Honorary senior lecturer, Hull York Medical School
Tutor in laparoscopic surgery
Royal College of Surgeons of England,
London, UK
Injury to the papillary dermal vessels not only allows effective treatment of facial telangiectasia medicine man pharmacy discount antivert 25mg fast delivery, but also leads to the subsequent healing process and new collagen formation symptoms 16 weeks pregnant order antivert 25 mg. Producing an effect on the microvascular supply of the sebaceous gland can reduce sebum production and improve pore size (17 20) symptoms quadriceps tendonitis cheap antivert 25 mg online. Near-infrared and infrared lasers/light sources together with skin cooling target the water content in the dermis translational medicine order antivert 25mg mastercard, and their photothermal effect, produced as a result of the lasertissue interaction, is to cause a rise in the dermal temperature (21 24). The consequences are collagen tightening, increased fibroblastic activity, and increased collagen production. Table 2 summarizes the use of different lasers for nonablative skin rejuvenation in ethnic skin. For non-ablative skin rejuvenation, repeated monthly treatment intervals are necessary to achieve the desired effect. More recently, combined modalities using different lasers and light sources in the same treatment session have been advocated (17,18,20). To reduce the risk of complications from such a combined approach, lower fluence is necessary. Although the results of some studies support the use of non-ablative skin rejuvenation for the treatment of acne scarring, ablative skin resurfacing can achieve a significantly superior result and therefore remains the gold standard for the treatment of acne scarring in ethnic skin. For laser resurfacing, patients are prescribed a systemic antiviral (Famciclovir 250 mg three times daily) and a systemic antibiotic (cefuroxime 250 mg three times daily) 48 hours before laser surgery and until complete re-epithelization. To further optimize the result, a punch biopsy and subcision two weeks before surgery is recommended. More recently, single pass laser resurfacing has been recommended by some investigators to reduce the morbidity that is associated with this procedure (25). Postoperatively, a closed dressing is applied for 48 hours, followed by an open dressing thereafter. Fractional resurfacing is a new technology that involves the use of a laser to generate microscopic spots of thermal injury that are surrounded by healthy skin tissue (26). By taking into account the discrepancy between epidermal and dermal healing properties (given the microscopic nature of the lesion, epidermal healing is completed within 24 hours, whereas dermal collagen remodeling takes 4 6 weeks), fractional resurfacing can lead to excellent clinical outcomes with minimal adverse effects. The initial device involves the use of a scan to deliver laser injury when the device moves across the skin surface (scanning mode), and the others involve the placement of the laser handpiece on the skin surface in a stamping fashion (stamping mode). The advantages and disadvantages of these two different modes are summarized in Table 3. For ethnic skin, fractional resurfacing can be particularly effective for the treatment of acne scarring, and is the main indication for its use. The degree of inflammation and the extent of derma-epidermal junction disruption are also important. The interval between treatment sessions can also be increased so that inflammation at the dermaepidermal junction can completely subside. The use of cooling is also important to reduce the risk of bulk tissue heating that occurs after repeat treatment at a short interval. As a result, it is common for laser to be used for the treatment of congenital melanocytic lesions in ethnic skin. Furthermore, categorization of the patches into histological subtypes did not help to predict the clinical outcome. One treatment with long-pulsed Alexandrite 755 nm laser, 40 J/cm2, 10 mm spot size, 3 ms pulse duration. Long-pulsed pigmented laser has also been used to remove hair and reduce pigmentation, but texture can still occur (34). The side effects were few, with transient hyperpigmentation after the first treatment being the most common (35). The original pigmentation could also recur in patients after complete laser-induced clearing, which is an important issue, especially for pediatric patients. Nevertheless, treatment is optimal at a younger age as there is a lower number of mean treatments and a lower rate of complications (40). Transit pigmentary disturbance is the main adverse effect, with hyperpigmentation particularly common during the first few treatment sessions. Melasma the results of previous studies have discouraged the use of laser in the treatment of melasma. The cause for such unwanted effects is unknown, but is probably related to the pathogenesis of melasma. It has been