Park JB. Enhanced astroglial GABA uptake attenuates tonic GABA A inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure. J Neurophysiol 114: 914 -926, 2015. First published June 10, 2015 doi:10.1152/jn.00080.2015.-␥-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents (I tonic ) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABA A receptors (GABA A Rs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of I tonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The I tonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced I tonic sensitivity to THIP argued for the decreased function of GABA A R ␦ subunits in HF, whereas similar I tonic sensitivity to benzodiazepines argued against the difference of ␥ 2 subunit-containing GABA A Rs in SHAM and HF rats. HF I tonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal I tonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF I tonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABA A Rs function, the enhanced astroglial GABA uptake-induced attenuation of I tonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure.

Background:The purpose of this study was to compare the effects of esmolol, esmolol and nicardipine or remifentanil on MBP, HR and recovery in gynecologic laparoscopic surgery.Methods: Eighty patients scheduled for gynecologic laparoscopic surgery were randomly allocated to four groups: group C (control group, n = 20); group E (esmolol group, n = 20) received esmolol 1 mg/kg, followed by 5 μg/kg/min; group EN (esmolol ＋ nicardipine group, n = 20) received esmolol 1 mg/kg and nicardipine 15 μg/kg, followed by an esmolol infusion 5 μg/kg/min; and group R (remifentanil group, n = 20) received remifentanil 1 μg/kg, followed by 0.05 μg/kg/min. The MBP and HR were measured at preinduction, after induction, at 1, 3, 5 min after intubation, before and after insufflation of CO2 and during surgical procedures. Recovery profiles and postoperative side effects were assessed.Results: The change of MBP after intubation was significantly decreased in group EN. The change of HR after intubation and during surgical procedure were significantly decreased in group E and group R. Recovery profiles were significantly faster in all study groups compared with group C.Conclusions: The use of esmolol in combination with nicardipine was effective in preventing the increase of MBP after intubation, whereas esmolol or remifentanil had attenuated the acute change of HR to noxious stimuli. Also the use of esmolol, nicardipine or remifentanil as an adjuvant to sevoflurane-N2O anesthesia in gynecologic laparoscopic surgery had facilitated the recovery.

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Curcumin, a hydrophobic polyphenol isolated from the Curcuma longa L. plant, has many pharmacological properties, including antioxidant, anti-inflammatory, and chemo-preventive activities. Curcumin has been shown to have potential in preventing nonalcoholic fatty liver disease (NAFLD). However, the low bioavailability of curcumin has proven to be a major limiting factor in its clinical adoption. Theracurmin, a highly bioavailable curcumin that utilizes micronized technology showed improved biological absorbability in vivo. The aim of this study was to investigate the role of theracurmin in modulating hepatic lipid metabolism in vivo. A fatty liver mouse model was produced by feeding mice a high fat diet (HFD; 60% fat) for 12 weeks. We found that treatment for 12 weeks with theracurmin significantly lowered plasma triacylglycerol (TG) levels and reduced HFD-induced liver fat accumulation. Theracurmin treatment lowered hepatic TG and total cholesterol (T-CHO) levels in HFD-fed mice compared to controls. In addition, theracurmin administration significantly reduced lipid peroxidation and cellular damage caused by reactive oxygen species in HFD-fed mice. Overall, these results suggest that theracurmin has the ability to control lipid metabolism and can potentially serve as an effective therapeutic remedy for the prevention of fatty liver.