Publications by authors named "Yoshiki Mino"

27 Publications

  • Page 1 of 1

Interaction of platinum agents, cisplatin, carboplatin and oxaliplatin against albumin in vivo rats and in vitro study using inductively coupled plasma-mass spectrometory.

Biopharm Drug Dispos 2019 Jul;40(7):242-249

Department of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.

The protein binding rates (PBR) of platinum-containing agents cisplatin (CDDP), carboplatin (CBDCA) and oxaliplatin (L-OHP) have been reported as 98%, 25-50% and 98%, respectively. To investigate the protein-binding properties of albumin with cisplatin, carboplatin and oxaliplatin, inductively coupled plasma mass spectrometry (ICP-MS) was used to measure their plasma concentration in rats over time. The study also examined the effects of cisplatin, carboplatin and oxaliplatin-binding on albumin in vitro, using CD spectrometry and native-polyacrylamide gel electrophoresis (native PAGE). The ratios of PBR to irreversible PBR, of cisplatin and oxaliplatin were 98%:98% and 90%:87%, respectively, indicating a higher affinity for irreversible binding with albumin. That of carboplatin was 25%:10%, indicating 60-70% reversible binding with albumin. The plasma protein binding rate concentrations of cisplatin, carboplatin and oxaliplatin after in vivo administration were 96%, 15% and 80%, respectively. The CD spectrometry of albumin was unaffected by cisplatin, carboplatin and oxaliplatin binding. Though similar protein binding rates were observed with oxaliplatin and cisplatin, oxaliplatin had a higher mobility rate during PAGE. It was confirmed that the binding of cisplatin and oxaliplatin with albumin affected its electric charge but not the structure. In conclusion, cisplatin and oxaliplatin bind irreversibly with albumin in plasma and may irreversibly interact with tissue protein and/or DNA. The difficulties involved with predicting the tissue concentrations of cisplatin and oxaliplatin from their plasma concentration inhibits their therapeutic drug monitoring. On the contrary, carboplatin, like some generic drugs, reversibly binds to plasma proteins. It is, therefore, possible to conduct therapeutic drug monitoring for carboplatin.
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http://dx.doi.org/10.1002/bdd.2197DOI Listing
July 2019

Environmental fate of pharmaceutical compounds and antimicrobial-resistant bacteria in hospital effluents, and contributions to pollutant loads in the surface waters in Japan.

Sci Total Environ 2019 Mar 3;657:476-484. Epub 2018 Dec 3.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

Environmental fate of 58 pharmaceutical compounds (PhCs) grouped into 11 therapeutic classes in the three different waters, hospital effluent, sewage treatment plant (STP) and river water, was estimated by combination of their quantitative concentration analysis and evaluation of their extent of contribution as loading sources. At the same time, distribution of six classes of antimicrobial-resistant bacteria (AMRB) in the same water samples was estimated by screening of individual PhC-resistant microbes grown on each specific chromogenic medium. The results indicate that 48 PhCs were detected ranged from 1 ng/L (losartan carboxylic acid) to 228 μg/L (acetaminophen sulfate) in hospital effluent, and contribution of the pollution load derived from hospital effluent to STP influent was estimated as 0.1% to 15%. On the other hand, contribution of STP effluent to river water was high, 32% to 60% for antibacterials, antipertensives and X-ray contrast media. In the cases for AMRB, detected numbers of colonies of AMRB in hospital effluent ranged from 29 CFU/mL to 1805 CFU/mL, and the estimated contribution of the AMRB pollution load derived from hospital effluent to STP influent was as low as 0.1% (levofloxacin and olmesartan) to 5.1% (N-desmethyl tamoxifen). Although the contribution of STPs as loading sources of PhCs and AMRB in surface waters was large, ozonation as an advanced water treatment system effectively removed a wide range of both PhCs and AMRB in water samples. These results suggest the importance of reducing environmental pollutant loads (not only at STPs but also at medical facilities) before being discharged into the surface waters, to both conserve water and keep the water environment safe. To our knowledge, this is the first report to show the distribution and contribution of AMRB from hospital effluent to the surface waters.
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http://dx.doi.org/10.1016/j.scitotenv.2018.11.433DOI Listing
March 2019

Performance and efficiency of removal of pharmaceutical compounds from hospital wastewater by lab-scale biological treatment system.

Environ Sci Pollut Res Int 2018 May 12;25(15):14647-14655. Epub 2018 Mar 12.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.

