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OBJECTIVES: The present study aimed to evaluate the desensitizing effect of toothpaste for sensitive teeth on patient tooth sensitivity and on bleaching efficacy of the 38% hydrogen peroxide bleaching agent used for in-office bleaching compared to a regular toothpaste in a randomized clinical trial. METHODS AND MATERIALS: Forty-eight patients having maxillary right central incisors with darkness greater than A1 were selected for the present double-blind randomized clinical trial. Patients were randomly allocated into two groups: the placebo group, which used regular toothpaste, and the experimental group, which used sensitivity toothpaste. The intervention consisted of applying toothpaste with the aid of an individual tray for a period of 4 minutes daily, starting one week before the first bleaching session and interrupting use immediately after the second session. After allocation to one of the groups, individuals received in-office dental bleaching with a 40-minute application of 38% hydrogen peroxide for two sessions with an interval of one week. The incidence and intensity of sensitivity were assessed using a visual analogue scale and a numeric analogue scale. Sensitivity was measured immediately before each session, 1 hour, 24 hours, and 48 hours after each bleaching session and four weeks after the second bleaching session. Tooth shade was evaluated using a spectrophotometer and by comparison with the VITA Classical Shade Guide (Vita Zahnfabrik, Bad Säckingen, Germany). Tooth shade was evaluated before the first bleaching session, one week after the first bleaching session, one week after the second bleaching session and four weeks after the second bleaching session. Participants and professionals who performed the bleaching, shade, and sensitivity assessments were blinded to the group of patients they were treating or assessing. For the incidence of hypersensitivity, the results were evaluated by comparing the groups at different evaluation times with the Mann-Whitney test for comparison between groups, the Friedman test for repeated measures, and the Tukey test for comparison of times. Shade change on the guide was analyzed using the Mann-Whitney test for comparison between groups and the Wilcoxon test for comparison between times. Shade change by the spectrophotometer was analyzed using the t-test for comparison between groups and the paired t-test for comparison between times. All analyses were performed with a significance level of 5%. RESULTS: There was no difference in the pattern of dental hypersensitivity between groups. For all shade measures, there was no difference between the bleaching results, and no statistically significant difference was observed between the study groups. CONCLUSION: The use of arginine-based desensitizing toothpaste did not interfere with the bleaching ability of hydrogen peroxide and was not effective in reducing the sensitivity caused by in-office tooth bleaching.
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Sensibilidade da Dentina , Clareadores Dentários , Clareamento Dental , Humanos , Sensibilidade da Dentina/etiologia , Peróxido de Hidrogênio/uso terapêutico , Cremes Dentais/uso terapêutico , Clareadores Dentários/uso terapêutico , Clareamento Dental/efeitos adversos , Clareamento Dental/métodos , Resultado do TratamentoRESUMO
Restenosis remains a major problem after angioplasty in peripheral artery disease despite stenting. It occurs in 30 - 50% / year depending on lesion localization and characteristics. One main reason for restenosis is neointimal hyperplasia, which can be suppressed by the topical administration of antiproliferative drugs. In percutaneous coronary intervention the concept of "local drug delivery" has been used for almost a decade with great success. In recent years, drug-eluting stents and drug coated balloons have also been increasingly used in the treatment of peripheral arterial disease as a consequence of positive results of clinical trails. The following article is an overview of the currently available data of completed trials, ongoing and planned studies. Evidence suggests that "drug-coating technology" is reliable, safe and efficient in reducing the target lesion revascularization and binary restenosis rate significantly. With regard to limb salvage and mortality in critical limb ischemia, there is no benefit shown in current published studies.
