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Biomedical subjects

E Coutinho

Publications and source records attributed to E Coutinho.

At least 19 recordsLinked to original sources

Development of a self-etch adhesive for resin-modified glass ionomers.

The favorable self-adhesiveness of resin-modified glass ionomers (RMGIs) might be even further improved if the time-consuming and technically sensitive etch-and-rinse pre-treatment step with polyalkenoic acids could be avoided. We undertook this study to assess the effectiveness of an experimental self-etch adhesive for RMGIs that does not need to be rinsed off. Ultrastructural analysis and micro-tensile bond strength testing to enamel and dentin of a RMGI restorative material and a RMGI adhesive were performed after 4 different surface pre-treatments: no conditioning; 25% polyalkenoic acid; an experimental self-etch adhesive; and 37.5% phosphoric acid followed by the experimental self-etch adhesive. The use of an experimental self-etch adhesive increased the bond strength of RMGIs, especially after an additional conditioning step. Interfacial analysis showed the formation of a thin hydroxyapatite-containing hybrid layer. The self-etch technique enhances the user-friendliness of RMGIs and lowers their technique-sensitivity, while maintaining desirable characteristics of the conventional etch-and-rinse approach with polyalkenoic acids.

Acid Etching, Dental↗

Monomer-solvent phase separation in one-step self-etch adhesives.

One-step adhesives bond less effectively to enamel/dentin than do their multi-step versions. To investigate whether this might be due to phase separation between adhesive ingredients, we characterized the interaction of 5 experimental and 3 commercial self-etch adhesives with dentin using transmission electron microscopy. All adhesives were examined for homogeneity by light microscopy. Bonding effectiveness to dentin was determined with the use of a micro-tensile bond-strength protocol. The lower bond strength of the one-step adhesives was associated with light-microscopic observation of multiple droplets that disappeared slowly. Interfacial analysis confirmed the entrapment of droplets within the adhesive layer. The prompt disappearance of droplets upon application of a small amount of HEMA (2-hydroxyethyl methacrylate) or a HEMA-containing bonding agent, as well as the absence of droplets at the interface of all HEMA-containing adhesives, strongly suggests that the adhesive monomers separate from water upon evaporation of ethanol/acetone. Upon polymerization, the droplets become entrapped within the adhesive, potentially jeopardizing bond durability. This can be avoided by strong air-drying of the adhesive, thereby removing interfacial water and thus improving bonding effectiveness.

Acid Etching, Dental↗

Mental illness in an adult sample admitted to public hostels in the Rio de Janeiro metropolitan area, Brazil.

BACKGROUND: The number of homeless people of any country is a major social and health issue, but to date only a few descriptive and focused studies have been undertaken in Brazil on the matter. METHOD: In order to fill this gap, a cross-sectional study was carried out in a random representative sample (n=330) out of 1,977 homeless people lodged in the five public hostels of the Rio de Janeiro metropolitan area. Full data were collected by two trained researchers in a face-to-face interview with 319 (96.7 %) out of the 330 lodgers, using the CIDI (Composite International Development Interview) to assess psychiatric diagnosis. RESULTS: The main findings concern prevalence rate of major mental illness, which was 19.4% for the 12 months before data collection, and 22.6% lifetime prevalence rate. Other 12-month prevalence rates were 31% for alcohol abuse/dependence, 4.1% for drug abuse/addiction, 15% for severe cognitive impairment, and 49.2% for any mental disorder. The rate was 65.2% when organic mental disorders were added. Moreover, 23.9% of the sampled lodgers reported previous psychiatric admission. Their demographic characteristics were a mean age of 44.8 years old, 75.8% of them were male, 78.9% were single, 94.7% had a low level of schooling, and 79.2% were long-term unemployed. CONCLUSIONS: This study demonstrates the high rates of psychiatric morbidity in the homeless, but these rates are exceeded by the apparent poverty and illiteracy of the sample. Given the lack of delivery of community services now in Brazilian cities, this group is likely to be marginalized. Some special teams to assess the hostel residents need to be created.

