Exogenous NO induces retinal neurotoxicity, suggesting that NO plays a pathogenic role in degenerative retinal diseases. BDNF and CNTF protect retinal neurons from NO-mediated neurotoxicity.
Microtoena patchoulii (Labiatae) is a perennial herb that grows in southern China. In the present study, the sedative activity of the essential oil of the leaves was evaluated using mice when the volatile oil was administered by inhalation. The inhalation of the oil by mice significantly reduced the spontaneous motor activity. Fractionation of the oil revealed that the main constituents in the oil were 1-octen-3-ol, terpinolene, patchouli alcohol, and methyl salicylate. Each 1-octen-3-ol, terpinolene, or patchouli alcohol significantly reduce the locomotor activity when it was administered singly. However, the essential oil fraction containing both patchouli alcohol and methyl salicylate did not exhibit any effects. It is suggested that methyl salicylate might negate the sedative effect of patchouli alcohol, and that the concentration ratios of the compounds in vapor would play important roles as sedatives. In order to clarify the mechanism of action, the effects of these compounds on caffeine-induced excitation and pentobarbital-induced elongation of sleeping time in mice were tested. Each 1-octen-3-ol or terpinolene reduced the locomotor activity excited by caffeine to those of normal levels. Elongation of sleeping time induced by pentobarbital was further elongated by the inhalation of terpinolene, but not by that of 1-octen-3-ol. It is indicated that terpinolene is a potent suppressor of the central nervous system.
osteomyelitis and disseminated MAC infection. We tested interferon (IFN)-γ production of peripheral blood mononuclear cells (PBMC) of the patient after phytohemagglutinin (PHA)-stimulation and found that these cells produced no or undetectable levels of IFN-γ in the presence of autologous plasma while produced almost normal levels of IFN-γ in the presence of healthy donor's plasma. Since this neutralizing activity was co-purified in the IgG fraction, the immunodeficient state of the patient seemed to be caused by autoantibody to IFN-γ. As far as we know, this is the first report of a Japanese case of disseminated MAC infection presumably due to autoantibody to IFN-γ.
IOP measured by DCT correlates with IOP measured by GAT or NCT with a roughly 3.0 mm Hg higher value, and these differences were greater in the patients with a thinner CCT. IOP measurements by both GAT and NCT significantly correlated with CCT; however, IOP measurement by DCT did not correlate with CCT. Our findings also indicate that OPA measured using DCT shows a positive correlation with patient age, IOP measurement by DCT, and pulse pressure.
Terpinolene is a cyclic monoterpene compound found in some Labiatae herbs. In our previous study, we evaluated the sedative effect of inhaled essential oils of Microtoena patchoulii leaves in mice and isolated terpinolene as an active ingredient. We investigated the structure-activity relationships of terpinolene to identify the structural part essential to its sedative effect. Comparison of terpinolene analog activities showed that a double bond in the side-chain or pi bonds in the six-membered ring play important roles in the sedative effect. In another experiment using olfactory impaired mice, we further revealed that inhaled terpinolene exerted the effect after nasal absorption into the body.
Summary
Dysregulated glycolysis, including the cancerous Warburg effect, is closely involved in pathological mechanisms of diseased states. Among glycolytic enzymes, phosphoglycerate mutase (PGAM) has been known to exert certain physiological impact
in vitro
, whereas its regulatory role on glycolysis remains unclear. Here, we identified that PGAM plays a key role in regulating glycolysis in cancer cells but not in standard cells. Cancer-prone phenotype by PGAM overexpression
in vivo
was associated with upregulated glycolytic features. PGAM interacts and cooperates with Chk1 to regulate the enhanced glycolysis in cancer cells, especially under oncogenic Ras expressing conditions. Genetic or chemical interference of the PGAM-Chk1 interaction, with intact PGAM activity, abrogated the maintenance of cancerous enhanced glycolysis. Thus, the nonenzymatic function of PGAM is essential for the Warburg effect that accompanies cancerous proliferation.
1 A newly synthesized benzothiazepine derivative, JTV-519 (JT) has been reported to be cardioprotective. However, the precise mechanism underlying the cardioprotective eect of this drug is unknown. 2 Coronary-perfused guinea-pig ventricular muscles were subjected to 20-min no-¯ow ischaemia followed by 60-min reperfusion (I/R). I/R signi®cantly decreased the contraction in untreated preparations (control group, 34+4% of baseline value, n=6). Brief administration of JT (1.0 mM) prior to ischaemia signi®cantly improved the postischaemic contractile recovery (63+5% of baseline value, n=4), as compared to the control group. 3 JT (1.0 mM) slightly prolonged action potential duration before ischaemia and induced conduction disturbance (2 : 1 block) after the initiation of ischaemia. 4 The cardioprotective eect of JT was antagonized by chelerythrine (CH, 5.0 mM), an inhibitor of protein kinase C (PKC) or by 5-hydroxydecanoic acid (5-HD, 400 mM), an inhibitor of mitochondrial ATP-sensitive K + (K ATP ) channels. 5 These results suggest that the protective eect of JT is due to the opening of mitochondrial K ATP channels, which, in turn, is linked to PKC activation.
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