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Angioplastia com Balão/instrumentação , Fármacos Cardiovasculares/administração & dosagem , Catéteres , Materiais Revestidos Biocompatíveis , Stents Farmacológicos , Doença Arterial Periférica/terapia , Angioplastia com Balão/efeitos adversos , Angioplastia com Balão/mortalidade , Desenho de Equipamento , Medicina Baseada em Evidências , Humanos , Salvamento de Membro , Doença Arterial Periférica/mortalidade , Desenho de Prótese , Medição de Risco , Fatores de Risco , Prevenção Secundária , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate the influence of heat application on the degree of conversion (DC) of the 3M Single Bond Universal Adhesive System, as well as its transdentinal cytotoxicity and microtensile bond strength to dentin. METHODS: Experimental groups were established according to the time and temperature of the air jet: G1: 5 seconds-25°C; G2: 10 seconds-25°C; G3: 20 seconds-25°C; G4: 5 seconds-50°C; G5: 10 seconds-50°C; G6: 20 seconds-50°C. In control group (G7), no treatment was performed. The DC was assessed using the Fourier transform infrared spectroscopy-attenuated total reflectance (FTIR-ATR) technique. For the transdentinal cytotoxicity test, dentin discs fitted in artificial pulp chambers (APC) received the application of the adhesive system and the air jets. For the microtensile bond strength, healthy molars were restored and submitted to the microtensile test after 24 hours and 6 months, respectively. RESULTS: Significant reduction in viability of Mouse Dental Papilla Cell-23 (MDPC-23), which exhibited morphological changes, was observed in all experimental groups compared to control (p<0.05). Although all tested protocols resulted in transdentinal diffusion of 2-hydroxyethyl methacrylate (HEMA), the group G6 presented the highest degree of monomeric conversion and the lowest cytotoxic effect, with higher dentin bond strength values in comparison to group G1 (p<0.05). CONCLUSIONS: Applying an air blast at 50°C for 20 seconds increases the DC and microtensile bond strength of the 3M Single Bond Universal Adhesive System to dentin, as well as reduces the transdentinal cytotoxicity of the material to pulp cells.
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Colagem Dentária , Adesivos Dentinários , Animais , Resinas Compostas/química , Cimentos Dentários , Dentina , Adesivos Dentinários/química , Teste de Materiais , Camundongos , Cimentos de Resina/química , Temperatura , Resistência à TraçãoRESUMO
BACKGROUND: Evidence suggests that eutopic endometrium from women with endometriosis (US-E) has intrinsic functional anomalies compared with women without endometriosis (US-C). We hypothesized that differences in endometrial haptoglobin (eHp) mRNA and protein levels exist between eutopic endometrium from US-E and US-C and that inflammatory mediators may be involved. METHODS: Endometrial stromal cells and tissue explants from US-E (n = 18) and US-C (n = 18) were cultured (24 h/48 h for cells/explants) with interleukin (IL)-1alpha, -1beta, -6, -8 or tumor necrosis factor-alpha (TNF-alpha) at 0-100 ng/ml. eHp protein in media and mRNA levels were quantified by enzyme-linked immunosorbent assay and quantitative PCR. RESULTS: In eutopic endometrial stromal cells from US-E, IL-1beta, IL-6 and TNF-alpha (10 ng/ml) increased eHp mRNA levels (P = 0.002, P < 0.001 and P < 0.001, respectively) and eHp protein (P = 0.023, 0.031 and 0.006, respectively) versus control. In endometrial tissues from US-E, IL-1beta, IL-6 and TNF-alpha increased eHp mRNA (P < 0.001, P = 0.017 and P < 0.001, respectively) and eHp protein (P < 0.001, P = 0.007 and 0.039, respectively) versus control. IL-1alpha and IL-8 had small or no effects on isolated endometrial cells or tissues. In US-C, IL-1beta, IL-8 and TNF-alpha each reduced eHp mRNA in endometrial stromal cells (all P < 0.001) versus control; IL-1alpha and IL-6 had no effect. eHp mRNA increased in endometrial tissues from US-C in response to IL-1beta (P = 0.008), IL-6 (P = 0.015) and TNF-alpha (P = 0.031) versus control; IL-1alpha or IL-8 had no effect. CONCLUSIONS: Endometrium from US-E differentially responds to specific inflammatory cytokines by production of eHp. We propose that up-regulation of endometrial eHp by inflammatory mediators disrupts normal endometrial function and may facilitate the pathogenesis of endometriosis.
