Oral intake of bucillamine, carvedilol, metformin, or phenformin does not protect against UVR-induced squamous cell carcinomas in hairless mice.

Squamous cell carcinoma represents the second most common type of keratinocyte carcinoma with ultraviolet radiation (UVR) making up the primary risk factor. Oral photoprotection aims to reduce incidence rates through oral intake of photoprotective compounds. Recently, drug repurposing has gained traction as an interesting source of chemoprevention. Because of their reported photoprotective properties, we investigated the potential of bucillamine, carvedilol, metformin, and phenformin as photoprotective compounds following oral intake in UVR-exposed hairless mice. Tumour development was observed in all groups in response to UVR, with only the positive control (Nicotinamide) demonstrating a reduction in tumour incidence (23.8%). No change in tumour development was observed in the four repurposed drug groups compared to the UV control group, whereas nicotinamide significantly reduced carcinogenesis (P = 0.00012). Metformin treatment significantly reduced UVR-induced erythema (P = 0.012), bucillamine and phenformin increased dorsal pigmentation (P = 0.0013, and P = 0.0005), but no other photoprotective effect was observed across the repurposed groups. This study demonstrates that oral supplementation with bucillamine, carvedilol, metformin, or phenformin does not affect UVR-induced carcinogenesis in hairless mice.

Highlighting nuances of blue light phototherapy: Mechanisms and safety considerations.

The efficacy of blue light therapy in dermatology relies on numerous clinical studies. The safety remains a topic of controversy, where potentially deleterious effects were derived from in vitro rather than in vivo experiments. The objectives of this work were (1) to highlight the nuances behind "colors" of blue light, light propagation in tissue and the plurality of modes of action; and (2) to rigorously analyze studies on humans reporting both clinical and histological data from skin biopsies with focus on DNA damage, proliferation, apoptosis, oxidative stress, impact on collagen, elastin, immune cells, and pigmentation. We conclude that blue light therapy is safe for human skin. It induces intriguing skin pigmentation, in part mediated by photoreceptor Opsin-3, which might have a photoprotective effect against ultraviolet irradiation. Future research needs to unravel photochemical reactions and the most effective and safe parameters of blue light in dermatology.

Is paradoxical hair growth caused by low-level radiant exposure by home-use laser and intense pulsed light devices?

INTRODUCTION AND OBJECTIVES: This qualitative review of paradoxical hair growth, following professional treatments reviews, clarifies whether low fluence is the most probable cause of unwanted hair regrowth after at home light-based treatments. MATERIALS AND METHODS: The proposed causes of unexpected hair regrowth are examined, and our scientific understanding of absorption and scattering of light in turbid tissue is reviewed. Published reports of paradoxical hair growth are assessed. RESULTS: Early laser hair removal studies failed to record the occurrence of hair induction despite the significant numbers of subjects treated. Neither published paradoxical hair growth studies following home-based laser or intense pulsed light (IPL) hair removal treatments, nor randomised or controlled studies documenting paradoxical hair growth following professional treatments could be found. Several authors directly proposed inflammatory response to be the primary cause of hair growth induction. CONCLUSIONS: It is unlikely that hair regrowth several centimetres or more away from the irradiated tissue can be attributed to the laser or IPL used. In many cases of paradoxical hair growth, other causes may be responsible for the unexpected hair growth. The primary cause of instances of 'true' paradoxical hair growth is probably limited to darker phototypes with one or more other characteristics including polycystic ovarian syndrome or other androgen hormonal irregularities following high energy treatments with the corresponding inflammatory sequelae.

Fractional CO2 laser resurfacing for atrophic acne scars: a randomized controlled trial with blinded response evaluation.

