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1.
Occup Med (Lond) ; 72(9): 598-603, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36516221

RESUMO

BACKGROUND: Low back pain (LBP) and poor subjective sleep quality (SSQ) are major risk factors for presenteeism. However, no studies have investigated whether combined LBP and poor SSQ are associated with presenteeism. AIMS: We aimed to examine whether a combination of LBP and poor SSQ is associated with presenteeism. METHODS: This cross-sectional study included 936 workers (median age, 38 years; men, 89%), with evaluated presenteeism using the work limitations questionnaire. We divided them into 'no presenteeism' and 'presenteeism' categories. The presence of LBP was defined as a numerical rating scale (NRS) score of ≥1 in current pain intensity. SSQ was assessed using a single question regarding whether the participants typically got enough sleep. We categorized the participants into four groups: (i) LBP + poor SSQ, (ii) non-LBP + poor SSQ, (iii) LBP + good SSQ and (iv) non-LBP + good SSQ. Logistic regression analysis was used to investigate the association between presenteeism and the presence of LBP and poor SSQ, adjusting for age, sex, work type, education, marital status, smoking status, body mass index and weekly working hours. RESULTS: The data from 533 participants were used for analysis (median age, 38 years; men, 90%, response rate, 66%). Combined LBP and poor SSQ were significantly associated with presenteeism (non-LBP + poor SSQ: adjusted odds ratio = 0.56, 95% CI 0.32-0.96; LBP + good SSQ: 0.33, 0.20-0.56; non-LBP + good SSQ: 0.29, 0.18-0.48). CONCLUSIONS: Evaluating both LBP and SSQ may be beneficial in considering presenteeism.


Assuntos
Dor Lombar , Masculino , Humanos , Adulto , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Qualidade do Sono , Estudos Transversais , Fatores de Risco , Sono , Inquéritos e Questionários
2.
Nat Genet ; 24(1): 45-8, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10615125

RESUMO

Familial expansile osteolysis (FEO, MIM 174810) is a rare, autosomal dominant bone disorder characterized by focal areas of increased bone remodelling. The osteolytic lesions, which develop usually in the long bones during early adulthood, show increased osteoblast and osteoclast activity. Our previous linkage studies mapped the gene responsible for FEO to an interval of less than 5 cM between D18S64 and D18S51 on chromosome 18q21.2-21.3 in a large Northern Irish family. The gene encoding receptor activator of nuclear factor-kappa B (RANK; ref. 5), TNFRSF11A, maps to this region. RANK is essential in osteoclast formation. We identified two heterozygous insertion mutations in exon 1 of TNFRSF11A in affected members of four families with FEO or familial Paget disease of bone (PDB). One was a duplication of 18 bases and the other a duplication of 27 bases, both of which affected the signal peptide region of the RANK molecule. Expression of recombinant forms of the mutant RANK proteins revealed perturbations in expression levels and lack of normal cleavage of the signal peptide. Both mutations caused an increase in RANK-mediated nuclear factor-kappaB (NF-kappaB) signalling in vitro, consistent with the presence of an activating mutation.


Assuntos
Proteínas de Transporte , Glicoproteínas de Membrana , Mutação , Osteólise/genética , Sinais Direcionadores de Proteínas/genética , Receptores do Fator de Necrose Tumoral/química , Receptores do Fator de Necrose Tumoral/genética , Sequência de Bases , DNA , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Linhagem , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B
3.
J Viral Hepat ; 19(9): 615-22, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22863265

