Multichannel monitoring of cerebral circulatory and oxygenation status using optical topography during deep hypothermic retrograde cerebral perfusion

In this study, we evaluated changes in the cerebral circulatory and oxygenation status during deep hypothermic total circulatory arrest (TCA) and retrograde cerebral perfusion (RCP) using optical topography, a form of multichannel near-infrared spectrophotometry, to monitor the broad area perfused by the middle cerebral artery. Seven patients underwent thoracic aortic surgery with TCA and RCP via the superior vena cava. Pressure-regulated RCP was performed under pH-stat. No postoperative neurologic complications occurred. Using optical topography, the relative changes in oxy-, deoxy-, and total hemoglobin (oxy-Hb, deoxy-Hb, total Hb) were simultaneously measured from 24 points in both hemispheres. Deoxy-Hb was used for evaluating the regional oxygenation status under RCR The values of deoxy-Hb at the beginning of RCP were regarded as the basal values, and the rate of increase in deoxy-Hb per minute (deoxy-Hb/min) was calculated at each site. Deoxy-Hb/min during TCA was also calculated. In every case, both oxy-Hb and total Hb decreased and deoxy-Hb increased during TCA. When RCP was initiated, the decrease in oxy-Hb and the increase in deoxy-Hb were attenuated. Deoxy-Hb/min was significantly lower under RCP than during TCA in all portions. There was no significant difference of deoxy-Hb/min between any portions during RCP Our results showed that the status of circulation and oxygenation might be uniform in the brain during RCP and better than that under TCA.     

Protective role of intramuscularly administered vitamin E on the levels of lipid peroxidation and the activities of antioxidant enzymes in the lens of rats made cataractous with gamma-irradiation

PURPOSE: To determine the antioxidant role of vitamin E (VE) (10 mg/kg/day) against radiation-induced cataract in lens after total-cranium irradiation of rats with a single dose of 5 Gy. METHODS: Sprague-Dawley rats were divided into three groups. Group 1 did not receive VE or irradiation but received both 0.1 ml physiologic saline intraperitoneally and sham irradiation (control group). Group 2 received to total cranium 5 Gy of gamma irradiation as a single dose (RT group) plus 0.1 ml physiologic saline intraperitoneally. Group 3 received irradiation to total cranium plus 10 mg/kg/day VE (RT+VE group). The rats were irradiated using a cobalt-60 teletherapy unit. Chylack's cataract classification (1) was used in this study. At the end of 10 days, the rats were killed and their eyes were enucleated to measure the antioxidant enzymes (the activity of superoxide dismutase [SOD], glutathione peroxidase [GSH-Px]) and lipid peroxidation level (malondialdehyde [MDA]). RESULTS: While grade 1 cataract development was detectable in seven rats in the RT group, it was detectable only in two rats in the RT+VE group, whereas none of the rats in the control group exhibited any biomicroscopic change in their lenses. MDA level and GSH-Px activity in the rat lens in the RT group was significantly higher than in the control group. SOD activity in the RT group was lower than in the control group. The activity of SOD and GSH-Px enzymes was higher in the RT+VE group, but MDA level was lower in the RT+VE group when compared with the RT group. CONCLUSIONS: Vitamin E has a protective effect on radiation-induced cataract by decreasing oxidative stress.     

Effect of change in cellular GSH levels on mitochondrial damage and cell viability loss due to mitomycin c in small cell lung cancer cells

The effect of GSH depletion on mitochondrial damage and cell death due to mitomycin c (MMC) was assessed in small cell lung cancer (SCLC) cells. Cytotoxicity of MMC was attenuated by Tempol and dicumarol, inhibitors of the enzymatic reduction, and increased by xanthine oxidase. The MMC-induced cell death and decrease in the GSH contents in SCLC cells were inhibited by caspase inhibitors (z-DQMD.fmk, z-IETD.fmk and z-LEHD.fmk) and antioxidants (N-acetylcysteine, dithiothreitol and N-(2-mercaptopropionyl)glycine, melatonin, rutin and carboxy-PTIO). Thiol compounds, melatonin and rutin attenuated the MMC-induced nuclear damage, decrease in mitochondrial transmembrane potential, release of cytochrome c and activation of caspase-3. Treatment of MMC caused a significant decrease in GSH contents in SCLC cells, which was followed by increase in the formation of reactive oxygen species. Depletion of GSH due to L-buthionine sulfoximine enhanced the MMC-induced activation of caspase-3 and cell death in SCLC cells. Antioxidants, including N-acetylcysteine, depressed formations of nitric oxide, malondialdehyde and carbonyls due to MMC in SCLC cells. The results show that the reductive activation of MMC may cause cell death in SCLC cells by inducing mitochondrial dysfunction, leading to caspase-3 activation, and by activation of caspase-8. The MMC-induced change in the mitochondrial membrane permeability, followed by cell death, in SCLC cells may be significantly enhanced by decrease in the intracellular GSH contents due to oxidative attack of free radicals.     

