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Aim To evaluate the clinical characteristics, treatment course, and prognosis of patients with acute retinal necrosis (ARN), which can rapidly progress and cause severe vision loss. Design Single-center retrospective case series. Subjects and methods Six patients and seven eyes diagnosed with ARN at Teikyo University Hospital were included in this study. The clinical presentation and treatment prognosis were investigated based on data obtained from medical records. Results The mean age of the patients at the initial diagnosis was 63.6 years. Although the mean Logarithm of the Minimum Angle of Resolution (LogMAR) visual acuity tended to decrease from 0.77 at the first visit to 1.29 at the last visit, the difference was not statistically significant. Intraocular manifestations observed during the study period included ocular hypertension (14.3%), anterior uveitis (100.0%), retinal hemorrhage (71.4%), vitreous opacity (100.0%), retinal exudative vasculitis (85.7%), optic nerve atrophy (85.7%), retinal vascular occlusion (85.7%), choroidal atrophy (85.7%), macular edema (100.0%), subretinal fluid in the macula (71.4%), and retinal detachment (85.7%). Treatment modalities included oral and intravitreal antivirals (85.7%), antiplatelet medications (85.7%), steroid eye drops (85.7%), subcapsular (57.1%) and vitreous (42.9%) steroid injections, oral steroids (71.4%), and surgical intervention (85.7%). Vitrectomy led to retinal recovery in all five eyes that underwent the procedure. Conclusions The visual prognosis of patients with ARN is poor, particularly in those with preexisting visual impairment. Early detection coupled with antiviral therapy and prompt surgical intervention have been identified as potential factors that influence visual outcomes. Given the severity of ARN, collecting data from multiple centers could aid in devising future diagnostic and therapeutic strategies.
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Acute zoster-associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster-associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster-associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double-blind, placebo-controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min after dosing. Seventeen patients were randomly assigned to the low-dose fosphenytoin group (n = 6, median age 62.5 years, range 39-75 years), high-dose fosphenytoin group (n = 5, median age 69.0 years, range 22-75 years), and placebo group (n = 5, median age 52.0 years, range 38-72 years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group (P < 0.001 and P = 0.016, respectively). Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10-15 µg/mL. Treatment-emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster-associated pain. Trial Registration: ClinicalTrials.gov NCT04139330.
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Herpes Zoster , Dor , Fenitoína , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Analgésicos , Analgésicos não Narcóticos/farmacologia , Método Duplo-Cego , Herpes Zoster/complicações , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3 , Dor/tratamento farmacológico , Dor/etiologia , Fenitoína/efeitos adversosRESUMO
OBJECTIVES: The aim of this study was to examine the potential for S-LEC™ Solar Control Film L, a heat insulating interlayer film for laminated glass developed by Sekisui Chemical Co., Ltd., to reduce the burning sensation caused by near infrared (NIR) radiation. METHODS: A crossover study was performed in 49 male and female subjects, using three different combinations of laminated glass with interlayer films. Subjects placed their right hand under each glass in an NIR irradiation device. The dorsal side of the right hand was irradiated with NIR for 30 s and the onset and degree of a burning sensation was measured. RESULTS: Laminated glass with S-LEC™ Solar Control Film L reduced the burning sensation caused by NIR and delayed the onset of the sensation, compared with the control glasses. CONCLUSION: The use of S-LEC™ Solar Control Film L in the laminated glass of vehicles may improve passenger comfort and prevent skin disorders such as photoaging caused by prolonged exposure to NIR.
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Raios Infravermelhos , Luz Solar , Masculino , Humanos , Feminino , Estudos Cross-Over , SensaçãoRESUMO
As near-infrared radiation (NIR), which is a composition of sunlight with an 780-1400 nm wavelength, is associated with skin aging such as wrinkles and slacks, the biological actions of NIR with high dermal penetration remains unclear. In the present study, we found that NIR irradiation (40 J/cm2 ) at different levels of irradiance (95-190 mW/cm2 ) using a laboratory device with a xenon flash lamp (780-1700 nm) caused sebaceous gland enlargement concomitantly with skin thickening in the auricle skin of hamsters. The sebaceous gland enlargement resulted from the proliferation of sebocytes due to an increase in the number of proliferating cell nuclear antigen (PCNA)- and lamin B1-positive cells in vivo. In addition, NIR irradiation transcriptionally augmented the production of epidermal growth factor receptor (EGFR) accompanied with an increase in the reactive oxygen species (ROS) level in hamster sebocytes in vitro. Furthermore, the administration of hydrogen peroxide increased the level of EGFR mRNA in the sebocytes. Therefore, these results provide novel evidence that NIR irradiation causes the hyperplasia of sebaceous glands in hamsters by mechanisms in which EGFR production is transcriptionally augmented through ROS-dependent pathways in sebocytes.
