関: dimethyl sulphoxide、dimethylsulfoxide、DMSO

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/06/09 02:28:56」(JST)

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Dimethyl sulfoxide (DMSO) is an organosulfur compound with the formula (CH₃)₂SO. This colorless liquid is an important polar aprotic solvent that dissolves both polar and nonpolar compounds and is miscible in a wide range of organic solvents as well as water.

It penetrates the skin very readily and has the unusual property that many individuals perceive a garlic-like taste in the mouth after contact of DMSO with the skin.^[2] This perceived garlic odor may be due to nonolfactory activation of TRPA1 receptors in trigeminal ganglia.^[3] Unlike dimethyl and diallyl disulfide (also with odors resembling garlic), the mono- and tri- sulfides (typically disgusting), and similar structures, the pure chemical DMSO is odorless.

Although it has some niche medicinal uses, it also has significant known side effects. It has been discussed as treatment for cancer and other conditions.^[4]^[5]

1 Synthesis and production
2 Reactions
- 2.1 Reactions with electrophiles
- 2.2 Acidity
- 2.3 Oxidant
- 2.4 Ligand
3 Applications
- 3.1 Solvent
- 3.2 Biology
- 3.3 Medicine
- 3.4 Alternative medicine
- 3.5 Veterinary medicine
4 Safety
- 4.1 Toxicity
- 4.2 Explosions
5 See also
6 References
7 External links

Synthesis and production

It was first synthesized in 1866 by the Russian scientist Alexander Zaytsev, who reported his findings in 1867.^[6] Dimethyl sulfoxide is produced from dimethyl sulfide, a by-product of kraft pulping. It is industrially produced by oxidation of dimethyl sulfide with oxygen or nitrogen dioxide.^[7]

Reactions

Reactions with electrophiles

The sulfur center in DMSO is nucleophilic toward soft electrophiles and the oxygen is nucleophilic toward hard electrophiles. With methyl iodide it forms trimethylsulfoxonium iodide, [(CH₃)₃SO]I:

(CH₃)₂SO + CH₃I → [(CH₃)₃SO]I

This salt can be deprotonated with sodium hydride to form the sulfur ylide:

[(CH₃)₃SO]I + NaH → [(CH₃)₂CH₂SO + NaI + H₂

Acidity

The methyl groups of DMSO are only weakly acidic, with a pK_a=35. For this reason, the basicities of many weakly basic organic compounds have been examined in this solvent.

Deprotonation of DMSO requires strong bases like lithium diisopropylamide and sodium hydride. Stabilization of the resultant carbanion is provided by the S(O)R group. The sodium derivative of DMSO formed in this way is referred to as "dimsyl sodium". It is a base, e.g., for the deprotonation of ketones to form sodium enolates, phosphonium salts to form Wittig reagents, and formamidinium salts to form diaminocarbenes. It is also a potent nucleophile.

Oxidant

In organic synthesis, DMSO is used as a mild oxidant,^[8] as illustrated by the Pfitzner-Moffatt oxidation and the Swern oxidation.^[9]

Ligand

Related to its ability to dissolve many salts, DMSO is a common ligand in coordination chemistry.^[10] Illustrative is the complex dichlorotetrakis(dimethyl sulfoxide)ruthenium(II), RuCl₂(dmso)₄. In this complex, three DMSO ligands are bonded to ruthenium through sulfur. The fourth DMSO is bonded through oxygen. In general, the oxygen-bonded mode is more common.

Applications

Solvent

Distillation of DMSO requires a partial vacuum to achieve a lower boiling point.

DMSO is a polar aprotic solvent and is less toxic than other members of this class, such as dimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone, and HMPA. DMSO is frequently used as a solvent for chemical reactions involving salts, most notably Finkelstein reactions and other nucleophilic substitutions. It is also extensively used as an extractant in biochemistry and cell biology.^[11] Because DMSO is only weakly acidic, it tolerates relatively strong bases and as such has been extensively used in the study of carbanions. A set of non-aqueous pKa values (C-H, O-H, S-H and N-H acidities) for thousands of organic compounds have been determined in DMSO solution.^[12]^[13]

Because of its high boiling point, 189 °C (372 °F), DMSO evaporates slowly at normal atmospheric pressure. Samples dissolved in DMSO cannot be as easily recovered compared to other solvents, as it is very difficult to remove all traces of DMSO by conventional rotary evaporation, one technique to fully recover samples is removal of the organic solvent by evaporation followed by addition of water (to dissolve DMSO) and lyophilisation to remove both DMSO and water. Reactions conducted in DMSO are often diluted with water to precipitate or phase-separate products. The relatively high freezing point of DMSO, 18.5 °C (65.3 °F), means that at, or just below, room temperature it is a solid, which can limit its utility in some chemical processes (e.g. crystallization with cooling).

