RESUMO
Marijuana (MJ) is the most commonly used illicit drug in the United States. Its abuse is associated with cognitive dysfunctions and increased resistance to blood flow in the cerebral vasculature. In addition, MJ abuse is associated with increased risks of potentially serious cardiovascular disorders. In the present study, we used the protein chip platform based on surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF-MS) to test the possibility that MJ abuse might be associated with changes in serum protein levels. Indeed, MJ users showed significant increases in three protein peaks, which were identified as three isoforms of apolipoprotein (apo) C-III. Immunoprecipitation using an apoC-III antibody also validated the identification of the proteins. Marijuana-induced increases in apoC-III levels might occur through chronic stimulation of hepatic cannabinoid receptors (CB1 and/or CB2) by its active ingredient, Delta(9)tetrahydrocannibol (THC). Thus, chronic MJ abuse might cause increased transcription and/or translation of apoC-III in the liver with corresponding changes reflected in the plasma of these patients. In any case, because apoC-III is a cardiovascular risk factor, the increased levels observed in MJ users might explain, in part, the cardiac and cerebral abnormalities reported in these patients.
Assuntos
Apolipoproteína C-III/sangue , Abuso de Maconha/sangue , Proteômica/métodos , Adolescente , Adulto , Análise de Variância , Biomarcadores/sangue , Feminino , Humanos , Lipídeos/sangue , Masculino , Peso Molecular , Análise Serial de Proteínas/métodos , Proteínas/metabolismo , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Frações Subcelulares/metabolismo , Adulto JovemRESUMO
Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with (15)O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence.
Assuntos
Transtornos Relacionados ao Uso de Cocaína/fisiopatologia , Tomada de Decisões/fisiologia , Lobo Frontal/fisiopatologia , Adulto , Circulação Cerebrovascular , Transtornos Relacionados ao Uso de Cocaína/diagnóstico por imagem , Feminino , Lobo Frontal/irrigação sanguínea , Lobo Frontal/diagnóstico por imagem , Jogo de Azar/psicologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Córtex Pré-Frontal/irrigação sanguínea , Córtex Pré-Frontal/diagnóstico por imagem , Córtex Pré-Frontal/fisiopatologia , Desempenho Psicomotor/fisiologia , Tomografia Computadorizada de EmissãoRESUMO
It is well documented that acute administration of the benzodiazepine hypnotic drug triazolam (Halcion) impairs episodic memory encoding. We examined the neuroanatomical substrates of this effect in healthy adult volunteers using a double-blind, within-subject design. Following oral capsule administration (0.25 mg/70 kg triazolam or placebo), regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) with 15O-H(2)O during the performance of semantic categorization, orthographic categorization, and visual fixation (resting) tasks. rCBF associated with episodic memory encoding was measured by the difference in rCBF during the orthographic categorization task relative to that during the semantic categorization task. Results in the placebo condition (n = 9) replicated those of previous nonpharmacological encoding studies (activation in the left prefrontal cortex, cerebellum, anterior cingulate cortex, temporal cortex, and occipital cortex). Relative to placebo, results in the triazolam condition (n = 6) revealed significantly impaired memory performance, and deactivation during encoding in a subset of areas shown previously to be associated with encoding (anterior cingulate cortex, cerebellum, and precuneus). Results are discussed in relation to triazolam's effects on mnemonic versus attentional processes.
Assuntos
Encéfalo/diagnóstico por imagem , Moduladores GABAérgicos/farmacologia , Memória/efeitos dos fármacos , Triazolam/farmacologia , Adulto , Encéfalo/efeitos dos fármacos , Circulação Cerebrovascular/efeitos dos fármacos , Cognição/efeitos dos fármacos , Método Duplo-Cego , Humanos , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/psicologia , Desempenho Psicomotor/efeitos dos fármacos , Tomografia Computadorizada de EmissãoRESUMO
A high-affinity radioligand for CRHR1 has been prepared that can serve as a template for the development of SPECT imaging agents. The 5-chloro-N-cyclopropylmethyl-N-(2,6-dichloro-4-iodophenyl)-2-methyl-N-propylpyrimidine-4,6-diamine (6b, Ki = 14 nM), and the corresponding 4-bromophenyl analogue (6a, Ki = 21 nM), were synthesized in four steps from compound 3.
