Influence of food on plasma concentration of mycophenolic acid in a heart transplant patient receiving concomitant tacrolimus.
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Biomedical subjects
Publications and source records attributed to Naoki Matsuda.
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Pimobendan, an oral inotropic drug with phosphodiesterase III-inhibitory activity, induces cAMP-dependent relaxation of vascular smooth muscle in the pulmonary artery, as well as in the systemic cardiovascular system. We report here a patient with severe primary pulmonary hypertension (PPH), who had developed right heart failure (New York Heart Association functional class IV) despite uptitrated intravenous epoprostenol, and who was treated with extremely low-dose (0.625-1.25 mg daily) pimobendan as an adjunct to prostacyclin therapy. The combination therapy of low-dose pimobendan, prostacyclin, intravenous epoprostenol and oral beraprost has been continued for over 2 years without occurrence of fatal arrhythmia, and her six-minute walk test has exceeded 400 m. We suggest that low-dose pimobendan may enhance the hemodynamic effect of prostacyclin in severe PPH.
Brain natriuretic peptide (BNP) is a powerful neurohormonal marker of left ventricular function and prognosis. Amiodarone either has no effect or improves the haemodynamics in patients with left ventricular dysfunction, but its effect on BNP is unknown. This study evaluated the effect of amiodarone on plasma BNP level in patients with heart failure and ventricular tachyarrhythmia. Plasma BNP level was studied in 46 patients with heart failure ventricular tachyarrhythmia, before (baseline) and at week 2 and months 1, 3 and 6 of amiodarone treatment. In addition, 21 patients with heart failure and ventricular tachyarrhythmia, who received an implantable cardioverter defibrillator, but not amiodarone, were studied on the same schedule. All patients had previously received potent vasodilator and beta-blocker therapy. Echocardiography and Holter monitoring were also performed. Amiodarone significantly decreased plasma BNP levels at week 2 to month 6 during therapy. Heart rates and frequencies of premature ventricular complexes were markedly reduced by amiodarone. Echocardiographic findings did not show a change in left ventricular end-diastolic dimensions, despite a slight increase in fraction shortening at month 6 during amiodarone therapy. The above parameters showed no change in patients without amiodarone. The effect of heart rate, premature ventricular complexes, fraction shortening, serum creatinine or thyroid stimulating hormone level was not significantly associated with decrease in BNP level during amiodarone therapy by a multivariate analysis. Among amiodarone-treated patients, mortality was higher in 24 with BNP levels >/=100 pg/ml at month 6 than in 22 with BNP levels <100 pg/ml during a mean follow-up period of 31 months. Amiodarone appears to have a decreasing effect on plasma BNP level, as well as an antiarrhythmic effect, in patients with heart failure and ventricular tachyarrhythmia.
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Slab optical waveguide (SOWG) spectroscopy was used to observe the adsorption behavior of three important heme proteins, namely cytochrome c, myoglobin and hemoglobin, in a quartz surface. Using prism-coupled polychromatic visible light propagated into a quartz waveguide by internal total reflection, the real-time monitoring of evanescent wave absorption revealed a strong dependence of the protein-surface interaction on the protein concentration, the solution pH and the ionic strength. For the three proteins studied, the absorbance-bulk concentration ratio was higher at low bulk concentrations, and decreased at higher concentrations. For cytochrome c and myoglobin, the absorbance approached a limiting value, but buffered hemoglobin surprisingly did not show any indication of forming a signal plateau. Moreover, the slow introduction of protein into the solution lessened the total adsorbed amount per unit area. These observations suggested a possible conformational transition of the protein molecules at the quartz surface after adsorption. For a bulkier protein, hemoglobin, adsorption onto the quartz surface was enhanced in the presence of a phosphate buffer, while the opposite effect was observed for the smaller cytochrome c and myoglobin molecules. The results of pH studies concurred with the electrostatic interactions predicted from the isoelectric data of proteins and the quartz surface.
DNA and gold nanoparticles are co-immobilized at a gold electrode through elaborate self-assembly processes. This configuration has proven to be useful as a sensor for phenothiazine drugs, taking advantage of the well-known, relatively large surface area of gold nanoparticles and the strong intercalation between dsDNA and phenothiazine drugs. This modified electrode has demonstrated good sensitivity and stability towards the oxidation of two model phenothiazine drugs: promethazine and chlorpromazine. A linear dependence between the concentration of phenothiazine drugs and the peak current is observed, with a concentration range of 2.0 x 10(-5)-1.6 x 10(-4) M and 1.0 x 10(-5)-1.2 x 10(-4) M, and a detection limit of 1.0 x 10(-5) M and 7.0 x 10(-6) M, for promethazine and chlorpromazine, respectively.