In its deuterated form (DMSO-d₆), it is a useful solvent for NMR spectroscopy, again due to its ability to dissolve a wide range of analytes, the simplicity of its own simple spectrum, and its suitability for high-temperature NMR spectroscopic studies. Disadvantages to the use of DMSO-d₆ are its high viscosity, which broadens signals, and its hygroscopicity, which leads to an overwhelming H₂O resonance in the ¹H NMR spectrum. It is often mixed with CDCl₃ or CD₂Cl₂ for lower viscosity and melting points.

DMSO is finding increased use in manufacturing processes to produce microelectronic devices.^[14] It is widely used to strip photoresist in TFT-LCD 'flat panel' displays and advanced packaging applications (such as wafer-level packaging / solder bump patterning). It also used in biopreservation especially stem cell banking. DMSO is an effective paint stripper, being safer than many of the others such as nitromethane and dichloromethane.

Because of its ability to dissolve many kinds of compounds, DMSO plays a role in sample management and high-throughput screening operations in drug design.^[15]

Biology

DMSO is used in PCR to inhibit secondary structures in the DNA template or the DNA primers. It is added to the PCR mix before reacting, where it interferes with the self-complementarity of the DNA, minimizing interfering reactions.^[16] DMSO in a PCR reaction is applicable for supercoiled plasmids (to relax before amplification) or DNA templates with high GC content (to decrease thermostability). For example, 10% final concentration of DMSO in the PCR mixture with Phusion® decreases primer annealing temperature (i.e. primer melting temperature) by 5.5-6.0°C. ^[17]

DMSO may also be used as a cryoprotectant, added to cell media to reduce ice formation and thereby prevent cell death during the freezing process.^[18] Approximately 10% may be used with a slow-freeze method, and the cells may be frozen at −80 °C or stored in liquid nitrogen safely.

DMSO has been used as a co-solvent to assist absorption of the flavonol glycoside Icariin into the C. elegans nematode worm.^[19]

In cell culture, DMSO is used to induce differentiation of P19 embryonic carcinoma cells into cardiomyocytes and skeletal muscle cells.

Medicine

Use of DMSO in medicine dates from around 1963, when an Oregon Health & Science University Medical School team, headed by Stanley Jacob, discovered it could penetrate the skin and other membranes without damaging them and could carry other compounds into a biological system. In medicine, DMSO is predominantly used as a topical analgesic, a vehicle for topical application of pharmaceuticals, as an anti-inflammatory, and an antioxidant.^[20] Because DMSO increases the rate of absorption of some compounds through organic tissues, including skin, it is used in some transdermal drug delivery systems. Its effect may be enhanced with the addition of EDTA. It is frequently compounded with antifungal medications, enabling them to penetrate not just skin but also toe and fingernails.

DMSO has been examined for the treatment of numerous conditions and ailments, but the U.S. Food and Drug Administration (FDA) has approved its use only for the symptomatic relief of patients with interstitial cystitis.^{[citation needed]} A 1978 study concluded that DMSO brought significant relief to the majority of the 213 patients with inflammatory genitourinary disorders that were studied.^[21] The authors recommended DMSO for genitourinary inflammatory conditions not caused by infection or tumor in which symptoms were severe or patients failed to respond to conventional therapy.

In interventional radiology, DMSO is used as a solvent for ethylene vinyl alcohol in the Onyx liquid embolic agent, which is used in embolization, the therapeutic occlusion of blood vessels.

