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  • Wiley  (7)
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  • 1
    Online Resource
    Online Resource
    The median effective concentration of propofol with different doses of esketamine during gastrointestinal endoscopy in elderly patients: A randomized controlled trial
    Wiley ; 2022
    In:  British Journal of Clinical Pharmacology Vol. 88, No. 3 ( 2022-03), p. 1279-1287
    Details
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 88, No. 3 ( 2022-03), p. 1279-1287
    Abstract: Propofol may result in hypotension, bradycardia and loss of protective reflexes, especially in elderly patients, while esketamine, a N‐methyl‐D‐aspartate receptor antagonist, has analgesic, anaesthetic and sympathomimetic properties and is known to cause less cardiorespiratory depression. We hypothesized that esketamine may reduce the median effective concentration (EC 50 ) of propofol and coadministration is less likely to produce hypotension during gastrointestinal endoscopy in elderly patients. Methods Ninety elderly patients, aged 65–89 years, undergoing gastrointestinal endoscopy were randomly assigned into 3 groups: SK0 (control) group (0 mg/kg esketamine); SK0.25 group (0.25 mg/kg esketamine); and SK0.5 group (0.5 mg/kg esketamine). Anaesthesia was achieved by plasma target‐controlled infusion of propofol with different bolus doses of esketamine. The EC 50 of propofol for gastrointestinal endoscopy was determined by using the up‐and‐down method of Dixon. The initial plasma target concentration is 2.5 μg/mL and the adjacent concentration gradient is 0.5 μg/mL. Cardiovascular variables were also measured. Results Propofol EC 50 s and its 95% confidence interval for gastrointestinal endoscopy in elderly patients were 3.69 (2.59–4.78), 2.45 (1.85–3.05) and 1.71 (1.15–2.27) μg/mL in the SK0, SK0.25 and SK0.5 groups, respectively ( P   〈  .05). The average percent change from baseline mean arterial pressure was −19.7 (7.55), −15.2 (7.14) and −10.1 (6.73), in the SK0, SK0.25 and SK0.5 groups, respectively ( P  〈  .001). Conclusion Combination medication of propofol with esketamine reduced the propofol EC 50 during gastrointestinal endoscopy in elderly patients compared with administration of propofol without esketamine. Increasing doses of SK with propofol are less likely to produce hypotension with shorter recovery time.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
    URL: Article
    DOI: 10.1111/bcp.v88.3
    DOI: 10.1111/bcp.15072
    RVK:
    XA 33650
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 1498142-7
    SSG: 15,3
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  • 2
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    Online Resource
    An LC–MS/MS method for determination of bioactive components of liquorice and Semen Strychni in rat plasma: Application to a pharmacokinetics study
    Wiley ; 2018
    In:  Drug Testing and Analysis Vol. 10, No. 2 ( 2018-02), p. 262-271
    Details
    In: Drug Testing and Analysis, Wiley, Vol. 10, No. 2 ( 2018-02), p. 262-271
    Abstract: Semen Strychni is known for its treatment of rheumatic arthritis with a low therapeutic index. Liquorice contributes a lot in herb detoxification according to the traditional Chinese medicine theory. A simple, rapid, and sensitive liquid chromatography–mass spectrometric method (LC–MS) was developed and validated for simultaneous determination of main bioactive ingredients in liquorice and Semen Strychni in rat plasma. Using moclobemide and cyproterone acetate as the internal standards, the analytes were pretreated via protein precipitation with methanol. An Ultimate AQ‐C18 column (3.0 μm, 3.0 × 100 mm) was employed for chromatographic separation, combining with gradient elution. The mobile phase consisted of 0.07% formic acid and 0.12% ammonium acetate in aqueous phase (A) and acetonitrile in organic phase (B). The elution program was as follows: 0–0.5 min, 20% B; 0.5–1 min, 20–60% B; 1–7 min, 60–85% B; and 7–7.5 min, returned to 20% B, then continued to 12 min. Selected reaction monitoring was performed in both positive and negative ESI. Positive mode was adopted for detection of strychnine, brucine, and moclobemide, while negative mode was used for glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, isoliquiritigenin, liquiritin, and cyproterone acetate. The method was validated for specificity, linearity, matrix effect, recovery, precision, accuracy, and stability. The results show that this method is sensitive, accurate and robust for biological matrix analysis. Moreover, the proposed method was applied to a pharmacokinetic study in Sprague–Dawley rats for investigating the mechanism of which liquorice detoxifies Semen Strychni.
