RESUMO
Paclitaxel, an antineoplastic agent used for the treatment of ovarian cancer, is metabolized by cytochrome P450 (CYP)3A4 and CYP2C8 and is excreted from cells by ATP-binding cassette (ABCB1) (multi-drug resistance [MDR1], P-glycoprotein). Expression of these proteins is regulated by pregnane X receptor (PXR). Although there are common genetic polymorphisms in the genes encoding these proteins, their effect on the clinical efficacy of paclitaxel is unclear. We therefore examined the relationship of the paclitaxel pharmacokinetics in 13 patients with ovarian cancer to polymorphisms in CYP2C8, CYP3A5, ABCB1, and PXR. We found high interindividual variability in the plasma concentrations of two metabolites, 6alpha-hydroxypaclitaxel and p-3'-hydroxypaclitaxel. All the patients were genotyped as CYP2C8*1/*1. Neither the CYP3A5 A6986G (CYP3A5*3) nor the PXR C-25385T alleles were associated with altered plasma concentrations of paclitaxel and its metabolites. ABCB1 T-129C, T1236C, and G2677(A,T), however, was associated with lower area under the plasma concentration-time curve (AUC) of paclitaxel. We also observed a significant correlation between the AUC (r=-0.721) or the total clearance of paclitaxel (CL(tot)) (r= 0.673) and the ABCB1 mutant allele dosage in each patient. Taken together, our findings suggest that interindividual variability in paclitaxel pharmacokinetics could be predicted by ABCB1 genotyping.
Assuntos
Variação Genética , Transportadores de Ânions Orgânicos/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Paclitaxel/farmacocinética , Subfamília B de Transportador de Cassetes de Ligação de ATP , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Adulto , Idoso , Área Sob a Curva , Hidrocarboneto de Aril Hidroxilases/genética , Citocromo P-450 CYP2C8 , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Genótipo , Humanos , Japão , Dose Máxima Tolerável , Taxa de Depuração Metabólica/efeitos dos fármacos , Pessoa de Meia-Idade , Modelos Biológicos , Neoplasias Ovarianas/metabolismo , Paclitaxel/sangue , Paclitaxel/uso terapêutico , Receptor de Pregnano X , Receptores de Esteroides/genética , Estatística como AssuntoRESUMO
We studied the effect of peroxisome proliferator-activated receptor gamma (PPARgamma) activation on thromboxane A(2)(TXA(2)) and prostaglandin E(2)(PGE(2)) production in monocyte/macrophage cell lines. In present experiment, we used human peripheral blood monocyte (PBMC), monocyte-cell line THP-1 and mouse macrophage-like cell line RAW264.7. The expression of PPARgamma is reported in PBMC and THP-1. Synthetic PPARgamma ligands (troglitazone or BRL49653) inhibited TXA(2) production and enhanced PGE(2) production of PBMC and THP-1. When treated with 0.5-10 microM of troglitazone, there were no significant changes of TXA(2) and PGE(2) production of RAW264.7 cells, which express very low levels of PPARgamma. When RAW264.7 cells was transfected with PPARgamma expression plasmid and treated with troglitazone, PPARgamma was activated in a dose-dependent manner. In PPARgamma-transfected RAW264.7, TXA(2) production was decreased and PGE(2) production was increased by troglitazone treatment. But it needs high concentration of troglitazone (10 microM) for increasing PGE(2) production. These results suggest that PPARgamma may have negative effect on TXA(2) production, and also have slightly positive effect on PGE(2) production of macrophage.
Assuntos
Dinoprostona/biossíntese , Receptores Citoplasmáticos e Nucleares/fisiologia , Tiazolidinedionas , Tromboxano A2/biossíntese , Fatores de Transcrição/fisiologia , Animais , Linhagem Celular , Cromanos/farmacologia , Humanos , Ligantes , Macrófagos/metabolismo , Monócitos/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Tiazóis/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Transfecção , TroglitazonaRESUMO
A liquid chromatographic-tandem mass spectrometric (LC/MS-MS) method was developed for the simultaneous quantification of prostaglandin (PG) E(2), PGF(2alpha), 6-keto-PGF(lalpha) and thromboxane (TX) B(2). These eicosanoids and their deuterium derivatives, using as internal standards, were extracted by solid-phase extraction and analyzed using LC/MS-MS in the selected reaction-monitoring (SRM) mode. A good linear response over the range of 10 pg to 10 ng for each eicosanoid was demonstrated. The accuracy of added eicosanoids ranged from 94.1 to 106.6% and coefficients of variation ranged from 0.62 to 7.8%. Furthermore, we applied this method for the determination of eicosanoids in the human synovial cell-cultured medium, stimulated by lipopolysaccharide (LPS). LPS produced each eicosanoid and they increased in a time-dependent manner. The production levels after 24 h stimulation were 6-keto-PGF(1alpha) > PGE(2) > TXB(2) >> PGF(2alpha). This simultaneous quantification method is so useful to clarify the function of synovial cells in rheumatoid arthritis (RA).
