Diagnosis of
complex pulmonary disease (MAC-PD) requires positive culture of expectorated sputum or specimens acquired by bronchoscopy. Whether patients diagnosed using bronchoscopy have milder ...disease and milder progression than those diagnosed using sputum remains uncertain.
To clarify whether disease severity and progression differ according to the diagnostic method.
We retrospectively analysed 92 patients with MAC-PD. We compared characteristics of patients and disease progression according to the diagnostic methods used: sputum or bronchoscopy. Additionally, we investigated the impact of these methods on disease progression using multivariate analysis.
Patients diagnosed using sputum were younger than those diagnosed using bronchoscopy; however, there were small differences from the viewpoint of clinical practice in disease severity, and estimated progression-free survival rate did not differ significantly. The predictors of disease progression were disease forms other than non-cavitary nodular/bronchiectatic disease, hypoalbuminemia and severe radiographic scores.
The diagnostic methods had no significant impact on disease severity and disease progression of MAC-PD. If the diagnosis cannot be established by sputum culture or if sputum cannot be obtained in the patients with risk factors for disease progression, bronchoscopy would be useful to provide opportunity of treatment for MAC-PD.
Aims This study aims to produce hydroxy fatty acids efficiently. Methods and Results Escherichia coli overexpressing linoleic acid Delta9 hydratase from Lactobacillus plantarum AKU 1009a was employed ...to produce hydroxy fatty acids with industrial potential. We found that 280 g l-1 of linoleic acid (1 mol l-1) was converted into (S)-10-hydoxy-cis-12-octadecenoic acid (HYA) with a high conversion rate of 98% (mol/mol) and more than 99·9% enantiomeric excess (e.e.) by recombinant E. coli cells in the presence of FAD and NADH. In the same way, many kinds of C18 unsaturated fatty acids with Delta9 carbon double bond (280 g l-1) were converted into corresponding 10-hydroxy fatty acids with the conversion rates over 95% (mol/mol). We also produced HYA at a high rate of accumulation (289 g l-1) with a high yield (97 mol%) in a reaction mixture that contained glucose instead of NADH. Conclusions We developed a process for producing several types of hydroxy fatty acids with high accumulation rates and high yields. Significance and Impact of the Study Hydroxy fatty acids are important materials for the chemical, food, cosmetic and pharmaceutical industries, and thus they have recently attracted much interest in a variety of research fields. However, the mass production of hydroxy fatty acids has been limited. This method of hydroxy fatty acids production will facilitate the widespread application of hydroxy fatty acids in various industries.
Aims
This study aims to produce hydroxy fatty acids efficiently.
Methods and Results
Escherichia coli overexpressing linoleic acid Δ9 hydratase from Lactobacillus plantarum AKU 1009a was employed to ...produce hydroxy fatty acids with industrial potential. We found that 280 g l−1 of linoleic acid (1 mol l−1) was converted into (S)‐10‐hydoxy‐cis‐12‐octadecenoic acid (HYA) with a high conversion rate of 98% (mol/mol) and more than 99·9% enantiomeric excess (e.e.) by recombinant E. coli cells in the presence of FAD and NADH. In the same way, many kinds of C18 unsaturated fatty acids with Δ9 carbon double bond (280 g l−1) were converted into corresponding 10‐hydroxy fatty acids with the conversion rates over 95% (mol/mol). We also produced HYA at a high rate of accumulation (289 g l−1) with a high yield (97 mol%) in a reaction mixture that contained glucose instead of NADH.
Conclusions
We developed a process for producing several types of hydroxy fatty acids with high accumulation rates and high yields.
Significance and Impact of the Study
Hydroxy fatty acids are important materials for the chemical, food, cosmetic and pharmaceutical industries, and thus they have recently attracted much interest in a variety of research fields. However, the mass production of hydroxy fatty acids has been limited. This method of hydroxy fatty acids production will facilitate the widespread application of hydroxy fatty acids in various industries.
Background
There is rapidly developing interest into the role of several anti‐inflammatory agents to resolve inflammation in periodontal disease. A bioactive polyunsaturated fatty acid, ...10‐oxo‐trans‐11‐octadecenoic acid (KetoC), is known to have various beneficial physiological effects; however, the effect of KetoC on inflammation remains unclear. Here, we investigated the effect of KetoC on RAW 264.7 cells stimulated with Porphyromonas gingivalis lipopolysaccharide, and explored the intracellular mechanism responsible for its anti‐inflammatory effects.