Inhibitory effects of flavonoids on phosphodiesterase isozymes from guinea pig and their structure-activity relationships

The structure-activity relationships of flavonoids with regard to their inhibitory effects on phosphodiesterase (PDE) isozymes are little known. The activities of PDE1-5 were measured by a two-step procedure using cAMP with [(3)H]-cAMP or cGMP with [(3)H]-cGMP as substrates. In the present results, PDE1, 5, 2, and 4 isozymes were partially purified from guinea pig lungs in that order, and PDE3 was from the heart. The IC(50) values of PDE1-5 were greater than those reported previously for the reference drugs, vinpocetin, EHNA, milrinone, Ro 20-1724, and zaprinast, by 5-, 5-, 7-, 5-, and 3-fold, respectively. As shown in Table 2, luteolin revealed non-selective inhibition of PDE1-5 with IC(50) values in a range of 10-20 microM, as did genistein except with a low potency on PDE5. Daidzein, an inactive analogue of genistein in tyrosine kinase inhibition, showed selective inhibition of PDE3 with an IC(50) value of around 30 microM, as did eriodictyol with an IC(50) value of around 50 microM. Hesperetin and prunetin exhibited more-selective inhibition of PDE4 with IC(50) values of around 30 and 60 microM, respectively. Luteolin-7-glucoside exhibited dual inhibition of PDE2/PDE4 with an IC(50) value of around 40 microM. Diosmetin more-selectively inhibited PDE2 (IC(50) of 4.8 microM) than PDE1, PDE4, or PDE5. However, biochanin A more-selectively inhibited PDE4 (IC(50) of 8.5 microM) than PDE1 or PDE2. Apigenin inhibited PDE1-3 with IC(50) values of around 10-25 microM. Myricetin inhibited PDE1-4 with IC(50) values of around 10-40 microM. The same was true for quercetin, but we rather consider that it more-selectively inhibited PDE3 and PDE4 (IC(50) of < 10 microM). In conclusion, it is possible to synthesize useful drugs through elucidating the structure-activity relationships of flavonoids with respect to inhibition of PDE isozymes at concentrations used in this in vitro study.     

Structure-activity relationship studies on chalcone derivatives: potent inhibition of platelet aggregation

In an effort to develop potent antiplatelet agents with anti-inflammatory action, a novel series of anti-inflammatory chalcones was screened to evaluate their antiplatelet effects. Structure-activity relationships and mode of action were investigated and characterized. The antiplatelet effects of the chalcones on washed rabbit platelets and human platelet-rich plasma were evaluated. Arachidonic acid-induced platelet aggregation was potently inhibited by almost all the chalcone derivatives. Collagen-induced platelet aggregation was potently inhibited by all the chalcone derivatives at 300 microM, except for compound 4 at 100 microM. Compounds 6, 7 and 9 significantly inhibited the aggregation of washed rabbit platelets induced by platelet-activating factor at 300 microM. Of the compounds tested in human platelet-rich plasma, compounds 2, 8 and 9 showed significant inhibition of secondary aggregation induced by adrenaline. It is concluded that the antiplatelet effect of 2, 8 and 9 is mainly owing to an inhibitory effect on thromboxane formation. The inhibitory effect of 6, 7 and 9 on platelet aggregation induced by platelet-activating factor could be owing to a calcium antagonizing effect or inhibition of intracellular calcium mobilization.     