Assuntos
Ciclopropanos , Pirimidinas , Compostos Radiofarmacêuticos , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Animais , Ciclopropanos/síntese química , Ciclopropanos/metabolismo , Humanos , Radioisótopos do Iodo , Ligantes , Ligação Proteica , Pirimidinas/síntese química , Pirimidinas/metabolismo , Relação Estrutura-AtividadeRESUMO
A defining feature of drug addiction is persistent drug use despite long-term adverse consequences. This study examined the performance of drug abusers on a neuropsychological test that requires evaluation of long-term outcomes in the presence of a complex set of mixed reward/punishment contingencies (the Gambling Task). In order to control for generalized deficits related to choice and planning, subjects were also administered the Wisconsin Card Sorting Task. Thirty polysubstance abusers were compared to a comparison group of 24 subjects who did not use illicit drugs of abuse. Drug abusers performed much more poorly on the Gambling Task (net score = 10.2 +/- 4.7, mean +/- s.e.m.) than controls (26.0 +/- 5.3), but did not differ from controls on the Wisconsin Card Sorting Task. The results show that drug abusers are more likely to make maladaptive decisions in the Gambling Task that result in long-term losses exceeding short-term gains. These findings indicate that the Gambling Task may be a useful model in laboratory studies of cognitive dysfunctions associated with drug abuse.
Assuntos
Tomada de Decisões/efeitos dos fármacos , Drogas Ilícitas/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Feminino , Jogo de Azar/psicologia , Humanos , Masculino , Motivação , Testes Neuropsicológicos , Aprendizagem por Probabilidade , Resolução de Problemas/efeitos dos fármacos , Transtornos Relacionados ao Uso de Substâncias/diagnósticoRESUMO
We evaluated the effects of the lipophilic nonpeptide corticotropin-releasing hormone (CRH) type 1 receptor antagonist antalarmin on the behavioral, neuroendocrine, and autonomic components of the stress response in adult male rhesus macaques. After oral administration, significant antalarmin concentrations were detected in the systemic circulation and the cerebrospinal fluid by a mass spectrometry-gas chromatography assay developed specifically for this purpose. Pharmacokinetic and dose-response studies suggested that an oral dose of 20 mg/kg was optimal for behavioral and endocrine effects. We then administered this dose in a double-blind, placebo-controlled fashion to monkeys exposed to an intense social stressor: namely, placement of two unfamiliar males in adjacent cages separated only by a transparent Plexiglas screen. Antalarmin significantly inhibited a repertoire of behaviors associated with anxiety and fear such as body tremors, grimacing, teeth gnashing, urination, and defecation. In contrast, antalarmin increased exploratory and sexual behaviors that are normally suppressed during stress. Moreover, antalarmin significantly diminished the increases in cerebrospinal fluid CRH as well as the pituitary-adrenal, sympathetic, and adrenal medullary responses to stress. We conclude that CRH plays a broad role in the physiological responses to psychological stress in primates and that a CRH type 1 receptor antagonist may be of therapeutic value in human psychiatric, reproductive, and cardiovascular disorders associated with CRH system hyperactivity.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Hormônio Liberador da Corticotropina/fisiologia , Pirimidinas/uso terapêutico , Pirróis/uso terapêutico , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Estresse Psicológico/tratamento farmacológico , Administração Oral , Hormônio Adrenocorticotrópico/sangue , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/farmacologia , Ansiedade/etiologia , Arginina Vasopressina/líquido cefalorraquidiano , Hormônio Liberador da Corticotropina/líquido cefalorraquidiano , Método Duplo-Cego , Avaliação Pré-Clínica de Medicamentos , Epinefrina/sangue , Comportamento Exploratório/efeitos dos fármacos , Medo/efeitos dos fármacos , Hidrocortisona/sangue , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Macaca mulatta , Masculino , Norepinefrina/sangue , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/fisiopatologia , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Pirróis/administração & dosagem , Pirróis/farmacologia , Receptores de Hormônio Liberador da Corticotropina/fisiologia , Comportamento Sexual Animal/efeitos dos fármacos , Predomínio Social , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologiaRESUMO
A series of fluoro-substituted 4-(dialkylamino)pyrrolo[2,3-d]pyrimidines was synthesized and their binding affinity for corticotropin-releasing hormone type 1 receptor (CRHR1) was investigated. Compounds 11a and 11b possessed very high CRHR1 affinity (Ki=3.5, 0.91 nM, respectively). They are promising candidates for the development of 18F-containing nonpeptide PET radioligands for CRHR1.
