and antipyrine (41.7 micrograms/min/kg) for 30 h. The infusions took place after the dams had been chronically catheterized at 128 +/- 0.8 days of gestation. In a third infusion, the dams alone received a higher dosage of dideoxyinosine (425 micrograms/min/kg) and the same dosage of antipyrine (41.7 micrograms/min/kg). Samples of maternal and fetal blood and amniotic fluid were collected at intervals for up to 30 h. The concentrations of dideoxyinosine and antipyrine were determined by high-performance liquid chromatography. The transplacental maternal-fetal drug clearances were compared by the paired Student's t test. The ratio (mean +/- standard deviation) of the steady-state plasma dideoxyinosine concentration in the fetus to that in the dam was 0.49 +/- 0.10 at the low dideoxyinosine infusion rate and 0.51 +/- 0.00 at the high dideoxyinosine infusion rate. The clearance associated with maternal-fetal transfer of the drug, CLdf (0.38 +/- 0.21 ml/min/kg), was not significantly different (P > 0.05) from the clearance associated with fetal-maternal transfer of the drug, CLfd (0.56 +/- 0.27 ml/min/kg). Also, CLdf was not significantly different (P > 0.05) from CLfd when normalized with respect to the corresponding transplacental clearance of antipyrine (0.07 +/- 0.04 CLdf versus 0.09 +/- 0.04 CLfd). ur data indicate that passage of dideoxyinosine across the placenta in pregnant M. nemestrina near term is passive and constant over the dosage range studied.

Amniotic Fluid↗

Pharmacokinetics of dideoxyinosine in neonatal pigtailed macaques.

To determine whether age affects the pharmacokinetics of dideoxyinosine in neonatal pigtailed macaques (Macaca nemestrina), dideoxyinosine (10 mg/kg of body weight) was administered as a single intravenous bolus to macaques at ages < 1 week, 1 month, and 4 months. Clearance from plasma at < 1 week of age was significantly lower (P < 0.05) and the terminal half-life was significantly higher than the corresponding values obtained at 1 month and 4 months of age. Our data indicate that the pharmacokinetics of dideoxyinosine change significantly with age in M. nemestrina.

Aging↗

Stability of captopril in tap water.

The stability of captopril in tap water was studied. Twenty 25-mg captopril tablets were crushed separately, added to 25 mL of tap water in individual volumetric flasks, and shaken vigorously. Five flasks each were incubated at 25, 50, and 75 degrees C in a shaking water bath and refrigerated at 5 degrees C. Samples were taken from each flask immediately after dissolving the drug and at intervals up to 28 days for 5 and 25 degrees C, 15 days for 50 degrees C, and 16 days for 75 degrees C. Captopril concentrations were analyzed by high-performance liquid chromatography. First-order rate constants were calculated for each temperature setting, and the Arrhenius plot was applied to estimate the shelf life of captopril at 5 degrees C. More than 90% of the initial concentration of captopril remained after 28 days at 5 degrees C. Captopril concentration in the samples stored at 75, 50, and 25 degrees C decreased to 90% of the initial concentration at calculated times (mean +/- S.E.) of 2.1 +/- 0.1, 3.6 +/- 0.4, and 11.8 +/- 1.2 days, respectively. The estimated time required for the concentration of a 1-mg/mL solution of captopril stored at 5 degrees C to decrease to 90% of initial concentration was 27 days. The shelf life of a solution of captopril 1 mg/mL in tap water stored at 5 degrees C was 27 days.

Captopril↗

The pharmacokinetics of captopril in infants with congestive heart failure.

The use of the angiotensin-converting enzyme inhibitor captopril in infants with congestive heart failure (CHF) has been empirical owing to a lack of relevant pharmacokinetic data. To determine standard pharmacokinetic parameters for the drug in this population, we administered captopril, 1 mg/kg, orally to 10 infants aged 6.8 +/- 4.6 months. Sequential plasma unchanged and total (sum of unchanged and dimerized) captopril concentrations were determined using a high-performance liquid chromatographic method. Arterial pressure, systemic and pulmonary resistance, heart rate, and respiratory rate were all significantly decreased 1 h after the first dose of captopril. Plasma renin activity was not significantly increased. For unchanged captopril, the maximum concentration (Cmax) was 350 +/- 184 ng/ml; the time to Cmax (Tmax), 1.6 +/- 0.4 h; elimination half-life (t1/2), 3.3 +/- 3.3 h; oral clearance (Clo), 1.1 +/- 0.4 L/h/kg. For total captopril, Cmax was 1,088 +/- 621 ng/ml; Tmax, 2.7 +/- 1.1 h; t1/2, 3.4 +/- 1.0 h. Thus, we conclude that the pharmacokinetic parameters for captopril in infants with CHF are within the range reported for adults with CHF. Also, the hemodynamic changes, measured 1 h after the first dose, indicate that the acute effects of captopril in infants with CHF are beneficial.

Administration, Oral↗