In medical research, DMSO is often used as a drug vehicle in in vivo and in vitro experiments. However, when a researcher is unaware of its pleiotropic effects, or when the control groups are not carefully planned, a bias can occur; an effect of DMSO can be falsely attributed to the drug.^[22] For example, even a very low dose of DMSO has a powerful protective effect against acetaminophen induced liver injury in mice.^[23]

In cryobiology DMSO has been used as a cryoprotectant and is still an important constituent of cryoprotectant vitrification mixtures used to preserve organs, tissues, and cell suspensions. Without it, up to 90% of frozen cells will become inactive. It is particularly important in the freezing and long-term storage of embryonic stem cells and hematopoietic stem cells, which are often frozen in a mixture of 10% DMSO, a freezing medium, and 30% fetal bovine serum. In the cryogenic freezing of heteroploid cell lines (MDCK, VERO, etc.) a mixture of 10% DMSO with 90% EMEM (70% EMEM + 30% fetal bovine serum + antibiotic mixture) is used. As part of an autologous bone marrow transplant the DMSO is re-infused along with the patient's own hematopoietic stem cells.

DMSO is metabolized to dimethyl sulfide and dimethyl sulfone. It is subject to renal and pulmonary excretion. A possible side effect of DMSO is therefore elevated blood dimethyl sulfide, which may cause a blood borne halitosis symptom.

Alternative medicine

DMSO is marketed as an alternative medicine via books with titles such as DMSO: Nature's healer. Its popularity as an alternative cure is stated to stem from a 60 Minutes documentary featuring an early proponent.^[5] It is listed by the U.S. FDA as a fake cancer cure^[4] and the FDA has had a "running battle" with distributors.^[5] This has included Mildred Miller who promoted DMSO for a variety of disorders including arthritis, mental illness, emphysema, and cancer and wrote a book touting DMSO entitled A Little Dab Will Do Ya! (Quality Advertising, 1981). The use of DMSO as a alternative treatment for cancer is of particular concern, as it has been show to interfere with a variety of chemotherapy drugs, including cisplatin, carboplatin and oxaliplatin^[24] It is still listed as an ineffective alternative cancer cure by the American Cancer Society;^[25] for most conditions there is insufficient evidence to state any effect^[26] and most sources agree that its history of side effects when tested indicates caution when using it as a dietary supplement, for which it is heavily marketed with the usual disclaimer.

Veterinary medicine

DMSO is commonly used in veterinary medicine as a liniment for horses, alone or in combination with other ingredients. In the latter case, often, the intended function of the DMSO is as a solvent, to carry the other ingredients across the skin. Also in horses, DMSO is used intravenously, again alone or in combination with other drugs. It is used alone for the treatment of increased intracranial pressure and/or cerebral edema in horses.

Safety

Toxicity

Early clinical trials with DMSO were stopped because of questions about its safety, especially its ability to harm the eye. The most commonly reported side effects include headaches and burning and itching on contact with the skin. Strong allergic reactions have been reported.^{[full citation needed]} DMSO can cause contaminants, toxins, and medicines to be absorbed through the skin, which may cause unexpected effects. DMSO is thought to increase the effects of blood thinners, steroids, heart medicines, sedatives, and other drugs. In some cases this could be harmful or dangerous.^[25] It is a developmental neurotoxin.^[27]

In Australia it is listed as a schedule 4 poison, and a company has been prosecuted for adding it to products as a preservative.^[28]

Because DMSO easily penetrates the skin, substances dissolved in DMSO may be quickly absorbed. Glove selection is important when working with DMSO. Butyl rubber, fluoroelastomer, neoprene, or thick (15 mil) latex gloves are recommended.^[29] Nitrile gloves, which are very commonly used in chemical laboratories, may protect from brief contact but have been found to degrade rapidly with exposure to DMSO.^[30]

On September 9, 1965, the Wall Street Journal reported that a manufacturer of the chemical warned that the death of an Irish woman after undergoing DMSO treatment for a sprained wrist may have been due to the treatment, although no autopsy was done, nor was a causal relationship established.^[31] Clinical research using DMSO was halted and did not begin again until the National Academy of Sciences (NAS) published findings in favor of DMSO in 1972.^[32] In 1978, the US FDA approved DMSO for treating interstitial cystitis. In 1980, the US Congress held hearings on claims that the FDA was slow in approving DMSO for other medical uses. In 2007, the US FDA granted "fast track" designation on clinical studies of DMSO's use in reducing brain tissue swelling following traumatic brain injury.^[32] DMSO exposure to developing mouse brains can produce brain degeneration. This neurotoxicity could be detected at doses as low as 0.3 mL/kg, a level exceeded in children exposed to DMSO during bone marrow transplant.^[33]

