WordNet

give (hair) the appearance of being fuller by using a rat
a pad (usually made of hair) worn as part of a womans coiffure
any of various long-tailed rodents similar to but larger than a mouse
catch rats, especially with dogs
desert ones party or group of friends, for example, for ones personal advantage
employ scabs or strike breakers in
relating to or involved in therapy; "therapeutic approach to criminality" (同)therapeutical
the relative magnitudes of two quantities (usually expressed as a quotient)
branch of medicine concerned with the treatment of disease

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『ネズミ』 / ひきょう者,裏切り者 / ネズミをつかまえる / 《話》(人を)裏切る,密告する《+『on』+『名』〈人〉》
治療[上]の
『比』,比率,『割合』;『比例』
治療学

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/01/16 19:49:48」(JST)

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The therapeutic index (also known as therapeutic ratio) is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death (in animal studies) or toxicity (in human studies).^[1]

Quantitatively, it is the ratio given by the lethal or toxic dose divided by the therapeutic dose.

In animal studies, the therapeutic index is the lethal dose of a drug for 50% of the population (LD₅₀) divided by the minimum effective dose for 50% of the population (ED₅₀).

Lethality is not determined in human clinical trials; instead, the dose that produces a toxicity in 50% of the population (TD₅₀) is used to calculate the therapeutic index.

While the lethal dose is important to determine in animal studies, there are usually severe toxicities that occur at sublethal doses in humans, and these toxicities often limit the maximum dose of a drug. A higher therapeutic index is preferable to a lower one: a patient would have to take a much higher dose of such a drug to reach the lethal/toxic threshold than the dose taken to elicit the therapeutic effect.

in animal studies, or for humans,

Generally, a drug or other therapeutic agent with a narrow therapeutic range (i.e. having little difference between toxic and therapeutic doses) may have its dosage adjusted according to measurements of the actual blood levels achieved in the person taking it. This may be achieved through therapeutic drug monitoring (TDM) protocols.

The therapeutic index varies widely among substances: most forgiving among the opioid analgesics is remifentanyl, which offers a therapeutic index of 33,000:1; tetrahydrocannabinol, a sedative and analgesic of herbal origin (genus Cannabis), has a safe therapeutic index of 1000:1, while diazepam, a benzodiazepine sedative-hypnotic and skeletal muscle relaxant has a less-forgiving index of 100:1 and morphine, a sedative, antidepressant, and analgesic also of herbal origin (genus Papaver) has an index of 70:1^[2] (which, however, is still considered very safe).

Less safe are cocaine, a stimulant and local anaesthetic; ethanol, a widely available sedative consumed world-wide: the therapeutic indices for these substances are 15:1 and 10:1 respectively. Even less-safe are drugs such as digoxin, a cardiac glycoside; its therapeutic index is approximately 2:1.^[3] Other examples of drugs with a narrow therapeutic range, which may require drug monitoring both to achieve therapeutic levels and to minimize toxicity, include: dimercaprol, theophylline, warfarin and lithium carbonate. Some antibiotics require monitoring to balance efficacy with minimizing adverse effects, including: gentamicin, vancomycin, amphotericin B (nicknamed 'amphoterrible' for this very reason), and polymyxin B.

The effective therapeutic index can be affected by targeting, in which the therapeutic agent is concentrated in its area of effect. For example, in radiation therapy for cancerous tumors, shaping the radiation beam precisely to the profile of a tumor in the "beam's eye view" can increase the delivered dose without increasing toxic effects, though such shaping might not change the therapeutic index. Similarly, chemotherapy or radiotherapy with infused or injected agents can be made more efficacious by attaching the agent to an oncophilic substance, as is done in peptide receptor radionuclide therapy for neuroendocrine tumors and in chemoembolization or radioactive microspheres therapy for liver tumors and metastases. This concentrates the agent in the targeted tissues and lowers its concentration in others, increasing efficacy and lowering toxicity.

Sometimes the term safety ratio is used instead, particularly when referring to psychoactive drugs used for non-therapeutic (e.g. nonmedical) purposes.^[4] In such cases, the "effective" dose is the amount and frequency that produces the desired effect, which can vary, and can be greater or less than the therapeutically effective dose.

