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an antibiotic obtained from an actinomycete and used (as a sulphate under the trade name Neobiotic) as an intestinal antiseptic in surgery (同)fradicin, Neobiotic

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/08/10 21:28:26」(JST)

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Neomycin is an aminoglycoside antibiotic found in many topical medications such as creams, ointments, and eyedrops. The discovery of neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951. Neomycin belongs to aminoglycoside class of antibiotics that contain two or more aminosugars connected by glycosidic bonds. Neamine (two rings), ribostamycin (three rings), paromomycin (four rings), and lividomycin (five rings) are some other examples of aminoglycosides. They have shown tremendous potential as antibacterials. One of them, gentamicin, has been used extensively in clinical practice. Due to the inherent oto- and nephrotoxicity of these substances, systemic use has declined, as safer alternatives have become available.

Uses

Neomycin is overwhelmingly used as a topical preparation, such as Neosporin. It can also be given orally, where it is usually combined with other antibiotics. Neomycin is not absorbed from the gastrointestinal tract and has been used as a preventive measure for hepatic encephalopathy and hypercholesterolemia. By killing bacteria in the intestinal tract, it keeps ammonia levels low and prevents hepatic encephalopathy, especially prior to GI surgery. It has also been used to treat small intestinal bacterial overgrowth. It is not given intravenously, as neomycin is extremely nephrotoxic (causes kidney damage), especially compared to other aminoglycosides. The exception is when neomycin is included, in very small quantities, as a preservative in some vaccines - typically 0.025 mg per dose.^[1]

Molecular biology

Neomycin resistance is conferred by either one of two aminoglycoside phosphotransferase genes.^[2] A neo gene is commonly included in DNA plasmids used by molecular biologists to establish stable mammalian cell lines expressing cloned proteins in culture; many commercially available protein expression plasmids contain neo as a selectable marker. Non-transfected cells will eventually die off when the culture is treated with neomycin or similar antibiotic. Neomycin or kanamycin can be used for prokaryotes, but geneticin (G418) is, in general, needed for eukaryotes.

Spectrum

Similar to other aminoglycosides, neomycin has excellent activity against Gram-negative bacteria, and has partial activity against Gram-positive bacteria. It is relatively toxic to humans, and many people have allergic reactions to it.^[3] See: Hypersensitivity. Physicians sometimes recommend using antibiotic ointments without neomycin, such as Polysporin.^[4]

History

Neomycin was discovered in 1949 by the microbiologist Selman Waksman and his student Hubert Lechevalier at Rutgers University. It is produced naturally by the bacterium Streptomyces fradiae.^[5]

Neomycin as a DNA binder

Neomycin belongs to the family of aminoglycosides. This family includes many other medicinally important drugs: streptomycin, paromomycin and kanamycin . Aminoglycosides are known for their ability to bind to duplex RNA with high affinity. A study done by Daniel Pilch, Associate Professor Dept. of Pharmacology at Rutgers University, and his coworkers determined the association constant for neomycin with A-site RNA was found to be in the ~10⁹ M^-1 range. However, more than 50 years after its discovery, its DNA-binding properties were still unknown. In 2000, Dev P. Arya, currently Director of the Laboratory of Medicinal Chemistry at Clemson University, and his coworkers discovered that neomycin induces enormous thermal stabilization of triplex DNA while having little or almost no effect on the B-DNA duplex stabilization. They also showed that neomycin binds to structures that adopt A-form structure, triplex DNA being one of them. They later went on to show that neomycin even induces DNA:RNA hybrid triplex formation.

References

^ "Medscape article". http://www.medscape.com/viewarticle/516045_6.
^ "G418/neomycin-cross resistance?". http://www.bio.net/bionet/mm/methods/1999-March/073912.html. Retrieved 2008-10-19.
^ DermNet dermatitis/neomycin-allergy
^ "Your Medicine Cabinet". DERMAdoctor.com, Inc.. http://www.dermadoctor.com/article_Your-Medicine-Cabinet_43.html. Retrieved 2008-10-19.
^ "The Nobel Prize in Physiology or Medicine 1952". Nobel Foundation. http://nobelprize.org/nobel_prizes/medicine/laureates/1952/waksman-bio.html. Retrieved 2008-10-29.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 外耳炎：治療 external otitis treatment
2. 成人における肝性脳症：治療 hepatic encephalopathy in adults treatment
3. スタチン系およびフィブラート系以外の薬剤による脂質低下 lipid lowering with drugs other than statins and fibrates
4. 予防接種に対するアレルギー反応 allergic reactions to vaccines
5. 幼児、小児、および思春期における麻疹、ムンプス、および風疹ワクチン measles mumps and rubella immunization in infants children and adolescents

English Journal

Expression pattern of a single transgene cassette located in endogenous GLIS3 of cloned pigs; a nested situation.

