Phenylephrine enhances glutamate release in the medial prefrontal cortex through interaction with N-type Ca2+ channels and release machinery.

α1 -adrenoceptors (α1 -ARs) stimulation has been found to enhance excitatory processes in many brain regions. A recent study in our laboratory showed that α1 -ARs stimulation enhances glutamatergic transmission via both pre- and post-synaptic mechanisms in layer V/VI pyramidal cells of the rat medial prefrontal cortex (mPFC). However, a number of pre-synaptic mechanisms may contribute to α1 -ARs-induced enhancement of glutamate release. In this study, we blocked the possible post-synaptic action mediated by α1 -ARs to investigate how α1 -ARs activation regulates pre-synaptic glutamate release in layer V/VI pyramidal neurons of mPFC. We found that the α1 -ARs agonist phenylephrine (Phe) induced a significant enhancement of glutamatergic transmission. The Phe-induced potentiation was mediated by enhancing pre-synaptic glutamate release probability and increasing the number of release vesicles via a protein kinase C-dependent pathway. The mechanisms of Phe-induced potentiation included interaction with both glutamate release machinery and N-type Ca(2+) channels, probably via a pre-synaptic Gq /phospholipase C/protein kinase C pathway. Our results may provide a cellular and molecular mechanism that helps explain α1 -ARs-mediated influence on PFC cognitive functions. Alpha1 -adrenoceptor (α1 -ARs) stimulation has been reported to enhance glutamatergic transmission in layer V/VI pyramidal neurons of the rat medial prefrontal cortex (mPFC). We found that α1 -ARs agonist phenylephrine (Phe) increases pre-synaptic glutamate release probability and the number of released vesicles via interaction with both glutamate release machinery and N-type Ca(2+) channels. Our results may provide a cellular and molecular mechanism that helps explain α1 -ARs-mediated influence on PFC cognitive functions. Gq, Gq protein; PLC, phospholipase C; PKC, protein kinase C; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-d-aspartate; Glu, glutamate; Phe, phenylephrine.

[Treating Elderly Coronary Heart Disease Patients by Different Approaches of Percutaneous Coronary Intervention: an Observation of Clinical Efficacy].

OBJECTIVE: To observe thee efficacy of different ways of percutaneous coronary intervention (PCI) for treating elderly coronary heart disease (CHD) patients. METHODS: Totally 470 elderly CHD patients were classified to three age brackets (equal to or more than 85 years old, 60 to 74 years old, 75 to 84 years old). They were assigned to the transradial intervention (TRI) group (236 cases) and the transfemoral intervention (TFI) group (234 cases) according to different intervention pathways. Correlated indices and postoperative clinical efficacy were compared between the two groups. RESULTS: A higher successful rate of surgery was obviously got in patients 85 years old or older than 85 than in those 60 to 74 years old and 75 to 84 years old (P <0. 05). The incidence of major cardiovascular events (MACE) was reduced at post-operative 12 and 24 months in patients 85 years old or older than 85 (P <0. 05). The case number for changing intervention pathway were increased in the TRI group with statistical difference (P <0. 05). Compared with the TFI group, the case number for changing intervention pathway was increased; the time for arteriopuncture, the time for catheterization, and the time for X-ray exposure were prolonged; the time for postoperative bedding were obviously shortened; the incidence of vascular complications at the puncture site were lowered. The incidence of postoperative 12-month MACE was lowered, all with statistical difference (all P <0. 05). The incidence of MACE within postoperative 24-month MACE decreased in patients 60 to 74 years old and 75 to 84 years old (P <0. 05). The incidence of MACE within postoperative 24 months increased in patients 85 years old or older than 85 of the TRI group with statistical difference (P <0. 05). CONCLUSION: TRI can be preferably chosen for PC in treating elderly CHD patients.

Activation of α1-adrenoceptors enhances excitatory synaptic transmission via a pre- and postsynaptic protein kinase C-dependent mechanism in the medial prefrontal cortex of rats.

The physiological effects of α1-adrenoceptors (α1-ARs) have been examined in many brain regions. However, little is known about the mechanism of modulation on synaptic transmission by α1-ARs in the medial prefrontal cortex (mPFC). The present study investigated how α1-AR activation regulates glutamatergic synaptic transmission in layer V/VI pyramidal cells of the rat mPFC. We found that the α1-AR agonist phenylephrine (Phe) induced a significant enhancement of the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs). The facilitation effect of Phe on the frequency of mEPSCs involved a presynaptic protein kinase C-dependent pathway. Phe produced a significant enhancement on the amplitude of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R)- and N-methyl-D-aspartic acid receptor (NMDA-R)-mediated evoked excitatory postsynaptic currents (eEPSCs). Phe enhanced inward currents evoked by puff application of glutamate or NMDA. The Phe-induced facilitation of AMPA-R- and NMDA-R-mediated eEPSCs required, in part, postsynaptic Gq , phospholipase C and PKC. These findings suggest that α1-AR activation facilitates excitatory synaptic transmission in mPFC pyramidal cells via both pre- and post-synaptic PKC-dependent mechanisms.