BACKGROUND: The treatment of acne scars with fractional CO(2) lasers is gaining increasing impact, but has so far not been compared side-by-side to untreated control skin. OBJECTIVE: In a randomized controlled study to examine efficacy and adverse effects of fractional CO(2) laser resurfacing for atrophic acne scars compared to no treatment. METHODS: Patients (n = 13) with atrophic acne scars in two intra-individual areas of similar sizes and appearances were randomized to (i) three monthly fractional CO(2) laser treatments (MedArt 610; 12-14 W, 48-56 mJ/pulse, 13% density) and (ii) no treatment. Blinded on-site evaluations were performed by three physicians on 10-point scales. Endpoints were change in scar texture and atrophy, adverse effects, and patient satisfaction. RESULTS: Preoperatively, acne scars appeared with moderate to severe uneven texture (6.15 ± 1.23) and atrophy (5.72 ± 1.45) in both interventional and non-interventional control sites, P = 1. Postoperatively, lower scores of scar texture and atrophy were obtained at 1 month (scar texture 4.31 ± 1.33, P < 0.0001; atrophy 4.08 ± 1.38, P < 0.0001), at 3 months (scar texture 4.26 ± 1.97, P < 0.0001; atrophy 3.97 ± 2.08, P < 0.0001), and at 6 months (scar texture 3.89 ± 1.7, P < 0.0001; atrophy 3.56 ± 1.76, P < 0.0001). Patients were satisfied with treatments and evaluated scar texture to be mild or moderately improved. Adverse effects were minor. CONCLUSIONS: In this single-blinded randomized controlled trial we demonstrated that moderate to severe atrophic acne scars can be safely improved by ablative fractional CO(2) laser resurfacing. The use of higher energy levels might have improved the results and possibly also induced significant adverse effects.

Hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in a rat model of acute hyperammonemia.

UNLABELLED: Intravenous infusion of magnesium sulfate prevents seizures in patients with eclampsia and brain edema after traumatic brain injury. Neuroprotection is achieved by controlling cerebral blood flow (CBF), intracranial pressure, neuronal glutamate release, and aquaporin-4 (Aqp4) expression. These factors are also thought to be involved in the development of brain edema in acute liver failure. We wanted to study whether hypermagnesemia prevented development of intracranial hypertension and hyperperfusion in a rat model of portacaval anastomosis (PCA) and acute hyperammonemia. We also studied whether hypermagnesemia had an influence on brain content of glutamate, glutamine, and aquaporin-4 expression. The study consisted of three experiments: The first was a dose-finding study of four different dosing regimens of magnesium sulfate (MgSO4) in healthy rats. The second involved four groups of PCA rats receiving ammonia infusion/vehicle and MgSO4) /saline. The effect of MgSO(4) on mean arterial pressure (MAP), intracranial pressure (ICP), CBF, cerebral glutamate and glutamine, and aquaporin-4 expression was studied. Finally, the effect of MgSO4 on MAP, ICP, and CBF was studied, using two supplementary dosing regimens. In the second experiment, we found that hypermagnesemia and hyperammonemia were associated with a significantly higher CBF (P < 0.05, two-way analysis of variance [ANOVA]). Hypermagnesemia did not lead to a reduction in ICP and did not affect the brain content of glutamate, glutamine, or Aqp-4 expression. In the third experiment, we achieved higher P-Mg but this did not lead to a significant reduction in ICP or CBF. CONCLUSION: Our results demonstrate that hypermagnesemia does not prevent intracranial hypertension and aggravates cerebral hyperperfusion in rats with PCA and hyperammonemia.

Paring and intense pulsed light versus paring alone for recalcitrant hand and foot warts: a randomized clinical trial with blinded outcome evaluation.