    Type of Medium: Online Resource
    ISSN: 1942-7603 , 1942-7611
    URL: Issue
    URL: Article
    DOI: 10.1002/dta.v10.2
    DOI: 10.1002/dta.2210
    Language: English
    Publisher: Wiley
    Publication Date: 2018
    detail.hit.zdb_id: 2462344-1
    SSG: 15,3
    SSG: 31
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  • 3
    Online Resource
    Online Resource
    P7C3‐A20 alleviates fatty liver by shaping gut microbiota and inducing FGF21/FGF1, via the AMP‐activated protein kinase/CREB regulated transcription coactivator 2 pathway
    Wiley ; 2021
    In:  British Journal of Pharmacology Vol. 178, No. 10 ( 2021-05), p. 2111-2130
    Details
    In: British Journal of Pharmacology, Wiley, Vol. 178, No. 10 ( 2021-05), p. 2111-2130
    Abstract: Non‐alcoholic fatty liver disease (NAFLD) is a worldwide public health problem with no established pharmacological therapy. Here, we explored the potential benefit of P7C3‐A20, a novel aminopropyl carbazole compound with neuroprotective activity, in a NAFLD model, induced in mice by a high‐fat diet (HFD). Experimental Approach C57BL/6J mice were given a HFD (42% fat content) for 16 weeks to induce NAFLD. P7C3‐A20 (20 mg·kg −1 ·day −1 ) was given by gavage for 2 weeks. Indirect calorimetry, histological analysis, immunoblotting, immunohistochemistry, and biomedical examinations were performed. Gut microbiota were determined using a 16S ribosomal RNA sequencing analysis. Key Results P7C3‐A20 treatment reduced body weight gain/adiposity, improved insulin resistance, promoted energy expenditure (O 2 consumption/CO 2 production), inhibited lipid oxidation, suppressed hepatic inflammation (Kupffer cell number and pro‐inflammatory factors), decreased necroptosis/apoptosis (receptor‐interacting protein kinase 3, cleaved caspase‐3, and TUNEL), and alleviated liver fibrosis and injury. Mechanistically, P7C3‐A20 stimulated FGF21 and FGF1 via activating liver kinase B1 (LKB1) and AMP‐activated protein kinase (AMPK), which further resulted in a reduced nuclear translocation of CREB‐regulated transcription coactivator 2 (CRTC2). In AMPKα2 knockout mice, the protection of P7C3‐A20 against HFD‐induced metabolism abnormalities and fat accumulation, as well as the elevation of blood FGF21 and FGF1, was abolished. P7C3‐A20 increased the gut microbiota species richness. Moreover, it enhanced the proportions of Akkermansia , Lactobacillus , and Prevotellaceae, while reducing the proportions of Enterobacteriaceae, Escherichia , and Parasutterella. Conclusions and Implications P7C3‐A20 increased levels of NAD+ and alleviated NAFLD through stimulating FGF21 and FGF1 in an LKB1/AMPK/CRTC2‐dependent manner and shaping gut microbiota. LINKED ARTICLES This article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc
    Type of Medium: Online Resource
    ISSN: 0007-1188 , 1476-5381
    URL: Issue
    URL: Article
    DOI: 10.1111/bph.v178.10
    DOI: 10.1111/bph.15008
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2029728-2
    SSG: 15,3
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  • 4
    Online Resource
    Online Resource
    Hepatitis C virus reinfection in patients on haemodialysis after achieving sustained virologic response with antiviral treatment
    Wiley ; 2022
    In:  Alimentary Pharmacology & Therapeutics Vol. 55, No. 4 ( 2022-02), p. 434-445
    Details
    In: Alimentary Pharmacology & Therapeutics, Wiley, Vol. 55, No. 4 ( 2022-02), p. 434-445
    Abstract: Data are limited regarding the risk of hepatitis C virus (HCV) reinfection after treatment‐induced sustained virologic response (SVR) in patients on haemodialysis. Aims To assess the risk of HCV reinfection among patients on haemodialysis with treatment‐induced SVR. Methods Patients on haemodialysis patients who achieved SVR 12 with interferon (IFN) or direct‐acting antiviral (DAA)‐based treatment received follow‐up at SVR 24 and then biannually with HCV RNA measurements. HCV reinfection was defined as the resurgence of viremia by different viral strains beyond SVR 12 . The low‐risk general population who achieved SVR 12 and who underwent the same post‐SVR 12 surveillance served as the reference group. Crude reinfection rates per 100 person‐years (PYs) were calculated. Multivariate Cox regression analysis was performed to estimate the relative risk of HCV reinfection between the two groups. Results We recruited 374 patients on haemodialysis and 1571 reference patients with a mean post‐SVR 12 follow‐up of 4.7 and 6.1 years. All haemodialysis patients who achieved SVR 12 also achieved SVR 24 . The incidence rates of HCV reinfection were 0.23 per 100 PYs (95% confidence interval [CI]: 0.09‐0.59) in haemodialysis patients and 0.16 per 100 PYs (95% CI: 0.10‐0.26) in the reference group. The risk of HCV reinfection in patients on haemodialysis was comparable to that in the reference patients (hazard ratio [HR] : 1.39; 95% CI: 0.44‐4.38, P  = 0.57). Conclusions The risk of HCV reinfection in patients on haemodialysis who achieve SVR 12 is low and comparable to that in the low‐risk general population. HCV microelimination in this special population is feasible once universal screening and scaled‐up treatment are implemented.