Assuntos
Meios de Cultivo Condicionados/química , Prostaglandinas/análise , Líquido Sinovial/citologia , Líquido Sinovial/metabolismo , Calibragem , Linhagem Celular , Cromatografia Líquida , Humanos , Espectrometria de Massas , Prostaglandinas/química , Sensibilidade e EspecificidadeRESUMO
To elucidate the relationship between the thromboxane A2/prostacyclin (TXA2/PGI2) ratio and diabetic complications, the levels of 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1alpha, the urinary metabolites of thromboxane A2 and prostacyclin, were measured in diabetics by gas chromatography/selected ion monitoring. We compared the TXA2/PGI2 ratio in healthy volunteers and diabetics. The TXA2/PGI2 ratio of diabetics was significantly higher than that of healthy volunteers and we could reconfirm the hypercoagulable condition in diabetics. We also investigated the difference of TXA2/PGI2 levels in diabetics with retinopathy and neuropathy. The TXA2/PGI2 ratio of diabetics with retinopathy showed significantly higher level than without retinopathy. However, the TXA2/PGI2 ratio of diabetics with neuropathy was the same as without neuropathy. These results suggest that the TXA2/PGI2 ratio reflects the pathological conditions of diabetes, especially the change of vasculature. The monitoring and improvement of TXA2/PGI2 ratio could be useful for the prevention of diabetic vascular complications.
Assuntos
6-Cetoprostaglandina F1 alfa/análogos & derivados , Diabetes Mellitus Tipo 2/urina , Nefropatias Diabéticas/urina , Neuropatias Diabéticas/urina , Epoprostenol/urina , Tromboxano B2/análogos & derivados , Tromboxano B2/urina , 6-Cetoprostaglandina F1 alfa/urina , Adulto , Cromatografia Gasosa , Diabetes Mellitus Tipo 2/terapia , Nefropatias Diabéticas/terapia , Neuropatias Diabéticas/terapia , Feminino , Humanos , MasculinoRESUMO
We investigated production of prostacyclin and the urinary ratio of thromboxane and prostacyclin in patients with rheumatoid arthritis. The prostacyclin production level was assessed according to the level of urinary 2,3-dinor-6-keto-prostaglandin F(1 alpha)measuring by gas chromatography/selected ion monitoring. In patients receiving medication, the prostacyclin level was lower and the thromboxane/prostacyclin ratio was greater compare with that of healthy volunteers. The prostacyclin level in patients without medication was approximately 4-fold higher than that of healthy volunteers and 8-fold higher than those of medicated groups. Although the ratio of the group without medication was similar to that of healthy volunteers, the urinary levels of each prostanoid were higher than those of other groups. Then, the ratios of groups receiving steroids were higher than that of other groups owing to high TX level. The present findings demonstrated that endogenous prostacyclin and thromboxane production increased in patients without medication, and prostacyclin production decreased with medication.
Assuntos
Artrite Reumatoide/urina , Cromatografia Gasosa/métodos , Epoprostenol/urina , Íons/metabolismo , Tromboxanos/urina , 6-Cetoprostaglandina F1 alfa/urina , Idoso , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We investigated the influence of anesthesia on the brain distribution of [11C]methamphetamine (MAP) obtained by the positron emission tomography (PET) using the normal rhesus monkeys. We clarified that the brain uptake of [11C]MAP under halothane anesthesia was faster and higher than that under pentobarbital. The difference of the effect of anesthesia is an important problem in pharmacokinetic study in PET with experimental animals.