The fate of pharmaceuticals after discharged from hospital into wastewater was clarified experimentally by using a new lab-scale conventional activated sludge (CAS) treatment reactor. The 43 target compounds belong to nine therapeutic classes (antivirals, antibacterials, anticancer drugs, psychotropics, antihypertensives, analgesic-antipyretics, contrast media, herbal medicines, and phytoestrogens) were selected with inclusion of 16 newly estimated compounds. The efficiency of the present reactor was estimated by comparing the reaction rate constant of the solid-water partition coefficients (log K) between liquid and solid samples and half-life during 48-h experiment obtained by using hospital effluents with those obtained by using STP wastewater. The results that no significant difference in removal efficiency was observed between both water samples (P > 0.05) indicate high reliability of the present lab-scale reactor. The actual rates of removal when hospital effluent was applied varied widely (mean, 59 ± 40%) independent of type of the pharmaceuticals. More than 90% of 17 compounds were removed after 8 h of treatment. However, the values for psychotropics (mean, 19 ± 26%) and contrast media (mean, 24 ± 17%) were generally low, indicating high stability. The log K values ranged from 1.3 to 4.8. Notably, clarithromycin, acridine, and glycitein could be removed in both liquid and solid phases. The dominant removal mechanisms were found to be different for individual pharmaceutical. These results suggest the effectiveness of introduction of the lab-scale biological treatment system for development of a new solution for discharge of pharmaceuticals from hospital.
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http://dx.doi.org/10.1007/s11356-018-1688-9DOI Listing
May 2018

[Bioinorganic Chemistry of Iron].

Authors:
Yoshiki Mino

Yakugaku Zasshi 2018 ;138(3):373-387

Osaka University of Pharmaceutical Sciences.

 The X-ray crystallographic analysis of the single-crystal mugineic acid-Cu(II) complex showed that mugineic acid acts as a hexadentate ligand. Mugineic acid, a typical phytosiderophore, shows a marked stimulating effect on Fe-uptake and chlorophyll synthesis in rice plants. A salient feature is the higher reduction potential of the mugineic acid-Fe(III) complex than those of bacterial siderophores. X-ray diffraction study of the structurally analogous Co(III) complex of the mugineic acid-Fe(III) complex demonstrates that the azetidine nitrogen and secondary amine nitrogen, and both terminal carboxylate oxygens, coordinate as basal planar donors, and the hydroxyl oxygen and intermediate carboxylate oxygen bind as axial donors in a nearly octahedral configuration. The iron-transport mechanism in gramineous plants appears to involve the excretion of mugineic acid from the roots, which aids Fe(III)-solubilization and reduction of Fe(III) to Fe(II). Manganese peroxidase (MnP) is a component of the lignin degradation system of the basidiomycetous fungus, Phanerochaete chrysosporium. To elucidate the heme environment of this novel Mn(II)-dependent extracellular enzyme, we studied its ESR and resonance Raman spectroscopic properties. Consequently, it is most likely that the heme environment of MnP resembles that of cytochrome c peroxidase. In addition, degradation methods using basidiomycetous fungi or Fe-HO mixed reagent were developed for dioxins and polychlorinated biphenyls. The complete amino acid sequences of respective [2Fe-2S] ferredoxins were determined and compared with those of other higher plants. Finally, the toxic effects of iron on human health and the development of novel antibacterial drugs capable of inhibiting the iron transport system of Vibrio vulnificus are described.
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http://dx.doi.org/10.1248/yakushi.17-00154DOI Listing
March 2018

Distribution of six anticancer drugs and a variety of other pharmaceuticals, and their sorption onto sediments, in an urban Japanese river.

Environ Sci Pollut Res Int 2017 Aug 28;24(23):19021-19030. Epub 2017 Jun 28.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.

The distributions of 31 pharmaceuticals grouped into nine therapeutic classes, including six anticancer drugs, were investigated in the waters and sediments of an urban river in Japan. The coefficients of sorption (logK ) to the river sediments were also determined from the results of a field survey and laboratory-scale experiment. Three anticancer drugs-bicalutamide, doxifluridine, and tamoxifen-were detected in the river sediments at maximum concentrations of 391, 392, and 250 ng/kg, respectively. In addition, the transformation products of psychotropic carbamazepine (2-hydroxy carbamazepine, acridine, and acridone) were detected in the range of 108 ng/kg (2-hydroxy carbamazepine) to 2365 ng/kg (acridine), and the phytoestrogen glycitein was detected in the range of N.D. to 821 ng/kg. The logK values of the targeted pharmaceuticals in river sediments in the field survey ranged from 0.5 (theophylline) to 3.3 (azithromycin). These results were in accord with those of the laboratory-scale sorption experiment. To the best of our knowledge, this is the first report of the detection of the anticancer drugs bicalutamide and tamoxifen, the transformation products of carbamazepine (2-hydroxy carbamazepine, acridine, and acridone), and the phytoestrogen genistein in river sediments.
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http://dx.doi.org/10.1007/s11356-017-9525-0DOI Listing
August 2017

A method for evaluating the pharmaceutical deconjugation potential in river water environments.