    Type of Medium: Online Resource
    ISSN: 0269-2813 , 1365-2036
    URL: Issue
    URL: Article
    DOI: 10.1111/apt.v55.4
    DOI: 10.1111/apt.16697
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2003094-0
    SSG: 15,3
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  • 5
    Online Resource
    Online Resource
    ALTERED l ‐ARGININE/NITRIC OXIDE SYNTHASE/NITRIC OXIDE PATHWAY IN THE VASCULAR ADVENTITIA OF RATS WITH SEPSIS
    Wiley ; 2006
    In:  Clinical and Experimental Pharmacology and Physiology Vol. 33, No. 12 ( 2006-12), p. 1202-1208
    Details
    In: Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 33, No. 12 ( 2006-12), p. 1202-1208
    Abstract: In recent studies, the vascular adventitia has been established as an important source of inducible nitric oxide synthase (iNOS) and subsequent nitric oxide (NO) production, even more powerful than the media in response to certain inflammatory factors, such as lipopolysaccharide (LPS). The adventitia has an independent l ‐arginine ( l ‐Arg)/NOS/NO pathway and is involved in the regulation of vascular function. In the present study, we explored the changes in and the pathophysiological significance of the l ‐Arg/NOS/NO pathway in the adventitia of rats with sepsis. Sepsis was induced by caecal ligation and puncture in order to observe changes in l ‐Arg transport, NOS gene expression and activity and NO generation in the vascular adventitia to determine the mechanism of activation of the l ‐Arg/NOS/NO pathway. Severe sepsis resulted in severe disturbance of haemodynamic features, with decreased mean arterial blood pressure, brachycardia and inhibited cardiac function (decreased left ventricular ±dP/dt max ). Left ventricular end‐diastolic pressure was elevated threefold ( P   〈  0.01) under anaesthesia. Rats with sepsis showed severe glucopenia and lacticaemia. Plasma levels of the inflammatory factors macrophage chemoattractant protein‐1 and interleukin‐8 were increased five‐ and 29‐fold, respectively ( P   〈  0.01). In the adventitia of the thoracic and abdominal aortas, the l ‐Arg/NO pathway was similarly characterized: the uptake of [ 3 H]‐ l ‐Arg was Na + independent, with the peak occurring at approximately 40 min incubation. Total NOS activity was largely calcium independent ( 〉  90%). The V max of l ‐Arg transport in the sepsis group was increased by 83.5% ( P   〈  0.01), but the K m value was not significantly different compared with controls. The mRNA levels of cationic amino acid transporter (CAT)‐1 and CAT‐2B in the sepsis group were increased by 86 and 62%, respectively (both P   〈  0.01). Inducible NOS activity was increased 2.8‐fold compared with controls ( P   〈  0.01) and iNOS mRNA levels were elevated approximately sixfold ( P   〈  0.01). The NO levels in the plasma and incubation media (incubation for 40 min) in the sepsis group were increased by 144 and 273%, respectively (both P   〈  0.01). The Arg/NOS/NO pathway was activated in the vascular adventitia of rats with sepsis shock. The l ‐Arg/NOS/NO pathway in the aortic adventitia may play an important role in the pathogenesis of sepsis and septic shock.