Assuntos
Meios de Contraste/síntese química , Meios de Contraste/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Animais , Cerebelo/metabolismo , Meios de Contraste/metabolismo , Flúor/química , Pirimidinas/metabolismo , Pirróis/química , Ensaio Radioligante , Ratos , Tomografia Computadorizada de EmissãoRESUMO
The use of bleach (hypochlorite) as a disinfectant for drug injection equipment in the intravenous-drug-using population was recommended early in the HIV-1/AIDS epidemic. Epidemiological studies have challenged the use of bleach as an effective measure to prevent HIV-1 transmission. However, in vitro HIV-1 coculture studies have shown that a high concentration of bleach is an effective cytotoxic and potentially virucidal agent. In this study, we demonstrate that HIV-1 peripheral blood mononuclear cell cocultures containing low concentrations of hypochlorite in the media showed earlier conversion to HIV-1 positivity, as measured by the presence of p24 antigen. HIV-1 cocultures with high concentrations of hypochlorite in the culture media, which appeared to be highly cytotoxic, and HIV-1 cocultures without bleach in the media did not exhibit this early p24 antigen positivity. Hypochlorite chemically disinfects by releasing free chlorine that is a potent oxidant. In injection drug equipment, a low residual concentration of bleach is likely to remain in cleaned equipment despite rinsing with water. Low concentrations of oxidants have been shown to enhance tissue inflammation, in vivo, as well as HIV-1 replication in vitro. Previous studies have shown that despite vigorous cleaning of blood-contaminated injection syringes with bleach followed by water, microaggregates of residual blood remained in bleach-cleaned blood-contaminated syringes. Hypothetically, oxidant effects of the residual bleach in the bleach-cleaned syringes could enhance the possibility of infection by remaining HIV-1 contained in a contaminated syringe. We suggest that the likelihood of an injection drug user contracting HIV-1 through the sharing of a bleach-cleaned blood-contaminated syringe may be increased by the cotransmission of residual bleach and its localized tissue-inflammatory effects; however, this has not been statistically proven in epidemiological studies.
Assuntos
Desinfetantes/farmacologia , Infecções por HIV/transmissão , HIV-1/fisiologia , Leucócitos Mononucleares/virologia , Hipoclorito de Sódio/farmacologia , Seringas , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , Desinfecção , Relação Dose-Resposta a Droga , Contaminação de Equipamentos , Proteína do Núcleo p24 do HIV/análise , HIV-1/efeitos dos fármacos , Humanos , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Agulhas/virologia , Oxidantes/farmacologia , Abuso de Substâncias por Via Intravenosa/complicações , Seringas/virologia , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: While usually not the only factor in obese patients, prescription medications, which may increase appetite or body weight, can be important in some individuals. The cause of weight gain in such cases may go unrecognized or lead to cessation of medication with or without the practitioner's knowledge or approval. METHODS: We found illustrative cases among patients treated at the Johns Hopkins Weight Management Center, searched MEDLINE and the Micromedex Drug Information database, and organized this information by drug mechanism and indications for use. RESULTS: Most reports of medication-induced weight gain are anecdotal or gleaned from clinical trials. Notable offenders include hormones (especially corticosteroids and insulinotropic agents), and psychoactive medications (especially tricyclic antidepressants, lithium, and some antipsychotics). CONCLUSIONS: Medication-related increases in appetite and body weight are under-recognized and cause noncompliance with pharmacotherapy. A high index of awareness of the known mechanisms by which medications can lead to weight gain has the potential to prevent most medication-related contributions to weight gain and obesity.
Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Obesidade/induzido quimicamente , Cooperação do Paciente , Aumento de Peso/efeitos dos fármacos , Adulto , Fármacos Cardiovasculares/efeitos adversos , Feminino , Glucocorticoides/efeitos adversos , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Psicotrópicos/efeitos adversosRESUMO
The objective of this study is to determine, by using rigorous methods, if pulmonary perfusion defects were detectable by ventilation-perfusion scintigraphy after percutaneous thrombolysis of clotted hemodialysis access grafts. Thirteen patients were studied. Four patients underwent pharmacomechanical thrombolysis with urokinase and the remainder had mechanical thrombolysis alone. Pre- and postthrombolysis scintigraphic studies were performed on all patients. Perfusion defects were described as vascular (well-defined borders confined to segmental boundaries) or nonvascular. Vascular defects were graded by severity (0 to 3) and area (0 to 3) for each involved segment. Nonvascular defects were graded by severity (0 to 1) and area (0 to 1). Two experienced readers evaluated the scans blinded to each other's results and all other clinical data, including thrombolysis outcomes. Twelve patients did not have any significant worsening of their perfusion defect scores postthrombolysis. In only one patient did a study show a new nonvascular perfusion defect with a matching ventilation abnormality. The defect was believed to be caused by mucus plugging. The patient had no evidence of pulmonary embolism. Our study suggests emboli that resulted from the pharmacomechanical or mechanical thrombolysis procedure were either small, underwent lysis before impacting the lung, or were below the limit of detection of ventilation-perfusion scintigraphy.
Assuntos
Angioplastia com Balão/efeitos adversos , Derivação Arteriovenosa Cirúrgica , Oclusão de Enxerto Vascular/terapia , Embolia Pulmonar/diagnóstico por imagem , Diálise Renal , Terapia Trombolítica/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Embolia Pulmonar/etiologia , Radiografia , Cintilografia , Compostos Radiofarmacêuticos , Agregado de Albumina Marcado com Tecnécio Tc 99m , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Relação Ventilação-Perfusão , Radioisótopos de XenônioRESUMO
The diagnosis and management of infectious complications associated with injection drug use (IDU) are among some of the more challenging aspects of working with substance abusing populations. As the population of injection drug users age, we expect the number and severity of these complications to increase. Commonly seen infections, such as bacterial endocarditis and bacterial infections of bones, joints, and soft tissue, are now frequently complicated by concurrent immunodeficiency. Parenterally and sexually transmitted viral hepatitis is responsible for significant IDU morbidity and mortality. The human leukemia/lymphoma virus types I and II are increasing in prevalence in the IDU with uncertain long-term clinical effects. Immune dysfunction has been described in the IDU for decades, but the impact of host immune compromise on the transmission and the course of HIV-1 has yet to be fully appreciated. The integration of the treatment of substance abuse and its concurrent psychiatric disorders with the management of infectious complications, including immunodeficiency, promises to improve patient compliance with possible savings of overall medical costs.
Assuntos
Infecções/terapia , Abuso de Substâncias por Via Intravenosa/complicações , Humanos , Infecções/etiologiaRESUMO
A small cohort of high-risk intravenous drug users (IVDU) from the Baltimore, MD, area was evaluated for HIV1 infection status and viral load. Quantitative dilution endpoint HIV1 DNA polymerase chain reaction (PCR) results, from HIV proviral DNA from quantitated peripheral blood mononuclear cell (PBMC) lysates, were compared to the dilution endpoint results for HIV PBMC micrococulture. The quantitative dilution endpoint HIV1 PCR was more rapid, sensitive and reproducible. In addition, an HIV1 capture RT-PCR technique was used to qualitatively detect the presence or absence of intact HIV1 virus in IVDU plasma and was compared with plasma culture detection, for HIV1 viraemia. Using the results of the PCR techniques, a rapid molecular assessment of the HIV1 infection status can be attained, which is important, as the IVDU population can be difficult to study prospectively. The PCR techniques can also be used to assess HIV1 burden as well as the potential effectiveness of antiviral therapies. These molecular techniques can be used to monitor the progression of HIV in patients and to evaluate the clinical effects of concurrent substance abuse.