RESUMO

Pegylated interferon (PEG-IFN)/ribavirin combination therapy is the standard-of-care (SOC) treatment for chronic hepatitis C patients infected with hepatitis C virus (HCV) genotype 1b and high viral load. The addition of fluvastatin to SOC treatment has been suggested to be effective for better outcome in retrospective pilot analyses. We investigated whether the combination of fluvastatin with PEG-IFN/ribavirin could actually improve sustained viral response (SVR) in patients with HCV genotype 1b and high viral load. A randomized, open-labeled, controlled study was conducted between July 2008 and December 2009 in 101 chronic hepatitis C patients allocated to PEG-IFN/ribavirin combination therapy with or without fluvastatin. SVR rates were calculated in groups, stratifying host and viral factors. We also analyzed predictive factors for SVR among patients on fluvastatin with multivariate regression analysis. Rapid and early virological, and end of treatment response rates in the fluvastatin group were not significantly different from those in the non-fluvastatin group. Notwithstanding, SVR rate was significantly higher in the fluvastatin group than in the non-fluvastatin group (63.0%vs 41.7%, P = 0.0422). Comparison of the two groups stratifying demographic data and HCV characteristics showed significantly higher SVR rates to more than 80% in males, more than two mutations in the interferon sensitivity determining region (ISDR), and a history of relapse among the fluvastatin group than the non-fluvastatin group. Being male and major genotype IL28B single nucleotide polymorphisms (SNPs) were independent predictive factors for SVR among patients on fluvastatin with multivariate analysis. Fluvastatin-combined with PEG-IFN/ribavirin therapy significantly improves SVR rates in patients with HCV genotype 1b and high viral load. Male and major genotype IL28B SNPs were independent predictors for SVR among patients on fluvastatin combination therapy.


Assuntos
Antivirais/administração & dosagem , Ácidos Graxos Monoinsaturados/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Indóis/administração & dosagem , Interferons/administração & dosagem , Ribavirina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticolesterolemiantes/administração & dosagem , Quimioterapia Combinada/métodos , Feminino , Fluvastatina , Genótipo , Hepacivirus/classificação , Hepacivirus/isolamento & purificação , Humanos , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Resultado do Tratamento , Carga Viral
4.
J Oral Rehabil ; 39(6): 399-404, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22115393

RESUMO

The objectives of this study were to quantitatively evaluate the gender differences in the lip-closing force (LCF) generated during pursing-like lip-closing movement using a multidirectional LCF measurement system in healthy young adults. In 40 healthy subjects (20 women, 20 men; median age = 26·5 years, range = 22-41 years), LCF was recorded in eight directions during the performance of a voluntary pursing-like lip-closing task in four measurement sessions. The correlations between the total sum of the forces generated in all eight directions [total LCF (TLCF)] and each directional LCF (DLCF) and those between opposing DLCF were statistically analysed. The TLCF obtained from the highly reproducible measurements acquired in the four different sessions was normally distributed in both genders. The TLCF in men was significantly greater than that in women. Among the eight pairs of opposing DLCF, seven pairs of opposing DLCF showed significant correlations in men, while five pairs were significantly correlated in women. In men, no significant difference was observed between opposing DLCF; however, three pairs of opposing DLCF were significantly different in women. The present results quantitatively indicate that there are gender differences in the magnitude and directional specificity of the LCF produced during pursing-like lip-closing movement in healthy young adults.


Assuntos
Expressão Facial , Músculos Faciais/fisiologia , Lábio/fisiologia , Movimento/fisiologia , Adulto , Feminino , Humanos , Masculino , Fatores Sexuais , Adulto Jovem
5.
J Oral Rehabil ; 38(8): 579-87, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21251043

RESUMO

The objectives of this study were to identify the regulatory relationship between tactile sensation at the vermilion of the lips and the output of pursing-like lip-closing force (LCF), as measured by a multidirectional LCF measurement system. Thirty-six healthy subjects were divided into Anaesthesia and Vaseline groups. The tactile detection threshold (TDT) at six sites on the vermilion and the maximum voluntary LCFs in eight directions were recorded before and during partial or whole application of the agent and 6 h after whole application (Recovery). Five per cent lidocaine gel and Vaseline was applied to the vermilion in the Anaesthesia and Vaseline groups, respectively. These agents were applied to either the right part of the vermilion of the lower lip (Partial) or the whole vermilion (Whole). Partial application of 5% lidocaine gel significantly decreased the magnitudes of six of eight directional LCFs, while it only increased the TDT at one site. The subsequent whole application of 5% lidocaine gel did not affect the magnitude of the LCFs in five of these six directions although its application increased the TDTs at all sites. These reductions in LCF were reversed after recovery from surface anaesthesia. Vaseline application did not affect either TDT or LCF in any conditions. We concluded that tactile sensation at the vermilion of the lips is related to the output of LCF, without any particular directional specificity. The present results suggest the presence of a common synaptic drive ordering the pursing of the relevant muscles.