Adult↗

Detection of testosterone and estrogen receptors in the postmenopausal endometrium.

OBJECTIVE: To detect the presence of testosterone and estrogen receptors in the stroma and glandular epithelium in the malignant and non-malignant endometrium. METHODS: One hundred and forty-five consecutively-enrolled peri- or postmenopausal patients were submitted to diagnostic or operative hysteroscopy. These patients either had a history of abnormal uterine bleeding or they were asymptomatic with an endometrial echo greater than 4 mm. The presence of estrogen and testosterone receptors was determined in endometrial samples by immunohistochemistry, using monoclonal antibodies and a streptavidin-biotin peroxidase complex system with diamino benzidine as the chromogen. RESULTS: Testosterone receptors were detected mainly in the stroma in the non-malignant endometrial lesions and in the atypical glandular epithelium in cases of estrogen-positive endometrial carcinomas. CONCLUSIONS: The presence of testosterone receptors in estrogen receptor positive endometrial carcinomas may be involved in the mechanism of cell proliferation in these tumors. The strong staining reaction for testosterone receptors in the endometrial glands can be considered one of the features of invasive malignancy.

Adult↗

Conformation of N-terminal HIV-1 Tat (fragment 1-9) peptide by NMR and MD simulations.

The N-terminal portion of HIV-1 Tat covering residues 1-9 is a competitive inhibitor of dipeptidyl peptidase IV (DP IV). We have used 1H NMR techniques, coupled with molecular dynamics methods, to determine the conformation of this peptide in the three diverse media: DMSO-d6, water (pH 2.7) and 40% HFA solution. The results indicate that in both DMSO-d6 and HFA the peptide has a tendency to acquire a type I beta-turn around the segment Asp5-Pro6-Asn7-IIe8. The N-terminal end is seen to be as a random coil. In water, the structure is best described as a left-handed polyproline type II (PPII) helix for the mid segment region Asp2 to Pro6. The structures obtained in this study have been compared with an earlier report on Tat (1-9).

Acetone↗

Carbohydrate metabolism in sickle cell patients using a subdermal implant containing nomegestrol acetate (Uniplant).

Uniplant, a second-generation contraceptive implant, has been demonstrated to promote a significant improvement in the overall well-being of women with sickle cell anemia. It has been suggested that the discrete increase in blood glucose levels observed in Uniplant users could be a contributory factor for clinical improvement. Ten healthy sickle cell patients were enrolled in the study. An oral glucose tolerance test was performed prior to implant insertion and at 1, 6, and 12 months of therapy. Blood glucose and insulin were measured before and at 30, 60, 120, and 180 min after a 75-g glucose load. The glucose and insulin areas under the curves were calculated. Fasting glycosylated hemoglobin was also measured. No significant changes were observed in glycosylated hemoglobin, glucose or insulin. We conclude that Uniplant is a safe contraceptive for sickle cell patients.

Adult↗

Hysteroscopic and immunohistochemical findings in type I and type II endometrial carcinomas.

STUDY OBJECTIVE: To determine whether types I and II endometrial carcinomas have different precursor lesions recognized at hysteroscopy and immunohistochemistry. DESIGN: Single center case study (Canadian Task Force classification II-2). SETTING: A private, university affiliated hospital. PATIENTS: One hundred forty-six postmenopausal women with endometrial pathology diagnosed by hysteroscopy and biopsy. INTERVENTION: Hysteroscopy and immunohistochemical determination of p53 overexpression. MEASUREMENTS AND MAIN RESULTS: The number of cells showing p53 overexpression was low in endometrial polyps, hyperplasia, and G1 endometrioid carcinomas. A marked increase was seen only in high-grade G2-G3 endometrioid carcinomas and in cases of uterine papillary serous carcinoma. In the latter, strong p53 overexpression was detected in early forms still confined to endometrial polyps. Hysteroscopy could not differentiate between high- and low-grade endometrioid carcinomas. CONCLUSION: The p53-driven pathway plays an important role in the origin of papillary serous carcinoma but not in G1 endometrioid cancer that evolves from estrogen-stimulated endometrium. However, this pathway is important for progression of low-grade endometrioid carcinomas to higher-grade tumors.