BACKGROUND AND OBJECTIVES: Treatment of recalcitrant viral warts remains a therapeutic challenge. Intense pulsed light (IPL) has been suggested effective to clear wart tissue. The objective was in a randomized controlled trial to assess the efficacy of paring followed by IPL versus paring alone for recalcitrant hand and foot warts. MATERIALS AND METHODS: Eighty-nine patients with recalcitrant hand and foot warts were included and randomized (1:1) to three treatments at 3-week intervals with either paring of warts followed by IPL or paring of warts alone. IPL was given with the Ellipse Flex IPL system (Danish Dermatologic Development A/S, Hørsholm, Denmark, 400-950 nm, 5.5 millisecond pulse duration in double pulses with a 2 millisecond interval, 26.0-32.5 J/cm(2) repetitive passes). The primary outcome was complete and partial clearance of warts evaluated by blinded photo assessment at 6 weeks after final treatment. Secondary outcomes were treatment related pain and adverse reactions. RESULTS: We found no significant difference in clearance of warts between the two intervention groups (OR 1.64, 95% confidence interval 0.62-4.38). Paring followed by IPL resulted in complete or partial clearance of wart tissue in nine (22%) and five patients (12.2%) versus five (13.5%) and four patients (10.8%) from paring alone. Mostly plantar warts were treated (92.1%). The pain intensity after paring and IPL was moderate and significantly higher than the pain intensity after paring alone (P<0.0005). No adverse reactions were observed from the two interventions. CONCLUSION: Paring followed by IPL did not differ significantly from paring alone in clearance of recalcitrant hand and foot warts but caused significantly more pain.

Low density, non-ablative fractional CO2 laser rejuvenation.

BACKGROUND AND OBJECTIVES: Fractional skin rejuvenation has gained increased interest since its introduction in 2003. Both non-ablative and ablative lasers as well as different treatment techniques have been devised. Recent clinical studies indicate that a paradigm of low spot density combined with high fluences tend to produce better clinical results and less risk of post-inflammatory hyperpigmentation in darker skin types. The present study is focused on investigations of the clinical outcome by non-ablative fractional CO(2) treatments with a single pass with low spot density. METHODS AND MATERIALS: A CO(2) laser was equipped with a scanner enabling it to perform fractional treatments with 36, 64 or 100 microthermal zones (MTZ)/cm(2). Twelve patients participated in the study. The perioral area was treated three times with 1-month intervals using a spot density of 64 MTZ/cm(2), a spot diameter of 0.5 mm, a micro-beam energy of 36-60 mJ, and a pulse duration of 3-5 milliseconds. Follow-up was performed 3 months after the last treatment. RESULTS: At the 3-month follow-up 72.7% of the volunteers had obtained improvement in ultrasonographically determined dermal density, and the average improvement was 40.2% (SD: 48.0%). This improvement was statistically significant (P<0.006). Eighty percent of the volunteers rated the reduction in visible perioral wrinkles to be fair, good or excellent. For reduction of irregular pigmentation, fair, good or excellent clearance was reported by 62.5% of the volunteers. CONCLUSIONS: The present study demonstrates subjective improvements in wrinkles, skin texture and mottled pigmentation as well as statistically significant objectively measured improvements in ultrasonographical dermal density after three non-ablative fractional CO(2) laser treatments.

Relevance of the structure of time-resolved spectral output to light-tissue interaction using intense pulsed light (IPL).

BACKGROUND AND OBJECTIVES: High quality IPLs can offer simple, safe and effective treatments for long-term hair removal, removal of benign vascular and pigmented skin abnormalities, skin rejuvenation and acne treatments. Significant differences in clinical outcome have been recorded among different free-discharge and constant current IPLs despite identical settings. We investigated the differences in optical output of 19 IPLs in normal clinical use in the UK to evaluate spectral output, energy density values and pulse structure and propose a correlation between light-tissue interaction and spectral output as measured by time-resolved photo-spectrometry. STUDY DESIGN/MATERIALS AND METHODS: Using a fast spectrometer, generating 1,000 full spectral scans per second, time resolved spectral data of IPL outputs was captured with a resolution of 0.035 nm. IPL spectral outputs were calculated and graphically modelled using MathCAD software for comparison. RESULTS: Several IPLs, which professed matching of pulse durations to the thermal relaxation times of specific follicular or vascular targets were shown to have effective pulse durations that were vastly shorter than those claimed. Some IPLs claiming 'square pulse' characteristics failed to show constant spectral output across the duration of the pulse or sub-pulses. CONCLUSIONS: This study provides a suitable method to determine accurately key parameters of the emitted light pulses from IPLs and confirms the direct correlation between the electrical discharge current profile and the output energy profile. The differences measured between first generation free discharge systems and modern square pulse systems may have important clinical consequences in terms of different light-tissue interactions and hence clinical efficacy and safety. IPL manufacturers should provide time-resolved spectroscopy graphs to users.

