RESUMO
BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.
Assuntos
Antioxidantes/farmacologia , Apolipoproteína B-48/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Hiperlipidemias/prevenção & controle , Lipoproteínas HDL/efeitos dos fármacos , Isquemia Miocárdica/prevenção & controle , Vitamina E/farmacologia , Animais , Apolipoproteína B-48/sangue , Cardiotônicos/farmacologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/prevenção & controle , Citocinas/sangue , Dieta Aterogênica , Suplementos Nutricionais , Ensaio de Imunoadsorção Enzimática , Feminino , Hiperlipidemias/sangue , Immunoblotting , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas HDL/sangue , Masculino , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/sangue , Proteínas de Transferência de Fosfolipídeos/sangue , Valores de Referência , Reprodutibilidade dos Testes , Receptores Depuradores Classe B/sangue , Receptores Depuradores Classe B/efeitos dos fármacos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.
Assuntos
Animais , Masculino , Feminino , Ácido Ascórbico/farmacologia , Vitamina E/farmacologia , Isquemia Miocárdica/prevenção & controle , Apolipoproteína B-48/efeitos dos fármacos , Hiperlipidemias/prevenção & controle , Lipoproteínas HDL/efeitos dos fármacos , Antioxidantes/farmacologia , Valores de Referência , Doença da Artéria Coronariana/prevenção & controle , Doença da Artéria Coronariana/sangue , Ensaio de Imunoadsorção Enzimática , Cardiotônicos/farmacologia , Immunoblotting , Reprodutibilidade dos Testes , Citocinas/sangue , Resultado do Tratamento , Isquemia Miocárdica/sangue , Suplementos Nutricionais , Proteínas de Transferência de Fosfolipídeos/sangue , Dieta Aterogênica , Receptores Depuradores Classe B/efeitos dos fármacos , Receptores Depuradores Classe B/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Apolipoproteína B-48/sangue , Hiperlipidemias/sangue , Lipoproteínas HDL/sangue , Camundongos Endogâmicos C57BLRESUMO
Literature data relevant to the decision to allow a waiver of in vivo bioequivalence (BE) testing for the approval of immediate release (IR) solid oral dosage forms containing acetazolamide are reviewed. Acetazolamide's solubility and permeability characteristics according to the Biopharmaceutics Classification System (BCS), as well as its therapeutic use and therapeutic index, its pharmacokinetic properties, data related to the possibility of excipient interactions and reported BE/bioavailability (BA) problems are taken into consideration. The available data on solubility, on oral absorption and permeability are not sufficiently conclusive to classify acetazolamide with certainty. Taking a conservative approach, no biowaiver is considered justified for the registration of new multisource drug products. However, SUPAC level 1 and level 2 postapproval changes and most EU Type I variations can be approved waiving in vivo BE studies.
Assuntos
Acetazolamida/administração & dosagem , Inibidores da Anidrase Carbônica/administração & dosagem , Acetazolamida/farmacocinética , Administração Oral , Inibidores da Anidrase Carbônica/farmacocinética , Formas de Dosagem , Excipientes , Humanos , Solubilidade , Equivalência TerapêuticaRESUMO
A field assay was performed in an impoverished hill grassland of the Sierras of Córdoba, with the objective of evaluating the effects of Azospirillum spp on gramineous plants. Native grasses were inoculated with different strains of Azospirillum lipoferum and Azospirillum brasilense, during two consecutive years. The inoculation effect on yield, nitrogen content and number of Azospirillum spp was evaluated in three annual harvests. The first and the second inoculation increased significantly the diazotroph number of the grasses with respect to the controls. This positive effect on the rhizophere population did not correlate with a significant increase in the forage quantity and quality as was expected.
Assuntos
Azospirillum/fisiologia , Poaceae/crescimento & desenvolvimento , Microbiologia do Solo , Altitude , Argentina , Biomassa , Fixação de Nitrogênio , Proteínas de Plantas/análise , Poaceae/químicaRESUMO
The authors proceeded to a skin examination of 1,194 consecutive workers in a cutlery industry with 3,692 employees, in order to detect any cutaneous alterations among them. Only 223 (18.7%) had no skin pathology. Most of them, 971 (81.3%) presented some cutaneous disorder, related or not with their work. Hyperkeratosis of the fingers and hands (262 cases) caused by repeated traumas due to the manipulation of the instruments of work were the most noticeable and specific occupational skin alteration. In second place in order of frequency were the intertriginous mycotic inflammation of the toes: 255 cases. The authors call attention to the low incidence of the sexually transmitted diseases as well as of scabies, pediculosis and impetigo.