Cell Nucleus↗

Zuclopenthixol acetate in psychiatric emergencies: looking for evidence from clinical trials.

BACKGROUND: Case series and reviews have suggested the effectiveness of zuclopenthixol acetate in the acute management of disturbed behaviour caused by serious mental illnesses. This review investigates the trial-based evidence for these suggestions. METHODS: All randomized clinical trials comparing zuclopenthixol acetate to other 'standard' treatments for the acute management of those with serious mental illnesses were identified and, if possible, their results summated. RESULTS: Six trials were identified. All had methodological problems and one did not meet the minimal methodological inclusion criteria. The summary data do not demonstrate that zuclopenthixol acetate is better than 'standard care' for altering behaviour, decreasing the need for supplementary medication, avoiding side-effects, or postponing early discharge against medical advice. One trial, however, presented data that suggested an earlier, more intense level of sedation. CONCLUSIONS: Recommendations of reviews and open studies for the use of zuclopenthixol acetate in preference to 'standard' treatments in the psychiatric emergency are not supported by evidence from randomized controlled trials.

Adolescent↗

Zuclopenthixol decanoate for schizophrenia and other serious mental illnesses.

BACKGROUND: There is a clear link between stopping antipsychotic medications and a relapse of psychotic symptoms. A series of long-acting intra-muscular preparations has been developed since the 1960s in the hope of reducing the frequency of relapse and, hence, overall disability. These depot preparations, active for weeks at a time, are frequently used for those who find taking oral medication on a regular basis difficult or unacceptable. It has, however, been a consistent concern that any reduction in relapse rate afforded by depot preparations may be offset by an increase in adverse effects such as drug-induced movement disorders. OBJECTIVES: To compare zuclopenthixol decanoate to oral zuclopenthixol and other antipsychotic preparations for the treatment of schizophrenia and similar serious mental illness. SEARCH STRATEGY: Electronic searches of Biological Abstracts (1982-1998), CINAHL (1982-1998), The Cochrane Library (Issue 2, 1998), The Cochrane Schizophrenia Group's Register (April 1998), EMBASE (1980-1998), MEDLINE (1966-1998), and PsycLIT (1974-1998) were searched. References of all eligible studies were searched for further trials. The manufacturer of zuclopenthixol was contacted. SELECTION CRITERIA: Inclusion criteria were that the clinical study should be randomised, focus on people with schizophrenia or other serious mental illness with psychotic symptoms, and compare the use of zuclopenthixol decanoate to oral zuclopenthixol or other antipsychotic preparations. DATA COLLECTION AND ANALYSIS: Data was extracted independently by two reviewers (EC, MF). Authors of trials were contacted for additional and missing data. Odds ratios (ORs) and 95% confidence intervals (CIs) of homogenous dichotomous data were calculated with the Peto method. Where possible the number needed to treat (NNT) and its 95% confidence interval was also calculated. MAIN RESULTS: Four studies relating to zuclopenthixol decanoate were included. All compared zuclopenthixol decanoate with other depot preparations. Zuclopenthixol decanoate prevented or postponed relapses when compared to other depots (NNT 8, CI 5-53). However, zuclopenthixol decanoate may induce more adverse effects (NNH 5, CI 3-31) although it decreases need for anticholinergic medication when compared to a group of other depot preparations (NNT 9, CI 5-38). For the risk of leaving the study early, there was also a trend for benefit to those allocated to zuclopenthixol decanoate. None of the studies reported outcomes on service utilisation, costs, or quality of life. REVIEWER'S CONCLUSIONS: Choice of which depot to use must always take into account clinical judgement and the preferences of the recipients of care and their carers. Limited trial data suggests, however, that there are real differences between zuclopenthixol decanoate and other depots and these differences largely favour the former. This review highlights the need for good controlled clinical trials to fully address the effects of zuclopenthixol decanoate for those with schizophrenia. Future studies should report service utilisation data, as well as satisfaction with care and economic outcomes. Duration of such trials should be of a longer duration than the included studies (12 months or more).