Assuntos
Anestésicos Locais/administração & dosagem , Músculos Faciais/fisiologia , Lábio/fisiologia , Contração Muscular/fisiologia , Tato/fisiologia , Adulto , Músculos Faciais/anatomia & histologia , Músculos Faciais/efeitos dos fármacos , Feminino , Humanos , Lábio/anatomia & histologia , Lábio/efeitos dos fármacos , Masculino , Contração Muscular/efeitos dos fármacos , Reprodutibilidade dos Testes , Tato/efeitos dos fármacos
6.
J Oral Rehabil ; 38(1): 18-26, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20722773

RESUMO

This study aimed to quantify the directional specificity of multidirectional lip-closing force (LCF) and evaluate the reliability of multidirectional LCF measurements made using a novel system. In fourteen healthy subjects (seven females, seven males, median age = 28 years), LCFs in eight directions and electromyograms (EMGs) from four parts of the orbicularis oris muscles (OOM) were recorded during voluntary pursing-like lip closure tasks. The quantitative reliability was assessed from repeated measurements of the LCFs in the eight directions and from summed values for all eight directions [total lip-closing force (TLCF)]. The intra- and inter-investigator reliabilities for TLCF were assessed by the interclass correlation of the measurements by the same investigator and two investigators, respectively. Lip-closing forces showed directional specificity in vertical, horizontal and oblique directions but those in oblique and horizontal directions were symmetrical bilaterally. The quantitative reliability of measurements was between 0·735 and 0·948 in the eight directions and that of TLCF was 0·934. Interclass correlations of intra- and inter-investigator reliabilities were 0·96 [lower limit of 95% confidence interval (95% LL), 0·87] and 0·96 (95% LL, 0·91), respectively. The intra- and inter-investigator differences of measurements were randomly distributed in the whole range of measurements. The 95% confidence intervals of these differences were significantly narrower than those of the limits of agreement (mean ± 1·96 s.d.). In 13 subjects, Pearson's correlation coefficients between LCF and EMGs from OOM were above 0·95. We conclude that this system has a reasonable quality and reliability for quantitative measurements of multidirectional LCF for evaluating lip functions.


Assuntos
Músculos Faciais/fisiologia , Lábio/fisiologia , Adulto , Eletromiografia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes
7.
J Oral Rehabil ; 38(12): 921-8, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21790715

RESUMO

The objectives of this study were to estimate the effects of cleft lip and/or palate (CLP) repair on the multidirectional lip-closing forces (LCF) produced during maximum voluntary pursing-like lip-closing movement in children. Thirty Japanese children were divided into the control group and repaired unilateral CLP (RUCL) group, which was subdivided into the unilateral cleft lip and/or alveolus (UCLA) and the unilateral cleft lip and cleft palate (UCLP) groups. The maximum voluntary LCF were recorded in eight directions. No significant differences in any of the directional LCF (DLCF) or total LCF were observed between RUCL and control groups. Symmetrical DLCF were seen in the oblique directions on both sides of the upper lip in the control group, while the oblique DLCF on the non-cleft side was significantly greater than that on the cleft side in RUCL group. Furthermore, symmetrical vertical DLCF were observed in the upper and lower directions in control and UCLA groups, while the vertical DLCF obtained from the lower direction was significantly greater than that obtained from the upper direction in UCLP group. These results indicate that children with repaired CLP display impaired directional specificity, which may cause secondary deformities. These findings aid our understanding of the pathology of secondary deformities in CLP patients after primary surgery for cleft lip or palate. We propose that quantitative assessments of lip-closing function based on the directional specificity of the multidirectional LCF produced during maximum voluntary pursing-like lip-closing movement are useful for assessing the nature of lip-closing dysfunctions.


