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1.
Oper Dent ; 48(6): 627-637, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37881142

RESUMEN

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.


Asunto(s)
Sensibilidad de la Dentina , Blanqueadores Dentales , Blanqueamiento de Dientes , Humanos , Sensibilidad de la Dentina/etiología , Peróxido de Hidrógeno/uso terapéutico , Pastas de Dientes/uso terapéutico , Blanqueadores Dentales/uso terapéutico , Blanqueamiento de Dientes/efectos adversos , Blanqueamiento de Dientes/métodos , Resultado del Tratamiento
2.
Vasa ; 41(4): 248-61, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22825858

RESUMEN

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.


Asunto(s)
Angioplastia de Balón/instrumentación , Fármacos Cardiovasculares/administración & dosificación , Catéteres , Materiales Biocompatibles Revestidos , Stents Liberadores de Fármacos , Enfermedad Arterial Periférica/terapia , Angioplastia de Balón/efectos adversos , Angioplastia de Balón/mortalidad , Diseño de Equipo , Medicina Basada en la Evidencia , Humanos , Recuperación del Miembro , Enfermedad Arterial Periférica/mortalidad , Diseño de Prótesis , Medición de Riesgo , Factores de Riesgo , Prevención Secundaria , Factores de Tiempo , Resultado del Tratamiento
3.
Oper Dent ; 47(1): 87-96, 2022 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-34624102

RESUMEN

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.


Asunto(s)
Recubrimiento Dental Adhesivo , Recubrimientos Dentinarios , Animales , Resinas Compuestas/química , Cementos Dentales , Dentina , Recubrimientos Dentinarios/química , Ensayo de Materiales , Ratones , Cementos de Resina/química , Temperatura , Resistencia a la Tracción
4.
Hum Reprod ; 25(5): 1241-50, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20176595

RESUMEN

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.


Asunto(s)
Citocinas/farmacología , Endometriosis/genética , Endometriosis/metabolismo , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Haptoglobinas/biosíntesis , Haptoglobinas/genética , Citocinas/metabolismo , Endometriosis/etiología , Femenino , Humanos , Técnicas In Vitro , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/farmacología , Interleucina-1alfa/farmacología , Interleucina-1beta/farmacología , Interleucina-6/farmacología , Interleucina-8/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Regulación hacia Arriba/efectos de los fármacos
5.
Int J Surg ; 74: 101-105, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31927032

RESUMEN

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.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Adrenalectomía/efectos adversos , Adulto , Anciano , Estudios de Factibilidad , Femenino , Humanos , Laparoscopía/métodos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Espacio Retroperitoneal/cirugía , Estudios Retrospectivos
7.
Science ; 220(4593): 208-10, 1983 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-17795832

RESUMEN

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.

8.
Science ; 185(4153): 783-4, 1974 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-17799054

RESUMEN

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.

9.
Chirurg ; 77(5): 432-8, 2006 May.
Artículo en Alemán | MEDLINE | ID: mdl-16437228

RESUMEN

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.


Asunto(s)
Trastornos del Desarrollo Sexual , Identidad de Género , Complicaciones Posoperatorias/psicología , Calidad de Vida/psicología , Transexualidad/cirugía , Adulto , Femenino , Estudios de Seguimiento , Indicadores de Salud , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Factores Socioeconómicos , Transexualidad/psicología
10.
Cancer Res ; 61(7): 2822-6, 2001 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-11306451

RESUMEN

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.


Asunto(s)
Antígeno Carcinoembrionario/genética , Neoplasias Colorrectales/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/secundario , Mutación Puntual , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Antígeno Carcinoembrionario/sangre , Cromatografía Líquida de Alta Presión , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Neoplasias Hepáticas/inmunología , Masculino , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Ratas , Ratas Sprague-Dawley
11.
J Mol Biol ; 290(3): 757-79, 1999 Jul 16.
Artículo en Inglés | MEDLINE | ID: mdl-10395828

RESUMEN

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.


Asunto(s)
Conformación Proteica , Proteínas/química , Secuencia de Aminoácidos , Bases de Datos Factuales , Datos de Secuencia Molecular , Pliegue de Proteína , Homología de Secuencia de Aminoácido
12.
J Clin Endocrinol Metab ; 80(12): 3784-7, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8530636

RESUMEN

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.


