RESUMO
The importance of proximal tubules dysfunction to diabetic albuminuria is uncertain. OVE26 mice have the most severe albuminuria of all diabetic mouse models but it is not known if impaired tubule uptake and processing are contributing factors. In the current study fluorescent albumin was used to follow the fate of albumin in OVE26 and normal mice. Compared to normal urine, OVE26 urine contained at least 23 times more intact fluorescent albumin but only 3-fold more 70 kD fluorescent dextran. This indicated that a function other than size selective glomerular sieving contributed to OVE26 albuminuria. Imaging of albumin was similar in normal and diabetic tubules for 3 hrs after injection. However 3 days after injection a subset of OVE26 tubules retained strong albumin fluorescence, which was never observed in normal mice. OVE26 tubules with prolonged retention of injected albumin lost the capacity to take up albumin and there was a significant correlation between tubules unable to eliminate fluorescent albumin and total albuminuria. TUNEL staining revealed a 76-fold increase in cell death in OVE26 tubules that retained fluorescent albumin. These results indicate that failure to process and dispose of internalized albumin leads to impaired albumin uptake, increased albuminuria, and tubule cell apoptosis.
Assuntos
Albuminas/metabolismo , Albuminúria/metabolismo , Diabetes Mellitus Experimental/metabolismo , Túbulos Renais/metabolismo , Albuminúria/patologia , Albuminúria/fisiopatologia , Animais , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Túbulos Renais/patologia , Túbulos Renais/fisiopatologia , Camundongos TransgênicosAssuntos
Encéfalo/enzimologia , Indóis/análise , Inibidores da Monoaminoxidase/análise , Animais , Transporte Biológico/efeitos dos fármacos , Encéfalo/metabolismo , Química Encefálica , Isótopos de Carbono , Bovinos , Fenômenos Químicos , Química , Indóis/sangue , Fígado/enzimologia , Camundongos , Mitocôndrias/enzimologia , Monoaminoxidase/análise , Monoaminoxidase/sangue , Inibidores da Monoaminoxidase/sangueAssuntos
Cannabis/metabolismo , Animais , Encéfalo/metabolismo , Cromatografia em Camada Fina , Rim/metabolismo , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Ratos , Respiração , TrítioRESUMO
Delta-THC (10 mg/kg, i.p.) administered to mice immediately after withdrawal from a 3-day exposure to ethanol vapor was found to intensify withdrawal reactions. No effect was seen when delta-THC was administered chronically during the exposure to ethanol.
Assuntos
Alcoolismo , Cannabis/farmacologia , Dronabinol/farmacologia , Síndrome de Abstinência a Substâncias , Animais , Etanol/sangue , Humanos , Masculino , Camundongos , PirazóisRESUMO
BetaTC6-F7 cells like normal Beta cells were found to be highly sensitive to hydrogen peroxide and to possess very low levels of catalase. Therefore we tested whether overexpression of catalase could enhance resistance to hydrogen peroxide. Enzyme activity was increased forty fold by transient transfection of a catalase transgene. To assess protection from hydrogen peroxide a cotransfection method using a human growth hormone reporter gene was developed. Human growth hormone secretion was shown to be a suitable marker for insulin secretion since both hormones demonstrated virtually identical glucose dose response curves. Catalase transfection was found to provide significant protection against hydrogen peroxide indicating that low catalase may contribute to the sensitivity of cells to hydrogen peroxide.
Assuntos
Catalase/genética , Regulação Enzimológica da Expressão Gênica/genética , Peróxido de Hidrogênio/toxicidade , Insulina/metabolismo , Ilhotas Pancreáticas/enzimologia , Transfecção/genética , Animais , Hormônio do Crescimento Humano/genética , Humanos , Secreção de Insulina , Insulinoma , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Camundongos , Concentração Osmolar , Neoplasias Pancreáticas , Transfecção/métodos , Células Tumorais CultivadasRESUMO
The effect of relaxation training, utilizing EMG biofeedback, on platelet monoamine oxidase (MAO) activity was examined in patients with a history of chronic anxiety. Anxiety scores and MAO activity were significantly lowered after 4 weeks of therapy. Kinetic studies, using phenylethylamine as substrate, indicated a significant increase of the Km constant while the Vmax showed no significant or consistent variation. It is thought that this phenomenon represents an adaptive response by the individual to maintain a homeostatic level of the biogenic amines.