DMSO disposed into sewers can also cause odor problems in municipal effluents: waste water bacteria transform DMSO under hypoxic (anoxic) conditions into dimethyl sulfide (DMS) that has a strong disagreeable odor, similar to rotten cabbage.^[34] However, chemically pure DMSO is odorless because of the lack of C-S-C (sulfide) and C-S-H (mercaptan) linkages. Deodorization of DMSO is achieved by removing the odorous impurities it contains.^[35]

Explosions

Dimethyl sulfoxide can produce an explosive reaction when exposed to acyl chlorides; at a low temperature, this reaction produces the oxidant for Swern oxidation.

DMSO can decompose at the boiling temperature of 189 °C at normal pressure,^[36] possibly leading to an explosion. The decomposition is catalyzed by acids and bases and therefore can be relevant at even lower temperatures.^[36] A strong to explosive reaction also takes place in combination with halogen compounds, metal nitrides, metal perchlorates, sodium hydride, periodic acid and fluorinating agents.^[36]^[37]^{[full citation needed]}

References

^ Matthews, W.S., Bares, J.E., Bartmess, J.E., Bordwell, F.G., Cornforth, F.J., Drucker, G.E., Margolin, Z., McCallum, R.J., McCollum, G.J., Vanier, N.R. (1975). "Equilibrium acidities of carbon acids. VI. Establishment of an absolute scale of acidities in dimethyl sulfoxide solution". J. Am. Chem. Soc. 97 (24): 7006. doi:10.1021/ja00857a010.
^ Novak, K. M., ed. (2002). Drug Facts and Comparisons (56th ed.). St. Louis, Missouri: Wolters Kluwer Health. p. 619. ISBN 1-57439-110-0.
^ "Transient Receptor Potential Channels Encode Volatile Chemicals Sensed by Rat Trigeminal Ganglion Neurons". PLOS One. October 21, 2013.
^ ^a ^b 187 fake cancer "cures" to avoid, FDA
^ ^a ^b ^c >DMSO, National Council Against Health Fraud
^ A. Saytzeff (1867) "Ueber die Einwirkung von Saltpetersäure auf Schwefelmethyl und Schwefeläthyl" (On the effect of nitric acid on methyl sulfide and ethyl sulfide) Annalen der Chemie und Pharmacie, 144: 148-156; see page 150, where dimethyl sulfoxide is called "Dimethylschwefeloxyd".
^ Kathrin-Maria Roy “Sulfones and Sulfoxides” Ullmann's Encyclopedia of Industrial Chemistry 2002, Wiley-VCH, Weinheim. doi:10.1002/14356007.a25_487
^ Epstein WW, Sweat FW (March 1967). "Dimethyl Sulfoxide Oxidations". Chemical Reviews 67 (3): 247–260. doi:10.1021/cr60247a001. PMID 6042131.
^ Tidwell TT. (1990). "Oxidation of Alcohols by Activated Dimethyl Sulfoxide and Related Reactions: An Update". Synthesis 1990 (10): 857–870. doi:10.1055/s-1990-27036.
^ Mario Calligaris "Structure and bonding in metal sulfoxide complexes: an update" oordination Chemistry Reviews 2004, vol. 248, pp. 351-375. doi:10.1016/j.ccr.2004.02.005
^ "DMSO". exactantigen.com. Retrieved 2009-10-02.
^ Bordwell FG (1988). "Equilibrium acidities in dimethyl sulfoxide solution". Accounts of Chemical Research 21 (12): 456–463. doi:10.1021/ar00156a004.
^ Bordwell pKa Table in DMSO
^ Kvakovszky G, McKim AS, Moore J. (2007). "A Review of Microelectronic Manufacturing Applications Using DMSO-Based Chemistries". ECS Transactions 11 (2): 227–234. doi:10.1149/1.2779383.
^ Balakin KV, Savchuk NP, Tetko IV. (2006). "In Silico Approaches to Prediction of Aqueous and DMSO Solubility of Drug-Like Compounds: Trends, Problems and Solutions". Current Medicinal Chemistry 13 (2): 223–241. doi:10.2174/092986706775197917. PMID 16472214.
^ Chakrabarti R, Schutt CE. (August 2001). "The enhancement of PCR amplification by low molecular-weight sulfones". Gene 274 (1–2): 293–298. doi:10.1016/S0378-1119(01)00621-7. PMID 11675022.
