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1.
Int J Nurs Pract ; 21 Suppl 1: 10-20, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25759197

RESUMO

This cohort study of primiparae was conducted to answer the following questions: Do older (≧ 35 years) and younger (20-29 years) Japanese primiparous mothers differ when comparing biomarkers of stress and measures of fatigue and depression? Are there changes in fatigue, depression and stress biomarkers when comparing older and younger mothers during the postpartum period? The Postnatal Accumulated Fatigue Scale and the Edinburgh Postnatal Depression Scale were administered in a time-series method four times: shortly after birth and monthly afterwards. Assays to measure biomarkers of stress, urinary 17-ketosteroids, urinary 17-hydroxycorticosteroids and salivary chromogranin-A, were collected shortly after delivery and at 1 month postpartum in both groups and a third time in older mothers at the 4th month. Statistical testing showed very little difference in fatigue, depression or stress biomarkers between older and younger mothers shortly after birth or 1 month later. Accumulated fatigue and depression scores of older mothers were highest 1 month after delivery. Additional cohort studies are required to characterize physical/psychological well-being of older Japanese primiparae.


Assuntos
Depressão Pós-Parto/etiologia , Fadiga/etiologia , Idade Materna , Período Pós-Parto , Estresse Psicológico/etiologia , 17-Hidroxicorticosteroides/urina , 17-Cetosteroides/urina , Adulto , Biomarcadores/análise , Cromogranina A/metabolismo , Estudos de Coortes , Depressão Pós-Parto/diagnóstico , Feminino , Humanos , Japão , Paridade , Saliva/metabolismo , Adulto Jovem
2.
J Forensic Sci ; 59(4): 1146-52, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24673726

RESUMO

We herein report an autopsy case involving a 27-year-old Caucasian woman suffering from chronic adrenocortical insufficiency with a background of a polyendocrine disorder. Postmortem biochemistry revealed pathologically decreased aldosterone, cortisol, and dehydroepiandrosterone levels in postmortem serum from femoral blood as well as decreased cortisol and 17-hydroxycorticosteroid in urine. Decreased vitreous sodium and increased 3-beta-hydroxybutyrate and C-reactive protein concentrations were observed. The cause of death was determined to be acute adrenocortical insufficiency. Fasting ketoacidosis was postulated to have precipitated the Addisonian crisis. Traumatic causes of death and third-party involvement were excluded. The case highlights the importance of systematically performing exhaustive postmortem biochemical investigations to formulate appropriate hypothesis regarding the pathophysiological mechanisms involved in the death process.


Assuntos
Doença de Addison/complicações , Cetose/etiologia , 17-Hidroxicorticosteroides/urina , Ácido 3-Hidroxibutírico/metabolismo , Adulto , Aldosterona/sangue , Proteína C-Reativa/metabolismo , Desidroepiandrosterona/sangue , Jejum , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Sódio/metabolismo , Corpo Vítreo/metabolismo
3.
Future Oncol ; 10(9): 1619-26, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24450574

RESUMO

AIM: We sought to determine the relationship between cancer-related fatigue, chemotherapy-associated adverse effects in patients with advanced stages of cancer, and the levels of TNF-α, IL-1 and 17-hydroxycorticosteroids (17-HCS). PATIENTS & METHODS: Two hundred cancer patients were recruited. They were given a Cancer Fatigue Scale survey to assess their general state of health before and after chemotherapy. Their plasma levels of TNF-α and IL-1 and urine levels of 17-HCS were also measured. RESULTS: Increased levels of TNF-α and IL-1 are common in cancer patients. Thirty-five (17.5%) patients suffered from chemotherapy-associated adverse effects, but their plasma levels of TNF-α and IL-1 were not significantly elevated after chemotherapy. However, the urinary levels of 17-HCS levels were significantly elevated in 23 patients after chemotherapy. CONCLUSION: Patients who had elevated urinary levels of 17-HCS before chemotherapy are accompanied by chemotherapy-associated adverse effects. Thus, elevated 17-HCS in urine could be a possible predictor for chemotherapy-associated adverse effects.