Jakobsen JE, Dantoft TM, Johansen MG, Jørgensen AL.AbstractOne of the main focus areas in transgenesis is the choice of a promoter driving stable expression over time of the gene of interest. Besides promoter identity, the genomic environment of the transgene plays a pivotal role in transcription regulation. Studies in higher mammals describing transgene expression from a defined locus are very limited. We set out to determine the expression pattern of two transgene promoters, the human PDGFβ and the viral SV40, in a single cassette positioned in the largest intron of the porcine GLIS3 locus. The PDGFβ promoter drives a variant of the amyloid precursor protein gene named APP695sw and the SV40 promoter drives the neomycin resistant gene, Neo. The nested gene scenario was investigated in three transgenic cloned pigs sacrificed at 3months, 2years and 3years of age. With identical genetic make-up and same environment, the three individual pigs are considered representative of 3year lifespan of a single pig. Selected organs from the pigs were analyzed by quantitative RT-PCR for transgene promoter activity as well as endogenous GLIS3 promoter activity. No apparent effect of the transgene cassette was observed on endogenous GLIS3 expression. In addition, one year old homozygous pigs showed no phenotypic signs of dysfunctional GLIS3. Both transgene promoters showed and retained their tissue specificity with stable expression over time. Our study indicates that transgenes inserted in a nested situation might be applicable for faithful and long term transgene expression.
Gene.Gene.2012 Jul 10;502(2):94-8. Epub 2012 Apr 25.
One of the main focus areas in transgenesis is the choice of a promoter driving stable expression over time of the gene of interest. Besides promoter identity, the genomic environment of the transgene plays a pivotal role in transcription regulation. Studies in higher mammals describing transgene ex
PMID 22555020

Optimization of an antibiotic sensitivity assay for Mycoplasma hyosynoviae and susceptibility profiles of field isolates from 1997 to 2011.

Schultz KK, Strait EL, Erickson BZ, Levy N.SourceVeterinary Diagnostic & Production Animal Medicine, Iowa State University, College of Veterinary Medicine, 1600 South 16th St., Ames, IA 50011, United States.
Veterinary microbiology.Vet Microbiol.2012 Jul 6;158(1-2):104-8. Epub 2012 Feb 11.
Mycoplasma hyosynoviae is a common agent responsible for polyarthritis leading to decreased production in swine herds worldwide. Antimicrobial agents are used to combat infections; however breakpoints for M. hyosynoviae have not yet been established. A number of methods have previously been utilized
PMID 22397937

Japanese Journal

In vitro flowering and viable seed setting of transgenic lettuce cultures

G. Franklin,A. L. Oliveira,A. C. P. Dias
Plant Biotechnology advpub(0), 1101260016, 2011
… Six days old cotyledons were co-cultivated with Agrobacterium tumefaciens strain EHA105 harbouring the binary vector pCAMBIA2301 carrying the reporter gene α-glucuronidase intron (GUS-INT) and the marker gene neomycin phosphotransferase (NPTII). …
NAID 40018743708

Usefulness of a Non-invasive Reporter System for Monitoring Reprogramming State in Pig Cells : Results of a Cell Fusion Experiment

OZAWA Akio,AKASAKA Eri,WATANABE Satoshi,YOSHIDA Mitsutoshi,MIYOSHI Kazuchika,SATO Masahiro
The Journal of reproduction and development 56(4), 363-369, 2010-08-01
… 5.4-kb mouse Oct-3/4 promoter linked to the EGFP cDNA and neomycin expression unit and produced a porcine embryonic cell line stably incorporating it in the genome. …
NAID 10026621377

Related Pictures

★リンクテーブル★

リンク元	「アミノグリコシド系抗菌薬」「ネオマイシン」「NM」
拡張検索	「neomycin A」「neomycin-resistant gene」「neomycin-resistant」