The concept of safety ratio/TI also ignores the ease or difficulty of reaching a toxic or lethal dose. This is more of a consideration for recreational drug users. While heroin and common alcohol may appear similarly dangerous based on their safety ratio (6 vs 10), an inexperienced drinker most likely vomits and falls asleep long before ingesting life-threatening amounts of alcohol. On the other hand, heroin users are at a much greater risk of death from a misjudged dose due to varying drug purity, individual tolerances, and influence-affected judgment.

Protective index is a similar concept, except that it uses TD₅₀ (median toxic dose) in place of LD₅₀. For many substances, toxic effects can occur at levels far below those needed to cause death, and thus the protective index (if toxicity is properly specified) is often more informative about a substance's relative safety. Nevertheless, the therapeutic index is still useful as it can be considered an upper bound for the protective index, and the former also has the advantages of objectivity and easier comprehension.

References

^ Katzung and Trevor's Pharmacology Examination & Board Review; 9th edition; A.J.Trevor, B.G. Katzung, S.B.Masters, McGraw Hill, 2010, p. 15.
^ Stanley, Theodore H (2000). "Anesthesia for the 21st century". Proc (Bayl Univ Med Cent) 13 (1): 7–10. PMC 1821133. PMID 16389318. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1821133/.
^ Becker, Daniel E (2007 Spring). "Drug Therapy in Dental Practice: General Principles Part 2—Pharmacodynamic Considerations". Anesth Prog. 54 (1): 19–24. doi:10.2344/0003-3006(2007)54[19:DTIDPG]2.0.CO;2. ISSN 0003-3006. PMC 1821133. PMID 17352523. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1821133/.
^ Gable,, Robert S (2004). "Comparison of acute lethal toxicity of commonly abused psychoactive substances" (PDF). Addiction (99): 686–696. doi:10.1111/j.1360-0443.2004.00744.x. PMID 15139867. http://web.cgu.edu/faculty/gabler/toxicity%20Addiction%20offprint.pdf.

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English Journal

Adverse events associated with botulinum toxin injection: a multidepartment, retrospective study of 5310 treatments administered to 1819 patients.

Kim BW1, Park GH, Yun WJ, Rho NK, Jang KA, Won CH, Chang SE, Chung SJ, Lee MW.Author information 1Department of Dermatology, Asan Medical Center, University of Ulsan College of Medicine , Seoul , Korea.AbstractBACKGROUND: The injection of botulinum toxin is now commonly used for many therapeutic and cosmetic purposes but because of its increased use more adverse events are being reported.
The Journal of dermatological treatment.J Dermatolog Treat.2014 Aug;25(4):331-6. doi: 10.3109/09546634.2013.789473. Epub 2013 Apr 24.
BACKGROUND: The injection of botulinum toxin is now commonly used for many therapeutic and cosmetic purposes but because of its increased use more adverse events are being reported.OBJECTIVE: To retrospectively evaluate and analyze the safety of botulinum toxin injections in terms of purpose and the
PMID 23537074

Characteristics of platelet gels combined with silk.

Pallotta I1, Kluge JA2, Moreau J2, Calabrese R2, Kaplan DL3, Balduini A4.Author information 1Tufts University, Department of Biomedical Engineering, 4 Colby Street, Medford, MA 02155, USA; University of Pavia, Department of Molecular Medicine, Via Forlanini 6, Pavia 27100, Italy.2Tufts University, Department of Biomedical Engineering, 4 Colby Street, Medford, MA 02155, USA.3Tufts University, Department of Biomedical Engineering, 4 Colby Street, Medford, MA 02155, USA. Electronic address: david.kaplan@tufts.edu.4Tufts University, Department of Biomedical Engineering, 4 Colby Street, Medford, MA 02155, USA; University of Pavia, Department of Molecular Medicine, Via Forlanini 6, Pavia 27100, Italy. Electronic address: alessandra.balduini@tufts.edu.AbstractPlatelet gel, a fibrin network containing activated platelets, is widely used in regenerative medicine due the capacity of platelet-derived growth factors to accelerate and direct healing processes. However, limitations to this approach include poor mechanical properties, relatively rapid degradation, and the lack of control of release of growth factors at the site of injection. These issues compromise the ability of platelet gels for sustained function in regenerative medicine. In the present study, a combination of platelet gels with silk fibroin gel was studied to address the above limitations. Mixing sonicated silk gels with platelet gels extended the release of growth factors without inhibiting gel-forming ability. The released growth factors were biologically active and their delivery was modified further by manipulation of the charge of the silk protein. Moreover, the silk gel augmented both the rheological properties and compressive stiffness of the platelet gel, tuned by the silk concentration and/or silk/platelet gel ratio. Silk-platelet gel injections in nude rats supported enhanced cell infiltration and blood vessel formation representing a step towards new platelet gel formulations with enhanced therapeutic impact.
Biomaterials.Biomaterials.2014 Apr;35(11):3678-87. doi: 10.1016/j.biomaterials.2013.12.065. Epub 2014 Jan 27.
Platelet gel, a fibrin network containing activated platelets, is widely used in regenerative medicine due the capacity of platelet-derived growth factors to accelerate and direct healing processes. However, limitations to this approach include poor mechanical properties, relatively rapid degradatio
PMID 24480538