Chemosphere 2017 Aug 10;180:476-482. Epub 2017 Apr 10.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

A new enzymatic assay method that uses deconjugation enzymes was developed to evaluate the presence and extent of conjugated pharmaceuticals in the form of glucuronide conjugates or sulphate conjugates in river environments. First, acetaminophen glucuronide (Ace Glu) and acetaminophen sulphate (Ace Sul) were used as model conjugated pharmaceuticals to determine the appropriate combination of deconjugation enzymes and reaction conditions, including temperature, duration and pH. Next, we applied the defined method to 19 pharmaceuticals grouped into nine therapeutic classes that were chosen based on previously detected levels and frequencies in sewage and river water. The enzymatic decomposition profile varied widely depending upon the enzyme preparations available. The effect of the water reaction temperature was small between 5 and 40 °C, and the reaction proceeded in for both glucuronide conjugates and sulphate conjugates at an approximately neutral pH (corresponding to usual river water conditions) within 1 h. Application of the method to environmental samples showed that some pharmaceuticals were present in both glucuronide conjugate and sulphate conjugated forms, although glucuronide conjugates were the primary forms in the river water environment. Water treatment systems at sewage treatment plants were found to be effective for the removal of these conjugated compounds. The present results should be valuable in the environmental risk assessment of conjugated pharmaceuticals and in keeping river environments clean. To the best of our knowledge, this is the first report that enables the evaluation of the pharmaceutical deconjugation potential in a river environment.
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http://dx.doi.org/10.1016/j.chemosphere.2017.04.040DOI Listing
August 2017

A Novel Analytical Method of Cisplatin Using the HPLC with a Naphthylethyl Group Bonded with Silica Gel (πNAP) Column.

Biol Pharm Bull 2017 Mar 14;40(3):290-296. Epub 2016 Dec 14.

Laboratory of Cardiovascular Pharmacotherapy and Toxicology, Osaka University of Pharmaceutical Sciences.

Cisplatin is the most widely used anticancer drug in the world. Mono-chloro and none-chloro complexes of cisplatin may be believed to be the activated compounds. The separation of these compounds using octa decyl silyl column or aminopropylsilyl silica gel column is difficult because of high-reactivity and structural similarity. In this study, cisplatin, hydroxo complexes, and OH-dimer were determined by HPLC using a naphthylethyl group bonded with silica gel (πNAP) column. The analytical conditions of HPLC were as follows: analytical column, πNAP column; wave length, 225 nm; column temperature, 40°C; mobile phase, 0.1 M sodium perchlorate, acetonitrile, and perchloric acid (290 : 10 : 3), flow rate, 1.0 mL/min. Sample (20 µL) was injected onto the HPLC system. Retention time of cisplatin, mono-chloride, OH-dimer, and none-chloride was 3.2, 3.4, 3.6, and, 4.3-6.6 min, respectively. Measurable ranges with this method were 1×10 to 4×10 M for cisplatin. Correlation coefficient of the calibration curves of cisplatin was 0.999 (p<0.01). The within- and between-day variations of coefficient of variation (CV) were 5% or lower. In this study, injectable formulations in physiological saline solution, water for injection, 5% glucose solution, and 7% sodium bicarbonate precisely were measured the stability and compositional changes upon mixing by πNAP column rather than C18 column. We successfully determined cisplatin, hydroxo complexes, and OH-dimer by HPLC using a πNAP column. Thus the measurement of cisplatin (cis-diamminedichloro-platinum(II), cis-[PtCl(NH)]) (CDDP) should be done using a πNAP column rather than a C18 column or aminopropylsilyl silica gel column.
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http://dx.doi.org/10.1248/bpb.b16-00760DOI Listing
March 2017

Fate of new three anti-influenza drugs and one prodrug in the water environment.

Chemosphere 2017 Feb 26;169:550-557. Epub 2016 Nov 26.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

We evaluated the environmental fate of new three anti-influenza drugs, favipiravir (FAV), peramivir (PER), and laninamivir (LAN), and an active prodrug of LAN, laninamivir octanoate (LANO), in comparison with four conventional drugs, oseltamivir (OS), oseltamivir carboxylate (OC), amantadine (AMN), and zanamivir (ZAN) by photodegradation, biodegradation, and sorption to river sediments. In addition, we conducted 9-month survey of urban rivers in the Yodo River basin from 2015 to 2016 (including the influenza season) to investigate the current status of occurrence of these drugs in the river environment. The results clearly showed that FAV and LAN rapidly disappeared through photodegradation (half-lives 1 and 8 h, respectively), followed by LANO which gradually disappeared through biodegradation (half-life, 2 days). The remained PER and conventional drugs were, however, persistent and transported from upstream to downstream sites. Rates of their sorption to river sediments were negligibly small. Detected levels remained were in the range from N.D. to 89 ng/L for the river waters and from N.D. to 906 ng/L in sewage effluent. However, all of the remained drugs were effectively removed by ozonation after chlorination at a sewage treatment plant. These findings suggest the importance of introducing ozonation for reduction of pollution loads in rivers, helping to keep river environments safe. To the best of our knowledge, this is the first evaluation of the removal effects of natural sunlight, biodegradation, and sorption to river sediments on FAV, PER, LAN, LANO, and a conventional drug, AMN.
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http://dx.doi.org/10.1016/j.chemosphere.2016.11.102DOI Listing
February 2017

Detection of pharmaceuticals and phytochemicals together with their metabolites in hospital effluents in Japan, and their contribution to sewage treatment plant influents.