「アミノグリコシド系抗菌薬」

Neomycin
Systematic (IUPAC) name
	(2S,3S,4S,5R)-5-amino-2-(aminomethyl)-6-((2R,3S,4R,5S)-5-((1R,2R,5R,6R)-3,5-diamino-2-((2R,3S,4R,5S)-3-amino-6-(aminomethyl)-4,5-dihydroxytetrahydro-2H-pyran-2-yloxy)-6-hydroxycyclohexyloxy)-4-hydroxy-2-(hydroxymethyl)tetrahydrofuran-3-yloxy)tetrahydro-2H-pyran-3,4-diol
Clinical data
Trade names	Neo-rx
AHFS/Drugs.com	monograph
MedlinePlus	a682274
Pregnancy cat.	?
Legal status	OTC
Routes	Topical, Oral
Pharmacokinetic data
Half-life	2 to 3 hours
Identifiers
CAS number	1404-04-2
ATC code	A01AB08 A07AA01, B05CA09, D06AX04, J01GB05, R02AB01, S01AA03, S02AA07, S03AA01
PubChem	CID 8378
IUPHAR ligand	709
DrugBank	DB00994
ChemSpider	8075
UNII	I16QD7X297
KEGG	D08260
ChEBI	CHEBI:7508
ChEMBL	CHEMBL449118
Chemical data
Formula	C23H46N6O13
Mol. mass	614.644 g/mol
	SMILES O([C@H]3[C@H](O[C@@H]2O[C@H](CO)[C@@H](O[C@H]1O[C@@H](CN)[C@@H](O)[C@H](O)[C@H]1N)[C@H]2O)[C@@H](O)[C@H](N)C[C@@H]3N)[C@H]4O[C@@H]([C@@H](O)[C@H](O)[C@H]4N)CN;
	InChI InChI=1S/C23H46N6O13/c24-2-7-13(32)15(34)10(28)21(37-7)40-18-6(27)1-5(26)12(31)20(18)42-23-17(36)19(9(4-30)39-23)41-22-11(29)16(35)14(33)8(3-25)38-22/h5-23,30-36H,1-4,24-29H2/t5-,6+,7-,8+,9-,10-,11-,12+,13-,14-,15-,16-,17-,18-,19-,20-,21-,22-,23+/m1/s1 ; Key:PGBHMTALBVVCIT-VCIWKGPPSA-N ;
(what is this?) (verify);

　　[★]

英: aminoglycoside antibiotic
関: 抗菌薬、アミノグリコシド系薬、アミノグリコシド

GOO. chapter.45

タンパク質合成阻害による抗菌薬は静菌的なのもが多いが、アミノグリコシド系抗菌薬は「殺菌的」に作用

構造

amino sugars linked to an aminocyclitol ring by glycosidic bonds (GOO.1155)
名前の通りアミノ基-NH₂を多数有しているため正電荷を帯びる

→経口吸収不良

→脳脊髄液に移行しにくい。

→腎排泄されやすい

動態

内服不可能→外来患者に使いにくい
細胞膜(内膜)の通過は膜電位ポテンシャルに依存している。ここが律速段階となる。　→　細胞内移行性悪

阻害、拮抗要素：二価陽イオン、高浸透圧、pHの低下、嫌気的条件

膿瘍など嫌気的条件、酸性の高浸透圧尿など細菌の膜電位ポテンシャルが低下する場合に薬効低下

作用機序

30Sリボソームに作用してタンパク質合成を阻害

1. 翻訳開始を阻害
2. 翻訳を停止させる
3. 誤ったアミノ酸を取り込ませる

異常蛋白が細胞膜に挿入され、膜の透過性を変えてさらにアミノグリコシド系抗菌薬の取り込みを促す

薬理作用

薬効は迅速。濃度依存的。
post-antibiotic effectがある。

抗菌薬の血漿濃度がminnimum inhibitory concentration以下になっても殺菌活性が残存。殺菌活性の残存時間は濃度依存的

抗菌スペクトル

広い

副作用

腎障害：近位尿細管の壊死変性。用量依存的
耳毒性：CN VIII障害。内耳の有毛細胞を破壊。用量依存的
神経・筋遮断作用：(稀であるが)神経筋遮断作用(およびこれによる無呼吸)を呈する。遮断作用はネオマイシンが一番強く、カナマイシン、アミカシン、ゲンタマイシン、トブラマイシンがこれに続く。通常、胸腔内、腹腔に大量投与した時に生じるが、静脈内、筋肉内、あるいは経口投与でも起こりうる。大抵の発作(神経筋接合部が遮断される発作)は麻酔薬やその他の神経筋接合部遮断薬の投与で生じる(←どういう意味？)。重症筋無力症の患者はアミノグリコシド系抗菌薬による神経筋接合部遮断作用を受けやすい。(GOO.1164)