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Receptores ErbB , Raios Infravermelhos , Doenças das Glândulas Sebáceas , Glândulas Sebáceas , Animais , Cricetinae , Receptores ErbB/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Doenças das Glândulas Sebáceas/etiologia , Doenças das Glândulas Sebáceas/metabolismo , Glândulas Sebáceas/metabolismo , Glândulas Sebáceas/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Raios Infravermelhos/efeitos adversosRESUMO
INTRODUCTION: Atopic dermatitis (AD), with its signs and symptoms of pruritus, dryness, and erythema, severely reduces the quality of life (QOL) of affected patients. We investigated the impact of nemolizumab 60 mg on QOL in Japanese patients aged ≥ 13 years with AD and inadequately controlled moderate-to-severe pruritus, using data derived from patient-reported outcome (PRO) measures. METHODS: PROs were the Insomnia Severity Index (ISI), Dermatology Life Quality Index (DLQI), Patient-Oriented Eczema Measure (POEM), and Work Productivity and Activity Impairment: Atopic Dermatitis questionnaire (WPAI-AD). Correlations between PRO scores and symptom severity, assessed by the pruritus visual analog scale (VAS) and the Eczema Area and Severity Index (EASI), were explored. RESULTS: The mean percent change (standard error) from baseline in the pruritus VAS and EASI scores at week 16 was, respectively, -45.6% (2.7) and -46.0% (3.2) in the nemolizumab group, and -24.1% (3.7) and -33.2% (4.9) in the placebo group. By week 16, significantly more patients in the nemolizumab group versus the placebo group had an ISI score of 0 for difficulty falling asleep (41.6% versus 13.1%, nominal p < 0.01) or difficulty staying asleep (45.4% versus 10.9%; nominal p < 0.01). Similarly, more nemolizumab- than placebo-treated patients had a DLQI score of 0 for interference with shopping, or home/garden activities (45.2% versus 18.6%, nominal p < 0.01), and 0 days per week of nighttime sleep disturbance (50.8% versus 16.9%, nominal p < 0.01) or bleeding skin (43.4% versus 7.5%, nominal p < 0.01) measured by POEM at week 16. Based on WPAI-AD scores, long-term administration of nemolizumab also improved the ability to conduct work activities. CONCLUSIONS: Subcutaneous administration of nemolizumab ameliorated pruritus and skin signs, and thereby produced improvement in patient QOL across multiple PRO measures, including sleep, interpersonal relationships, and the ability to conduct social or work activities. CLINICAL TRIAL REGISTRATION: JapicCTI-173740 (registered 20 October 2017).
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BACKGROUND: Data from the Japanese phase 3 Nemolizumab-JP01 study (JapicCTI-173740) found that nemolizumab in combination with topical treatments reduced pruritus associated with atopic dermatitis inadequately controlled with current therapies. METHODS: This post-hoc analysis examined associations between improvements in pruritus (visual analog scale [VAS]) and eczema (Eczema Area and Severity Index [EASI]), and achievement of other clinically relevant endpoints including the Insomnia Severity Index (ISI), Dermatology Life Quality Index (DLQI), and Patient-Oriented Eczema Measure (POEM). RESULTS: Pruritus VAS responders (≥50% improvement from baseline to week 16) showed greater improvements from baseline in these additional endpoints as early as week 1, compared with non-responders. Responders also had EASI improvement, and more than 80% achieved an ISI score ≤7, or had improvement in the DLQI or POEM. The percent change from baseline in VAS and EASI scores at week 16 was in favor of nemolizumab in all subgroups based on baseline characteristics. No specific factor affecting treatment response to nemolizumab was identified. CONCLUSIONS: In this post-hoc analysis, nemolizumab-treated patients who had greater pruritus reductions also showed improvements in other eczema symptoms; pruritus alleviation appeared to be responsible for the improvements in eczema, sleep and daily life.