suggested that in epidermal and mixed type melasma, which is characterized by epidermal hyperpigmentation, the pathogenesis involves an increased number of melanocytes and increased activity of melanogenic enzymes overlying dermal changes that are caused by solar radiation (48). This may explain the development of hyperpigmentation after the use of pigment laser for treatment. An increase in melanogenic enzyme activity suggests that melanocytes are hyperactive. Sublethal laser damage to these melanocytes by pigment lasers can increase the production of melanin and result in hyperpigmentation. The prolonged use of topical treatment is necessary as it does require more than six weeks for the follicular melanocytes to be affected. Even with the prolonged application of topical treatment, there is still a risk of hyperpigmentation. Despite, three months use of topical bleaching agents before recruitment into the study, two patients in the treatment group developed increases in pigmentation. To prevent increases in pigmentation, low fluence is essential, and one should look for the mildest clinical endpoint. In a small-scale study, 60% of the treated subjects were found to have a significant degree of improvement, 30% had a mild degree of improvement, and 10% had an increase in pigmentation (51). Fractional resurfacing in this study involved the formation of melanocytic epidermal necrotic debris that acted as a melanocytic shuttle and effectively removed epidermal pigmentation. Other factors that may contribute to the effectiveness of fractional resurfacing in the treatment of melasma include transit impairment of the epidermal barrier function, which allows better absorption of the topical agents, and ablative removal of abnormal hyperactive melanoctyes. Advocates have proposed that by reducing the melanocytic mass of the nevi, the risk of neoplastic changes can be reduced. Opponents are skeptical because there have been cases in which the use of laser delayed the diagnosis of melanoma or contributed to an incorrect diagnosis. Furthermore, whether there are long-term complications, such as increased risk of neoplastic changes, is not known. Whereas the use of laser for the treatment of melanocytic nevi in Caucasians is controversial, there are more justifications for doing so with dark-skinned patients (52). First, unlike in the Caucasian population, melanoma is less common among darker-skinned patients; genetic difference rather than a difference in skin type is likely to be the main reason. Furthermore, the only long-term follow up study looking at the use of laser for the treatment of congenital melanocytic nevi was from Japan, and it indicated no histological evidence of malignant changes eight years after normal ruby laser treatment for congenital nevi (53). As a result, the use of laser for the removal of melanocytic nevi can be justified in ethnic skin, provided that there is no family history of melanoma and the lesion is not acral in nature. In terms of the treatment approach, various pigmented lasers have been used in the removal of melanocytic nevi. However, other studies showed that depending on the depth of the nests of melanocytes, recurrence could be a problem. A previous study found that although 52% of the nevi showed a visible decrease in pigment, no lesion had complete histological clearance. Subtle microscopic scarring of the underlying nevus cells was considered to be important in creating the appearance of a significant reduction in pigmentation. For effective treatment, laser energy must be transmitted unimpeded through the skin toward the intended target of melanin within the hair shaft and follicle. The selective destruction of the melanin within the hair follicle, while sparing epidermal melanin is possible through the process of thermokinetic selectivity, which is a corollary of the theory of selective photothermolysis (58,59). Smaller structures (epidermal melanocytes) dissipate heat more quickly than larger structures of the same chromophore with a greater surface to volume ratio (hair follicle). The ability of these smaller structures to dissipate heat more quickly acts as a protective mechanism. Newer generation laser hair removal devices incorporate longer pulse durations and a variety of cooling devices, thus allowing the safer treatment of dark skin. Initial studies with the long-pulsed Alexandrite laser (60,61) demonstrated effective hair removal in darker skin with pulse durations of 40 ms and fluences of 11 to 15 J/cm. Lengthening the pulsewidth to 200 ms (62) and using the long-pulsed diode laser resulted in effective hair removal and no post treatment dyschromia. Transient adverse effects were erythema and perifollicular edema, and only one patient developed hypopigmentation, at week six, which resolved by week 36. Laser assisted hair removal is now a successful treatment for hypertrichosis and pseudofolliculitis barbae.
