To observe the serum concentration and evaluate clinical efficacy of piperacillin/tazobactam (TZP) prolonged infusion time in treatment of hospital acquired pneumonia (HAP).Fifty HAP patients admitted to intensive care unit (ICU) from March 1 to October 31, 2012 were enrolled. The bacterial drug sensitivity results showed that the minimum inhibitory concentration (MIC) of TZP was 8 mg/L or 16 mg/L. According to completely randomized grouping method, the patients were divided into treatment group (n=25) and control group (n=25). The therapeutic regimen in control group was TZP 4.5 g, in regular infusion every 6 hours and finished in 30 minutes; the treatment group was TZP 4.5 g, in prolonged infusion every 6 hours by using infusion pump for continuous intravenous infusion 3 hours. Acute physiology and chronic health evaluation II(APACHEII) score, clinical pulmonary infection score (CPIS) and procalcitonin (PCT) level were compared between the two groups 3 days after treatment. The treatment success rate, remedial treatment rate, antibiotic costs were recorded in both groups. Blood specimen was collected at 0.5, 1, 2, 3, 4, 6 hours at the beginning of administration, and the blood drug concentration of piperacillin and tazobactam was determined using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS).The PCT (2.16±0.17 μg/L vs. 4.77±0.25 μg/L), CPIS score(6.21±1.14 μg/L vs. 6.92±1.35 μg/L) and remedial treatment rate (12.0% vs. 52.0%) of the treatment group were significantly lower than those of the control group after administration for 3 days (P<0.05 or P<0.01), and APACHEII score was slightly lower than that in control group (21.38±7.37 vs. 22.15±5.46, P>0.05). After active remedial treatment, there were no significant difference in the treatment success rate (88.0% vs. 80.0%) and relapse rate (4.2% vs. 7.7%) between treatment group and control group (both P>0.05). But the antibiotic costs in treatment group were significantly lower than that of control group (4330.38±1087.24 Yuan vs. 5506.15±1361.73 Yuan, P<0.01). The treatment course of antibacterials in treatment group was significantly shorter than that in control group (6.00±1.05 days vs. 8.20±1.03 days, P<0.01). The infection by Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae was monitored, TZP serum concentration administrated at 0.5-6 hours in the treatment group was higher than MIC, but in the control group, TZP blood concentration was lower than MIC after administration for 2-3 hours. In treatment group, the percentage of duration of blood drug level higher than MIC account for dosing interval (%T>MIC) was 86.82%, while in the control group, the %T>MIC was 42.84%.TZP prolonged the infusion time dosing regimens using in Gram negative bacteria induced by high MIC value of HAP have more stable plasma concentration, curative clinical effect and reduce the cost of treatment.
Saturated branched chain fatty acids (BCFA) terminating with either an isopropyl or sec-butyl group, are common bioactive food components consumed from beef, fish, and dairy products. Little is known about their endogenous metabolism and the enzymes mediating their interconversion. Our main objective was to test the substrate specificity of the fatty acid elongases (ELOVL1–7) towards elongation of representative BCFA, anteiso-15:0 and iso-18:0. We also assessed competition between BCFA and normal saturated fatty acid (n-SFA). MCF7 human breast cancer cells are used for functional studies. PcDNA3.1 expression vector was used to clone seven open reading frames of ELOVL transcripts (ELOVL1–7). MCF7 cells were transiently transfected with specific ELOVL1–7 transgene vector or empty vector (control). After 24 h incubation, the transfected MCF7 cells were treated with BSA-bound substrates. After additional 24 h incubation, cells were harvested by trypsinization, fatty acid methyl esters prepared and analyzed quantitatively by GC-FID. Fatty acid composition was characterized by gas chromatography (GC) –electron ionization mass spectrometry (EIMS) and EIMS/MS for branched carbon chain. Transient transfection of ELOVL1–7 into MCF7 cells show that ELOVL6 had highest activity towards elongation of anteiso-15:0→anteiso-17:0, followed by ELOVL5 which showed moderate activity. ELOVL3 was found to be most active ELOVL mediating elongation of iso-18:0→iso-20:0. Our competition results show in ELOVL6 cells anteiso-15:0 competes with n-SFA n-16:0, whereas, in ELOVL3 cells iso-18:0 competes with n-18:0. The elongation of anteiso-15:0 and iso-18:0 BCFA is predominantly operated by the ELOVL6 and ELOVL3, respectively that are well known to operate on normal saturated fatty acids, rather than the ELOVL2 and ELOVL5 which operate on lower-melting polyunsaturated fatty acids. The competition between BCFA and n-SFA for ELOVL1–7 mediated elongation may have implications in the skin, sebaceous, and meibomian glands where both normal and BCFA are present at comparable levels. NIH grant R01 AT007003.
