PROHIBITED SUBSTANCES RULES P.1. INTRODUCTION 1.1. In these rules: a) prohibited substance means any substance (or any isomer, metabolite and/or analogue produced from the substance) that is a stimulant, depressant, tranquiliser, local anaesthetic, psychotropic (mood and/or behaviour altering) substance, or any other substance which might affect the performance of a horse and/or which might interfere with or mask any prohibited substance testing;
Medlaser.ruLASER HAIR REMOVAL: SCIENTIFIC PRINCIPLES AND
Christine C. Dierickx, MD Visiting Faculty Member Wellman Laboratories of Photomedicine Harvard Medical School The use of lasers for hair removal has been studied for a number of years. In this procedure,laser light is absorbed by melanin in the hair shaft, damaging the follicular epithelium. A clini-cal study evaluated the use of the LightSheer™ Diode Laser for hair removal. Of 92 patients,all had temporary hair loss and 89% had long-term hair loss. Regrowing hairs were shown tobe thinner and lighter than previously. Extensive clinical use of this high-power, pulsed diodelaser has resulted in recommendations for patient selection and proper use of the laser.
Appropriate fluence settings have been shown to cause long-term hair loss without damagingthe epidermis, regardless of skin type.
Laser hair removal focuses on the endogenous chromophore melanin, which is mainly found inthe hair shaft, with a small amount present in the upper third of the follicular epithelium (Figure1). When an appropriate energy source (such as a laser) is directed at the skin, light is primari-ly absorbed in the hair shaft melanin. Heat is generated and diffuses to the surrounding follicu-lar epithelium. A similar principle applies to laser treatment of vascular lesions, where the heatgenerated after absorption by hemoglobin is transferred from the blood to the vascular endothe-lial cells. Arrector pili muscle Figure 1. The anatomy of a typical terminal hair. Laser hair removaltargets the melanin in the hair shaft.
LASER HAIR REMOVAL: SCIENTIFIC PRINCIPLES AND
Christine C. Dierickx, MD Visiting Faculty Member Wellman Laboratories of Photomedicine Harvard Medical School Absorption (log scale) Figure 2. The absorption of various chromophores as a function of wavelength. Rubylasers operate at 694 nm, alexandrite lasers at 755 nm, diode lasers at 800 nm andNd:YAG lasers at 1064 nm. (Adapted from Boulnois JL. Photophysical processes in recentmedical laser developments: a review. Published in Lasers in Medical Science, Vol 1, 1986.) • Pulse duration (or pulse width) must be equal to or shorter than the thermal relax- ation time of the target to confine thermal damage. The thermal relaxation time ofthe whole follicular structure depends on its diameter and is on the order of tens ofmilliseconds. Consequently, the laser source must have a range of pulse widths toselectively damage different size follicles. • Pulse width must be matched with the appropriate amount of fluence (energy per unit area) necessary to cause follicular damage.
Hair removal devices available today include 694 nm ruby lasers, 755 nm alexandrite lasers,800 nm diode lasers, 1064 nm Nd:YAG lasers, and filtered xenon flashlamps. This paperfocuses on an 800 nm diode laser (LightSheer Diode Laser, Coherent, Santa Clara, CA). Thiswavelength effectively targets the melanin while deeply penetrating the dermis.
HAIR LOSS AND REGROWTH One hundred patients were treated in a clinical study with the high-power pulsed diode laser.
The study evaluated different combinations of fluence and pulse width in eight test sites. Thepatients were followed-up at one, three, six, nine, and 12 months. Ninety-two patients complet-ed the study. Hair loss was assessed from hair counts using digital photographs before treat-ment and at each follow-up visit. Tattoos identified the location of each test site. The study showed that the high-power diode laser induces two separate effects: temporary hairloss and long-term hair reduction.
Temporary hair loss occurs in all patients, for all hair colors and at all laser fluences. It usuallylasts from one to three months.
Long-term hair reduction is defined as a significant reduction in the number of terminal hairs ata given body site that is stable for a period of time longer than the follicles' complete growthcycle (Figure 3, Table I). Test sites were mainly given on the back and thighs, where completehair growth cycles vary between six months and a year. A one year follow-up allowed time forone to two complete growth cycles at these anatomic sites. Figure 3. Hair growth cycle. Anagen is the active growth phase, catagenis the regression phase, telogen is a resting phase.
Table I. Duration of hair growth cycles.
There is a difference between long-term hair reduction and complete hair loss. Complete hairloss implies that there are no regrowing hairs. This can be a temporary or permanent phenome-non. The LightSheer Diode Laser usually produces complete but temporary hair loss, followedby a partial but long-term hair reduction. This is an important distinction to make when settingpatient expectations.
