TNF-alpha rapidly antagonizes the beta-adrenergic responses of the chloride current in guinea-pig ventricular myocytes.

The purpose of this study was to test the hypothesis that tumor necrosis factor-alpha (TNF-alpha) rapidly antagonizes the beta-adrenergic responses of the chloride current and to clarify the intracellular mechanisms responsible for the anti-adrenergic action. The whole-cell patch-clamp technique was used to monitor the anti-adrenergic effects of TNF-alpha on the cAMP-dependent chloride current (I(Cl)) recorded from isolated guinea-pig ventricular myocytes. Ramp pulses (+/-120 mV; dv/dt = +/-0.4 V/s) were applied from the holding potential of -40 mV. TNF-alpha rapidly (<15 min) inhibited the isoproterenol (Iso, 0.1 micromol/L)-induced I(Cl) in a concentration-dependent manner (30-1,000 U/ml, IC (50) = 144 U/ml, n=30). The inhibitory action of TNF-alpha was also observed when I(Cl) had been previously stimulated by 1 micromol/L forskolin (n=5). Prior exposure of myocytes to 5 microg/ml pertussis toxin (PTX) hardly affected the anti-adrenergic action of TNF-alpha (n=4). However, when I(Cl) was induced by both 8-bromo-cAMP (100 micromol/L) and isobutylmethylxanthine (0.1 mmol/L), TNF-alpha (1,000 U/ml) failed to decrease I(Cl) amplitude (n=5). Prior exposure of myocytes to 5 mg/ml pertussis toxin (PTX) hardly affected the anti-adrenergic action of TNF-alpha (n=4). Furthermore, despite of the presence of nitro-L-arginine methyl ester (0.1 mmol/L), a nitric oxide synthase (NOS) inhibitor, TNF-alpha reversed the Iso-induced increase in I(Cl) (n=5). These results suggest that TNF-alpha rapidly antagonizes the beta-adrenergic responses of I(Cl) by reducing cAMP concentration. This anti-adrenergic action is mediated by neither the PTX-sensitive G proteins regulatory pathway nor constitutive NOS activation.     

Seasonal variation in relapse rate of graves' disease after thionamide drug treatment

OBJECTIVE: Controversy abounds on the issue of seasonal variation in new onset of Graves' disease, partly due to the difficulty of precisely dating the exact start of symptoms. To address the possible relationship between climatic changes and disease activity from a different perspective, we reviewed time of relapse during regular follow-up after successful drug treatment with thionamides. DESIGN: Retrospective analysis of a case series in a university clinic. PATIENTS AND MEASUREMENTS: We consecutively registered patients who experienced re-emergence of hyperthyroidism between 1992 and 2001 after successful antithyroid drug therapy. Excluded were subjects with superimposing painless thyroiditis, in postpartum, on immunomodulatory drugs, or off thionamides prematurely on their own volition. RESULTS: Fifty-two patients recurred 2 to 36 months after drug cessation. The frequency was higher in spring and summer (March to August) than in autumn and winter (September to February). With a new coated-tube radioreceptor assay, TSH binding inhibitor immunoglobulin activity was detected in sera from 87.5% of the reworsened patients. CONCLUSIONS: Graves' disease tends to relapse more frequently in spring and summer. Further clinical studies are warranted to clarify underlying mechanism (s) for this seasonal variation.     

Nasal CPAP improves the quality of life and lessens the depressive symptoms in patients with obstructive sleep apnea syndrome

OBJECTIVE: To assess changes in response to nasal continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea syndrome (OSAS) concerning excessive daytime sleepiness (EDS), depressive state, and quality of life (QOL). PATIENTS AND METHODS: We assessed for EDS using the Epworth sleepiness scale (ESS), for mood using The Zung self-depression scale (SDS), and for QOL using Short-Form 36 (SF-36) in 132 patients with obstructive sleep apnea syndrome (OSAS) and control subjects. Patients had severe OSAS (apnea-hypopnea index, 59.4+/-23.8/h) and were more hypersomnolent and depressed, and had poorer QOL than 38 age- and gender-matched controls. RESULTS: Before treatment most QOL domains in the SF-36 were significantly associated with patients' SDS scores. With nasal CPAP, ESS and SDS scores were respectively decreased from 9.7+/-4.5 to 4.0+/-2.4 (p<0.0001) and from 49.2+/-10.4 to 45.1+/-9.6 (p<0.0005). Total SF-36 score and scores for seven of eight domains were increased significantly with treatment. Thus, nasal CPAP lessens EDS and depression, and improves QOL, in patients with severe OSAS. Further, magnitudes of changes in total SF-36 scores and in five of eight domains correlated significantly with magnitude of change in SDS score upon nasal CPAP treatment. No relationship was evident between treatment-associated score changes in SF-36 domains and ESS score change. CONCLUSION: Although patients with severe OSAS have poorer QOL than control subjects, nasal CPAP appears to improve QOL by alleviating depression.     

