Non-N-methyl-D-aspartate glutamate receptors mediate oxygen--glucose deprivation-induced oligodendroglial injury

Cells of oligodendroglial lineage are susceptible to oxygen and glucose deprivation. When oligodendrocyte-like cells differentiated from CG-4-immortalized rat O-2A progenitor cells were exposed to hypoxia alone or glucose deprivation alone for 48 h, release of lactate dehydrogenase (LDH) into the culture medium did not increase. However, when cells were deprived of both oxygen and glucose for 6 or 12 h preceding reoxygenation for 2 h, LDH release increased. Adding glucose to the medium protected against cell death and increased lactate production in a concentration-dependent manner. Cell damage induced by deprivation of oxygen and glucose was prevented by calcium-free medium or by non-N-methyl-D-aspartate glutamate receptor (GluR) antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione or LY293558, but not by the voltage-dependent calcium channel blocker, nimodipine, or by the N-methyl-D-aspartate GluR antagonist, MK-801. The glutamate concentration in the medium from cells exposed to oxygen-glucose deprivation for 12 h was 49.70+/-3.04 microM/l, which is sufficient to activate GluRs during deprivation of oxygen and glucose. Apoptotic cells detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) or Hoechst 33258 staining did not increase in cells exposed to oxygen-glucose deprivation for 12 h and subsequent reoxygenation for 2 h. No DNA laddering was detected by agarose gel electrophoresis from cells exposed to deprivation of oxygen and glucose. Neither acetyl-YVAD-CHO, an inhibitor of caspase-1-like proteases, nor acetyl-DEVD-CHO, an inhibitor of caspase-3-like proteases, prevented oxygen-glucose deprivation-induced injury. Thus, oxygen and glucose deprivation causes calcium-influx-induced necrotic cell damage in cells of oligodendroglial lineage via non-N-methyl-D-aspartate GluR channels.     

Biosurfactant MEL-A dramatically increases gene transfection via membrane fusion.

Biosurfactants, which are surface-active compounds produced by microorganisms growing on water-insoluble substrates, have many biological activities. We studied here three different biosurfactants, mannosylerythritol lipid (MEL) or 4-O-[(4',6'-di-O-acetyl-2',3'-di-O-alkanoyl)-beta-D-mannopyranosyl] meso-erythritol (MEL-A), 4-O-[(6'-O-acetyl-2',3'-di-O-alkanoyl)-beta-D-mannopyranosyl] meso-erythritol (MEL-B) and 4-O-[(4'-O-acetyl-2',3'-di-O-alkanoyl)-beta-D-mannopyranosyl] meso-erythritol (MEL-C). MEL-A enhanced the efficiency of gene transfection by cationic liposomes, but MEL-B and MEL-C did not. We also studied the localization of FITC-conjugated antisense DNAs (15-mer oligonucleotides; phosphorothioate) in the target cells by confocal laser scanning microscopy (CLSM). The FITC-conjugated antisense oligonucleotides were temporarily on the plasma membrane of the target cells, thereafter they were transferred into the nucleus of the target cells. In the case of MEL-B and MEL-C, such localization of DNA was not observed both in the plasma membrane and in the nucleus. The results obtained by CLSM images were in good agreement with the transfection efficiency. This suggests that MEL-A induces the membrane fusion between the target cells and the cationic liposomes, accelerating the efficiency of gene transfection dramatically.     

Nanomolar concentrations of tri-n-butyltin facilitate gamma-aminobutyric acidergic synaptic transmission in rat hypothalamic neurons

Tri-n-butyltin (TBT), an environmental pollutant, is accumulated in edible mollusks and fishes. It has also become a health concern in today's society. In the present study, to elucidate the possible neurotoxic action of TBT, the effect on spontaneous gamma-aminobutyric acid (GABA) release from GABAergic nerve terminals projecting to rat ventromedial hypothalamic neurons was examined using "synaptic bouton" preparation with a nystatin perforated patch recording mode under voltage-clamp conditions. The threshold concentration of TBT to affect the synaptic transmission was 10 to 30 nM. TBT at 30 nM or higher concentrations increased the frequency of GABAergic miniature inhibitory postsynaptic currents in a dose-dependent manner, whereas the current amplitude and current kinetics were not affected. The removal of either external Ca2+ or application of Cd2+ attenuated the TBT-induced facilitation of neurotransmission. TBT at 1 microM induced an inward current in more than one-half of the cells. This current persisted even after TBT was washed out. The present results indicate that TBT at environmentally relevant concentrations (30-100 nM) facilitates the GABAergic neurotransmission in the mammalian brain and the external Ca2+ is needed in this facilitation. Because the concentration of TBT accumulated in some mollusks and fishes has been reported to reach levels of 100 nM or more, such accumulation of TBT in some mollusks and fishes is thus suggested to be hazardous to the health of humans.     