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Dermatite Atópica , Eczema , Humanos , Dermatite Atópica/complicações , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/diagnóstico , Qualidade de Vida , Prurido/tratamento farmacológico , Prurido/etiologia , Índice de Gravidade de Doença , Resultado do Tratamento , Método Duplo-CegoRESUMO
BACKGROUND: Visualization of aqueous humor flow in MR contrast images using gadolinium is challenging because of the delayed contrast effects associated with the blood-retinal and blood-aqueous humor barriers. However, oxygen-17 water (H2 17 O) might be used as an ocular contrast agent. PURPOSE: To observe the distribution of H2 17 O in the human eye, and its flow in and out of the anterior chamber, using dynamic T2-weighted MRI. STUDY TYPE: Prospective. POPULATION: Six ophthalmologically normal volunteers (20-37 years, six females). FIELD STRENGTH/SEQUENCE: A 3 T/dynamic T2-weighted MRI. ASSESSMENT: H2 17 O eye drops were administered to the right eye. Time-series images were created by subtracting the image before the eye drops from each of the images obtained after the eye drops. The normalized signal intensity of the right anterior chamber (nAC) was obtained by dividing the signal intensity of the right anterior chamber region by that of the left. The inflow and outflow constants of H2 17 O and H2 17 O concentration were calculated from the nAC. STATISTICAL TESTS: A paired t-test was used to compare the flow-related values and temporal changes in signal intensity. P-values < 0.05 were considered statistically significant. RESULTS: Significantly decreased signal intensity was observed in the right anterior chamber but not the right vitreous body (P = 0.39). The nAC signal intensity decreased significantly and then recovered. The inflow and outflow constants were 0.36-0.94 min-1 and 0.023-0.13 min-1 , respectively. The maximum H2 17 O concentration was 0.078%-0.24%. DATA CONCLUSION: H2 17 O were distributed in the anterior chamber. The H2 17 O inflow into the anterior chamber was significantly faster than that of the outflow. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.
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Humor Aquoso , Movimentos da Água , Feminino , Humanos , Soluções Oftálmicas , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodosRESUMO
Amenamevir (ASP2151), a novel, non-nucleoside analog, antiviral drug, inhibits the enzyme activities of helicase and primase, which are essential for replication of herpes viral genomic DNA. In this phase 3, randomized, double-blind, placebo-controlled, multicenter study, the authors investigated the efficacy and safety of a single patient-initiated dose of amenamevir to treat recurrent herpes labialis. Adult immunocompetent patients with recurrent herpes labialis who had the experience and ability to recognize prodromal symptoms were randomly assigned to administer amenamevir 1200 mg or placebo as a patient-initiated therapy within 6 hours after onset of prodromal symptoms. The primary efficacy end point was time to healing of all herpes labialis lesions in the modified intention-to-treat population. Secondary efficacy end points were time to crusting of all herpes labialis lesions, time to resolution of pain accompanying herpes labialis, proportion of patients with aborted lesions, and time to resolution of subjective symptoms accompanying herpes labialis. The modified intention-to-treat population, which excluded patients with aborted lesions, comprised 298 patients who self-initiated amenamevir and 307 who took placebo. Amenamevir demonstrated superiority over placebo for the primary end point; the median time to all lesion healing was 5.1 days for amenamevir versus 5.5 days for placebo (hazard ratio, 1.24; 95% confidence interval, 1.06-1.46; p = 0.0085). Time to crusting of all lesions was significantly shorter with amenamevir versus placebo (p = 0.0065); there were no significant between-group differences in other secondary outcomes. Treatment-emergent adverse events in both groups were generally mild in severity; there were two moderate events that were judged unrelated to study treatment, and no severe or serious events. In summary, a single patient-initiated dose of amenamevir 1200 mg taken within 6 hours of prodromal symptom onset significantly shortened the time to all lesion healing of recurrent herpes labialis compared with placebo, with no clinically important safety concerns.
