Blockade of arginine vasotocin signaling reduces aggressive behavior and c-Fos expression in the preoptic area and periventricular nucleus of the posterior tuberculum in male Amphiprion ocellaris.

Many marine fishes change sex in response to social cues when the dominance hierarchy is perturbed. Arginine-vasotocin (AVT) and the mammalian homolog arginine vasopressin are neuropeptides involved in social and reproductive behaviors across vertebrate taxa. The goal of this study was to determine whether AVT signaling influences aggression and expression of c-Fos, a marker of neuroplasticity, in key brain regions of the social decision circuit in Amphiprion ocellaris clownfish, a species where behavioral dominance precedes gonadal sex change from male to female. In experiment 1, juvenile clownfish (average mass 2.5g) were paired together in a tank (a total of 24 pairs), matched approximately for size with one fish randomly receiving either an intraperitoneal injection of the arginine vasopressin V1a receptor antagonist (Manning compound) or saline vehicle, and evaluated for aggressive and submissive behaviors over a 10-min period. The second experiment was a repeat of the first using five pairs of mature, reproductive males, except the animals interacted for 90-min immediately followed by euthanasia for immunohistochemical detection of c-Fos protein. Numbers of c-Fos-positive cells were quantified in the preoptic area of the hypothalamus (POA), the anterior tuberal nucleus (aTn), and periventricular nucleus of the posterior tuberculum (TPp). Manning compound significantly reduced aggression and the probability of winning the contest relative to saline (vehicle) controls. In experiment 2, saline-treated fish displayed approximately twice as many c-Fos-positive cells in the POA and 25% more in the TPp than the Manning-treated fish, no differences were observed in the aTn. Taken together, results suggest AVT signaling is necessary for aggressive behavior and expression of neuroplasticity in the POA and TPp that likely contributes to behavioral dominance and hence, sex change in A. ocellaris.

Edema hemorrágico agudo en un lactante / Acute hemorrhagic edema of infancy

Niña de 20 meses de edad que había presentado la semana previa un cuadro catarral febril, en la que aparecieron placas edematosas, equimótico-purpúricas en las extremidades inferiores de forma simétrica, ni dolorosas a la palpación ni pruriginosas. No había lesiones en la cara y su estado general era bueno. Se realizó el diagnóstico de edema agudo hemorrágico del lactante (EAHL) por el aspecto clínico de las lesiones. Se le realizó un control evolutivo en el centro de salud, sin que requiriera tratamiento específico, y las lesiones desaparecieron completamente en el plazo de 2 semanas. El edema agudo hemorrágico del lactante es una vasculitis leucocitoclástica de pequeños vasos, con unas manifestaciones cutáneas muy llamativas, por el aspecto, la rapidez y la brusquedad de aparición de las lesiones, a pesar de lo cual tiene una evolución benigna, puesto que no hay afectación del estado general. El diagnóstico debe ser clínico y no es preciso instaurar ningún tratamiento (AU)

We present a case of a 20-month baby girl who had shown the previous week a febrile upper respiratory tract infection. During this process edematous plaques appeared, ecchymotic purpuric with symmetrical form on the lower extremities, they did not itch or were painful to touch. There were no lesions on the face and the patient's general medical state was satisfactory. A diagnosis of acute hemorrhagic edema of infancy (AHEI) was made based on the clinical aspect of the lesions. Regular checkups were performed in the clinic to monitor the progress of the condition and without requiring specific treatment the lesions disappeared completely within a period of two weeks. AHEI is a type of cutaneous leukocyteclastic vasculitis of small blood vessels and is striking due to its appearance the speed and abruptness at which the lesions spreads. Despite all it has a benign prognosis given that it does not negatively affect the general medical state of the patient. The diagnosis should be clinical and no treatment is necessary (AU)

Phototherapy with ultraviolet radiation: a study of hormone parameters and psychological effects.