A comparative study of intense pulsed light alone and its combination with photodynamic therapy for the treatment of facial acne in Asian skin.

BACKGROUND AND OBJECTIVES: The reaction to intense pulsed light (IPL) on Asian skin often differs from that on Caucasian skin. The study reported herein evaluated the effect on acne vulgaris of IPL alone and when IPL was combined with photodynamic therapy (PDT) using topical methyl aminolevulinate (MAL) in Asians. STUDY DESIGN/MATERIALS AND METHODS: Thirty Chinese subjects with phototypes IV or V and moderate acne were enrolled for a randomized, half-facial treatment study with IPL alone, IPL with PDT, or as controls. Sixteen percent MAL cream was applied to half of the face 30 minutes before treatment in the PDT group. The IPL was provided by the Ellipse Flex system (Danish Dermatologic Development, Denmark), which emitted wavelengths of 530 to 750 nm. The subjects were treated four times at 3-week intervals. Single passes of double pulses with a 10 milliseconds delay and a pulse duration of 2.5 milliseconds were used. The assessment of inflammatory and non-inflammatory acne lesions by two blinded investigators was based on standardized photographs that were taken before each treatment, and at 4 and 12 weeks after the final treatment. RESULTS: Twenty-three patients completed the study. The mean reduction of the inflammatory lesion count was 53% in the PDT group, 22% in the IPL group, and 72% in the control group at 4 weeks, and 65% in the PDT group, 23% in the IPL group, and 88% in control group at 12 weeks. The mean clearance of non-inflammatory lesions was 52% in the PDT group, 15% in the IPL group, and 14% in the control group at 4 weeks, and 38% in the PDT group and 44% in the IPL group at 12 weeks, when and an increase of 15% was noted in the control group. Most patients experienced a reduction of inflammatory lesions that was not statistically significant on the PDT-treated side (P = 0.06) or the IPL-treated side (P = 0.82) at 12 weeks after treatment. Pretreatment with MAL resulted in a better clearance of inflammatory acne than IPL alone. There were no statistically significant differences between the intervention groups and the control group in the mean reduction of inflammatory lesions. Significant reductions of non-inflammatory lesions were observed in the MAL-PDT group (38%, P = 0.05) and IPL groups (43%, P = 0.00) 12 weeks after treatment. Twenty-five percent of the subjects in the PDT group withdrew because of intolerance to procedure-related discomfort. CONCLUSIONS: MAL-PDT using IPL and MAL in Asians did not lead to significant improvement of moderate inflammatory acne compared with the control group. However, there was a delayed effect on non-inflammatory lesions, with significant reductions in both the PDT and IPL groups. A proportion of patients could not tolerate the discomfort that was related to PDT despite the short MAL incubation.

Skin rejuvenation using intense pulsed light: a randomized controlled split-face trial with blinded response evaluation.