Early hepatitis B viral DNA clearance predicts treatment response at week 96.

AIM: To investigate whether hepatitis viral DNA load at 24 wk of treatment predicts response at 96 wk in patients with chronic hepatitis B. METHODS: A total of 172 hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B patients who received initial treatment at 16 tertiary hospitals in Hunan Province, China were enrolled in this study. All patients received conventional doses of lamivudine and adefovir dipivoxil, telbivudine, entecavir dispersible tablets, or entecavir tablets for 96 wk. Patients who used other antiviral drugs or antitumor and immune regulation therapy were excluded. Patients were stratified into three groups according to their viral DNA load at 24 wk: < 10 IU/mL (group 1), 10-103 IU/mL (group 2), and > 103 IU/mL (group 3). Correlations of 24-wk DNA load with HBeAg negative status and HBeAg seroconversion at 96 wk were analyzed. Receiver operating characteristic curve analysis was used to test the predictive value of the HBV DNA load at 24 wk for long-term response. RESULTS: The rates of conversion to HBeAg negative status and HBeAg seroconversion rates were 53.7% and 51.9%, respectively, in group 1; 35.21% and 32.39% in group 2; and 6.38% and 6.38% in group 3. The receiver operating characteristic curves for the three subgroups revealed that the lowest DNA load (< 10 IU/mL) was better correlated with response at 96 wk than a higher DNA load (10-103 IU/mL). Nested PCR was used for amplifying and sequencing viral DNA in patients with a viral DNA load > 200 IU/mL at 96 wk; resistance mutations involving different loci were present in 26 patients, and three of these patients had a viral DNA load 10-103 IU/mL at 96 wk. CONCLUSION: Hepatitis B viral DNA load at 24 wk of antiviral treatment in patients with chronic hepatitis B is a predictor of the viral load and response rate at 96 wk.

Behavioral representation of cost and benefit balance in rats.

Decision making is dependent upon individual motivation. Previous studies showed that animals with higher levels of motivation are more likely to invest more time to acquire larger rewards rather than acquiring smaller rewards with less time to wait. However, little is known about how this motivation mediates the cognitive effort animals devote upon making said decisions in detail. In the present study, we investigated the behavioral response in a goal-directed action under a differential reward schedule by training rats to perform a "Do more, get more" (DM-GM) task using a nosepoke operandum when longer nosepoke durations resulted in correspondingly larger rewards. In general, the subjects learned this DM-GM rule and reached a steady behavioral state within 15days. During the training stage, the rats found the most cost-effective action choice and behaved according to that guideline more frequently than other possible actions. In addition, when the cost-benefit ratio changed, the rats again found a new most cost-effective choice to obtain maximum rewards. Our results demonstrate that there is a "balance point" of cost and benefit in rat valuation system and that this "balance point" not only guides the rats to make the appropriate decision, but that this point can be modified upon new situations to choose a newer optimum action plan.

Reduction of glutamate release probability and the number of releasable vesicles are required for suppression of glutamatergic transmission by ß1-adrenoceptors in the medial prefrontal cortex.

The prefrontal cortex (PFC) plays a critical role in cognitive functions, including working memory, attention regulation and behavioral inhibition. Microinjection of ß1-adrenoceptor (ß1-AR) agonist into the PFC has been shown to impair PFC cognitive function. However, the underlying cellular and molecular mechanisms have not been determined yet. In the present study, we tested the hypothesis that ß1-AR mediated modulation of excitatory synaptic transmission contributes to PFC dysfunction. We found that 1) the ß1-AR agonist Dobutamine (Dobu) suppressed the amplitude evoked excitatory postsynaptic currents (eEPSCs). 2) Dobu induced a significant suppression of the frequency and amplitude of miniature EPSCs (mEPSCs). 3) Dobu-suppressed glutamate release was mediated via decreasing release probability and the number of releasable vesicles. 4) Dobu suppressed inward currents evoked by puff application of glutamate or NMDA via postsynaptic PKA-dependent pathway. The present study indicates that ß1-AR activation suppresses excitatory synaptic transmission in medial PFC (mPFC) via both pre- and post-synaptic PKA-dependent mechanisms. Our results may provide a cellular and molecular mechanism that helps explain ß1-AR-induced PFC dysfunction.