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Herpes Labial , Adulto , Humanos , Herpes Labial/tratamento farmacológico , Herpes Labial/induzido quimicamente , Sintomas Prodrômicos , Recidiva Local de Neoplasia/tratamento farmacológico , Antivirais/efeitos adversos , Método Duplo-Cego , RecidivaRESUMO
Purpose: Asian dust poses a serious global health hazard. Airborne particles adhering to contact lenses may cause substantial damage to the ocular surface. The recently released one-day disposable silicone hydrogel soft contact lens (SCL), the verofilcon A, has a smooth surface with SMARTSURFACE® technology, which is designed to prevent adhesion of protein components and foreign bodies. The purpose of this study was to verify the protective quality of verofilcon A SCL against adhesion of Asian dust particles to its surface. Methods: Verofilcon A and etafilcon A (control lens) SCLs were used (n=16 per group), and 0.2 mL of physiological saline containing 0.01 mg/mL of Asian dust particles was dropped on the surface of SCLs, allowed to stand for 1 hour, shaken for 1 minute, and rinsed three times with saline (after rinsing). In addition, the samples were agitated by a vortex mixer for 1 minute and rinsed three times with saline (after vortex). The number of Asian dust particles adhering to the SCLs and percentage of the surface area occupied by the Asian dust particles was determined before washing, after rinsing, and after vortexing. Results: The number of adherent Asian dust particles was lower on verofilcon A SCL (297 ± 116 after rinsing, and 5 ± 14 after vortexing) than on etafilcon A SCL (523 ± 212 after rinsing, p=0.003, and 378 ± 268 after vortexing, p<0.001). The Asian dust adhesion area was also lower on verofilcon A SCL (3.6 ± 2.3% after rinsing and 0.0 ± 0.1% after vortexing than on etafilcon A (10.2 ± 2.1% after rinsing, p=0.002, and 5.2 ± 3.0% after vortexing, p<0.001). Conclusion: These findings indicate that verofilcon A SCL has the property of low adhesion of Asian dust particles. Verofilcon A SCL can be recommended for SCL wearers during windy and Asian dust days.
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Purpose: The purpose of this study was to determine the effect of brilliant blue G (BBG) staining of the inner limiting membrane (ILM) on macular function. Method: Fourteen eyes of 14 patients consisting of 9 men and 5 women who underwent vitreous surgery with ILM peeling were studied. The mean age of the patients was 68.8 ± 9.14 years. Three eyes had a macular hole and eleven eyes had an epiretinal membrane. The ILM was made more visible by spraying 0.25% BBG into the vitreous cavity. The macular function was assessed by recording intraoperative focal macular electroretinograms (iFMERGs) before and after the intravitreal spraying of the BBG dye. The iFMERGs were recorded three times after core vitrectomy. The first recording was performed before the BBG injection (Phase 1, baseline), the second recording was performed after the spraying of the BBG and washing out the excess BBG (Phase 2), and the third recording was performed after the ILM peeling (Phase 3). All recordings were performed after 5 min of light-adaptation and stabilization of the intraocular conditions. The iFMERGs were recorded twice at each phase. The implicit times and amplitudes of the a- and b-wave, the PhNR, and the d-wave were measured. Wilcoxon signed-rank test were used to determine the significance of differences of the findings at Phase 2 vs. Phase 1 and Phase 3 vs. Phase 1. A p value < 0.05 was taken to be statistically significant. Results: The average implicit times of the a-wave, b-wave, PhNR, and d-wave were not significantly different in Phase 1, 2, and 3. The average a-wave, b-wave, PhNR, and d-wave amplitudes at Phase 1 did not differ significantly from that at Phase 2 and at Phase 3. Conclusions: The results indicated that the intravitreal injection of BBG does not alter the physiology of the macula, and we conclude that BBG is safe. We also conclude that iFMERGs can be used to monitor the macular function safely during intraocular surgery.
