Sakai S

References (11)

Title : Impact of the lipase inhibitor orlistat on the human gut microbiota - Uehira_2023_Obes.Res.Clin.Pract__
Author(s) : Uehira Y , Ueno H , Miyamoto J , Kimura I , Ishizawa Y , Iijima H , Muroga S , Fujita T , Sakai S , Samukawa Y , Tanaka Y , Murayama S , Sakoda H , Nakazato M
Ref : Obes Res Clin Pract , : , 2023
Abstract : Orlistat, an anti-obesity agent, inhibits the metabolism and absorption of dietary fat by inactivating pancreatic lipase in the gut. The effect of orlistat on the gut microbiota of Japanese individuals with obesity is unknown. This study aimed to explore the effects of orlistat on the gut microbiota and fatty acid metabolism of Japanese individuals with obesity. Fourteen subjects with visceral fat obesity (waist circumference <=85 cm) took orlistat orally at a dose of 60 mg, 3 times a day for 8 weeks. Body weight; waist circumference; visceral fat area; levels of short-chain fatty acids, gut microbiota, fatty acid metabolites in the feces, and gastrointestinal hormones; and adverse events were evaluated. Body weight, waist circumference, and blood leptin concentrations were significantly lower after orlistat treatment (mean +/- standard deviation, 77.8 +/- 9.1 kg; 91.9 +/- 8.7 cm; and 4546 +/- 3211 pg/mL, respectively) compared with before treatment (79.4 +/- 9.0 kg; 94.4 +/- 8.0 cm; and 5881 +/- 3526 pg/mL, respectively). Significant increases in fecal levels of fatty acid metabolites (10-hydroxy-cis-12-octadecenoic acid, 10-oxo-cis-12-octadecenoic acid, and 10-oxo-trans-11-octadecenoic acid) were detected. Meanwhile, no significant changes were found in abdominal computed tomography parameters, blood marker levels, or short-chain fatty acid levels in the feces. Gut microbiota analysis revealed that some study subjects had decreased abundance of Firmicutes, increased abundance of Bacteroidetes, and increased alpha-diversity indices (Chao1 and ACE) after 8 weeks of treatment. The levels of Lactobacillus genus and Lactobacillus gasseri were significantly higher after 8 weeks of treatment. None of the subjects discontinued treatment or experienced severe adverse events. This study suggested that orlistat might alter gut microbiota composition and affect the body through fatty acid metabolites produced by the modified gut bacteria.
ESTHER : Uehira_2023_Obes.Res.Clin.Pract__
PubMedSearch : Uehira_2023_Obes.Res.Clin.Pract__
PubMedID: 37679239

Title : Assessment of drug-drug interaction and optimization in capecitabine and irinotecan combination regimen using a physiologically based pharmacokinetic model - Sakai_2021_J.Pharm.Sci__
Author(s) : Sakai S , Kobuchi S , Ito Y , Sakaeda T
Ref : J Pharm Sci , : , 2021
Abstract : Capecitabine and irinotecan (CPT-11) combination regimen (XELIRI) is used for colorectal cancer treatment. Capecitabine is metabolized to 5-fluorouracil (5-FU) by three enzymes, including carboxylesterase (CES). CES can also convert CPT-11 to 7-ethyl-10-hydroxycamptotecin (SN-38). CES is involved in the metabolic activation of both capecitabine and CPT-11, and it is possible that drug-drug interactions occur in XELIRI. Here, a physiologically based pharmacokinetic (PBPK) model was developed to evaluate drug-drug interactions. Capecitabine (180 mg/kg) and CPT-11 (180 mg/m(2)) were administered to rats, and blood (250 microL) was collected from the jugular vein nine times after administration. Metabolic enzyme activities and K(i) values were calculated through in vitro experiments. The plasma concentration of 5-FU in XELIRI was significantly decreased compared to capecitabine monotherapy, and metabolism of capecitabine by CES was inhibited by CPT-11. A PBPK model was developed based on the in vivo and in vitro results. Furthermore, a PBPK model-based simulation was performed with the capecitabin dose ranging from 0 to 1000mol/kg in XELIRI, and it was found that an approximately 1.7-fold dosage of capecitabine was required in XELIRI for comparable 5-FU exposure with capecitabine monotherapy. PBPK model-based simulation will contribute to the optimization of colorectal cancer chemotherapy using XELIRI.
ESTHER : Sakai_2021_J.Pharm.Sci__
PubMedSearch : Sakai_2021_J.Pharm.Sci__
PubMedID: 34965386

