RESUMO
D-003 is a mixture of long-chain fatty acids isolated and purified from sugar cane wax with cholesterol-lowering properties. D-003 given orally (500 and 1000 mg/kg/day) to female rats for 15 days prior to mating, through mating and gestation to day 21 of lactation and male rats for 4 weeks prior and during mating did not induce toxic effects on reproduction. There were no significant reductions in the number of animals that conceived, in the numbers of pups born to those that did conceive, in the numbers of pups that survived until weaning, and in their body weights at weaning. Drug-treated and control groups' offspring were comparable in growth, physical and behavioral development, spontaneous activity and reproductive performance. Pregnant New Zealand rabbits were given D-003 as oral doses of 500 and 1000 mg/kg/day on days 6 through 18 of gestation without any evidence of embryotoxicity or teratogenicity. The no-observed-effect dose in these two experimental studies was 1000 mg/kg/day. After assessment of the potential of high doses of D-003 to act on developing embryo and reproduction process, no evidence supports the conclusion that D-003 is a reproductive and developmental toxicant/teratogen.
Assuntos
Ácidos Graxos/toxicidade , Reprodução/efeitos dos fármacos , Teratogênicos , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Fertilidade/efeitos dos fármacos , Lactação/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Gravidez , Coelhos , Ratos , Ratos Sprague-Dawley , Aumento de Peso/efeitos dos fármacosRESUMO
OBJECTIVES: To identify and describe the work related injuries in both the formal and informal work sectors captured in an emergency department based injury surveillance system in Managua, Nicaragua. SETTING: Urban emergency department in Managua, Nicaragua serving 200-300 patients per day. METHODS: Secondary analysis from the surveillance system data. All cases indicating an injury while working and seen for treatment at the emergency department between 1 August 2001 and 31 July 2002 were included. There was no exclusion based on place of occurrence (home, work, school), age, or gender. RESULTS: There were 3801 work related injuries identified which accounted for 18.6% of the total 20 425 injures captured by the surveillance system. Twenty seven work related fatalities were recorded, compared with the 1998 International Labor Organization statistic of 25 occupational fatalities for all of Nicaragua. Injuries occurring outside of a formal work location accounted for more than 60% of the work related injuries. Almost half of these occurred at home, while 19% occurred on the street. The leading mechanisms for work related injuries were falls (30%), blunt objects (28%), and stabs/cuts (23%). Falls were by far the most severe mechanism in the study, causing 37% of the work related deaths and more than half of the fractures. CONCLUSIONS: Occupational injuries are grossly underreported in Nicaragua. This study demonstrated that an emergency department can be a data source for work related injuries in developing countries because it captures both the formal and informal workforce injuries. Fall prevention initiatives could significantly reduce the magnitude and severity of occupational injuries in Managua, Nicaragua.
Assuntos
Acidentes de Trabalho/estatística & dados numéricos , Serviço Hospitalar de Emergência , Ferimentos e Lesões/epidemiologia , Acidentes Domésticos/mortalidade , Acidentes de Trabalho/mortalidade , Acidentes de Trânsito , Adolescente , Adulto , Criança , Emprego , Feminino , Humanos , Masculino , Nicarágua/epidemiologia , Saúde Ocupacional , Vigilância da População/métodos , Distribuição por Sexo , Saúde da População Urbana , Local de Trabalho , Ferimentos e Lesões/mortalidade , Ferimentos Perfurantes/epidemiologiaRESUMO
INTRODUCTION: Paraneoplastic motor neuron disease are rare among patients with renal cell carcinoma. OBJECTIVE: Present the clinical and electrophysiological evolution of a patient with a motor neuron disease and hypernephrome. CASE REPORT: A 60 years old woman, affected only by high level pressure since 10 years ago. She noticed sudden palsy of the left leg and 10 months later an abdominal ultrasound showed a renal cell carcinoma, discovered without other symptoms than neurologic. After radical nephrectnomy, the patient was treated with recombinant interferon alpha 2b. The neurologic damage advanced and she has a flaccid weakness and muscle atrophy in the legs and brisk reflexes, also in wasted limbs. There is Babinski, fasciculations, light flaccid dysarthria and laryngospasm. Peripheral nerve conduction studies are within normal limits. The electromyogram show positive sharp waves in both legs and left hand. Recruitment patterns are decreased and there are fasciculations in the tongue, upper and lower limbs. The magnetic resonance of the brain and spinal cord is normal. There are not evidence of metastasis. The question of whether or not this is a paraneoplastic form of motor neuron disease remain unclear. CONCLUSION: This case suggest the need to consider a renal cell carcinoma in the course of a motor neuron disease.
