Wei-Hong Ge

Pharmacist Interventions for Prophylactic Antibiotic Use in Urological Inpatients Undergoing Clean or Clean-Contaminated Operations in a Chinese Hospital

Objectives To evaluate the impact and cost-benefit value of pharmacist interventions for prophylactic antibiotic use in surgical patients undergoing clean or clean-contaminated operations. Methods A pre-to-post intervention study was performed in the Department of Urological Surgery of a tertiary hospital. Patients admitted from January through June 2011, undergoing clean or clean-contaminated surgery, served as the pre-intervention group; patients admitted from January through June 2012 formed the post-intervention group. Pharmacist interventions were performed for the surgeries in the post-intervention group. The criteria for the rational use of antibiotic prophylaxis were established by the hospital administration. The pharmacist interventions included real-time monitoring of medical records and controlling of the prescriptions of prophylactic antibiotics against the criteria. The pre- and post-intervention groups were then compared to evaluate the outcomes of the pharmacist interventions. A cost-benefit analysis was performed to determine the economic effects of implementing the pharmacist intervention on preoperative antibiotic prophylaxis. Results After the pharmacist intervention, a significant decrease was found in the rate of no indications for prophylactic antibiotic use (p = 0.004), the rate of broad-spectrum antibiotic use (p<0.001), the rate of drug replacement (p<0.001) and the rate of prolonged duration of prophylaxis (p<0.001). Significant reductions were observed in the mean antibiotic cost (p<0.001), the mean duration of antibiotic prophylaxis (p<0.001) and the mean number of antibiotics used (p<0.001). A significant increase was observed in the rate of correct choice of antibiotics (p<0.001). The ratio of the net mean cost savings for antibiotics to the mean cost of pharmacist time was approximately 18.79∶1. Conclusion Real-time interventions provided by a clinical pharmacist promoted rational use of prophylactic antibiotics, with a significant reduction in antibiotic costs, thus leading to favorable economic outcomes.

Dihydromyricetin modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate ethanol-induced hepatic injury

Increasing evidence has demonstrated that dihydromyricetin (DMY) contains highly effective antioxidative, anti-inflammatory, anti-microbial and anti-diabetic properties. Nevertheless, the underlying hepatoprotective mechanisms of DMY have infrequently been reported thus far. In the present study, C57BL/6 mice were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as a control diet with or without DMY (75 and 150mg/kg/d bw) for 6 weeks. DMY significantly attenuated hepatic enzyme release, hepatic lipid peroxidation and triglyceride deposition induced by chronic alcohol exposure. In addition, DMY dramatically attenuated the alcohol-triggered elevation of the level of inflammatory cytokines and partially recovered hepatic pathological changes. Notably, DMY remarkably modified aberrant expression of CYP2E1, Keap-1 and HO-1 in the liver and simultaneously ameliorated disordered nuclear localization of NF-κB and Nrf2 to exert its hepatoprotective effects. Further mechanistic exploration suggested that DMY activated Nrf2, possibly mediated through the autophagy pathway. Analysis of the crosstalk among p62, Keap-1 and Nrf2 demonstrated that the p62 upregulation caused by DMY contributes to a positive feedback loop in Nrf2 activation. In summary, DMY likely modulates p62 and autophagy crosstalk with the Keap-1/Nrf2 pathway to alleviate liver steatosis and the inflammatory response in the pathological progression of ALD.

Electrophysiological characterization of methyleugenol: a novel agonist of GABA(A) receptors.

Methyleugenol (ME) is a natural constituent isolated from many plant essential oils having multiple biological effects including anticonvulsant and anesthetic activities, although the underlying mechanisms remain unclear. Here, we identify ME as a novel agonist of ionotropic γ-aminobutyric acid (GABA) receptors. At lower concentrations (∼30 μM), ME significantly sensitized GABA-induced, but not glutamate- or glycine-induced, currents in cultured hippocampal neurons, indicative of a preferentially modulatory role of this compound for A type GABA receptors (GABAARs). In addition, ME at higher concentrations (≥100 μM) induced a concentration-dependent, Cl(-)-permeable current in hippocampal neurons, which was inhibited by a GABAAR channel blocker, picrotoxin, and a competitive GABAAR antagonist, bicuculline, but not a specific glycine receptor inhibitor, strychnine. Moreover, ME activated a similar current mediated by recombinant α1-β2-γ2 or α5-β2-γ2 GABAARs in human embryonic kidney (HEK) cells. Consequently, ME produced a strong inhibition of synaptically driven neuronal excitation in hippocampal neurons. Together, these results suggest that ME represents a novel agonist of GABAARs, shedding additional light on future development of new therapeutics targeting GABAARs. The present study also adds GABAAR activation to the list of molecular targets of ME that probably account for its biological activities.