Sci Total Environ 2016 Apr 21;548-549:189-197. Epub 2016 Jan 21.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

The occurrence of 41 pharmaceuticals and phytochemicals (PPs) including their metabolites was surveyed in hospital effluent in an urban area of Japan. A detailed survey of sewage treatment plant (STP) influent and effluent, and river water was also conducted. Finally, mass balances with mass fluxes of the target PPs through the water flow were evaluated and the degree of contribution of hospital effluent to the environmental discharge was estimated. The results indicate that 38 compounds were detectable in hospital effluent over a wide concentration range from ng/L to μg/L, with a maximum of 92μg/L. The contributions of PPs in the hospital effluent to STP influent varied widely from <0.1% to 14.8%. Although almost all of the remaining components could be removed below 1.0ng/L at STPs by the addition of ozone treatment, a number of PPs still remained above 10ng/L in STP effluent. These findings suggest the importance of applying highly developed treatments to hospital effluents and at STPs in the future to reduce the environmental risks posed by PPs. To our knowledge, this is the first demonstration of the presence of two conjugated metabolites of acetaminophen, acetaminophen glucuronide and acetaminophen sulfate, as well as of loxoprofen and loxoprofen alcohol, in hospital effluent, STP, and river waters.
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http://dx.doi.org/10.1016/j.scitotenv.2015.12.157DOI Listing
April 2016

Occurrence and fate of selected anticancer, antimicrobial, and psychotropic pharmaceuticals in an urban river in a subcatchment of the Yodo River basin, Japan.

Environ Sci Pollut Res Int 2015 Dec 17;22(23):18676-86. Epub 2015 Jul 17.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.

Pollution status of six anticancer agents in the river water and effluents of sewage treatment plants (STPs) in Japan was surveyed with comparative analysis of the levels of four microbial and one psychotropic pharmaceuticals widely used for therapeutic medication. The area of survey is located in the Kanzaki-Ai River basin which is a major subcatchment of the Yodo River basin and is centered on a highly populated area that includes the middle and downstream reaches of the Yodo River. Selected cancer agents were bicalutamide, capecitabine, cyclophosphamide, doxifluridine, tamoxifen, and tegafur. A combination of strong anion solid-phase extraction cartridge under pH 11 for adsorption and optimization of liquid chromatography-tandem mass spectroscopy (LC-MS/MS) system was necessary to ensure high recovery rates (63-124% for river water and 52-115% for STP effluent). The year-round survey of these compounds in four seasons showed that all anticancer compounds were detected at median concentrations ranged from not detected to 32 ng/L in the river water and from not detected to 245 ng/L in the effluents of sewage treatment plants not using ozonation. In the case of bicalutamide (an active antiandrogen used to treat prostate cancer), the maximum concentration detected was 254 ng/L in river water and 1032 ng/L in non-ozonated sewage treatment plant effluents. Based on the mass balance, sewage treatment plants were the primary sources of anticancer compounds as well as the other pharmaceuticals in the river, and the attenuation effect of the river water was small. Ozonation at sewage treatment plants was effective in removing these compounds. To the best of our knowledge, this study is the first to report the existence of bicalutamide, doxifluridine, and tegafur in the river environment.
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http://dx.doi.org/10.1007/s11356-015-5013-6DOI Listing
December 2015

Detection of peramivir and laninamivir, new anti-influenza drugs, in sewage effluent and river waters in Japan.

PLoS One 2015 25;10(6):e0131412. Epub 2015 Jun 25.

Osaka University of Pharmaceutical Sciences, Takatsuki, Osaka, Japan.

This is the first report of the detection of two new anti-influenza drugs, peramivir (PER) and laninamivir (LAN), in Japanese sewage effluent and river waters. Over about 1 year from October 2013 to July 2014, including the influenza prevalence season in January and February 2014, we monitored for five anti-influenza drugs-oseltamivir (OS), oseltamivir carboxylate (OC), zanamivir (ZAN), PER, and LAN-in river waters and in sewage effluent flowing into urban rivers of the Yodo River system in Japan. The dynamic profiles of these anti-influenza drugs were synchronized well with that of the numbers of influenza patients treated with the drugs. The highest levels in sewage effluents and river waters were, respectively, 82 and 41 ng/L (OS), 347 and 125 ng/L (OC), 110 and 35 ng/L (ZAN), 64 and 11 ng/L (PER), and 21 and 9 ng/L (LAN). However, application of ozone treatment before discharge from sewage treatment plants was effective in reducing the levels of these anti-influenza drugs in effluent. The effectiveness of the ozone treatment and the drug dependent difference in susceptibility against ozone were further evidenced by ozonation of a STP effluent in a batch reactor. These findings should help to promote further environmental risk assessment of the generation of drug-resistant influenza viruses in aquatic environments.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0131412PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4482326PMC
April 2016

The RND protein is involved in the vulnibactin export system in Vibrio vulnificus M2799.

Microb Pathog 2014 Oct 6;75:59-67. Epub 2014 Sep 6.