Title : Assessment of pharmacokinetic variations of capecitabine after multiple administration in rats: a physiologically based pharmacokinetic model - Sakai_2020_Cancer.Chemother.Pharmacol__
Author(s) : Sakai S , Kobuchi S , Ito Y , Sakaeda T
Ref : Cancer Chemother Pharmacol , : , 2020
Abstract : PURPOSE: Capecitabine is a prodrug of 5-fluorouracil (5-FU) used for the treatment of colorectal cancer, with a two-week course of administration. However, the variance in plasma concentration and metabolic enzyme activities after multiple administration of capecitabine and its metabolites is unknown. The aim of this study was to identify the variance and predict the plasma concentration profile of capecitabine and its metabolites, using metabolic enzyme activities, to develop a more effective and safer medication. METHODS: Rats orally received 180 mg/kg of capecitabine once a day for two weeks. Blood samples were collected nine times, and plasma concentration was measured on day 1, 7, and 14. The liver and small intestine were removed after blood sampling and were used in vitro to evaluate metabolic enzyme activities of carboxylesterase, cytidine deaminase, and thymidine phosphorylase. A physiologically based pharmacokinetic (PBPK) model was developed using in vitro results. RESULTS: Area under the plasma concentration-time curve from 0 h to infinity of 5-FU on day 7 and day 14 was significantly lower than that on day 1. Intrinsic clearance of thymidine phosphorylase in the liver on day 7 and day 14 was 1.4 and 1.3 times lower than that on day 1, respectively. The PBPK model described the observed plasma concentration of capecitabine and its metabolites. CONCLUSION: The decreased plasma concentration of capecitabine was caused by decreased metabolic enzyme activity. Efficacy can be improved by dose adjustment of capecitabine based on metabolic enzyme activities, using the PBPK model.
ESTHER : Sakai_2020_Cancer.Chemother.Pharmacol__
PubMedSearch : Sakai_2020_Cancer.Chemother.Pharmacol__
PubMedID: 32240335

Title : Structure-activity relationship of atorvastatin derivatives for metabolic activation by hydrolases - Mizoi_2019_Xenobiotica__1
Author(s) : Mizoi K , Takahashi M , Sakai S , Ogihara T , Haba M , Hosokawa M
Ref : Xenobiotica , :1 , 2019
Abstract : 1. We investigated the structure-activity relationship of 31 kinds of synthesized atorvastatin esters, thioesters, amides, and lactone, selected as prodrug models, for metabolic activation by microsomes and hydrolases. 2. The susceptibility to human carboxylesterase 1 (hCES1) was influenced not only by the size of the acyl group and alkoxy group, but also by the degree of steric crowding around the alkoxy group. 3. The susceptibility to human carboxylesterase 2 (hCES2) increased with a decrease in electron density around the alkoxy group of the substrate. 4. Lactone was specifically hydrolyzed by paraoxonase 3 (PON3). 5. These findings should be useful in prodrug design for controlling metabolic activation.
ESTHER : Mizoi_2019_Xenobiotica__1
PubMedSearch : Mizoi_2019_Xenobiotica__1
PubMedID: 31173561

Title : Genome sequence of a mesophilic hydrogenotrophic methanogen Methanocella paludicola, the first cultivated representative of the order Methanocellales - Sakai_2011_PLoS.One_6_e22898
Author(s) : Sakai S , Takaki Y , Shimamura S , Sekine M , Tajima T , Kosugi H , Ichikawa N , Tasumi E , Hiraki AT , Shimizu A , Kato Y , Nishiko R , Mori K , Fujita N , Imachi H , Takai K
Ref : PLoS ONE , 6 :e22898 , 2011
Abstract : We report complete genome sequence of a mesophilic hydrogenotrophic methanogen Methanocella paludicola, the first cultured representative of the order Methanocellales once recognized as an uncultured key archaeal group for methane emission in rice fields. The genome sequence of M. paludicola consists of a single circular chromosome of 2,957,635 bp containing 3004 protein-coding sequences (CDS). Genes for most of the functions known in the methanogenic archaea were identified, e.g. a full complement of hydrogenases and methanogenesis enzymes. The mixotrophic growth of M. paludicola was clarified by the genomic characterization and re-examined by the subsequent growth experiments. Comparative genome analysis with the previously reported genome sequence of RC-I(MRE50), which was metagenomically reconstructed, demonstrated that about 70% of M. paludicola CDSs were genetically related with RC-I(MRE50) CDSs. These CDSs included the genes involved in hydrogenotrophic methane production, incomplete TCA cycle, assimilatory sulfate reduction and so on. However, the genetic components for the carbon and nitrogen fixation and antioxidant system were different between the two Methanocellales genomes. The difference is likely associated with the physiological variability between M. paludicola and RC-I(MRE50), further suggesting the genomic and physiological diversity of the Methanocellales methanogens. Comparative genome analysis among the previously determined methanogen genomes points to the genome-wide relatedness of the Methanocellales methanogens to the orders Methanosarcinales and Methanomicrobiales methanogens in terms of the genetic repertoire. Meanwhile, the unique evolutionary history of the Methanocellales methanogens is also traced in an aspect by the comparative genome analysis among the methanogens.
ESTHER : Sakai_2011_PLoS.One_6_e22898
PubMedSearch : Sakai_2011_PLoS.One_6_e22898
PubMedID: 21829548