Preparation of chitosan-collagen-alginate composite dressing and its promoting effects on wound healing

The present study aimed to prepare a composite dressing composed of collagen, chitosan, and alginate, which may promote wound healing and prevent from seawater immersion. Chitosan-collagen-alginate (CCA) cushion was prepared by paintcoat and freeze-drying, and it was attached to a polyurethane to compose CCA composite dressing. The swelling, porosity, degradation, and mechanical properties of CCA cushion were evaluated. The effects on wound healing and seawater prevention of CCA composite dressing were tested by rat wound model. Preliminary biosecurity was tested by cytotoxicity and hemocompatibility. The results revealed that CCA cushion had good water absorption and mechanical properties. A higher wound healing ratio was observed in CCA composite dressing treated rats than in gauze or chitosan treated ones. On the fifth day, the healing rates of CCA composite dressing, gauze, and chitosan were 48.49%±1.07%, 28.02%±6.4%, and 38.97%±8.53%, respectively. More fibroblast and intact re-epithelialization were observed in histological images of CCA composite dressing treated rats, and the expressions of EGF, bFGF, TGF-β, and CD31 increased significantly. CCA composite dressing showed no significant cytotoxicity, and favorable hemocompatibility. These results suggested that CCA composite dressing could prevent against seawater immersion and promote wound healing while having a good biosecurity.

Preparation of total flavonoids from loquat flower and its protective effect on acute alcohol-induced liver injury in mice

This study aimed to research the preparation techniques of total flavones from loquat flower (TFLF), its anti-oxidation capacity, and its protective effect on hepatic injury. The best extraction parameters by orthogonal experimentation were water at 100°C, extraction time 2.5 hours, solid/liquid ratio 1:20, and three decoctions. The chromogenic reaction to the flavones showed that loquat flowers mainly contained flavone, flavonol, and flavanone compounds combining ortho-phenolic hydroxyl group structure in the 10-30% ethanol fraction. The anti-oxidant capacity of O2-· was 26.09% and of OH-·was 83.01% by salicylic acid and pyrogallol auto-oxidation. Compared with the model group, TFLF lowered the levels of alanine aminotransferase, aspartate aminotransferase, triglyceride, and malondialdehyde and liver index significantly, and upregulated the expression of adipose triglyceride lipase and Heine oxygenase-1 mRNA. The present findings suggest that TFLF has protective effect on acute alcoholinduced liver injury in mice and may be related to its antioxidant and free-radical scavenging activity.

Curcumol allosterically modulates GABA(A) receptors in a manner distinct from benzodiazepines

Inhibitory A type γ-aminobutyric acid receptors (GABAARs) play a pivotal role in orchestrating various brain functions and represent an important molecular target in neurological and psychiatric diseases, necessitating the need for the discovery and development of novel modulators. Here, we show that a natural compound curcumol, acts as an allosteric enhancer of GABAARs in a manner distinct from benzodiazepines. Curcumol markedly facilitated GABA-activated currents and shifted the GABA concentration-response curve to the left in cultured hippocampal neurons. When co-applied with the classical benzodiazepine diazepam, curcumol further potentiated GABA-induced currents. In contrast, in the presence of a saturating concentration of menthol, a positive modulator for GABAAR, curcumol failed to further enhance GABA-induced currents, suggesting shared mechanisms underlying these two agents on GABAARs. Moreover, the benzodiazepine antagonist flumazenil did not alter the enhancement of GABA response by curcumol and menthol, but abolished that by DZP. Finally, mutations at the β2 or γ2 subunit predominantly eliminated modulation of recombinant GABAARs by curcumol and menthol, or diazepam, respectively. Curcumol may therefore exert its actions on GABAARs at sites distinct from benzodiazepine sites. These findings shed light on the future development of new therapeutics drugs targeting GABAARs.

Tat-HA-NR2B9c attenuate oxaliplatin-induced neuropathic pain

&NA; Oxaliplatin is a commonly used chemotherapy drug, which can produce acute and chronic peripheral neurotoxicity. Currently, there is no good therapeutic drug in clinic. Excessive stimulation of N‐methyl‐D‐aspartate receptors (NMDARs) is crucial for the transmission of pain signals. However, directly inhibiting NMDARs can cause severe side effects because they have key physiological functions in the Central nervous system (CNS). Several years ago, we prepared a polypeptide Tat‐HA‐NR2B9c which can disturb NMDARs–postsynaptic density protein‐95 (PSD‐95) interaction. In this study, we studied whether Tat‐HA‐NR2B9c could be an effective treatment for oxaliplatin‐induced neuropathic pain. To conform it, a rat model of oxaliplatin‐induced neuropathic was established, and analgesic effect of Tat‐HA‐NR2B9c was studied. Here, we show that oxaliplatin induces the interaction of NMDARs with PSD‐95. Uncoupling the complex by Tat‐HA‐NR2B9c has potent analgesic effect in oxaliplatin‐induced cold hyperalgesia and mechanical allodynia without suppressing general behavioral. Tat‐HA‐NR2B9c neither inhibits NMDARs function nor impacts antitumor activity of oxaliplatin. Thus, this new drug may serve as a treatment for oxaliplatin‐induced neuropathic pain, perhaps without major side effects.