Diseases
Environment associated hypertension
Neurosyphilis
Penis agenesia
Angiosarcoma
Thost Unna palmoplantar keratoderma
Occult spinal dysraphism
Ouvrier Billson syndrome
Pterygium colli
Agranulocytosis due to treatment with phenothiazines was reported already in the fifties [21] treatment 1860 neurological buy antivert 25 mg cheap. Clinical symptoms can be observed 20 to 40 days after the onset of treatment medicine 018 cheap 25 mg antivert otc, and bone marrow investigations disclose marked marrow hypocellularity treatment dry macular degeneration cheap antivert 25 mg without a prescription. However nail treatment cheap antivert 25 mg on line, clozapine, the first atypical drug, is known to cause an annual incidence of 8000 cases of agranulocytosis/million patients [2]. To our knowledge this investigation is the only published prospective study in this area. Seven cases of agranulocytosis were detected, one while on clozapine and six while on perazine (three in combinations with other drugs) [19]. So far no risk rates for blood dyscrasia with the newer atypical neuroleptics have been published. Much less observations exist on the hematological risk profile of other groups of psychotropic changes, such as antidepressants [18]. In brief, in the naturalistic setting of routine psychiatric inpatient treatment all marketed psychotropic drugs are under surveillance. However, the participating hospitals also contribute largely as the drug monitors serve this function in addition to their usual routine work. The individual events are rated and classified according to the probability of a causal relationship between the application of a drug and the observed adverse event. There are five degrees: no (0), possible (1), probable (2) or definite (3) relationship assumed, or not assessable (4). In such cases, the drugs used in combination therapy are considered as common offenders if the time sequence does not allow a decision on the causative agent or if additive effects are assumed. Dosage, time sequence, and potential risk are taken into account for each drug separately, which may lead to different degrees of probability for the drugs in question in each case. Data on the drug utilization in the participating centers is derived from reference days (twice per year and hospital). The participating centers also provide information on the number of inpatients monitored per year as well as the mean duration of inpatient treatment for all monitored patients. The following definitions of severe drug-induced hematologic reactions are based on common hematological standards: thrombocytopenia: platelet counts < 100. Pancytopenia is defined as neutropenia and thrombocytopenia in combination with anemia. Blood Dyscrasias Induced ј Pharmacopsychiatry 2004; 37 Suppl 1: S70 ± S78 Leukocytes, neutrophils, and platelets are counted in newly admitted patients by all participating hospitals. Additionally, controls of the white blood cell counts are performed at least monthly during psychopharmacological treatment in about 75 % of the participating hospitals, and more frequently ± every 2 weeks ± in about 25 %. The number of patients exposed to a drug (or drug group) is predicted by data collected at two reference days per year from every hospital under surveillance and by the number of patients per year. In view of the very low rate of serious side effects and the large number of patients exposed, confidence intervals are calculated according to the exact (asymmetric) method first described by Clopper and Pearson [7], avoiding the bias of the commonly used approximate methods (for a discussion of methods see. Table 1 Hematological changes due to psychotropic drugs and presence of clinical signs. Only four of these cases were rated as definitely drug-related on the basis of a positive rechallenge (two cases of neutropenia, one of agranulocytosis, and one of pancytopenia), 75 were rated as probably drug-related, and 28 cases were rated as only Єpossiblyє drug-related. Clinical symptoms were present in three of the patients with thrombocytopenia (hemorrhage); six of those with neutropenia and seven of those with agranulocytosis had fever and/or infections. The imputed drugs were discontinued in 104 cases, in the remaining three their dosage was reduced. The highest rates of Єsevere neutropeniasє were observed during treatment with anticonvulsants. Among the typical neuroleptic drugs phenothiazines caused the highest incidence (0. For rarely used drugs, incidence rates may be an artifact and are not really comparable with that of drugs used more often. Blood Dyscrasias Induced ј Pharmacopsychiatry 2004; 37 Suppl 1: S70 ± S78 Table 2 Frequency of Єsevere neutropeniaє for different psychotropic drug groups and subgroups; all cases, and only cases rated as probably or definitely drug-related. All: drug or drug group was imputed alone or in combination with other drugs as probable or definite; imputed alone: only this drug or drug group was imputed with a probable or definite rating (that is, other drugs may be imputed as well but only with a possible rating). Exposed patients* All N N 91 21 19 66 6 16 12 29 7 12 4 4 1 Episodes with the drug all probabilities All n 72 21 8 43 1 8 7 27 1 6 0 2 1 16 5 39 1 7 7 25 0 4 0 1 1 Imputed alone n All (%) 0. Exposed episodes with the patients* drug, imputed at all alone n n incidence imputed at all alone (%) (%) 0. There was a clear peak of Єsevere neutropeniasє between the 20th and 30th day after onset of treatment. The time course of the clozapine-induced changes, however, showed another pattern: the main peak appeared later, between the 40th and 50th day of treatment. Trimipramine Lorazepam Carbamazepine Valproate As regards potential risk factors, the distribution of gender was nearly the same in the group of all