OBJECTIVEWe established a method of UPLC-MS/MS that was to detect fifteen precursors of perfluoroalkyl sulfonates (PFSA) and perfluoroalkyl carboxylates (PFCA) in serum.

METHODSBriefly, TBAS solution was added to sera, then the mixed solution was extracted with aliquots of MTBE. The MTBE aliquots were combined, evaporated to dryness under nitrogen, and reconsituted in 0.25 ml of methanol and water (1:1). Then the reconstituted solution through 0.2 µm nylon syringe filter was collected. Chromatographic separation was performed using a Waters ACQUITY (TM) BEH ¹⁸C column (50 mm × 2.1 mm × 1.7 mm). Analyte quantitation was performed in the negative electrospray ionization mode and multiple reaction monitoring (MRM).

RESULTSThree target substances, 6: 6PFPi, 6: 8PFPi, 8: 8PFPi, were externally confirmed by standard addition. Rates of recovery for these three chemicals were from 41.01% to 112.13% in two standard levels. And the relative standard deviations (RSD) were lower than 11.63% and higher than 1.80%. The other twelve substances were quantified with internal standard. Moreover in two standard levels, rate of recovery for these chemicals ranged from 70.25% to 127.51%. And RSD were more than 1.23% and less than 15.45%. And the corresponding limit of detection (LOD) and limit of quantitation (LOQ) for all target substances were 0.1-5.0 pg/ml and 0.2-10.0 pg/ml. Then we detected these target substances in ten different human serum samples. The levels of few substances were higher than LOD. And the ranges of FOSA-M, N-EtFOSA-M, N-MeFOSAA, N-EtFOSAA were respectively < LOD-0.94 pg/ml, < LOD-10.08 pg/ml, < LOD-6.74 pg/ml, < LOD-1.04 pg/ml.

CONCLUSIONThe method, with high sensitivity and accuracy, could meet the actual testing requirements.

BACKGROUND/AIMS: To evaluate associations between delayed gastric emptying (GE) assessed by the octanoic acid breath test and upper gastrointestinal (GI) symptoms. METHODS: A historical, prospective study included 111 consecutive symptomatic adults referred for a GE breath test because of upper abdominal symptoms suggestive of delayed GE. Exclusion criteria included underlying organic disease associated with delayed GE. Patients completed a symptom questionnaire and underwent a GE octanoic breath test. Patients with delayed GE were compared with those with normal results, for upper GI symptoms. RESULTS: Early satiety was the only symptom significantly associated with delayed GE. It was observed in 52% of subjects with delayed GE compared to 33% patients with no evidence of delayed GE (P = 0.005). This association was seen for all degrees of severity of delayed GE. Patients with early satiety had a t1/2 of 153.9 +/- 84.6 minutes compared to 110.9 +/- 47.6 minutes in subjects without it (P = 0.002). In a logistic regression model, early satiety was significantly associated with delayed GE (OR, 2.29; 95% CI, 1.01-5.18; P = 0.048). CONCLUSIONS: Early satiety is the only patient-reported GI symptom associated with delayed GE. The utility of GE tests as a clinical diagnostic tool in the work-up of dyspeptic symptoms may be overrated.
Adult ; Breath Tests ; Caprylates ; Dyspepsia ; Gastric Emptying ; Humans ; Logistic Models ; Prospective Studies ; Surveys and Questionnaires

Ginsenoside Rh_2,firstly isolated from red ginseng,is protopanaxadiol type of steroidal saponin. Rh_2 possessed variety of activities,but bioavailability of oral administration Rh_2 was extremely low due to poor absorption. Moreover,ginsenoside Rh_2 exhibited toxicity on human normal cells. Therefore,to improve stronger anti-tumor activity and attenuate toxicity,it was essential to design and optimize chemical structure of ginsenoside Rh_2. Through n-octanoylchloride modifications,a novel ester derivative of ginsenoside Rh_2 named caprylic acid monoester of Rh_2( C-Rh_2) was designed and synthesized. Structure of novel ginsenoside derivative was identified by1 D and 2 D NMR,as well as ESI-MS analyses. Anti-tumor effect of C-Rh_2 was tested on H22 tumor bearing mice. C-Rh_2 displayed certain anti-tumor activities and exhibited less toxicity than Rh_2. In the present study,C-Rh_2 as ester form of ginsenoside Rh_2 showed better anti-tumor activity and less toxicity,but the specific mechanism needs further investigation.
Animals ; Caprylates ; Ginsenosides ; chemical synthesis ; pharmacology ; Mice ; Molecular Structure ; Neoplasms, Experimental ; drug therapy ; Saponins

Perfluorinated compounds, especially Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are widely detected in water environments in China. Considering the potential health risks of drinking water exposure routes, PFOA and PFOS have been added to the water quality reference index of the newly issued "Standards for Drinking Water Quality (GB5749-2022)", with limit values of 40 and 80 ng/L, respectively. This study analyzed and discussed the relevant technical contents for determining the limits of the hygiene standard, including the environmental existence level and exposure status of PFOA and PFOS, health effects, derivation of safety reference values, and determination of hygiene standard limits. It also proposed prospects for the future direction of formulating drinking water standards.
Humans ; Water Quality ; Drinking Water ; Fluorocarbons/analysis* ; Caprylates/analysis* ; China ; Water Pollutants, Chemical/analysis*