    Type of Medium: Online Resource
    ISSN: 0305-1870 , 1440-1681
    URL: Issue
    URL: Article
    DOI: 10.1111/cep.2006.33.issue-12
    DOI: 10.1111/j.1440-1681.2006.04498.x
    Language: English
    Publisher: Wiley
    Publication Date: 2006
    detail.hit.zdb_id: 2020033-X
    SSG: 15,3
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  • 6
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    Online Resource
    Effect of different doses of dexmedetomidine on the median effective concentration of propofol during gastrointestinal endoscopy: a randomized controlled trial
    Wiley ; 2023
    In:  British Journal of Clinical Pharmacology Vol. 89, No. 6 ( 2023-06), p. 1799-1808
    Details
    In: British Journal of Clinical Pharmacology, Wiley, Vol. 89, No. 6 ( 2023-06), p. 1799-1808
    Abstract: Dexmedetomidine could be an ideal adjuvant to propofol during gastrointestinal endoscopy because it provides both analgesia and sedation without respiratory depression. This study investigates the effect of different doses of dexmedetomidine on the median effective concentration of propofol during gastrointestinal endoscopy. Methods Ninety adult patients were randomly assigned to Group Control, Group DEX0.5 (0.5 μg/kg dexmedetomidine) or Group DEX1.0 (1.0 μg/kg dexmedetomidine). Anaesthesia during endoscopy was implemented by plasma target‐controlled infusion (TCI) of propofol with different doses of dexmedetomidine. TCI concentration of the first patient for each group was 2.5 μg/mL and the consecutive adjacent concentration gradient was 0.5 μg/mL. Median effective concentration (EC 50 ) of propofol by TCI for gastrointestinal endoscopy was determined by using the modified Dixon's up‐and‐down method. Cardiovascular variables were also measured. Results EC 50 of propofol by TCI and 95% confidence interval (CI) for gastrointestinal endoscopy were 3.77 (3.48–4.09), 2.51 (2.27–2.78) and 2.10 (1.90–2.33) μg/mL in Group Control, Group DEX0.5 and Group DEX1.0, respectively. The average percent change from heart rate (HR) baseline was 2.8 (8.9), −7.4 (7.7) and −10.5 (8.8) ( P   〈  .001), and the average percent change from mean arterial pressure (MAP) baseline was −10.6 [−24.7; 3.5], −9.5 [−29.2; 11.4] and −4.0 [−27.3; 15.5] ( P  = .034) in Group Control, Group DEX0.5 and Group DEX1.0, respectively. Conclusions Dexmedetomidine reduced the EC 50 of propofol by TCI. A 0.5–1 μg/kg dose of dexmedetomidine caused a decrease in HR without bradycardia. The decrease in dosage of propofol with increasing doses of dexmedetomidine caused more stable MAP. Dexmedetomidine is an ideal adjuvant drug to propofol during gastrointestinal endoscopy.
    Type of Medium: Online Resource
    ISSN: 0306-5251 , 1365-2125
    URL: Issue
    URL: Article
    DOI: 10.1111/bcp.v89.6
    DOI: 10.1111/bcp.15647
    RVK:
    XA 33650
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 1498142-7
    SSG: 15,3
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  • 7
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    Online Resource
    Hepatic NAD + deficiency as a therapeutic target for non‐alcoholic fatty liver disease in ageing
    Wiley ; 2016
    In:  British Journal of Pharmacology Vol. 173, No. 15 ( 2016-08), p. 2352-2368
    Details
    In: British Journal of Pharmacology, Wiley, Vol. 173, No. 15 ( 2016-08), p. 2352-2368
    Abstract: Ageing is an important risk factor of non‐alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD + ), a ubiquitous coenzyme, links ageing with NAFLD. Experimental Approach Hepatic concentrations of NAD + , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD + biosynthesis, were compared in middle‐aged and aged mice or patients. The influences of NAD + decline on the steatosis and steatohepatitis were evaluated in wild‐type and H247A dominant‐negative, enzymically‐inactive NAMPT transgenic mice (DN‐NAMPT) given normal or high‐fat diet (HFD). Key Results Hepatic NAD + level decreased in aged mice and humans. NAMPT‐controlled NAD + salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle‐age DN‐NAMPT mice displayed systemic NAD + reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro‐inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α‐SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD + precursor, completely corrected these NAFLD phenotypes induced by NAD + deficiency alone or HFD, whereas adenovirus‐mediated SIRT1 overexpression only partially rescued these phenotypes. Conclusions and Implications These results provide the first evidence that ageing‐associated NAD + deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD + substrates may be a promising therapeutic strategy to prevent and treat NAFLD.
    Type of Medium: Online Resource
    ISSN: 0007-1188 , 1476-5381
    URL: Issue
    URL: Article
    DOI: 10.1111/bph.v173.15
    DOI: 10.1111/bph.13513
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2029728-2
    SSG: 15,3
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