Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice

Extensive pharmacological studies have recently emerged indicating that group 2 metabotropic glutamate receptors (mGluRs) comprising mGluR2 and mGluR3 subtypes are associated with several neurological and psychiatric disorders. mGluR2 is widely distributed both presynaptically and postsynaptically in a variety of neuronal cells, but the physiological role of mGluR2 in brain function is poorly understood. This investigation involves a comprehensive behavioral analysis of mGluR2-/- knockout (KO) mice to explore the physiological role of mGluR2 in brain function. Although, under general observation, mGluR2-/- KO mice appeared to have no behavioral abnormalities, they exhibited several lines of behavioral alterations in the enforcing and defined behavioral tests. They showed a significant increase in locomotor sensitization and conditioned place preference in association with repeated cocaine administration, indicating that mGluR2 contributes to behavioral responses implicated in reinforcement and addiction of cocaine. Upon in vivo microdialysis analysis after cocaine administration, not only did extracellular levels of dopamine increase but also the response pattern of glutamate release markedly changed in the nucleus accumbens of mGluR2-/- KO mice. The mGluR2-/- KO mice also showed significant impairment in motor coordination in the accelerating rota-rod test and exhibited hyperlocomotion in novel environmental and stressful conditions, when assessed by the open-field and forced-swim tests. These results indicate that the inhibitory mGluR2 plays a pivotal role in synaptic regulation of glutamatergic transmission in the neural network.     

Three episodes of inferior acute myocardial infarction due to thrombotic occlusion of the right coronary artery: a case report

A 77-year-old female with two previous inferior myocardial infarctions was transferred to our medical center with a third inferior acute myocardial infarction. Coronary angiography revealed 99% stenosis with rich thrombus in the distal right coronary artery [Thrombolysis in Myocardial Infarction (TIMI) grade 2 flow]. The angiographic appearance of the right coronary artery was similar to the two previous myocardial infarctions. Coronary aspiration was performed and TIMI grade 3 flow was established. To confirm the presence of thrombus, intravascular ultrasound (IVUS) and coronary angioscopy were performed at pre-discharge. IVUS showed a thrombus-like low-density area at the mid right coronary artery. Red thrombi were observed in the same area using coronary angioscopy. Although warfarin had been prescribed for secondary prevention since the first acute myocardial infarction, both the second and third acute myocardial infarction occurred after cessation of warfarin. Patients with acute myocardial infarction due to thrombotic occlusion, confirmed by IVUS or angioscopy, might be good candidates for permanent warfarin therapy.     

Prevention of vertical transmission of Group B Streptococcus

Group B Streptococcus (GBS) are pathogens that involve a risk of vertical transmission. They are the infecting organism in approximately one quarter of all cases of neonatal sepsis and meningitis, making prevention of GBS infection an important goal. The United States Centers for Disease Control and Prevention (CDC) recommends administration of antibiotic prophylaxis to GBS-colonized pregnant women at least 4 hours before delivery, but the time of antibiotic prophylaxis administration is not generally reported in Japan. The purpose of the present study was to identify the care provided to GBS-colonized pregnant and intrapartum women in order to prevent of vertical transmission of GBS. The subjects were women (n=150) judged during pregnancy to have been colonized by GBS, who delivered vaginally at one of two hospitals between January 2000 and December 2004, and their neonates (n=151). The relation between the care provided and GBS transmission was analyzed. GBS was transmitted to the neonates of 18 of the 150 women (transmission rate 12.0%). The relation between transmission to the neonate and time between administration of antibiotic prophylaxis and delivery was investigated, and transmission to the neonate was found to be significantly greater when it was less than 3.5 hours (transmission to 9 neonates of 53 women) than more than 3.5 hours (transmission 4 neonates of 83 women) (p < 0.05). The time between admission and delivery was significantly shorter in the cases of transmission (p < 0.05). This indicates the need for thorough health guidance for expectant mothers, especially multipara, during pregnancy regarding the timing of admission for delivery, in order to ensure sufficient time between administration of antibiotic prophylaxis and delivery.     

Surface composition and texture of titanium polished with colloidal silica suspension and chromic oxide slurry

CP titanium was polished with a colloidal silica suspension and chromic oxide slurry under low and high pressures. The polished surfaces were characterized by means of EPMA and XPS. Irrespective of polishing pressure, colloidal silica suspension successfully created a mirror-like surface that was clean at EPMA level. However, XPS detected a small amount of silicon on the outermost surface. On the other hand, chromic oxide slurry under high pressure yielded a very uneven surface with numerous scratches. The EPMA and XPS results suggested the presence of chromium-containing species in the polished surface, which might include hydroxides as well as oxides. In addition, the level of oxygen concentration was noticeably raised, which probably resulted from the increase of surface oxide film thickness or the extension of oxide-to-metal transition zone.     