Assuntos
Fenda Labial/fisiopatologia , Fissura Palatina/fisiopatologia , Músculos Faciais/fisiopatologia , Contração Muscular , Sulco Nasogeniano/fisiopatologia , Adolescente , Povo Asiático , Criança , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Músculos Faciais/cirurgia , Feminino , Humanos , Masculino , Sulco Nasogeniano/cirurgia , Resultado do Tratamento
8.
J Bone Miner Res ; 11(2): 178-82, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8822341

RESUMO

We compared the effects of three different regimens of intravenous clodronate in a retrospective study of 60 patients with Paget disease. A total dose of 1500 mg of clodronate was given as 300 mg for 5 consecutive days (n = 20), 1500 mg as a single infusion (n = 20), or 300 mg as a single infusion for 5 consecutive months (n = 20). The response to treatment and the duration of the effect were assessed from sequential changes in the activity of serum alkaline phosphatase. Treatment with clodronate induced a significant response in 85% of patients. The response rate was comparable in patients treated with 5 daily infusions (90%), with a single infusion (75%), and with 5 monthly infusions (90%). The median duration of response from the start of treatment was 11 months for those treated with five daily infusions and 12 months for the other two regimens. At one year, 22, 40, and 44% of patients had maintained their response in the daily, single, and monthly infusion regimen, respectively (NS). Six patients (32%) treated with 5 daily infusions achieved a remission (complete response) compared with 3 patients treated with a single infusion and 5 monthly infusions, respectively (16 and 15% respectively, NS). Patients attaining a complete response had a significantly longer duration of response compared with partial responders (median time 15.0 versus 11.5 months, respectively, p < 0.05). We conclude that intravenous clodronate (total dose 1500 mg) suppresses disease activity in the majority of patients with Paget disease of bone. The degree and duration of response were similar for the three regimens. Thus, in the treatment of Paget disease, the choice of regimen is a matter of convenience.


Assuntos
Ácido Clodrônico/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Idoso , Análise de Variância , Esquema de Medicação , Estudos de Avaliação como Assunto , Feminino , Humanos , Infusões Intravenosas , Masculino , Estudos Retrospectivos
9.
J Bone Miner Res ; 13(6): 911-7, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9626621

RESUMO

Paget's disease of bone is a common condition characterized by bone pain, deformity, pathological fracture, and an increased incidence of osteosarcoma. Genetic factors play a role in the pathogenesis of Paget's disease but the molecular basis of the disease remains unclear. Previous genetic linkage studies have mapped the rare Paget's disease-like bone dysplasia familial expansile osteolysis (FEO) to chromosome 18q21-22, and recent work has shown evidence of linkage between this locus and Paget's disease in one family. Here we studied the relationship between the 18q21-22 locus and Paget's disease in eight large multiplex families from diverse ethnic backgrounds with inherited Paget's disease. Paget's disease was inherited as an autosomal dominant trait in all families, with high penetrance by the sixth decade. Analysis of seven highly polymorphic markers from chromosome 18q21-22 showed positive summated two-point log10 odds ratio (lodscores) of +2.97 with the marker D18S42 at a recombination fraction (theta) = 0.05, and of +2.95 with the marker D18S60 at theta = 0.00, values which are close to the cut-off of +3.0, which is generally accepted as evidence of linkage. Segregation analysis of the haplotypes and formal statistical analysis using the HOMOG program provided evidence for genetic heterogeneity, however, with evidence for linkage in five families and against linkage in the remaining three families (chi square 8.82; df = 2; p < 0.025). Multipoint linkage analysis in the five linked families showed lodscores of above +3.5 across the whole susceptibility region and a maximum summated lodscore of 3.89 at the marker D18S465. In the three nonlinked families, negative multipoint results were obtained for the whole region, with lodscores below -2.0 in one family, excluding this as a candidate locus for the disease. Our studies demonstrate the importance of hereditary factors in the pathogenesis of Paget's disease and confirm evidence of linkage between Paget's disease and chromosome 18q21-22 in some families. This raises the possibility that Paget's disease and FEO may share a common molecular basis, perhaps due to different mutations in the same gene or family of genes. Data from three families did not support evidence of linkage to 18q21-22 however, indicating that Paget's disease is genetically heterogeneous and suggests the presence of at least one additional locus which remains to be discovered.