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Citocinas/farmacologia , Endometriose/genética , Endometriose/metabolismo , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Haptoglobinas/biossíntese , Haptoglobinas/genética , Citocinas/metabolismo , Endometriose/etiologia , Feminino , Humanos , Técnicas In Vitro , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/farmacologia , Interleucina-1alfa/farmacologia , Interleucina-1beta/farmacologia , Interleucina-6/farmacologia , Interleucina-8/farmacologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVES: Posterior retroperitoneoscopic adrenalectomy (PRA) is used for removal of benign adrenal lesions. Though literature shows low complication rate in this procedure, there is no consensus about safety profile of PRA in high-risk patients. This study aimed to determine the feasibility and safety profile of PRA in high-risk patients. METHODS: This retrospective study recruited all patients who underwent PRA for benign adrenal lesions in the study center. Patients with an American Society of Anesthesiologists (ASA) score of ≥3, on anticoagulant therapy or a body mass index (BMI) over 30 were classified as high-risk patients. We analyzed patients' demographics, comorbidities, perioperative mean arterial pressure and operative time, postoperative complications and tumor characteristics. Mortality and morbidity rates and length of hospital stay of the high-risk and low-risk groups were compared. The chi-square and t tests were used to determine relationships between categorical variables between groups. RESULTS: Forty two PRA procedures were done on 21 men and 21 women; mean age of 50 years in low and 62 years in high risk groups. Twenty six (61.9%) patients had high-risk profile. We recorded 4 (9.5%) intra- and postoperative complications, while one (2.3%) PRA was converted to open due to intra-operative hemorrhage. Mean operative time of 86.45 and 108.19 min (p = 0.204), and postop hospital stay of 4.44 and 6.65 (p = 0.25) days were recorded for low and high risk groups, respectively. Intraoperative arterial pressure of ≥170 mmHg was noted for 6 low and 11 high risk patients (p = 885). CONCLUSION: Our results indicate that PRA for benign adrenal lesions is safe and feasible in patients with a high-risk profile without a risk of increased peri- and postoperative complications.
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Neoplasias das Glândulas Suprarrenais/cirurgia , Adrenalectomia/métodos , Adrenalectomia/efeitos adversos , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Espaço Retroperitoneal/cirurgia , Estudos RetrospectivosRESUMO
Larvae and adults of the marine bryozoan Watersipora cucullata invariably possess numerous extracellular mycoplasma-like, organisms. Mesodermally encapsulated groups of these atypical bacteria occur in the visceral coeloms of all colony members. In contrast, thousands of the symbionts are externally attached to each larva along a unique superficial groove; the microorganisms are internalized during the complex metamorphosis, thus inoculating the incipient colony. The consequences to the bryozoan of this association are not known.
RESUMO
Monticules, regularly arranged modified areas on Paleozoic Bryozoa, may represent regions from which water currents produced by lophophores of adjacent feeding zoids escaped. Such circulation Patterns have been observed Recent forms.
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BACKGROUND: More and more frequently, the registration of life satisfaction is being used to evaluate different medical treatments. So far, there have been only few such surveys on transsexuals (TS). Therefore, the aim of this study was to evaluate the general and the health-related life satisfaction of transsexuals after gender transformation operations. PATIENTS AND METHODS: Forty patients took part in this German cross-sectional study. The Questions on Life Satisfaction Module (FLZ) and free questions on different aspects of the new gender identity were used as measuring instruments. RESULTS: Of the TS studied, 85-95% were "very satisfied" or "satisfied" with the results of their gender transformation operation in respect to gender identity. The TS were significantly less satisfied (P>0.001) in overall "general life satisfaction" than the general population. In overall FLZ scores for "health-related life satisfaction", no differences were seen. CONCLUSION: These data indicate a discrepancy between subjective satisfaction with new gender identity and current life situation, and they identify problems with life satisfaction.