Assuntos
17-Hidroxicorticosteroides/urina , Antineoplásicos/efeitos adversos , Fadiga/sangue , Interleucina-1/sangue , Neoplasias/sangue , Fator de Necrose Tumoral alfa/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Fadiga/etiologia , Fadiga/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Neoplasias/urina , Adulto Jovem
4.
Bull Exp Biol Med ; 154(6): 714-7, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23658905

RESUMO

It was found that the response of the adrenal cortex to graded bicycle exercise in children depends on the initial autonomic tonus and is adequate to the background excretion level of hormone metabolites. Seven-year-old sympathotonic girls with increased excretion of 17-hydroxycorticosteroids at rest demonstrated the lowest increase in this parameter after exercise in comparison with more pronounced increment in vagotonics with relative low initial level of glucocorticoid metabolites. Enhanced excretion of glucocorticoid metabolites with a decrease in androgens observed in 9-year-old sympathotonic girls attests to predominance of catabolic processes over anabolic ones and low efficiency of switching from muscle exercise to recovery in children.


Assuntos
Córtex Suprarrenal/fisiologia , Sistema Nervoso Autônomo/fisiologia , Esforço Físico , 17-Hidroxicorticosteroides/urina , Criança , Feminino , Frequência Cardíaca , Humanos
7.
Endocrine ; 37(1): 106-14, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19882252

RESUMO

Cortisol availability is modulated by several enzymes: 11ß-HSD2, which transforms cortisol (F) to cortisone (E) and 11ß-HSD1 which predominantly converts inactive E to active F. Additionally, the A-ring reductases (5α- and 5ß-reductase) inactivate cortisol (together with 3α-HSD) to tetrahydrometabolites: 5αTHF, 5ßTHF, and THE. The aim was to assess 11ß-HSD2, 11ß-HSD1, and 5ß-reductase activity in hypertensive patients. Free urinary F, E, THF, and THE were measured by HPLC-MS/MS in 102 essential hypertensive patients and 18 normotensive controls. 11ß-HSD2 enzyme activity was estimated by the F/E ratio, the activity of 11ß-HSD1 in compare to 11ß-HSD2 was inferred by the (5αTHF + 5ßTHF)/THE ratio and 5ß-reductase activity assessed using the E/THE ratio. Activity was considered altered when respective ratios exceeded the maximum value observed in the normotensive controls. A 15.7% of patients presented high F/E ratio suggesting a deficit of 11ß-HSD2 activity. Of the remaining 86 hypertensive patients, two possessed high (5αTHF + 5ßTHF)/THE ratios and 12.8% had high E/THE ratios. We observed a high percentage of alterations in cortisol metabolism at pre-receptor level in hypertensive patients, previously misclassified as essential. 11ß-HSD2 and 5ß-reductase decreased activity and imbalance of 11ß-HSDs should be considered in the future management of hypertensive patients.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , 17-Hidroxicorticosteroides/urina , Hipertensão/enzimologia , Hipertensão/urina , Oxirredutases/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 1/metabolismo , 17-Hidroxicorticosteroides/química , 3-alfa-Hidroxiesteroide Desidrogenase (B-Específica)/metabolismo , Adulto , Algoritmos , Chile , Cromatografia Líquida de Alta Pressão , Cortisona/química , Cortisona/urina , Feminino , Humanos , Hidrocortisona/química , Hidrocortisona/urina , Hipertensão/classificação , Masculino , Pessoa de Meia-Idade , Síndrome de Excesso Aparente de Minerolocorticoides/diagnóstico , Síndrome de Excesso Aparente de Minerolocorticoides/enzimologia , Síndrome de Excesso Aparente de Minerolocorticoides/urina , Espectrometria de Massas em Tandem , Tetra-Hidrocortisol/química , Tetra-Hidrocortisol/urina , Tetra-Hidrocortisona/química , Tetra-Hidrocortisona/urina
8.
Int Arch Occup Environ Health ; 82(5): 557-64, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18925412