Assuntos
Aberrações Cromossômicas/genética , Cromossomos Humanos 21-22 e Y/genética , Cromossomos Humanos Par 18/genética , Osteíte Deformante/genética , Transtornos Cromossômicos , Marcadores Genéticos/genética , Predisposição Genética para Doença , Humanos , Japão , Repetições de Microssatélites , Linhagem , Espanha , Reino Unido
10.
Am J Clin Nutr ; 56(1 Suppl): 265S-267S, 1992 07.
Artigo em Inglês | MEDLINE | ID: mdl-1615897

RESUMO

Calcium homeostasis during a very-low-calorie diet (VLCD) was examined. During the treatment, intact parathyroid hormone tended to decrease initially, bone Gla-protein increased significantly in the third week, and tartrate-resistant acid phosphatase decreased during the entire treatment. Serum ketone bodies showed significant correlations with intact parathyroid hormone and bone Gla-protein in some cases. Regarding bone mineral content, bone mineral content of the head increased while that of the legs decreased, resulting in no significant changes in total bone mineral content. These results suggest that VLCD treatment alters calcium homeostasis, which may cause regional bone mineral changes.


Assuntos
Densidade Óssea/fisiologia , Cálcio/metabolismo , Dieta Redutora , Ingestão de Energia/fisiologia , Obesidade Mórbida/dietoterapia , Fosfatase Ácida/sangue , Adulto , Calcitonina/sangue , Cálcio/sangue , Cálcio/urina , Feminino , Homeostase , Humanos , Corpos Cetônicos/sangue , Obesidade Mórbida/metabolismo , Osteocalcina/análise , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Fosfatos/urina
11.
Bone ; 18(2): 185-90, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8833213

RESUMO

We studied retrospectively 51 patients with Paget's disease of bone treated with oral clodronate, 1600 mg daily given for 1 (n = 23), 3 (n = 13), or 6 months (n = 15), to compare the effect of a variable length of treatment on the response rate to treatment and the duration of disease suppression. Activity of alkaline phosphatase and urinary hydroxyproline excretion were measured before treatment at monthly intervals for a year and every 3 months thereafter until biochemical relapse. Before treatment, patients given the three regimens had similar disease activity as judged by serum alkaline phosphatase and urinary hydroxyproline values. There was no significant difference in the time to response between groups (median = 2 months). The proportion of patients attaining normal values of alkaline phosphatase activity was significantly higher in patients treated for 6 months (71%, p < 0.03) compared with those treated for 1 or 3 months (23% and 39%, respectively). The time to relapse from the start of treatment was significantly shorter in patients treated for 1 month compared with those treated for 3 or 6 months (median = 11, 18, and 23 months, respectively). Thus, at 2 years all patients treated for 1 month had relapsed, whereas 31% and 40% were still relapse-free in patients receiving treatment for 3 and 6 months, respectively. The length of treatment was the only variable identified by stepwise linear regression that significantly affected the duration of response. We conclude that oral clodronate (1600 mg daily) suppresses disease activity in the vast majority of patients with Paget's disease of bone. The magnitude of the response and its duration depend on the duration of treatment or the total dose administered, so that several months of treatment with oral clodronate are required when a durable response is desired.


Assuntos
Ácido Clodrônico/uso terapêutico , Osteíte Deformante/tratamento farmacológico , Administração Oral , Idoso , Fosfatase Alcalina/sangue , Análise de Variância , Esquema de Medicação , Feminino , Humanos , Hidroxiprolina/urina , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/metabolismo , Análise de Regressão , Indução de Remissão/métodos , Retratamento , Estudos Retrospectivos
12.
J Med Chem ; 29(6): 906-12, 1986 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3712380

RESUMO

One of the pattern recognition techniques, the SIMCA method, has been applied to structure-taste studies on L-aspartyl dipeptides (L-Asp-NH-R). The sweet and bitter taste class models of the peptides were obtained by using five structural descriptors, such as molar refractivity, and four kinds of STERIMOL parameters. The classification rates were calculated to be 87% and 81% for sweet and bitter peptides, respectively. The SIMCA method has also suggested that two factors, shape and size, of the C-terminal amino acid moiety R in the dipeptides are extremely important to model their taste qualities.


