Nicorandil metabolism in rat myocardial mitochondria

The in vitro study using rats was carried out to clarify the hypothesis that nicorandil is denitrated and then may produce nitric oxide (NO) in myocardial mitochondria. In the presence of a NADPH-generating system, [14C]nicorandil, which was incubated in mitochondrial and microsomal fractions of the lung, heart, or liver, was converted to its main denitrated metabolite, SG-86 and other metabolites. Apparent Km and Vmax for nicorandil in mitochondrial and microsomal fractions of the heart were considerably similar to those of the lung, but completely different from those of the liver. It seems that glutathione-S-transferases (GSTs) are not primarily involved in the conversion of nicorandil to SG-86, because a known GST inhibitor, indomethacin, did not affect the nicorandil degradation in the mitochondrial fraction. Nitrite, the stable metabolite of NO, was measured by the Griess reaction. In the presence of an NADPH-generating system, nicorandil significantly increased nitrite production in myocardial mitochondria, but SG-86 did not. These data strongly indicate that nicorandil is metabolized to SG-86 in myocardial mitochondria, then releasing NO, and that GSTs are not primarily responsible for the conversion of nicorandil to SG-86.     

Effects of local inactivation of monkey medial frontal cortex in learning of sequential procedures.

To examine the role of the medial frontal cortex, supplementary motor area (SMA), and pre-SMA in the acquisition and control of sequential movements, we locally injected muscimol into 43 sites in the medial frontal cortex while monkeys (n = 2) performed a sequential button-press task. In this task, the monkey had to press two of 16 (4 x 4 matrix) buttons illuminated simultaneously in a predetermined order. A total of five pairs were presented in a fixed order for completion of a trial. To clarify the differential contribution of the medial frontal cortex for new acquisition and control of sequential movements, we used novel and learned sequences (that had been learned after extensive practice). We found that the number of errors increased for novel sequences, but not for learned sequences, after pre-SMA inactivations. A similar, but insignificant, trend was observed after SMA injections. The reaction time of button presses for both novel and learned sequences was prolonged by inactivations of both SMA and pre-SMA, with a trend for the effect to be larger for SMA inactivations. These findings suggest that the medial frontal cortex, especially pre-SMA, is related to the acquisition, rather than the storage or execution, of the correct order of button presses.     

Augmented acetylcholine-induced translocation of RhoA in bronchial smooth muscle from antigen-induced airway hyperresponsive rats

Acetylcholine (ACh)-induced translocation of RhoA in bronchial smooth muscle of repeatedly antigen-challenged rats that have a marked airway hyperresponsiveness (AHR) was examined. ACh induced time- and concentration-dependent translocation of RhoA to the plasma membrane, indicating an activation of RhoA in bronchial smooth muscle. The level of ACh-induced RhoA translocation was further increased markedly in the AHR group as compared to that in the control group. It is suggested that the augmented activation of RhoA observed in the hyperresponsive bronchial smooth muscle might be responsible for the enhanced ACh-induced Ca(2+) sensitization of bronchial smooth muscle contraction associated with AHR.     

External beam radiotherapy for angiographically diagnosed arteriovenous malformation involving the entire pancreas

Ultrasonography of a 66-year-old man with abdominal discomfort detected an abnormality of the pancreas. Multiphase contrast-enhanced computed tomography (CT) and angiography revealed arteriovenous malformation (AVM) involving the entire pancreas. The large number of dilated and tortuous feeding arteries contraindicated surgical resection or transcatheter embolization. Hemorrhage into the main pancreatic duct occurred 1 month after diagnosis. The patient underwent external radiotherapy with a total dose of 44 Gy following a conventional fractionation schedule of 2 Gy daily for 22 days administered 5 days per week. Contrast-enhanced CT after treatment confirmed disappearance of feeding vessels and nidi with no complication. Evidence of recurrence was not detected on contrast-enhanced CT 6 months after irradiation.     

Serum levels of matrix metalloproteinase‐13 in patients with eosinophilic fasciitis

Matrix metalloproteinase‐13 (MMP‐13), a member of the collagenase family, has been implicated in the pathogenesis of connective tissue diseases characterized by extracellular matrix remodeling. Since serum MMP‐13 levels reflect disease severity of systemic sclerosis and localized scleroderma, we evaluated the clinical significance of serum MMP‐13 levels in eosinophilic fasciitis (EF). All the EF patients had serum MMP‐13 levels lower than the mean – 2SD of healthy controls. Serum MMP‐13 levels were also significantly decreased in EF patients compared with diffuse cutaneous systemic sclerosis, limited cutaneous systemic sclerosis, and generalized morphea patients. Although serum MMP‐13 levels did not reflect any clinical and serological features of EF, these results indicate that MMP‐13 may be involved in the development of this disease.     

Rebleeding from intracranial dissecting aneurysm in the vertebral artery

We describe two patients with rebleeding from intracranial vertebral artery dissecting aneurysms during the acute stage. One patient had excellent results after emergency surgery. A review of recent reports including 60 patients with this disorder revealed a rebleeding rate of 30%, mostly during the acute stage. This suggests that a ruptured dissecting aneurysm in the vertebral artery is at risk for rebleeding during the acute stage, similar to a saccular aneurysm in the same location.