RESUMO
INTRODUCTION: Corticosteroids may modulate addiction. We previously described subjective, physiological, and endocrine effects of 0.5 mg/kg of intravenous methamphetamine after augmenting cortisol level with hydrocortisone or blocking cortisol response with the corticosteroid synthesis inhibitor metyrapone in a double-blind, balanced crossover study. Although the pharmacologic manipulations produced the expected hormonal changes, pleasurable subjective effects of methamphetamine were unchanged. Metyrapone was followed by frequent premature ventricular complexes (PVCs) in two subjects during methamphetamine administration. In order to better understand these results, we examined changes in two plasma catecholamine metabolites, homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), and their relationship to the previously reported hormonal changes and physiological and subjective responses. METHODS: Plasma from 10 methamphetamine subjects from the earlier study was assayed for HVA and MHPG by high performance liquid chromatography. RESULTS: HVA levels were greater after hydrocortisone or metyrapone pretreatment compared to placebo, and MHPG levels were greater after metyrapone pretreatment. Hydrocortisone pretreatment diminished HVA and MHPG increases after methamphetamine (perhaps explaining the lack of expected increase in pleasurable effects), but metyrapone did not. HVA and MHPG concentrations were not correlated with pleasurable drug effects but were inversely related to reports of "Bad Drug Effect." Increases in MHPG and DHEA concentrations were positively correlated. Metyrapone pre-treated subjects with PVCs had lower HVA and MHPG concentrations. CONCLUSION: Raising cortisol concentration and blocking cortisol synthesis did not produce opposite effects, perhaps because of metyrapone's effect on the hypothalamic-pituitary-adrenal axis, its stress-like effects, and its effects on neurosteroids.
Assuntos
Nível de Alerta/efeitos dos fármacos , Dextroanfetamina/farmacologia , Hidrocortisona/sangue , Recompensa , Adulto , Estudos Cross-Over , Método Duplo-Cego , Interações Medicamentosas , Eletrocardiografia/efeitos dos fármacos , Ácido Homovanílico/sangue , Humanos , Hidrocortisona/antagonistas & inibidores , Hidrocortisona/farmacologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Infusões Intravenosas , Masculino , Metoxi-Hidroxifenilglicol/sangue , Metirapona/farmacologia , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Pré-MedicaçãoRESUMO
OBJECTIVE: Reports of low levels of dehydroepiandrosterone (DHEA) or its sulphate (DHEA-S) in some schizophrenic patients and in some persons with poorer motoric and cognitive functioning led us to examine clinical correlates of serum DHEA and DHEA-S levels in schizophrenic patients. METHOD: Ratings of abnormal movements, memory and psychiatric symptoms in 17 medicated chronic schizophrenic or schizoaffective inpatients at a state hospital were correlated with serum DHEA and DHEA-S levels, and their ratios with serum cortisol. RESULTS: Controlling for age, higher DHEA levels and/or higher DHEA/cortisol ratios were significantly correlated with lower symptom ratings on the Brief Psychiatric Rating Scale, better performance on some measures of memory, and lower ratings of parkinsonian symptoms. CONCLUSION: Relatively low DHEA levels or DHEA/cortisol ratios may identify a particularly impaired subgroup of medicated patients with chronic schizophrenia. Potential implications are discussed.
Assuntos
Desidroepiandrosterona/sangue , Transtornos da Memória/sangue , Transtornos da Memória/complicações , Transtornos dos Movimentos/sangue , Transtornos dos Movimentos/complicações , Transtornos Psicóticos/sangue , Transtornos Psicóticos/complicações , Esquizofrenia/sangue , Esquizofrenia/complicações , Psicologia do Esquizofrênico , Adulto , Idoso , Antipsicóticos/efeitos adversos , Clorpromazina/efeitos adversos , Feminino , Humanos , Hidrocortisona/sangue , Masculino , Pessoa de Meia-Idade , Transtornos Parkinsonianos/sangue , Transtornos Parkinsonianos/complicações , Postura , Transtornos Psicóticos/tratamento farmacológico , Esquizofrenia/tratamento farmacológicoRESUMO
Buprenorphine and naloxone sublingual (s.l.) dose formulations may decrease parenteral buprenorphine abuse. We evaluated pharmacologic interactions between 8 mg s.l. buprenorphine combined with 0, 4, or 8 mg of naloxone in nine opiate-dependent volunteers stabilized on 8 mg s.l. buprenorphine for 7 days. Combined naloxone and buprenorphine did not diminish buprenorphine's effects on opiate withdrawal nor alter buprenorphine bioavailability. Opiate addicts stabilized on buprenorphine showed no evidence of precipitated opiate withdrawal after s.l. buprenorphine-naloxone combinations. Buprenorphine and naloxone bioavailability was approximately 40 and 10%, respectively. Intravenous buprenorphine and naloxone produced subjective effects similar to those of s.l. buprenorphine and did not precipitate opiate withdrawal.
Assuntos
Buprenorfina/uso terapêutico , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/reabilitação , Administração Sublingual , Adulto , Pressão Sanguínea/efeitos dos fármacos , Buprenorfina/administração & dosagem , Buprenorfina/farmacologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Injeções Intravenosas , Masculino , Naloxona/administração & dosagem , Naloxona/farmacologia , Antagonistas de Entorpecentes/administração & dosagem , Antagonistas de Entorpecentes/farmacologia , Fatores de TempoRESUMO
The Fatigue Severity Scale (FSS) is a self-report instrument used to assess levels of fatigue and its effect on daily functioning. The FSS was normed on individuals with multiple sclerosis and has been used in studies examining such factors as obstructive sleep apnea and aerobic exercise. Current research has extended it to obese subjects to assess their level of fatigue in conjunction with a 16-week obesity treatment program. Participants were 118 females with an average age of 45.24 (SD = 11.44). The results yield high pre- and post-test reliability for the FSS and weight loss.