Semen hoveniae extract ameliorates alcohol-induced chronic liver damage in rats via modulation of the abnormalities of Gut-Liver Axis

BACKGROUND Hovenia dulcis Thunb. is considered as a traditional herbal medicine that has been used in the treatment for ethanol-induced liver disease for centuries. Recently, substantial studies demonstrated that Semen hoveniae extract (SHE) not only suppressed the hepatic steatosis caused by chronic ethanol exposure, but also inhibited lipopolysaccharide-stimulated inflammatory responses. Nevertheless, the underlying molecular mechanisms largely remained elusive. AIM To determine the hepatoprotective effects of SHE on ethanol-triggered liver damage and further elucidate its potential mechanisms. METHODS In the present study, the Sprague-Dawley rats were fed with the Lieber-DeCarli diet containing alcohol or isocaloric maltose dextrin as control diet with or without SHE (300 and 600 mg/kg/d bw) for 8 weeks. The levels of serum biomarkers (ALT, AST and LDH) and LPS were detected by biochemical assay kits and endotoxin detection LAL kit, respectively. The histopathological changes of liver and intestinal tissues were observed by hematoxylin and eosin (H&E) staining and Transmission electron microscope (TEM). The expressions of CD14, TLR4, MyD88, NF-κB, Iκ-B, P-Iκ-B and TNF-α in liver, and ZO-1 and occludin in intestine were determined by western blot. The faecal microbial composition was determined by16S rRNA Gene Sequencing Analysis. RESULTS Biochemical and histopathological analysis revealed that SHE significantly alleviated the lipid deposition and inflammation response in liver induced by ethanol. SHE remarkably inhibited the TLR4 pathway and its downstream inflammatory mediators, and up-regulated the expressions of ZO-1 and occludin in the intestine. The further investigations suggested SHE dramatically reversed ethanol-induced alterations in the intestinal microbial flora and decreased the generation of gut-derived endotoxin. CONCLUSION In summary, SHE probably modulated abnormalities of gut-liver axis and inhibited TLR4-associated inflammatory mediators activation to exert its hepatoprotective properties. These findings suggested that SHE as a traditional therapeutic options which may play an essential role in protecting against the chronic ethanol-triggered liver injury.

Quercetin Reduces Cortical GABAergic Transmission and Alleviates MK-801-Induced Hyperactivity

An imbalance between neuronal excitation and inhibition represents a core feature in multiple neuropsychiatry disorders, necessitating the development of novel strategies to calibrate the excitatory–inhibitory balance of therapeutics. Here we identify a natural compound quercetin that reduces prefrontal cortical GABAergic transmission and alleviates the hyperactivity induced by glutamatergic N-methyl-d-aspartate receptor antagonist MK-801. Quercetin markedly reduced the GABA-activated currents in a noncompetitive manner in cultured cortical neurons, and moderately inhibited spontaneous and electrically-evoked GABAergic inhibitory postsynaptic current in mouse prefrontal cortical slices. Notably, systemic and prefrontal-specific delivery of quercetin reduced basal locomotor activity in addition to alleviated the MK-801-induced hyperactivity. The effects of quercetin were not exclusively dependent on α5-subunit-containing A type GABA receptors (GABAARs), as viral-mediated, region-specific genetic knockdown of the α5-subunit in prefrontal cortex improved the MK-801-evoked psychotic symptom but reserved the pharmacological responsivity to quercetin. Both interventions together completely normalized the locomotor activity. Together, quercetin as a negative allosteric GABAAR modulator exerted antipsychotic activity, facilitating further therapeutic development for the excitatory–inhibitory imbalance disorders.

Chimeric Peptide Tat-HA-NR2B9c Improves Regenerative Repair after Transient Global Ischemia

Transient global ischemia (TGI) is a major public health problem, and it heightens the need of effective treatments. The present study was undertaken to investigate whether recombinant polypeptide Tat-HA-NR2B9c improves spatial learning and memory deficits in rats after TGI. Rats were subjected to 20-min ischemia induced by four-vessel occlusion (4-VO) method and daily injected with Tat-HA-NR2B9c (1.12 mg/kg) for 1 week. Tat-HA-NR2B9c increased CREB activity, upregulated B-cell lymphoma-2 (Bcl-2) expression after treated for 24 h. There was a significant increase in dendrite spine density in hippocampal CA1 region and BrdU-positive cells and BrdU/NeuN-positive cells in the dentate gyrus after Tat-HA-NR2B9c treatment, compared with ischemia group at postischemic day 28. Inhibition of the CREB activation by recombinant lentivirus, LV-CREB133-GFP, abolished the upregulation effects of Tat-HA-NR2B9c on Bcl-2 expression. Moreover, Tat-HA-NR2B9c improved the impaired spatial learning and memory ability in Morris water maze. These results suggest that Tat-HA-NR2B9c substantially ameliorated the TGI-induced loss of dendrite spine in hippocampal CA1, increased neurogenesis in dentate gyrus, and significantly improved cognitive abilities by the CREB pathway in rats after transient global cerebral ischemia. It may be served as a treatment for TGI.