RESUMO
STUDY OBJECTIVE: To describe sleep characteristics and rapid eye movement (REM) sleep behavior disorder in patients with Guadeloupean atypical parkinsonism (Gd-PSP), a tauopathy resembling progressive supranuclear palsy that mainly affects the midbrain. It is possibly caused by the ingestion of sour sop (corossol), a tropical fruit containing acetogenins, which are mitochondrial poisons. DESIGN: Sleep interview, motor and cognitive tests, and overnight videopolysomnography. PATIENTS: Thirty-six age-, sex-, disease-duration- and disability-matched patients with Gd-PSP (n = 9), progressive supranuclear palsy (a tauopathy, n = 9), Parkinson disease (a synucleinopathy, n = 9) and controls (n = 9). SETTINGS: Tertiary-care academic hospital. RESULTS: REM sleep behavior disorder was found in 78% patients with Gd-PSP (43% of patients reported having this disorder several years before the onset of parkinsonism), 44% of patients with idiopathic Parkinson disease, 33% of patients with progressive supranuclear palsy, and no controls. The percentage of muscle activity during REM sleep was greater in patients with Gd-PSP than in controls (limb muscle activity, 8.3%+/-8.7% vs 0.1%+/- 0.2%; chin muscle activity, 24.3%+/- 23.7% vs 0.7%+/-2.0%) but similar to that of other patient groups. The latency and percentage of REM sleep were similar in patients with Gd-PSP, patients with Parkinson disease, and controls, whereas patients with progressive supranuclear palsy had delayed and shortened REM sleep. CONCLUSION: Although Gd-PSP is a tauopathy, most patients experience REM sleep behavior disorder. This suggests that the location of neuronal loss or dysfunction in the midbrain, rather than the protein comprising the histologic lesions (synuclein versus tau aggregation), is responsible for suppressing muscle atonia during REM sleep. Subjects with idiopathic REM sleep behavior disorder should avoid eating sour sop.
Assuntos
Álcoois Graxos/toxicidade , Frutas/toxicidade , Lactonas/toxicidade , Transtornos Parkinsonianos/induzido quimicamente , Transtorno do Comportamento do Sono REM/induzido quimicamente , Tauopatias/induzido quimicamente , Acetogeninas , Idoso , Demência/induzido quimicamente , Demência/diagnóstico , Diagnóstico Diferencial , Avaliação da Deficiência , Sonhos/efeitos dos fármacos , Feminino , Guadalupe , Humanos , Masculino , Mesencéfalo/efeitos dos fármacos , Pessoa de Meia-Idade , Atividade Motora/efeitos dos fármacos , Exame Neurológico/efeitos dos fármacos , Doença de Parkinson/diagnóstico , Transtornos Parkinsonianos/diagnóstico , Polissonografia/efeitos dos fármacos , Estudos Prospectivos , Transtorno do Comportamento do Sono REM/diagnóstico , Transtornos da Transição Sono-Vigília/induzido quimicamente , Transtornos da Transição Sono-Vigília/diagnóstico , Paralisia Supranuclear Progressiva/induzido quimicamente , Paralisia Supranuclear Progressiva/diagnóstico , Tauopatias/diagnósticoRESUMO
Over the last 60 years an abnormally high prevalence of atypical Parkinsonism has been reported in 5 different geographic isolates. It was first described on Guam, later in New Guinea and in the Kii peninsula, on Guadeloupe, and in New Caledonia. We investigated the phenotype of atypical Parkinsonism in three of these foci and observed several similarities with dementia in most and amyotrophic lateral sclerosis in some. This disappearance of this disease in two places--Guam and New Guinea--suggested an environmental origin which has not been clarified before the disease ended. The exposure to annonaceae acetogenins and/or rotenone has been documented in four of these places, and experimental studies in animals demonstrated annonaceae acetogenins neurotoxicity, which is similar to rotenone neurotoxicity. Simultaneous exposure to acetogenins and rotenone could produce a synergistic toxicity on neurons.
Assuntos
Diamino Aminoácidos/toxicidade , Annonaceae/toxicidade , Álcoois Graxos/toxicidade , Lactonas/toxicidade , Doença dos Neurônios Motores/induzido quimicamente , Neurotoxinas/toxicidade , Doença de Parkinson Secundária/induzido quimicamente , Rotenona/toxicidade , Tauopatias/induzido quimicamente , Clima Tropical , Acetogeninas , Toxinas de Cianobactérias , Sinergismo Farmacológico , Guadalupe , Guam , Humanos , Japão , Doença dos Neurônios Motores/epidemiologia , Doença de Parkinson Secundária/epidemiologiaRESUMO
Botanical insecticides have long been touted as attractive alternatives to synthetic chemical insecticides for pest management because botanicals reputedly pose little threat to the environment or to human health. The body of scientific literature documenting bioactivity of plant derivatives to arthropod pests continues to expand, yet only a handful of botanicals are currently used in agriculture in the industrialized world, and there are few prospects for commercial development of new botanical products. Pyrethrum and neem are well established commercially, pesticides based on plant essential oils have recently entered the marketplace, and the use of rotenone appears to be waning. A number of plant substances have been considered for use as insect antifeedants or repellents, but apart from some natural mosquito repellents, little commercial success has ensued for plant substances that modify arthropod behavior. Several factors appear to limit the success of botanicals, most notably regulatory barriers and the availability of competing products (newer synthetics, fermentation products, microbials) that are cost-effective and relatively safe compared with their predecessors. In the context of agricultural pest management, botanical insecticides are best suited for use in organic food production in industrialized countries but can play a much greater role in the production and postharvest protection of food in developing countries.