surveyed patients Stьbner S et al. The age of the affected patients on clozapine (n = 27) showed a similar distribution to that of all patients having received clozapine (n = 15,414). After her hospitalization, venlafaxine and (briefly) indomethacine had been added. About 8 weeks after onset of venlafaxine, the dosage of which had reached 225 mg, neutrophil counts of 1. The bone marrow biopsy disclosed hypocellularity of hematopoiesis, which was interpreted as drug-induced toxic damage. Since the discontinuation of indomethacine did not lead to any improvement, venlafaxine was suspected for having possibly caused the hematologic changes. To our knowledge venlafaxine has not yet been reported to cause hematological changes. However, in this case the time course of the events strongly suggests a causal role for venlafaxine. As the patient also had an anemia due to iron deficiency, she also had to take ferrosulfate. After approximately 1 week of treatment, neutrophil counts were slightly reduced compared to those before treatment (2,900/ml versus 3,300/ml). Perazine was promptly discontinued, and 3 days later, the antibiotic treatment course was finished. In this case, perazine was imputed to be the probable causative agent, an additional effect of antibiotics on the severity of the neutropenia was rated as only possible, because neutrophils had begun to increase again the very first day after the last dose of cotrimoxazol. Patients often are treated with combinations of psychopharmacological drugs and in addition a medication for accompanying internal diseases. In one case both carbamazepine and lovastatine were rated as probable causative agents in combination, because the time course did not allow to distinguish between both drugs as being potentially responsible for pancytopenia. In the second case, pancytopenia was observed during a treatment with trimipramine. Thrombocytopenia Thrombocytopenia was observed in 20 patients (in four of these neutropenia was present simultaneously) and considered to be probably caused by psychotropic drugs in ten cases. In five of these episodes carbamazepine as combined treatment was involved (incidence 0. In one case only valproate was judged to be the cause; in the other four cases, perazine (twice), dibenzepine and risperidone were involved. Fourteen days after carbamazepine was added, she developed vertigo, nausea, and an exanthema with little spots. An internal consultation was made, and the drugs thought to cause the hematological changes were discontinued: carbamazepine probably, and atenolol, chlorthalidone, and clomipramine possibly caused the thrombocytopenia. As a consequence, lormetazepam had to be added, and lithium was applied in order to stabilize the mood. This treatment led to a rapid improvement of platelet counts and the clinical signs. Furthermore, it could be shown that discontinuation of the offending drugs generally leads to fast improvement of blood cell counts. In contrast, severe neutropenia during treatment with antidepressants was very rare (0. Discussion Our current investigation has extended over 8 years, and more than 120,000 patients have been under surveillance.
Neurofeedback for AttentionDeficit/Hyperactivity Disorder: Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials withdrawal symptoms buy antivert 25 mg with amex. Effects of methylphenidate on executive functioning in attention-deficit/hyperactivity disorder across the lifespan: a meta-regression analysis medications look up 25 mg antivert otc. Diagnostic Accuracy of Rating Scales for AttentionDeficit/Hyperactivity Disorder: A Metaanalysis symptoms 9 weeks pregnancy effective antivert 25 mg. Diagnostic value of resting electroencephalogram in attentiondeficit/hyperactivity disorder across the lifespan medications vitamins generic antivert 25mg online. Effect of Poly Unsaturated Fatty Acids Administration on Children with Attention Deficit Hyperactivity Disorder: A Randomized Controlled Trial. Cardiovascular measures in children and adolescents with attention-deficit/hyperactivity disorder who are new users of methylphenidate and atomoxetine. Health-related quality of life and functional outcomes from a randomizedwithdrawal study of long-term lisdexamfetamine dimesylate treatment in children and adolescents with attentiondeficit/hyperactivity disorder. Clinical response and symptomatic remission in children treated with lisdexamfetamine dimesylate for attention-deficit/hyperactivity disorder. A Secondary Analysis of a Prospective, 24Month Open-Label Study of Osmotic-Release Methylphenidate. Omega-3/omega-6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents. The effect of phosphatidylserine containing Omega3 fatty-acids on attention-deficit hyperactivity disorder symptoms in children: a double-blind placebo-controlled trial, followed by an openlabel extension. Homoeopathic management of attention deficit hyperactivity disorder: A randomised placebocontrolled pilot trial. The influence of short-chain essential fatty acids on children with attention-deficit/hyperactivity disorder: a double-blind placebo-controlled study. Long-term safety and efficacy of guanfacine extended release in children and adolescents with attention-deficit/hyperactivity disorder. Acute and Long-Term Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder. Effect of atomoxetine on Tanner stage sexual development in children and adolescents with attention deficit/hyperactivity disorder: 18month results from a double-blind, placebocontrolled trial. Efficacy and safety of methylphenidate and pemoline in children with attention deficit hyperactivity disorder. Comparative effects of methylphenidate and mixed salts amphetamine on height and weight in children with attention-deficit/hyperactivity disorder. Does extended medication