Department of Microbiology, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. Electronic address:

Vibrio vulnificus, an opportunistic marine bacterium that causes a serious, often fatal, infection in humans, requires iron for its pathogenesis. This bacterium exports vulnibactin for iron acquisition from the environment. The mechanisms of vulnibactin biosynthesis and ferric-vulnibactin uptake systems have recently been reported, while the vulnibactin export system has not been reported. Mutant growth under low-iron concentration conditions and a bioassay of the culture supernatant indicate that the VV1_0612 protein plays a crucial role in the vulnibactin secretion as a component of the resistance-nodulation-division (RND)-type efflux system in V. vulnificus M2799. To identify which RND protein(s) together with VV1_0612 TolC constituted the RND efflux system for vulnibactin secretion, deletion mutants of 11 RND protein-encoding genes were constructed. The growth inhibition of a multiple mutant (Δ11) of the RND protein-encoding genes was observed 6 h after the beginning of the culture. Furthermore, ΔVV1_1681 exhibited a growth curve that was similar to that of Δ11, while the multiple mutant except ΔVV1_1681 showed the same growth as the wild-type strain. These results indicate that the VV1_1681 protein is involved in the vulnibactin export system of V. vulnificus M2799. This is the first genetic evidence that vulnibactin is secreted through the RND-type efflux systems in V. vulnificus.
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http://dx.doi.org/10.1016/j.micpath.2014.09.001DOI Listing
October 2014

Induction of viable but non-culturable (VBNC) state in Salmonella cultured in M9 minimal medium containing high glucose.

Biol Pharm Bull 2014 9;37(10):1617-25. Epub 2014 Aug 9.

Laboratory of Biodefense & Regulation, Osaka University of Pharmaceutical Sciences.

An environmental isolate of Salmonella enterica serovar Enteritidis (SE) clone, SE Cl#15-1, loses its culturability during 72-h culture in M9 minimal medium containing 0.8% glucose, a concentration twice higher than that in normal M9 medium, whereas the bacterium retains its culturability in normal M9 medium. Live/dead analysis using the 5-cyano-2,3-di(p-tolyl) tetrazolium chloride (CTC)-reduction assay revealed that SE cells cultured in M9 medium containing 0.8% glucose died with time when in the "viable but non-culturable" (VBNC) state. Assay of the culturability of SE cells in the used supernatant (0.4 spent M9 or 0.8 spent M9) also indicated that 0.8 spent M9 soon showed a lethal effect on intact SE cells. These results suggest that large amounts of glucose metabolites might have been responsible for the toxicity. Analysis of the 0.8 spent M9 revealed that formate rapidly accumulated in the medium. The pH of the medium rapidly dropped to 4.7, leading to conversion of formate to formic acid, which might have damaged the bacterial cell membrane. These results suggest that the excessive amount of glucose in the M9 medium might have injured SE cells in the VBNC state by being metabolized to formic acid and other acidic compounds.
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http://dx.doi.org/10.1248/bpb.b14-00322DOI Listing
June 2015

Second- and higher-order structural changes of DNA induced by antitumor-active tetrazolato-bridged dinuclear platinum(II) complexes with different types of 5-substituent.

J Inorg Biochem 2013 Oct 9;127:169-74. Epub 2013 May 9.

Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, Japan.

Here, we used circular dichroism (CD) and fluorescence microscopy (FM) to examine the interactions of a series of antitumor-active tetrazolato-bridged dinuclear platinum(II) complexes, [{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)](n+) (R=CH3 (1), C6H5 (2), CH2COOCH2CH3 (3), CH2COO(-) (4), n=2 (1-3) or 1 (4)), which are derivatives of [{cis-Pt(NH3)2}2(μ-OH)(μ-tetrazolato-N2,N3)](2+) (5-H-Y), with DNA to elucidate the influence of these interactions on the secondary or higher-order structure of DNA and reveal the mechanism of action. The CD study showed that three derivatives, 1-3, with a double-positive charge altered the secondary structures of calf thymus DNA but that 4, the only complex with a single positive charge, induced almost no change, implying that the B- to C-form conformational change is influenced by ionic attraction. Unexpectedly, single-molecule observations with FM revealed that 4 changed the higher-order structure of T4 DNA into the compact-globule state most efficiently, at the lowest concentration, which was nearly equal to that of 5-H-Y. These contradictory results suggest that secondary structural changes are not necessarily linked to higher-order ones, and that the non-coordinative interaction could be divided into two distinct interactions: (1) ionic attraction and (2) hydrogen bonding and/or van der Waals contact. The relationship between diffusion-controlled non-coordinative DNA interactions and cytotoxicities is also discussed.
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http://dx.doi.org/10.1016/j.jinorgbio.2013.05.004DOI Listing
October 2013

Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.

J Nutr Sci Vitaminol (Tokyo) 2011 ;57(2):192-6

Organization of Medical Education, Osaka Medical College, 2-7 Daigakuchou, Takatsuki, Osaka, Japan.

Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus. Deficiency of cellular nicotinamide adenine dinucleotide (NAD(+)) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions. Adenosine thiamine triphosphate (AThTP) exists in small amounts in mammals; however, the function(s) of this metabolite remains unresolved. The structure of AThTP resembles NAD(+). Recent experimental studies demonstrate beneficial impacts of high-dose thiamine treatment of diabetic complications. These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1. We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity. AThTP inhibited the PARP-1 activity at 10 µM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site. The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.
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http://dx.doi.org/10.3177/jnsv.57.192DOI Listing
December 2011

Detection of organic free radicals in irradiated Foeniculi fructus by electron spin resonance spectroscopy.

J Nat Med 2009 Jan 1;63(1):28-31. Epub 2008 Aug 1.

Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan.

Foeniculi fructus were irradiated with an electron beam and organic free radicals were detected by electron spin resonance (ESR) spectroscopy for the purpose of identifying radio-disinfected and sterilized herbal drugs. An ESR single-line spectrum near g = 2.005 was observed in the sample before irradiation. After irradiation, the intensity of the signal near g = 2.005 increased. In addition, two subsignals derived from cellulose radicals were observed approximately 3 mT to either side of the main signal, at g = 2.023 and g = 1.987. The intensity of the subsignal at g = 2.023 was proportional to the absorbed dose of radiation. The decrease in intensity of the signals was considerable 2 weeks after irradiation, and continued to decrease steadily thereafter. Among the signals, the fading of the subsignal at g = 2.023 was relatively small. The intensity of the subsignal at g = 2.023 was detectable for over 1 year in the sample that had been irradiated to the level of disinfection and sterilization. Therefore, organic free radicals in irradiated Foeniculi fructus can be measured rapidly and with high sensitivity by ESR spectroscopy. The stable signal at g = 2.023 is a promising indicator of the detection of irradiated herbal drugs.
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http://dx.doi.org/10.1007/s11418-008-0284-6DOI Listing
January 2009

Protein chemotaxonomy. XIII. Amino acid sequence of ferredoxin from Panax ginseng.

Authors:
Yoshiki Mino

Biol Pharm Bull 2006 Aug;29(8):1771-4

Department of Environmental Analysis, Osaka University of Pharmaceutical Sciences, Japan.

The complete amino acid sequence of [2Fe-2S] ferredoxin from Panax ginseng (Araliaceae) has been determined by automated Edman degradation of the entire S-carboxymethylcysteinyl protein and of the peptides obtained by enzymatic digestion. This ferredoxin has a unique amino acid sequence, which includes an insertion of Tyr at the 3rd position from the amino-terminus and a deletion of two amino acid residues at the carboxyl terminus. This ferredoxin had 18 differences in its amino acid sequence compared to that of Petroselinum sativum (Umbelliferae). In contrast, 23-33 differences were observed compared to other dicotyledonous plants. This suggests that Panax ginseng is related taxonomically to umbelliferous plants.
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http://dx.doi.org/10.1248/bpb.29.1771DOI Listing
August 2006

Significance of angiotensin II receptor blocker lipophilicities and their protective effect against vascular remodeling.

Hypertens Res 2005 Jul;28(7):593-600

Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.

Although the lipophilicities of the various angiotensin II receptor blockers (ARBs) are very different, the relationship between lipophilicity and the protective effect against vascular remodeling is unclear. In this study, we compared the protective effects of a highly lipophilic ARB, telmisartan, and an ARB with low lipophilicity, losartan, on vascular function and oxidative stress in stroke-prone spontaneously hypertensive rats (SHR-SP). SHR-SP received oral placebo, 1 mg/kg telmisartan, or 10 mg/kg losartan for 2 weeks. The blood pressure (BP) in SHR-SP was significantly higher than that in Wistar-Kyoto (WKY) rats before treatment, and the BP was reduced equally in telmisartan- and losartan-treated SHR-SP compared to placebo-treated SHR-SP. Acetylcholine-induced vasorelaxation in isolated carotid arteries was significantly weaker in SHR-SP than in WKY rats, but in both telmisartan- and losartan-treated SHR-SP, acetylcholine-induced vasorelaxation was significantly higher than in placebo-treated SHR-SP. Moreover, acetylcholine-induced vasorelaxation in telmisartan-treated rats was significantly stronger than in losartan-treated SHR-SP. The expression of the endothelial nitric oxide synthase gene was significantly higher in telmisartan- and losartan-treated rats than in placebo-treated SHR-SP, and was significantly higher in telmisartan-treated rats than in losartan-treated rats. In contrast, the expression of the NAD(P)H oxidase subunit p22phox gene in telmisartan-treated SHR-SP was significantly lower than that in losartan-treated SHR-SP. Immunohistochemistry showed that angiotensin II expression in the aorta was significantly lower in telmisartan-treated SHR-SP than in losartan-treated SHR-SP. In conclusion, a highly lipophilic ARB, telmisartan, may be useful for preventing NAD(P)H oxidase activity, and thereby for conferring vascular protection.
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http://dx.doi.org/10.1291/hypres.28.593DOI Listing
July 2005

Role of chymase-dependent angiotensin II formation in regulating blood pressure in spontaneously hypertensive rats.