RESUMO

OBJECTIVES: In the present study, the metabolism of steroid hormones has been investigated to determine whether and how xenobiotics like lead (Pb) and polychlorinated biphenyls (PCBs) interfere with steroid hormone biotransformation in humans. METHODS: Three groups of subjects were tested for concentration of urinary total steroids, 17-ketosteroids (n = 5), pregnane derivates (n = 6), 17-hydroxycorticosteroids (n = 11) and their sulfonated compounds: 14 workers exposed to lead, with a mean Pb blood concentration (PbB) of 29.21 microg/dl; 15 subjects exposed to PCBs, with a mean PCB blood concentration (PCBB) of 61.69 microg/l; a control group (n = 25). RESULTS: The urinary concentrations of 17-ketosteroids and 17-hydroxycorticosteroids were significantly lower in the PCB-exposed groups. There were significantly fewer sulfonated 17-hydroxycorticosteroids in the subjects exposed to PCBs as compared to the controls, while the percentage of sulfonated steroids was lower for both 17-ketosteroids and 17-hydroxycorticosteroids in the PCB-exposed subjects, but only for the 17-hydroxycorticosteroids in the group of subjects exposed to Pb (P < 0.05). Pregnane derivate urinary concentrations did not differ between the three groups. CONCLUSION: Our results suggest that PCBs and Pb act on steroid hormone metabolism with different effects and only partially using the same hormone pathways; they may cause changes in endogenous hormone homeostasis and interfere with the xenobiotic phase II of detoxification. PCBs interfere on a larger number of steroids and cause more significant effects than Pb. It is likely that different mechanisms are involved in steroid hormone metabolism interference.


Assuntos
17-Hidroxicorticosteroides/urina , 17-Cetosteroides/urina , Intoxicação por Chumbo/metabolismo , Chumbo/efeitos adversos , Bifenilos Policlorados/efeitos adversos , Pregnanos/urina , Adulto , Humanos , Chumbo/sangue , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/efeitos adversos , Bifenilos Policlorados/sangue , Ácidos Sulfônicos/metabolismo
9.
J Pediatr Endocrinol Metab ; 22(11): 1009-15, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20101886

RESUMO

The aim of this study was to assess the circadian hormonal profile of two circadian markers, melatonin and cortisol, as well as other steroids in prepubertal boys (Tanner stage I). Nine volunteer healthy prepubertal boys aged 10.8 +/- 0.11 years participated in this study. Concentrations of daily salivary and urinary hormones were quantified around 24-hours, every 3 hours, in daytime samples (collected between 07.00 h +/- 30 min and 21.00 h +/- 30 min) and night-time samples (collected between 21.00 h +/- 30 min and 07.00 h +/- 30 min). Significant differences (p < 0.01) were found between day- and nighttime secretion of salivary melatonin and urinary 6-sulphatoxymelatonin, whereas no significant differences were found between day- and nighttime secretion of salivary and urinary cortisol nor between day- and nighttime secretion of 17-hydroxycorticosteroids (17-OHCS). The circadian profiles of salivary melatonin and cortisol showed large amplitude with a peak occurring at night (approximately 03.00 h) for melatonin and in the early morning (between 06.00 and 09.00 h) for cortisol. The curve patterns of the urinary 6-sulphatoxymelatonin and steroids (free cortisol and 17-OHCS) were coherent with data on saliva. The pattern of salivary androstenedione and testosterone were undetectable due to the very low concentrations of these steroids in the saliva of the prepubertal children. A strong significant positive correlation was observed between the daily salivary melatonin levels and the daily urinary 6-sulphatoxymelatonin excretion (R = 0.968, p < 0.001), and between free urinary cortisol and urinary 17-OHCS (R = 0.733, p = 0.025). The salivary and urinary hormones studied were independent of body mass index. This study shows the relevance of salivary cortisol and melatonin, although lower than in plasma, in testing adrenal and pineal function as markers of circadian rhythms. The data are of interest for the diagnosis and treatment of chronobiological disorders in prepubertal children.


