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Atopic dermatitis (AD) is characterized by chronic, relapsing, pruritic inflammatory skin disease. Adiponectin has been reported to have anti-inflammatory effects not only on metabolic disorders but also on various inflammatory disorders. The study aimed to validate adiponectin as a potential biomarker for AD disease severity and treatment response. Seventy-five patients with AD and 28 healthy volunteers were enrolled in the study. Patient information, including Eczema Area and Severity Index (EASI) scores and pruritus numeric rating scales (NRSs), were collected. An enzyme linked immunosorbent assay (ELISA) was conducted to measure levels of serum adiponectin. Additionally, sera of patients treated with dupilumab were collected and measured at 16 and 52 weeks from baseline. Serum adiponectin levels were significantly lower in moderate and severe AD patients than in the control and mild AD patients. Serum adiponectin level was negatively correlated with the EASI score and pruritus NRS. However, no significant changes were observed according to biologic treatment for AD. Low serum adiponectin levels are associated with moderate to severe AD, suggesting a potential role for adiponectin as a biomarker for severity assessment of AD.

Nonablative 1,450-nm diode laser (DL) and visible blue light (BL) have been effectively used for acne with superior safety profiles.To evaluate synergistic effects of sequential DL and BL application for acne.A 20-week, randomized split-face study was conducted to compare clinical courses between 2 facial sides either receiving sequential application of DL and BL or BL alone in 24 patients with mild to moderate facial acne vulgaris. Patients were scheduled to receive 3 consecutive sessions at 4-week intervals. Objective assessments, including revised Leeds grades, lesion counts, and sebum output measurements, and patients' subjective satisfaction were investigated.Both combination and BL sides demonstrated steady improvement of inflammatory acne lesions with 62.3% and 35.2% decreases at the 12-week follow-up visit compared with baseline respectively. For noninflammatory lesions and seborrhea, only combination regimen demonstrated improvement. Patients' subjective assessments paralleled objective findings. For safety profiles, no severe adverse effect was observed on both sides, and mild symptoms resolved spontaneously within a day.The combination regimen demonstrated synergistic efficacies for acne and seborrhea, with satisfactory safety profiles. Therefore, a few sessions of these light-based applications would be a viable option for acne treatments.

BACKGROUND While a considerable number of cases with papulopustular rosacea (PPR) are resistant to conventional medications, therapeutic regimens are not currently established. Pulsed dye laser (PDL) and fractional microneedling radiofrequency (FMR) have previously demonstrated satisfactory results for anti-angiogenesis, anti-inflammation, and dermal remodeling. AIMS To evaluate the efficacy and safety of novel combination regimen with low-dose oral isotretinoin, PDL, and FMR in the treatment of recalcitrant PPR. PATIENTS AND METHODS A retrospective study was undertaken for recalcitrant PPR patients to evaluate the clinical course of novel combination regimen. Twenty-five PPR patients who had failed in previous first-line therapies were enrolled. They were treated with three sessions of PDL and FMR consecutively at 4-week intervals, maintaining daily oral administration of 10 mg isotretinoin for 8 weeks. Objective assessments, erythema index measurement, and patients' subjective satisfaction were evaluated at each visit and 16 weeks after the final treatment. RESULTS At the final follow-up visit, the number of papules and pustules decreased by 71%, and erythema index by 54% compared with baseline (P

A variety of applications of human adipose tissue stem cell-derived exosomes have been suggested as novel cell-free therapeutic strategies in the regenerative and aesthetic medical fields. This study evaluated the clinical efficacy and safety of adipose tissue stem cell-derived exosomes as an adjuvant therapy after application of fractional CO2 laser for acne scars. A 12-week prospective, double-blind, randomized, split-face trial was performed. A total of 25 patients received 3 consecutive treatment sessions of fractional CO2 laser to the whole face, with a follow-up evaluation. Post-laser treatment regimens were applied; for each patient, one side of the face was treated with adipose tissue stem cell-derived exosomes gel and the other side was treated with control gel. Adipose tissue stem cell-derived exosomes-treated sides had achieved a significantly greater improvement than the control sides at the final follow-up visit (percentage reduction in echelle d'evaluation clinique des cicatrices d'acne scores: 32.5 vs 19.9%, p < 0.01). Treatment-related erythema was milder, and post-treatment downtime was shorter on the applications of human adipose tissue stem cell-derived exosomes-treated side. In conclusion, the combined use of this novel material with resurfacing devices would provide synergistic effects on both the efficacy and safety of atrophic acne scar treatments.