Assuntos
Anestésicos/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Radioisótopos de Carbono/farmacocinética , Metabolismo Energético/efeitos dos fármacos , Metanfetamina/farmacocinética , Tomografia Computadorizada de Emissão , Adjuvantes Anestésicos/farmacologia , Anestésicos Inalatórios/farmacologia , Animais , Encéfalo/metabolismo , Circulação Cerebrovascular/efeitos dos fármacos , Circulação Cerebrovascular/fisiologia , Metabolismo Energético/fisiologia , Halotano/farmacologia , Macaca mulatta , Masculino , Pentobarbital/farmacologiaRESUMO
Intraperitoneal injection of benzodiazepine receptor agonists (estazolam, zopiclone, triazolam: 0.03-0.24 mmol/kg) induces the head twitch response (HTR). The present study was undertaken to examine the possible participation of the serotonergic system in the mechanism of head twitches induced by benzodiazepine receptor agonists (BZ-RAs). The HTR induced by BZ-RAs was suppressed by pretreatment with ketanserine (1 mg/kg, i.p.), a selective 5-HT(2) receptor antagonist. Pretreatment with fluoxetine (10 mg/kg, i.p.), a 5-HT reuptake inhibitor, and 8-hydroxy-2-(di-n-propylamino)tetralin, a 5-HT(1A) receptor agonist, also suppressed the HTR induced by BZ-RAs. These results suggest that the HTR induced by BZ-RAs may be the result of an activation of postsynaptic 5-HT(2) receptors, probably due to direct action.
Assuntos
Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Estazolam/farmacologia , Agonistas de Receptores de GABA-A , Piperazinas/farmacologia , Triazolam/farmacologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Ansiolíticos/administração & dosagem , Compostos Azabicíclicos , Di-Hidroxitriptaminas/farmacologia , Estazolam/administração & dosagem , Fluoxetina/farmacologia , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/farmacologia , Ketanserina/farmacologia , Masculino , Camundongos , Piperazinas/administração & dosagem , Receptores de GABA-A/metabolismo , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Triazolam/administração & dosagemRESUMO
When a narrow region of the fresh water coenocytic alga, Vaucheria terrestris sensu Götz is irradiated with moderately intense blue light, a branch is induced from the center of the irradiated region after 4-5 h. Movement of organelles and microtubule bundles during the photocytomorphogenetic response were investigated. Chloroplasts in the cortical layer immediately started to accumulate in the blue light-irradiated region and their accumulation almost completely finished 30-40 min after the onset of light when the nuclei residing in endoplasm started to accumulate. Accumulation of nuclei was synchronized with disorientation and shortening of microtubule bundles, which originally run parallel to the cell axis. Not only amiprophos-methyl, a potent microtubule-decomposing reagent, but also cytochalasin A strongly inhibited the branch induction. Amiprophos-methyl completely and cytochalasin A mostly destroyed microtubules and completely inhibited nuclear accumulation, but both drugs allowed the accumulation of chloroplasts in the cortical layer of irradiated region. These indicate that the accumulation of nuclei is indispensable for branch induction while the chloroplast accumulation is insufficient by itself for branch induction. The ineffectiveness of cytochalasin A on chloroplast movement brings the conventional view of sliding movement of chloroplast on a long actin cable into question. The morphological and functional relationship between a nucleus and a microtubular bundle are discussed.
Assuntos
Eucariotos/fisiologia , Núcleo Celular/fisiologia , Cloroplastos/fisiologia , Citocalasinas , Herbicidas , Luz , Microtúbulos/fisiologia , Nitrobenzenos , Compostos Organotiofosforados , Fatores de TempoRESUMO
BACKGROUND: Synthesis of cysteinyl leukotrienes (LTs) is known to play a part in the pathogenesis of inflammatory diseases. OBJECTIVES: To define the involvement of cysteinyl LTs in atopic dermatitis (AD). METHODS: Synthesis of cysteinyl LTs was assessed in patients with AD and healthy volunteers by measuring urinary LTE4, a useful index of systemic cysteinyl LT synthesis, using liquid chromatography/tandem mass spectrometry. RESULTS: Mean +/- SD urinary LTE4 levels in patients with AD (125 +/- 69 pg mg(-1) creatinine, n = 20) were significantly higher (P < 0.01) than in healthy volunteers (60 +/- 19 pg mg(-1) creatinine, n = 17). A significant correlation between urinary LTE4 and total serum IgE levels in patients with AD was observed (r = 0.643, P < 0.05). CONCLUSIONS: Our findings demonstrate an enhanced synthesis of cysteinyl LTs in patients with AD and suggest that cysteinyl LTs are involved in the pathophysiology of AD.