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Transtornos do Desenvolvimento Sexual , Identidade de Gênero , Complicações Pós-Operatórias/psicologia , Qualidade de Vida/psicologia , Transexualidade/cirurgia , Adulto , Feminino , Seguimentos , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Fatores Socioeconômicos , Transexualidade/psicologiaRESUMO
Carcinoembryonic antigen (CEA) expression is used clinically to monitor patients with colorectal and other cancers. A subset of patients have extraordinarily high CEA levels that cannot be attributed solely to tumor load. We have shown mutations in the region of CEA (PELPK motif) responsible for its hepatic clearance in three of eight patients with high CEA levels. We used denaturing high-performance liquid chromatography to provide evidence of polymorphism in these patients. These mutations were scored by DNA cycle sequencing and shown to be heterozygous. The patients with mutations in the PELPK motif showed remarkably reduced circulatory clearance rates in an animal model. A patient without mutation in the region showed normal clearance rates. Mutations in PELPK may affect structural stability and binding affinity to the Kupffer cell receptor in the liver. These studies have implications for the role of CEA as a facilitator of hepatic metastasis.
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Antígeno Carcinoembrionário/genética , Neoplasias Colorretais/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundário , Mutação Puntual , Sequência de Aminoácidos , Animais , Sequência de Bases , Antígeno Carcinoembrionário/sangue , Cromatografia Líquida de Alta Pressão , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/imunologia , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Polimorfismo Genético , Ratos , Ratos Sprague-DawleyRESUMO
We present the recursive dynamic programming (RDP) method for the threading approach to three-dimensional protein structure prediction. RDP is based on the divide-and-conquer paradigm and maps the protein sequence whose backbone structure is to be found (the protein target) onto the known backbone structure of a model protein (the protein template) in a stepwise fashion, a technique that is similar to computing local alignments but utilising different cost functions. We begin by mapping parts of the target onto the template that show statistically significant similarity with the template sequence. After mapping, the template structure is modified in order to account for the mapped target residues. Then significant similarities between the yet unmapped parts of the target and the modified template are searched, and the resulting segments of the target are mapped onto the template. This recursive process of identifying segments in the target to be mapped onto the template and modifying the template is continued until no significant similarities between the remaining parts of target and template are found. Those parts which are left unmapped by the procedure are interpreted as gaps. The RDP method is robust in the sense that different local alignment methods can be used, several alternatives of mapping parts of the target onto the template can be handled and compared in the process, and the cost functions can be dynamically adapted to biological needs. Our computer experiments show that the RDP procedure is efficient and effective. We can thread a typical protein sequence against a database of 887 template domains in about 12 hours even on a low-cost workstation (SUN Ultra 5). In statistical evaluations on databases of known protein structures, RDP significantly outperforms competing methods. RDP has been especially valuable in providing accurate alignments for modeling active sites of proteins.RDP is part of the ToPLign system (GMD Toolbox for protein alignment) and can be accessed via the WWW independently or in concert with other ToPLign tools at http://cartan.gmd.de/ToPLign.html.
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Conformação Proteica , Proteínas/química , Sequência de Aminoácidos , Bases de Dados Factuais , Dados de Sequência Molecular , Dobramento de Proteína , Homologia de Sequência de AminoácidosRESUMO
De novo synthesized endometriosis protein-II (ENDO-II; M(r) 28,000 to 32,000; pI 7.0 to 9.0) was partially purified from rat endometriotic tissue culture media using affinity chromatography and two-dimensional SDS-PAGE. The protein was electrophoretically transferred to polyvinyl difluoride membranes which were stained with Coomassie blue R-250. The stained protein corresponding to ENDO-II (M(r) 28,000 to 32,000; pI 7.0 to 9.0) was cut from the membranes for amino acid sequencing. Partial amino acid sequence was determined by automated Edman degradation using a gas phase sequencer and phenylthiohydantoin analyzer. Sequence analysis of ENDO-II yielded 25 residues: C S C A P T H P Q T A F C N S D L V I R K F M G. Comparison to sequence databanks demonstrated significant homology with rat (100%) and human (84%) tissue inhibitor of metalloproteinases-1 (TIMP-1). Western blot analysis using a TIMP-1 antibody confirmed amino acid sequence analysis. In conclusion, ENDO-II shares sequence homology with TIMP-1 and cross-reactivity with TIMP-1 antibody and subsequently identifies production of TIMP-1 by endometriotic tissues. The synthesis and secretion of TIMP-1 by endometriosis may derange the normal proteolytic milieu of the peritoneal cavity and contribute to the etiology and underlying physiological sequelae associated with the disease endometriosis.