Assuntos
Controle de Insetos/métodos , Repelentes de Insetos , Inseticidas , Extratos Vegetais , Acetogeninas , África , Animais , Ásia , Chrysanthemum cinerariifolium/química , Chrysanthemum cinerariifolium/toxicidade , Comércio , Ésteres , Europa (Continente) , Álcoois Graxos/farmacologia , Álcoois Graxos/toxicidade , Glicerídeos/química , Lactonas/farmacologia , Lactonas/toxicidade , Limoninas/química , Limoninas/farmacologia , Limoninas/toxicidade , Melia azedarach/química , América do Norte , Óleos Voláteis/farmacologia , Rotenona/farmacologia , Rotenona/toxicidade , América do Sul , Terpenos/químicaRESUMO
D-002 is a mixture of high-molecular-weight aliphatic alcohols, obtained from bees wax (Apis mellifera), with mild anti-inflammatory properties and effective anti-ulcer activities demonstrated in experimental models. This study investigated the oral toxicity of D-002 administered for 1 year to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in three experimental groups (four animals per group): a control and two treated groups received D-002 at 50 and 250 mg kg(-1) (7 days/week) by gastric gavage. Overall, D-002 was well tolerated throughout the study. No signs or symptoms of toxicity were observed, and no mortality occurred during the study. All groups showed similar weight gain and food consumption. No hematological, blood biochemical or histopathological disturbances attributable to treatment were observed. This study shows no drug-related toxicity induced by long-term administration of up to 250 mg kg(-1) D-002 to beagle dogs.
Assuntos
Antiulcerosos/toxicidade , Álcoois Graxos/toxicidade , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Cães , Ingestão de Alimentos , Álcoois Graxos/administração & dosagem , Feminino , Masculino , Distribuição Aleatória , Aumento de PesoRESUMO
D-002 is a mixture of higher aliphatic alcohols, primarily isolated and purified from beeswax, that has moderate anti-inflammatory and effective anti-ulcer activity. In the present study the developmental toxicity in Sprague-Dawley rats and New Zealand White rabbits was evaluated. Doses of 100, 320 and 1000 mg kg(-1) were administered once daily by gavage to pregnant females on gestation days 6-15 (rats) or 6-18 (rabbits). Reproductive indices were determined and foetuses were examined for external, visceral and skeletal malformations. There was no indication of embryotoxicity, fetotoxicity or teratogenicity in any of the treated groups. It is concluded that D-002 is devoid of teratogenic or embryotoxic effects in these strains.
Assuntos
Álcoois Graxos/toxicidade , Teratogênicos/toxicidade , Animais , Feminino , Masculino , Troca Materno-Fetal , Gravidez , Coelhos , Ratos , Ratos Sprague-DawleyRESUMO
D-002 is a mixture of higher aliphatic primary alcohol isolated from bees wax (Apis mellifera) with effective antiulcer effects demonstrated in different experimental models. Oral toxicity of D-002 (5-5000 mg/kg) was evaluated in sub-acute (14 days), subchronic (90 days) and chronic (1 year) studies in Sprague-Dawley rats from both sexes. There was no treatment-related toxicity. Thus, effects on body weight, food consumption, clinical observations, blood parameters, organ weight ratios and histopathological findings were similar in control and treated groups. These short and long-term studies support a wide safety margin for this product.