In Korea, there is a high dependency on oriental medicine and folk remedies (Korean J Asthma Allergy Clin Immunol, 25, 2005, 110). In addition, inaccurate information available through the Internet is increasing (Korean J Dermatol, 44, 2006, 137). So, there is always a possibility that patients may have difficulty obtaining accurate information about atopic dermatitis (AD). The aim was to determine the awareness, treatment behavior and treatment satisfaction of patients with AD and their caregivers. In October 2017, patients diagnosed with AD at nine hospitals were enrolled in this study. A questionnaire was completed by each patient. A total of 371 subjects were surveyed. In response to the question asking about knowledge of AD, the correct answer rate was 55.4%. Bathing using soap, body scrub and moisturizer showed favorable outcomes. A total of 54.9% patients responded that they were reluctant to use steroid ointment. When asked about their previous treatment, 39.6% reported using oriental medicine and 26.5% had tried folk remedies. The hospital treatment satisfaction score was 6.6. Patients usually applied their knowledge in their daily lives. However, there was a lot of inaccurate knowledge. Therefore, it is important for patients to understand the characteristics of this disease and obtain correct information.

Although the discovery of new biomarkers in atopic dermatitis (AD) is challenging, it is valuable in diagnosis, assessment of severity, and evaluation of treatment response.This study was designed to identify and validate new candidate protein biomarkers of AD via proteomic analysis.Comparison of protein expression in the patients' serum before- and after-treatment and in patients without AD was performed via two-dimensional gel electrophoresis (2-DE), followed by image analysis. Spots showing differential expression in 2-DE image analysis were identified subsequently via nanoscale liquid chromatography-tandem mass spectrometry (LC-MS/MS) experiments. Blood tests were conducted to validate the results obtained by measuring the levels of candidate proteins.Based on LC-MS/MS analysis and database search, we identified ceruloplasmin (Cp) as a candidate protein. Serum Cp levels were significantly decreased in in pre-treated AD group than in control group. Additionally, the serum Cp level was higher in the mild group than in the moderate group of AD based on the Eczema Area and Severity Index (EASI) score.Low serum Cp levels are associated with AD, suggesting the potential role of Cp as a biomarker for diagnosis and severity assessment of AD.

Background While device-based acne treatments are widely applied for patients not tolerating conventional medications, related controlled studies have been still limited. Recently, non-ablative 1450-nm diode laser (DL) and fractional microneedling radiofrequency (FMR) have been effectively used for acne, in addition to well-recognized dermal remodelling effects. Objective To compare the clinical course of acne treatment between DL and FMR. Methods Twenty-five Korean patients with mild-to-moderate facial acne completed treatments with DL and FMR through a 20-week, randomized split-face study. One randomly assigned half side of each patient's face received DL and the other side by FMR. Treatments were scheduled to receive three consecutive sessions at 4-week intervals. Objective assessments including revised Leeds grades, lesion counts, sebum output measurements, and patients' subjective satisfaction were investigated. Results Both DL and FMR demonstrated steady improvement of acne and seborrhoea during treatment sessions. While results between two devices were similar during treatment sessions, FMR was superior to DL in the 12-week follow-up. Patients' subjective assessments for seborrhoea improvement were similar between two devices, while those for acne, skin texture, and acne scars were more satisfactory for FMR. For safety profile, no significant difference was observed between two regimens, while mild postinflammatory hyperpigmentation was observed only in DL side. Conclusion Both DL and FMR demonstrated efficacies for acne and seborrhoea, with reasonable safety profile. FMR was more effective than DL for the long-term maintenance, and subjective assessments for texture and scar improvements. Therefore, a few sessions of these devices would be a viable option for acne treatments.

The histologic responses to varied parameters of 1,927-nm fractional thulium fiber laser treatment have not yet been sufficiently elucidated.This study sought to evaluate histologic changes immediately after 1,927-nm fractional thulium fiber laser session at various parameters.The dorsal skin of Yucatan mini-pig was treated with 1,927-nm fractional thulium fiber laser at varied parameters, with or without skin drying. The immediate histologic changes were evaluated to determine the effects of varying laser parameters on the width and the depth of treated zones.The increase in the level of pulse energy widened the area of epidermal changes in the low power level, but increased the dermal penetration depth in the high power level. As the pulse energy level increased, the increase in the power level under the given pulse energy level more evidently made dermal penetration deeper and the treatment area smaller. Skin drying did not show significant effects on epidermal changes, but evidently increased the depth of dermal denaturation under both high and low levels of pulse energy.These results may provide important information to establish treatment parameters of the 1,927-nm fractional thulium fiber laser for various skin conditions.