BACKGROUND AND OBJECTIVES: Patients report well-being as they are treated with phototherapy. We investigated hormone parameters and psychological well-being after phototherapy in a placebo-controlled study. METHODS: A total of 77 patients with dermatological conditions and 22 healthy volunteers were divided into four groups. The patients received phototherapy either on the whole body or only on hands and/or feet. The volunteers were given either whole-body phototherapy or placebo light. Serum or plasma samples were analysed for cortisol, calcium, magnesium, phosphate, TSH, T(4), T(3) and 25-hydroxyvitamin D, and urine samples for cortisol. Patients and volunteers answered a questionnaire before and 6 weeks after phototherapy/placebo light. Psychiatric ratings were performed according to the Comprehensive Psychopathological Self-rating Scale for Affective Syndromes, a self-report version of which has been transformed to correspond to the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: In the patients who received whole-body irradiation, we observed a significant improvement in both MADRS score and cognitive-symptom score after the completion of phototherapy. We also observed a significantly higher level of 25-hydroxyvitamin D after phototherapy, but no difference in the other hormone parameters. CONCLUSION: Whole-body phototherapy of patients with dermatological conditions results in improved well-being and significantly higher levels of 25-hydroxyvitamin D in serum.

Short incubation with methyl aminolevulinate for photodynamic therapy of actinic keratoses.

BACKGROUND: Photodynamic therapy (PDT) using methyl aminolevulinate (MAL) is an effective first-line treatment for actinic keratoses. A reduced incubation period may have practical advantages. OBJECTIVE: This study aims to evaluate the effect of incubation time (1 vs. 3 h), MAL concentration (160 mg/g vs. 80 mg/g) and lesion preparation in the setting of MAL-PDT for treatment of actinic keratosis (AK). DESIGN: Open, randomized, parallel-group multicentre study. SETTING: Outpatient dermatology clinics. SUBJECTS: One hundred and twelve patients with 384 previously untreated AK. Most lesions (87%) were located on the face and scalp and were thin (55%) or moderately thick (34%). METHODS: Lesions were debrided, and MAL cream (160 mg/g or 80 mg/g) was applied before illumination with red light (570-670 nm; light dose, 75 J/cm2). Patients were followed up at 2 and 3 months. Sixty patients (54%) were re-treated and assessed at 6 months. MAIN OUTCOME: Complete lesion response rates 3 and 12 months after last treatment. RESULTS: For lesions on the face/scalp, lesion complete response rates were 78% for thin AK and 74% for moderately thick AK lesions after 1 h vs. 96% and 87% after 3 h incubation with MAL 160 mg/g. Lesion recurrence rates at 12 months after two treatments were similar [19% (3 of 16) with 1 h vs. 17% (3 of 18) with 3 h 160 mg/kg MAL-PDT] and lower than for 80 mg/g MAL-PDT (44-45%). CONCLUSION: MAL-PDT using a 1-h incubation may be sufficient for successful treatment of selected AK lesions.

The difficult clinical diagnosis of erythropoietic protoporphyria.

We give a short survey of the Swedish erythropoietic protoporphyria patients (EPP) with respect to the lapsed time between symptom debut and diagnosis. With two examples we illustrate the consequence of undiagnosed EPP for the patient and also the family. We recall efforts to spread information among health workers in order to investigate patients suffering from extreme sun-exposure intolerance for this uncommon kind of porphyria as well.

Photodynamic therapy of actinic keratosis at varying fluence rates: assessment of photobleaching, pain and primary clinical outcome.