Axonal transport of rubidium and thallium in the olfactory nerve of mice

Following intranasal administration of radioactive (86)Rb(+) and (201)Tl(+) in mice, we observed this direct transport via the olfactory nerve pathway. The (86)RbCl and (201)TlCl solutions were administered to two groups of mice, the unilateral intranasal and intravenous administration groups. After sacrifice, their heads were divided into the right and left side, which were then subdivided into seven parts; the nasal mucosa and brain regions were separated. Following the unilateral intranasal administration, uptake after 6 h by the olfactory bulb was significantly higher on the ipsilateral side ((86)Rb, 0.7 %dose; (201)Tl, 0.5 %dose) than on the contralateral side ((86)Rb, 0.08 %dose; (201)Tl, 0.15 %dose). Moreover, the (86)Rb and (201)Tl that accumulated in the olfactory bulb were gradually transported to other brain regions of the olfactory tract, the telencephalon and the diencephalon on the side corresponding to the nostril used for administration. Significant differences were observed between the right and left side of the brain regions 6 and 12 h after administration. Further, (201)Tl autoradiography clearly showed striped patterns of dense accumulation, localized in the region around the glomerular layer and granule cell layer of the olfactory bulb and around the olfactory cortex. These results provide clear evidence of axonal transport via the olfactory nerve pathway, from nasal cavity to the olfactory bulb, as well as to the olfactory cortex through the synaptic junctions. The olfactory transport of the (86)Rb(+) and (201)Tl(+) is thought to represent the behavior of K(+) in the olfactory system.     

Effects of bifemelane on the calcium level and ATP release of the human origin astrocyte clonal cell

The effect of bifemelane hydrochloride (bifemelane) was examined on human origin astrocyte clonal cells (Kings-1). Bifemelane (125 - 1,000 microM) induced a dose-dependent increase in the intracellular calcium concentration ([Ca(2+)](i)). In the highest concentration (1,000 microM), the drug caused the second large increase in [Ca(2+)](i) during the washing. The increase that occurred during the administration partially remained in the Ca(2+)-free medium and was blocked by 2-aminoethoxydiphenyl borate (2-APB), an IP(3)-receptor blocker, indicating that the source of Ca(2+) for the increase could be ascribed to the intracellular store. The increase in [Ca(2+)](i) was not observed during washing with Ca(2+)-free medium, but was observed when the washing was performed with Ca(2+)-containing medium. Bifemelane caused a dose-dependent ATP release, but histamine and carbachol, which induced a large increase in [Ca(2+)](i), had no effects on the ATP release. The effects on the [Ca(2+)](i) were blocked by pretreatment with pyridoxal phosphate-6-azophenyl-2',4' disulfonic acid, a P2-receptor antagonist. Although the mechanisms of ATP release induced by the drug have not been elucidated yet, the present results demonstrate that the increase in [Ca(2+)](i) induced by bifemelane is not due to its direct effect on the cells, but is dependent upon the ATP released from the cells.     

Procurement of the human pancreas for pancreatic islet transplantation from marginal cadaver donors

BACKGROUND: Recent advances in pancreatic islet transplantation (PIT) have contributed significantly to the treatment of patients with type 1 diabetes. The specific aim of this study was to develop an effective technique for the procurement of pancreas for PIT from nonheart-beating-donor (NHBDs). METHODS: Between January 2004 and August 2004, eight human pancreata were procured and processed for isolation of islets at a cell processing center. After confirmation of brain death status, a double balloon catheter was inserted to prevent warm ischemic damage to the donor pancreas by using an in situ regional organ cooling system that was originally developed for procurement of kidneys. The catheter position of the cooling system was modified specifically for the pancreas and kidney. Furthermore, we worked in cooperation with a kidney procurement team to protect the pancreas during kidney procurement. RESULTS: Warm ischemic time could be controlled with the modified in situ regional cooling system at 3.0 +/- 0.8 min (mean +/- SE). The operations for procurement of the kidneys and pancreata lasted 45.6 +/- 3.6 min and 10.6 +/- 1.8 min, respectively. Islet yield per isolation was 444,426 +/- 35,172 IE (islet equivalent). All eight cases met the criteria for PIT based on the Edmonton protocol. CONCLUSION: We developed a novel procurement technique in cooperation with our kidney procurement team. This protocol for the procurement of pancreas and kidney from a NHBD enabled us to transplant islets into a type 1 diabetic patient and kidney into a renal failure patient.