Assuntos
Ritmo Circadiano/fisiologia , Hidrocortisona/urina , Melatonina/urina , Saliva/metabolismo , 17-Hidroxicorticosteroides/urina , Criança , Humanos , Masculino , Melatonina/análogos & derivados , Saliva/química
10.
Pediatrics ; 120(3): e575-86, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17698579

RESUMO

OBJECTIVE: Endogenous Cushing syndrome in children is a rare disorder that is most frequently caused by pituitary or adrenocortical tumors. Diagnostic criteria have generally been derived from studies of adult patients despite significant differences in both the physiology of the hypothalamic-pituitary-adrenal axis and the epidemiology of Cushing syndrome in childhood. The purpose of this study was to identify the tests that most reliably and efficiently diagnose pituitary or adrenal tumors in a large cohort of pediatric patients with Cushing syndrome. METHODS: A retrospective review of clinical data of children who were referred to a tertiary care center for evaluation for Cushing syndrome during the years 1997 to 2005 was conducted. A total of 125 consecutive children were studied retrospectively; 105 were found to have Cushing syndrome, which was confirmed histologically; and 20 children who did not have Cushing syndrome or any other endocrinopathy served as the control group. The following tests were performed in all children: midnight and morning cortisol, corticotropin hormone, urinary free cortisol and 17-hydroxycorticosteroid levels, ovine corticotropin-releasing hormone stimulation test, and overnight high-dosage dexamethasone suppression test. Imaging of the pituitary and adrenal glands was also obtained. The main outcome measure was the sensitivity of these parameters for the diagnosis and differential diagnosis of Cushing syndrome at 100% specificity. RESULTS: A midnight cortisol value of > or = 4.4 microg/dL confirmed the diagnosis of Cushing syndrome in almost all children, with a sensitivity of 99% and a specificity of 100%. Suppression of morning cortisol levels > 20% in response to an overnight, high-dosage dexamethasone test excluded all patients with adrenal tumors and identified almost all patients with pituitary tumors (sensitivity: 97.5%; specificity: 100%). CONCLUSIONS: Our study suggests that among children who were referred for the evaluation of possible Cushing syndrome, a single cortisol value at midnight followed by overnight high-dosage dexamethasone test led to rapid and accurate confirmation and diagnostic differentiation, respectively, of hypercortisolemia caused by pituitary and adrenal tumors.


Assuntos
Síndrome de Cushing/diagnóstico , 17-Hidroxicorticosteroides/urina , Adolescente , Doenças das Glândulas Suprarrenais/diagnóstico , Glândulas Suprarrenais/patologia , Hormônio Adrenocorticotrópico/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Hormônio Liberador da Corticotropina , Síndrome de Cushing/etiologia , Dexametasona/sangue , Feminino , Seguimentos , Hormônios , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Imagem por Ressonância Magnética , Masculino , Testes de Função Hipofisária , Hipófise/patologia , Neoplasias Hipofisárias/diagnóstico , Valor Preditivo dos Testes , Encaminhamento e Consulta , Estudos Retrospectivos , Sensibilidade e Especificidade , Distribuição por Sexo , Tomografia Computadorizada por Raios X
11.
Tohoku J Exp Med ; 211(2): 161-9, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17287600

RESUMO

Oxygen-derived free radicals play important roles in pathophysiological processes in critically ill patients, but the data characterizing relationships between radicals and neuroendocrine system response are sparse. To search the cue to reduce the oxidative cellular damage from the point of view of neuroendocrine system response, we studied the indicators of neuroendocrine and inflammatory responses excreted in urine in 14 burn patients (42.3 +/- 31.4 years old, and 32.3 +/- 27.6% burn of total body surface area [%TBSA]) during the first seven days post burn. The daily mean amounts of urinary excretion of 8-hydroxy-2'-deoxy-guanosine (8-OHdG), a marker of oxidative cellular damage, were above the upper limit of the standard value during the studied period. The total amount of urinary excretion of 8-OHdG in the first day post burn correlated with burn severity indices: %TBSA (r = 0.63, p = 0.021) and burn index (r = 0.70, p = 0.008). The daily urinary excretion of 8-OHdG correlated with the daily urinary excretion of norepinephrine and nitrite plus nitrate (NOx) during the studied period except day 2 post burn, and correlated with the daily urinary excretion of 17-hydroxycorticosteriod (17-OHCS) in days 2, 3, and 7 post burn. These data suggest that oxidative cellular damage correlates with burn severity and neuroendocrine system response modulates inflammation and oxidative cellular damage. Modulation of neuroendocrine system response and inflammation in the treatment in the early phase of burn may be useful to reduce the oxidative cellular damage and to prevent multiple organ failures in patients with extensive burn.


