Nurses' Attitudes Toward Internet-Based Home Care: A Survey Study.

Internet-based home care has emerged as a way to relieve the burden of hospitals and meet patients' need for home care. This study aims to explore nurses' attitudes toward Internet-based home care. A cross-sectional online survey was conducted in Ningbo City in China. A self-designed Internet-based home care attitudes questionnaire for nurses (23 items) was used. There were 2039 nurses from 13 hospitals who participated in this online survey. Results reveal that, 1369 nurses (67.1%) were willing to provide Internet-based home care. However, there were significant differences in the attitudes of nurses with different ages (H = 11.86, P = .001), years of work experience (H = 24.257, P = .000), positions (H = 8.850, P = .031), and types of phones (H = 13.096, P = .001). More than 80% of nurses were willing to provide hypodermic and intramuscular injection. But there was a significant difference in the attitudes toward hypodermic injection, intramuscular injection, and pressure ulcer care in nurses with different ages (H = 13.039, P = .005; H = 9.178, P = .027; H = 10.997, P = .012) and a significant difference in the attitudes toward pressure ulcer care in nurses with different years of work experience (H = 15.259, P = .002). Results also indicated that most nurses were worried about their own safety and personal rights protection during Internet-based home care.

Involvement of UDP-glucuronosyltransferases in higenamine glucuronidation and the gender and species differences in liver.

OBJECTIVES: Higenamine (HG), an active ingredient of Aconite root in Chinese herbal medicine, is mainly metabolized by UDP-glucuronosyltransferases (UGT). However, the systematic glucuronidation of HG in humans remains unclear. The purpose of this study was to investigate the glucuronidation of HG. METHODS: 12 recombinant human UGT (rUGT) isozymes were used to characterize the HG glucuronidation. Liver microsomes from male and female mice, rats, guinea pigs, dogs, and humans were used to determine the species and gender differences using liquid chromatography-mass spectrometry. KEY FINDINGS: One monoglucuronide was detected in reactions catalyzed by rUGT1A6, rUGT1A8, rUGT1A9, also human and dog liver microsomes. UGT1A9 is the most important glucuronosyltransferase that metabolizes HG. Because carvacrol, a specific inhibitor of UGT1A9, can significantly decrease the glucuronidation of HG in Human liver microsomes and UGT1A9. HG metabolism by UGT1A9 described in Michaelis-Menten kinetics (Km=15.4 mM,Vmax=2.2 nmol/mg/min) and glucuronidation in liver microsomes were species dependent. Gender did not affect the kinetic parameters among species except in rats. CONCLUSIONS: UGT1A9 is a major isoenzyme responsible for the glucuronidation of HG in Human liver microsomes (HLMs). Dog may be an appropriate animal model to evaluate HG metabolism.

Reductive metabolism of oxymatrine is catalyzed by microsomal CYP3A4.

Oxymatrine (OMT) is a pharmacologically active primary quinolizidine alkaloid with various beneficial and toxic effects. It is confirmed that, after oral administration, OMT could be transformed to the more toxic metabolite matrine (MT), and this process may be through the reduction reaction, but the study on the characteristics of this transformation is limited. The aim of this study was to investigate the characteristics of this transformation of OMT in the human liver microsomes (HLMs) and human intestinal microsomes (HIMs) and the cytochrome P450 (CYP) isoforms involved in this transformation. The current studies demonstrated that OMT could be metabolized to MT rapidly in HLMs and HIMs and CYP3A4 greatly contributed to this transformation. All HLMs, HIMs, and CYP3A4 isoform mediated reduction reaction followed typical biphasic kinetic model, and Km, Vmax, and CL were significant higher in HLMs than those in HIMs. Importantly, different oxygen contents could significantly affect the metabolism of OMT, and with the oxygen content decreased, the formation of metabolite was increased, suggesting this transformation was very likely a reduction reaction. Results of this in vitro study elucidated the metabolic pathways and characteristics of metabolism of OMT to MT and would provide a theoretical basis and guidance for the safe application of OMT.

Breast cancer resistance protein-mediated efflux of luteolin glucuronides in HeLa cells overexpressing UDP-glucuronosyltransferase 1A9.

PURPOSE: UDP-glucuronosyltransferases (UGTs) are responsible for the formation of glucuronides of polyphenolic flavonoids. This study investigated the UGT1A9-mediated glucuronidation of luteolin and the kinetics of luteolin glucuronide efflux. METHOD: HeLa cells overexpressing UGT1A9 (HeLa-UGT1A9) were used to determine the kinetics of breast cancer resistance protein (BCRP)-mediated transport of luteolin glucuronides. Human UGT isoforms were used to determine glucuronidation rates. RESULTS: UGT1A9 was found to catalyze the production of four luteolin glucuronides, including three known monoglucuronides and a novel 3', 4'-diglucuronide. Ko143, a potent specific inhibitor of BCRP, significantly inhibited efflux of luteolin monoglucuronides from HeLa1A9 cells and increased their intracellular levels in a dose-dependent manner. The formation of luteolin diglucuronide was observed when intracellular concentration of total monoglucuronides went above 0.07 nM. CONCLUSIONS: Intracellular accumulation of diglucuronide was detected at high monoglucuronide concentrations (>0.07 nM). Diglucuronide production is speculated to be a compensatory pathway for luteolin disposition.

