Age-associated cardiomyopathy in heterozygous carrier mice of a pathological mutation of carnitine transporter gene,OCTN2

The purpose of this study was to test whether heterozygotes of juvenile visceral steatosis mice, a model for systemic carnitine deficiency, may develop age-associated cardiomyopathy. Tissue morphological observations were carried out by light and electron microscopy to compare the heterozygous and age-matched control mice at periods of 1 and 2 years. Possible effects of the pathological mutation on lipid and glucose levels was also evaluated in humans and mice. Except mild increases in serum cholesterol levels in male heterozygous mice and humans, no changes were found in other factors, indicating that none of the confounding factors seems to be profound. Results demonstrated that heterozygous mice had larger left ventriclular myocyte diameters than the control mice. Morphological changes in cardiac muscles by electron microscopy revealed age-associated changes of lipid deposition and abnormal mitochondria in heterozygous mice. Two out of 60 heterozygous cohort and one out of nine heterozygous trim-kill mice had cardiac hypertrophy at ages older than 2 years. The present study and our previous work suggest that the carrier state of OCTN2 pathological mutations might be a risk factor for age-associated cardiomyopathy.     

A mitochondrial superoxide theory for oxidative stress diseases and aging

Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed ”the Superoxide Theory,” which postulates that superoxide (O₂^•−) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q₁₀) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich’s seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.     

Early and Long-Term Outcomes in Japanese Patients Aged 80 Years or Older Undergoing Conventional Aortic Valve Replacement

In this study, we investigated the early and long-term results of conventional aortic valve replacement (AVR) in very old patients.Methods: Seventy-five patients with aortic stenosis underwent conventional AVR for patients aged 80 years.We examined early death and major adverse cardiovascular and cerebrovascular event (MACCE).Results: The operative mortality was 0% for isolated AVR and 19.2% for concomitant surgery. The postoperative survival rate and MACCE free-rate were no significant differences between the isolated AVR and the concomitant surgery. Univariate analysis confirmed that cardiac dysfunction, severe chronic kidney disease (CKD), hemodialysis, + coronary artery bypass grafting, and norepinephrine use were risk factor of early death. Univariate analysis confirmed that severe CKD, BNP >1000 pg/ml, aortic cross clamping time (ACCT) >180 min, and non-use carperitide and multivariate analysis confirmed that ACCT >180 min, and non-use carperitide were risk factor of MACCE.Conclusions: This study showed that the results of conventional AVR in very old patients were not satisfactory. However, the results obtained with isolated AVR were favorable with no operative deaths. The present study demonstrated that preoperative cardiac function, preoperative renal function, and operative factors have an important impact on early mortality and MACCE.     

HLA-B52-positive vasculo-Behçet disease: usefulness of magnetic resonance angiography, ultrasound study, and computed tomographic angiography for the early evaluation of multiarterial lesions

We report a case of HLA-B52-positive Behçet disease accompanied by multiarterial lesions. A 24-year-old woman was suffering from sporadic high fever and recurrent oral and genital ulcers, and laboratory data revealed severe inflammation. A diagnosis of Behçet disease was made. Magnetic resonance angiography, ultrasound study, and computed tomographic angiography demonstrated multiarterial lesions that had caused no symptoms. These noninvasive examinations were extremely useful in evaluating asymptomatic early vascular lesions.