BACKGROUND: Although photodynamic therapy (PDT) is becoming an important treatment method for skin lesions such as actinic keratosis (AK) and superficial basal cell carcinoma, there are still discussions about which fluence rate and light dose are preferable. Recent studies in rodents have shown that a low fluence rate is preferable due to depletion of oxygen at high fluence rates. However, these results have not yet been verified in humans. OBJECTIVES: The objective was to investigate the impact of fluence rate and spectral range on primary treatment outcome and bleaching rate in AK using aminolaevulinic acid PDT. In addition, the pain experienced by the patients has been monitored during treatment. PATIENTS/METHODS: Thirty-seven patients (mean age 71 years) with AK located on the head, neck and upper chest were treated with PDT, randomly allocated to four groups: two groups with narrow filter (580-650 nm) and fluence rates of 30 or 45 mW cm(-2), and two groups with broad filter (580-690 nm) and fluence rates of 50 or 75 mW cm(-2). The total cumulative light dose was 100 J cm(-2) in all treatments. Photobleaching was monitored by fluorescence imaging, and pain experienced by the patients was registered by using a visual analogue scale graded from 0 (no pain) to 10 (unbearable pain). The primary treatment outcome was evaluated at a follow-up visit after 7 weeks. RESULTS: Our data showed a significant correlation between fluence rate and initial treatment outcome, where lower fluence rate resulted in favourable treatment response. Moreover, the photobleaching dose (1/e) was found to be related to fluence rate, ranging from 4.5 +/- 1.0 J cm(-2) at 30 mW cm(-2), to 7.3 +/- 0.7 J cm(-2) at 75 mW cm(-2), indicating higher oxygen levels in tissue at lower fluence rates. After a cumulative light dose of 40 J cm(-2) no further photobleaching took place, implying that higher doses are excessive. No significant difference in pain experienced by the patients during PDT was observed in varying the fluence rate from 30 to 75 mW cm(-2). However, the pain was found to be most intense up to a cumulative light dose of 20 J cm(-2). CONCLUSIONS: Our results imply that the photobleaching rate and primary treatment outcome are dependent on fluence rate, and that a low fluence rate (30 mW cm(-2)) seems preferable when performing PDT of AK using noncoherent light sources.

Flashlamp pulsed dye laser and argon-pumped dye laser in the treatment of port-wine stains: a clinical and histological comparison.

BACKGROUND: Port-wine stains (PWS) are congenital vascular malformations occurring in 0.3% of children. The pulsed dye laser is a well established treatment for PWS. OBJECTIVES: To compare, clinically and histologically, the effects of the flashlamp pulsed dye laser with the argon-pumped dye laser in the treatment of PWS. METHODS: Thirty patients were treated on two to four test areas with both laser types using different energy fluences. A flashlamp pulsed dye laser with 0.45 ms pulse duration and a spot size of 5 mm was compared with an argon-pumped dye laser, with a spot size of 1 mm delivered with a robotic scanning laser handpiece (Hexascan) and 70-190 ms pulse duration. Both were tuned to 585 nm. Twelve weeks later the degree of lightening was evaluated and biopsies were taken. To count the vessels the skin sections were stained with CD34 using an immunohistochemical technique. The vessels were divided into three groups by diameter (d): d < 10 microm, 10 < or = d < 20 microm, d > or = 20 microm. RESULTS: The clinical results showed a significantly better lightening using the flashlamp pulsed dye laser than with the argon-pumped dye laser. The histological results showed a significant decrease in the number of vessels of diameter larger than 20 microm in treated compared with untreated lesions. We found no histological difference in the number of vessels between the two laser treatments. However, there was a tendency towards more small vessels (diameter < 10 microm) after one treatment with the flashlamp pulsed dye laser compared with untreated PWS. CONCLUSIONS: The flashlamp pulsed dye laser is clinically superior to the argon-pumped dye laser in the treatment of PWS.

Photodynamic therapy with topical 5-aminolevulinic acid for mycosis fungoides: clinical and histological response.

There is no curative treatment for mycosis fungoides (MF), the most common primary cutaneous T-cell lymphoma. The aim of this study was to investigate the response of single lesions to photodynamic therapy (PDT). The study included 10 plaque MF lesions and 2 tumour MF lesions from 10 patients. First, 20% 5-aminolevulinic acid was applied topically to the lesion and adjacent skin for 5-6 h. The lesion was then exposed to red light at around 630nm. Skin biopsies were taken before treatment, after clinical improvement and after clinical remission. The expression of CD3, CD4, CD7, CD8, CD1a, CD34, CD68, CD71, Ki-67, bcl-2 and p53 was studied immunohistochemically. There was complete clinical clearance in seven of nine plaque lesions. Neither tumour lesion responded to PDT. The biopsies confirmed a regression of the infiltrate after treatment. In the sparse remaining infiltrate a few CD4+ and CD8+ cells were found, most of which showed normal bcl-2. There were also fewer proliferating cells, illustrated by a decrease in Ki-67 and CD71. In conclusion, PDT has good clinical and histological effects in treating local plaque MF lesions.