^ https://www.neb.com/protocols/2012/06/01/guidelines-for-pcr-optimization-with-phusion-high-fidelity-dna-polymerase. Missing or empty |title= (help) Guidelines for PCR Optimization with Phusion High-Fidelity DNA Polymerase
^ Pegg, DE. (2007). "Principles of Cryopreservation". In Day JG, Stacey GN. Cryopreservation and Freeze-Drying Protocols, Second Edition. Methods in Molecular Biology (Humana Press) 368: 39–57. doi:10.1007/978-1-59745-362-2_3. ISBN 978-1-58829-377-0. ISSN 1064-3745. PMID 18080461.
^ Cai WJ, Huang JH, Zhang SQ, Wu B, Kapahi P, Zhang XM, Shen ZY (2011). "Icariin and its derivative icariside II extend healthspan via insulin/IGF-1 pathway in C. elegans". In Blagosklonny, Mikhail V. Plos One 6 (12): e28835. doi:10.1371/journal.pone.0028835. PMC 3244416. PMID 22216122.
^ Johannes Geiss (2001). The century of space science. Kluwer Academic. p. 20. ISBN 0-7923-7195-X. Retrieved Aug 7, 2011.
^ Shirley SW, Stewart BH, Mirelman S. (March 1978). "Dimethyl Sulfoxide in Treatment of Inflammatory Genitourinary Disorders". Urology 11 (3): 215–220. doi:10.1016/0090-4295(78)90118-8. PMID 636125.
^ Kelava T, Cavar I (Nov 2011). actions of drug solvents) "Biological actions of drug solvents". Periodicum Biologorum 113 (3): 311–320.
^ Kelava T, Cavar I (Oct 2010). "Influence of small doses of various drug vehicles on acetaminophen-induced liver injury". Can J Physiol Pharmacol 88 (10): 980–87. doi:10.1139/Y10-065. PMID 20962895.
^ Hall, M. D.; Telma, K. A.; Chang, K.-E.; Lee, T. D.; Madigan, J. P.; Lloyd, J. R.; Goldlust, I. S.; Hoeschele, J. D.; Gottesman, M. M. (8 May 2014). "Say No to DMSO: Dimethylsulfoxide Inactivates Cisplatin, Carboplatin and Other Platinum Complexes". Cancer Research. doi:10.1158/0008-5472.CAN-14-0247. PMID 24812268. Cite uses deprecated parameters (help)
^ ^a ^b DMSO information from American Cancer Society
^ DMSO at WebMD
^ Hanslick, JL; Lau, K; Noguchi, KK; Olney, JW; Zorumski, CF; Mennerick, S; Farber, NB (2009). "Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system". Neurobiology of disease 34 (1): 1–10. doi:10.1016/j.nbd.2008.11.006. PMC 2682536. PMID 19100327.
^ Brisbane drug company convicted of counterfeiting, Therapeutic Goods Agency
^ Rubber Chemical Resistance Chart
^ "Chemical hygiene plan" (PDF). Cornell University. October 1999. Retrieved 2010-04-12.
^ Carley W. (September 9, 1965). "DMSO may have caused death of woman, makers of 'Wonder' drug warn doctors". Wall Street Journal (New York City).
^ ^a ^b http://www.fda.gov/ForIndustry/ImportProgram/ImportAlerts/ucm162294.htm^{[dead link]}
^ Hanslick JL, Lau K, Noguchi KK, Olney JW, Zorumski CF, Mennerick S, Farber NB. (April 2009). "Dimethyl sulfoxide (DMSO) produces widespread apoptosis in the developing central nervous system". Neurobiology of Disease 34 (1): 1–10. doi:10.1016/j.nbd.2008.11.006. PMC 2682536. PMID 19100327.
^ Glindemann D, Novak J, Witherspoon J. (January 2006). "Dimethyl sulfoxide (DMSO) waste residues and municipal waste water odor by dimethyl sulfide (DMS): the North-East WPCP plant of Philadelphia". Environmental Science and Technology 40 (1): 202–207. doi:10.1021/es051312a. PMID 16433352.
^ George Kvakovszky, et. al., “Process for preparing low malodorous dimethyl sulfoxide”, US patent application number 20090005601 (2009).
^ ^a ^b ^c Roth/Weller: Gefährliche Chemische Reaktionen, ecomed Sicherheit, Verlagsgruppe Hüthig Jehle Rehm, Landsberg/Lech, 31. Ergänzungslieferung 8/2000.
^ Thieme Römpp Online

See "Dimethylsulphoxide", Martin & Hauthal, Wiley, NY, 1975 for a review of all aspects.

