Acute myocardial infarction: comparison of results of Tl-201, Tc-99m pyrophosphate and In-111 antimyosin Fab imagings]

To evaluate the extent and characteristics of infarct areas, we performed indium-111 monoclonal antimyosin Fab (InAM), thallium-201 (TL) and Tc-99m pyrophosphate (PYP) imagings in 17 patients with acute myocardial infarction, and tried to find out the mechanism that causes difference of these imagings. In each study, the extent scores as an index of the infarct area were obtained by single photon emission computed tomography (SPECT), and comparisons were made between the results obtained. The overlap between InAM and TL imagings obtained by SPECT was evaluated. Location, severity, extent and patterns of accumulation were compared between InAM and PYP with both planar image and SPECT. The extent scores of InAM correlated well with those of TL (r = 0.73, p < 0.01). However, the overlap of both methods was recognized in 8 of 17 patients, in whom wall thickness of the infarct area as obtained by echocardiography was well preserved. The left ventricular regional asynergy was mild in 6 of these 8 patients. Coronary angiography showed poor or no collateral circulation in these cases. Although there were generally close correlations of the extent scores between InAM and PYP, discrepancy was noted in 2 cases for location; 2 for severity, 5 for extent, and 3 for patterns of accumulation. These differences may be attributed to the timings of imaging, coronary reperfusion and different mechanisms of accumulation. In conclusion, the extent of acute myocardial infarction obtained by InAM correlates well with those obtained by TL and PYP, with some exceptions.     

Molecular cloning of a novel human papillomavirus (type 60) from a plantar cyst with characteristic pathological changes.

In a plantar cyst composed of the wall of the squamous cell layer and the horny inner substance in the lower dermis, we found characteristic pathological changes, such as cytoplasmic eosinophilic inclusions and vacuolated structure, and, immunohistochemically, the papillomavirus capsid antigen. The human papillomavirus (HPV) DNA cloned from the cyst showed no homology with other known prototypes of HPV (HPV 1 through HPV 59) by Southern blot analysis under stringent conditions and was named as HPV 60. HPV 60 DNA was found in three other cases of plantar cyst with the identical pathological changes, but not in a plantar cyst without such changes. The results suggest that HPV 60 has unique biological properties to induce a plantar cyst as a distinct type of cutaneous HPV.     

Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteoclastogenic potentials in mice.

To investigate the relationship between the effects of bone turnover and bone marrow cell development in bone cells, we developed a mouse voluntary climbing exercise model. Climbing exercise increased bone volume and transient osteogenic potential of bone marrow. This model would be suitable for investigating the mechanistic roles of mechanical loading. INTRODUCTION: The relationship between bone mass gain and local bone formation and resorption in mechanically loaded bone is not well understood. MATERIALS AND METHODS: Sixty-five C57BL/6J mice, 8 weeks of age, were assigned to five groups: a baseline control and two groups each of ground control and climbing exercise mice for 2 and 4 weeks. Mice were housed in a 100-cm tower and had to climb toward a bottle placed at the top to drink water. RESULTS: Compared with the ground control, bone mineral density of the left femur increased in the climbing mice at 4 weeks. At 2 and 4 weeks, bone formation rate (BFR/BS) of periosteal surface, the cross-sectional area, and moment of inertia were increased in the climbing mice, whereas BFR/BS and eroded surface (ES/BS) of endosteal surface did not differ. The trabecular bone volume (BV/TV) of the proximal tibia increased in climbing mice, and osteoclast surface (Oc.S/BS) and osteoclast number decreased at 2 weeks. At 4 weeks, there were increases in BV/TV and parameters of bone formation, including mineralized surface, mineral apposition rate, and bone formation rate. In marrow cell cultures from the tibia, the number of alkaline phosphatase+ colony forming units-fibroblastic and the area of mineralized nodule formation in climbing mice were increased, and the number of osteoclast-like TRACP+ multinucleated cells was lower at 2 weeks. At 4 weeks, these parameters recovered to the levels of the ground controls. CONCLUSION: Our results indicate that climbing increased trabecular bone volume and reduced bone resorption, with a subsequent increase in bone formation. Intermittent climbing downregulates marrow osteoclastogenic cells and upregulates osteogenic cells initially, but further exercise seemed to desensitize them. Cortical envelopes were enlarged earlier, but the response seems to differ from trabecular bone.     

Effect of nebracetam on the disruption of spatial cognition in rats.