Assuntos
Queimaduras/metabolismo , Dano ao DNA , Desoxiguanosina/análogos & derivados , Sistemas Neurossecretores/metabolismo , 17-Hidroxicorticosteroides/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Queimaduras/patologia , Queimaduras/urina , Criança , Pré-Escolar , Desoxiguanosina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nitratos/urina , Norepinefrina/urina
12.
Nat Clin Pract Endocrinol Metab ; 2(1): 53-7; quiz following 57, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16932253

RESUMO

BACKGROUND: A 48-year-old woman presented to our clinic 1 year after hypertension was discovered on a routine screening visit. During the previous year, she had noticed weight gain in the face and abdomen, easy bruising, oligomenorrhea and facial and periareolar hair growth. On presentation, she reported no weakness, fracture, back pain, depression, irritability, problem with cognition or memory, increased appetite, hot flashes or altered sleep. Previous medication history included 2.5 mg lisinopril daily and 25.0 mg hydrochlorothiazide daily for 12 months. INVESTIGATIONS: Measurement of urine glucocorticoid excretion, evening plasma and salivary cortisol levels, and basal and corticotropin-releasing-hormone-stimulated adrenocorticotropic hormone and cortisol levels. An overnight 8 mg dexamethasone suppression test, pituitary MRI, inferior-petrosal-sinus sampling, cavernous sinus and jugular venous sampling were performed. DIAGNOSIS: Cushing disease. MANAGEMENT: The patient underwent trans-sphenoidal resection, assessment of remission and subsequent treatment with hydrocortisone.


Assuntos
Hipersecreção Hipofisária de ACTH/diagnóstico , 17-Hidroxicorticosteroides/urina , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Dexametasona/administração & dosagem , Feminino , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Pessoa de Meia-Idade , Flebografia , Hipersecreção Hipofisária de ACTH/tratamento farmacológico , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/cirurgia , Saliva/metabolismo , Osso Esfenoide/cirurgia
14.
Pediatr Int ; 48(3): 265-7, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16732792

RESUMO

BACKGROUND: School non-attendance is a major social problem in Japan. Many children stop attending school for a variety of reasons. The authors previously reported stress barometer values for healthy Japanese children. In this study, the authors examined the stress barometer values of children with school non-attendance. METHODS: The authors measured stress barometer values, that is, urinary 17-hydroxycorticosteroids (17-OHCS) and 17-ketosteroid sulfates (17-KS-S) in 65 children (40 girls and 25 boys; 7-15 years of age) with school non-attendance, except for pervasive developmental disorder and mental retardation, who attended the outpatient department of Dokkyo University School of Medicine Hospital, Tochigi, Japan, during the past 4 years. RESULTS: A total of 24 (36.9%) of the 65 children had urinary 17-OHCS values above 2SD, and 14 (21.5%) had urinary 17-OHCS below 2SD. In total, 10 (15.4%) children had urinary 17-KS-S values above 2SD, and four (6.2%) had urinary 17-KS-S below 2SD. Five (7.7%) children had urinary 17-KS-S/17-OHCS values above 2SD, and 10 (15.4%) had urinary 17-KS-S/17-OHCS below 2SD. CONCLUSION: The stress barometer values appear to be clinically useful for evaluating objectively whether children with school non-attendance have emotional stress.


Assuntos
17-Hidroxicorticosteroides/urina , 17-Cetosteroides/urina , Absenteísmo , Estresse Psicológico/urina , Adolescente , Criança , Feminino , Humanos , Japão , Masculino , Transtornos Mentais/diagnóstico , Transtornos Mentais/psicologia , Transtornos Mentais/urina , Estresse Psicológico/diagnóstico
15.
Clin Endocrinol (Oxf) ; 64(1): 37-45, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16402926