Administration, Oral↗

A new vaginal antimicrobial contraceptive formulation: phase I clinical pilot studies.

Pilot clinical trials were performed with a new vaginal suppository called "Long Acting, Sustained Release of Spermicide" ("LASRS"). No visual or colposcopic lesions or patient complaints occurred as a result of using LASRS with increasing doses of nonoxynol-9 (up to 20%) for 5 days or of applying the highest dose of nonoxynol-9 (20%; total 400 mg) for 8 h. Colposcopic or visual lesions were also not induced when LASRS with 20% nonoxynol-9 was used for 7 consecutive days by the study participants except for those who developed symptomatic monilia vaginitis. Symptoms were reported although these were mostly minor. A long-lasting, bioadhesive, translucent layer (film) of formulation formed over the vaginal and cervical surfaces. Postcoital spermicidal studies showed LASRS to be highly effective for prolonged periods of time. Although intercourse was delayed for 5 to 8.5 h after insertion of the formulation, an average of only 0. 2 motile sperm/HPF could be found in cervical mucus. These studies suggest LASRS to possess advantages over presently marketed formulations by having long-term efficacy and by forming a bioadhesive, presumably protective layer over the genital tract epithelium. The results also suggest the formulation to decrease the vaginal irritation caused by nonoxynol-9 as noted by colposcopy. These pilot data support a more extensive study with the LASRS suppository.

Adult↗

Protective effect of L-arginine against lipid peroxidation in goat epididymal spermatozoa.

L-arginine plays an important role in physiology of spermatozoa and is shown to enhance the metabolism of these cells. We report here the effect of L-arginine on membrane lipid peroxidation of goat epididymal spermatozoa. Both natural peroxidation as well as that induced by UV radiation, freezing and oxidizing agents have been studied. Irrespective of the nature of induction of peroxidation, L-arginine reduces the extent of lipid peroxidation in a concentration dependent manner. Both L-arginine and alpha-tocopherol act synergistically in protecting against lipid peroxidation induced by the above methods. Thus, in order to provide protection against lipid peroxidation, L-arginine may be added in media used to preserve spermatozoa.

Animals↗

Replacement of phe(8) in substance P by tyr (Tyr(8)-SP) alters the conformation of the peptide in DMSO, water, and lipid bilayers.

The conformation of [Tyr(8)]SP (Y8SP) in dimethylsulfoxide (DMSO), water, and dipalmitoyl phosphatidylcholine (DPPC) bilayers has been investigated by two-dimensional nmr and molecular dynamics simulations. Molecular modeling of the conformation of Y8SP by incorporating nuclear Overhauser effects as distance restraints shows wide differences in its conformation in the three media. In DMSO, the main structural features are gamma-bends along with a nonspecific bend around Gln(6)-Phe(7)-Tyr(8). The random coil structure seen in water is transformed into a beta-turn around the segment Gln(5)-Gln(6)-Phe(7)-Tyr(8) when Y8SP is incorporated into DPPC bilayers. The lower biological activity of Y8SP compared to the native peptide (SP) has been attributed to the absence of any helix like structure at the central residues, a feature shown to be an important prerequisite for SP and SP agonists to bind to the neurokinin 1 tachykinin receptor.

1,2-Dipalmitoylphosphatidylcholine↗

Calculation of relative binding free energy difference of DHFR inhibitors by a finite difference thermodynamic integration (FDTI) approach.

We have implemented a Finite Difference Thermodynamic Integration (FDTI) approach to estimate the binding free energy relative to methotrexate (MTX) of three unreported inhibitors of DHFR. The validity of the calculation methodology was first proved by evaluating the relative binding free energy difference for two well-known anticancer agents aminopterin and methotrexate. The usefulness of the method in drug design has been demonstrated by the fact that inhibitor 5, designed by us was found to bind more tightly than MTX, by as much 7.5 kcal/mole and is a worthy candidate for further pharmacological investigations.

