Metoprine, a histamine N-methyltransferase inhibitor, attenuates methamphetamine-induced hyperlocomotion via activation of histaminergic neurotransmission in mice.

Metoprine increases the content of histamine in brain by inhibiting histamine N-methyltransferase (HMT), a centrally acting histamine degrading enzyme. We present data demonstrating that pretreatment with metoprine attenuates the hyperlocomotive effects of METH in mice using a multi-configuration behavior apparatus designed to monitor four behavioral outcomes [horizontal locomotion, appetitive behavior (food access), and food and water intake]. Metoprine pretreatment itself induced hyperlocomotion in mice challenged with saline during the large part of light phase. The trend was also observed during the following dark phase. This is the first report that metoprine has a long-lasting locomotor stimulating property. Similarly, in a tail suspension test, a single injection of metoprine significantly reduced total time of immobility in mice, consistent with the idea that metoprine possesses motor stimulating properties. Metoprine pretreatment did not affect other aspects of behavior. Metoprine did not affect the appetitive and drinking behavior while exerted an effect on stereotypy. No stereotyped behavior was observed in mice pretreated with vehicle followed by METH, while stereotyped sniffing was observed in mice pretreated with metoprine followed by METH. The metoprine pretreatment attenuated METH-induced hyperlocomotion during the first 2 h of light phase, suggesting that metoprine-induced locomotor stimulating property might be different from that of METH. The hypothalamic content of histamine (but not its brain metabolite) was increased after metoprine or METH administration. Both METH and metoprine reduced dopamine and histamine turnover in the striatum and the nucleus accumbens and the hypothalamus, respectively, and there is a significant metoprine pretreatment x METH challenge interaction in the histamine turnover. It is likely that metoprine may attenuate METH-induced hyperlocomotion via activation of histaminergic neurotransmission. Metoprine also might induce a long-lasting locomotor stimulating effect via a putative mechanism different from that whereby METH induces the locomotor stimulating effect.

Characterization of the biliary tract by virtual ultrasonography constructed by gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging.

PURPOSE: This study aimed at prospectively evaluating bile duct anatomy on ultrasonography and evaluating the safety and utility of radiofrequency ablation (RFA) assisted by virtual ultrasonography from gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI). METHODS: The institutional review board approved this study, and patients provided written informed consent prior to entry into the study. Bile duct anatomy was assessed in 201 patients who underwent Gd-EOB-DTPA-enhanced MRI for the evaluation of hepatic tumor. Eighty-one of these patients subsequently underwent RFA assisted by ultrasound imaging. In 23 patients, the tumor was located within 5 mm of the central bile duct, as demonstrated by MRI. RESULTS: Virtual ultrasonography constructed by Gd-EOB-enhanced MRI was able to visualize the common bile duct, left hepatic duct, and right hepatic duct in 96.5, 94.0, and 89.6 % of cases, respectively. The target hepatic tumor nodule and biliary duct could be detected with virtual ultrasonography in all patients, and no severe complications occurred. CONCLUSION: The running pattern of the bile ducts could be recognized on conventional ultrasound by referencing virtual ultrasonography constructed by Gd-EOB-DTPA-enhanced MRI. RFA assisted by this imaging strategy did not result in bile duct injury.

Risk of hypervascularization in small hypovascular hepatic nodules showing hypointense in the hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with chronic liver disease.

PURPOSE: The purpose of this study was to elucidate the incidence and risk factors for the progression of hypointense nodules observed in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) of hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Hypovascular nodules (112) showing hypointensity in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were examined in 54 patients. All patients underwent computed tomography during hepatic arteriography and computed tomography during arterial portography (CTAP) within a month after Gd-EOB-DTPA-enhanced MRI. According to the tumor size, 112 nodules were divided into two groups: those >10 mm in diameter (group A, n = 39) and those ≤10 mm in diameter (group B, n = 73). The incidence of progression to hypervascular HCC was calculated using the Kaplan-Meier method. RESULTS: The incidence of hypervascularization was significantly higher in group A nodules than in group B nodules (p < 0.0001). Tumor size (p < 0.0001) and hypoattenuation in CTAP (p = 0.0004) showed significant correlation with hypervascularization. CONCLUSION: Hypointense nodules observed in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI with diameters of >10 mm had a high probability of hypervascularization.