Effects on human skin of repetitive ultraviolet-A1 (UVA1) irradiation and visible light.

BACKGROUND: Ultraviolet radiation (UVR) has a variety of effects on human skin. Best known are the effects of UVB (290-320 nm) and UVA2 (320-340 nm), which cause DNA damage and increased risk of cancer. However, the effects of UVA1 (340-400 nm) have been not completely investigated. METHODS: The effects of repetitive low doses of UVA1 and visible light were studied in 12 healthy individuals. A part of the buttock was exposed to 20 J/cm2 UVA1 and another part of 126 J/cm2 of visible light three times a week for 4 weeks. Repeated punch biopsies were taken during the 4 weeks of treatment and also 2 weeks after the last irradiation. The avidin-biotin-immunoperoxidase technique was used to investigate the expression of p53, p21WAF, bcl-2, Ki67 and cyclin A. RESULTS: By comparison to untreated skin, an increased expression of p53 but not p21WAF in keratinocytes was seen. The bcl-2 protein expression increased slightly after both UVA1 and visible light. An increased staining with Ki67 and cyclin A after UVA1 but not after visible light was observed as a sign of increased proliferation. CONCLUSION: These results suggest that suberythemal doses of UVA1 and even visible light may cause DNA damage.

Stability of 5-aminolevulinic acid in aqueous solution.

The chemical stability of 5-aminolevulinic acid (ALA) was studied in aqueous solution as a function of concentration, pH, temperature and in the presence of ethylenediaminetetraacetic acid (EDTA). The degradation of ALA was followed by reversed-phase liquid chromatography using a pH where ALA is protonated (pKa1=3.90; pKa2=8. 05, as determined potentiometrically). ALA was degraded by a reaction following second order kinetics. Stock solutions of 1% (60 mM) ALA were incubated at 50 degrees C. At pH 2.35, ALA was stable during the whole incubation period (37 days). The half-lives for the second-order decomposition of 1% ALA at pH 4.81 and 7.42 were 257 and 3.0 h, respectively. The degradation rate increased about 1.5 times with each 10 degrees C rise in temperature at pH 7.53 within the range studied (37-85 degrees C). The energy of activation, Ea, for the second-order decomposition of ALA was 43.7 kJmol-1. EDTA did not influence the degradation of ALA when a mixture of 1% ALA and 1% EDTA was incubated at pH 7.42.

[Porphyria cutanea tarda is the most common type of porphyria. Medical control is a team work]. / Porphyria cutanea tarda vanligaste porfyriformen. Den medicinska kontrollen ett lagarbete.

Porphyria cutanea tarda (PCT) is probably the most common of the porphyrias. The development of skin fragility and blisters are the symptoms that generally bring the patient to the notice of the dermatologist. During the past decade the disease has been recognised as being of heterogeneous aetiology, and a pathogenetic classification has been proposed. The significance of subtyping for the choice of management strategy is currently appreciated, as is the need of close monitoring owing to the risk of the common PCT-associated liver conditions. Preferably the PCT patient should be managed by a dermatologist and a hepatologist working in concert and supported by a specialised porphyria laboratory. The use of a structured management protocol should be considered.

[Risk of liver failure in erythropoietic protoporphyria. Be alert for sings of cholestatic development!]. / Risk för leversvikt vid erytropoetisk protoporfyri. Var uppmärksam på kolestatisk utveckling!