Methods
RAW 264.7 cells were pre‐treated with or without KetoC, and then stimulated with or without P. gingivalis lipopolysaccharide. Levels of tumor necrosis factor α (TNFα), interleukin (IL)‐6 and IL‐1β were determined by real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. Specific antagonists for G protein‐coupled receptor (GPR)40 and GPR120 were used to clarify the receptor for KetoC. The intracellular mechanism was investigated using western blotting analysis to separate nuclear and cytosolic NF‐κB p65 protein.
Result
KetoC (5 μmol/L) was not toxic to RAW 264.7 cells, and significantly reduced the expression of TNFα and IL‐6 mRNA and protein, and IL‐1β mRNA. No protein production of IL‐1β was observed. Additionally, when bound to GPR120, KetoC trended to downregulate nuclear NF‐κB p65 protein levels. However, the antagonist for GPR40 failed to diminish the action of KetoC.
Conclusion
KetoC suppressed the proinflammatory cytokines TNFα, IL‐6 and IL‐1β via NF‐κB p65, by binding to its receptor GPR120. KetoC is a promising candidate in future studies as a bioactive anti‐inflammatory agent in treating periodontal disease.
Optimal production conditions of conjugated γ-linolenic acid (CGLA) from γ-linolenic acid using washed cells of Lactobacillus plantarum AKU 1009a as catalysts were investigated. Washed cells of Lact. ...plantarum AKU 1009a exhibiting a high level of CGLA productivity were obtained by cultivation in a nutrient medium supplemented with 0·03% (w/v) α-linolenic acid as an inducer. Under the optimal reaction conditions with 13 mg ml⁻¹γ-linolenic acid as a substrate in 5 -ml reaction volume, the washed cells 32% (wet cells, w/v) corresponding to 46 mg ml⁻¹ dry cells as the catalysts produced 8·8 mg CGLA per millilitre reaction mixture (68% molar yield) in 27 h. The produced CGLA was a mixture of two isomers, i.e., cis-6,cis-9,trans-11-octadecatrienoic acid (CGLA1, 40% of total CGLA) and cis-6,trans-9,trans-11-octadecatrienoic acid (CGLA2, 60% of total CGLA), and accounted for 66% of total fatty acid obtained. The CGLA produced was obtained as free fatty acids adsorbed mostly on the surface of the cells of Lact. plantarum AKU1009a. The practical process of CGLA production from γ-linolenic acid using washed cells of Lact. plantarum AKU 1009a was successfully established. We presented the first example of microbial production of CGLA. CGLA produced by the process is valuable for evaluating their physiological and nutritional effects, and chemical characteristics.
Results No significant difference in creatinine clearance over time was observed between patients with CYP3A5*1 allele and patients without CYP3A5*1 allele, suggesting that the degrees of recovery in ...renal function after living kidney transplantation are similar in the two groups.
Objectives
Micafungin (MCFG) is an antifungal agent that is widely used for the treatment of invasive fungal infection. Although the pharmacokinetics of MCFG is considered to depend on the hepatic ...metabolism, the impact of hepatic function on the pharmacokinetics of MCFG has been inconsistent among previous studies. The object of this study was to evaluate the relationship between plasma MCFG concentration and clinical and laboratory data.
Patients and methods
We examined the plasma concentration of MCFG in 10 patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). MCFG at 150 mg/day was administered intravenously a median of 58.5 days after HSCT. Trough and peak concentrations of MCFG (Cmin and Cmax) were measured at a median of 5.5 days after the first administration of MCFG.
Results
The presence of graft‐versus‐host disease involving the liver at blood sampling was associated with significantly higher Cmin and Cmax of MCFG. Among the laboratory data, Cmin and Cmax were significantly higher in patients with severely impaired hepatic function defined as serum total bilirubin (TBi) level >5 mg/dL and/or serum gamma‐glutamyltransferase (γ‐GTP) level >500 IU/L, but the presence of mildly impaired hepatic function defined as serum TBi level >2 mg/dL and/or serum γ‐GTP level >200 IU/L did not affect Cmin and Cmax. Renal function did not show significant impact on Cmin and Cmax.