with amphetamine or methylphenidate reduce growth in hyperactive children? Omega-3 fatty acid supplementation for the treatment of children with attention-deficit/hyperactivity disorder symptomatology: systematic review and metaanalysis. Parent-based therapies for preschool attention-deficit/hyperactivity disorder: a randomized, controlled trial with a community sample. Omega-3 fatty acid treatment of children with attention-deficit hyperactivity disorder: A randomized, double-blind, placebo-controlled study. Using mental health consultation to decrease disruptive behaviors in preschoolers: adapting an empiricallysupported intervention. Multimethod psychoeducational intervention for preschool children with disruptive behavior: two-year post-treatment follow-up. Multi-method psycho-educational intervention for preschool children with disruptive behavior: preliminary results at post-treatment. Multisetting assessment-based intervention for young children at risk for attention deficit hyperactivity disorder: Initial effects on academic and behavioral functioning. Outcomes of a multi-component intervention for preschool children at-risk for attentiondeficit/hyperactivity disorder. Practice Parameter for the Assessment and Treatment of Children and Adolescents With AttentionDeficit/Hyperactivity Disorder. Removed records with a registration date of December 31, 2004 or earlier; records with an enrollment start date of December 31, 2004 or earlier; records of recruiting studies; records with a population age above 17 years; studies that were explicitly designated as Phase 0 or 1-497 records. Total number of results for screening: 195 National Guidelines Clearinghouse (November 28, 2016) Platform: These studies adhere to the commonly held concepts of high quality, including the following: a clear description of the population, setting, approaches, and comparison groups; appropriate measurement of outcomes; appropriate statistical and analytical methods and reporting; no reporting errors; a low dropout rate; and clear reporting of dropouts. These studies are susceptible to some bias, but not enough to invalidate the results. They do not meet all the criteria required for a rating of good quality because they have some deficiencies, but no flaw is likely to cause major bias. The study may be missing information, making it difficult to assess limitations and potential problems. They have serious errors in design, analysis, or reporting; large amounts of missing information; or discrepancies in reporting. Healthrelated quality of life and functional outcomes from a randomized-withdrawal study of long-term lisdexamfetamine dimesylate treatment in children and adolescents with attention-deficit/hyperactivity disorder. Can computerized cognitive tests assist in the clinical diagnosis of attentiondeficit hyperactivity disorder. One-year prospective follow-up of pharmacological treatment in children with attention-deficit/hyperactivity disorder. Effect of n-3 supplementation on hyperactivity, oxidative stress and inflammatory mediators in children with attention-deficithyperactivity disorder. Omega-3/omega6 fatty acids for attention deficit hyperactivity disorder: a randomized placebo-controlled trial in children and adolescents. Theta-phase gammaamplitude coupling as a neurophysiological marker of attention deficit/hyperactivity disorder in children. Effectiveness of a telehealth service delivery model for treating attentiondeficit/hyperactivity disorder: a community-based randomized controlled trial. Safety of psychotropic drug prescribed for attention-deficit/hyperactivity disorder in Italy. The influence of shortchain essential fatty acids on children with attentiondeficit/hyperactivity disorder: a double-blind placebocontrolled study. Ginkgo biloba for attention-deficit/hyperactivity disorder in children and adolescents: a double blind, randomized controlled trial. Acute and LongTerm Cardiovascular Effects of Stimulant, Guanfacine, and Combination Therapy for Attention-Deficit/Hyperactivity Disorder. Ginkgo biloba in the treatment of attention-deficit/hyperactivity disorder in children and adolescents. Neurofeedback and cognitive attention training for children with attentiondeficit hyperactivity disorder in schools. Group therapy for adolescents with attention-deficit/hyperactivity disorder: a randomized controlled trial. List of Excluded Studies All studies listed below were reviewed in their full-text version and excluded for the reasons cited. Reasons for exclusion signify only the usefulness of the articles for this study and are not intended as criticisms of the articles. Not a Full Publication or Full Text Not Available Ang A, Hillhouse M, Jenkins J, et al. Cognitive effects of stimulant, guanfacine, and combined treatment in child and adolescent attention-deficit/hyperactivity disorder. Long-term safety and efficacy of lisdexamfetamine dimesylate by age subgroup in children and adolescents with attention deficit hyperactivity disorder. Relative efficacy of lisdexamfetamine dimesylate and osmotic controlled-release methylphenidate in attention-deficit/ hyperactivity disorder patients. Guanfacine extended release: Daytime sleepiness outcomes from a phase 3 clinical study in adolescents with attention-deficit/hyperactivity disorder. Prediction of stimulant response in patients with adhd utilizing acute medication challenge studies. Sleep disturbance in children and adolescents with adhd: Unique effects of medication, adhd subtype, and comorbid status. Impulsive choice in unmedicated and medicated children diagnosed with adhd: Examining the variables of reward type and adhd subtype. Neurofeedback as an intervention to improve reading achievement in students with attention deficit hyperactivity disorder, inattentive subtype.