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Glicoproteínas/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/isolamento & purificação , Sequência de Aminoácidos , Animais , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Dados de Sequência Molecular , Ratos , Homologia de Sequência de Aminoácidos , Inibidores Teciduais de MetaloproteinasesRESUMO
In eight patients with a history of alcoholism (on average 9 years), cyclic 3',5'-monophosphate (AMP) and cyclic 3',5'-monophosphate (GMP) were determined in CSF in the acute untreated phase of delirium tremens and at 2 weeks later when clinical symptoms had vanished. Before the second lumbar puncture a drug-free period of 1 week had existed. The results were compared with an age- and sex-matched neurological control group. CSF cyclic AMP concentrations were markedly reduced by 62% (p less than 0.005) in the acute state of delirium tremens and remained at the same level 2 weeks later; cyclic GMP concentrations were increased by 37% (p = 0.05) and showed a small further increase (p less than 0.05) at the second lumbar puncture. A negative correlation existed between age and cyclic AMP content of CSF (r = -0.756; p less than 0.05) in the patients group. The data indicate that the earlier observed increase in norepinephrine turnover in the acute state of delirium tremens (Athen et al., 1977) seems not to induce an increase of cyclic AMP content in CSF.
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Delirium por Abstinência Alcoólica/líquido cefalorraquidiano , AMP Cíclico/líquido cefalorraquidiano , GMP Cíclico/líquido cefalorraquidiano , Psicoses Alcoólicas/líquido cefalorraquidiano , Adulto , Etanol/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/metabolismo , Fatores de TempoRESUMO
Monoamine oxidase inhibitors can elicit increases in systolic blood pressure after tyramine ingestion (cheese effect). Moclobemide is a new, reversible, preferential monoamine oxidase A inhibitor with antidepressant properties. Its potentiation of the tyramine pressor effect during 200 mg t.i.d. chronic treatment was compared with tranylcypromine, 10 mg b.i.d., in a double-blind, parallel-group, placebo-controlled study (n = 16). Tyramine was mixed with food and ingested in increasing daily doses, during a normal meal, until a systolic blood pressure increase of at least 30 mm Hg was achieved (tyramine 30). When compared with the usual fasting oral tyramine tests performed in the same subjects, the mean tyramine 30 dose with a meal was 2.8 times higher. The mean tyramine 30 dose with a meal decreased from 1450 mg (range, 800 to 2000 mg) during placebo to 306 mg (range, 150 to 500 mg) during moclobemide (factor, 5.0) and from 1200 mg (range, 1000 to 1600 mg) during placebo to 35 mg (range, 20 to 50 mg) during tranylcypromine (factor, 38.2). The duration of the systolic blood pressure increase was longer with tranylcypromine (126 minutes) than with moclobemide (69 minutes) (p less than 0.01).
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Benzamidas/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Inibidores da Monoaminoxidase/uso terapêutico , Tranilcipromina/uso terapêutico , Tiramina/farmacologia , Administração Oral , Adulto , Benzamidas/efeitos adversos , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Sinergismo Farmacológico , Humanos , Masculino , Moclobemida , Inibidores da Monoaminoxidase/efeitos adversos , Placebos , Pressorreceptores/efeitos dos fármacos , Distribuição Aleatória , Valores de Referência , Tranilcipromina/efeitos adversos , Tiramina/administração & dosagemRESUMO
The investigation of enzyme and neurotransmitter levels and/or their metabolites in the CSF of patients with senile dementia of Alzheimer's type (SDAT) could become a promising approach for a clinical research and diagnostic procedure. To learn more about the metabolic reflections of central metabolism in the CSF of patients with SDAT, we measured CSF levels of gamma-aminobutyric acid (GABA) and homovanillic acid (HVA), the dopamine metabolite. In 16 female patients with SDAT and in eight matched control patients, CSF GABA levels were measured by ion exchange with fluorimetric detection, and HVA levels were measured fluorimetrically. The GABA content of the CSF was significantly reduced in patients with SDAT, whereas the HVA level was unchanged.