Assuntos
Carcinoma de Células Renais/complicações , Neoplasias Renais/complicações , Doença dos Neurônios Motores/complicações , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/cirurgia , Eletromiografia , Feminino , Humanos , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Doença dos Neurônios Motores/diagnóstico por imagem , Doença dos Neurônios Motores/cirurgia , RadiografiaRESUMO
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
INTRODUCTION: The treatment selection in the carpal tunnel syndrome according to the damage of the median nerve is important and all of these have adverse effects. A good alternative without undesired reactions is irradiation of the carpal tunnel with not coherent light between 920 and 940 nm emitted by gallium arsenide diodes, resembling the physic and therapeutic laser effects. PATIENTS AND METHODS: Twenty-six female patients with idiopathic middle carpal tunnel syndrome were irradiated 15 minutes daily during three weeks. The median nerve motor and sensitive neuroconduction was studied before and immediately after the treatment. RESULTS: The abnormal neuroconduction variables (latency, amplitude and velocity conduction) did not modify when treatment concluded, in spite of all the patients reported disappearance of pain and numbness in damaged hands. CONCLUSIONS: Not coherent light does not change the fibers functional state explored by conventional neuroconductions techniques. It remains to know if this light produces fine fibers improvement.
Assuntos
Síndrome do Túnel Carpal/fisiopatologia , Síndrome do Túnel Carpal/terapia , Lasers , Nervo Mediano/fisiologia , Fototerapia , Arsenicais/uso terapêutico , Síndrome do Túnel Carpal/patologia , Feminino , Gálio/uso terapêutico , Humanos , Masculino , Nervo Mediano/patologia , Pessoa de Meia-Idade , Condução Nervosa , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A set of amphiphilic p-menthan-3,9-diols have been investigated by molecular dynamics simulations. These are four stereoisomers than can be specifically obtained from two terpenoids widely used in biorganic chemistry. For this purpose, the p-menthan-3,9-diols have been explicitly parametrized using both semiempirical and ab initio quantum mechanical calculations. The reliability of these parameters has been validated by predicting different molecular and thermodynamic properties. Molecular dynamics simulations in aqueous solution have been performed with the new parameters. The results provide useful insights about the conformational properties of this family of compounds and the formation of intra- and intermolecular hydrogen bonds.
Assuntos
Tensoativos/química , Terpenos/química , Desenho de Fármacos , Ligação de Hidrogênio , Modelos Moleculares , Conformação Molecular , Eletricidade Estática , TermodinâmicaRESUMO
This paper contains the reference data for the main physiological indicators of three species of laboratory animals: mice, rabbits and dogs. Data listed include the mean and the standard deviation of haematology, serum biochemistry and organ weight to body weight ratio. In addition, pathological studies including microscopical examination of organs and tissues were also done. Comparisons between sexes were analysed.
Assuntos
Animais de Laboratório/fisiologia , Cães/fisiologia , Camundongos/fisiologia , Coelhos/fisiologia , Animais , Peso Corporal , Feminino , Masculino , Tamanho do Órgão , Valores de ReferênciaRESUMO
D-003 is a mixture of higher aliphatic primary acids purified from sugar cane wax (Saccharum officinarum) with cholesterol-lowering and antiplatelet effects experimentally proven. The present work reports the results of two studies investigating the acute and subchronic oral toxicity of D-003 in rats. Oral acute toxicity of D-003 (2000 mg/kg) was investigated according to the Acute Toxic Class (ATC) method (an alternative for the classical LD(50) test), which was performed in Wistar rats. The results obtained in this study defined D-003 oral acute toxicity as unclassified. In the subchronic study, rats of both sexes were orally treated with D-003 at 50, 200 and 1250 mg/kg for 90 days. At this time, animals were sacrificed. No evidence of treatment-related toxicity was detected during the study. Thus, data analysis of body weight gain, food consumption, clinical observations, blood biochemical, haematology, organ weight ratios and histopathological findings did not show significant differences between control and treated groups. It is concluded that D-003 orally administered to rats was safe and that no drug-related toxicity was detected even at the highest doses investigated in both acute (2000 mg/kg) and subchronic (1250 mg/kg) studies.
Assuntos
Anticolesterolemiantes/toxicidade , Ácidos Graxos/uso terapêutico , Inibidores da Agregação Plaquetária/toxicidade , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Dose Letal Mediana , Masculino , Ratos , Ratos Sprague-Dawley , Ratos WistarRESUMO
INTRODUCTION: This study was undertaken to evaluate the efficacy, safety, and tolerability of policosanol, a new cholesterol-lowering drug, in patients with type II hypercholesterolemia and additional coronary risk factors. PATIENTS AND METHODS: After 5 weeks of a standard step-1 lipid-lowering diet, 437 patients were randomized to receive, under double-blind conditions, 5 mg policosanol or placebo once a day with the evening meal for 12 weeks and 10 mg policosanol or placebo for the next 12 weeks. RESULTS: Both groups were similar at randomization. Policosanol (5 and 10 mg/day) significantly reduced (P < .001) serum low-density lipoprotein cholesterol (18.2% and 25.6%, respectively) and cholesterol (13.0% and 17.4%), and it significantly raised (P < .01) high-density lipoprotein cholesterol (15.5% and 28.4%). Triglycerides remained unchanged after the first 12 weeks and lowered significantly (5.2%; P < .01) at study completion. Policosanol was safe and well tolerated, and no drug-related disturbances were observed. Two male patients who received placebo died during the study--one because of a myocardial infarction and the other because of a cardiac arrest that occurred during a surgical intervention. There were 11 serious adverse events (5.1%) in 10 patients who received placebo (4.6%), 7 of which were vascular, compared with no serious adverse events reported in patients receiving policosanol (P < .01). CONCLUSIONS: Subjects in the group treated with policosanol did not have serious adverse events during the 24-week study. This study shows that policosanol is effective, safe, and well tolerated in patients with hypercholesterolemia and concomitant coronary risk factors.
Assuntos
Anticolesterolemiantes/farmacologia , Doença das Coronárias/etiologia , Álcoois Graxos/farmacologia , Hipercolesterolemia/complicações , Hipercolesterolemia/tratamento farmacológico , Idoso , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
A reference database comprising body weight gain, exploratory activity, hot plate response, serum biochemistry, haematology, organ weight (%) and a complete anatomopathological study containing non-neoplastic and neoplastic lesions over 1200 Sprague-Dawley rats from 6 to 32 months is described. Comparisons between age and sex were analysed.
Assuntos
Sistemas de Gerenciamento de Base de Dados , Ratos Sprague-Dawley/fisiologia , Padrões de Referência , Animais , Comportamento Exploratório , Feminino , Incidência , Masculino , Neoplasias Experimentais , Tamanho do Órgão , Dor/fisiopatologia , Ratos , Ratos Sprague-Dawley/anatomia & histologia , Aumento de PesoRESUMO
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
To study the effect of general anesthesia with diazepam, fentanyl and nitric oxide, a common combination during the intraoperative recording of visual evoked potentials (VEP) in transsphenoidal surgery, we compared the amplitude and latency of VEP components before anesthesia and at four moments after induction during the first hour of elective breast surgery in 20 patients with no neurological deficits. The results for these patients (group I) before anesthesia and 15 min after induction were also compared to presurgical recordings for 19 patients with hypophysial tumors and histories visual field and acuity involvement (group II). Latency increased significantly as a result of anesthesia whereas amplitude was affected to a lesser degree. Changes in latency of the main positive component was after anesthesia was the only parameter that was significantly different for the two group studied, variation being greater in group II.
Assuntos
Anestesia Geral , Anestésicos Intravenosos/uso terapêutico , Diazepam/uso terapêutico , Potenciais Evocados Visuais , Fentanila/uso terapêutico , Mamoplastia , Óxido Nítrico/uso terapêutico , Osso Esfenoide/cirurgia , Adulto , Anestésicos Intravenosos/administração & dosagem , Diazepam/administração & dosagem , Feminino , Fentanila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Óxido Nítrico/administração & dosagem , Neoplasias Hipofisárias/cirurgia , Transtornos da VisãoRESUMO
Policosanol is a new drug whose cholesterol-lowering effects have been demonstrated in experimental models, healthy volunteers, and patients with type II hypercholesterolaemia. The effect of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted on healthy volunteers. This included a trial of the effects of single doses (5 to 50 mg) and a study of the effects of repeated doses administered for 7 days. In the single-dose study, the percentage of platelet aggregation in response to the threshold concentration of ADP and epinephrine measured from 8:00 to 10:00 increased significantly in the placebo group, while policosanol (5, 10, 25 and 50 mg), administered orally, inhibited the increase of platelet aggregation induced by ADP and epinephrine determined at the same time. Policosanol administered at 20 mg/day for 7 days significantly inhibited platelet aggregation induced by ADP and epinephrine, although the inhibition reached by the 10 mg/day dose tended to be less significant (p = 0.06). A modest effect (p = 0.068) on collagen-induced platelet aggregation was only observed at the highest dose (50 mg/day). The low dose (5 mg/day) was ineffective. Policosanol did not affect the coagulation time when administered at single or repeated doses. No side-effects were reported in treated or placebo groups.