Introduction Branched chain fatty acids (BCFA) are a component of dairy products and beef. The bacterial origin of BCFA suggests they may be rich in fermented foods. We previously found BCFA was at 1% of total fatty acids in sauerkraut and in freshwater fishes. However, dairy products are still the major food source of BCFA, with about 2% BCFA in milkfat, supporting a per capita consumption of 500mg/d BCFA in the United States. In Asian countries where dairy consumption is low, BCFA intake is unlikely to parallel U.S. levels insofar as foods sources are concerned. Natto is a popular Japanese food. It is fermented with bacillus subtilis , which is among species inherently rich in BCFA because of de novo biosynthesized BCFA. Our objective was to determine the BCFA of widely available, traditionally produced natto. Methods Two natto products from a Japanese manufacturer were purchased in a local Asian grocery. They were fermented and maintained at refrigerated temperature, and otherwise similar in most ways except being seasoned by different sauces. Total fatty methyl esters were prepared via a modified one‐step hydrolysis procedure and quantified with GC‐FID. BCFA were identified with EIMS/MS. Results Natto has 1.6% ± 0.02% BCFA of totally fatty acids, mean of both products. Natto is about 30% calories as fat. Consuming one serving (90 g) of natto would provide 7 g fat and 112 mg of BCFA. The major BCFA in natto are iso ‐14:0 , iso ‐15:0 , anteiso ‐15:0 , iso ‐16:0 , iso ‐17:0 and anteiso ‐17:0, substantially recapitulating the BCFA profile of fluid milk except anteiso ‐17:0 is lower in natto. Regular consumption of natto in Japan could contribute significant BCFA to overall intake, supplementing Japanese consumption of beef and other known BCFA sources. Conclusion Natto may contribute substantially to BCFA consumption where dairy consumption is low. Support or Funding Information Internal funds
Branched-chain fatty acids (BCFA) are bioactive food components that constitute about 2 % of fatty acids in cows' milk fat. There are few systematic data available on the BCFA content of other foods to estimate dietary intakes. In the present study, we report BCFA distribution and content of fresh and processed foods representing the major foods in the American diet and estimate BCFA intake. BCFA are primarily components of dairy and ruminant food products, and are absent from chicken, pork and salmon. The mean BCFA intake of 500 mg/d was delivered primarily from dairy and beef food products; by comparison, average intake of the widely studied long-chain PUFA EPA and DHA has been estimated to be 100 mg/d. Common adjustments in the diet could double the daily intake of BCFA. The fermented foods sauerkraut and miso had appreciable fractions of BCFA, but, overall, they are low-fat foods providing very small amounts of BCFA in the diet, and other fermented foods did not contain BCFA as might have been expected from the influence of microbial exposure. These data support the quantitative importance of BCFA delivered primarily from dairy and beef food products and highlight the need for research into their effects on health.
The role of lipid metabolism in epithelial stem cell (SC) function and carcinogenesis is poorly understood. The transcription factor Runx1 is known to regulate proliferation in mouse epithelial hair follicle (HF) SCs in vivo and in several mouse and human epithelial cancers. We found a novel subset of in vivo Runx1 HFSC target genes related to lipid metabolism and demonstrated changes in distinct classes of lipids driven by Runx1. Inhibition of lipid-enzymes Scd1 and Soat1 activity synergistically reduces proliferation of mouse skin epithelial cells and of human skin and oral squamous cell carcinoma cultured lines. Varying Runx1 levels induces changes in skin monounsaturated fatty acids (e.g., oleate, a product of Scd1) as shown by our lipidome analysis. Furthermore, varying Runx1 levels, the inhibition of Scd1, or the addition of Scd1-product oleate, individually affects the plasma membrane organization (or fluidity) in mouse keratinocytes. These factors also affect the strength of signal transduction through the membranes for Wnt, a pathway that promotes epithelial (cancer) cell proliferation and HFSC activation. Our working model is that HFSC factor Runx1 modulates the fatty acid production, which affects membrane organization, facilitating signal transduction for rapid proliferation of normal and cancer epithelial cells. Stem Cells 2018;36:1603-1616.
The net action of ruminal bacteria and endogenous bovine enzymes are responsible for cow’s milk having the most complex fatty acid profiles among common foods. About 40 monounsaturated fatty acids below 1.5% w/w are known. Analysis of trace and ultratrace fatty acids is a challenge to the highest resolution chromatography even with prior fractionation. We employ solvent-mediated covalent adduct chemical ionization (CACI) tandem mass spectrometry (MS/MS) to enable rapid, unambiguous identification of unsaturated fatty acid methyl esters (FAME) at high sensitivity. Fifty-four monounsaturated fatty acids (C10–24) were completely characterized, with the discovery of 15 novel fatty acids including nine at ultratrace levels 10–100 ppm, g/106 g fatty acids (lowest concentration 19:1n-6 (10 ± 11 ppm, w/w (0.001%, w/w))). Ultratrace monoenes were typically odd chain lengths and all analyzed in a single 20 min analysis. These data establish the abundance of 15 new monoene fatty acids in bovine milkfat and a strategy for rapid unambiguous analysis of ultratrace monounsaturated fatty acids.
Dairy and fermented foods are common sources of dietary branched-chain fatty acids (BCFA) of chain lengths C13–C18 serving a putative prebiotic role and a component of human integument. Few studies have reported on nonfermented plant-derived BCFA in human diets or cosmetics. A three-ion monitoring method was adapted to confirm branch position of ultratrace (<0.01%, w/w) BCFA. We identified chia as a new source of BCFA with C15–C35 chain lengths. Surprisingly, even-numbered very long-chain BCFA (VLC BCFA), anteiso-22:0, anteiso-24:0, and anteiso-26:0 were unequivocally identified in natural products for the first time. Plant-derived BCFA are predominantly anteiso, in contrast with similar iso and anteiso levels in ruminant and fermented foods. Chia seeds contain 0.4% BCFA, w/w of total fatty acids, or 32 mg BCFA in a food serving, surpassing other plant oils. Topical administration of chia seed oil containing VLC BCFA may have a role in skin and hair functionality.
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