Seiichiro Saegusa

Interleukin-6-Induced Reciprocal Expression of SERCA and Natriuretic Peptides mRNA in Cultured Rat Ventricular Myocytes

We investigated the effect of interleukin-6 (IL-6) expression on sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) mRNA levels in cultured rat neonatal ventricular myocytes. IL-6 plays a key role in regulating cardiac hypertrophy and the development of heart failure, and SERCA, ANP and BNP are all cardiac hormones with regulatory properties. Compared with baseline measurements, treatment with 50 U/ml IL-6 significantly decreased SERCA gene expression, but significantly increased ANP and BNP gene expression in the cardiac myocytes. These results suggest that the clinical overproduction of IL-6 in response to infection, autoimmune disease and cancer might be responsible for cardiac hypertrophy. Cardiac hypertrophy may result from the imbalance of both natriuretic peptides and SERCA transciption levels, caused by elevated IL-6 expression.

Adiponectin, T-cadherin and Tumour Necrosis Factor-α in Damaged Cardiomyocytes from Autopsy Specimens

This study determined the presence of adiponectin, T-cadherin (an adiponectin receptor) and tumour necrosis factor-α (TNF-α) in damaged myocytes from autopsied patients with acute or old myocardial infarction (MI) or dilated cardiomyopathy (DCM), using immunohistochemical staining. The enrolled patients included eight with acute MI, six with old MI and seven with DCM. Four autopsied individuals with no cardiac lesions were also enrolled as controls. Adiponectin and TNF-α were not observed in normal myocytes from control subjects, but T-cadherin was weakly detected. Immunoreactivity for adiponectin and T-cadherin was observed at the periphery of damaged myocytes from MI and DCM patients; intracellular reactivity for TNF-α was also seen. There were no statistically significant differences in the degree of reactivity for each molecule in the myocytes between the MI and DCM patients. These results suggest that the presence of adiponectin and TNF-α in damaged myocytes may contribute to the processes of myocardial injury occurring in MI and DCM.

Adiponectin Replacement Therapy Attenuates Myocardial Damage in Leptin-deficient Mice with Viral Myocarditis

The effects of adiponectin replacement therapy on myocardial damage were studied in leptin-deficient (OB) mice with acute viral myocarditis. Encephalomyocarditis virus was injected intraperitoneally into OB and wild-type (WT) mice. One subgroup of OB mice received no intervention and another subgroup received daily adiponectin replacement, simultaneously with viral inoculation. Differences in heart weight, cardiac histological score, numbers of infiltrating or apoptotic cells in the myocardium and the immunoreactivity of adiponectin receptors in myocytes were determined. The reactivity of adiponectin receptor 1 in myocytes from OB mice on day 4 and day 8 after viral inoculation was significantly decreased compared with that in myocytes from WT mice; the OB mice also had elevated cardiac weights and severe inflammatory myocardial damage. Adiponectin replacement in OB mice inhibited the development of severe myocarditis by augmenting myocyte adiponectin receptor 1 reactivity. Exogenously administered adiponectin may inhibit the progression of viral myocarditis through binding to the adiponectin receptor 1 in leptin-deficient conditions.

Effect of the Serotonin Blocker Sarpogrelate on Circulating Interleukin-18 Levels in Patients with Diabetes and Arteriosclerosis Obliterans

We aimed to evaluate the effect of treatment with sarpogrelate, a serotonin 2A receptor antagonist, on circulating interleukin (IL)-18 levels in patients with diabetes and arteriosclerosis obliterans. Patients received sarpogrelate (100 mg 3 times daily) for 2 months. We evaluated the degree of cryaesthesia (a feeling of cold in the foot and toes) as the clinical outcome, and measured circulating IL-18, IL-6 and lipid protein concentrations. An improvement in clinical outcome occurred after initiation of sarpogrelate therapy;a significant decrease in IL-18 levels was observed after 2 months of therapy. Levels of IL-6 and lipid proteins, including triglyceride, total cholesterol and high-density lipoprotein cholesterol, were not significantly altered by treatment. Our data suggest that by reducing circulating IL-18 levels, sarpogrelate treatment may contribute to the inhibition of arteriosclerosis obliterans progression in patients with diabetes.

Effect of Hochu-ekki-to (TJ-41), a Japanese Herbal Medicine, on Daily Activity in a Murine Model of Chronic Fatigue Syndrome

We aimed to evaluate the effect of a Japanese herbal medicine, Hochu-ekki-to (TJ-41), on daily activity in a murine model of chronic fatigue syndrome (CFS). CFS was induced by repeated injection of Brucella abortus (BA) antigen every 2 weeks. TJ-41 was orally administered to mice in a dose of 500 mg/kg/day for 1 week before injecting BA and for 4 weeks thereafter. We evaluated daily running activity in mice receiving TJ-41 as compared with that in untreated mice. Survival of both mouse groups was also monitored during the observation period. Body weight (BW), spleen weight (SW), SW/ BW ratio and expression levels of interleukin-10 (IL-10) mRNA in spleen were determined in both groups at the time of sacrifice. The daily activity was significantly higher in the treated group than in the control. Two mice in the untreated group died 2 days after the second injection of BA, whereas no mice in the group treated with TJ-41 died. The SW and SW/BW ratio were significantly lower in the treated mice than in the control. Suppressed IL-10 mRNA levels were observed in the spleens of the mice treated with TJ-41. Our data suggest that Hochu-ekki-to might possess an inhibitory effect on the marked decrease in running activity following BA injection.

Panic attack symptoms in a patient with left temporal lobe epilepsy.

We describe a 56-year-old woman with left temporal lobe epilepsy who developed symptoms of a panic attack. Owing to normal electroencephalography and brain magnetic resonance imaging results, she was initially diagnosed as suffering from panic attacks and treated for anxiety neurosis. The symptoms persisted and she was re-examined in our department. An interictal electroencephalogram showed paroxysmal spike waves in the left mesial temporal lobe region and this was the basis for a diagnosis of left temporal lobe epilepsy. This report suggests that left temporal lobe epilepsy should be considered as the differential diagnosis when patients frequently complain of fear or anxiety.