Aminopterin↗

Comparative conformational studies on cyclic hexapeptides corresponding to message sequence His-Phe-Arg-Trp of alpha-melanotropin by NMR.

Solution conformation of cyclo(Gly1-His2-Phe3-Arg4-Trp5-Gly6) and its D-Phe analog corresponding to the message sequence [Gly-alpha-MSH5-10] of alpha-MSH has been studied by 1D and 2D proton magnetic resonance spectroscopy in dimethyl sulfoxide (DMSO)-d6 solution and in a DMSO-d6/H2O cryoprotective mixture. The NMR data for both the analogs in solution at 300 K cannot be interpreted based on a single ordered conformation, as evidenced by the broadening of only -NH resonances as well as the temperature coefficients of the amide protons. An analysis of the nuclear Overhauser effect (NOE) cross-peaks in conjunction with temperature coefficient data indicates an equilibrium of multiple conformers with a substantial population of particular conformational states at least in the D-analog. The molecular dynamics simulations without and with NOE constraints also reveal numerous low-energy conformers with two gamma-turns, a gamma-turn and a beta-turn, two beta-turns, etc. for both the analogs. The observed NMR spectra can be rationalized by a dynamic equilibrium of conformers characterized by a gamma-bend at Gly6, two gamma-bends at Phe3 and Gly6 and a conformer with a single beta-turn and a gamma-bend for the L-Phe analog. On the other hand, a conformation with two fused beta-turns around the two tetrads His2-D-Phe3-Arg4-Trp5 and Trp5-Gly6-Gly1-His2 dominates the equilibrium mixture for the D-Phe analog. For the D-Phe analog, the experimentally observed average conformation is corroborated by molecular dynamics simulations as well as by studies in cryoprotective solvent.

Magnetic Resonance Spectroscopy↗

An investigation of the conformation of peptide-T and its D-Ala analog by NMR and molecular dynamics simulations.

Peptide-T (ASTTTNYT) and its D-Ala analog (D-ASTTTNYT-NH2) have been designed to block the adsorption of HIV to CD4 receptors on T-cell lymphocytes, thus inhibiting viral infectivity. The conformation of these important peptides has been investigated by 2D-NMR and molecular dynamics simulations. The NMR studies in DMSO show that the peptides exist in solution as a mixture of conformations. beta-Turns and non-specific folded conformations are present in a small proportion in the ensemble of conformations, which is largely dominated by more or less extended structures. This result is in line with molecular dynamics simulations where beta-turns were found to occur with a low frequency and with energies 10 to 17 kcal/mole higher than the global minimum structure. Our findings differ from previous reports on the conformation of peptide-T determined by NMR.

Antiviral Agents↗

Changes in the menstrual bleeding of users of a subdermal contraceptive implant of nomegestrol acetate (Uniplant) do not influence sexual frequency, sexual desire, or sexual enjoyment.

OBJECTIVE: To evaluate the effect of menstrual changes induced by a nomegestrol acetate subdermal contraceptive implant (Uniplant; Thermex, Bahia, Brazil) on users' sexuality. DESIGN: Prospective observational survey. SETTING: San Borja-Arriarán Hospital, University of Chile, School of Medicine. PATIENT(S): Normally cycling healthy women and their partners. INTERVENTION(S): Structured interview before and during use of the contraceptive. MAIN OUTCOMES MEASURE(S): Sexual frequency, desire, and enjoyment; perception of health; and contraceptive satisfaction. RESULT(S): During the use of the implant more women reported irregular cycles (32% versus 11%) and vaginal spotting (38% versus 19%). Frequency of sexual relations was unchanged (2.3 versus 2.5/wk) but the percent of couples engaging in sexual relations during vaginal spotting increased (28% versus 11%). There was no significant difference in the percent of men or women who reported an increase, or decrease, in perceived sexual desire, sexual enjoyment, or perception of health during the use of Uniplant. CONCLUSION(S): Despite the alterations in menstrual cyclicity and the occurrence of spotting, the use of a contraceptive subdermal implant of nomegestrol acetate did not effect desire for, enjoyment of, or frequency of sexual relations in users.

Adolescent↗