Topical application of T4N5 liposomes for one year in patients with xeroderma pigmentosum resulted in decreased formation of new actinic kertoses and basil cell carcinomas treatment canker sore order 25 mg antivert fast delivery, as compared to the controlled group (43) symptoms week by week cheap antivert 25mg. Investigations are ongoing on the effect of this novel preparation as chemoprevention of skin cancers in otherwise healthy individual treatment 4 syphilis discount 25mg antivert otc. There exist only limited data on its action in humans symptoms low potassium antivert 25 mg low price, and more research is needed to see if photolyase works with all degrees of sunburn and whether it can reduce risk of skin cancer. Polypodium Leucotomos Polypodium leucotomos is an extract from a fern plant grown in Central America. It is available in the United States and in many parts of the world as an over-the-counter vitamin supplement. Miscellaneous Agents Other agents that have been reported to have photoprotective properties are listed in Table 7 (4). Understanding and labeling of photoprotectiveness of clothing have improved very significantly. Taken together, these developments are of great benefit to our patients in reducing the acute and chronic effects of sun exposure. Sensitivity to sunburn is associated with susceptibility to ultraviolet radiation-induced suppression of cutaneous cell-mediated immunity. Additional criteria and procedures for classifying over-the-counter drugs as generally recognized as safe and effective and not misbranded. Over-the-counter drug products; safety and efficacy review; additional sunscreen ingredients, [Docket No. Change of ultraviolet absorbance of sunscreens by exposure to solar-stimulated radiation. Sun protective clothing in Australia and the Australian/ New Zealand standard: an overview. Effectiveness of antioxidants (vitamin C and E) with and without sunscreens as topical photoprotectants. Effect of topically applied T4 endonucleaseV in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Evaluation of photolyase (Photosome) repair activity in human keratinocytes after a single dose of ultraviolet B irradiation using the comet assay. Oral Polypodium leucotomos extract decreases ultraviolet-induced damage of human skin. Whereas their benefit in preventing sunburn, actinic keratoses and squamous cell carcinomas is undisputed, their role in prevention of other forms of skin cancer is still controversial (4,5). In this chapter, some of the new developments in photoprotection will be reviewed. What is relatively new is the interest in (i) developing methods to quantify sun protection performance of fabrics, (ii) understanding how to engineer sun protection performance into fabrics, (iii) establishing procedures for labeling garments with sun protection information, and (iv) providing understandable guidelines to individuals about how to select garments (those labeled and not labeled for sun protection performance) for wearing out-of-doors on summer days. The focus in this chapter is to compare and contrast the use of fabric and topical sunscreens for sun protection effectiveness. Textiles may be regarded as the ideal sunscreen when compared with topical products and their ability to prevent sunburn. However, the common belief that clothings protect the skin reliably from sunburn and other sun-induced damages is not generally correct. Application of broad-spectrum sunscreens along with garment is part of the proper photoprotection strategy. Oral ingestion of vitamins E and C, carotenoids, and polyphenols, for example, from green tea, is commonly done (10). Amantadine, bufexamac, tryptophan, melatonin, propranolol, and hyaluronic acid were found to have antioxidative property, whereas pro-oxidative effects were shown with ascorbic acid. In vivo experiments with antioxidants should follow to allow in vitro in vivo correlation and clinical interpretation of the data. In a randomized clinical study of the effects of liposomal T4 endonuclease V in patients with xeroderma pigmentosum, the rate of formation of actinic keratoses and basal cell carcinoma was reduced by 68% and 30%, respectively, compared to the control group (13). With this technique, the organic filter is entrapped in the capsule, decreasing the probability of allergic, photoallergic, or irritant contact dermatitis. The drawback of this technology is that it is rather expensive, and thus only a few sunscreen manufacturers have incorporated