Staged repair of pentalogy of Cantrell with ectopia cordis and ventricular septal defect

Pentalogy of Cantrell is a rare congenital anomaly characterized by a combination of severe defects in the middle of the chest and abdomen including intracardiac defects. Survival rate after cardiac surgery is extremely low. We present a successful staged complete repair of an omphalocele, a ventricular septal defect and a sternal defect in a case of pentalogy of Cantrell.     

A case of primary pulmonary hypertension treated with prazosin and isosorbide dinitrate

Successful vasodilator therapy of a 27-year-old woman with primary pulmonary hypertension is described. Prazosin 2 mg, orally in combination with isosorbide dinitrate 10 mg, sublingually caused a marked fall in pulmonary vascular resistance. Pulmonary hemodynamics reevaluated after 3 months of combination therapy with prazosin 1 mg qid and isosorbide dinitrate 5 mg qid showed sustained improvement. Therefore, in selected patients with primary pulmonary hypertension, this combination therapy can be used.     

A case with pseudo-scimitar syndrome: "scimitar sign" with normal pulmonary venous drainage

The case reported here showed a radiological appearance of hypoplasia of the right lung, dextroposition of the heart, and a curved vascular shadow in the right lower lung field known as a scimitar sign. However, a computed tomography of the chest showed this abnormal vascular shadow draining into the left atrium (pseudo-scimitar sign). Therefore, in patients with a radiological appearance of the scimitar syndrome, computed tomography of the chest should be indicated to rule out the pseudo-scimitar sign.     

Differences of side branch jailing between left main–left anterior descending artery stenting and left main–left circumflex artery stenting with Nobori biolimus-eluting stent

The aim of this study is to indicate differences of side branch jailing between the left main (LM)–left anterior descending artery (LAD) stenting and the LM–left circumflex artery (LCx) stenting. Thirty-one patients who underwent single-stenting using a two-link ten-crowns biolimus-eluting stent (Japanese design of BES, J-BES) and subsequent kissing balloon dilation (KBD) on an LM bifurcation with optical coherence tomography (OCT) were divided into two groups according to the stented vessel. Bifurcation angles were measured by three-dimensional (3D) quantitative coronary analysis. The jailing pattern on a side branch ostium was evaluated by stent-enhanced 3D-OCT. Incomplete stent apposition (ISA) after KBD was compared between the stented vessels. The to-be-stented angle of the LM–LCx stenting (n = 11) was significantly steeper than that of the LM–LAD stenting (n = 20) (132.6° ± 16.9° vs. 150.7° ± 10.6°, p < 0.01). The incidence of the free carina type, which has no stent links bridging from a carina, in the LM–LCx stenting was significantly higher than that in the LM–LAD stenting (90.9 vs. 45.0 %, p = 0.02). The percentage of ISA at the bifurcation segment in the LM–LCx stenting was significantly smaller than that in the LM–LAD stenting (4.4 ± 8.2 vs. 12.7 ± 9.2 %, p = 0.0003). This study showed, by higher incidence of the favorable configuration, that the LM–LCx stenting achieved a smaller percentage of ISA than the LM–LAD stenting. These insights may help guide LM bifurcation stenting with J-BES.     

Investigation concerning demand and vaccination applicants to traveler's vaccines (typhoid fever and meningococcal vaccines) not marketed in Japan

In recent years, the number of Japanese traveling to foreign countries is increasing. Most of them travel to Asian regions where many infectious diseases that are rare or don't occur in Japan still remain endemic or epidemic. Of these infectious diseases typhoid fever and meningococcal infection are now preventable because safe and effective vaccines have been developed and now marketed. However, these vaccines are hardly available in Japan because the Japanese Government has not admitted them. To investigate the demand for the two vaccines, the author personally imported inactivated polysaccharide typhoid vaccine and groups A, C,Y and W135 combined polysaccharide meningococcal vaccine, both manufactured by Aventis-Pasteur. After obtaining approval of the ethical committee of our hospital, vaccination was started. From May 6, 2003 to September 30, 2004, 124 applicants received typhoid vaccine and 35 were injected with meningococcal vaccine. Of 124 vaccinees of typhoid vaccine, 46 went to Afghanistan, 15 to India, 8 to Thailand. Of 35 vaccinees of meningococcal vaccine 6 went to the USA, 5 to Guinea and 3 to England. In addition a total of 12 physicians and nurses having no international scheduled trip were also immunized with meningococcal vaccine. None of these vaccines are widely known in Japan now. Based on our results, however, the expansion of recognition and demand for these two vaccines is expected.