BACKGROUND Novel picosecond lasers using a diffractive optical element (P-DOE) have been available for skin resurfacing with distinct mechanisms. However, there are limited data directly comparing P-DOE and conventional fractional lasers for the treatment of atrophic acne scarring. OBJECTIVES We sought to compare the efficacy and safety of a 1064-nm neodymium-doped yttrium aluminium garnet P-DOE and a non-ablative fractional laser (NAFL) in the treatment of acne scarring. METHODS A prospective, randomized, split-face, controlled trial was performed. One randomly assigned half-side of each patient's face (n = 25) was treated with four consecutive sessions of P-DOE at 3-week intervals and the other side with NAFL, with subsequent follow-up for 8 weeks after the final sessions. The efficacy and safety of the two lasers were determined by the Echelle d'Evaluation Clinique des Cicatrices d'acne (Scale of Clinical Evaluation of Acne Scars; ECCA) grading scale, Investigator's Global Assessment (IGA) score and patients' reports at the final visit. Histologic analysis was also performed. RESULTS The P-DOE-treated side achieved a significantly better improvement in acne appearance (ECCA per cent reduction: 55% vs. 42%) with less severe pain (4.3 vs. 5.6) (P

Mast cells and their mediators play important roles in chronic spontaneous urticaria (CSU) pathogenesis. Transglutaminase 2 (TG2) is expressed in activated mast cells and contributes to airway inflammation in allergic asthma.To investigate the role of TG2 in CSU.Patients with CSU (n = 72) and healthy controls (n = 51) were evaluated. Skin biopsy specimens were obtained from 5 patients with CSU and 2 healthy controls. Cord blood-derived human mast cells and peripheral blood-derived human mast cells were activated with IgE. TG2 activity and inflammatory mediators, such as histamine, leukotriene C4, and cytokines, were measured in serum or supernatant from cultured mast cells by enzyme-linked immunosorbent assay. Colocalization of mast cells and TG2 was determined in skin tissues by immunofluorescence.TG2 activity was significantly higher in serum samples from patients with CSU than in serum samples from healthy controls (P.001). Colocalization of mast cell surface marker c-kit and TG2 was significantly increased in the lesional skin of patients with CSU compared with that in healthy controls. The levels of histamine, leukotriene C4, tumor necrosis factor α, transforming growth factor β, and interleukins 4, 5, and 6 were significantly higher in patients with CSU than in healthy controls (P.001). Serum TG2 levels had positive correlations with each inflammatory mediator (P.001). TG2 activity was increased in cord blood-derived human mast cells (CBMCs) and peripheral blood-derived human mast cells activated with IgE compared with those without activation (P.05).Our findings suggest that TG2 expressed in and released from mast cells plays an important role in CSU pathogenesis.

Background Although a 1450-nm diode laser has been shown to be effective for acne, the conventional high-energy stamp-only regimen is often associated with pain and hyperpigmentation, especially for dark-skinned individuals. Aims To evaluate whether the novel dual regimen has clinical advantages for acne treatments compared with conventional regimen in Asian patients. Patients and methods Twenty-four Korean patients with facial acne were treated with a 1450-nm diode laser through a 20-week, randomized, split-face study. The patients were treated with three consecutive sessions at 4-week intervals. One half of the face received a dual regimen consisting of low-fluence stamping mode (5-6 J/cm2 ) for inflammatory acne lesions only, followed by 4-5 passes of moving mode for the full face. The other side received a single-pass treatment of conventional high-fluence stamp mode (14-15 J/cm2 ). Evaluations for acne, sebum secretion measurements, and safety profiles were performed. Results At the final 12-week follow-up evaluations, the dual-mode side demonstrated better improvements in both inflammatory and noninflammatory lesion counts, acne severity assessments, and reduction in sebum secretion compared with stamp-only side. Subjective satisfaction for the improvement for acne, seborrhea, and texture correlated well with objective assessments. In addition, degrees of pain and treatment-related side effects were remarkably decreased in the novel dual mode. Conclusion This novel dual regimen of the 1450-nm laser demonstrated improved efficacies for acne and seborrhea with satisfactory safety profiles. Therefore, this regimen would be a viable option for acne treatments either as monotherapy or as combination therapy.