Assuntos
Álcoois Graxos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Adulto , Testes de Coagulação Sanguínea , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacosRESUMO
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
The effects of policosanol (50-500 mg/kg) administered orally for 24 months to Sprague Dawley rats of both sexes were investigated. No differences related to daily clinical observations, weight gain, food consumption, or mortality (survival analysis) between groups were found. Histopathological study showed that the frequency of the occurrence of non-neoplastic and neoplastic (benign and malignant) lesions was similar in the control and policosanol-treated groups. The lesions observed in this study were similar to the spontaneous lesions reported in this species in previous studies. Since no drug-related increase in the occurrence of malignant or benign neoplasms was found, nor acceleration in tumors growth in any specific group was observed, this study shows no evidence of policosanol induced carcinogenicity in this strain of rats.
Assuntos
Álcoois Graxos/farmacologia , Neoplasias/induzido quimicamente , Animais , Anticolesterolemiantes/farmacologia , Peso Corporal/efeitos dos fármacos , Testes de Carcinogenicidade , Feminino , Masculino , Neoplasias Experimentais/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Análise de SobrevidaRESUMO
Policosanol is a natural mixture of higher aliphatic primary alcohols. Oral toxicity of policosanol was evaluated in a 12-month study in which doses from 0.5 to 500 mg/kg were given orally to Sprague Dawley (SD) rats (20/sex/group) daily. There was no treatment-related toxicity. Thus, effects on body weight gain, food consumption, clinical observations, blood biochemistry, hematology, organ weight ratios and histopathological findings were similar in control and treated groups. This study supports the wide safety margin of policosanol when administered chronically.
Assuntos
Álcoois Graxos/toxicidade , Inibidores da Agregação Plaquetária/toxicidade , Administração Oral , Análise de Variância , Animais , Biomarcadores/sangue , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Álcoois Graxos/administração & dosagem , Feminino , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Masculino , Tamanho do Órgão/efeitos dos fármacos , Inibidores da Agregação Plaquetária/administração & dosagem , Ratos , Ratos Sprague-DawleyRESUMO
La maniobra de apertura y cierre de los ojos es una de la más frecuentes en electroencefalografía para identificar el ritmo alfa por inspección visual. El objetivo principal de este trabajo es comprobar si mediante el análisis cuantitativo del EEG pueden detectarse los cambios que se observan, por inspección visual, entre segmentos de registro con los ojos abiertos y con los ojos cerrados. Para ello se recogió el EEG de 10 sujetos normales (25 a 35 años de edad) en las condiciones "ojos abiertos" y "ojoss cerrados" mediante un sistema computarizado de registro y análisis de EEG. A partir de los registros fueron obtenidos las medidas espectrales de banda ancha (MEBAS) y los parámetros del Modelo Xi-ALFA. Se encontró que los poderes absolutos, así como la frecuencia dominante son los que reflejan con mayor claridad un incremento de actividad en la banda alfa (regiones posteriores principalmente) en la condición "ojoss cerrados". Los parámetros del Modelo Xi-ALFA mostraron gran congruencia con las MEBAS. Se concluye que por medio del análisis cuantitativo del EEG se pueden detectar cambios en el EEG al comparar segmentos de registros con ojos abiertos, de segmentos con ojos cerrados
Assuntos
Humanos , Masculino , Feminino , Adulto , Eletroencefalografia , Análise Espectral/métodos , Sistemas ComputacionaisRESUMO
Se analiza el efecto producido por diferentes dosis de diazepam sobre el EEG de ratas utilizando las Medidas Espectrales de Banda Ancha y el Espectro de Potencia. De estas medidas las que presentan diferencias significativas son: Poder Relativo, Frecuencia Dominante y la Coherencia sólo para la dosis más alta: observándose mayor energia en las frecuencias más rápidas alfa y beta y menor energía para las frecuencias más lentas delta y theta. Estos resultados brindan la posibilidad de utilizar este método en la caracterización electroencefalográfia de drogas psicotrópicas relacionadas con los ansiolíticos