Assuntos
Infecções por HIV/virologia , HIV-1/isolamento & purificação , Reação em Cadeia da Polimerase , Abuso de Substâncias por Via Intravenosa/complicações , Estudos de Coortes , DNA Viral/sangue , Infecções por HIV/sangue , Infecções por HIV/complicações , HIV-1/genética , Humanos , Leucócitos Mononucleares/virologia , RNA Viral/sangueRESUMO
Evidence accumulated over more than 45 years has indicated that environmental stimuli can induce craving for drugs of abuse in individuals who have addictive disorders. However, the brain mechanisms that subserve such craving have not been elucidated. Here a positron emission tomographic study shows increased glucose metabolism in cortical and limbic regions implicated in several forms of memory when human volunteers who abuse cocaine are exposed to drug-related stimuli. Correlations of metabolic increases in the dorsolateral prefrontal cortex, medial temporal lobe (amygdala), and cerebellum with self-reports of craving suggest that a distributed neural network, which integrates emotional and cognitive aspects of memory, links environmental cues with cocaine craving.
Assuntos
Encéfalo/fisiopatologia , Cocaína , Glucose/metabolismo , Memória/fisiologia , Transtornos Relacionados ao Uso de Opioides/fisiopatologia , Transtornos Relacionados ao Uso de Opioides/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Análise de Variância , Encéfalo/diagnóstico por imagem , Desoxiglucose/análogos & derivados , Desoxiglucose/farmacocinética , Feminino , Radioisótopos de Flúor/farmacocinética , Fluordesoxiglucose F18 , Lateralidade Funcional , Humanos , Masculino , Transtornos Relacionados ao Uso de Opioides/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/diagnóstico por imagem , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Tomografia Computadorizada de EmissãoRESUMO
Heroin dependence remains a serious and costly public health problem, even in patients receiving methadone maintenance treatment. This study used a within-subject reversal design to assess the effectiveness of voucher-based abstinence reinforcement in reducing opiate use in patients receiving methadone maintenance treatment in an inner-city program. Throughout the study subjects received standard methadone maintenance treatment involving methadone, counseling, and urine monitoring (three times per week). Thirteen patients who continued to use opiates regularly during a 5-week baseline period were exposed to a 12-week program in which they received a voucher for each opiate-free urine sample provided: the vouchers had monetary values that increased as the number of consecutive opiate-free urines increased. Subjects continued receiving standard methadone maintenance for 8 weeks after discontinuation of the voucher program (return-to-baseline). Tukey's posthoc contrasts showed that the percentage of urine specimens that were positive for opiates decreased significantly when the voucher program was instituted. (P < or = 0.01) and then increased significantly when the voucher program was discontinued during the return-to-baseline condition (P < or = 0.01). Rates of opiate positive urines in the return-to-baseline condition remained significantly below the rates observed in the initial baseline period (P < or = 0.01). Overall, the study shows that voucher-based reinforcement contingencies can decrease opiate use in heroin dependent patients receiving methadone maintenance treatment.
Assuntos
Dependência de Heroína/reabilitação , Metadona/uso terapêutico , Motivação , Abuso de Substâncias por Via Intravenosa/reabilitação , Reforço por Recompensa , Adulto , Feminino , Dependência de Heroína/psicologia , Humanos , Masculino , Cooperação do Paciente/psicologia , Detecção do Abuso de Substâncias , Abuso de Substâncias por Via Intravenosa/psicologia , Resultado do TratamentoRESUMO
Chloroquine continues to have a limited role in the chemoprophylaxis against malaria. Although periodic ophthalmologic examinations are recommended with weekly suppressive dosing, the occurrence of retinopathy associated with this regimen is unproven. Surveillance of career missionaries was conducted to explore the association between total body burden of chloroquine and the development of retinopathy. Five hundred eighty-eight missionaries, reflecting 6,250 person-years of chloroquine exposure were surveyed; 53 persons reflecting 560 person-years exposure with a median cumulative chloroquine dose in excess of 300 g were examined. Only one case of chloroquine-induced retinopathy was detected. This occurred in a missionary who had inappropriately taken chloroquine daily for at least six years as an anti-inflammatory agent for a connective tissue disorder. We also observed that expatriates often overused chloroquine because of apprehension about malaria and used the drug for unrelated conditions. Our results failed to demonstrate an association between a weekly chloroquine dosing regimen and drug-induced retinopathy.