Erythropoietic protoporphyria (EPP) presents clinically as a painful skin reaction to sun-light exposure. The profoundly disabling psychosocial consequences of the disease often go unnoticed by the physician, and the need to monitor the patient for hepatic complications is not generally recognised. The article describes the clinical and biochemical course in a 51-year-old man with EPP, who within a few days developed signs of acute hepatic failure. The case emphasises the importance of a well designed monitoring programme that allows close evaluation of the patient's current porphyrin metabolism, and indicates what measures should be considered.

7 years experience of photopatch testing with sunscreen allergens in Sweden.

Since 1990 7 sunscreen allergens have been included in the standard photopatch protocol at 2 Swedish dermatology clinics. 355 consecutive patients with suspected photosensitivity were tested, and in 28 of these (7.9%), a total of 42 allergic reactions were found. 80% of the reactions were of photocontact origin. The most common allergen was benzophenone-3 (Eusolex 4360), with 15 photocontact and 1 contact allergic reactions, followed by isopropyl dibenzoylmethane (Eusolex 8020) (8 photocontact, 4 contact) and butyl methoxydibenzoylmethane (Parsol 1789), with 6 photocontact reactions. There were 2 cases of photocontact allergy to phenylbenzimidazole sulfonic acid (Eusolex 232), which has not been reported previously. 1 case of contact urticaria from benzophenone-3 was accidentally found. In addition, 21 + reactions of doubtful relevance were noted in 14 patients: 16 on irradiated and 5 on non-irradiated test sites. Among these, irritant and phototoxic reactions may be included. These results indicate that the inclusion of UV filters in the standard photopatch protocol is important. Immediate-type testing for urticaria could also be of value.

Photosensitivity in lupus erythematosus, UV photoprovocation results compared with history of photosensitivity and clinical findings.

Photosensitivity, one of the presenting symptoms in lupus erythematosus (LE), is still poorly defined and varying prevalence figures have been reported. The possibility of a coexisting photodermatosis, especially polymorphous light eruption (PLE), has often not been taken into account. We report the results of ultraviolet A (UVA) and B (UVB) photoprovocation tests in 67 clinically photosensitive patients who had confirmed discoid LE (DLE), systemic LE (SLE) or subacute cutaneous LE (SCLE). The results are compared with a detailed history of photosensitivity and with clinical and serological findings. A pathological photoprovocation reaction, graded as weak, moderate or strong, was induced with either UVA or UVB in 69% of patients with LE, in 100% of those with SCLE, in 70% of those with SLE and in 64% of those with DLE, but in none of 14 controls. Only 16% of the pathological reactions were strong and long-lasting, resembling LE lesions, while 48% were moderate or weak and transient, clinically like PLE. Fifty-three per cent of the provocation reactions which were biopsied showed a PLE-like histology or a non-specific inflammatory reaction, and most of them were clinically moderate or weak reactions of short duration. In the remaining, mostly clinically strong or long-lasting reactions, the histology was consistent with LE. A history of sunlight sensitivity did not predict a pathological photoprovocation result but a positive association between the presence of SSA/Ro or SSB/La antibodies and a pathological photoprovocation reaction was found. We have shown that PLE coexists with LE and that both PLE- and LE-like lesions can be induced with UV radiation in LE patients.

The treatment of port-wine stains with the pulsed dye laser at 600 nm.

The standard wavelength in the treatment of port-wine stains (PWS) with the pulsed dye laser is 585 nm. In many cases, the response to therapy is not adequate despite many treatments, depending partly on vessels out of reach of the laser. Longer wavelengths penetrate deeper into the dermis, but are absorbed less by oxyhaemoglobin, and require higher fluences. In this study, 22 patients with PWS were treated with the flashlamp-pumped pulsed dye laser using two different wavelengths, 585 and 600 nm. Four adjacent sites with PWS were treated on one occasion with 585 nm, 600 nm and equal fluence, and with 1.5 and 2 times the 585 nm fluence. The test areas were examined blindly, by four evaluators, an average of 12.5 weeks later. There was significantly less lightening with 600 nm than with 585 nm (P < or = 0.001) when equal fluences were used. When 1.5 and 2 times the 585 nm fluence were applied, with 600 nm the lightening was equal to that after 585 nm. However, in individual cases (11 of 22) 600 nm showed a superior lightening of at least 20% compared to 585 nm. There was slight hyperpigmentation and hypopigmentation, but no atrophy or scarring. In conclusion, 585 nm remains the wavelength of choice in treatment of PWS with the pulsed dye laser. However, in cases that do not respond satisfactorily with 585 nm, it may be worth trying 600 nm with a fluence that is at least 1.5-2 times the 585 nm fluence.