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Background: Amenamevir is a helicase-primase inhibitor with novel mechanisms of antiherpetic action. A patient-initiated single-dose regimen showed clinical efficacy for genital herpes in a phase 2 study. Methods: In this phase 3 study, adult immunocompetent patients with recurrent genital herpes and able to accurately recognize prodromal symptoms were randomly assigned to administer amenamevir 1200â mg or placebo as a patient-initiated therapy within 6â hours after onset of prodromal symptoms. The primary efficacy endpoint was time to healing of all genital herpes lesions. Results: In the modified intention-to-treat population, which excluded patients with aborted lesions (amenamevir, n = 89; placebo, n = 97), the median time to all lesion healing was 4.0 days for amenamevir versus 5.1 days for placebo (hazard ratio, 1.60 [95% confidence interval, 1.19-2.15]; P = .0018), indicating superiority of amenamevir. All treatment-emergent adverse events in both groups were mild in severity. Conclusions: Patient-initiated single-dose amenamevir reduced the time to all lesion healing of recurrent genital herpes versus placebo, with no safety concerns, suggesting it could be an effective treatment option for patients with recurrent genital herpes. Clinical Trials Registration. JapicCTI-194955.
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INTRODUCTION: Amenamevir is a new anti-varicella-zoster virus drug that inhibits the helicase-primase complex involved in viral replication. Amenamevir has the same effect as valaciclovir on acute pain and skin eruption, but no studies have examined the presence of long-term zoster-associated pain (ZAP) or postherpetic neuralgia (PHN) after amenamevir treatment. METHODS: A total of 785 herpes zoster patients treated with amenamevir were followed up for 12 months. Patients recorded their pain status on a questionnaire once a month. RESULTS: The proportion of patients with pain was 20.8% at 90 days, 8.0% at 180 days, 3.8% at 270 days, and 2.7% at 360 days after treatment. The median residual pain duration was 48 days. ZAP resolution rate slowed between 90 and 120 days, suggesting that the main feature of ZAP is a shift from nociceptive pain to neuropathic pain. Older age and more severe skin symptoms at the first visit were associated with a higher risk of developing PHN. Median ZAP duration was high for the head, face, and upper back and chest. Regarding the nature of pain, sudden pain attacks that felt like electric shocks, sensation of numbness, burning sensation, and cold/heat pain tended to remain as PHN. CONCLUSIONS: Although conclusions must remain tentative without further comparative studies, amenamevir seems to have a similar effect on PHN as conventional nucleoside analogs, despite having a different action mechanism. CLINICAL TRIAL REGISTRATION: UMIN000035938.
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A decrease in the ceramide content of the stratum corneum is known to cause dry and barrier-disrupted skin. In this literature review, the clinical usefulness of preparations containing natural or synthetic ceramides for water retention and barrier functions was evaluated. The PubMed, Cochrane Library, and Igaku Chuo Zasshi databases were searched using keywords such as "ceramide", "skincare products", "barrier + hydration + moisture + skin", and "randomized trial". All database searches were conducted in February 2019. Forty-one reports were selected based on the following criterion: comparative control studies that evaluated the effects of ceramide-containing formulations based on statistical evidence. Among the 41 reports, 12 were selected using the patient, intervention, comparison, and outcome approach. These 12 reports showed that external ceramide-containing preparations can improve dry skin and barrier function in patients with atopic dermatitis. However, a double-blinded comparative study with a large sample size is warranted for appropriate clinical use.
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Dermatite Atópica , Eczema , Ceramidas , Dermatite Atópica/tratamento farmacológico , Epiderme , Humanos , ÁguaRESUMO
PURPOSE: Pollen and proteins attached to soft contact lenses (SCLs) exacerbate allergic conjunctivitis. The material of SCLs may affect the pollen adhesion to the SCLs. The factors associated with the number of pollen particles that are adherent to daily disposable SCL were investigated. METHODS: Pollen particles were experimentally exposed to the contact lens surface of 12 types of SCLs for 1 hour, and the SCLs were washed and rinsed with a physiological saline (n=10 for each SCL type). A total of 120 contact lenses were used in this study. The pollen particles attached to the SCL were observed and photographed under a microscope. The influence of the materials of the SCLs on the degree of pollen adhesion were investigated. RESULTS: The number of residual pollen particles attached to SCLs was in the range from 0-293/area of 200×200 µm. Percentage of pollen adhesion area of the surface of the SCL was in the range from 0.01% to 3.25%. There were significant differences in both the number and adhesion area of pollen particles among the 12 types of SCLs tested (P<0.0001 and P<0.0001, respectively). The number of pollen particles adhered to SCLs was significantly higher in colored SCLs than clear SCLs (unpaired t-test, p<0.001). The portion of pollen adhesion area was the lowest in the silicone hydrogel SCLs made with delefilcon-A (0.01 ± 0.02%). CONCLUSION: Pollen adhesion in daily disposable SCLs depends on the characteristics and materials of the SCLs and was high in colored SCLs and lowest in delefilcon-A silicone hydrogel SCL. These results suggest that colored SCLs are not preferred during pollen season.
