RESUMO
We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1% cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with 3H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 +/- 0.056 and 0.170 +/- 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 +/- 0.033 h-1) was considerably greater than CE-FCR (0.046 +/- 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 +/- 0.1475 and CE = 0.2135 +/- 0.1580%/g) but in cholesterol-fed animals FC uptake (0.0890 +/- 0.0319%/g) was greater than CE uptake (0.0595 +/- 0.0207%/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.
Assuntos
Aterosclerose/metabolismo , Ésteres do Colesterol/farmacocinética , Colesterol/farmacocinética , Hiperlipidemias/metabolismo , Lipoproteínas LDL/sangue , Animais , Colesterol/administração & dosagem , Ésteres do Colesterol/administração & dosagem , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/farmacocinética , Emulsões Gordurosas Intravenosas/farmacocinética , Lipídeos/sangue , Lipoproteínas LDL/metabolismo , Masculino , Nanopartículas , CoelhosRESUMO
We have shown that the free cholesterol (FC) and the cholesteryl ester (CE) moieties of a nanoemulsion with lipidic structure resembling low-density lipoproteins show distinct metabolic fate in subjects and that this may be related to the presence of dyslipidemia and atherosclerosis. The question was raised whether induction of hyperlipidemia and atherosclerosis in rabbits would affect the metabolic behavior of the two cholesterol forms. Male New Zealand rabbits aged 4-5 months were allocated to a control group (N = 17) fed regular chow and to a 1 percent cholesterol-fed group (N = 13) during a 2-month period. Subsequently, the nanoemulsion labeled with ³H-FC and 14C-CE was injected intravenously for the determination of plasma kinetics and tissue uptake of the radioactive labels. In controls, FC and CE had similar plasma kinetics (fractional clearance rate, FCR = 0.234 ± 0.056 and 0.170 ± 0.038 h-1, respectively; P = 0.065). In cholesterol-fed rabbits, the clearance of both labels was delayed and, as a remarkable feature, FC-FCR (0.089 ± 0.033 h-1) was considerably greater than CE-FCR (0.046 ± 0.010 h-1; P = 0.026). In the liver, the major nanoemulsion uptake site, uptake of the labels was similar in control animals (FC = 0.2256 ± 0.1475 and CE = 0.2135 ± 0.1580 percent/g) but in cholesterol-fed animals FC uptake (0.0890 ± 0.0319 percent/g) was greater than CE uptake (0.0595 ± 0.0207 percent/g; P < 0.05). Therefore, whereas in controls, FC and CE have similar metabolism, the induction of dyslipidemia and atherosclerosis resulted in dissociation of the two forms of cholesterol.
Assuntos
Animais , Masculino , Coelhos , Aterosclerose/metabolismo , Ésteres do Colesterol/farmacocinética , Colesterol/farmacocinética , Hiperlipidemias/metabolismo , Lipoproteínas LDL/sangue , Ésteres do Colesterol/administração & dosagem , Colesterol na Dieta/administração & dosagem , Colesterol na Dieta/farmacocinética , Colesterol/administração & dosagem , Emulsões Gordurosas Intravenosas/farmacocinética , Lipídeos/sangue , Lipoproteínas LDL/metabolismo , NanopartículasRESUMO
An open, retrospective, uncontrolled study was carried out to evaluate efficacy and tolerability of immunosuppressive therapy used in the period 1982-1990 in patients with clinically definite multiple sclerosis. Of 42 patients 43% were treated with one drug, and the others with more than one. Tolerability was evaluated after at least 6 months of therapy in 6 patients on prednisone, 26 on azathioprine, 17 on methyl-prednisolone and 15 on cyclophosphamide pulses. Reversible mild or moderate side-effects were noted in 54% of the patients on azathioprine, leading to change in dose or withdrawal. There were similar side-effects in 83% of the patients on prednisone, 40% of those on cyclophosphamide, and in 12% of those on methylprednisolone. Efficacy was evaluated in 15 patients with a follow-up of at least 2 years, measured by objective scales. The results indicated therapy appeared to arrest progress of disability. We conclude that this study supports the use of immunosuppression in selected cases with rapidly evolving neurological deficits.