Assuntos
Dipeptídeos/farmacologia , Edulcorantes/farmacologia , Paladar , Ácido Aspártico , Humanos , Modelos Estruturais , Conformação Proteica , Relação Estrutura-Atividade
13.
Invest Ophthalmol Vis Sci ; 26(8): 1109-16, 1985 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-4019102

RESUMO

The indoleamine-accumulating amacrine cells in the rabbit's retina were destroyed by intravitreal injections of 5,7-DHT according to the technique of Ehinger and Florén. One week after the injections, histofluoresence microscopy failed to show the IA-cells in the retina. At this time, the b-wave of the treated eyes was significantly smaller, the OPs were more prominent, and the duration of the b-wave was longer. The a- and c-waves and the off-response were not affected. The loss of the IA-cells resulted in a reduction in the range of dark-adaptation but did not affect the rate of recovery of the threshold. The loss of the IA-cells also had no effect on the response of the retina to flickering light. In a double-flash experiment, the suppression of the response to the second flash was significantly weaker in the treated eyes. These results can be explained by the loss of a negative feedback circuit that has been proposed for the IA-cells from morphologic studies.


Assuntos
Eletrorretinografia , Retina/fisiologia , 5,7-Di-Hidroxitriptamina/metabolismo , Animais , Coelhos , Retina/citologia , Retina/efeitos dos fármacos
14.
J Biochem ; 101(2): 365-76, 1987 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2953711

RESUMO

Ca2+-Transporting ATPase of rabbit skeletal muscle sarcoplasmic reticulum contains several SH groups which are reactive with N-ethylmaleimide (MalNEt) at pH 7.0. The location of the one which is most reactive with MalNEt (SHN, Kawakita et al. J. Biochem. 87, 609 (1980)) was identified on the amino acid sequence of the ATPase. SHN was labeled by reacting sarcoplasmic reticulum membranes with [14C] MalNEt to a labeling density of 1 mol/mol ATPase. [14C]MalNEt-labeled membranes were digested with thermolysin and 14C-labeled SHN peptides were fractionated by Sephadex LH-20 chromatography to give two major peaks of radioactivity. [14C]-MalNEt-labeled peptides were further purified to homogeneity by C18-reversed phase HPLC. Two radioactive peptides containing modified cysteine (Cys), Leu-Gly-Cys-Thr-Ser and Val-Cys-Lys-Met, were finally obtained in roughly equal amounts and in reasonable recovery. Both of these sequences were found in the amino acid sequence of Ca2+-transporting ATPase (Brandl et al. Cell 44, 597 (1986)), and Cys344 and Cys364 were identified as the targets of MalNEt-modification. Thus, 0.5 mol/mol ATPase of each Cys residue actually reacted rapidly with MalNEt under the conditions leading to SHN-modification. Modification of either one with MalNEt may negatively affect the reactivity of the other. Both of the highly reactive SH groups are located in the neighborhood of Asp351, the phosphorylation site of ATPase.


Assuntos
Adenosina Trifosfatases/metabolismo , Etilmaleimida/metabolismo , Retículo Sarcoplasmático/enzimologia , Compostos de Sulfidrila/metabolismo , Aminoácidos/análise , Animais , Sítios de Ligação , Cromatografia Líquida de Alta Pressão , Fragmentos de Peptídeos/análise , Coelhos
15.
J Clin Pharmacol ; 37(1): 58-63, 1997 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9048274