OBJECTIVES: Nonischemic heart disease, especially idiopathic dilated cardiomyopathy, is relatively common among Japanese patients receiving amiodarone for concomitant ventricular arrhythmia, but the hemodynamic effects of amiodarone in these Japanese patients are unclear. The hemodynamic changes during chronic amiodarone administration were retrospectively studied in patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia. METHODS: Fifty-two patients [42 males, 10 females, 53 +/- 2 years (mean age +/- SE)] with ventricular tachyarrhythmia and idiopathic dilated cardiomyopathy with left ventricular ejection fraction of 27 +/- 1% (mean +/- SE) were treated with 200-400 mg daily of oral amiodarone as the loading dose for the initial 14 days and 100-200 mg daily maintenance dose for a further 6 months. No patients were taking beta-blockers or positive inotropic drugs. Echocardiographic examination was performed before (baseline), at week 2 and at month 6 of amiodarone therapy. Twenty four-hour Holter monitoring during the same time period was also performed in 34 patients. Seventeen patients underwent right heart catheterization before and at week 2. RESULTS: Echocardiographic measurements showed no significant change in left ventricular end-diastolic dimension, although there was a slight increase in fractional shortening from 16 +/- 1% to 19 +/- 1% (p < 0.05) and 18 +/- 1% (mean +/- SE) (p < 0.01) at week 2 and month 6 of amiodarone therapy, respectively. Amiodarone markedly reduced the mean heart rate and the frequency of premature ventricular complexes on ambulatory monitoring. The cardiac index did not change and the pulmonary capillary wedge pressure tended to decrease slightly at week 2 in the 17 patients who underwent catheterization. CONCLUSIONS: This retrospective study showed no worsening of the hemodynamic state during chronic amiodarone administration in Japanese patients with idiopathic dilated cardiomyopathy and ventricular arrhythmia.
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The tissue distribution of amiodarone and desethylamiodarone, its active metabolite, was examined in an autopsied case, an 85-year-old man, with arrhythmogenic right ventricular cardiomyopathy (ARVC) who had been receiving amiodarone for 4 years. High concentrations of amiodarone, a very highly lipophilic compound, were found in adipose and bone marrow tissues. Despite a low dose (100 mg daily), the concentrations of amiodarone were higher in the epicardial fat (570.4 microg/g) and in the right atrium (165.3 microg/g) than previously reported in patients with other cardiac diseases. The ratios of amiodarone/ desethylamiodarone concentrations in both tissues were >1. This unique distribution demonstrates the involvement of histological characteristics of ARVC, such as fatty replacement of myocardium. We anticipate that a low dose of amiodarone would be effective in preventing arrhythmia in some patients with ARVC.
Pimobendan is an inotropic and vasodilating drug with phosphodiesterase (PDE) III-inhibiting and calcium-sensitizing effects. It may also have a bronchodilatory effect by inhibiting PDE III in airway smooth muscle. We tried a beta-blocker combined with low-dose pimobendan in 2 patients who had refractory heart failure of NYHA functional class III or IV with idiopathic dilated cardiomyopathy (DCM) and chronic obstructive pulmonary disease (COPD). Both of them had previously failed to tolerate beta-blocking drugs because of the exacerbation of bronchospasm. After pimobendan was administered at 1.25 to 2.5 mg daily, metoprolol could be successfully introduced from a low dose of 1.25 mg daily without decreasing the peak expiratory flow rate. Over the next 1 to 2 years, they have continued beta-blocker therapy. One is currently receiving 10 mg daily of bisoprolol and another is taking 15 mg daily of metoprolol, and both are in NYHA functional class II without worsening heart failure or COPD. The combination of beta-blocker with low-dose pimobendan may be helpful for patients with DCM and COPD, but further clinical investigation is required.
The efficacy of enamel matrix derivative (EMD) as an adjunct to periodontal regenerative therapy has been demonstrated in recent clinical studies, however, little is known about its molecular mechanism (s). We examined the mitogenic response of cultured periodontal ligament (PDL) cells to EMD and characterized associated changes in proliferation-related intracellular signaling molecules, including mitogen-activated protein kinases (MAPK) and Akt kinases/protein kinase B (Akt/PKB) kinases. The DNA synthesis of PDL cells increased following treatment with EMD at concentrations higher than 1 microg ml(-1). This mitogenic response to EMD was associated with the selective activation of extracellular signal-regulated kinase (ERK) 1/2. No other MAPKs, or Akt/PKB kinases, responded to EMD stimulation. The EMD induction of DNA synthesis and activation of ERK 1/2 were diminished by pretreatment with suramin, an inhibitor of receptor tyrosine kinases (RTK). The signaling pathway induced by EMD from RTK to ERK 1/2 was similar to that activated by epidermal growth factor (EGF), although the specific binding of 125I-EGF to PDL cells was not affected by pretreatment or concomitant treatment with EMD. These findings suggest that EMD elicits its mitogenic signal through an EMD-specific RTK towards ERK 1/2.
