The average musical Do-It-Yourselfer starts building guitar effects by making a distortion pedal of some sort. It's a good introduction to musical electronics, and pretty simple as well, since getting a circuit NOT to be linear has never been hard. But there comes a time when you have to stop thrashing the strings in your bedroom, get up on stage and *play*. When you get to there, you run into all kinds of little problems that you never encountered back in your room.

If you've crossed the line and play guitar or bass and also sing in a band, you're almost certain to have run into the situation that you step away from the mike to do a solo (or one of those neato, expressive dance steps, or a facial impression of the pain you're pouring out to make these dulcet tones...), and had the mike pick up some unfortunate noise to funnel into the PA. You may even have fumbled for the mike mute switch as you stepped away and back to it, but that's almost terminally clumsy, as you have your hands full of your instrument. Wouldn't it be nice if the microphone was only 'listening' when you stepped up to it?

It's easy. Here's how.

Muting a microphone is simple. Knowing when is hard. The real trick is having the microphone be smart enough to figure out that you want to sing now. When my amp-tech friend first asked me to figure out a way to mute a mike when the singer stepped away, I went on these little flights of fancy with infrared motion detectors, ultrasonic range finders and other even less practical stuff, but what finally came out was a cross pollenization idea. Most singer/guitarists stand up to sing (except for you intimate acoustic types!) and that means they touch the floor. The home burglar alarm industry has come up with a simple and durable way to detect people standing on a floor.

There is a burglar detection product that is a laminated plastic film affair with metal strips inside that normally don't touch each other, but anything over about 5 pounds of force causes them to touch. The strips are brought out to leads to sense the contact. These contact mats are normally placed under carpets in places that intruders are likely to step. The pressure sensitive mats are available in two foot by three foot sections for a reasonable price at most burglar alarm suppliers. (Ask to talk to the installation tech, not the sales person!)

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You can't just use the mat contacts to open and close the mike lines directly because they would almost certainly cause unendurable hum, buzz and noise pickup. To avoid the noise, you need to use some switch element that is controlled by the mat contacts, but that does not couple the mat noise or clicks to the signal path. It turns out that there are lots of ways to do this, and I'll later describe several ways to do this.

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The mechanical setup at the mike itself is as important as the electronics, because it HAS to work properly for the way you use the mike and the way it's set up and transported to and from gigs. The pressure switch mat should be placed on the floor where you'll stand, and a rubber or carpet mat over it to protect the pressure mat from hard edged shoes. There is a small box containing the electronics that is attached to the mike stand in some way. I used velcro strips attached to the box for this. The box needs connectors for the signal cable from the mike, the switched audio cable to the sound board or PA, and a connector for the pressure strip contacts. It's fully possible to build these connections into the mike stand base if you have your own, or to use an external box like I did.

Clearly, there are a thousand ways to do this. You could even do it the Brute Force way, and just put a stomp switch into a box on the floor to punch the mike on and off as you tapdance away and toward the mike stand. However, you have to think about doing things like that, and unless you're a lot more chilled out and together on stage than I am, you'll forget at some crucial moment. The advantage of the smart Mike Muter is that it's automatic. You only have to get yourself to and from the microphone, it takes care of the rest.

Trifluridine (also called trifluorothymidine or TFT) is an anti-herpesvirusantiviral drug, used primarily on the eye. It was sold under the trade name Viroptic by Glaxo Wellcome, now merged into GlaxoSmithKline. The brand is now owned by Monarch Pharmaceuticals, which is wholly owned by King Pharmaceuticals.

Trifluridine was approved for medical use in 1980.^[1] It is also a component of the anti-cancer drug trifluridine/tipiracil, which is taken by mouth.

Medical uses[edit]

Trifluridine eye drops are used for the treatment of keratitis and keratoconjunctivitis caused by the herpes simplex virus types 1 and 2, as well as for prevention and treatment of vaccinia virus infections of the eye.^[2]

A Cochrane Systematic Review showed that trifluridine and aciclovir were a more effective treatment than idoxuridine or vidarabine,^[3] significantly increasing the relative number of successfully healed eyes in one to two weeks.^[4]

For cancer treatment, the combination trifluridine/tipiracil is used.