RESUMO

OBJECTIVE: To further analyse the significance and mutual relationship of thyroid function-linked alterations in cortisol metabolism that have been separately and variously reported. PATIENTS AND MEASUREMENTS: Twenty-four-hour urine samples from 21 patients with hyperthyroidism (Graves' disease), 16 patients with hypothyroidism (Hashimoto's thyroiditis), 21 healthy age- and sex-matched controls for hyperthyroidism, and 16 healthy age- and sex-matched controls for hypothyroidism were evaluated for 6beta-hydroxycortisol (6beta-OHF), tetrahydrocortisol (THF), tetrahydrocortisone (THE), allo-tetrahydrocortisol (allo-THF), urinary free cortisol (UFF), urinary free cortisone (UFE) and 17-hydroxycorticosteroid (17-OHCS). RESULTS: Urinary 17-OHCS, THE and allo-THF levels increased considerably in hyperthyroid patients compared to the controls, while UFF and THF showed no difference between the two groups. Urinary 6beta-OHF was significantly lower in the hyperthyroid patients than in the controls. Both the urinary allo-THF + THF/THE and the UFF/UFE ratios were significantly lower in the hyperthyroid patients than in the controls, whereas only the former was significantly higher in the hypothyroid patients than in the controls. The urinary allo-THF/THF ratio was significantly higher in the hyperthyroid patients and significantly lower in the hypothyroid patients than in the controls. In an analysis of pooled subjects including all groups (n = 64), free T4 levels correlated negatively (P < 0.0001) with the urinary allo-THF + THF/THE ratio but not with the UFF/UFE ratio. The serum levels of free T4 correlated positively (P < 0.0001) with the urinary allo-THF/THF ratio. CONCLUSION: The thyroid hormones seem to affect the total 11beta-HSD activity (allo-THF + THF/THE) more strongly than the renal 11beta-HSD2 activity (UFF/UFE). 5alpha-reductase activity (allo-THF/THF) is also enhanced in hyperthyroidism, while the reduction of urinary 6beta-OHF in hyperthyroidism might be a secondary effect of the altered activity of the total 11beta-HSD and 5alpha-reductase.


Assuntos
Doença de Graves/urina , Doença de Hashimoto/urina , Hidrocortisona/metabolismo , 17-Hidroxicorticosteroides/urina , Adulto , Idoso , Estudos de Casos e Controles , Cortisona/urina , Cortodoxona/análogos & derivados , Cortodoxona/urina , Feminino , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/urina , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Tetra-Hidrocortisol/urina , Tetra-Hidrocortisona/urina
18.
Ann Clin Biochem ; 41(Pt 4): 335-7, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15298747

RESUMO

BACKGROUND: The correlation between the urinary 6beta-hydroxycortisol/17-hydroxycorticosteroids (6beta-OHF/17-OHCS) ratio and the metabolic capacity of the most abundant form of hepatic cytochrome P450 (CYP3A4) after induction remains unclear. METHODS: Concentrations of 6beta-OHF and 17-OHCS in spot urine specimens obtained from 61 epileptic children receiving continuous carbamazepine therapy were measured by high-performance liquid chromatography. The relationship between the urinary 6beta-OHF/17-OHCS ratio and the serum carbamazepine concentration, corrected for dose and body weight, was examined. RESULTS: Serum carbamazepine was inversely associated with the urinary 6beta-OHF/17-OHCS ratio, and the hyperbolic relationship between the two parameters was statistically significant (P < 0.01). DISCUSSION: Carbamazepine is well known as a potent inducer and a substrate of hepatic CYP3A4. The present results suggest that measurement of the urinary 6betaOHF/17-OHCS ratio is helpful for assessing individuals' hepatic CYP3A4 capacity after enzyme induction.


Assuntos
17-Hidroxicorticosteroides/urina , Sistema Enzimático do Citocromo P-450/metabolismo , Hidrocortisona/análogos & derivados , Hidrocortisona/urina , Fígado/enzimologia , Adolescente , Adulto , Carbamazepina/sangue , Carbamazepina/uso terapêutico , Criança , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/biossíntese , Indução Enzimática/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Feminino , Humanos , Masculino
19.
Eur J Med Res ; 9(2): 51-4, 2004 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-15090289

