A simple in vivo atrial fibrillation model of rat induced by transesophageal atrial burst pacing

A simple in vivo closed-chest atrial fibrillation (Af) model of rats was developed. Af was reproducibly induced by transesophageal atrial burst pacing for 30 s in each of the pentobarbital-anesthetized rats, whereas the cardiohemodynamic condition as well as the inducibility and duration of Af episode was stable over time. Moreover, the anti-Af effect of the class Ic drug pilsicainide was confirmed in this model, which was essentially the same as those reported previously in other Af animal models and clinical practice. Thus, this new model may become an alternative to current techniques.     

Adult T-cell leukemia with leukemic cell infiltration in the conjunctiva

A 77-year-old Japanese woman who had suffered from skin eruptions since 1986 was admitted in January, 1990. A diagnosis of adult T-cell leukemia/lymphoma (ATL) was made on the basis of clinical and laboratory data. On admission, erythematous lesions were present in both eyelids. Yellowish-white elevated lesions were found along the limbal conjunctiva, and extended segmentally into the cornea of both eyes. Microscopically, leukemic infiltration into the subepithelial layer of the conjunctiva was observed. Ophthalmic manifestations in ATL have not been well described, because of a little attention paid to them.     

Halothane sensitizes the canine heart to pharmacological IKr blockade

The effects of halothane and pentobarbital on the cardiovascular system were compared using the in vivo canine models. The ventricular repolarization process was longer under the halothane-anesthesia than pentobarbital-anesthesia. Intravenous administration of a selective blocker of rapidly activating delayed rectifier K+ currents (I(Kr)) sematilide prolonged the ventricular repolarization period without affecting the intraventricular conduction under both anesthesia; however, the potency was about 1.5-folds greater under the halothane-anesthesia than pentobarbital-anesthesia. These results suggest that halothane can more effectively sensitize the heart to pharmacological I(Kr) blockade, resulting in the excessive QT interval prolongation. Thus, the halothane-anesthetized canine model can be useful for predicting the in vivo I(Kr) blocking property of new drugs.     

Alzheimer's disease beta-amyloid peptides are released in association with exosomes

Although the exact etiology of Alzheimer's disease (AD) is a topic of debate, the consensus is that the accumulation of beta-amyloid (Abeta) peptides in the senile plaques is one of the hallmarks of the progression of the disease. The Abeta peptide is formed by the amyloidogenic cleavage of the amyloid precursor protein (APP) by beta- and gamma-secretases. The endocytic system has been implicated in the cleavages leading to the formation of Abeta. However, the identity of the intracellular compartment where the amyloidogenic secretases cleave and the mechanism by which the intracellularly generated Abeta is released into the extracellular milieu are not clear. Here, we show that beta-cleavage occurs in early endosomes followed by routing of Abeta to multivesicular bodies (MVBs) in HeLa and N2a cells. Subsequently, a minute fraction of Abeta peptides can be secreted from the cells in association with exosomes, intraluminal vesicles of MVBs that are released into the extracellular space as a result of fusion of MVBs with the plasma membrane. Exosomal proteins were found to accumulate in the plaques of AD patient brains, suggesting a role in the pathogenesis of AD.     

The endothelium-dependent vasodilator action of a new beverage made of red wine vinegar and grape juice

A new non-alcoholic beverage made of red wine vinegar and grape juice (Budo-no-megumi) has been recently demonstrated to lower the blood pressure of human as well as rats. In this study, we pharmacologically analyzed the mechanism of its hypotensive action. The thoracic aorta with intact endothelium was isolated from Sprague-Dawley rats, and incubated with a Tyrode's solution. The beverage in concentrations of 0.25 to 2% relaxed the pre-contracted aorta with an alpha-adrenoceptor agonist phenylephrine in a concentration-dependent manner, 2% of which induced 59% relaxation. In contrast, the vasodilator response disappeared in the aorta without endothelium. L-Nitro-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, significantly reduced the vasodilator effect of the beverage, whereas indomethacin, an inhibitor of cyclooxygenase, hardly affected it. These results suggest that the beverage can activate the nitric oxide synthase activity to exert vasodilation, which may partly explain its previously reported hypotensive action.