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Doença de Alzheimer/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Ácido Homovanílico/líquido cefalorraquidiano , Fenilacetatos/líquido cefalorraquidiano , Ácido gama-Aminobutírico/líquido cefalorraquidiano , Idoso , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Retrospective epidemiologic studies suggest that individuals exposed to anti-inflammatory agents such as nonsteroidal anti-inflammatory drugs have a lower probability of developing AD as well as an older age at onset for the illness. Neuroinflammation may play an important role in the pathogenesis of AD. Interleukin 1 (IL-1), a potent proinflammatory cytokine, is colocalized immunohistochemically to neuritic plaques, a requisite neuropathologic feature for AD. A polymorphism in the 5'-flanking regulatory region at -889 of the IL-1 alpha gene (a C-to-T transition designated as IL-1A[-889] allele 2) may cause an overexpression of IL-1 alpha, a finding shown to be associated with inflammatory diseases. The IL-1A(-889) allele 2 polymorphism may be associated with AD pathogenesis. METHODS: A total of 259 patients with AD and 192 nondemented control subjects were included from two different centers (Indianapolis, IN, and Munich, Germany). Genotyping for APOE alleles and IL-1A(-889) allele 2 was performed by PCR-based amplification followed by restrictive endonuclease digestion. Statistical analyses were conducted by center-, gender group-, and age group-stratified Mantel-Haenszel odds ratios, CI, and p values. RESULTS: The allele frequency of IL-1A(-889) allele 2 was 46% in clinically diagnosed patients with probable AD versus 34% in control subjects from the combined centers. CONCLUSION: The authors found an increased risk for AD with an estimated Mantel-Haenszel odds ratio of 1.68 (95% CI 1.1 to 2.6; p = 0.022) for heterozygous carriers and 7.2 (95% CI 2.0 to 24.5; p = 0.003) for individuals homozygous for IL-1A(-889) allele 2. They found no evidence for an interaction between the IL-1A and the apoE epsilon 4 polymorphisms (carriers and homozygotes), age, or gender with regard to conferred risk. The data strongly support an association between the IL-1A(-889) allele 2, especially in homozygotes, and later-onset AD.
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Doença de Alzheimer/genética , Interleucina-1/genética , Polimorfismo Genético/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/imunologia , Apolipoproteína E4 , Apolipoproteínas E/genética , Estudos de Casos e Controles , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Frequência do Gene , Triagem de Portadores Genéticos , Genótipo , Heterozigoto , Homozigoto , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de RiscoRESUMO
BACKGROUND: alpha2 Macroglobulin is a panproteinase inhibitor that is found immunohistochemically in neuritic plaques, a requisite neuropathologic feature of AD. Recently, a pentanucleotide deletion near the 5' end of the "bait region" of the alpha2 macroglobulin (A2M) gene was reported to be associated with AD in a large cohort of sibpairs, in which the mutation conferred a similar odds ratio with AD as the APOE-epsilon4 allele for carriers of at least one copy of the A2M gene (Mantel-Haenszel odds ratio, 3.56). METHODS: We studied three independent association samples of AD patients (n = 309) with an age range of 50 to 94 years and representative controls (n = 281) to characterize the allele frequency of the pentanucleotide deletion in this cohort. We detected the mutation near the 5' splice site of exon 18 using standard PCR and restriction fragment length polymorphism methods. The results were adjusted for age, gender, education, and APOE polymorphism. RESULTS: We found that the A2M gene polymorphism conferred an increased risk for AD, with an estimated Mantel-Haenszel ratio of 1.5 (95% CI 1.1 to 2.2; p = 0.025). There was no age- or gender-dependent increase in A2M gene allele frequencies in AD patients compared with controls. The combined sample showed the expected association between AD and APOE-epsilon 4. In one of our three samples there was an interaction between the A2M and APOE-epsilon4 genes, but the other two samples showed no interaction between the two risk factors. CONCLUSIONS: Our data support an association between the A2M gene and AD. This association is less pronounced, however, in our cohort than in the previously reported sample of sibpairs.