With this laser, 100% of the patients experienced temporary hair loss, while 89% of the patientshad long-term hair loss at one year follow-up. Of the 11% of patients who did not have long-term hair loss, most had blond hair. Because blond hair contains less melanin than darker hair,there is less chromophore for the laser to target, and the response is less. However, thesepatients experienced temporary hair loss.
Numbers cited for hair loss only take into account the absolute number of hairs. They do notreflect the fact that the regrowing hairs are lighter and thinner than before, which also adds toapparent clinical hair loss. Hair color was measured by calculating the absorption coefficientfrom the hairs' transmission of 700 nm light. Hair diameter was measured from digital pho-tographs. The study showed that the regrowing hairs appeared lighter (with a transmissioncoefficient 1.41 times higher than the value before treatment) and were thinner (with a decreasein the mean hair diameter by 19.9%) than the original hairs.
Histologic observations support two mechanisms for long-term hair loss: miniaturization ofcoarse hair follicles to vellus-like hair follicles, and destruction of the hair follicle with granulo-matous degeneration, leaving a fibrotic remnant. Clinically, both of these mechanisms pro-duced reduction in hair. The study design used a fixed set of fluence-pulse-width combinations in each patient, regard-less of skin type. If skin type and color had been matched to appropriate fluences, the inci-dence of side effects could have been reduced. Epidermal damage was seen in 6% of cases.
Textural change occurred in 3% of cases, where triple pulsing was used at the highest fluence.
These changes disappeared after three months. Transient pigment changes were seen in about10% of cases and usually occurred in the darker skin types or in patients who had tans at thetime of treatment.
DIODE LASER CHARACTERISTICS The characteristics of the LightSheer Diode Laser are seen in Table II. The ChillTip™ hand-piece directs the laser onto the skin through an integrated cold (approximately 5 degrees C) sap-phire window. 5 to 30 milliseconds 9 by 9 millimeters 10 to 40 Joules/cm2* 1 pulse per second* Table II. LightSheer Diode Laser characteristics.
*Other LightSheer models have expanded capabilities for these specifications.
The laser has a range of pulse widths from 5 to 30 milliseconds, which is longer than the ther-mal relaxation time of the epidermis and comparable to that of the follicle. This pulse widthrange can effectively damage the follicle. However, the epidermis also contains some melaninand must be protected. A sapphire window (ChillTip) with high thermal conductivity is put indirect contact with the skin. It cools the epidermis before, during, and after the laser pulse.
Because of index matching, it also reduces internal reflection of back-scattered light. Thesecombined thermal and optical cooling effects protect the epidermis from damage.
Besides preserving the epidermis, compressing the skin with the ChillTip has two other advan-tages. The pressure removes oxyhemoglobin, a chromophore that competes with melanin. Italso flattens the epidermis, bringing the hair roots closer to the surface. Hair roots closer to thesurface have a greater probability of absorbing the laser light.
CLINICAL GUIDELINES Patient SelectionBy studying hair color and skin type it is easy to determine which patients will have the bestresults with laser hair removal. Patients with red, gray, or blond hair can be advised that theyshould not expect long-term hair reduction. It is especially important to see if the patient has atan or not. If patients have a tan they should be instructed to stay out of the sun, use a bleach-ing cream and sun block, and return for treatment when the tan is gone.
Because the hair shaft is the chromophore, it is essential that the hair shaft is present in the hairfollicle at the time of treatment. Patients are therefore not allowed to pluck, wax, or have elec-trolysis for at least six weeks before the laser treatment. Shaving and depilatory creams areallowed because they leave the hair shaft in the follicle.
It is important to take a history, including an endocrine history. Female patients with hirsutismcan be treated regardless of the cause.
Patients with a history of herpes simplex or genitalis should be put on oral antiviral drugs(Zovirax® or Famvir®) beginning the day before treatment. This is important when treating anupper lip or even a bikini line because reactivation of herpes simplex and genitalis has beenreported after laser treatment.
There is no consensus on how long Accutane® should be stopped before treatment. The generalrule is to stop Accutane® treatments for six months before laser hair removal.
Treatment MethodsIt is important to shave before beginning the treatment. If the external hair shaft is present thelaser will burn it, in turn burning the skin. Depilatory creams can be used with patients whoobject to shaving.
Anesthesia is usually not required; however, this depends on the patient and body area. Whentreating the upper lip some kind of anesthesia is recommended.
There is a high risk for eye damage with the laser because the retina has a very high concentra-tion of melanin. For this reason treatment must not be carried out inside the bony area of theeye. It is important that the patient, nurse, and doctor all wear goggles.
