Molecular characterization of atmospheric NO2-responsive germin-like proteins in azalea leaves.

Atmospheric nitrogen dioxide (NO(2)) is an environmental oxidant that is removed through direct uptake by foliage, but plant responses to this highly reactive gas are not well understood at the molecular level. From NO(2)-exposed leaves of a woody azalea (Rhododendron mucronatum), we cloned two cDNAs (RmGLP1 and RmGLP2) for germin-like proteins (GLPs), a group of ubiquitous plant proteins that have been implicated in various plant physiological and developmental processes. Quantitative analysis of mRNA expression, together with immunoblotting data, showed that foliar exposure to NO(2) caused a robust induction of these GLP-encoding genes. When produced in tobacco cell culture, recombinant RmGLP2 was secreted into the apoplast, where it exhibited superoxide dismutase activity. RmGLP1 and RmGLP2 represent the first examples of plant genes that are responsive to airborne NO(2). These enzymes might have a potential role in extracellular defense mechanisms through attenuation of interactions between reactive nitrogen and oxygen species.

A pharmaco-EEG study on antipsychotic drugs in healthy volunteers.

RATIONALE: Both psychotropic drugs and mental disorders have typical signatures in quantitative electroencephalography (EEG). Previous studies found that some psychotropic drugs had EEG effects opposite to the EEG effects of the mental disorders treated with these drugs (key-lock principle). OBJECTIVES: We performed a placebo-controlled pharmaco-EEG study on two conventional antipsychotics (chlorpromazine and haloperidol) and four atypical antipsychotics (olanzapine, perospirone, quetiapine, and risperidone) in healthy volunteers. We investigated differences between conventional and atypical drug effects and whether the drug effects were compatible with the key-lock principle. METHODS: Fourteen subjects underwent seven EEG recording sessions, one for each drug (dosage equivalent of 1 mg haloperidol). In a time-domain analysis, we quantified the EEG by identifying clusters of transiently stable EEG topographies (microstates). Frequency-domain analysis used absolute power across electrodes and the location of the center of gravity (centroid) of the spatial distribution of power in different frequency bands. RESULTS: Perospirone increased duration of a microstate class typically shortened in schizophrenics. Haloperidol increased mean microstate duration of all classes, increased alpha 1 and beta 1 power, and tended to shift the beta 1 centroid posterior. Quetiapine decreased alpha 1 power and shifted the centroid anterior in both alpha bands. Olanzapine shifted the centroid anterior in alpha 2 and beta 1. CONCLUSIONS: The increased microstate duration under perospirone and haloperidol was opposite to effects previously reported in schizophrenic patients, suggesting a key-lock mechanism. The opposite centroid changes induced by olanzapine and quetiapine compared to haloperidol might characterize the difference between conventional and atypical antipsychotics.

Increased omega complexity and decreased microstate duration in nonmedicated schizophrenic patients.

To explore brain functions in schizophrenic patients, the global analytic strategy of multichannel EEG was performed that combines measures of global complexity (Omega), total power (Sigma) and generalized frequency (Phi), and EEG microstate analysis was applied to multichannel EEG data for 24 nonmedicated patients and 24 healthy subjects. The patients had higher Omega and Sigma values, and lower Phi values compared with healthy subjects. Three topographical classes were obtained from all EEG data by EEG microstate analysis. The mean duration of one topographical class in the patients was shortened compared to healthy subjects. These results indicated looser cooperativity, or decreased connectivity of the active brain process and deviant brain information processing in schizophrenic patients.

EEG Global Field Power spectrum changes after a single dose of atypical antipsychotics in healthy volunteers.

Effects of four novel atypical antipsychotic drugs (olanzapine, perospirone, quetiapine, and risperidone) on scalp-recorded multi-channel EEGs were compared with two conventional antipsychotic drugs (chlorpromazine and haloperidol) and placebo in 14 healthy male volunteers. All subjects went through seven sessions. In each session, EEGs were recorded before and 2, 4 and 6 hours after drug administration. Global Field Power (GFP) in delta frequency band (1.5-6 Hz) increased around the time of peak serum concentration of quetiapine and risperidone compared to baseline. The increase of GFP in delta activity after quetiapine was significantly prominent in comparison to two other atypical antipsychotic drugs, perospirone and olanzapine, as well as to typical antipsychotic drugs, chlorpromazine and haloperidol (p<0.05). The increase in GFP of delta after risperidone was more prominent in comparison to after haloperidol (p<0.05). The greater sedative effects after quetiapine and risperidone may reflect the high affinity to A1 and H1 receptor bindings of these drugs. According to Low Resolution Electromagnetic Tomography (LORETA), olanzapine increased the delta in the posterior region indicating a frontal shift of brain activity, suggesting that olanzapine may be useful against negative symptoms in schizophrenics.

Effects of argatroban and heparin on thrombus formation and tissue plasminogen activator-induced thrombolysis in a microvascular thrombosis model.

Effects of (2R,4R)-4-methyl-1-[N(2)-(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl]-2-piperidine-carboxylic acid monohydrate (argatroban) and unfractionated heparin (UFH) were compared with respect to thrombus formation and tissue-type plasminogen activator (t-PA)-induced thrombolysis in a microvasculature thrombosis model. The antithrombotic activities of anticoagulants were evaluated with respect to the time required for the initiation of thrombus formation (T(i)) and the time required for the thrombus to stop blood flow (T(s)). The effects of anticoagulants administered with t-PA were evaluated by percent stenosis of the vessel and percent area of the thrombus. Argatroban (1-3 mg/kg/bolus) significantly prolonged T(i) and T(s) in a dose-dependent fashion compared to control. Argatroban (3 mg/kg/bolus) significantly prolonged both the T(i) and T(s) more effectively than UFH (100 anti-XaU (a-XaU)/kg/bolus), despite equivalent prolongation of the activated partial thromboplastin time (aPTT). Higher doses of UFH (300-500 a-XaU/kg) were required to significantly prolong T(i) and T(s), but at these doses, UFH caused over-prolongation of aPTT (>180 s), which might consequently cause bleeding complications. Argatroban (0.1-0.3 mg/kg/h) significantly accelerated thrombolysis by t-PA in both a dose- and time-dependent fashion. Although argatroban (0.1-0.2 mg/kg/h) did not significantly prolong the aPTT and bleeding time (BT) as compared with control, it significantly accelerated thrombolysis by t-PA at these doses of lower bleeding risk. Argatroban (0.3 mg/kg/h) significantly enhanced thrombolysis by t-PA, while UFH (12.5 anti-XaU/kg/h) attenuated it again, despite equivalent prolongation of the aPTT and BT. We conclude that argatroban seems to be a more efficient and safer anticoagulant than UFH for the prevention of thrombus formation and acceleration of t-PA-induced thrombolysis.