RESUMO

OBJECTIVE: To investigate whether cytochrome P450-dependent enzymes are influenced by amphotericin B (Am-B) during the treatment of Candida oesophagitis in HIV-infected patients. METHODS: Twelve HIV-infected, antiretroviral-naive patients (CDC/WHO stage C3) with Candida oesophagitits were enrolled into a prospective clinical trial. The patients were treated with Am-B (0.4 mg/kg body weight) for two weeks. At baseline and after Am-B therapy the clearance of antipyrine and its metabolites were investigated by high-performance liquid chromatography. In addition, the urinary excretion of 6-beta-hydroxycortisol and 17-hydroxycorticosteroids was assessed by means of a radioimmunoassay. RESULTS: The following significant changes were observed after Am-B treatment (P < 0.01): increase of antipyrine half-life (12.4 h vs 16.8 h) and the area under the plasma concentration-time curve (27.9 mg min/ml vs 38.1 mg min/ml); decrease of the total body clearance (61.2 ml/min vs 43.7 ml/min); decrease of the renal clearance of antipyrine metabolites - norantipyrine (7.45 ml/min vs 5.31 ml/min), 4-hydroxyantipyrine (15.4 ml/min vs 10.3 ml/min), hydroxymethylantipyrine (4.31 ml/min vs 3.65 ml/min); decrease of urinary 6-beta-hydroxycortisol excretion (453 microg/24h vs 298 microg/24h) and the ratio of 6-beta-hydroycortisol to 17-hydroxycorticosteroids (8.8% vs 6.4%). CONCLUSIONS: Our data indicate that Am-B therapy has an inhibitory effect on cytochrome P450-dependent enzymes in HIV-infected patients. These results are of particular significance for HIV-infected patients who are concomitantly treated with drugs that are predominantly metabolised in the liver. A careful drug monitoring system seems advisable, especially for proteinase inhibitor experienced HIV-1-infected subjects.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/enzimologia , Anfotericina B/farmacologia , Sistema Enzimático do Citocromo P-450/efeitos dos fármacos , Hidrocortisona/análogos & derivados , 17-Hidroxicorticosteroides/urina , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/urina , Antibacterianos/farmacologia , Antipirina/farmacocinética , Candidíase/complicações , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/metabolismo , Esofagite/tratamento farmacológico , Esofagite/etiologia , Esofagite/microbiologia , Humanos , Hidrocortisona/urina , Hospedeiro Imunocomprometido
20.
J Clin Endocrinol Metab ; 89(3): 1222-6, 2004 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15001614

RESUMO

Low-dose dexamethasone suppression testing has been recommended for biochemical screening when Cushing's syndrome is suspected. The criterion for normal suppression of cortisol after dexamethasone is controversial. To assess diagnostic utility (sensitivity), we report the results of low-dose dexamethasone suppression testing in 103 patients with spontaneous Cushing's syndrome. There were 80 patients with Cushing's disease (78%), 13 with the ectopic ACTH syndrome (13%), and 10 with cortisol-producing adrenocortical adenomas (10%). Fourteen (18%) of 80 patients with Cushing's disease suppressed serum cortisol to less than 5 micro g/dl (<135 nmol/liter) after the overnight 1-mg test, whereas six patients (8%) actually showed suppression of serum cortisol to less than 2 micro g/dl (<54 nmol/liter). In addition, the 2-d, low-dose dexamethasone suppression test yielded false-negative results in 38% of patients when urine cortisol was used and 28% when urinary 17-hydroxycorticosteroids were used. Serum cortisol after the 1-mg test correlated with baseline urinary free cortisol (r = 0.705, P < 0.001), plasma ACTH level (r = 0.322, P = 0.001), and urinary free cortisol after the 2-d test (r = 0.709, P = 0.001). This study provides evidence that low-dose dexamethasone may suppress either plasma cortisol or urinary steroids to levels previously thought to exclude Cushing's syndrome and that these tests should not be used as the sole criterion to exclude the diagnosis of endogenous hypercortisolism.


Assuntos
Síndrome de Cushing/diagnóstico , Dexametasona , Glucocorticoides , 17-Hidroxicorticosteroides/urina , Adulto , Idoso , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Humanos , Hidrocortisona/sangue , Hidrocortisona/urina , Programas de Rastreamento , Sensibilidade e Especificidade
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