Assuntos
Dermatite Atópica/urina , Leucotrieno E4/urina , Adolescente , Adulto , Cromatografia Líquida , Dermatite Atópica/sangue , Dermatite Atópica/imunologia , Feminino , Humanos , Imunoglobulina E/sangue , Masculino , Espectrometria de MassasRESUMO
Thromboxane and leukotrienes have been implicated in inflammation. However, the production level of these eicosanoids in patients with rheumatoid arthritis is still unclarified. In the present study, endogenous synthesis of thromboxane and cysteinyl leukotrienes in patients was investigated. The production of eicosanoids in patients is assessed by measuring stable urinary metabolites,11-dehydro thromboxane B2 and leukotriene E4, using gas chromatography/selected ion monitoring and liquid chromatography/tandem mass spectrometry. The level of urinary thromboxane in patients was significantly higher than that in healthy volunteers (P < 0.05). Furthermore, we investigated the effects of administered drugs on the production of these eicosanoids. The urinary thromboxane level of the untreated group (1630 +/- 613 pg/mg creatinine) was much higher than that of healthy volunteers (342 +/- 263 pg/mg creatinine). The level in the group receiving NSAID alone was similar to that in healthy volunteers, and the group receiving steroid alone showed slightly lower thromboxane levels than the untreated group. On the other hand, the leukotriene E4 level in patients (280 +/- 360 pg/mg creatinine) was also significantly higher than that in healthy volunteers (59 +/- 54 pg/mg creatinine, P < 0.05). In particular, the group receiving methotrexate (904 +/- 685 pg/mg creatinine) had higher leukotriene levels than not only healthy volunteers but also other medicated groups. These findings demonstrated that endogenous thromboxane and leukotriene production in patients with rheumatoid arthritis are enhanced, and the effects of medication on the production of these eicosanoids differed in thromboxane and leukotriene E4.
Assuntos
Artrite Reumatoide/urina , Leucotrieno E4/urina , Tromboxano B2/análogos & derivados , Tromboxano B2/urina , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Creatinina/urina , Humanos , Pessoa de Meia-Idade , Valores de Referência , Esteroides/uso terapêutico , Tromboxano A2/metabolismoRESUMO
Bronchoconstrictor cysteinyl leukotrienes (LT) and thromboxane (TX) A2 have been implicated in the pathogenesis of asthma. Determination of urinary leukotriene E4 (LTE4) and 11-dehydro-TXB2 levels are often used to assess cysteinyl LT and TXA2 production in humans. To define the potential role in the pathogenesis of asthma, we investigated the urinary LTE4 and 11-dehydro-TXB2 levels. LTE4 and 11-dehydro-TXB2 levels were determined using liquid chromatography/tandem mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS), respectively. Urinary LTE4 levels in asthmatic patients (192 +/- 122 pg/mg creatinine, n = 14) were significantly higher (P < 0.005) than those in healthy volunteers (55 +/- 16 pg/mg creatinine, n = 13), but no significant difference in 11-dehydro-TXB2 levels was observed. A significant inverse correlation (r = -0.821, P < 0.005) was found between urinary LTE4 levels and the forced expiratory volume in 1 s (FEV1) but no significant correlation was observed between urinary 11-dehydro-TXB2 levels and FEV1. The present findings suggest that cysteinyl LTs play a more important role in the pathogenesis of asthma than TXA2.
Assuntos
Asma/urina , Leucotrieno E4/urina , Tromboxano B2/análogos & derivados , Tromboxano B2/urina , Adulto , Idoso , Asma/fisiopatologia , Cromatografia Líquida , Feminino , Volume Expiratório Forçado , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Valores de ReferênciaRESUMO
We have identified a genomic DNA fragment, using the PCR method with degenerate oligonucleotide primers which contain the conserved sequence of the RING finger domain. Using the DNA fragment as a probe, a novel cDNA was cloned from human and mouse testis. The cDNA had a domain structure of the typical RING-B box-coiled coil (RBCC)-B30.2 domain and therefore was named testis-abundant finger protein (tfp). Indeed, the transcript was highly expressed in the testis, although it was also found ubiquitously in various organs by Northern blot analysis. The tfp gene was mapped at the class I region of the human MHC (major histocompatibility complex), within which some known RBCC-B30.2 proteins such as RFP, RFB30/HERF1, AFP, and HZF had been localized. These findings demonstrate that several RBCC-B30.2 proteins including tfp, which are non-HLA proteins, are clustered within the class I region of the human MHC.