Title : Immobilization of Pseudomonas cepacia lipase onto electrospun polyacrylonitrile fibers through physical adsorption and application to transesterification in nonaqueous solvent - Sakai_2010_Biotechnol.Lett_32_1059
Author(s) : Sakai S , Liu Y , Yamaguchi T , Watanabe R , Kawabe M , Kawakami K
Ref : Biotechnol Lett , 32 :1059 , 2010
Abstract : The lipase of Pseudomonas cepacia was immobilized onto electrospun polyacrylonitrile (PAN) fibers and used for the conversion of (S)-glycidol with vinyl n-butyrate to glycidyl n-butyrate in isooctane. The rate of reaction with the adsorbed lipase was 23-fold higher than the initial material. After 10 recyclings, the initial reaction rate was 80% of the original rate. This system of enzyme immobilization is therefore suitable for carrying out transesterification reactions in nonaqueous solvents.
ESTHER : Sakai_2010_Biotechnol.Lett_32_1059
PubMedSearch : Sakai_2010_Biotechnol.Lett_32_1059
PubMedID: 20424890

Title : Production of butyl-biodiesel using lipase physically-adsorbed onto electrospun polyacrylonitrile fibers - Sakai_2010_Bioresour.Technol_101_7344
Author(s) : Sakai S , Liu Y , Yamaguchi T , Watanabe R , Kawabe M , Kawakami K
Ref : Bioresour Technol , 101 :7344 , 2010
Abstract : Butyl-biodiesel production using electrospun polyacrylonitrile fibers with Pseudomonas cepacia lipase immobilized through physical adsorption was studied. About 80% conversion to butyl-biodiesel was achieved after 24h by suspending the catalyst at 2.4 mg/mL in a mixture of rapeseed oil and n-butanol at a molar ratio of 1:3, containing water at 8000 ppm at 40 degrees C. A further 24h of operation resulted in 94% conversion. The initial reaction rate detected for this process was 65-fold faster than those detected for Novozym 435 on a total catalyst mass basis. The immobilized lipase continued to work as a catalyst for 27 d, within a 15% reduction in conversion yield at the outlet of the reactor compared with the average value detected during the first 3d of operation in a continuous butyl-biodiesel production system.
ESTHER : Sakai_2010_Bioresour.Technol_101_7344
PubMedSearch : Sakai_2010_Bioresour.Technol_101_7344
PubMedID: 20493682

Title : Transesterification by lipase entrapped in electrospun poly(vinyl alcohol) fibers and its application to a flow-through reactor - Sakai_2008_J.Biosci.Bioeng_105_687
Author(s) : Sakai S , Antoku K , Yamaguchi T , Kawakami K
Ref : J Biosci Bioeng , 105 :687 , 2008
Abstract : We entrapped lipase in electrospun poly(vinyl alcohol) fibers of approximately 1 mum in diameter and evaluated the transesterification activity by converting (s)-glycidol to glycidyl n-butyrate with vinyl n-butyrate. The initial transesterification rate of the entrapped lipase was 5.2-fold faster than that of non-treated lipase. The fibrous membrane could be used as a component of a flow-through reactor for continuous transesterification.
ESTHER : Sakai_2008_J.Biosci.Bioeng_105_687
PubMedSearch : Sakai_2008_J.Biosci.Bioeng_105_687
PubMedID: 18640613