A lipoprotein lipase activator,NO-1886 prevents impaired endothelium-dependent relaxation of aorta caused by exercise in aged rats

Exercise decreases plasma total cholesterol and triglycerides, and simultaneously, increases high density lipoprotein (HDL) cholesterol. As a result, exercise is believed to aid in preventing atherosclerosis. However, we do not know whether exercise protects against the development of atherosclerosis in the elderly. The aim of this study was to ascertain whether the lipoprotein lipase activator NO-1886 had an effect on the prevention of atherosclerosis in aged rats which undergo exercise. Exercise for 3 months did not affect plasma lipids but decreased the accumulation of visceral fat in 2-year-old rats (aged rat). Exercise also resulted in an elevation of plasma lipid peroxide (LPO) levels and impaired the endothelium-dependent relaxation of the thoracic aorta caused by acetylcholine in aged rats. On the other hand, NO-1886 decreased plasma triglycerides and increased HDL cholesterol and suppressed the elevation of plasma LPO levels caused by exercise. Furthermore, NO-1886 prevented impaired endothelium-dependent relaxation caused by exercise. In summary, the results of our study indicate that exercise may cause impaired endothelium-dependent relaxation by elevation of LPO in aged rats, and that NO-1886 prevents this impaired endothelium-dependent relaxation of aorta by reducing plasma triglycerides, elevating HDL cholesterol, and suppressing the elevation of plasma LPO caused by exercise.     

Late giant coronary aneurysm associated with a fracture of sirolimus eluting stent: a case report

A 73-year-old female underwent percutaneous coronary intervention (PCI) because of stable angina. An elective PCI for the RCA lesion was first performed with deploying sirolimus eluting stents (SES). Three weeks later, PCI was also provided in the residual LAD lesion. Eight months later, she presented with new angina. CAG revealed an in-stent restenosis in the mid LAD and a large eccentric saccular coronary aneurysm (17 mm x 9 mm) at the proximal RCA. Intravascular ultrasound (IVUS) showed absence of stent struts around the orifice of aneurysm, which suggested a fracture of SES stent. The entry of coronary aneurysm was finally sealed with a polytetrafluoroethylene-covered stent. This report documented a rare case of late giant coronary artery aneurysm associated with a fracture of SES.     

A case of jejunal gastrinoma diagnosed by percutaneous transhepatic portal venous sampling

A 63-year-old male was admitted to our department for further examination of hypergastrinemia. Secretin provocation test and calcium infusion test suggested Zollinger-Ellison syndrome and percutaneous transhepatic portal venous sampling (PTPVS) demonstrated gastrinoma in the jejunum, although CT, ultrasonography and angiography could not accurately detect the location of the gastrinoma. Laparatomy findings showed a solid tumor 1.5 cm in diameter in the jejunal mesentery 5 cm distal to the ligament of Treitz, and primary gastrinoma was confirmed in the submucosa of the jejunum immediately adjacent to this tumor. An immunohistochemical study using the PAP method revealed gastrin secreting cells in the tumor. In addition to this case of jejunal gastrinoma, a review of literature in Japan and other countries was presented.     

Left Atrial Contribution to Left Ventricular Filling in Patients with Mitral Stenosis: Combined Analysis of Transmitral and Pulmonary Venous Flow Velocities

We recorded transmitral and pulmonary venous flow velocities using transthoracic continuous-wave and transesophageal pulsed Doppler echocardiography, respectively, in 36 patients with mitral stenosis who were in sinus rhythm to investigate the left atrial contribution to left ventricular filling in mitral stenosis. The mitral valve area was determined by transthoracic two-dimensional short-axis echocardiography. Patients were classified as having mild stenosis (± 1.5 cm², n = 17) or moderate stenosis (< 1.5 cm², n = 19). The mean pulmonary capillary wedge pressure and left atrial maximal diameter were significantly larger, and left atrial volume change during atrial contraction was significantly smaller in the moderate group than in the mild group. The percent left atrial contribution to left ventricular filling, estimated from the transmitral flow velocity, the peak atrial systolic velocity, and the percent ratio of left atrial systolic regurgitation to left atrial filling, estimated from the pulmonary venous flow velocity, were significantly lower in the moderate group than in the mild group. The percent left atrial contribution to left ventricular filling, the peak atrial systolic velocity, and the percent ratio of left atrial systolic regurgitation to left atrial filling were positively correlated with the mitral valve area and negatively correlated with the mean pulmonary capillary wedge pressure. These results suggest that the left atrial contribution to left ventricular filling in patients with mitral stenosis in sinus rhythm decreases as the severity of valve stenosis increases, and that analysis of the atrial systolic waves of the transmitral and pulmonary venous flow velocities provides important information for evaluation of left atrial systolic performance in patients with mitral stenosis.