Conclusion
These findings suggest that the pharmacokinetics of MCFG is affected only by severely impaired liver function.
Ricinoleic acid (12-hydroxy-cis-9-octadecaenoic acid) was an effective substrate for conjugated linoleic acid (CLA) production by washed cells of Lactobacillus plantarum AKU 1009a. The CLA produced ...was a mixture of cis-9,trans-11- and trans-9,trans-11-octadecadienoic acids. Addition of α-linolenic acid to the culture medium increased the CLA productivity of the washed cells. In the presence of lipase, castor oil, in which the main fatty acid component is ricinoleic acid, also was a substrate for CLA.
Bio-process development for isomer selective and efficient production of cis-9,trans-11-octadecadienoic acid (CLA) from trans-vaccenic acid (t-VA, trans-11-octadecenoic acid) through microbial fatty ...acid Δ9-desaturation reaction. A total of 550 strains of fungi and yeasts were screened for CLA production from t-VA through Δ9 desaturation. Delacroixia coronata IFO 8586 was selected as a potent producer of CLA from t-VA. Efficient CLA production was observed during cultivation in medium supplemented with the methyl ester of t-VA (t-VAME). Under the optimal conditions with 33·3 mg ml⁻¹ of t-VAME as substrate, 10·5 mg ml⁻¹ CLA was produced by D. coronata IFO 8586 after 7 days of cultivation in the medium containing dextrin (5·0%), tryptone (2·0%) and thiourea (0·83 μmol ml⁻¹). The strain produced the cis-9,trans-11 isomer of CLA selectively (98% of total CLA), with a small amount of the trans-9,trans-11 isomer (2% of total CLA), mainly in the form of triacylglycerols (69% of total CLA). A practical bio-process for selective production of cis-9,trans-11 isomer of CLA using filamentous fungus D. coronata IFO 8586 was successfully established. Isomer selective bio-process for the practical production of cis-9,trans-11-CLA was first established. The process is benefitable for expanding the application of CLA for medicinal and nutraceutical purposes.
Aims The F1S and A genetic variants of α1‐acid glycoprotein (AAG) change under various physiological and pathological conditions. They also vary in their drug binding abilities. We have studied the ...stereoselective binding ability of each of the AAG variants using enantiomers of disopyramide (DP) and warfarin (WR).
Methods The AAG variants were separated by hydroxyapatite chromatography. Binding of drug enantiomers to the AAG variants was studied by the Hummel–Dreyer method. The characteristics of the binding activities were examined by Scatchard plot analysis. The first five amino‐terminal amino acids (residues 112–116) of the cyanogen bromide (CNBr) fragment (residues 112–181) of each of the separated AAG fractions were elucidated by Edman degradation.
Results Commercial AAG was separated into two main fractions. Residues 112–116 of fraction 2 were identical to the amino acid sequences predicted from the AAG A gene, LAFDV, and encode the F1S variant. In fraction 3, the deduced amino acid sequence of the AAG B gene, FGSYL, was established, and encodes the A variant. The binding affinities of both DP enantiomers in fraction 3 were significantly higher than those in fraction 2. The differences between dissociation constants (Kd) in fractions 2 and 3 were 5.2‐fold for (S)‐DP (P < 0.05) and 3.7‐fold for (R)‐DP (P < 0.001). The dissociation constant of (S)‐DP (0.39 ± 0.08 µm) was lower than that of (R)‐DP (0.53 ± 0.10 µm) in fraction 3 95% confidence interval (CI) − 0.282, − 0.010; P < 0.05, although the binding activities of the DP enantiomers were almost the same in fraction 2. By contrast WR enantiomers had a higher binding affinity in fraction 2 than in fraction 3, the differences in dissociation constants between fractions 2 and 3 being 12.6‐fold for (S)‐WR (P < 0.001) and 8.3‐fold for (R)‐WR (P < 0.001). The dissociation constant of (S)‐WR (0.28 ± 0.10 µm) was significantly lower than that of (R)‐WR (0.48 ± 0.08 µm) in fraction 2 (95% CI − 0.369, − 0.028; P < 0.05), but there were no significant differences between the binding activities of WR enantiomers in fraction 3.
Conclusions DP and WR enantiomers bind preferentially to fraction 3 and fraction 2, respectively. Fractions 2 and 3 are encoded by the AAG A and the AAG B genes, respectively.
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