External links

International Chemical Safety Card 0459
Dimethyl Sulfoxide Information Center

UpToDate Contents

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4. 続発性（AA）アミロイドーシスの治療 treatment of secondary aa amyloidosis
5. 造血幹細胞移植後の支持療法 supportive care after hematopoietic cell transplantation

English Journal

Fluorescence spectroscopy of Rhodamine 6G: Concentration and solvent effects.

Zehentbauer FM1, Moretto C1, Stephen R1, Thevar T1, Gilchrist JR2, Pokrajac D1, Richard KL3, Kiefer J4.Author information 1School of Engineering, University of Aberdeen, Fraser Noble Building, Aberdeen AB24 3UE, Scotland, United Kingdom.2Gilden Photonics, 9 South Avenue, Clydebank Business Park, Clydebank G81 2NR, Scotland, United Kingdom.3Magdalen College School, Oxford, United Kingdom.4School of Engineering, University of Aberdeen, Fraser Noble Building, Aberdeen AB24 3UE, Scotland, United Kingdom; Erlangen Graduate School in Advanced Optical Technologies, University of Erlangen-Nuremberg, 91052 Erlangen, Germany. Electronic address: j.kiefer@abdn.ac.uk.AbstractRhodamine 6G (R6G), also known as Rhodamine 590, is one of the most frequently used dyes for application in dye lasers and as a fluorescence tracer, e.g., in the area of environmental hydraulics. Knowing the spectroscopic characteristics of the optical emission is key to obtaining high conversion efficiency and measurement accuracy, respectively. In this work, solvent and concentration effects are studied. A series of eight different organic solvents (methanol, ethanol, n-propanol, iso-propanol, n-butanol, n-pentanol, acetone, and dimethyl sulfoxide (DMSO)) are investigated at constant dye concentration. Relatively small changes of the fluorescence spectrum are observed for the different solvents; the highest fluorescence intensity is observed for methanol and lowest for DMSO. The shortest peak wavelength is found in methanol (568nm) and the longest in DMSO (579nm). Concentration effects in aqueous R6G solutions are studied over the full concentration range from the solubility limit to highly dilute states. Changing the dye concentration provides tunability between ∼550nm in the dilute case and ∼620nm at high concentration, at which point the fluorescence spectrum indicates the formation of R6G aggregates.
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.Spectrochim Acta A Mol Biomol Spectrosc.2014 Mar 5;121:147-51. doi: 10.1016/j.saa.2013.10.062. Epub 2013 Oct 25.
Rhodamine 6G (R6G), also known as Rhodamine 590, is one of the most frequently used dyes for application in dye lasers and as a fluorescence tracer, e.g., in the area of environmental hydraulics. Knowing the spectroscopic characteristics of the optical emission is key to obtaining high conversion ef
PMID 24239710

Luteolin sensitizes the antiproliferative effect of interferon α/β by activation of Janus kinase/signal transducer and activator of transcription pathway signaling through protein kinase A-mediated inhibition of protein tyrosine phosphatase SHP-2 in cancer cells.

