RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: H. longipes S.F. Blake (Asteraceae) is a Mexican plant, whose roots are traditionally used as a condiment, as a mouth anesthetic, and as an antiparasitic. Affinin is the alkamide present in higher amounts in the roots of H. longipes. AIM OF THE STUDY: To date, there are no published studies regarding the relation between the analgesic properties, in vivo cytotoxicity, and DNA-damaging potential of H. longipes ethanol extract (HLEE). MATERIALS AND METHODS: The HLEE was chromatographically fingerprinted to validate its affinin contents. Biological evaluation was conducted in sets of 6-8 CD1(+) mice. Antinociceptive effect was evaluated using the writhing and hot-plate tests, and mutagenic and cytotoxic effects were evaluated with micronucleous test in CD1(+) mice. For histopathological studies, biological samples from liver, heart, kidneys, spleen, lung, and brain were collected and stained. RESULTS: Oral administration of HLEE (3-100 mg/kg) produced a dose-dependent antinociceptive effect in both assays. In micronucleus assay, the variability in the number of micronucleated polychromatic erythrocytes (MNPE) induced, and PE/NE index, the ratio of polychromatic erythrocytes with respect to the number of normochromatic erythrocytes induced by HLEE in the evaluated schedule, were small and nonsignificant. After histopathological results, HLEE showed polioencephalomalacia with 1000 mg/kg dose. CONCLUSIONS: This work provides evidence that HLEE exerts analgesic effects, with no genotoxic effects in vivo. These findings would be an important contribution to explain the use of H. longipes root as an effective analgesic in traditional medicine, and to establish for the first time the absence of genotoxic and cytotoxic effects of the root in bioactive doses in vivo.
Assuntos
Analgésicos/farmacologia , Asteraceae , Dor/prevenção & controle , Extratos Vegetais/farmacologia , Ácido Acético , Administração Oral , Analgésicos/administração & dosagem , Analgésicos/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Temperatura Alta , Dose Letal Mediana , Masculino , Camundongos , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Testes para Micronúcleos , Mutagênicos/toxicidade , Dor/etiologia , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Raízes de PlantasRESUMO
There is a broad epidemiologic evidence related with the increase of the incidence and prevalence of diabetes mellitus type 2 throughout the world, especially in Western populations, at rates considered epidemic. Cerebrovascular disease and myocardial infarction are two of the most important complications of this disease and they have very high social and economic consequences. Treatment of this disease is directed good metabolic control, diminishing toward obtain co-morbidity, and reducing acute and chronic diabetic complications. Diet, hypoglycemic drugs or insulin, and programs of physical activity are used for this purpose. This document presents some thoughts on the difficulties related with the prescription of physical exercise in the diabetic patient and a brief proposal to solve those problems in the clinical practice.
Assuntos
Diabetes Mellitus Tipo 2/terapia , Exercício Físico , Fatores Etários , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Angiopatias Diabéticas/prevenção & controle , Exercício Físico/fisiologia , Guias como Assunto , Humanos , Fatores Sexuais , Fatores de TempoRESUMO
Oxidative stress has been involved in the pathogenic process of a variety of diseases including diabetes mellitus. The production of oxidative reactive products has been involved in biochemical changes in bio-molecules that might produce tissue damage directly related to some of the main vascular complications in the diabetic patient. On the other hand, exercise, paradoxically, is a well-recognized model of oxidative stress and also an important therapeutic tool in diabetes management. Therefore, the relationship between oxidative stress and exercise in diabetic patients implies an interesting biochemical paradox due to some of the negative effects of exercise principally by the increase of oxidative species in plasma. The effect of oxidative stress during an acute exercise and after an aerobic training period on those patients remains unknown and needs to be studied.
Assuntos
Diabetes Mellitus/fisiopatologia , Exercício Físico/fisiologia , Estresse Oxidativo , Diabetes Mellitus/sangue , Humanos , Modelos Biológicos , Esforço Físico , Espécies Reativas de Oxigênio/fisiologiaRESUMO
Oxidative stress has been defined as a loss of counterbalance between free radical or reactive oxygen species production and the antioxidant systems, with negative effects on carbohydrates, lipids, and proteins. It is also involved in the progression of different chronic diseases and apoptosis. Diabetes mellitus is associated to a high oxidative stress level through different biochemical pathways, i.e. protein glycosylation, glucose auto-oxidation, and the polyol pathway, mainly induced by hyperglycemia. Oxidative stress could also be involved in the pathogenesis of atherosclerotic lesions and other chronic diabetic complications. Measurement of oxidative stress could be useful to investigate its role in the initiation and development processes of chronic diabetic complications and also to evaluate preventive actions, including antioxidative therapy. Different attempts have been made to obtain a practical, accurate, specific, and sensitive method to evaluate oxidative stress in clinical practice. However, this ideal method is not currently available to date and the usefulness of the current methods needs to be confirmed in daily practice. We suggest quantifying oxidated and reduced glutation (GSSG/GSH) and the thiobarbituric reactive substances (TBARS) with currently alternatives. Currently available alternative methods while we await better options.
