Metformin induces up-regulation of blood-brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells.

Blood-brain barrier (BBB) disruption occurs frequently in CNS diseases and injuries. Few drugs have been developed as therapeutic candidates for facilitating BBB functions. Here, we examined whether metformin up-regulates BBB functions using rat brain microvascular endothelial cells (RBECs). Metformin, concentration- and time-dependently increased transendothelial electrical resistance of RBEC monolayers, and decreased RBEC permeability to sodium fluorescein and Evans blue albumin. These effects of metformin were blocked by compound C, an inhibitor of AMP-activated protein kinase (AMPK). AMPK stimulation with an AMPK activator, AICAR, enhanced BBB functions. These findings indicate that metformin induces up-regulation of BBB functions via AMPK activation.

Rhabdomyolysis associated with antimicrobial drug-resistant Mycoplasma pneumoniae.

We describe a case of rhabdomyolysis in a patient infected with antimicrobial drug-resistant Mycoplasma pneumoniae The patient's acute-phase serum levels of interleukin-18 and tumor necrosis factor-α were high, which suggests a pathogenic role for M. pneumoniae. In an era of increasing antimicrobial drug resistance, a system for rapidly identifying resistant M. pneumoniae would be beneficial.

Clinical implications of interleukin-18 levels in pediatric patients with Mycoplasma pneumoniae pneumonia.

The immunological pathogenesis of Mycoplasma pneumoniae pneumonia is known to involve several cytokines. The serum levels of interleukin-18 (IL-18) were examined using enzyme-linked immunosorbent assay in 23 pediatric patients (median age 6 years; range 4-13 years; 14 girls and 9 boys) with M. pneumoniae pneumonia admitted to our hospital. Serum levels of IL-18 ranged from 22 to 1808 pg/ml with a mean of 543 pg/ml. We started steroid therapy in two cases with IL-18 values greater than 1000 pg/ml without being aware of IL-18 levels. Examination of associations between IL-18 levels determined by enzyme-linked immunosorbent assay and a routine laboratory test showed that levels of lactate dehydrogenase (LDH) and IL-18 were significantly correlated. To determine the appropriateness of steroid administration in M. pneumoniae pneumonia patients, serum LDH should be examined. Patients with elevated levels of LDH are likely to have significantly elevated IL-18 values (≥1000 pg/ml) and thus can be candidates for steroid therapy.

Clinical features in adults with coronary arterial lesions caused by presumed Kawasaki disease.

There exists a population of adults with undiagnosed coronary arterial lesions due to Kawasaki disease occurring before 1967. We report the clinical features in 6 adult males with coronary arterial lesions caused by presumed Kawasaki disease, whose dates of birth ranged from 1945 to 1963. The age of the diagnosed coronary arterial lesions due to presumed Kawasaki disease ranged from 26 to 48 years. In 4 patients, there was a history of probable Kawasaki disease. The presenting features were chest pain in 2; syncope in 1, an abnormal electrocardiogram in 2; a history of presumed Kawasaki disease in 1, and symptomatic myocardial infarction in the final patient. Coronary angiograms revealed multi-vessel disease in 5 patients, with segmental stenosis in 5, and calcified giant aneurysms in the proximal portion of the coronary arteries also in 5. Low left ventricular ejection fractions of less than 40% were found in 3. Of the patients, 3 had undergone coronary arterial bypass grafting. A defibrillator had been implanted in 2 because of rapid ventricular tachycardia with syncope induced during electrophysiologic studies. We conclude that, in patients with multi-vessel disease or left ventricular dysfunction caused by presumed Kawasaki disease, symptoms and serious cardiac events occur in adult life with the onset of ageing, although the patients had been asymptomatic for many years after the onset of Kawasaki disease itself.