Assuntos
Cloroquina/efeitos adversos , Malária/prevenção & controle , Missões Religiosas , Doenças Retinianas/induzido quimicamente , Adulto , Cloroquina/administração & dosagem , Cloroquina/uso terapêutico , Estudos de Coortes , Esquema de Medicação , Feminino , Fibromialgia/tratamento farmacológico , Humanos , Missionários , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoRESUMO
Prior studies have reported men with coronary artery disease (CAD) to have elevated plasma levels of estrogens and reduced concentrations of dehydroepiandrosterone (DHEA) or DHEA-sulfate (DHEAS). We investigated whether gonadal steroids or DHEAS are risk factors for CAD in men, using a prospective design, in a well characterized population studied at regular intervals. We studied 46 men (Cardiac group) who developed CAD and 124 men (Control group) who remained free of CAD (mean follow-up, 9.5 years). We measured testosterone (T), estradiol (E2), and DHEAS, as well as plasma binding of T and E2, in samples stored before the onset of CAD (Cardiac group) or at matched times (Control group). Body mass index, blood pressure, and total serum cholesterol were measured at each visit. Both systolic blood pressure (SBP; P less than 0.001) and cholesterol (P less than 0.001) were increased in the Cardiac group, but no significant differences were found in total or free T or E2, the ratio of E2/T, or DHEAS between the two groups. The difference in cholesterol was significant only in men less than or equal to 65 years old (P less than 0.001), and SBP only in men greater than 65 years old (P less than 0.005). Cholesterol (P less than 0.05) and E2 (P less than 0.001) appeared to decrease with age in the Cardiac, but not the Control, group. Moreover, total (P less than 0.01) and free E2 (P less than 0.05) were lower only in Cardiac men less than or equal to 55 years old.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Doença das Coronárias/sangue , Desidroepiandrosterona/análogos & derivados , Estradiol/sangue , Testosterona/sangue , Adulto , Baltimore , Colesterol/sangue , Estudos de Coortes , Doença das Coronárias/mortalidade , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de RiscoRESUMO
The insulin-like effects of ionic zinc (Zn2+) were studied in isolated rat adipocytes. Concentrations of Zn2+ between 250 and 1000 microM stimulated 3-O-methylglucose transport and glucose metabolism to CO2, glyceride-fatty acid, and glyceride-glycerol. Selective stimulation of the pentose phosphate cycle was observed since a Zn2+-induced increase in glucose carbon 1 oxidation persisted even when glucose transport was blocked with 50 microM cytochalasin B or when transport was no longer rate-limiting for metabolism at high concentrations of glucose. Enhanced pentose phosphate cycle activity may have been due to a selective inhibition of glutathione reductase by the ion, which was also accompanied by a fall in cellular glutathione content. Zn2+ also inhibited lipolysis stimulated by the beta-adrenergic agent ritodrine in the absence of glucose. The effects of Zn2+ on glucose oxidation and stimulated rates of lipolysis were inhibited by extracellular catalase, indicating that they were largely a result of H2O2 generation. The H2O2 production appeared for the most part to be caused by zinc-catalyzed autoxidation of sulfhydryl groups present on external cell membranes, although involvement of sulfhydryl groups on bovine serum albumin in the buffer could also have contributed. The insulin-like effects of Zn2+ in adipocytes are therefore caused not only by direct effects of the ion on intracellular metabolism but also by indirect effects related to H2O2 generation.