Hypertens Res 2005 May;28(5):457-64

Department of Pharmacology, Osaka Medical College, Takatsuki, Japan.

Vascular smooth muscle cells in spontaneously hypertensive rats (SHR) express angiotensin II-forming chymase (rat vascular chymase [RVCH]), which may contribute to blood pressure regulation. In this study, we studied whether chymase-dependent angiotensin II formation contributes to the regulation of blood pressure in SHR. The systolic blood pressure in 16-week-old Wistar-Kyoto (WKY) rats was 113 +/- 9 mmHg, compared to 172 +/- 3 mmHg in SHR. Using synthetic substrates for measuring angiotensin-converting enzyme (ACE) and chymase activities, it was found that both ACE and chymase activities in extracts from SHR aortas were significantly higher than in those from WKY rat aortas. Using angiotensin I as a substrate, angiotensin II formation in SHR was found to be significantly higher than that in WKY rats, and its formation was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. RVCH mRNA expression could not be detected in aorta extracts from either WKY rats or SHR. In carotid arteries isolated from WKY rats and SHR, angiotensin I-induced vasoconstriction was completely suppressed by an ACE inhibitor, but not by a chymase inhibitor. Angiotensin I-induced pressor responses in both WKY rats and SHR were also completely inhibited by an ACE inhibitor, but they were not affected by a chymase inhibitor. In SHR, an ACE inhibitor and an angiotensin II receptor blocker showed equipotent hypotensive effects, but a chymase inhibitor did not have a hypotensive effect. These results indicated that chymase-dependent angiotensin II did not regulate blood pressure in SHR in the present study.
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http://dx.doi.org/10.1291/hypres.28.457DOI Listing
May 2005

Amino acid sequences of ferredoxins from Atropa belladonna and Hyoscyamus niger: their similarities to those in other tropane-alkaloid-containing plants.

Biol Pharm Bull 2005 Aug;28(8):1535-8

Department of Environment Analysis, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

The complete amino acid sequences of [2Fe-2S] ferredoxin from Atropa belladonna and Hyoscyamus niger have been determined by automated Edman degradation of the entire S-carboxymethylcysteinyl proteins and of the peptides obtained by enzymatic digestion. These two ferredoxins exhibited 1-8 differences in their amino acid sequences compared to those of other tropane-alkaloid-containing plants (Scopolia japonica, Datura stramonium, D. metel, and D. arborea), and only 1 or 4 differences compared to S. japonica and D. arborea. In contrast, 9-23 differences were observed among the other solanaceous ferredoxins. This suggests that tropane-alkaloid-containing plants are closely related taxonomically.
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http://dx.doi.org/10.1248/bpb.28.1535DOI Listing
August 2005

Comparison of the nucleotide sequences of ferredoxin-cDNAs among some Datura plants.

Biol Pharm Bull 2004 Dec;27(12):2038-41

Department of Environmental Analysis, Osaka University of Pharmaceutical Sciences, Osaka, Japan.

The nucleotide sequences of partial ferredoxin (Fd)-cDNAs (corresponding to the amino acid sequence of 22-87 in the total 97 amino acids of ferredoxin) were determined for Datura arborea, D. stramonium, D. metel, and related Datura plants. Non-synonymous substitutions were noted at 4 positions and a synonymous substitution was seen at position 82 (Gln [CAA] (arborea) vs. Gln [CAG] (stramonium and metel)). The nucleotide sequence of Fd-cDNA may provide more detailed information regarding the relative taxonomic positions of plants than the amino acid sequence. However, Datura plants in the same section (metel, fastuosa, and innoxia) and of different varieties (stramonium var. stramonium and stramonium var. tatula) showed identical Fd-cDNA nucleotide sequences. This result suggests that there are very close relationships among the plants in each group.
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http://dx.doi.org/10.1248/bpb.27.2038DOI Listing
December 2004

Degradation of 2,7-dichlorodibenzo-p-dioxin by Fe(3+)-H(2)O(2) mixed reagent.

Chemosphere 2004 Nov;57(5):365-72

Department of Environmental Analysis, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

Fe(3+)-H(2)O(2) mixed reagent, but not Fe(2+)-H(2)O(2), was found to be capable of degrading 2,7-dichlorodibenzo-p-dioxin (DCDD). A reaction mixture of FeCl(3) (8 mM) and H(2)O(2) (1%) caused approximately 50% degradation within 6 h and >90% degradation within 24 h at 27 degrees C. Increasing the temperature remarkably stimulated degradation: at 70 degrees C, approximately 100% degradation was achieved within 15 min. When DCDD-treated model soil (5 micrograms/g) was conducted, approximately 100% of the DCDD was degraded within 30 min at 70 degrees C (both reagents were added every 10 min). These results suggest that Fe(3+)-H(2)O(2) mixed reagent may be a new tool for combating persistent environmental pollutants such as dioxins and polychlorinated biphenyls.
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http://dx.doi.org/10.1016/j.chemosphere.2004.06.023DOI Listing
November 2004

Brain temperature in patients with chronic hydrocephalus after subarachnoid hemorrhage.