Assuntos
Antiulcerosos/toxicidade , Álcoois Graxos/toxicidade , Administração Oral , Animais , Antiulcerosos/administração & dosagem , Aorta Abdominal/efeitos dos fármacos , Aorta Abdominal/metabolismo , Contagem de Células Sanguíneas , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Álcoois Graxos/administração & dosagem , Feminino , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Masculino , Miocárdio/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Timo/metabolismoRESUMO
The effects of Policosanol, a newly developmented hypocholesterolemic drug administered during the perinatal and postnatal periods, were studied in Sprague-Dawley rats. This compound was administered orally to female rats at dose levels of 0 (control), 5, 50, and 500 mg/kg/day, from day 15 of pregnancy to day 21 after parturition. The animals were allowed to deliver and their offspring were examined for postnatal growth and development. No signs of toxic effects related to the test material were observed in the dams F0 during pregnancy and lactation. No adverse effects were observed on the postnatal growth, behaviours, or reproductive ability of pups F1. The physical and sensorial development of pups F2 was also normal. These results confirm that Policosanol does not affect the reproductive performance or fetal/neonatal development.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Anticolesterolemiantes/toxicidade , Álcoois Graxos/toxicidade , Animais , Anticolesterolemiantes/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Álcoois Graxos/administração & dosagem , Feminino , Lactação/efeitos dos fármacos , Masculino , Gravidez , Prenhez/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Razão de Masculinidade , Taxa de SobrevidaRESUMO
Policosanol (trade name Ateromixol) is a new cholesterol-lowering drug that has been isolated and purified from sugar cane wax. The effects of policosanol (50-500 mg/kg) administered orally for 18 months to male and female Swiss mice were investigated. No differences in daily clinical observations, weight gain, food consumption and mortality (survival analysis) between groups were found. Histopathological study showed that the frequency of neoplastic (benign and malignant) lesions was similar in the control and policosanol-treated groups. The lesions observed were similar to the spontaneous lesions in Swiss mice reported in previous studies. As no drug-related increase in the occurrence of malignant or benign neoplasm was found, nor acceleration in tumour growth in any specific group observed, this study shows no evidence of policosanol-induced carcinogenicity in Swiss mice.
Assuntos
Anticolesterolemiantes/toxicidade , Álcoois Graxos/toxicidade , Neoplasias Experimentais/induzido quimicamente , Administração Oral , Análise de Variância , Animais , Anticolesterolemiantes/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Álcoois Graxos/administração & dosagem , Feminino , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Estudos Longitudinais , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Camundongos , Miocárdio/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/metabolismo , Análise de Sobrevida , Timo/efeitos dos fármacos , Timo/metabolismo , Aumento de Peso/efeitos dos fármacosRESUMO
Policosanol is a new chemical entity composed of 8 higher aliphatic alcohols obtained from sugar cane (Saccharum officinarum), L. wax, whose cholesterol-lowering effects have been demonstrated in experimental models, healthy volunteers and patients with type II hypercholesterolemia. This study investigated the oral toxicity of policosanol administered for 52 weeks to beagle dogs. Twenty-four beagle dogs (12 males and 12 females) were distributed randomly in 3 experimental groups (4 animals/group): a control and 2 treated groups receiving policosanol at 30 and 180 mg/kg daily (7 days/week) by gavage. No mortality was observed in any group. Overall, policosanol was well tolerated throughout the study and no toxic symptoms were observed. All groups showed similar weight gain and food consumption. Lipid profile determinations showed that policosanol decreased total cholesterol by 20% approximately from 8 to 52 weeks. Cholesterol-lowering effects did not wear off during the study, thus demonstrating the persistence of the effectiveness. Triglycerides and high density lipoprotein-cholesterol (HDL-C) were not changed significantly. No blood biochemistry or histopathological disturbances attributable to treatment were observed. This study has shown that no drug-related toxicity was induced by policosanol administered up to 180 mg/kg/day for 52 weeks to beagle dogs. Since this dose is approximately 620 times higher than the maximal recommended therapeutic dose (20 mg/day) it indicates a good safety margin of this product.
Assuntos
Anticolesterolemiantes/toxicidade , Álcoois Graxos/toxicidade , Administração Oral , Animais , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Cães , Feminino , Lipídeos/sangue , Masculino , Tamanho do Órgão/efeitos dos fármacos , Distribuição Aleatória , Fatores de TempoRESUMO
Policosanol, administered orally, has shown a cholesterol-lowering effect in different experimental models. Because lipid-lowering therapy is administered chronically, it is necessary to know the effects of these drugs after long-term administration. 18 adult male Macaca arctoides monkeys were used to study the cholesterol-lowering effects and possible toxicity produced by oral administration of policosanol (0.25, 2.5 and 25 mg/kg) for 54 wk. After 8 wk, a significant reduction of serum total cholesterol and low-density lipoprotein cholesterol was observed in policosanol-treated animals when compared with the controls; this effect persisted throughout the study. The animals' behavioural repertoire, physical condition, haematology and blood biochemistry, as well as spermiogram analysis and electrocardiography, were monitored during the study; ophthalmological and pathological anatomy examinations were performed at the end of the administration period. No drug-related toxicity was detected by any examination. The results gave further evidence of the marked and persistent cholesterol-lowering effects of policosanol that had been observed in different experimental models. There was a significant reduction of spontaneous aortic atherosclerotic lesions in treated animals compared with controls. Policosanol (0.25-25 mg/kg) administered orally for 54 wk brought about a persistent reduction in blood cholesterol levels and was very safe and well tolerated during long-term administration.