Assuntos
Proteínas de Transporte/genética , Genes MHC Classe I , Genoma Humano , Testículo , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , Genoma , Antígenos de Histocompatibilidade/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Camundongos , Dados de Sequência Molecular , Alinhamento de Sequência , Proteínas com Motivo Tripartido , Ubiquitina-Proteína LigasesRESUMO
Effects of troglitazone, an antidiabetic thiazolidinedione that enhances insulin sensitivity, on thromboxane (TX) production were assessed in human erythroleukemia (HEL) cells and human platelets. Measurement of TX was performed by using the gas chromatography/selected ion monitoring (GC/SIM) method. We found that troglitazone reduced the TX production from HEL cells and human platelets. Furthermore, troglitazone also reduced arachidonic acid (AA)-induced TX production from HEL cell and thrombin-induced TX release from platelets. In addition, we compared the effect of troglitazone with that of alpha-tocopherol and BRL 49653. Other thiazolidinedione compound BRL 49653 had effects similar to troglitazone, but alpha-tocopherol had no effect on TX production. Our findings suggest that the thiazolidinedione group had an antithrombotic effect and was beneficial in preventing vascular complications often observed in diabetes mellitus.
Assuntos
Cromanos/farmacologia , Fibrinolíticos/farmacologia , Tiazóis/farmacologia , Tiazolidinedionas , Tromboxano A2/metabolismo , Ácido Araquidônico/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Diabetes Mellitus Tipo 2 , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Leucemia Eritroblástica Aguda , Rosiglitazona , Troglitazona , Células Tumorais Cultivadas , Vitamina E/farmacologiaRESUMO
We describe the effect of (-) epigallocatechin gallate (EGCg), one of catechins known in tea, on the prostacyclin (PGI) production by bovine aortic endothelial cells. The amounts of 6-keto-PGF(1alpha) and Delta(17)-6-keto-PGF(1alpha), stable metabolites of PGI(2) and PGI(3), released in culture medium were measured using gas chromatography/selected ion monitoring (GC/SIM). The prostacyclin production of endothelial cells was increased by EGCg in a dose- and time-dependent manner. The effect by EGCg was stronger than any other catechins (catechin, epicatechin, epigallocatechin, and epicatechin gallate). When endothelial cells incubated with EGCg and arachidonic acid (AA) or eicosapentaenoic acid (EPA), PGI(2), and PGI(3) production were increased greater than those incubated with AA or EPA alone. Furthermore, gallic acid, that also has a pyrogallol structure, increased PGI(2) production. These observations indicate that catechins increase the prostacyclin production and that the pyrogallol structure is significant to this function.
Assuntos
Catequina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Epoprostenol/biossíntese , Animais , Ácido Araquidônico/farmacologia , Catequina/análogos & derivados , Catequina/química , Bovinos , Células Cultivadas , Relação Dose-Resposta a Droga , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Endotélio Vascular/metabolismo , Epoprostenol/metabolismo , Fibrinolíticos/farmacologia , Ácido Gálico/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Estrutura Molecular , Inibidores da Agregação Plaquetária/farmacologia , Tromboxanos/metabolismoRESUMO
Liquid chromatography-tandem mass spectrometry (LC/MS-MS) was applied to the quantitative analysis of urinary 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) level. 8-Epi-PGF(2alpha) and its internal standard, [(2)H(4)]-8-epi-PGF(2alpha), were extracted from urine by using a solid phase extraction cartridge and loaded to LC/MS-MS in selected reaction monitoring (SRM) mode. The standard curve showed good linearity in the range of 40 pg to 10 ng (r = 0. 997). The accuracy of the added 8-epi-PGF(2alpha) ranged from 96.8 to 104.9% with a mean +/- SD of 99.5+/-2.5%. The average level +/- SD of urinary 8-epi-PGF(2alpha) in 13 healthy volunteers (five women and eight men, 31+/-7.4 years old) was 429.4+/-149.6 pg/mg creatinine. The level of seven patients with noninsulin dependent diabetes mellitus (two women and five men, 40+/-13.6 years old), 630.9+/-275.6 pg/mg creatinine, was statistically higher than that of healthy volunteers (P<0.05). This finding suggested that diabetics are in a highly oxidative condition. This simple and rapid LC/MS-MS method can be used to elucidate the pathophysiological feature of diabetes or for monitoring the curative effect.