Title : Development of a silica monolith microbioreactor entrapping highly activated lipase and an experiment toward integration with chromatographic separation of chiral esters - Kawakami_2007_J.Sep.Sci_30_3077
Author(s) : Kawakami K , Abe D , Urakawa T , Kawashima A , Oda Y , Takahashi R , Sakai S
Ref : J Sep Sci , 30 :3077 , 2007
Abstract : Microbioreactors are effective for high-throughput production of expensive products from small amounts of substrates. Lipases are versatile enzymes for chiral syntheses, and are highly activated when immobilized in alkyl-substituted silicates by the sol-gel method. For practical application of sol-gel immobilized lipases to a flow system, a microbioreactor loaded with a macroporous silica monolith is well suited, because it can be easily integrated with a chromatographic separator for optical resolution. We attempted to develop a microbioreactor containing a silica monolith-immobilized lipase. A nonshrinkable silica monolith was first formed from a 4:1 mixture of methyltrimethoxysilane (MTMS) and tetramethoxysilane (TMOS). It was then coated with silica precipitates entrapping lipase, derived from a 4:1 mixture of n-butyltrimethoxysilane (BTMS) and TMOS. As a result, monolith treated with the BTMS-based silicate entrapping lipase exhibited approximately ten times higher activity than nontreated monolith-immobilized lipase derived from the MTMS-based silicate, in transesterification between glycidol and vinyl n-butyrate in isooctane. A commercially available chiral column was connected in series to the monolith microbioreactor, and a pulse of substrate solution was supplied at the inlet of the reactor. Successful resolution of the racemic ester produced was achieved in the chromatographic column.
ESTHER : Kawakami_2007_J.Sep.Sci_30_3077
PubMedSearch : Kawakami_2007_J.Sep.Sci_30_3077
PubMedID: 17924370

Title : Preparation of the methyl ester of hyaluronan and its enzymatic degradation - Hirano_2005_Carbohydr.Res_340_2297
Author(s) : Hirano K , Sakai S , Ishikawa T , Avci FY , Linhardt RJ , Toida T
Ref : Carbohydr Res , 340 :2297 , 2005
Abstract : A methyl ester of hyaluronan in which the carboxyl groups were fully esterified was prepared using trimethylsilyl diazomethane. This derivative, while not depolymerized by hyaluronan lyases or hyaluronan hydrolases, was a substrate for both chondroitin ACI lyase (EC from Flavobacterium heparinum and chondroitin ACII lyase (EC from Arthrobacter aurescens. The major product isolated in these depolymerization reactions was methyl alpha-L-threo-hex-4-enepyranosyluronate-(1-->3)-2-acetamido-2-deoxy-alpha,beta-D- glucopyranoside as determined by 1H NMR spectroscopy and MALDITOF mass spectrometry.
ESTHER : Hirano_2005_Carbohydr.Res_340_2297
PubMedSearch : Hirano_2005_Carbohydr.Res_340_2297
PubMedID: 16098492

Title : [A nutritional investigation of homeless patients with tuberculosis] - Yamanaka_2001_Kekkaku_76_363
Author(s) : Yamanaka K , Sakai S , Nomura F , Akashi T , Usui T
Ref : Kekkaku , 76 :363 , 2001
Abstract : A retrospective case-control study was performed with TB patients who were admitted to our hospital over the two years from Jan. 1997 to Dec. 1998 and healthy men who underwent a health screening in April 2000 in the same hospital. Thirty-two non-homeless TB patients (the first control group) and 32 healthy men (the second control group) were matched with 32 homeless TB patients according to age. All 3 groups were male. Total protein, albumin, cholesterol, cholinesterase, hemoglobin level and lymphocyte count on admission were significantly lower in the homeless patients than in the non-homeless patients and healthy men. Albumin, cholesterol, cholinesterase, hemoglobin level, white blood cell count and lymphocyte count on admission were significantly lower in non-homeless patients than healthy men. Height, weight and body mass index were significantly lower in the homeless patients than in the healthy men. However, there were no significant differences in these body characteristics between the homeless and non-homeless patients. Twenty-five percent of homeless patients died during hospitalization, compared with 6.3 percent of non-homeless patients. Lymphocyte counts among homeless patients who died during hospitalization were significantly lower than among those who survived during hospitalization. Total protein, albumin, cholesterol, cholinesterase, hemoglobin level and weight were lower in patients who died than in those who survived, although the differences were statistically not significant.
ESTHER : Yamanaka_2001_Kekkaku_76_363
PubMedSearch : Yamanaka_2001_Kekkaku_76_363
PubMedID: 11398327