Tai Z1, Lin Y2, He Y1, Huang J1, Guo J1, Yang L1, Zhang G3, Wang F4.Author information 1Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.2Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China; Key Laboratory of Bio-resources and Eco-environment (Ministry of Education), College of Life Sciences, Sichuan University, Chengdu, China.3Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China. Electronic address: zhanggl@cib.ac.cn.4Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China; Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, China. Electronic address: wangfei@cib.ac.cn.AbstractNew negative regulators of interferon (IFN) signaling, preferably with tissue specificity, are needed to develop therapeutic means to enhance the efficacy of type I IFNs (IFN-α/β) and reduce their side effects. We conducted cell-based screening for IFN signaling enhancer and discovered that luteolin, a natural flavonoid, sensitized the antiproliferative effect of IFN-α in hepatoma HepG2 cells and cervical carcinoma HeLa cells. Luteolin promoted IFN-β-induced Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway activation by enhancing the phosphorylation of Jak1, Tyk2, and STAT1/2, thereby promoting STAT1 accumulation in the nucleus and endogenous IFN-α-regulated gene expression. Of interest, inhibition of phosphodiesterase (PDE) abolished the effect of IFN-β and luteolin on STAT1 phosphorylation. Luteolin also increased the cAMP-degrading activity of PDE bound with type I interferon receptor 2 (IFNAR2) and decreased the intracellular cAMP level, indicating that luteolin may act on the JAK/STAT pathway via PDE. Protein kinase A (PKA) was found to negatively regulate IFN-β-induced JAK/STAT signaling, and its inhibitory effect was counteracted by luteolin. Pull-down and immunoprecipitation assays revealed that type II PKA interacted with IFNAR2 via the receptor for activated C-kinase 1 (RACK-1), and such interaction was inhibited by luteolin. Src homology domain 2 containing tyrosine phosphatase-2 (SHP-2) was further found to mediate the inhibitory effect of PKA on the JAK/STAT pathway. These data suggest that PKA/PDE-mediated cAMP signaling, integrated by RACK-1 to IFNAR2, may negatively regulate IFN signaling through SHP-2. Inhibition of this signaling may provide a new way to sensitize the efficacy of IFN-α/β.
Cellular signalling.Cell Signal.2014 Mar;26(3):619-28. doi: 10.1016/j.cellsig.2013.11.039. Epub 2013 Dec 12.
New negative regulators of interferon (IFN) signaling, preferably with tissue specificity, are needed to develop therapeutic means to enhance the efficacy of type I IFNs (IFN-α/β) and reduce their side effects. We conducted cell-based screening for IFN signaling enhancer and discovered that luteol
PMID 24333668

Toxicity and intracellular accumulation of bile acids in sandwich-cultured rat hepatocytes: Role of glycine conjugates.

Chatterjee S1, Bijsmans IT2, van Mil SW3, Augustijns P4, Annaert P5.Author information 1KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, O&N2, Herestraat 49 - Bus 921, 3000 Leuven, Belgium. Electronic address: Sagnik.Chatterjee@pharm.kuleuven.be.2Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: i.bijsmans@umcutrecht.nl.3Department of Metabolic Diseases, University Medical Center Utrecht, Utrecht, The Netherlands. Electronic address: s.w.c.vanmil@umcutrecht.nl.4KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, O&N2, Herestraat 49 - Bus 921, 3000 Leuven, Belgium. Electronic address: Patrick.Augustijns@pharm.kuleuven.be.5KU Leuven Department of Pharmaceutical and Pharmacological Sciences, Drug Delivery and Disposition, O&N2, Herestraat 49 - Bus 921, 3000 Leuven, Belgium. Electronic address: Pieter.Annaert@pharm.kuleuven.be.AbstractExcessive intrahepatic accumulation of bile acids (BAs) is a key mechanism underlying cholestasis. The aim of this study was to quantitatively explore the relationship between cytotoxicity of BAs and their intracellular accumulation in sandwich-cultured rat hepatocytes (SCRH). Following exposure of SCRH (on day-1 after seeding) to various BAs for 24h, glycine-conjugated BAs were most potent in exerting toxicity. Moreover, unconjugated BAs showed significantly higher toxicity in day-1 compared to day-3 SCRH. When day-1/-3 SCRH were exposed (0.5-4h) to 5-100μM (C)DCA, intracellular levels of unconjugated (C)DCA were similar, while intracellular levels of glycine conjugates were up to 4-fold lower in day-3 compared to day-1 SCRH. Sinusoidal efflux was by far the predominant efflux pathway of conjugated BAs both in day-1 and day-3 SCRH, while canalicular BA efflux showed substantial interbatch variability. After 4h exposure to (C)DCA, intracellular glycine conjugate levels were at least 10-fold higher than taurine conjugate levels. Taken together, reduced BA conjugate formation in day-3 SCRH results in lower intracellular glycine conjugate concentrations, explaining decreased toxicity of (C)DCA in day-3 versus day-1 SCRH. Our data provide for the first time a direct link between BA toxicity and glycine conjugate exposure in SCRH.
Toxicology in vitro : an international journal published in association with BIBRA.Toxicol In Vitro.2014 Mar;28(2):218-30. doi: 10.1016/j.tiv.2013.10.020. Epub 2013 Nov 7.
Excessive intrahepatic accumulation of bile acids (BAs) is a key mechanism underlying cholestasis. The aim of this study was to quantitatively explore the relationship between cytotoxicity of BAs and their intracellular accumulation in sandwich-cultured rat hepatocytes (SCRH). Following exposure of
PMID 24211540