BACKGROUND AND OBJECTIVES: Glutaraldehyde (GA) has been used as a representative method of tissue preservation in cardiovascular surgery. However, GA has showed limited durability including calcification, mechanical failure and toxicity. To overcome those unsolved problems, we analyzed the crosslinking differences of primary amines, GA and genipin in their mechanical and biochemical properties with a single or double crosslinking agent for clinical application. MATERIALS AND METHODS: Samples were divided into 3 groups; control, single crosslinking fixation and double crosslinking fixation after decellurarization using bovine pericardium. For analysis of the biochemical and mechanical properties of each crosslinking method, tensile strength, percentage strain, thermal stability, resistance to pronase, nynhydrin and cytotoxicity test were studied. RESULTS: Combined hexamethylene diamine and suberic acid in the carbodiimide hydrochloride/N-hydroxysucinimide solution (EDC/NHS) after decellurarization, tensile strength and strain percentage were not statistically significant compared to the single crosslinking treated groups (p>0.05). Tissue crosslinking stability was weak in single treatment of diphenylphosphoryl azide, suberic acid, low concentration of EDC, hexamethylene diamine and procyanidin groups, but thermal stability and resistance to the pronase and ninhydrin were markedly increased in concentrated EDC/NHS or after combined double treatment with low concentration of GA or genipin (p<0.001). CONCLUSION: Single or double crosslinking with low concentration of carbodiimide, diphenylphosphonyl azide, procyanidin, suberic acid and hexane diamine were not as effective in mechanical, biochemical, cytotoxic and crosslinking properties compared to GA or genipin fixation, but their mechanical and chemical properties were much improved when combined with low concentrations of GA or genipin in the double crosslinking process.
Amines ; Azides ; Biflavonoids ; Bioprosthesis ; Caprylates ; Catechin ; Dicarboxylic Acids ; Glutaral ; Iridoids ; Ninhydrin ; Pericardium ; Proanthocyanidins ; Pronase ; Sprains and Strains ; Tensile Strength ; Tissue Preservation

China has richly and inexpensive fat and oils from animal and plants, but these resources could not get effectively utilization. In order to make the best of these resources, lipase-catalyzed acidolysis of lard with caprylic acid to produce functional lipid in solvent free system was investigated. Of the five lipases that were tested in the initial screening, immobilized lipase TL IM fromca T. languginosa resulted in the highest incorporation of capry lic acid into lard. This enzyme was further studied for the effect of enzyme load, substrate ratib, reaction time, reaction temperature and added water content on the incorporation of caprylic acid into lard. HPLC analyzed the products from the acidolysis reaction. The highest incorporation was attained at 20% enzyme load. Time course studied suggest that the incorporation of caprylic acid into lard was increased up to 38.77 mol% after 24h. Desirable mole ratio of substrates was 1:2 (lard: caprylic acid), caprylic acid incorporation up to 30.95 mol%. In the range of 45 - 60 degrees C , temperature had no significant effect on enzyme activity and caprylic acid incorporation changed little. When temperature was above 60 degrees C, incorporation of caprylic acid into lard was decreased. The highest incorporation of caprylic acid into lard 35.76 mol% was attained when added water content was 2.5%.
Caprylates ; chemistry ; Catalysis ; Chromatography, High Pressure Liquid ; Dietary Fats ; metabolism ; Enzymes, Immobilized ; metabolism ; Lipase ; metabolism ; Lipids ; chemical synthesis ; Solvents

In response to the market demand for therapeutic antibodies, the upstream cell culture scale and expression titer of antibodies have been significantly improved, while the production efficiency of downstream purification process is relatively fall behind, and the downstream processing capacity has become a bottleneck limiting antibody production throughput. Using monoclonal antibody mab-X as experimental material, we optimized the caprylic acid (CA) precipitation process conditions of cell culture fluid and low pH virus inactivation pool, and studied two applications of using CA treatment to remove aggregates and to inactivate virus. Based on the lab scale study, we carried out a 500 L scale-up study, where CA was added to the low pH virus inactivation pool for precipitation, and the product quality and yield before and after precipitation were detected and compared. We found that CA precipitation significantly reduced HCP residuals and aggregates both before and after protein A affinity chromatography. In the aggregate spike study, CA precipitation removed about 15% of the aggregates. A virus reduction study showed complete clearance of a model retrovirus during CA precipitation of protein A purified antibody. In the scale-up study, the depth filtration harvesting, affinity chromatography, low pH virus inactivation, CA precipitation and depth filtration, and cation exchange chromatography successively carried out. The mixing time and stirring speed in the CA precipitation process significantly affected the CA precipitation effect. After CA precipitation, the HCP residue in the low pH virus inactivation solution decreased 895 times. After precipitation, the product purity and HCP residual meet the quality criteria of monoclonal antibodies. CA precipitation can reduce the chromatography step in the conventional purification process. In conclusion, CA precipitation in the downstream process can simplify the conventional purification process, fully meet the purification quality criterion of mab-X, and improve production efficiency and reduce production costs. The results of this study may promote the application of CA precipitation in the purification of monoclonal antibodies, and provide a reference for solving the bottleneck of the current purification process.
Cricetinae ; Animals ; Antibodies, Monoclonal/metabolism* ; Caprylates/chemistry* ; Cell Culture Techniques ; Chromatography, Affinity ; CHO Cells ; Cricetulus ; Chemical Precipitation