Serum biomarkers for personalization of nanotherapeutics-based therapy in different tumor and organ microenvironments.

Yokoi K1, Tanei T2, Godin B2, van de Ven AL2, Hanibuchi M3, Matsunoki A3, Alexander J2, Ferrari M4.Author information 1Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, Houston, TX 77030, USA; Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: kyokoi2@tmhs.org.2Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, Houston, TX 77030, USA.3Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.4Department of Nanomedicine, Houston Methodist Research Institute, 6670 Bertner Street, Houston, TX 77030, USA. Electronic address: mferrari@tmhs.org.AbstractEnhanced permeation and retention (EPR) effect, the mechanism by which nanotherapeutics accumulate in tumors, varies in patients based on differences in the tumor and organ microenvironment. Surrogate biomarkers for the EPR effect will aid in selecting patients who will accumulate higher amounts of nanotherapeutics and show better therapeutic efficacy. Our data suggest that the differences in the vascular permeability and pegylated liposomal doxorubicin (PLD) accumulation are tumor type as well as organ-specific and significantly correlated with the relative ratio of MMP-9 to TIMP-1 in the circulation, supporting development of these molecules as biomarkers for the personalization of nanoparticle-based therapy.
Cancer letters.Cancer Lett.2014 Apr 1;345(1):48-55. doi: 10.1016/j.canlet.2013.11.015. Epub 2013 Dec 24.
Enhanced permeation and retention (EPR) effect, the mechanism by which nanotherapeutics accumulate in tumors, varies in patients based on differences in the tumor and organ microenvironment. Surrogate biomarkers for the EPR effect will aid in selecting patients who will accumulate higher amounts of
PMID 24370567

Japanese Journal

Concentrated autologous bone marrow aspirate transplantation treatment for corticosteroid-induced osteonecrosis of the femoral head in systemic lupus erythematosus

Yoshioka Tomokazu,Mishima Hajime,Akaogi Hiroshi,Sakai Shinsuke,Li Meihua,Ochiai Naoyuki,三島初,落合直之
International orthopaedics 35(6), 823-829, 2011-05
… This cell concentration was significantly higher after concentration, and the mean concentration ratio was 5.5. … CABMAT using our centrifugation technique is an effective, safe and low-cost procedure of therapeutic osteogenesis for corticosteroid-induced ONFH in SLE. …
NAID 120003133764

The Clinical Course and Incidence of Supraventricular Tachyarrhythmias After Extra-Cardiac Conduit Fontan Procedures in Relation to an Atrial Situs

MIYAZAKI Aya,SAKAGUCHI Heima,OHUCHI Hideo,YAMADA Osamu,KITANO Masataka,YAZAKI Satoshi,SUGIYAMA Hisashi,KUROSAKI Ken-ichi,KAGISAKI Koji,YAGIHARA Toshikatsu,TSUDA Etsuko
Circulation journal : official journal of the Japanese Circulation Society 75(2), 413-420, 2011-01-25
… For the atrial isomerism, the predictors of SVT ≥3 months after the EC were a history of an AV valve repair (risk ratio (RR) 1.9; … A comprehensive therapeutic strategy should be considered. …
NAID 10027427238