Central cholinergic hypofunction causes the disruption of spatial cognition, while cholinomimetics improve this disruption in rats. Scopolamine (0.5 mg/kg, i.p.) has also been reported to disrupt radial maze performance in rats. Nebracetam (WEB 1881 FU), a new nootropic candidate, was able to correct this scopolamine-induced disruption of spatial cognition at the dose of 10 mg/kg, p.o. Furthermore, nebracetam enhanced oxotremorine-induced tremors in mice. These results indicate that nebracetam has a cholinergic enhancing effect. The scopolamine-induced disruption of spatial cognition has been previously reported to improve not only by cholinomimetics but also by brain noradrenergic drugs such as L-threo-DOPS and amantadine. Nebracetam reversed the change of brain noradrenaline contents in the frontal cortex and hippocampus in which the noradrenaline content decreased by treatment with scopolamine. Nebracetam also decreased the delta 9-tetrahydrocannabinol (6 mg/kg, i.p.)-induced disruption of spatial cognition, which was reported to be related to the lymbic noradrenergic function. These results suggest that the cognitive enhancing effect of nebracetam involves not only cholinergic mechanisms but also involves lymbic and hippocampal noradrenergic mechanisms.     

Ectopic cervico-mediastinal thymoma confirmed by flow cytometric analysis of tumor-derived lymphocytes

Ectopic cervical or cervico-mediastinal thymomas are very rare and most of them are asymptomatic, except for the presence of a cervical mass. We present the case of a 71-year-old man with an ectopic cervico-mediastinal thymoma threatening superior vena cava syndrome. He had a slight headache and presented with venous dilatation on the chest wall. A computed tomographic scan and magnetic resonance, imaging of the chest demonstrated a mass extending from the right neck to the hilum, that indented the trachea and compressed and displaced the brachiocephalic veins anteriorly. Under a right hemicollar incision and median sternotomy, the mass was resected en bloc together with the thymus. The resected specimen was an encapsulated mass measuring 11×7×4 cm. The pathological diagnosis was type AB, non-invasive thymoma, confirmed by 3-color flow, cytometry of tumor-derived lymphocytes. Flow cytometry using biopsy material may contribute to the preoperative diagnosis of ectopic thymoma.     

Improved expression of gamma-aminobutyric acid receptor in mice with cerebral infarct and transplanted bone marrow stromal cells: an autoradiographic and histologic analysis.

Recent studies have indicated that bone marrow stromal cells (BMSC) have the potential to improve neurologic function when transplanted into animal models of central nervous system disorders. However, how the transplanted BMSC restore the lost neurologic function is not clear. In the present study, therefore, we aimed to elucidate whether BMSC express the neuron-specific gamma-aminobutyric acid (GABA) receptor when transplanted into brain that has been subjected to cerebral infarction. METHODS: The BMSC were harvested from green fluorescent protein-transgenic mice and were cultured. The mice were subjected to permanent middle cerebral artery occlusion. The BMSC or vehicle was transplanted into the ipsilateral striatum 7 d after the insult. Using autoradiography and fluorescence immunohistochemistry, we evaluated the binding of 125I-iomazenil and the expression of GABA receptor protein in and around the cerebral infarct 4 wk after transplantation. RESULTS: Binding of 125I-iomazenil was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. Likewise, the number of the GABAA receptor-positive cells was significantly higher in the periinfarct neocortex in the BMSC-transplanted animals than in the vehicle-transplanted animals. A certain subpopulation of the transplanted BMSC expressed a neuron-specific marker, microtubule-associated protein 2, and the marker protein specific for GABAA receptor in the periinfarct area. CONCLUSION: These findings suggest that BMSC may contribute to neural tissue regeneration through migrating toward the periinfarct area and acquiring the neuron-specific receptor function.     

Fibrate for treatment of primary biliary cirrhosis

Recent studies of the effectiveness of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cirrhosis (PBC) reported that UDCA therapy did not necessarily stop the progression of liver fibrosis in all patients, even those with early stage PBC. Thus, there is a need for more effective treatments that could prevent asymptomatic PBC from progressing to the icteric stage. Bezafibrate is effective in approximately two-thirds of non-icteric patients who have not shown a complete response to UDCA. Serum bilirubin, aspartate aminotransferase and γ-guanosine 5'-triphosphate levelswere significantly lower in patients who responded to additional bezafibrate on univariate analysis. The putative mechanism by which bezafibrate acts in cholestasis is by increasing phospholipid output into bile, which forms micelles with the hydrophobic bile acid that reduces its toxicity.     

Antinociceptive Interaction of Intrathecal alpha sub 2 -adrenergic Agonists, Tizanidine and Clonidine, with Lidocaine in Rats

Background: The intrathecal alpha2 -adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2 -adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine.

Methods: Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2 -adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored.

Results: Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in micro gram) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure.