Involvement of reactive oxygen species-mediated NF-kappa B activation in TNF-alpha-induced cardiomyocyte hypertrophy

We examined the intracellular signaling mechanism for tumor necrosis factor-alpha (TNF-alpha)-induced cardiac hypertrophy in isolated rat neonatal cardiomyocytes. TNF-alpha enhanced the expression of a kappa B-dependent reporter gene construct in a dose-dependent manner, which was transiently transfected in cardiomyocytes. Electrophoretic mobility shift assay demonstrated that TNF-alpha induced nuclear factor- kappa B (NF-kappa B)-specific DNA binding. Cultured cardiomyocytes were infected with a recombinant adenoviral vector expressing a degradation-resistant mutant of I kappa B alpha (AdI kappa B alpha 32/36A). The I kappa B alpha mutant suppressed NF-kappa B activation induced by TNF- alpha. In cardiomyocytes infected with AdI kappa B alpha 32/36A, TNF-alpha-induced hypertrophic responses, including increases in cell size, protein synthesis and atrial natriuretic factor production and enhancement of sarcomeric organization, were remarkably attenuated compared to the cells infected with an adenovirus expressing bacterial beta-galactosidase. Using a reactive oxygen species (ROS)-sensitive fluorescent dye, 2', 7'-dichlorofluorescin, we observed an increase in fluorescent signal in cardiomyocytes over time, upon addition of TNF-alpha. Preincubation of n-acetyl cysteine (NAC), an antioxidant, prior to TNF-alpha treatment, abolished TNF-alpha -induced ROS generation. NAC abolished TNF-alpha-induced NF-kappa B activation and hypertrophic responses. These findings indicated that TNF-alpha-induced cardiomyocyte hypertrophy is mediated through NF-kappa B activation via the generation of ROS.     

Celiprolol increases coronary blood flow and reduces severity of myocardial ischemia via nitric oxide release

Celiprolol is a selective beta(1)-adrenoceptor antagonist with antihypertensive actions, which causes renal vasodilation by increasing tissue nitric oxide (NO) levels. The authors tested whether celiprolol increases coronary blood flow (CBF) by increasing cardiac NO release in the ischemic heart in vivo. In open-chest dogs, coronary perfusion pressure of the left anterior descending coronary artery was reduced so that CBF decreased to 60% of control levels, and thereafter, coronary perfusion pressure was maintained constant. Ten minutes after the reduction of coronary perfusion pressure, we infused celiprolol into the left anterior descending coronary artery and measured fractional shortening and lactate extraction ratio as indices of regional myocardial contractility and metabolism. CBF significantly increased from 51.5 mL/100 g/min +/- 1.9 to 67.0 mL/100 g/min +/- 5.1 20 minutes after celiprolol infusion without changes in coronary perfusion pressure, while fractional shortening and lactate extraction ratio increased. Celiprolol also increased cardiac NO release. The L omega-nitroarginine methyl ester, the inhibitor of NO synthase, attenuated the increases in CBF, fractional shortening, lactate extraction ratio, and cardiac NO release due to celiprolol. ICI 118551, a beta(2)-adrenoceptor antagonist, did not blunt the effects of celiprolol and a nonselective beta-adrenoceptor antagonist, propranolol, increased neither CBF nor cardiac NO release, indicating that the effect of celiprolol is independent of beta-adrenoceptor blockade. It was concluded that celiprolol mediates coronary vasodilation and improves myocardial ischemia through NO-dependent mechanisms.     

Malignant fibrous histiocytoma of the lung

Primary malignant fibrous histiocytoma (MFH) of the lung is very rare. To date, only 32 reports of 63 cases of primary MFH of the lung have appeared in English, excluding tumors arising from the pulmonary arteries and pleura. We describe a patient with primary MFH of the lung who developed brain metastasis and involvement of pulmonary great vessels. In addition, we reviewed previously reported cases to establish the clinical characteristics and most appropriate management of primary pulmonary MFH. When disease is sufficiently limited, complete resection remains the mainstay of treatment.     

Effects of round window membrane rupture on cochlear blood flow and endocochlear potential

The degree of hearing loss and audiogram shape vary in patients with perilymphatic fistula. The cause of variability is not well known. To determine the effect of perilymphatic fistula on cochlear function, we studied the effect of round window membrane rupture on cochlear blood flow (CBF) by placing a laser-Doppler probe to the basal turn in 20 guinea pigs. In 10, endocochlear potential (EP) was measured by inserting a glass microelectrode through the stria vascularis of the basal turn. During 60 minutes following round window membrane rupture, CBF decrease of more than 15% was observed in 9 of 20 animals, and EP decrease of more than 15% was observed in 5 of 10. A significant correlation was observed between the degree of CBF reduction and EP reduction. In 3 animals in which CBF decreased after round window membrane rupture, temporal bones were studied histologically. One cochlea showed endolymphatic hydrops and another cochlea showed significant hemorrhage in the scala tympani after rupture. These results suggested that CBF impairment is associated with cochlear dysfunction in perilymphatic fistula.     

Evaluation of increasing digital blood flow during early period of air-cooled cold test

The present study was performed to elucidate peripheral hemodynamic changes, especially, digital blood flow, caused by an air-cooled cold test. Experiments were carried out by placing the subject's left hand in a box that was kept at a temperature of about 18 degrees C by air-cooling. At the same time, the digital blood flow, digital blood pressure, compliances of the peripheral resistance and capacitance vessels were measured. These parameters were measured on the left forefinger of the cooled side, and also on the opposite side according to Kato's method at 3 points, 1) at normal condition (before cooling stated). 2) 30 seconds after the cooling began and 3) 10 minutes after the cooling began. The following results were obtained; 1) The systemic blood pressure, digital blood pressure and heart rate showed no statistically significant differences in measurements taken at the above three stages. 2) The mean value of the digital blood flow was found to have increased after 30 seconds, and to have decreased after 10 minutes of cooling. Statistically, significant differences were noted at the above three stages. 3) The mean value of the peripheral vascular resistance was found to have increased after 30 seconds, and to have decreased after 10 minutes. 4) Compliances of the peripheral resistance vessel and capacitance vessel showed no significant changes on either side except between normal condition and after 10 minutes of cooling.     

Imaging endolymphatic hydrops at 3 tesla using 3D-FLAIR with intratympanic Gd-DTPA administration.

PURPOSE: Visualization of endolymphatic hydrops by 3-dimensional fluid-attenuated inversion recovery-FLAIR using conventional turbo-spin-echo (3D-FLAIR-CONV) after intratympanic injection of Gd-DTPA has been reported in patients with Ménière's disease. Compared to 3D-FLAIR-CONV used in previous studies, the addition of a variable flip-angle technique (3D-FLAIR-VFL) enables very long echo trains and, therefore, shorter scan times. We evaluated whether 3D-FLAIR-VFL could replace 3D-FLAIR-CONV in detecting endolymphatic hydrops after intratympanic Gd-DTPA administration. METHODS: Eleven patients were included in this study. Twenty-four hours after Gd-DTPA injection, we performed 3D-FLAIR-CONV and 3D-FLAIR-VFL imaging at 3T. We compared the contrast-to-noise ratio (CNR) between cochlear fluid and the cerebellum between the 2 FLAIR sequences. We subjectively scored the size of the endolymphatic space in the cochlea and vestibule for each patient and correlated the scores with the clinical diagnoses. RESULTS: The CNR of 3D-FLAIR-CONV was significantly higher than that of 3D-FLAIR-VFL. Scores for the size of endolymphatic space in the vestibule were identical between the 2 sequences; however, those in the cochlea disagreed in 3 cases. 3D-FLAIR-CONV correlated better with the clinical diagnoses. CONCLUSIONS: Currently, we may not be able to replace 3D-FLAIR-CONV with 3D-FLAIR-VFL, at least not with the scanning parameters used in the present study.     

A note on responses of isolated guinea-pig tracheal strip preparation to electrical stimulation

Authors observed the mechanical response of the tracheal muscle to electrical stimulation using only one transverse strip preparation of isolated guinea-pig trachea, 4-5 mm in width, which included only one tracheal muscle strip. The effects of various pharmacological agents on these responses were also investigated. A biphasic response which is a contractile response followed by a relaxing response usually appeared when the preparation was stimulated with rectangular pulses (50 volt, 0.5 msec) at 40 Hz for a period of 5 sec. A monophasic contractile response also appeared, only rarely but this response was shifted to the biphasic response as the resting tonus level of the preparation gradually increased in the course of the experiment. When the preparation was stimulated electrically at intervals of 15 min, the resting tonus level of the preparation gradually decreased and it subsequently reached a stable state. Then the amplitude of contractile response and depth of relaxing response in the biphasic response evoked by electrical stimulation of constant condition were, respectively, almost constant, whenever the preparation was stimulated at intervals of 15 min. The amplitude of monophasic contractile response which appeared only rarely was relatively constant to every trial of electrical stimulation throughout the experiment. The amplitude of contractile response and depth of relaxing response in the biphasic response were 283 +/- 65 mg (mean +/- SD, n = 10) and 293 +/- 93 mg (mean +/- SD, n = 10), respectively. The monophasic contractile response was abolished by atropine (5 X 10(-7) g/ml) or tetrodotoxin (2 X 10(-7) g/ml). The contractile response in the biphasic response was abolished by atropine (5 X 10(-7) g/ml). In the presence of atropine (5 X 10(-7) g/ml), therefore, only the relaxing response appeared. This relaxing response was respectively reduced by guanethidine (1 X 10(-5) g/ml-1 X 10(-6) g/ml) and propranolol (1 X 10(-5) g/ml-1 X 10(-6) g/ml), but complete inhibition was never seen. These findings suggest that the excitatory innervation is cholinergic and the inhibitory innervation is both adrenergic and non-adrenergic. In addition, from the results of this work it is clear that the preparation used by the authors are good enough to observe the electrical stimulation-induced response of the preparation.