Adverse effects[edit]

Common side effects of trifluridine eye drops include transient burning, stinging, local irritation, and edema of the eyelids.^[2]

Adverse effects of the anti-cancer formulation have only been evaluated for the combination trifluridine/tipiracil, not for the individual components.

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Interactions[edit]

Only in vitro interaction studies are available. In these, trifluridine used the concentrative nucleoside transporter 1 (CNT1) and equilibrative nucleoside transporters 1 (ENT1) and 2 (ENT2). Drugs that interact with these transporters could influence blood plasma concentrations of trifluridine. Being a thymidine phosphorylase inhibitor, trifluridine could also interact with substrates of this enzyme such as zidovudine.^[5]

For the eye drops, trifluridine absorption is negligible,^[2] rendering interactions basically irrelevant.

Pharmacology[edit]

Mechanism of action (eye drops)[edit]

It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the –CF₃ group added to the uracil component blocks base pairing, thus interfering with viral DNA replication.

Pharmacokinetics (eye drops)[edit]

Trifluridine passes the cornea and is found in the aqueous humour. Systemic absorption is negligible.^[2]

Pharmacokinetics (oral)[edit]

H11f3

Pharmacokinetic data of oral trifluridine have only been evaluated in combination with tipiracil, which significantly affects biotransformation of the former. At least 57% of trifluridine are absorbed from the gut, and highest blood plasma concentrations are reached after two hours in cancer patients. The substance has no tendency to accumulate in the body. Plasma protein binding is over 96%. Trifluridine is metabolised by the enzyme thymidine phosphorylase to 5-trifluoromethyl-2,4(1H,3H)-pyrimidinedione (FTY), and also by glucuronidation. Elimination half-life is 1.4 hours on the first day and increases to 2.1 hours on the twelfth day. It is mainly excreted via the kidneys.^[5]

Tipiracil causes C_max (highest blood plasma concentrations) of trifluridine to increase 22-fold, and its area under the curve 37-fold, by inhibiting thymidine phosphorylase.^[5]

Chemistry[edit]

The substance is a white crystalline powder. It is freely soluble in methanol and acetone; soluble in water, ethanol, 0.01 M hydrochloric acid, and 0.01 M sodium hydroxide; sparingly soluble in isopropyl alcohol and acetonitrile; slightly soluble in diethyl ether; and very slightly soluble in isopropyl ether.^[6]

References[edit]

H11f3m

1. ^Long, Sarah S.; Pickering, Larry K.; Prober, Charles G. (2012). Principles and Practice of Pediatric Infectious Disease. Elsevier Health Sciences. p. 1502. ISBN978-1437727029.
2. ^ ^abcdDrugs.com: Monograph for Trifluridine.
3. ^Wilhelmus, Kirk R (2015-01-09). 'Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis'. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd. 1: CD002898. doi:10.1002/14651858.cd002898.pub5. PMC4443501. PMID25879115.
4. ^Wilhelmus, Kirk R (2015-01-09). Cochrane Eyes and Vision Group (ed.). 'Antiviral treatment and other therapeutic interventions for herpes simplex virus epithelial keratitis'. Cochrane Database of Systematic Reviews. 1: CD002898. doi:10.1002/14651858.CD002898.pub5. PMC4443501. PMID25879115.
5. ^ ^abcHaberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
6. ^FDA Professional Drug Information on Lonsurf.

External links[edit]

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• Costin D, Dogaru M, Popa A, Cijevschi I (2004). 'Trifluridine therapy in herpetic in keratitis'. Rev Med Chir Soc Med Nat Iasi. 108 (2): 409–12. PMID15688823.
• Kuster P, Taravella M, Gelinas M, Stepp P (1998). 'Delivery of trifluridine to human cornea and aqueous using collagen shields'. CLAO J. 24 (2): 122–4. PMID9571274.
• O'Brien W, Taylor J (1991). 'Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents'. Invest Ophthalmol Vis Sci. 32 (9): 2455–61. PMID1907950.
• 'Trifluridine Ophthalmic Solution, 1%'(PDF). Retrieved 2007-03-24.CS1 maint: discouraged parameter (link)

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