Additional Treatment with Fenofibrate for Patients Treated with Pitavastatin Under Ordinary Medical Practice for Hypertriglyceridemia in Japan (APPROACH-J Study).

Safety and efficacy of combination therapy of pitavastatin and fenofibrate were examined in consecutive case series with fasting serum triglycerides ≥ 150 mg/dL despite receiving pitavastatin 1 or 2 mg daily for over 2 months and additionally administered micronized fenofibrate 67 mg daily for another 4 to 16 weeks. Such low doses were selected in consideration of safety, and normal liver and renal functions were incorporated in inclusion criteria. In result, a total of 56 cases were examined. The addition of fenofibrate 67 mg to pitavastatin 1 mg/2 mg yielded a 36.8%/35.6% reduction in triglycerides and 6.4%/12.4% elevation in high-density lipoprotein cholesterol, respectively. Almost 70% of the patients achieved triglycerides <150 mg/dL. Statistically significant elevation and decrease were observed in high-density lipoprotein cholesterol level and low-density lipoprotein cholesterol, respectively. Laboratory tests for liver, renal and muscle function statistically significantly elevated after starting fenofibrate co-administration, which were considered comparable to the effect of fenofibrate alone. No myopathy or serious adverse events were reported. In conclusion, while the safety and tolerability need to be further examined over the longer term, and careful monitoring is still needed, this regimen could be considered as one of the treatment option for hypercholesterolemia associated with hypertriglyceridemia.

Protective effects of EGCg or GCg, a green tea catechin epimer, against postischemic myocardial dysfunction in guinea-pig hearts.

The protective effects of (-)-epigallocatechin-3-gallate (EGCg) or the C-2 epimer, (-)-gallocatechin-3-gallate (GCg), afforded by their antioxidative activity among green tea catechins were investigated in perfused guinea-pig Langendorff hearts subjected to ischemia and reperfusion. The recovery (%) of the left ventricular developed pressure from ischemia by reperfusion was 34.4% in the control, while in the presence of EGCg (3x10(-5) M) or GCg (3x10(-6) M, a more diluted concentration than that of EGCg), it led to a maximal increase of 78.4% or 76.2%, consistent with a significant preservative effect on the tissue level of ATP at the end of ischemia or reperfusion. In the perfused preparation of mitochondria, EGCg (10(-5) M) inhibited mitochondrial Ca(2+) elevation by changes in the Ca(2+) content or the acidification of perfusate, similarly to findings with cyclosporin A, a well known inhibitor of the mitochondrial permeability transition pore. By in vitro electron paramagnetic resonance (EPR), EGCg or GCg was found to directly quench the activity of active oxygen radicals, with the strongest activity in tea catechins. EGCg or GCg decreased the caspase-3 activity induced apoptosis. Therefore, it is concluded that the beneficial effects of EGCg or GCg play an important role in ischemia-reperfusion hearts in close relation with nitric oxide (NO), active oxygen radicals and biological redox systems in mitochondria.

Positive inotropic effect of purified green tea catechin derivative in guinea pig hearts: the measurements of cellular Ca2+ and nitric oxide release.

Each individual and pure catechin isolated from green tea was investigated as to its myocardial or blood pressure effects. The nitric oxide (NO) electrode and fluorometry were used to monitor changes in the NO and Ca(2+) contents of the heart, together with simultaneous recordings of the left ventricular developed pressure. The low dose of (-)-epigallocatechin-3-gallate (EGCg: 10(-6), 10(-5 )M) increased the left ventricular developed pressure with elevation of the transient fura-2 Ca(2+) signal (T(Ca)), but the high dose of EGCg (10(-4 )M) produced a maximum left ventricular developed pressure with decreases in the basal level of T(Ca) in a manner similar to the administration of the Ca-sensitizer pimobendan. However, the level of the transient NO signal (T(NO)) increased dose-dependently without any increases in the width of T(NO). In the isolated right atria, the contractile force of (-)-gallocatechin-3-gallate (GCg) at 10(-8)-10(-4 )M produced the highest pD(2) value, 6.7, in catechins (EGCg: 5.2, pimobendan: 5.1), but did not affect the heart rate. GCg, an artifact due to the epimerization of EGCg during the heating procedure, showed the most prolonged hypotensive effect in rabbits among the catechins. Each catechin (GCg or EGCg), like the NO donor, may have a therapeutic use as an NO-mediated vasorelaxant and may have an additional protective action in myocardial ischemia-reperfusion induced injury.

A role of anti-verotoxin antibody immunoreactive peptide, Virp5, from rat spinal cord.

An anti-verotoxin 2 (VT2) antibody immunoreactive 5-kDa polypeptide (Virp5), has been obtained through screening of the rat spinal cord cDNA library with the aid of anti-VT2 antibody. Virp5 was mainly expressed in the central nervous system, liver and kidney, and localized at glia-like cells and nerve fibers in the central nervous system, vascular endothelial cells and hepatic cells in the liver, as well as epithelial cells of distal tubules in the kidney. Intravenous administration of purified Virp5 elicited a dose-dependent increase in blood pressure. These results suggest that Virp5 commonly exists in the body, being partly playing a role in regulating the blood pressure.

Primary lymphoma of the heart: case report and literature review.

Primary cardiac lymphoma (PCL) is a rare and usually fatal neoplasma. A case of PCL in a 78-year-old man who complained of exertional dyspnea and peripheral edema is presented. Echocardiography revealed a mass in the right atrium and a diagnosis of low-grade B-cell lymphoma was obtained with the surgically resected tumor. The lesion appeared to have originated in the right atrium and involved the right ventricle. The patient died of bronchopneumonia 8 months after the initial consultation. The present case and 39 patients with PCL reported between 1995 and 2002 were reviewed. Forty patients showed various and non-specific symptoms such as dyspnea, edema, arrhythmia and pericardial effusion. Primary cardiac lymphoma occurred slightly more often in male patients (M : F = 23:17) and in the elderly in general (mean age, 67 years), with lesions found in the following locations, listed in order of frequency: right atrium, pericardium, right ventricle, left atrium, left ventricle, and other sites. Antemortem diagnosis was obtained in 37 of the 40 patients. Thirty-seven cases were of B-cell lineage and two cases were of T-cell lineage. Complete remission was obtained in only 15 of the 40 patients. Although PCL antemortem diagnoses have been made in the majority of recent cases, the prognosis still remains poor.

Prognostic significance of heart rate variability in centenarians.

We studied the significance for further survival of heart rate variability and other variables in the very elderly. In 1992, we assessed activities of daily living, cognitive function, and nutritional status in 27 centenarians with no disease, in addition to the power of the heart rate variability in the ultralow, very low, low (LF), and high frequency (HF) bands. In 1996, we assessed survival in these centenarians; 17 had died and 10 were still living. Logistic regression analysis using backward elimination detected three factors, dementia, LF/HF, and age, that independently influenced mortality. Mortality risk increased with greater age in 1992, more severe dementia, or lower LF/HF. Sympathetic nerve activity, represented as LF/HF, may be associated with prognosis for survival in centenarians.