Assuntos
Diabetes Mellitus Tipo 2/urina , Dinoprosta/análogos & derivados , Dinoprosta/urina , Adulto , Cromatografia Líquida , Creatinina/urina , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Padrões de Referência , Fumar/urinaRESUMO
A simple and sensitive semi-micro high-performance liquid chromatography (HPLC) was established for determining the serum levels of glycyrrhizin (GL) in humans. Butyl p-hydroxybenzoate was used as the internal standard and serum was deproteinized by methanol. The samples were separated on a Capcell Pak C18 UG120 column (150 x 1.5 mm i.d.; particle size, 5 microm). The detection limit of GL in serum was 100 ng/ml, which enables determination of serum levels of GL after administration of a therapeutic dose. The time-course study suggested that the elimination rate of GL differed between subjects for the same administered dose, although the sample was too small to allow a meaningful comment. In clinical practice, GL is used for its antiviral and anti-inflammatory effects. Excessive administration of GL can induce pseudoaldosteronism; however the optimal GL concentration in serum remains to be determined. The determination method reported here is expected to aid in the safe and efficient use of the drug in clinical practice.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Ácido Glicirrízico/sangue , Adulto , Ácido Glicirrízico/administração & dosagem , Humanos , Masculino , Padrões de Referência , Sensibilidade e EspecificidadeRESUMO
The thromboxane A2/prostacyclin (TX/PGI) ratios were measured in patients with renal diseases to elucidate the relationship between the ratios and the pathological changes of the diseases. Urinary stable metabolites of thromboxane A2 and prostacyclin, 11-dehydro-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F1alpha, respectively, were converted to 1-methyl ester-propylamide-9,12,15-tris-dimethylisopropylsilyl ether derivative and 1-methyl ester-6-methoxime-9,12,15-tris-dimethylisopropylsilyl ether derivative, respectively, and applied to a gas chromatography/selected ion monitoring. The TX/PGI ratios of 10 outpatients and 6 inpatients with chronic glomerulonephritis were higher than those of 13 healthy volunteers. In an inpatient with systemic lupus erythematoides, the TX/PGI ratios were gradually lowered to the normal level with the therapies. Furthermore, the ratios seemed to change in advance of the changes of the levels of urinary protein and hematuria. These observations suggested that the TX/PGI ratio was a useful index to assess the pathological condition of renal diseases and the effects of treatment.
Assuntos
Epoprostenol/urina , Glomerulonefrite/urina , Tromboxano A2/urina , Adulto , Estudos de Casos e Controles , Doença Crônica , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Íons , Masculino , Pessoa de Meia-IdadeRESUMO
The failure of patients to comply with treatment regimens recommended by their physicians is a significant clinical problem. Researches on the assessment of compliance have, however, been precluded by methodological difficulties such as lack of adequate measures. The purpose of this study was to develop a self-administered questionnaire to evaluate drug compliance. First, questionnaire containing a 52-items complied by two doctors, a pharmacist and a nurse, was tested on 81 outpatients, all volunteers, attending the departments of psychosomatic medicine and internal medicine. Four items were temporarily removed for later analysis because they directly inquired about drug compliance (drug compliance items). The other 48 items were analyzed and three factors consisting of 26 items were further studied: expectation on taking medicine, rejection to taking medicine and seeking knowledge of drugs. Chronback's alpha coefficients representing internal consistency of the three factors were sufficiently high (ranging from .75 to .84). Furthermore, we preformed a simplified pill count to validate the 4 drug compliance items. There was a weak to moderate correlation between the result of pill count and each of 4 drug compliance items. A new self-administered questionnaire of 30 items was thus developed and named the Drug Compliance Scale.
Assuntos
Esquema de Medicação , Cooperação do Paciente , Inquéritos e Questionários/normas , Análise Fatorial , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , AutoadministraçãoRESUMO
The purpose of this study was to investigate psychological factors affecting drug compliance in the department of psychosomatic medicine. Seventy-four outpatients were asked to answer a battery of self-administered questionnaire including the Drug Compliance Scale (DCS) that we had recently developed and other questionnaire evaluating psychological and vegetative symptoms, self-efficacy and attributional styles on the promotion of health and personality closely related to interpersonal relationships. Results of path analysis indicated that attributional styles and self-efficacy mainly affected three factors of DCS such as expectation on taking medicine, rejection to taking medicine and seeking knowledge of drugs, through which they influenced drug compliance, and also indicated that personality and self-efficacy mainly affected the stability of mood state, suggesting a further influence on drug compliance.