A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol x L(-1), D-glucose for 15 mmol x L(-1) and K+ for 5.5 mmol x L(-1). Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.
Animals ; Calcium ; metabolism ; Caprylates ; chemistry ; Digestion ; Glucose ; metabolism ; Glycerides ; chemistry ; Indomethacin ; chemistry ; Intestinal Absorption ; Lipids ; chemistry ; Lipolysis ; Models, Biological ; Potassium ; metabolism ; Rats ; Rats, Sprague-Dawley

BACKGROUND/AIMS: Lack of simple and repeatable tests hampers gastric emptying studies in rats. The aim of this study was to adapt the 14C-octanoate solid gastric emptying breath test for application in rats, and to validate it against radioscintigraphic method. METHODS: After ingestion of a meal containing 3 mCi 99mTc and 2 microCi 14C-octanoate, 23 male Wistar rats were placed on a gamma camera in a airflow container. Scintigraphic images were taken at regular intervals. The amount of 14CO2 in a regularly replaced hyamine hydroxide solution, capturing CO2 in the outflow air, was counted using liquid scintillation spectrometry. 99mTc gastric retention curves and 14CO2-excretion curves were fitted to their respective data. Three rats underwent the same procedures after administration of atropine. RESULTS: Overall Tr10% (time at which 10% of the original amount of 99mTc remained in the stomach) was 355 +/- 64 minutes; Te90% (time at which 90% of total amount of 14CO2 was excreted) was 325 +/- 106 minutes. Their correlation coefficient was 0.71, R-square 0.50 and P < 0.005. Tr1/2 (50% of original amount of 99mTc remained) was 124 +/- 28 minutes; Te1/2 (50% of total amount of 14CO2 excreted) 114 +/- 32 minutes. Their correlation coefficient was 0.83 with R-square of 0.69 and P < 0.00005. In 12 immobilized animals correlation was even better: correlation coefficient 0.84; R-square 0.71 and P < 0.001 (Tr10% was 388 +/- 117 minutes; Te90% 532 +/- 219 minutes; Tr1/2 of 165 +/- 54 minutes; Te1/2 of 175 +/- 67 minutes). Atropine significantly lengthened all emptying times: 904 +/- 307 and 1461 +/- 684 minutes for Tr10% and Te90%, respectively; and 432 +/- 117 minutes for Tr1/2 and 473 +/- 190 minutes for Te1/2. CONCLUSIONS: We adapted and validated the 14C-octanoate gastric emptying breath test for application in rats.
Animals ; Atropine ; Benzethonium ; Breath Tests ; Caprylates ; Eating ; Gamma Cameras ; Gastric Emptying ; Humans ; Hydroxides ; Male ; Meals ; Rats ; Rats, Wistar ; Retention (Psychology) ; Spectrum Analysis

OBJECTIVES: The objective of this study was to determine serum perfluorooctanoic acid (PFOA) concentrations and to investigate the relationship of lifestyle, health status and work-related factors among workers at manufacturing companies with possible occupational exposure to PFOA. METHODS: The study subjects were 315 workers (male 203, female 112) of manufacturing companies with possible exposure to PFOA from August to December, 2007. A questionnaire was administered to investigate lifestyle and work-related factors. Serum PFOA concentrations were analyzed by LCMS/ MS, and liver function and total cholesterol were also tested. RESULTS: Serum PFOA concentrations ranged from 1.0 to 40.9 ng/mL (mean 8.0 ng/mL). Serum PFOA concentrations increased with age. Male workers had higher PFOA concentration than female workers (male 9.0 ng/mL; female 6.3 ng/mL). According to stepwise multiple regression analysis, factors significantly associated with PFOA concentration were male, being older, higher total cholesterol, and lower body mass index. Adjusted for age and gender by logistic regression, dyeing and finishing textiles had significantly higher odds ratio (OR) of 6.16, and moulding patterns, moulds and industrial patterns (OR=4.84), sections for ships (OR=3.87), and plastics synthetic leather (OR=10.05) had marginally significantly high odds ratios. CONCLUSIONS: This study demonstrated the factors affecting serum PFOA concentration of workers at manufacturing companies. Further study is needed to ensure the effect of occupational exposure on serum PFOA concentration.
Body Mass Index ; Caprylates ; Cholesterol ; Dietary Sucrose ; Female ; Fluorocarbons ; Humans ; Life Style ; Liver ; Logistic Models ; Male ; Occupational Exposure ; Odds Ratio ; Plastics ; Questionnaires ; Ships ; Textiles