Although various minimal invasive approaches are available for aging skin laxity, they alone may not lead to notably satisfactory results.To evaluate the effectiveness and safety of combination regimen with monopolar radiofrequency (MRF) and intense-focused ultrasound (IFUS) in facial lifting and tightening.Twenty-two Korean participants with aging face received a sequential single session of MRF and IFUS treatment. Objective and subjective assessments for improvement were performed at the 20-week post-treatment. Safety profiles were also recorded, and skin biopsies were taken at baseline and follow-up visit.Based on the objective assessment for the overall facial skin tightening and laxity, 19 patients (90%) demonstrated "moderate" or better improvements (more than 25%) compared with baseline. Specifically, improvements of skin laxity and sagging, and droopy jaw line were more noticeable compared with that of superficial skin texture (P 0.05). Subjective satisfactions were generally consistent with objective findings, and no serious adverse effect was observed. Histologic evaluation showed increased dermal collagen fibers throughout the dermis after treatments (P 0.05).Combination treatment of MRF and IFUS has cumulative benefits for skin lifting and tightening with satisfactory safety profiles in Asian subjects.

Background: Despite the autologous serum skin test (ASST) and autologous plasma skin test (APST) is widely used test accessing whether a patient with chronic spontaneous urticaria (CSU) has autoreactivity or not, the clinician often encounter difficulty making correlation between the test result and clinical implications. Objective: This study was aimed to find any clinical and laboratory findings related to the ASST and APST response. Agreement and correlation between the two tests was also analyzed. Methods: A retrospective study was conducted on 300 CSU patients who underwent ASST, APST. The subjects were divided into four groups according to the skin test result. Also, the degree of serum and plasma response was recorded. Results: Both ASST and APST positive group had shorter duration of the disease, higher incidence of at least one episode of angioedema than negative group. There were no significant differences in the positivity for autoantibodies including antinuclear, ds-DNA, and thyroid-related between the two groups. The predicted positive rate of ASST and APST according to age showed bimodal peak and decreasing pattern according to disease duration. Predicted positivity of both tests declined with increase in total immunoglobuline E (IgE) level. In the correlation study, the two tests showed high correlation coefficients. Conclusion: ASST and APST positivity may be related to disease duration and severity of CSU. The two tests showed a generally consistent result. Autoreactivity may be gradually lost as disease continues. We suggest the autoreactivity in CSU could arise independently from IgE mediated immune process. (Ann Dermatol 32(4) 280∼288, 2020)

Green nail syndrome (chromonychia) is a nail disorder characterized by onycholysis and green-black discoloration of the nail bed. This condition is often associated with chronic paronychia. Pseudomonas aeruginosa is the most commonly identified organism in cultures from the affected area. Despite the various treatment options available, removal of the nail is still necessary in many cases. A 35-year-old man presented with dark-greenish discoloration of the nail plate and onycholysis on the left thumbnail. He had been treated with oral antifungal and antibiotic agents for several months; however, the lesion showed no improvement. The diagnosis of green nail syndrome was established after a positive bacterial culture, and on the basis of the antibiotic sensitivity test result, tobramycin eye drop (Tobrex®) was then prescribed. Three weeks later, the nail discoloration almost vanished but the onycholysis remained. Herein, we recommend the application of tobramycin eye drop as an easy and safe treatment option for green nail syndrome.

Chronic spontaneous urticaria (CSU) is a complex idiopathic disease of the skin with various cellular infiltrations. Although mast cells are key effector cells in the pathogenesis of CSU, CD4+ T helper 2 cells also have particular roles in the development and maintenance of CSU. Periostin is known as a downstream molecule of interleukin (IL)-4 and IL-13, key cytokines of type 2 immune responses. In this study, we examined periostin and IL-13 levels in the sera of patients with CSU (n=84) and healthy normal controls (NCs, n=43). Periostin levels were significantly lower in the CSU group than in NCs (71.4±21.8 vs 85.1±22.4 ng/mL, P=0.04). Periostin levels were also lower in the severe CSU group than those in mild CSU (59.7±18.0 vs 73.4±22.0 ng/mL, P=0.04). However, IL-13 levels were significantly higher in patients with CSU than in NCs (508.5±51.2 vs 200.7±13.3 pg/mL, P=0.001). In conclusion, periostin and IL-13 may be independently related to the pathogenesis of CSU.