Assuntos
Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Adolescente , Adulto , Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Esquema de Medicação , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos RetrospectivosRESUMO
The frequency of multiple sclerosis in Brasil is assumed to be lower than in some geographically comparable regions, but internationally available objective diagnostic criteria are not generally used. We have reviewed a number of such criteria and applied those of Poser and colleagues to all patients who could be examined specifically for this study; who had been under our care between 1982-87; with clinically satisfactory history, physical exam, ancillary investigations and follow-up; with enough information to warrant immunosuppressive therapy with azathioprine, methyl-prednisolone or cyclophosphamide. There were 35 (88%) females and 5 (12%) males, with clinically definite (85%), probable (10%) disease according to Poser and cols, as well as 2 patients with chronic progressive disease. Age at time of study was 39 +/- 11 years, age at onset had been 32 +/- 10 years, and length of history was 6 +/- 7 years (mean +/- sd). Mode of onset was a disturbance of gait in 50%, of vision in 25% and dizziness in 10%. Physical exam at time of study showed motor deficits in 92.5%, sensory in 67.5%, ocular visual in 65%, spastic bladder in 35%, and vestibulo-cerebellar disturbances in 32%. Visual evoked responses were abnormal in 65% of 31 cases, auditory in 23% of 22 cases, and somatosensory in 80% of 20 cases. This study shows that international diagnostic criteria, specifically those of Poser and colleagues are applicable in Brasil, providing clear guidelines for diagnosis of multiple sclerosis. We suggest objective diagnostic criteria form the backbone of teaching about the disease, at various levels of medical education. Their wide utilization will in due time provide conditions for epidemiological, clinical and therapeutic studies which have not as yet been carried out in this country.
Assuntos
Esclerose Múltipla/diagnóstico , Índice de Gravidade de Doença , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
The wide clinical spectrum of neurocysticercosis has led to many attempts at clinical, radiological, CSF and other classifications. Based on an objective review of the relevant literature and on a prospective study of 42 patients with active neurocysticercosis, a new classification is proposed, based on clinical, tomographic, magnetic resonance and CSF evidence of viability of cysts. The first step is to define whether the disease is active or not. Inactive disease may be parenchymal calcifications or hydrocephalus. Active disease may be intraparenchymal, extraparenchymal or mixed. Statistical analysis of 42 cases with active disease shows intraparenchymal disease to occur in younger patients, perhaps more frequently in females, and to have a better prognosis than extraparenchymal of mixed disease. The latter appears to have the worst prognosis. Therapeutic implications are that only active disease warrants etiological therapy. There remain doubts about the best therapy for some infrequent subtypes of extraparenchymal and mixed disease.
Assuntos
Doenças do Sistema Nervoso Central/diagnóstico , Cisticercose/diagnóstico , Adolescente , Adulto , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/tratamento farmacológico , Doenças do Sistema Nervoso Central/etiologia , Criança , Pré-Escolar , Cisticercose/líquido cefalorraquidiano , Cisticercose/tratamento farmacológico , Cisticercose/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Praziquantel/uso terapêutico , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
O amplo espectro clínico da neurocisticercose deu espaço a muitas tentativas de classificaçöes clínicas, radiológicas e de LCR, entre outras. Baseados em revisäo objetiva da literatura relevante e em estudo prospectivo de 42 casos de doença ativa, nova classificaçäo é proposta com base em evidências clínicas, tomográficas, de ressonância magnética ou LCR indicando viabilidade de cistos. O primeiro passo é establelecer se a doença é ou näo ativa. Doença ativa pode ser intra ou extraparenquimatosa, ou mista. Análise estatística de 42 casos com doença ativa demonstra que doença intraparenquimatosa ocorre em um grupo mais jovem, talvez mais no sexo feminino, e tem melhor prognóstico que doença extraparenquimatosa ou mista. Doença mista parece ter o pior prognóstico. Implicaçöes terapêuticas säo que somente doença ativa deve receber tratamento etiológico. Permanecem dúvidas sobre a melhor conduta em algumas formas infreqüentes de doença extraparenquimatosa ou mista
Assuntos
Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Cisticercose/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/líquido cefalorraquidiano , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/etiologia , Cisticercose/diagnóstico , Cisticercose/tratamento farmacológico , Cisticercose/etiologia , Imageamento por Ressonância Magnética , Praziquantel/uso terapêutico , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
Serum and CSF concentrations of praziquantel were analyzed in 8 patients with active neurocysticercosis aged 35 +/- 16 (mean +/- sd) years, in order to determine factors that may improve the therapeutic ratio. Praziquantel was given orally at 6-h intervals for 10 days at a daily dose of 100 mg/kg. Serum concentrations were determined at 1, 2 and 4 h, and CSF concentrations at 2 h after the morning dose. Peak serum concentrations occurred between 1 and 2 h after administration. There was a trend towards a drop in serum concentration from Days 1 through 5 to 10 of therapy. A fourfold increase in oral dose led to an eightfold rise in serum and CSF concentration, indicating saturation of hepatic metabolism. There were linear correlations (p less than 0.01) between serum and CSF concentrations of praziquantel, indicating free flow across the blood-brain barrier, above an apparent threshold, which may be related to occupation of plasma protein-binding sites. The results indicate that monitoring of serum concentrations may be clinically useful.