it so far. Micronization the microfine inorganic pigments TiO2 and ZnO have been improved considerably to allow the easier incorporation into formulations and to become cosmetically better accepted, but some limitations still remain (18). Micronization to primary particle sizes of,20 nm results in less scattering of visible light, hence minimizing the whitening effect. Microfine ZnO has a more uniform but weaker absorption at the 290 to 380 nm than microfine TiO2. To minimize the photocatalysis, inorganic filters are frequently coated with aluminum oxide. In order to optimize formulating properties, a coating of dimethicone or silica may be added. A new development is the coating of TiO2 with,1% of manganese (19) (Optisolw, Oxonica Healthcare, Oxfordshire, U. B B B B Efficacy Safety Registration Patent freedom In this chapter, the focus will be to demonstrate how the efficacy of new sunscreen actives is achieved. Although direct comparison with a new pharmaceutical drug is not appropriate, the development of a new sunscreen active for global use is highly demanding. The toxicological studies required for a global registration are listed in Table 2 (22). In the European Union, South America, Asia, and Africa, where sunscreens are regulated as cosmetics, approval is possible within one to two years of filing. In Australia, Japan and, the United States, where sunscreens are regulated as over-the-counter medications, the approval process normally takes longer. Patent Freedom Patenting of sunscreen actives and their applications deserve special attention (21). Patent freedom means the free use of sunscreen actives by any sunscreen manufacturer, that is, any infringement of any third party patent rights must be avoided. It is water-soluble, that is, will be in the water phase of an emulsion system and can thus act synergistically together with filters in the oil-phase. Siloxane groups were added to the benzotriazole chromophore for better water resistance. The microfine organic particles are dispersed in the water phase, leading to a synergistic effect together with oil-soluble filters. Numerous investigations have demonstrated that photostability is of key importance to the filters in order to provide long-term protection of polymer substrates (e. This is due to the presence of two electronic transitions with strong dipole moments, both of which are polarized perpendicular to each other (shown in. The entire photo-tautomeric cycle only lasts about 10212 seconds, leaving no time for undesirable side reactions (e. It is an aqueous dispersion containing 50% of colorless organic microfine particles with a size below 200 nm. The next step is the submission of the safety package containing additional preclinical long-term dermal cancer and photo-cocarcinogenicity studies; safety data are evaluated prior to approval (33,34). The "500 Dalton rule," known from the development of transdermal drugs, can be seen as a common denominator. The 500 Dalton rule for the skin penetration of chemical compounds and drugs states that when topical dermatological therapy or percutaneous systemic therapy is the objective, the development of new innovative compounds should be restricted to molecular weights of under 500 Dalton (35). As shown in Figure 6, the development over the past 50 years is clearly heading in that direction. However, it should be noted that the 500 Dalton rule is neither a necessity nor a sufficient condition for the safety of a new sunscreen active. Understanding Sun Protection Factor Historically, the sole purpose of sunscreens was to prevent sunburn. However, the actual protection provided by a sunscreen is a dynamic process; therefore, it is also important to choose a representation of the sunscreen beyond the static view commonly seen. This is best illustrated in Figure 7, inspired by the Australian Standard document (38). Some exposed sites are frequently missed, and with regular or outdoor activities, sunscreens are rubbed off, or washed off with water and sweat exposure. The example shows the minimal erythema dose received by skin phototype 1 or 2 with the assumption that the sunscreen is photostable, and sunscreens are applied at a concentration of 2 mg/cm2. It took several decades to gain global acceptance and public understanding of this concept. There are several in vivo and in vitro methods available, and there is also the possibility to assess the performance of a sunscreen by computer simulation, that is, in silico (Table 4).