Monoester-Diterpene Aconitum Alkaloid Metabolism in Human Liver Microsomes: Predominant Role of CYP3A4 and CYP3A5.

Aconitum, widely used to treat rheumatoid arthritis for thousands of years, is a toxic herb that can frequently cause fatal cardiac poisoning. Aconitum toxicity could be decreased by properly hydrolyzing diester-diterpene alkaloids into monoester-diterpene alkaloids. Monoester-diterpene alkaloids, including benzoylaconine (BAC), benzoylmesaconine (BMA), and benzoylhypaconine (BHA), are the primary active and toxic constituents of processed Aconitum. Cytochrome P450 (CYP) enzymes protect the human body by functioning as the defense line that limits the invasion of toxicants. Our purposes were to identify the CYP metabolites of BAC, BMA, and BHA in human liver microsomes and to distinguish which isozymes are responsible for their metabolism through the use of chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzyme. High-resolution mass spectrometry was used to characterize the metabolites. A total of 7, 8, and 9 metabolites were detected for BAC, BMA, and BHA, respectively. The main metabolic pathways were demethylation, dehydrogenation, demethylation-dehydrogenation, hydroxylation and didemethylation, which produced less toxic metabolites by decomposing the group responsible for the toxicity of the parent compound. Taken together, the results of the chemical inhibitors, monoclonal antibodies, and cDNA-expressed CYP enzymes experiments demonstrated that CYP3A4 and CYP3A5 have essential functions in the metabolism of BAC, BMA, and BHA.

Pharmacokinetic characterization of oxymatrine and matrine in rats after oral administration of radix Sophorae tonkinensis extract and oxymatrine by sensitive and robust UPLC-MS/MS method.

The purpose of this study is to systematically investigate the pharmacokinetic (PK) behaviors of radix Sophorae tonkinensis (S. tonkinensis) using oxymatrine (OMT) and matrine (MT) as the target markers (2 mg/kg OMT and 1.3 mg/kg MT, oral administration). The PK characteristics in radix S. tonkinensis extracts were also compared with those of pure OMT. A fast ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed. OMT absorption was very fast, and no significant differences were observed (p>0.05) in tmax, CL, and t1/2 for both pure OMT and extracts. Cmax and AUC0→∞ of pure OMT were significantly higher than those of S. tonkinensis extracts (Cmax, 61.64±6.65 vs. 43.24±10.14 ng/mL; AUC, 9894.48±2234.99 vs. 4730.30±3503.8 min ng/mL) (p<0.05). However, the absolute OMT bioavailability of pure OMT was higher than that of the compound in radix S. tonkinensis extracts (6.79±2.52% vs. 1.87±2.66%). By contrast, the bioavailability of total alkaloids (OMT+MT) after pure OMT administration was 81.14±8.83%, similar to that of radix S. tonkinensis extracts (69.36±17.37%) (p>0.05). It was presumed that OMT absorption has no effect on the bioavailability of the two alkaloids. Other constituents in radix S. tonkinensis extracts can influence the transformation of OMT to MT, which directly leads to variations in the PK behavior of OMT. In addition, the protein binding of OMT and MT in plasma was very low (4.80%-8.95% for OMT, 5.10-10.55% for MT). In conclusion, OMT in radix S. tonkinensis extracts exhibits different PK behaviors with pure OMT through the transformation of OMT to MT due to other complex ingredients.

Involvement of UDP-glucuronosyltranferases and sulfotransferases in the liver and intestinal first-pass metabolism of seven flavones in C57 mice and humans in vitro.

The present study investigated the involvement of UDP-glucuronosyltransferase and sulfotransferase in the extensive liver and intestinal first-pass glucuronidation and sulfation of flavones in both mice and humans. Seven structurally similar mono- and di-hydroxyflavones were chosen as model compounds. Human liver, C57 mouse liver and intestinal S9 fraction, as well as C57 intestinal perfusion model were used. In human and C57 mouse, all selected flavones were found to be glucuronidated with the highest rates at the 7-OH group. In contrast, flavones with 3-OH group were not sulfated at all. Both glucuronidation and sulfation preferred 4'- and 7-OH in human and mouse in vitro and in situ. There were differences in glucuronidation and sulfation in human and mouse observed for all flavones and it is based on substitutional positions of the hydroxyl groups. The S9 fractions could accurately model glucuronidation (as the slope of correlation curve was 0.7988 for those flavones with 4'- or 7-OH) and sulfation (as the slope of correlation curve was 0.9834) in situ. Conclusively, the sulfation and glucuronidation of the flavones was regiospecific- and speciesdependent. Sulfation and glucuronidation in the mouse intestine in vitro were correlated well with those in situ.