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BACKGROUND: Although the structural changes of the scalp in androgenetic alopecia (AGA) have been reported, these changes have been poorly understood. It is expected that modern MRI would visualize the scalp anatomy in vivo. This study aimed to explore whether AGA causes (a) changes in the thickness of the scalp, (b) anatomical changes in the hair follicles, and (c) changes in the signal intensity of MRI. MATERIALS AND METHODS: Twenty-seven volunteers underwent MRI for hair and scalp (MRH) and were categorized into two according to the Hamilton-Norwood Scale: the "AGA group" and the "normal group." Two radiologists analyzed the thickness and signal intensity of the scalp, and the depth of hair follicles. These measurements were compared between the two groups. RESULTS: The thickness of the hypodermis and the entire scalp was significantly thinner in the AGA group than in the control group. The AGA group had significantly shallower depth of hair follicles and relative depth of the hair follicles to that of the entire scalp than the normal group. The hypodermis showed higher signal intensity in the AGA group than the normal group. CONCLUSION: MRH allowed noninvasive visualization of the scalp anatomy and demonstrated the thinner nature of the entire scalp and hypodermis, along with the shallower depth of the hair follicles in the AGA group in comparison to the normal group. Additionally, MRH demonstrated the increased MR signal intensity in the scalp associated with AGA. MRH may be a promising new method for quantitative and objective analyses of AGA.
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Folículo Piloso , Couro Cabeludo , Alopecia/diagnóstico por imagem , Cabelo , Folículo Piloso/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Couro Cabeludo/diagnóstico por imagemRESUMO
PURPOSE: Although androgenetic alopecia (AGA) is a common cause of hair loss, little is known regarding the magnetic resonance imaging (MRI) of the AGA or scalp. This study aimed to analyze whether MRI for hair and scalp (MRH) can evaluate anatomical changes in the scalp caused by AGA. METHODS: Twenty-seven volunteers were graded for the severity of AGA using the Hamilton-Norwood Scale (HNS), commonly used classification system. All subjects underwent MRH; two radiologists independently analyzed the images. As a quantitative measurement, the number of hair follicles was analyzed and compared with the HNS. As a qualitative analysis, each MRH scan was visually graded in terms of the severity of alopecia, using a 4-point MR severity score. The scores were compared with the HNS. RESULTS: The volunteers were divided into two groups of 12 and 15 males without and with AGA at their vertex, respectively. Inter-observer agreements for the hair count and the MR severity score were excellent. The mean hair count on MRI in the normal group was significantly higher than that in the AGA group (P < 10-4). The MR severity score in the AGA group was significantly more severe than that in the control group (P < 10-4). In terms of the presence or absence of thinning hair, the MR severity score was consistent with the HNS determined by a plastic surgeon in 96% of cases. MR severity scores of clinically moderate AGA cases were significantly lower than those of severe cases (P = 0.022). CONCLUSION: MRH could depict scalp anatomy showing a clear difference between AGA and normal scalps, in both hair count and subjective visual assessment. The MR severity score was in good agreement with the clinical stages by HNS. The results support the potential of MRH as a promising imaging technique for analyzing healthy and pathological scalps.