OBJECTIVE: To evaluate efficacy and adverse effects of intense pulsed light rejuvenation in a homogeneous group of patients. DESIGN: Randomized controlled split-face trial. SETTING: University dermatology department. PATIENTS: Thirty-two female volunteers with Fitzpatrick skin type I through III and class I or II rhytids. INTERVENTIONS: Subjects were randomized to 3 intense pulsed light treatments at 1-month intervals or to no treatment of right or left sides of the face. MAIN OUTCOME MEASURES: Primary end points were skin texture and rhytids. Secondary end points were telangiectasia, irregular pigmentation, and adverse effects. Efficacy was evaluated by patient self-assessments and by blinded clinical and photographic evaluations up to 9 months after final treatment. Adverse effects were assessed clinically and by noninvasive skin reflectance measurements. RESULTS: Skin texture was significantly improved at all clinical assessments except at the 6-month examination (P<.006). The improvements peaked at 1 month after treatment, at which time 23 (82%) of 28 patients had better appearances of treated vs untreated sides. Most patients obtained mild or moderate improvements, and 16 patients (58%) self-reported mild or moderate efficacy on skin texture. Rhytids were not significantly different on treated vs untreated sides, and 19 patients (68%) reported uncertain or no efficacy on rhytids. Significant improvements of telangiectasia (P<.001) and irregular pigmentation (P<.03) were found at all assessments. Three patients withdrew from the study because of pain related to treatment. CONCLUSIONS: Three intense pulsed light treatments improved skin texture, telangiectasia, and irregular pigmentation but had no efficacy on rhytids. Adverse events were minimal, but included scar in 1 patient.

[Free versus non-free treatments with laser and intense pulsed light in dermatology: distinguishing medical laser treatments to be provided free of charge from cosmetic self-payment treatments]. / Dermatologisk behandling med laser og intenst pulserende lys: afgraensning af medicinske vederlagsfri versus kosmetiske ikkevederlagsfri behandlinger.

Lasers and light sources are increasingly used in dermatology. Due to the limited financial resources of the public health care system, the Danish Dermatological Society has developed recommendations for distinguishing medical laser treatments to be provided free of charge from cosmetic self-payment treatments. Several considerations underlie the recommendations: present legislation; the diagnosis, etiology, severity, and anatomical location of the disease; and the availability of evidence-based treatments. It is suggested that the recommendations constitute the basis for referring patients to dermatological treatment involving laser and intense pulsed light in Denmark.

420 nm intense continuous light therapy for acne.

BACKGROUND: Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy. However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity. Describe here is a high-intensity, narrow-band, blue light (ClearLight) system, and its therapeutic clinical effect is investigated on acne using cutaneous measurements, bacterial observations and ultrastructural changes. MATERIALS AND METHODS: A total of 28 adult healthy volunteers with facial acne (mean age 28.1 years, range 16-56 years) were recruited for this study. They were treated with a total of eight serial biweekly 15-minute treatment sessions. Clinical counts of acne, as well as moisture, sebum and pH measurements were taken between each session. Nine of the 28 patients were followed for 2-3 months after the last treatment. Detection of bacteria in acne pustules was analyzed by culture and by polymerase chain reaction (PCR). Ultrastructural changes were examined in eight patients after four sessions of the light therapy. RESULTS: All patients completed the study. Overall, there was a 64.7% improvement in acne lesions. There were no bacterial changes before or after the therapy, although damaged Propionibacterium acnes were observed at the ultrastructural level. CONCLUSIONS: ClearLight performed eight times over 4 weeks can be useful in the treatment of acne. Further investigation will be needed to elucidate the mechanism of action of ClearLight.

Facial photo rejuvenation using two different intense pulsed light (IPL) wavelength bands.