Cyclosporin A therapy for severe solar urticaria.

Solar urticaria is characterized by itching weals that occur a few minutes after exposure to visible or ultraviolet light. The symptoms may sometimes restrict normal daily life. Treatment is difficult in more severe cases. We describe one patient with solar urticaria who was successfully treated with cyclosporin A. The patient had first been treated with antihistamine, PUVA and chloroquine phosphate without effect. Cyclosporin was given in a dose of 4.5 mg/kg body weight/day. Phototesting before, during and after treatment showed a decreased light sensitivity to UVA, UVB and visible light during cyclosporin treatment compared with phototesting before therapy. The patient could be out in the sun for at least 1 h with minimal urticaria during cyclosporin therapy compared with only a few minutes previously. However, 1-2 weeks after cyclosporin therapy was discontinued, skin symptoms returned. Cyclosporin therapy is a possible treatment in severe cases of solar urticaria where other treatments have failed, especially in countries where treatment is necessary only for a few months during summer.

Occurrence of polymorphous light eruption in lupus erythematosus.

Photosensitivity is a well-known manifestation of lupus erythematosus (LE). Since there are no strict criteria for photosensitivity, varying prevalence figures have been reported. Also, distinction from polymorphous light eruption (PLE) can be difficult. The purpose of this study was to characterize photosensitivity in more detail and to determine the occurrence of PLE in a series of well-documented LE patients. A questionnaire was answered by 337 LE patients seen at dermatology departments in Finland and Sweden, and 63 of the patients were invited for interview. According to the questionnaire, LE lesions were made worse by sunlight in 242 (72%) patients. Symptoms consistent with PLE were reported by 165 (49%) patients. Detailed personal interviews supported the results from the questionnaire, and revealed that PLE had started 2-45 years before the onset of LE in 23 of 37 patients with both diagnoses, and more than 7 years before in 18 of 37 (49%). PLE proved to be common in patients with both systemic and cutaneous LE. The two conditions may often coexist and, in about half of the cases, PLE preceded LE. These two diseases may share pathogenic factors. PLE might predispose to LE in a subgroup of PLE patients.

Psoriasis response to the pulsed dye laser.

BACKGROUND AND OBJECTIVE: In psoriasis the blood vessels are enlarged and dilated. These vessels, the psoriatic microvasculature, have been implicated as participating in the pathogenesis of psoriasis. The purpose of this preliminary study was to use the flash-lamp-pumped pulsed dye laser, which selectively damages dermal vessels, to treat psoriatic plaques and to evaluate the role of the vasculature in the therapeutic response. MATERIALS AND METHODS: Ten patients with psoriasis were treated with the pulsed dye laser on single, stable psoriasis plaques. Treatments varied between one and three times, and the lesional response was graded using a scale for erythema, scaling, and infiltration. RESULTS: Six of 10 patients experienced a beneficial clinical effect after therapy. The psoriasis severity scale in these patients was reduced to 2.2 +/- 1.3 compared with a 7.2 +/- 1.7 grade for control areas. The plaques readily developed crusting with therapy, with one leg lesion healing with atrophy. Histopathology in three patients immediately after therapy showed no epidermal damage. One week after laser therapy, the necrotic former epidermis was apparent in superficial crusting. Epidermal thinning and regeneration was seen without any signs of psoriasis. CONCLUSIONS: Pulsed dye laser therapy may improve plaque psoriasis. This improvement may be related to the role the microvasculature plays in psoriasis.