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Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , alfa-Macroglobulinas/genética , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/genética , Éxons , Feminino , Deleção de Genes , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Fatores de RiscoRESUMO
Various bioinformatics problems require optimizing several different properties simultaneously. For example, in the protein threading problem, a scoring function combines the values for different parameters of possible sequence-to-structure alignments into a single score to allow for unambiguous optimization. In this context, an essential question is how each property should be weighted. As the native structures are known for some sequences, a partial ordering on optimal alignments to other structures, e.g., derived from structural comparisons, may be used to adjust the weights. To resolve the arising interdependence of weights and computed solutions, we propose a heuristic approach: iterating the computation of solutions (here, threading alignments) given the weights and the estimation of optimal weights of the scoring function given these solutions via systematic calibration methods. For our application (i.e., threading), this iterative approach results in structurally meaningful weights that significantly improve performance on both the training and the test data sets. In addition, the optimized parameters show significant improvements on the recognition rate for a grossly enlarged comprehensive benchmark, a modified recognition protocol as well as modified alignment types (local instead of global and profiles instead of single sequences). These results show the general validity of the optimized weights for the given threading program and the associated scoring contributions.
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Biologia Computacional/métodos , Algoritmos , Modelos Moleculares , Dobramento de Proteína , Proteínas/química , SoftwareRESUMO
RATIONALE: Previous studies showed that adjunctive paroxetine increases tricyclic antidepressant (TCA) serum levels by inhibiting cytochrome P4502D6. This effect has, however, been examined only in experimental studies using low doses of TCAs in healthy volunteers. OBJECTIVE: The present study investigated TCA serum level changes and side-effects after the addition of paroxetine in depressed patients treated with doses customarily used for inpatients. METHODS: 14 patients who had a moderate or severe depressive episode according to ICD-10 and who had not sufficiently responded (< or = 25% reduction of the Hamilton depression scale) to 3-week monotherapy with amitriptyline (n = 9) or imipramine (n = 5) with daily doses between 125 and 200 mg/day, received 20 mg/day paroxetine additionally under steady state conditions. RESULTS: After 2 weeks the serum levels of the metabolites nortriptyline (from 88 +/- 49 ng/ml to 176 +/- 57 ng/ml) and desipramine (from 152 +/- 78 ng/ml to 338 +/- 104 ng/ml) had risen to a significantly greater extent than those of the parent compounds amitriptyline (123 +/- 50 ng/ml to 195 +/- 128 ng/ml) and imipramine (from 75 +/- 36 ng/ml to 98 +/- 51 ng/ml). It is noteworthy that, with the exception of one case of incipient delirium, the combination therapy was well tolerated despite high TCA serum level rises. CONCLUSION: The higher increase of the metabolites as compared with the parent compounds can be explained by a paroxetine-induced inhibition of the liver enzyme cytochrome P4502D6, which catalyses the second step of the TCA metabolism, i.e. the hydroxylation of the metabolites. Blood levels should be meticulously monitored, if TCAs are combined with paroxetine.
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Antidepressivos de Segunda Geração/efeitos adversos , Antidepressivos Tricíclicos/efeitos adversos , Antidepressivos Tricíclicos/sangue , Transtorno Depressivo/sangue , Paroxetina/efeitos adversos , Inibidores do Citocromo P-450 CYP2D6 , Transtorno Depressivo/psicologia , Interações Medicamentosas , Humanos , Pacientes Internados , Estudos Prospectivos , Escalas de Graduação PsiquiátricaRESUMO
In 17 chronic schizophrenic patients under chronic neuroleptic treatment for 13 years, a 30-day drug withdrawal resulted in early relapse of four patients, slight deterioration in five, and slight amelioration in eight patients. No incidence of neuroleptic symptoms such as tardive dyskinesia occurred. Prolactin in plasma and cerebrospinal fluid (CSF), not being elevated under chronic treatment, decreased significantly after 30 days of withdrawal. Homovanillic acid and 3-methoxy-4-hydroxyphenylglycol in CSF ranged normally and did not change during withdrawal. In contrast, plasma noradrenaline was elevated and decreased after drug discontinuation. No unequivocal relationship between biochemical and psychopathological features was found.