For 2 years we administered high doses of coenzyme Q10 (CoQ) to a patient having mitochondrial encephalomyopathy with cytochrome c oxidase deficiency. Abnormal elevation of the serum lactate per pyruvate ratio and the increased concentration of serum lactate plus pyruvate induced by exercise decreased with CoQ treatment. This therapeutic effect continued for 2 years. 31P nuclear magnetic resonance spectroscopy showed acceleration of the postexercise recovery of the ratio of phosphocreatine to inorganic phosphate in muscle during CoQ treatment. These observations support the beneficial effect of CoQ on the impaired mitochondrial oxidative metabolism in muscle. Also, impaired central and peripheral nerve conductivities consistently improved during CoQ treatment. These results indicate that CoQ has clinical value in the long-term management of patients with mitochondrial encephalomyopathies, even though there are clinical limitations to the effects of this therapy.

Mitochondrial abnormalities and effectiveness of replacement therapy were examined in a murine model of systemic carnitine deficiency, namely the juvenile visceral steatosis (JVS) mouse. Homozygous JVS mice revealed severe lipid deposition and abnormal mitochondria in liver, heart, skeletal muscle, and kidney, but there was no pathological change in the nervous system, though they showed cerebral signs. There were numerous ragged-red fibers in muscles, but enzyme activities of the respiratory chain were intact. Histograms of oxidative and non-oxidative muscle fibers showed an increase in small and oxidative muscle fibers in 4-week-old JVS mice, but this difference no longer existed in 8-week- or 1-year-old JVS mice. On the contrary, Mn-superoxide dismutase immunostaining of muscle showed a focal increase in every age of JVS mice. With L-carnitine treatment, JVS mice could survive for a year, but to some extent, there were the same pathological changes as those seen in untreated mice.

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Background Presepsin, a subtype of soluble CD14, is an inflammatory marker, which largely reflects monocytic activation. Presepsin appears to be an accurate diagnostic marker of sepsis, but its clinical significance remains unclear in cardiovascular disease. Purpose This prospective study aimed to investigate the predictive value of plasma presepsin levels on admission to medical (non-surgical) cardiac intensive care units (MCICUs) for short-term mortality. Methods We examined 1560 patients hospitalized in MCICUs and measured the baseline plasma presepsin levels at admission. Results Acute coronary syndrome was present in 46% of the patients, and acute decompensated heart failure in 36%. Before MCICUs admission, emergent coronary angiography or percutaneous coronary intervention was performed in 36%, mechanical ventilation was required for respiratory insufficiency in 2.1%, and intraaortic balloon pumps were needed for hemodynamic instability in 8.9%. During 6 months after admission, there were 113 (7.2%) deaths. Patients who died were older (median: 77 vs. 71 years, P<0.0001); had higher levels of presepsin (263 vs. 119 pg/mL, P<0.0001), B-type natriuretic peptide (BNP: 696 vs. 186 pg/mL, P<0.0001), high-sensitivity troponin T (hsTnT: 81 vs. 47 pg/mL, P=0.004), and high-sensitivity C-reactive protein (13.8 vs. 2.2 mg/L, P<0.0001); and had lower levels of estimated glomerular filtration rate (50 vs. 65 mL/min/1.73m2, P<0.0001) and left ventricular ejection fraction (43% vs. 51%, P<0.0001) than those of the survivors. In the multivariate Cox regression analysis, higher levels of presepsin (P=0.0002), BNP (P=0.04), and hsTnT (P=0.009) were all independent predictors of 6-month deaths. Quartiles of presepsin levels were associated with higher mortality rates within 6 months after admission (Table). Adding presepsin levels to a baseline model that included established risk factors, BNP, and hsTnT further enhanced reclassification (P=0.004) and discrimination (P=0.003) beyond that of the baseline model. Mortality rates according to presepsin Presepsin quartile 1st 2nd 3rd 4th P value ≤80 pg/mL 81–124 pg/mL 125–232 pg/mL >232 pg/mL 1-month mortality 0.8% 2.0% 3.3% 8.0% <0.0001 6-month mortality 0.8% 3.8% 8.2% 16.3% <0.0001 Conclusions Presepsin levels at admission could improve the prediction of short-term mortality in patients hospitalized at MCICUs.