Age-dependent effects of 5,7-dihydroxytryptamine on serotonin transporter in different brain areas in the rat

In the present study, we investigated the [(3)H]citalopram binding using a quantitative autoradiography following intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) in neonatal and adult male Wistar rats. One group of animals was injected with 5,7-DHT at 3 days after birth while the second group received the neurotoxin at 3 months after birth. Control group was injected with saline. Afterwards, all rats were examined at 4(th) months after birth to determine the serotonin (5-HT) and catecholamines concentrations using the liquid chromatography with electrochemical detection HPLC system and distribution and density of [(3)H]citalopram binding sites in the brain using the quantitative autoradiography. A marked depletion of brain 5-HT was observed in rats lesioned either in postnatal or adult period of life. Rats lesioned in their adult period of life showed dramatic reduction of 5-HT transporter in all investigated brain areas (i.e.the frontal cortex, entorhinal cortex, hippocampus, caudate-putamen, nucleus accumbens and ventral tegmental area). On the other hand, administration of 5,7-DHT to newborn rats failed to reduce 5-HT transporter sites in the ventral tegmental area, and produced only slight or moderate reduction in the nucleus accumbens. Thus, it appears that the mesolimbic ventral tegmental area-nucleus accumbens systems are relatively more resistant to 5,7-DHT neurotoxicity in the early postnatal period.     

Intradermal acupuncture on shen-men and nei-kuan acupoints in patients with insomnia after stroke

This is the first study that focuses on the effects of intradermal acupuncture on insomnia after stroke. We enrolled hospitalized stroke patients with insomnia and assigned them into a real intradermal acupuncture group (RA group) or a sham acupuncture group (SA group) by randomization. The RA group received intradermal acupuncture on shen-men (He-7) and nei-kuan (EH-6) for 2 days, and the SA group received sham acupuncture on the same points. The effectiveness was measured by the Morning Questionnaire (MQ), Insomnia Severity Index (ISI), and Athens Insomnia Scale (AIS). These scales were examined by an independent, blinded neurologist before, and 1 and 2 days after treatment, repeatedly. Thirty subjects (15 in the RA group and 15 in the SA group) were included in the final analysis. The RA group showed more improvement on insomnia than the SA group. Repeated measures analysis detected that there were significant between-subjects effects in the MQ, the ISI and the AIS. In conclusion, we suggest that intradermal acupuncture on shen-men and nei-kuan is a useful treatment for post stroke-onset insomnia.     

Hypolipidemic effect of Glycine tomentella root extract in hamsters

The influence of the aqueous crude extract of Glycine tomentella root (Leguminosae) on lipid metabolism was investigated in hyperlipidemic hamsters. It was found that the administration of the G. tomentella extract (GTE) leads to a decrease of high serum cholesterol and triglyceride levels induced by high-fat diet. The GTE also increased serum high-density lipoprotein (HDL) cholesterol and decreased serum low-density lipoprotein (LDL) cholesterol. The reduction of serum triglyceride levels was accompanied by a significant decrease in the hepatic triglyceride content, while the cholesterol content was not changed. The results indicate that GTE is definitely an anti-hyperlipidemic agent, at least, in animals.     

A yang-promoting Chinese herbal suppository preparation enhances the antioxidant status of red cells in male human subjects

In the 16-week pilot study, the effect of a Yang-promoting Chinese herbal suppository preparation (VI-28) on the red cell antioxidant status was examined in 31 healthy male subjects aged 41-66 years old. VI-28 treatment for 12 weeks (one suppository (0.3 g) daily for week 1-4; one every 2 days for week 5-8; one every 3 days for week 9-12) produced a time/dose-dependent alteration in red cell antioxidant status. The VI-28-induced change is characterized by a slight depletion in cellular reduced glutathione (GSH) level and a decrease in susceptibility to peroxide-induced lipid peroxidation as well as increases in catalase (CAT) and Cu-Zn-superoxide dismutase (SOD) activities. While a reversal trend of change was observed in cellular GSH level, the susceptibility to lipid peroxidation as well as the CAT activity after the cessation of treatment for 4 weeks, the SOD activity exhibited a protracted increase. The results indicate that VI-28 treatment enhances red cell antioxidant status in male subjects. The beneficial effect of VI-28 treatment on red cells may re fl ect a corresponding change in antioxidant status of peripheral tissues.