Assuntos
Cisticercose/tratamento farmacológico , Praziquantel/uso terapêutico , Administração Oral , Humanos , Praziquantel/administração & dosagem , Praziquantel/sangue , Praziquantel/líquido cefalorraquidianoRESUMO
Standard therapeutic regimens of praziquantel for neurocysticercosis use daily doses of 50 mg/kg for 15-21 days, with prolonged remission being achieved in 60-80% patients. In this prospective study, 100 mg/kg daily was used for 10 days in 13 patients aged 32 +/- 15 years (mean +/- SD) with severe intra-, extra-parenchymal or mixed forms of neurocysticercosis. Patients were monitored with computerized tomography and cerebrospinal fluid (CSF) examination on days 1, 5 and 10. Full blood count, sedimentation rate, blood sugar, urea, creatinine, bilirubin, liver transaminases, alkaline phosphatase, urine analysis and electrocardiogram were carried out before and after treatment. Doses of dexamethasone and of other drugs used concomitantly were controlled. There was no toxicity, clinical or detected by the methods employed in the study. After 22 +/- 5 (mean +/- SD) months follow-up, 6 patients needed ventriculoperitoneal shunting, 2 had died, 7 were improved and led useful lives and 4 were in prolonged remission. There was no correlation between serum or CSF praziquantel correlation and outcome of treatment. The proposed regimen is well tolerated, may be as efficient as previously advocated regimens, requires less hospitalization time and may be adopted routinely for therapy of neurocysticercosis.
Assuntos
Cisticercose/tratamento farmacológico , Doenças do Sistema Nervoso/tratamento farmacológico , Praziquantel/uso terapêutico , Adolescente , Adulto , Ventrículos Cerebrais/cirurgia , Derivações do Líquido Cefalorraquidiano , Criança , Pré-Escolar , Cisticercose/líquido cefalorraquidiano , Feminino , Humanos , Hidrocefalia/fisiopatologia , Lactente , Pressão Intracraniana , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/líquido cefalorraquidiano , Doenças do Sistema Nervoso/psicologia , Praziquantel/administração & dosagem , Praziquantel/efeitos adversos , RecidivaRESUMO
As part of a prospective study about 347 cases of ischemic cerebral vascular disease (DCVI) admitted to a general hospital 36 diabetic and 36 non-diabetic patients with similar sex, age and blood pressure were evaluated with the objective of assessing the effect of diabetes mellitus on prognosis in DCVI. All patients had various types of DCVI (thrombosis, thromboembolism or cardiac embolism). The diabetic patients had statistically longer admissions (p less than 0.05), more complications during admission (p less than 0.05), more infectious complications (p less than 0.01) and a greater number of deaths at the end of follow-up (p less than 0.05). After 377 +/- 429 (mean +/- standard deviation) days of follow-up, 50% of the diabetics had died while after 387 +/- 405 days 25% of the non-diabetics had died. Deaths in both groups occurred in average at the 8th month after the vascular event that led to the first admission. There were no differences with respect to the number of deaths during admission or to neurological conditions of the survivors at the end of the first admission or at the end of follow-up.