Facial psoriasis is often observed in moderate to severe degrees of psoriasis. While we previously demonstrated construct validity of the facial Psoriasis Log-based Area and Severity Index (fPLASI) system for the cross-sectional evaluation of facial psoriasis, its reliability and accuracy to detect clinical improvement has not been confirmed yet. The aim of this study is to analyze whether the fPLASI properly represents the range of improvement for facial psoriasis compared with the existing facial Psoriasis Area and Severity Index (fPASI) after receiving systemic treatments in clinical practice settings. The changing severity of facial psoriasis for 118 patients was calculated by the scales of fPASI and fPLASI between two time points after systemic treatments. Then, percentage changes (ΔfPASI and ΔfPLASI) were analyzed from the perspective of both the Physician's Global Assessment of effectiveness (PGA) and patients' Subjective Global Assessment (SGA). As a result, the distribution of the fPASI was more heavily clustered around the low score range compared with the fPLASI at both first and second visits. Linear regression analysis between ΔfPASI and ΔfPLASI shows that the correlation coefficient was 0.94, and ΔfPLASI represented greater percentage changes than ΔfPASI. Remarkably, degrees of clinical improvement measured by the PGA matched better with ΔfPLASI, while ΔfPASI underestimated clinical improvements compared with ΔfPLASI from treatment-responding groups by the PGA and SGA. In conclusion, the fPLASI represented clinical improvement of facial psoriasis with more sensitivity and reliability compared with the fPASI. Therefore, the PLASI system would be a viable severity measurement method for facial psoriasis in clinical practice.

A 33-year old Korean man visited our department complaining of single mildly pruritic yellowish flat-topped papule on left upper eyelid. Lipid profile including low density lipoprotein-cholesterol and triglyceride level was above normal range. He remembered that the site was scalded by boiling oil about eight months ago. The patient was diagnosed with xanthelasma palpebrarum (XP) based on the clinical and histopathological findings, including diffuse infiltrate of large, pale-staining cells which have abundant foamy cytoplasm in the dermis. He was treated with CO2 laser ablation followed by application of 70% trichloroacetic acid with wooden stick. After a month, the skin lesion showed moderate improvement with disappearance of yellowish color and flattopped elevation. So far, case of XP developed after minor trauma has not been reported. This case illustrates that minor trauma could be a trigger factor in the development of the disorder.

Dermatological examination is critical for the evaluation of lupus erythematosus. However, little is known about the epidemiology and clinical characteristics of the lupus erythematosus patients that visit dermatology clinics with the chief complaint of skin lesions, especially among Asian populations. We performed this study to determine the epidemiology of cutaneous lupus erythematosus for three subtypes: acute cutaneous lupus erythematosus, subacute cutaneous lupus erythematosus, and chronic cutaneous lupus erythematosus, and for lupus erythematosus non-specific skin disease. Also, we sought to determine the relationship between each type of lupus erythematosus, by the skin manifestations and systemic lupus erythematosus. The medical records of lupus erythematosus patients that were diagnosed by their clinical manifestations, skin biopsy results, and laboratory findings from January 1998 through December 2007 were reviewed. A total of 117 patients were diagnosed with lupus erythematosus; 62 cases had chronic cutaneous lupus erythematosus, 11 had subacute cutaneous lupus erythematosus, and 41 had acute cutaneous lupus erythematosus. The remaining three had systemic lupus erythematosus features with lupus erythematosus non-specific skin lesions such as Raynaud phenomenon, livedo reticularis/vasculitis, non-scarring alopecia, and periungual telangiectasia. The acute cutaneous lupus erythematosus subgroup showed extreme female predominance (9.2:1) whereas subacute and chronic cutaneous lupus erythematosus subgroups did not. Patients with chronic cutaneous lupus erythematosus tended to be older than other groups (peak incidence in the fifth decade). Incidence of laboratory abnormalities, including positive connective tissue markers such as antinuclear, double-strand DNA, and Ro/SS-A antibodies, were present in the order acute, subacute, and chronic cutaneous lupus erythematosus. Acute cutaneous lupus erythematosus almost always indicated systemic involvement of lupus erythematosus, whereas chronic cutaneous lupus erythematosus did not predict the development or existence of systemic lupus erythematosus and had a benign clinical course. Careful consideration of lupus erythematosus non-specific skin lesions may help detect systemic lupus erythematosus regardless of the diagnosis of cutaneous lupus erythematosus. Lupus (2009) 18, 1320—1326.