During treatments it is important to regularly clean the handpiece. When the hair shaft car-bonizes it leaves debris on the sapphire window. This build up can make it hot, and can make itdifficult for the laser light to penetrate. Cleaning the ChillTip handpiece with alcohol preventsthis barrier from forming. There is a small but real risk of infection because the handpiece is indirect contact with the skin. Therefore, between patients the handpiece should be disinfectedwith a liquid disinfectant such as Virex.
Fluence SelectionHair color and skin color determine the best fluence to use. If tanned patients insist on treat- ment, 10 to 15 J/cm2 is the maximum fluence. Darker skin types IV to VI (Table III) can be treated between 10 and 20 J/cm2. Fair skin types I to III can take the highest fluences, from 25 to 40 J/cm2.
Type IAlways burns, never tans Always burns, sometimes tans Sometimes burns, always tans Rarely burns, always tans Moderately pigmented Type VIBlack skin Table III. Fitzpatrick classification of skin types.
Treatment should be performed with the highest fluence the skin can tolerate. Studies haveshown that the percentage hair loss is fluence-dependent, with higher percentages of hair loss athigher fluences. Each skin type has its own threshold fluence at which pigmentation changes occur. To mini-mize hypo- or hyperpigmentation, lower fluences than those suggested above should be usedwhile gaining clinical experience. With multiple pulsing the incidence of pigment changesincreases without an increase in efficacy. For this reason, double and triple pulsing are not rec-ommended. If hypo- or hyperpigmentation do occur, it is transient. The duration of these pig-ment changes, however, depends on the anatomic area.
The ChillTip handpiece must be in firm contact with the skin. A single pulse should be placedat test sites within or near the treatment area. If epidermal damage is present (blistering, abla-tion, graying or whitening of the epidermis, or a positive Nikolski sign) the fluence should be lowered by 5 to 10 J/cm2. Several pulses should then be placed next to one another while looking for the epidermalresponse. An effective fluence is one where the hair carbonizes, followed by very selective fol-licular swelling and redness (Figure 4). Figure 4. Immediately after laser treatment of the bikini area on a Fitzpatrick skin type II; treatment at 40 J/cm2 fluence and 20 ms pulse duration.
Some areas may be missed during treatment because the redness and swelling may becomeconfluent, and it may be difficult to distinguish the treated areas. A template or other skinmarking method can be helpful. A polarized light source with a magnifying loop (SyrisScientific LLC, Gray, ME) allows visualization of individual follicles, helping to define thetreated area.
Additionally, within several days of treatment there is a phenomenon in which hair casts, car-bonized by the laser, will be shed from the hair follicle. Patients may believe that these areregrowing hair. These hair casts can be pulled out easily with tweezers.
There is an additive effect for a second treatment. Second treatments should be given when thehair begins to regrow. This will occur at different times for different anatomical areas. For theface, armpit, and bikini it is usually after one to two months. On other sites such as the backand legs, the growth delay is usually two to three months. Follow-upPerifollicular swelling and redness are desired clinical endpoints. They indicate that the patienthas been treated with an appropriate fluence. The sunburned feeling and swelling usually lastone to three hours. Applying ice will give relief and reduce the swelling duration. A topicalcortisone cream can also be used. Redness can last for a few days, but can by easily covered byapplying makeup. If there are signs of epidermal damage, the patient should use an antibioticointment, or call if there are problems. Patients should avoid sun exposure.
Both temporary and long-term hair reduction can be achieved safely and effectively with theLightSheer Diode Laser. By matching pulse duration and fluence to specific hair color, skin color and type, the laser caneffectively treat a broad range of patients with excellent results. Eighty-nine percent of patientsstudied experienced long-term hair loss, and 100% had short-term hair loss. These results wereachieved with few, if any, adverse side effects.
Copyright 1999 Coherent and its logo are registered trademarks of Coherent, Inc. LightSheer™ and ChillTip™ are trademarks of Coherent, Inc.
Herbal Excipients in Novel Drug Delivery SystemsA. SHIRWAIKAR*, ANNIE SHIRWAIKAR1, S. LAKSHMANA PRABU AND G. ARAVIND KUMARDepartment of Pharmaceutics, 1Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Manipal-576 104, India Shirwaikar, et al.: Herbal excipients in NDDS The use of natural excipients to deliver the bioactive agents has been hampered by the synthetic materials. However advantages offered by these natural excipients are their being non-toxic, less expensive and freely available. The performance of the excipients partly determines the quality of the medicines. The traditional concept of the excipients as any component other than the active substance has undergone a substantial evolution from an inert and cheap vehicle to an essential constituent of the formulation. Excipients are any component other than the active substance(s) intentionally added to formulation of a dosage form. This article gives an overview of herbal excipients which are used in conventional dosage forms as well as novel drug delivery systems.