RESUMO

This study examined the effects of ophthalmic timolol and time of administration on cardiovascular and respiratory functions in healthy young male volunteers. Eight participants (mean age +/- standard deviation, 22 +/- 0.9 years) received either 50 microL of 0.5% timolol or placebo in the lower conjunctival sacs of both eyes in the morning or evening. Intraocular pressure, blood pressure, heart rate, and respiratory functions, including percent forced expiratory volume in 1 second and peak expiratory flow rate, were then measured for 3 hours after drug administration. Timolol reduced intraocular pressure and cardiovascular function at both administration times. However, a timolol-induced reduction in respiratory function was observed only in the evening: percent forced expiratory volume in 1 second, peak expiratory flow rate, and expiratory flow rate at 75% vital capacity were reduced by 3%, 7%, and 12%, respectively, 3 hours after administration. These results indicate that ophthalmic timolol reduces cardiovascular and respiratory functions in healthy young male subjects and that bronchial sensitivity to timolol differs between morning and evening.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Glaucoma/tratamento farmacológico , Timolol/uso terapêutico , Adulto , Análise de Variância , Pressão Sanguínea/efeitos dos fármacos , Estudos Cross-Over , Método Duplo-Cego , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas
16.
J Clin Pharmacol ; 40(2): 193-9, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10664926

RESUMO

Systemic adverse effects of timolol ophthalmic solution given at usual therapeutic doses have been well characterized. Timolol is partially metabolized by cytochrome P450 (CYP) 2D6. Cimetidine inhibits the activity of cytochrome P450, including CYP2D6, leading to reduced systemic clearance of concomitant drugs. Coadministration of cimetidine has been speculated to affect the pharmacological effects of timolol ophthalmic solution, resulting in increased blood concentration. To evaluate whether administration of cimetidine with timolol ophthalmic solution increased the degree of beta-blockade, 12 healthy Japanese male volunteers ages 19 to 26 received cimetidine (400 mg), on oral placebo, timolol maleate 0.5% (0.05 mL to each eye), or placebo eye drops in a randomized, double-blind, Latin-square design. The oral drug alone was given for 3 days, and on the 4th day, eye drops were applied after oral drug administration. At baseline and 1, 3, and 6 hours after eye drop administration, blood pressure and heart rate (HR) were measured before and after exercise. Intraocular pressure (IOP) was measured at rest. A visual analog scale (VAS) was used to assess subjective bodily feelings in exercise tolerance after every physical exercise. The exercise HR, exercise systolic blood pressure (SBP), and resting SBP were reduced following timolol with and without cimetidine compared with the placebo (p < 0.01, respectively). Administration of cimetidine with timolol ophthalmic solution resulted in additional reductions of the resting HR and IOP. VAS detected a significant reduction in exercise tolerance from timolol ophthalmic solution (p < .05). In conclusion, administration of cimetidine with timolol ophthalmic solution increased the degree of beta-blockade.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Cimetidina/farmacologia , Inibidores do Citocromo P-450 CYP2D6 , Inibidores Enzimáticos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Timolol/farmacologia , Adulto , Método Duplo-Cego , Interações Medicamentosas , Humanos , Masculino , Soluções Oftálmicas
17.
J Clin Pharmacol ; 38(1): 68-73, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9597562

RESUMO

Ocular perfusion is a critical factor in ischemic ocular diseases, and blood flow in the ophthalmic artery has a pronounced effect on perfusion. To evaluate the effects of dihydropyridine calcium channel blocker and nonselective beta-adrenergic antagonist on ocular perfusion, we investigated the short-term effects of single oral doses of nicardipine (40 mg) and propranolol (40 mg) on the blood flow velocity in the ophthalmic artery, intraocular pressure (IOP), systemic blood pressure, and heart rate in nine healthy Japanese male volunteers in a double-blind, placebo-controlled study using color Doppler imaging. Parameters were evaluated before and 60 and 120 minutes after administration. Nicardipine significantly increased the maximum systolic velocity and time-averaged blood flow velocity compared with placebo without significant increase in the resistance index. Propranolol had no significant effects on Doppler parameters. Propranolol exhibited a great reduction in IOP from placebo values. Systolic blood pressure and heart rate were significantly reduced by propranolol. Nicardipine significantly increased heart rate. These results suggest that nicardipine increased ophthalmic blood flow, but propranolol did not.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Hemodinâmica/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Nicardipino/farmacologia , Propranolol/farmacologia , Adulto , Método Duplo-Cego , Humanos , Masculino
18.
Biomed Pharmacother ; 54 Suppl 1: 7s-11s, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10914983