Assuntos
Fadiga/diagnóstico , Fadiga/epidemiologia , Obesidade/epidemiologia , Inquéritos e Questionários , Peso Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/terapia , Psicometria , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Redução de PesoRESUMO
BACKGROUND: The peripherally inserted central catheter (PICC) is increasingly used in protracted intravenous therapy. The device has several advantages for family practice, but its use has been chiefly described in nursing and interventional radiology literature. We investigated the use of the PICC in a family practice teaching hospital. METHODS: Forty PICCs were inserted from 1993 to 1995 in 29 patients. Available records and radiographs were reviewed for indication, nature of placement attempts, indwelling time, PICC role in therapy, and attendant complications. RESULTS: Successful placement was achieved in 95 percent of instances requiring PICC use. Fluoroscopically guided placement, usually without venography, was found to be preferable to unguided bedside placement. In a few cases in which PICCs were placed, no other access was subsequently required to complete therapy. Few clinically serious complications were encountered. Most complications were related to placement at bedside. CONCLUSIONS: Our experience supports the PICC as a minimally invasive, economical alternative for protracted intravenous therapy. Fluoroscopically guided placement was found preferable to unguided bedside placement. Physicians ordering or placing PICCs should understand fully how to assess placement.
Assuntos
Cateterismo Venoso Central/métodos , Cateteres de Demora , Adolescente , Adulto , Idoso , Antibacterianos/administração & dosagem , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Medicina de Família e Comunidade/métodos , Fluoroscopia/métodos , Humanos , Injeções Intravenosas/instrumentação , Injeções Intravenosas/métodos , Pessoa de Meia-Idade , Nutrição Parenteral/instrumentação , Nutrição Parenteral/métodos , Resultado do TratamentoRESUMO
We have examined the expression and cellular location of facilitated glucose transporter proteins (GLUT1, -3, and -5) in a human colonic epithelial cell line (Caco-2) by using peptide-specific antibodies. A differential cellular distribution of these transporters was observed in differentiated (greater than 14 days postconfluence) Caco-2 cells by immunofluorescence and immunoelectron microscopy. GLUT1 was localized primarily to the basolateral membrane, whereas GLUT3 was predominantly localized to the apical membrane. GLUT5, which was detected in only approximately 40% of fully differentiated Caco-2 cells, was found primarily in the apical membrane but was also present in both basolateral and intracellular membranes. A Na(+)-independent glucose transport system in the apical membrane of Caco-2 cells has been described previously [Blais, A., Bissonnette, A. & Berteloot, A. (1987) J. Membr. Biol. 99, 113-125], and we propose that GLUT3 mediates this process. The amino acid sequence identity (57%) and structural conservation between GLUT1 and GLUT3 may make these transporters an ideal model system for examining the molecular basis for polarized sorting of membrane proteins.
Assuntos
Proteínas de Transporte de Monossacarídeos/biossíntese , Adenocarcinoma , Sequência de Aminoácidos , Animais , Anticorpos , Encéfalo/metabolismo , Linhagem Celular , Neoplasias do Colo , Imunofluorescência , Humanos , Immunoblotting , Jejuno/metabolismo , Cinética , Microscopia Imunoeletrônica , Microvilosidades/metabolismo , Microvilosidades/ultraestrutura , Dados de Sequência Molecular , Proteínas de Transporte de Monossacarídeos/análise , Proteínas de Transporte de Monossacarídeos/isolamento & purificação , Oligopeptídeos/síntese química , Oligopeptídeos/imunologia , Ratos , Vacúolos/metabolismo , Vacúolos/ultraestruturaRESUMO
Insulin stimulates the movement of two glucose transporter isoforms (GLUT1 and GLUT4) to the plasma membrane (PM) in adipocytes. To study this process we have prepared highly purified PM fragments by gently sonicating 3T3-L1 adipocytes grown on glass coverslips. Using confocal laser immunofluorescence microscopy we observed increased PM labeling for GLUT1 (2.3-fold) and GLUT4 (eightfold) after insulin treatment in intact cells. EM immunolabeling of PM fragments indicated that in the nonstimulated state GLUT4 was mainly localized to flat clathrin lattices. Whereas GLUT4 labeling of clathrin lattices was only slightly increased after insulin treatment, labeling of uncoated PM regions was markedly increased with insulin. These data suggest that GLUT4 recycles from the cell surface both in the presence and absence of insulin. In streptolysin-O permeabilized adipocytes, insulin, and GTP gamma S increased PM levels of GLUT4 to a similar extent as observed with insulin in intact cells. In the absence of an exogenous ATP source the magnitude of these effects was considerably reduced. Removal of ATP per se caused a significant increase in cell surface levels of GLUT4 suggesting that ATP may be required for intracellular sequestration of these transporters. When insulin and GTP gamma S were added together, in the presence of ATP, PM GLUT4 levels were similar to levels observed when either insulin or GTP gamma S was added individually. Addition of GTP gamma S was able to overcome this ATP dependence of insulin-stimulated GLUT4 movement. GTP gamma S had no effect on constitutive secretion of adipsin in permeabilized cells. In addition, there was no effect of insulin or GTP gamma S on GLUT4 movement to the PM in noninsulin sensitive streptolysin-O-permeabilized 3T3-L1 fibroblasts overexpressing GLUT4. We conclude that the insulin-stimulated movement of GLUT4 to the cell surface in adipocytes may require ATP early in the insulin signaling pathway and a GTP-binding protein(s) at a later step(s). We propose that the association of GLUT4 with clathrin lattices may be important in maintaining the exclusive intracellular location of this transporter in the absence of insulin.