Asunto(s)
Glicoproteínas/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/aislamiento & purificación , Secuencia de Aminoácidos , Animales , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Datos de Secuencia Molecular , Ratas , Homología de Secuencia de Aminoácido , Inhibidores Tisulares de Metaloproteinasas
13.
Biol Psychiatry ; 17(7): 837-43, 1982 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-6288126

RESUMEN

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.


Asunto(s)
Delirio por Abstinencia Alcohólica/líquido cefalorraquídeo , AMP Cíclico/líquido cefalorraquídeo , GMP Cíclico/líquido cefalorraquídeo , Psicosis Alcohólicas/líquido cefalorraquídeo , Adulto , Etanol/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Norepinefrina/metabolismo , Factores de Tiempo
14.
Clin Pharmacol Ther ; 46(3): 344-51, 1989 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-2673623

RESUMEN

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).


Asunto(s)
Benzamidas/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Inhibidores de la Monoaminooxidasa/uso terapéutico , Tranilcipromina/uso terapéutico , Tiramina/farmacología , Administración Oral , Adulto , Benzamidas/efectos adversos , Ensayos Clínicos como Asunto , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Sinergismo Farmacológico , Humanos , Masculino , Moclobemida , Inhibidores de la Monoaminooxidasa/efectos adversos , Placebos , Presorreceptores/efectos de los fármacos , Distribución Aleatoria , Valores de Referencia , Tranilcipromina/efectos adversos , Tiramina/administración & dosificación
15.
Arch Neurol ; 41(6): 602-4, 1984 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-6721733

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Demencia/líquido cefalorraquídeo , Ácido Homovanílico/líquido cefalorraquídeo , Fenilacetatos/líquido cefalorraquídeo , Ácido gamma-Aminobutírico/líquido cefalorraquídeo , Anciano , Femenino , Humanos , Persona de Mediana Edad
16.
Neurology ; 55(4): 480-3, 2000 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-10953177

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer/genética , Interleucina-1/genética , Polimorfismo Genético/genética , Anciano , Anciano de 80 o más Años , Alelos , Enfermedad de Alzheimer/inmunología , Apolipoproteína E4 , Apolipoproteínas E/genética , Estudios de Casos y Controles , Estudios de Cohortes , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Tamización de Portadores Genéticos , Genotipo , Heterocigoto , Homocigoto , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Medición de Riesgo
17.
Neurology ; 54(2): 438-42, 2000 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-10668709

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/genética , alfa-Macroglobulinas/genética , Anciano , Anciano de 80 o más Años , Apolipoproteínas E/genética , Exones , Femenino , Eliminación de Gen , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Polimorfismo Genético , Factores de Riesgo
18.
J Comput Biol ; 7(3-4): 483-501, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11108475

RESUMEN

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.


Asunto(s)
Biología Computacional/métodos , Algoritmos , Modelos Moleculares , Pliegue de Proteína , Proteínas/química , Programas Informáticos
19.
Psychopharmacology (Berl) ; 73(1): 43-7, 1981.
Artículo en Inglés | MEDLINE | ID: mdl-6112769

RESUMEN

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.


Asunto(s)
Antipsicóticos/efectos adversos , Esquizofrenia/tratamiento farmacológico , Síndrome de Abstinencia a Sustancias/psicología , Adulto , Antipsicóticos/uso terapéutico , Enfermedades de los Ganglios Basales/inducido químicamente , Enfermedad Crónica , Humanos , Persona de Mediana Edad , Síndrome de Abstinencia a Sustancias/metabolismo
20.
Psychopharmacology (Berl) ; 147(4): 378-83, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10672631

RESUMEN

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.


Asunto(s)
Antidepresivos de Segunda Generación/efectos adversos , Antidepresivos Tricíclicos/efectos adversos , Antidepresivos Tricíclicos/sangre , Trastorno Depresivo/sangre , Paroxetina/efectos adversos , Inhibidores del Citocromo P-450 CYP2D6 , Trastorno Depresivo/psicología , Interacciones Farmacológicas , Humanos , Pacientes Internos , Estudios Prospectivos , Escalas de Valoración Psiquiátrica
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