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Alopecia/diagnóstico por imagem , Alopecia/patologia , Folículo Piloso/diagnóstico por imagem , Cabelo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Couro Cabeludo/diagnóstico por imagem , Adulto , Cabelo/patologia , Folículo Piloso/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Couro Cabeludo/patologiaRESUMO
A ceramide deficiency in the stratum corneum (SC) is an essential etiologic factor for the dry and barrier-disrupted skin of patients with atopic dermatitis (AD). Previously, we reported that sphingomyelin (SM) deacylase, which hydrolyzes SM and glucosylceramide at the acyl site to yield their lysoforms sphingosylphosphorylcholine (SPC) and glucosylsphingosine, respectively, instead of ceramide and/or acylceramide, is over-expressed in AD skin and results in a ceramide deficiency. Although the enzymatic properties of SM deacylase have been clarified, the enzyme itself remains unidentified. In this study, we purified and characterized SM deacylase from rat skin. The activities of SM deacylase and acid ceramidase (aCDase) were measured using SM and ceramide as substrates by tandem mass spectrometry by monitoring the production of SPC and sphingosine, respectively. Levels of SM deacylase activity from various rat organs were higher in the order of skin > lung > heart. By successive chromatography using Phenyl-5PW, Rotofor, SP-Sepharose, Superdex 200 and Shodex RP18-415, SM deacylase was purified to homogeneity with a single band of an apparent molecular mass of 43 kDa with an enrichment of > 14,000-fold. Analysis by MALDI-TOF MS/MS using a protein spot with SM deacylase activity separated by 2D-SDS-PAGE allowed its amino acid sequence to be determined and identified as the ß-subunit of aCDase, which consists of α- and ß-subunits linked by amino bonds and a single S-S bond. Western blotting of samples treated with 2-mercaptoethanol revealed that, whereas recombinant human aCDase was recognized by antibodies to the α-subunit at ~56 kDa and ~13 kDa and the ß-subunit at ~43 kDa, the purified SM deacylase was detectable only by the antibody to the ß-subunit at ~43 kDa. Breaking the S-S bond of recombinant human aCDase with dithiothreitol elicited the activity of SM deacylase with ~40 kDa upon gel chromatography. These results provide new insights into the essential role of SM deacylase expressed as an aCDase-degrading ß-subunit that evokes the ceramide deficiency in AD skin.
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Amidoidrolases , Dermatite Atópica/enzimologia , Pele/enzimologia , Ceramidase Ácida/química , Amidoidrolases/química , Amidoidrolases/isolamento & purificação , Animais , Ceramidas/deficiência , Humanos , Masculino , Ratos , Ratos Wistar , Pele/patologiaRESUMO
BACKGROUND: Nemolizumab is a subcutaneously administered humanized monoclonal antibody against interleukin-31 receptor A, which is involved in pruritus and inflammation in atopic dermatitis. In phase 2 studies, nemolizumab lessened the severity of atopic dermatitis. METHODS: In a 16-week, double-blind, phase 3 trial, we randomly assigned Japanese patients with atopic dermatitis and moderate-to-severe pruritus and an inadequate response to topical agents in a 2:1 ratio to receive subcutaneous nemolizumab (60 mg) or placebo every 4 weeks until week 16, with concomitant topical agents. The primary end point was the mean percent change in the visual-analogue scale (VAS) score for pruritus (range, 0 to 100, with higher scores indicating worse pruritus) from baseline to week 16. Secondary end points included the time course of change in the VAS score for pruritus up to week 4, the change in the Eczema Area and Severity Index (EASI) score (range, 0 to 72, with higher scores indicating greater severity), a score of 4 or less on the Dermatology Life Quality Index (DLQI; range, 0 to 30, with higher scores indicating a greater effect on daily life), a score of 7 or less on the Insomnia Severity Index (ISI; range, 0 to 28, with higher scores indicating greater severity), and safety. RESULTS: A total of 143 patients were randomly assigned to receive nemolizumab and 72 to receive placebo. The median VAS score for pruritus at baseline was 75. At week 16, the mean percent change in the VAS score was -42.8% in the nemolizumab group and -21.4% in the placebo group (difference, -21.5 percentage points; 95% confidence interval, -30.2 to -12.7; P<0.001). The mean percent change in the EASI score was -45.9% with nemolizumab and -33.2% with placebo. The percentage of patients with a DLQI score of 4 or less was 40% in the nemolizumab group and 22% in the placebo group; the percentage of patients with an ISI score of 7 or less was 55% and 21%, respectively. The incidence of injection-related reactions was 8% with nemolizumab and 3% with placebo. CONCLUSIONS: In this 16-week trial, the use of subcutaneous nemolizumab in addition to topical agents for atopic dermatitis resulted in a greater reduction in pruritus than placebo plus topical agents. The incidence of injection-site reactions was greater with nemolizumab than with placebo. Longer and larger trials are necessary to determine whether nemolizumab has a durable effect and is safe for atopic dermatitis. (Funded by Maruho; JapicCTI number, 173740.).