BACKGROUND AND OBJECTIVES: Intense pulsed light (IPL) systems are increasingly used for treatment of photo damaged skin. In the present study, we investigated the clinical efficacy and safety of two different wavelength bands generated by the same IPL device. STUDY DESIGN/MATERIALS AND METHODS: An IPL device was equipped with either a 555-950 nm filter (VL), or a 530-750 nm filter (PR). RESULTS: Fair, good or excellent clearance of visible telangiectasias was obtained in 81.8% of the patients (PR) and in 58.8% (VL). In the treatment of diffuse erythema, fair, good or excellent clearance was obtained in 72.7% (PR) and in 35.0% (VL). The PR filter was more efficient (P = 0.025) in reduction of diffuse erythema. The average number of treatments was 1.75 (PR) and 1.82 (VL). For the treatment of irregular pigmentation, fair, good or excellent clearance was obtained in 54.5% (PR) and in 61.9% (VL). Multiple treatments of irregular pigmentation were also evaluated. Using the VL filter more than two treatments did not induce further clinical improvement. The patients also scored their over-all satisfaction. Either fair, good or excellent results were reported by 66.7% (PR) and by 76.2% (VL). No skin atrophy, scarring or pigment disturbances were noted after the treatments. Swelling and erythema were registered by 2/3 (PR) and 1/3 (VL) of the patients. CONCLUSIONS: The two IPL wavelength bands were both found to be effective in the treatment of photo damaged facial skin. The clinical efficacy and safety of the two different treatment procedures were comparable to those reported in earlier studies, and finally treatment with these filter combinations required less than half the fluence, no active cooling and fewer treatments.

Dermal collagen production following irradiation by dye laser and broadband light source.

BACKGROUND: Improvement in the appearance of wrinkles has been observed following exposure to short-pulsed 585 nm laser light. The assumed effect is a specific absorption of light in the blood vessels of the superficial dermis, resulting in release of inflammatory mediators into the interstitium followed by stimulated fibroblast activity. The fibroblasts effectively initiate tissue repair mechanisms, which include enhanced new collagen production. METHODS: Quantitative measures of collagen synthesis rate in the skin can be obtained from determinations of the aminoterminal propeptide of type III procollagen level in suction blister fluid using a radioimmunoassay. RESULTS: A single laser treatment at subpurpura energy level showed that the 585 nm laser source induced an increase of 84% (p < 0.05) in the type III procollagen production rate compared with a non-treated control site. A broadband, pulsed, white light source at 4 J/cm(2) showed no measurable increase, whilst the skin area treated with 7 J/cm(2) increased the procollagen production rate by 17% (NS, p > 0.05). A second treatment 2 weeks later further improved the laser-induced increase in procollagen production rate to 148% (p < 0.05) compared with the control site. The broadband, pulsed, white light-irradiated skin sites showed that at 4 J/cm(2) the procollagen production rate was increased by 21.4% and at 7 J/cm(2) by 32.1% compared with the corresponding non-treated control site (NS, p > 0.05). CONCLUSIONS: Irradiation by the haemoglobin-specific short-pulsed 585 nm laser induced a fivefold increase in procollagen production rate compared with a biologically comparable fluence delivered in a broadband spectrum. An additional treatment after 2 weeks further increased the effect of the short-pulsed 585 nm laser to 148% of the control. Vascular-specific light/tissue interactions seem to play a key role in stimulating skin collagen production.

Quantitative evaluation of hypnotically suggested hyperaesthesia and analgesia by painful laser stimulation.

The ability to reduce both clinically and experimentally induced pain by hypnotic suggestion of analgesia is well known. However, the nature of hypnotic analgesia still remains uncertain. Attempts to demonstrate and identify specific psychophysiological mechanisms have, so far, been unsatisfactory. Methodological problems in inducing pain and monitoring physiological responses may be the reason for this lack of success. In the present study, we have attempted to eliminate some of these methodological problems. The sensory and pain thresholds to laser stimulation were determined, and the laser-evoked brain potentials were measured for 8 highly hypnotically susceptible subjects in 3 conditions: (1) waking state, (2) suggestion of hyperaesthesia, (3) suggestion of analgesia. The thresholds were reduced during induced hyperaesthesia and increased during analgesia. During hyperaesthesia sensations could be evoked by laser intensities which were below intensities that could be perceived in the awake state. The amplitude of the evoked brain potentials increased during hyperaesthesia and decreased during analgesia. The latency of the potential remained constant. The perception of pain during hypnosis can change very fast, indicating that slow endogenous mechanisms may play only a minor role in suggested hyperaesthesia/analgesia.