Japanese Journal

Surface morphology of fluorene thin film fabricated by electrospray deposition technique using two organic solvents: Application for organic light-emitting diodes

福田武司,本多善太郎,鎌田憲彦
Thin Solid Films 520(1), 600-605, 2011-10
… The root mean square (RMS) roughness of the F8BT thin film was reduced by the addition of dimethyl sulfoxide (DMSO) in tetrahydrofuran (THF). …
NAID 120003459945

Lipase-catalyzed synthesis of hydrophobically modified dextrans : Activity and regioselectivity of lipase from Candida rugosa(ENZYMOLOGY, PROTEIN ENGINEERING, AND ENZYME TECHNOLOGY)

Kaewprapan Kultida,Wongkongkatep Jirarut,Panbangred Watanalai,Phinyocheep Pranee,Marie Emmanuelle,Durand Alain,Inprakhon Pranee
Journal of bioscience and bioengineering 112(2), 124-129, 2011-08
… Vinyl decanoate-modified dextran macromolecules (DexT40-VD) were synthesized in dimethyl sulfoxide at 50℃ using lipase AY from Candida rugosa for catalyzing transesterification between polysaccharide and vinyl fatty esters. …
NAID 110008711112

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★リンクテーブル★

リンク元	「胆嚢直接溶解薬」「ジメチルスルホキシド」「DMSO」「dimethylsulfoxide」「dimethyl sulphoxide」

「胆嚢直接溶解薬」

Dimethyl sulfoxide
	; A sample of dimethyl sulfoxide
	IUPAC name Dimethyl sulfoxide
	Systematic name Methanesulfinylmethane (substitutive); Dimethyl(oxido)sulfur (additive)
	Other names Methylsulfinylmethane; Methyl sulfoxide
Identifiers
Abbreviations	DMSO, Me2SO
CAS number	67-68-5
PubChem	679
ChemSpider	659
UNII	YOW8V9698H
EC number	200-664-3
DrugBank	DB01093
KEGG	D01043
MeSH	Dimethyl+sulfoxide
ChEBI	CHEBI:28262
ChEMBL	CHEMBL504
RTECS number	PV6210000
ATC code	G04BX13,M02AX03
Beilstein Reference	506008
Gmelin Reference	1556
Jmol-3D images	Image 1; Image 2
	SMILES CS(=O)C CS(C)=O ;
	InChI InChI=1S/C2H6OS/c1-4(2)3/h1-2H3 ; Key: IAZDPXIOMUYVGZ-UHFFFAOYSA-N InChI=1/C2H6OS/c1-4(2)3/h1-2H3; Key: IAZDPXIOMUYVGZ-UHFFFAOYAR ;
Properties
Molecular formula	C2H6OS
Molar mass	78.13 g mol−1
Appearance	Colourless liquid
Density	1.1004 g cm−3
Melting point	19 °C (66 °F; 292 K)
Boiling point	189 °C (372 °F; 462 K)
Solubility in water	Miscible
Solubility in diethyl ether	very soluble
Acidity (pKa)	35
Refractive index (nD)	1.479; εr = 48
Viscosity	1.996 cP at 20 °C
Structure
Dipole moment	3.96 D
Hazards
MSDS	External MSDS
R-phrases	R36/37/38
S-phrases	S26, S37/39
Main hazards	Irritant and flammable
NFPA 704	2 1 0
Flash point	89 °C
Related compounds
Related sulfoxides	diethyl sulfoxide
Related compounds	sodium methylsulfinylmethylide,; dimethyl sulfide,; dimethyl sulfone,; acetone
Supplementary data page
Structure and; properties	n, εr, etc.
Thermodynamic; data	Phase behaviour; Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
	Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
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	Infobox references