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Anticorpos Monoclonais Humanizados/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Dermatite Atópica/tratamento farmacológico , Glucocorticoides/administração & dosagem , Antagonistas dos Receptores Histamínicos/uso terapêutico , Prurido/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/complicações , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Prurido/etiologia , Escala Visual Analógica , Adulto JovemRESUMO
Importance: The dupilumab regimen of 300 mg every 2 weeks is approved for uncontrolled, moderate to severe atopic dermatitis (AD). Objective: To assess the efficacy and safety of different dupilumab regimens in maintaining response after 16 weeks of initial treatment. Design, Setting, and Participants: The Study to Confirm the Efficacy and Safety of Different Dupilumab Dose Regimens in Adults With Atopic Dermatitis (LIBERTY AD SOLO-CONTINUE) was a randomized, double-blind, phase 3 clinical trial conducted from March 25, 2015, to October 18, 2016, at 185 sites in North America, Europe, Asia, and Japan. Patients with moderate to severe AD who received dupilumab treatment and achieved an Investigator's Global Assessment score of 0 or 1 or 75% improvement in Eczema Area and Severity Index scores (EASI-75) at week 16 in 2 previous dupilumab monotherapy trials (LIBERTY AD SOLO 1 and 2) were rerandomized in SOLO-CONTINUE. After completing SOLO-CONTINUE, patients were followed up for up to 12 weeks or enrolled in an open-label extension. Data were analyzed from December 5 to 12, 2016. Interventions: High-responding patients treated with dupilumab in SOLO were rerandomized 2:1:1:1 to continue their original regimen of dupilumab, 300 mg, weekly or every 2 weeks or to receive dupilumab, 300 mg, every 4 or 8 weeks or placebo for 36 weeks. Main Outcomes and Measures: Percentage change in EASI score from baseline during the SOLO-CONTINUE trial, percentage of patients with EASI-75 at week 36, and safety. Results: Among the 422 patients (mean [SD] age, 38.2 [14.5] years; 227 [53.8%] male), continuing dupilumab treatment once weekly or every 2 weeks maintained optimal efficacy, with negligible change in percent EASI improvement from SOLO 1 and 2 baseline during the SOLO-CONTINUE trial (-0.06%; P < .001 vs placebo); percent change with the other regimens dose-dependently worsened (dupilumab every 4 weeks, -3.84%; dupilumab every 8 weeks, -6.84%; placebo, -21.67%). More patients taking dupilumab weekly or every 2 weeks (116 of 162 [71.6%]; P < .001 vs placebo) maintained EASI-75 response than those taking dupilumab every 4 weeks (49 of 84 [58.3%]) or every 8 weeks (45 of 82 [54.9%]) or those taking placebo (24 of 79 [30.4%]). Overall adverse event incidences were 70.7% in the weekly or every 2 weeks group, 73.6% in the every 4 weeks group, 75.0% in the every 8 weeks group, and 81.7% in the placebo group. Treatment groups had similar conjunctivitis rates. Treatment-emergent antidrug antibody incidence was lower with more frequent dupilumab dose regimens (11.3% in the placebo group and 11.7%, 6.0%, 4.3%, and 1.2% in the dupilumab every 8 weeks, every 4 weeks, every 2 weeks, and weekly groups, respectively). Conclusions and Relevance: In this trial, continued response over time was most consistently maintained with dupilumab administered weekly or every 2 weeks. Longer dosage intervals and placebo resulted in a diminution of response for both continuous and categorical end points. No new safety signals were observed. The approved regimen of 300 mg of dupilumab every 2 weeks is recommended for long-term treatment. Trial Registration: ClinicalTrials.gov identifier: NCT02395133.