RESUMO

Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia due to excessive secretion of PTH, is usually associated with hypophosphatemia and elevated serum chloride. Although PHPT was often complicated by renal stone disease and osteitis fibrosa in the past, routine screening of serum calcium (Ca) and development of sophisticated assay of parathyroid hormone have contributed to earlier detection of asymptomatic PHPT (APHPT). The proportion of APHPT patients, who have a mild elevation of serum Ca levels, usually within 1.0 mg/dL above the upper limit of normal, rose from 10-20% to approximately 45% of all PHPT patients in 1990-1995 in our clinic. Although it has been reported that the prevalence of PHPT is about 0.1% of the American population, the prevalence of PHPT appears to be far less in the Japanese population. Determination of a strategy for the increasing number of APHPT patients, is a pressing need but has yet to be accomplished. Treatment with bone antiresorptive drugs has met with some success, although the long-term efficacy of this treatment is not clear. The therapeutic effects of Ca-sensing receptor agonists appear promising.


Assuntos
Hiperparatireoidismo/diagnóstico , Hiperparatireoidismo/fisiopatologia , Antagonistas de Hormônios/uso terapêutico , Humanos , Hiperparatireoidismo/tratamento farmacológico , Hiperparatireoidismo/etiologia
19.
Ann Clin Biochem ; 33 ( Pt 2): 127-31, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8729720

RESUMO

We evaluated a new immunoselective enzyme assay of bone-specific alkaline phosphatase (ALP). The monoclonal antibody used in this assay was raised against purified bone-specific ALP obtained from SAOS-2 human osteosarcoma cell line. Calibration was based on the enzyme's own activity. The relative activity of the antibody was 100% with bone ALP, 8.7% with liver ALP, and 0% with placental and intestinal ALPs. Intra- and inter-assay coefficients of variation were less than 4%. The sensitivity of the assay was 0.7 U/L, and the linearity extended from 2 to 140 U/L. The recovery of bone-specific ALP standard added to serum was 94-106%. The correlation coefficient between this method and the polyacrylamide gel (PAG) electrophoretic method was 0.94. The mean value of bone-specific ALP in 89 healthy adults (mean age 29 years, SD 5 years) was 18.5 U/L (SD 4.1 U/L). Interestingly, mean bone-specific ALP activities in 60 premenopausal women (mean age 39 years, SD 8 years) and 70 postmenopausal women (mean age 57 years, SD 5 years) were 20.3 U/L (SD 6.5 U/L) and 31.1 U/L (SD 11.1 U/L), respectively. The age-related increase in bone-specific ALP was significant and more pronounced in women (P < 0.01). We conclude that this new immunoassay of bone-specific ALP would be useful for clinical investigation of patients with osteoporosis or other metabolic diseases of bone.


Assuntos
Fosfatase Alcalina/análise , Osso e Ossos/enzimologia , Técnicas Imunoenzimáticas , Isoenzimas/análise , Adulto , Anticorpos Monoclonais , Especificidade de Anticorpos , Estudos de Casos e Controles , Eletroforese em Gel de Poliacrilamida , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência
20.
Plast Reconstr Surg ; 97(2): 338-44, 1996 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-8559816

RESUMO

A simplified procedure of maxillary augmentation with a porous hydroxyapatite block graft in the anterior aspect of the maxillary parapiriformis area is described. This procedure is an alternative for maxillary advancement osteotomy and is simple to perform for maxillofacial deformity of cleft lip and palate and other deformities. It is effective for facial aesthetics in association with mandibular surgery, such as mandibular setback by sagittal splitting osteotomy, mandibular segmental osteotomy with premolar extraction, bimaxillary osteotomy, and/or genioplasty. We used this procedure on 21 patients (15 for cleft lip and palate jaw deformity and 6 for aesthetic reasons). Although postoperative infection requiring removal of the hydroxyapatite block occurred in one cleft deformity patient, satisfactory results were obtained in all patients.


Assuntos
Ossos Faciais/anormalidades , Maxila/anormalidades , Maxila/cirurgia , Próteses e Implantes , Cirurgia Plástica/métodos , Adulto , Fenda Labial/complicações , Fissura Palatina/complicações , Durapatita , Feminino , Humanos , Masculino
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