Determination of dezocine in rabbit plasma by liquid chromatography-mass spectrometry and its application

A sensitive and selective liquid chromatography-mass spectrometry (LC–MS) method for determination of dezocine in rabbit plasma was developed and validated. After addition of diazepam as internal standard (IS), liquid–liquid extraction (LLE) was used for sample preparation, and chromatography involved Agilent SB-C18 column (2.1 mmx50 mm, 3.5 um) using 0.1 % formic acid in water and acetonitrile as a mobile phase with gradient elution. Detection involved positive ion mode electrospray ionization (ESI), and selective ion monitoring (SIM) mode was used for quantification of target fragment ions m/z 245.8 for dezocine and m/z 284.8 for diazepam (internal standard, IS). The assay was linear over the range of 5–500 ng/mL for dezocine, with a lower limit of quantitation (LLOQ) of 5 ng/mL for dezocine. Intra- and inter-day precisions were less than 13 % and the accuracies were in the range of 93.1-105.2 % for dezocine. This developed method was successfully applied for the determination of dezocine in rabbit plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of pantoprazole in rat plasma by LC–MS/MS and its application to pharmacokinetics

A highly sensitive liquid chromatographic mass spectrometric (LC-MS/MS) method for determination of pantoprazole in rat plasma using omeprazole as the internal standard (IS) was developed. Plasma samples were precipitated by acetonitrile and separated on a Zorbax SB-C18 column with gradient profile at a flow of 0.4 mL/min. Detection was carried out by SIM mode on an ion-trap LC-MS/MS system with an electrospray ionization interface. The lower limit of quantification (LLOQ) was 5 ng/mL. Calibration curve was linear over the range from 5 to 5000 ng/mL. The intra- and inter-run relative standard deviations of the assay were less than 7 %. The mean absolute recoveries determined at the concentrations of 25, 400, and 4000 ng/mL were 87.40 ± 4.40 %, 87.77 ± 3.30 %, and 92.78 ± 5.02 %, respectively. The method was applied to the pharmacokinetic of 15 mg/kg of pantoprazole in six rats.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Determination of esomeprazole in rabbit plasma by liquid chromatography-mass spectrometry and its application to a pharmacokinetic study

A sensitive and selective liquid chromatography-mass spectrometry (LC–MS) method for determination of esomeprazole in rabbit plasma was developed and validated. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation, and chromatography involved Agilent SB-C18 column (2.1 x 150 mm, 5.0 μm) using 0.1 % formic acid in water and acetonitrile as a mobile phase with gradient elution. Detection involved positive ion mode electrospray ionization (ESI), and selective ion monitoring (SIM) mode was used for quantification of target fragment ions m/z 198 for esomeprazole and m/z 326 for midazolam (internal standard, IS). The assay was linear over the range of 10–2000 ng/mL for esomeprazole, with a lower limit of quantitation (LLOQ) of 10 ng/mL for esomeprazole. Intra- and inter-day precisions were less than 14 % and the accuracies were in the range of 89.2-112.6 % for esomeprazole. This developed method was successfully applied for the determination of esomeprazole in rabbit plasma for pharmacokinetic study.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Glucose Starvation-Induced Rapid Death of Nrf1α-Deficient, but Not Nrf2-Deficient, Hepatoma Cells Results from Its Fatal Defects in the Redox Metabolism Reprogramming

Metabolic reprogramming exists in a variety of cancer cells, with the most relevance to glucose as a source of energy and carbon for survival and proliferation. Of note, Nrf1 was shown to be essential for regulating glycolysis pathway, but it is unknown whether it plays a role in cancer metabolic reprogramming, particularly in response to glucose starvation. Herein, we discover that Nrf1α-/- hepatoma cells are sensitive to rapid death induced by glucose deprivation, such cell death appears to be rescued by Nrf2 interference, but HepG2 (wild-type, WT) or Nrf2-/- cells are roughly unaffected by glucose starvation. Further evidence revealed that Nrf1α-/- cell death is resulted from severe oxidative stress arising from aberrant redox metabolism. Strikingly, altered gluconeogenesis pathway was aggravated by glucose starvation of Nrf1α-/- cells, as also accompanied by weakened pentose phosphate pathway, dysfunction of serine-to-glutathione synthesis, and accumulation of reactive oxygen species (ROS) and damages, such that the intracellular GSH and NADPH were exhausted. These demonstrate that glucose starvation leads to acute death of Nrf1α-/-, rather than Nrf2-/-, cells resulting from its fatal defects in the redox metabolism reprogramming. This is owing to distinct requirements of Nrf1 and Nrf2 for regulating the constructive and inducible expression of key genes involved in redox metabolic reprogramming by glucose deprivation. Altogether, this work substantiates the preventive and therapeutic strategies against Nrf1α-deficient cancer by limiting its glucose and energy demands

Risk factors for patients with acute hospital-acquired symptomatic pulmonary thromboembolism