Neurol Med Chir (Tokyo) 2004 Jan;44(1):1-4; discussion 5

Department of Neurosurgery, Toyama Medical and Pharmaceutical University, Toyama, Japan.

The relationships between temperature indices and clinical condition on admission or improvement after ventriculoperitoneal (VP) shunting were evaluated in patients with subarachnoid hemorrhage (SAH). Brain temperatures were measured at intervals of 1 cm from the brain surface to the lateral ventricle at shunt operation. Rectal temperature was also measured. The difference between intraventricular and rectal temperatures was correlated with age (p = 0.0486), Glasgow Coma Scale (p = 0.0129), Hunt and Hess grade (p = 0.0101), and improvement score after VP shunting (p = 0.0104). Measurement of brain temperature may predict the outcome of VP shunting in patients with SAH.
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http://dx.doi.org/10.2176/nmc.44.1DOI Listing
January 2004

Optochiasmal arachnoiditis following cotton wrapping of anterior communicating artery aneurysm treated by surgical removal of granuloma.

J Clin Neurosci 2003 Mar;10(2):254-7

Department of Neurosurgery, Aomori Prefectural Central Hospital, Aomori, Japan.

We report the case of a 50 year old female who presented with visual disturbance due to optochiasmal arachnoiditis and foreign body granuloma 9 months after cotton wrapping for ruptured anterior communicating artery (AcomA) aneurysm. Magnetic resonance imaging (MRI) revealed enhanced mass lesion around AcomA complex and hyperintense signal on optic chiasm and right optic tract by fluid-attenuated inversion recovery image. Despite the repeated steroid pulse therapy, she deteriorated and MRI showed expansion of the granulomatous lesion over 5 months. Surgical removal of foreign body granuloma resulted in marked improvement of visual disturbance as well as of the MRI findings. We conclude that the use of cotton sheet close to the optic nerve should be avoided, and that surgical removal of the granuloma would be the optimal choice especially for the patient in whom steroid therapy fails to improve clinical symptoms.
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http://dx.doi.org/10.1016/s0967-5868(02)00303-xDOI Listing
March 2003

Large differences in amino acid sequences among ferredoxins from several species of genus Solanum.

Phytochemistry 2003 Mar;62(5):657-62

Department of Environmental Analysis, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.

The complete amino acid sequences of [2Fe-2S] ferredoxins from four species of genus Solanum (S. nigrum, S. lyratum, S. indicum, and S. abutiloides) were determined by automated Edman degradation of the entire S-carboxymethylcysteinyl proteins and of the peptides obtained by enzymatic digestion. The amino acid sequences of these four ferredoxins differed from each other by 12-19, whereas 0-4 differences have been observed among ferredoxins from plants in the same genus and 14-40 differences were seen between different families. This suggests that these Solanum plants are distantly related to each other taxonomically.
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http://dx.doi.org/10.1016/s0031-9422(02)00485-5DOI Listing
March 2003

Amino acid sequences of ferredoxins from Scopolia japonica and Lycium chinense: their similarities to that of Datura arborea.

Authors:
Yoshiki Mino

Biol Pharm Bull 2002 Oct;25(10):1367-9

Department of Environmental Analysis, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.

The complete amino acid sequences of [2Fe-2S] ferredoxins from Scopolia japonica and Lycium chinense have been determined by automated Edman degradation of the entire Cm-proteins and of the peptides obtained by enzymatic digestions. These two ferredoxins exhibited only 2-7 differences in the amino acid sequence when compared to the Datura-ferredoxins (D. stramonium, D. metel, and D. arborea), and especially only 2 or 3 differences compared to D. arborea. On the contrary, 8-19 differences were observed among the other solanaceous ferredoxins. This suggests that S. japonica and L. chinense are closely related taxonomically to Datura plants, especially to D. arborea.
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http://dx.doi.org/10.1248/bpb.25.1367DOI Listing
October 2002

[Traumatic vertebral arteriovenous fistula caused by an injury due to penetration by pieces of glass: case report].

No Shinkei Geka 2002 Feb;30(2):205-8

Department of Neurosurgery, Saiseikai Takaoka Hospital, 387-1 Futatsuka, Takaoka-city, Toyama 933-8525, Japan.

We reported a case of a 79-year-old male with traumatic vertebral arteriovenous fistula. The patient was admitted with hemorrhagic shock due to arterial bleeding caused by a penetrating injury of the neck. Cervical CT showed free air at the level of the lamina of C1. Injury of the vertebral artery was suspected. The right vertebral angiogram showed an arteriovenous fistula between the V3 portion of the right vertebral artery and the suboccipital venous plexus with retrograde intracranial venous drainage. The patient underwent endovascular treatment of the parent vertebral artery occlusion, which successfully obliterated the arteriovenous fistula.
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February 2002
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