Background: Although rosacea is a chronic cutaneous inflammatory disorder that’s commonly seen in adults, the etiology and pathogenesis of the illness remain unclear. A well established diagnostic classification and grading system may play a critical role in performing research and it would serve as a diagnostic reference in the clinical field. Objective: We sought to classify the patients with the new standard classification and grading system and we wanted determine the peculiar features and relationships of each subtype. We also analyzed the relationships between the degree of sun exposure and each subtype. Methods: We reviewed the medical records and clinical photos of 168 patients who were diagnosed with rosacea from 2002 to 2007 at our hospital. The standard classification and grading system suggested by the National Rosacea Society (NRS) Expert Committee was adopted to evaluate each patient’s subtype and the severity. Results: The male：female ratio was 1： 2.29. The mean age at the time of diagnosis was 47.8 years. The mean duration of disease was 3.5 years. Sun exposure and hot baths/exercise were the two most common precipitating factors, while the majority of patients did not have any specific factor that relieved their symptoms. According to the NRS classification and grading system, the patients were classified into four subtypes. One hundred sixty two (96.4%) patients were diagnosed with the erythematotelangiectatic subtype irrespective of severity. Eighty five (50.6%) patients had the papulopustular subtype and 24 (14.3%) patients had ocular rosacea. Eight (4.8%) patients displayed mild phymatous change. The degree of sun exposure had significant correlation with the development and severity of the erythematotelangiectatic subtype (p

Summary A 76-year-old Korean woman presented with pruritic erythematous vesicles and crusted plaques over her entire body. She had been taking an angiotensin II receptor blocker (ARB) (candesartan) for 2 months before developing the skin lesions. The patients was diagnosed with pemphigus foliaceus based on the clinical and immunopathological criteria, including intra-epidermal bulla on skin histopathology, intercellular deposit of C3 and IgG on direct immunofluorescence, and autoantibodies to the 160-kDa antigen on both immunoblot and ELISA. The medication was changed to another antihypertensive agent and the patient was treated with prednisolone for 2 months. The vesiculobullous skin lesions gradually disappeared. However, the skin lesions reappeared 2 months after starting a different ARB (telmisartan). This case illustrates the importance of taking a complete drug history in patients who present with bullous diseases. Furthermore, ARBs should be added to the list of nonthiol drugs that can possibly induce pemphigus.

Background Avoidance behavior against positive allergens detected by using multiple allergen simultaneous test (MAST)-immunoblot assay in patients with urticaria has been rarely reported. Objective We aimed to assess the avoidance behavior of patients with urticaria against positive allergens detected with a MAST. Methods One hundred and one urticaria patients who showed positivity to at least one allergen on a MAST completed a questionnaire regarding their test results. The avoidance behavior of the patients was evaluated, and relevant determining factors of avoidance success/failure were statistically assessed. Results We detected 144 different data (n=51, food allergens; n=17, pollen allergens; and n=76, aeroallergens) from 101 patients with urticaria. The avoidance failure rates were 33.3% for food allergens, 70.6% for pollen allergens, and 30.3% for aeroallergens. The pollen group showed a significantly higher avoidance failure rate than the food and aeroallergen groups (p

This study aimed to investigate the effect of pituitary adenylate cyclase-activating peptide (PACAP) on the pacemaker activity of interstitial cells of Cajal (ICC) in mouse colon and to identify the underlying mechanisms of PACAP action. Spontaneous pacemaker activity of colonic ICC and the effects of PACAP were studied using electrophysiological recordings. Exogenously applied PACAP induced hyperpolarization of the cell membrane and inhibited pacemaker frequency in a dose-dependent manner (from 0.1 nM to 100 nM). To investigate cyclic AMP (cAMP) involvement in the effects of PACAP on ICC, SQ-22536 (an inhibitor of adenylate cyclase) and cell-permeable 8-bromo-cAMP were used. SQ-22536 decreased the frequency of pacemaker potentials, and cell-permeable 8-bromo-cAMP increased the frequency of pacemaker potentials. The effects of SQ-22536 on pacemaker potential frequency and membrane hyperpolarization were rescued by co-treatment with glibenclamide (an ATP-sensitive K(+) channel blocker). However, neither N (G)-nitro-L-arginine methyl ester (L-NAME, a competitive inhibitor of NO synthase) nor 1H-[1,2,4]oxadiazolo[4,3-α]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) had any effect on PACAP-induced activity. In conclusion, this study describes the effects of PACAP on ICC in the mouse colon. PACAP inhibited the pacemaker activity of ICC by acting through ATP-sensitive K(+) channels. These results provide evidence of a physiological role for PACAP in regulating gastrointestinal (GI) motility through the modulation of ICC activity.