Assuntos
Diabetes Mellitus/metabolismo , Estresse Oxidativo , HumanosRESUMO
Some drugs blocking glutamate release produce reduced brain injury in some animal models of cerebral ischemia whereas others lack a clear effect. Meta-analysis is a widely used technique in clinical and epidemiological studies. However, it has never been used in the analysis of preclinical studies. In order to estimate quantitatively the current state of the knowledge concerning the neuroprotective effect of drugs inhibiting glutamate release and to attempt to resolve the apparent controversy in relation to the neuroprotective properties of these drugs, a meta-analysis was performed. It identified a significant difference between drugs blocking glutamate release and controls. Therefore, we hypothesize that inhibition of presynaptic glutamate release could be a major goal in neuroprotection when ischemic brain damage is present and that meta-analysia could be a useful tool for preclinical studies,
Assuntos
Isquemia Encefálica/metabolismo , Ácido Glutâmico/metabolismo , Fármacos Neuroprotetores/farmacologia , Sinapses/efeitos dos fármacos , Humanos , Metanálise como AssuntoRESUMO
BACKGROUND: The use of protease inhibitors has revolutionized the treatment of HIV infection. These agents are well tolerated, although the Federal Drug Administration (FDA) has warned U.S. doctors that protease inhibitors may precipitate hyperglycemia and diabetes (DM), based on isolated reports from physicians. METHODS: Sixty-one patients with HIV infection with criterion of non-DM from the onset of the protease inhibitor therapy participated in the study. Plasma glucose levels were obtained every month during a 6-month period, with a basal determination prior to protease inhibitor therapy. RESULTS: All Mexican patients enrolled in this study had the same Hispanic-American ethnic origin. Four patients (6.55%) developed hyperglycemia related with saquinavir. One had family history of DM type II. These patients were controlled with diet. CONCLUSIONS: Based on present data, we believe the benefits of these drugs to patients suffering from HIV infection outweigh the various risks of taking protease inhibitors. However, physicians who use these drugs have to be on the alert for hyperglycemia in the Mexican population, while patients should know the warning symptoms of hyperglycemia and diabetes.
Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Hiperglicemia/induzido quimicamente , Adulto , Feminino , Humanos , Masculino , MéxicoRESUMO
Simplified reversed-phase high-performance liquid chromatographic method with ultraviolet detection at 280 nm without extraction procedure is described to quantify furosemide in rabbit and human urine. An internal standard was not used. The lower limit of quantitation was 0.750 microg/ml using 50 microl urine samples (100 microl of total injection volume), and linear response was tested from 0.750 to 250 microg/ml in both humans and rabbits. Within and between-day accuracy and precision were always below 10% at all analyzed concentrations. Validation data showed that this method is linear, sensitive, selective, specific, accurate and reproducible.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Diuréticos/urina , Furosemida/urina , Animais , Humanos , Coelhos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria UltravioletaRESUMO
Norethisterone (NET) and its metabolite 5alpha-norethisterone (5alpha-NET) are competitors for the androgen receptor. The sensitivity of the rat vas deferens to the contractile action of methoxamine and serotonin is regulated by hormonal and anatomical factors. The aim of this study was to evaluate the ability of NET and 5alpha-NET to induce the androgen-regulated contractile response to methoxamine and serotonin in the epididymal and prostatic portions of rat vas deferens. Adult male rats either intact, castrated or steroid-treated castrated were used. The contractility was recorded isometrically, and non-cumulative concentration-response curves to either methoxamine or serotonin were obtained. NET and 5alpha-NET partially restored the sensitivity to methoxamine and serotonin in the epididymal portion of castrated rats. The maximal responses to both agonists were significantly higher than those observed in castrated rats, and significantly lower than the responses observed in either intact or androgen-treated castrated rats. The prostatic portion was less responsive to both agonists than the epididymal portion, in all groups but castrated rats, as castration induced sensitivity to both agonists. NET and 5alpha-NET displayed a partial though similar androgenic activity in the rat vas deferens. These results contrast with previous reports where a decrease of androgenic effect due to the 5alpha-reduction of NET has been found.
Assuntos
Metoxamina/farmacologia , Contração Muscular/efeitos dos fármacos , Noretindrona/análogos & derivados , Noretindrona/farmacologia , Congêneres da Progesterona/farmacologia , Serotonina/farmacologia , Ducto Deferente/efeitos dos fármacos , Animais , Di-Hidrotestosterona/farmacologia , Epididimo/efeitos dos fármacos , Masculino , Orquiectomia , Próstata/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Testosterona/farmacologiaRESUMO
This study was designed to further characterize the sensitivity to serotonin of the isolated rat uterus. The contractile response to serotonin induced by the administration of estradiol was increased depending on the duration of estradiol-treatment, reaching the maximal contractility when ovariectomized rats were treated for 48 hours. Pretreatment with actinomycin D 1 hour before estrogen administration completely blocked estrogen-induced uterine sensitivity to serotonin. These results indicate that the sensitivity of rat uterus to serotonin in vitro induced by estradiol is a response occurring in the late phase and mediated by genomic activation. Following estradiol-administration uterine sensitivity to serotonin was similar in ovariectomized and ovariectomized-hypophysectomized rats, suggesting that in this response a pituitary factor is not required. The contractile responses to acetylcholine and oxytocin were not modified by estradiol; thus, estrogens induced specifically uterine sensitivity to serotonin. The present in vitro studies using pelanserin, a potent S2-antagonist, show that serotonin induced contractions in the rat uterus are mediated by interaction with S2-receptors, since pelanserin inhibited not-competitively the contractile response to serotonin.