In this paper, a poly(vinyl chloride) (PVC) membrane electrode is prepared for gemfibrozil, 2, 2-dimethyl-5-(2,5-xylyloxy) valeric acid, based on its ion pair complexes with hexadecyltrioctyl ammonium iodide (HTOA). The membrane composition of the electrode was optimized by using the sequential level elimination method for orthogonal experimental design. The electrode has a Nernstian response range from 2.5 x 10(-5) to 0.1 mol/l with an average slope of 55.3 mV/decade. The limit of detection is 7.1 x 10(-6) mol/l. The electrode responses were not affected by pH in the range 10.0-12.3. A Na2B4O7-Na2CO3 buffer of pH = 11.0 was selected as the background electrolyte solution for potentiometric measurements. The electrode was used for determining gemfibrozil in pharmaceutical preparations with satisfactory results.
The efficacy and safety of amiodarone in the management of atrial fibrillation (AF) or flutter in 108 Japanese patients with heart failure was retrospectively examined. Thirty-four (41%) of the 82 patients who were in sinus rhythm after 1 month of amiodarone administration had their first recurrence, 70% of cases occurring within 1 year of initiation. The cumulative rates of maintenance of sinus rhythm were 0.68, 0.55, and 0.47 at 1, 3, and 5 years, respectively. Amiodarone was more effective in maintaining sinus rhythm in patients with paroxysmal AF or flutter than in those with the persistent form (p<0.05). The cumulative rates for cases that remained in permanent AF were 0.04, 0.11, and 0.14 at 1, 3, and 5 years, respectively. Apart from suppressing AF, the mean heart rate during Holter monitoring was significantly decreased with amiodarone therapy in cases of permanent AF. Adverse effects requiring the discontinuation of amiodarone therapy occurred in 16% of patients. Low-dose amiodarone therapy may prevent AF or flutter in Japanese patients with heart failure.
OBJECTIVES: Nifekalant is a class III antiarrhythmic drug, which prolongs the refractory period of the atrial and ventricular myocardium, without negative inotropic action. Intravenous nifekalant was administered in four patients with atrial tachyarrhythmia and severe heart failure to terminate or prevent atrial tachyarrhythmia. METHODS AND RESULTS: Two of three episodes of atrial tachyarrhythmia were terminated by intravenous nifekalant (0.22 to 0.30 mg/kg) administration. Continuous intravenous infusion of nifekalant (0.15 to 0.40 mg/kg/hr) during six episodes to maintain the sinus rhythm, prevented recurrence of atrial tachyarrhythmia in five episodes in which prolongation of the QTc interval was observed to more than 450 msec. None of the patients showed worsening of the hemodynamics during treatment. One patient developed polymorphic ventricular tachycardia, which deteriorated into ventricular fibrillation. CONCLUSIONS: Nifekalant may be effective for treating atrial tachyarrhythmia in patients with severe heart failure. Further clinical studies are needed to confirm these findings.
Arrhythmogenic right ventricular cardiomyopathy (ARVC), also known as arrhythmogenic right ventricular dysplasia, is a disorder of the heart muscle of unknown origin. It is characterized by electrical instability of the heart as a result of replacement of the right ventricular myocardium with fatty or fibrous fatty tissue. Dilatation of the right ventricle; fatty tissue in conspicuous trabeculae of the right ventricle, especially in the anterior wall, apex, and inferior (diaphragmatic) wall; and a scalloped appearance (bulging) of the right ventricular wall are characteristic findings at helical computed tomography (CT) that may be used to diagnose ARVC. Fatty tissue in the left ventricle and ventricular septum is seen relatively frequently in ARVC, and fat in the ventricular septum is another useful finding for diagnosis of ARVC with helical CT. ARVC is usually diagnosed on the basis of clinical or pathologic findings, and electron-beam CT is superior to nongated helical CT in assessment of abnormal right ventricular function. However, with knowledge of the characteristic findings, standard nongated helical CT can be helpful in diagnosing ARVC.