Abstract This study aimed to identify independent risk factors for acute hospital-acquired symptomatic pulmonary embolism (HA-SPE) by comparing the clinical data of HA-SPE and acute nonhospital-acquired symptomatic pulmonary embolism (NHA-SPE). A total of 292 patients were included in the analysis and divided into two groups: 191 patients had acute NHA-SPE, and 101 patients had acute HA-SPE. The average age of these 292 patients was 63.2 years, and the sample included 145 males. Multivariate analysis showed that malignant tumour (OR, 3.811; 95% CI [1.914–7.586], P = 0.000), recent surgery (OR, 7.310; 95% CI 3.392–15.755], P = 0.000), previous VTE (OR, 5.973; 95% CI 2.194 16.262], P = 0. 000), and the length of stay (LOS) (OR, 1.075; 95% CI [1.040–1.111], P = 0.000) were independent risk factors for acute HA-AEP. The c-statistic for this model was 0.758 (95% CI [0.698–0.800], P < 0.0001). The K-M curve showed that the hazard ratio (HR) of the HA group to the NHA group in all-cause mortality was 3.807 (95% CI [1.987, 7.295], P = 0.0061). Strengthening the prevention and control of patients with these risk factors may reduce the incidence of acute HA-SPE

One New Phenolic Compound from <i>Castanea mollissima</i> Shells and its Suppression of HepatomaCell Proliferation and Inflammation by Inhibiting NF-κB Pathway

Shells of Castanea mollissima (CMS), an agricultural remain and often considered waste from chestnut processing industry, have been proven a resource for traditional Chinese medicine. One new phenol, named castanolB(1), andsix known phenolic compounds (2&#8315;7) were isolated froma water-soluble extract of CMS. Their chemical structures were determined using preparative HPLC and various spectral analyses, and then were compared to literatures, which indicated the first identification of the seven compounds from C. mollissima. The physicochemical property of compound (2) was also reported for the first time. After antiproliferative screening of compounds (1&#8315;7) on LPS-induced SMMC-7721 and HepG2 hepatoma cells, castanolB (1) showed the best suppression. CastanolB(1) also significantly induced cell apoptosis. Furthermore, castanolB (1) decreasedsecretion of TNF-&#945; and IL-6. Mechanistically, TLR4&#8315;NF-&#954;B pathway was inhibited bycastanolB (1) with downregulation of TLR4, IKK&#946;, and NF-&#954;B p65. This study presents a new phenol and shows its profiles of anticancer and anti-inflammation via inhibiting the TLR4&#8315;NF-&#954;B pathway

Molecular identification and epidemiological comparison of Cryptosporidium spp. among different pig breeds in Tibet and Henan, China

Abstract Background Cryptosporidium spp. are important zoonotic pathogens infecting a wide range of vertebrate hosts, and causing moderate to severe diarrhea in humans. Cryptosporidium infections are frequently reported in humans and animals worldwide, but little research has been done on local pig breeds such as Tibetan pigs and Yunan Black pigs and imported pig breeds such as Landrace pigs in China. Therefore, a total of 1089 pig fecal samples from four intensive farms in four areas of China, including Tibetan pigs from Gongbujiangda County (n = 180) and Mainling County (n = 434), Tibet, Yunan Black pigs from Sanmenxia, Henan Province (n = 246), and Landrace pigs from Kaifeng, Henan Province (n = 229), and were screened for the presence of Cryptosporidium with microscopy and nested PCR amplification of the small subunit rRNA gene. Results The total infection rate of Cryptosporidium in 1089 fecal samples of three different pig breeds was 2.11% (23/1089), and the infection rates of Tibetan pigs, Yunan Black pigs, and Landrace pigs were 0.49% (3/614), 0.41% (1/246), and 8.30% (19/229), respectively. The prevalence of Cryptosporidium infection was significantly higher in weaned piglets (1–2 months) (4.36%, 21/482) than in younger and older age groups (p  2 months). Conclusions This is the first report on the identification of Cryptosporidium spp. in Tibetan pigs, and our findings also elucidate the occurrence and distribution of Cryptosporidium in three different pig breeds in Tibet and Henan, China. More molecular epidemiological studies are required to better clarify the prevalence and public health significance of Cryptosporidium in different pigs

Purification, Preliminary Structural Characterization, and In Vitro Inhibitory Effect on Digestive Enzymes by β-Glucan from Qingke (Tibetan Hulless Barley)

Background and Objective. Qingke (Tibetan hulless barley, Hordeum vulgare L.) contains a high content of β-glucan among all the cereal varieties. Although β-glucan has multiple physiological functions, the physiological function of qingke β-glucan was few studied. In this study, the β-glucan was isolated, purified, determined the structural characterization, and measured the inhibitory activity to enzymes correlating blood sugar and lipid. Methods. β-Glucan was isolated from enzymatic aqueous extract of qingke by using deproteinization, decolorization, DEAE-52 column chromatography, and sepharose CL-4B agarose gel column chromatography. The structure of the β-glucan was determined using FT-IR and 13C-NMR spectra analysis, and molecular mass by use of HPSEC-dRI-LS. The kinematic viscosity was measured. The inhibitory effects of this β-glucan on four enzymes were investigated. Results. This β-glucan had a uniform molecular weight of 201,000 Da with β-(1⟶4) as the main chain and β-(1⟶3) as a side chain. The β-glucan presented a relatively strong inhibitory activity on α-glucosidase, moderate inhibition on invertase, and a weak inhibition on α-amylase, whereas it did not inhibit lipase. Conclusion. The study indicates that the enzymatic β-glucan from qingke has the potential as natural auxiliary hypoglycemic additives in functional medicine or foods