Patients' and caregivers' perspectives of the atopic dermatitis journey.

BACKGROUND: Understanding the patient journey is important to optimize care for patients with atopic dermatitis (AD) and overcome challenges in diagnosis and management. OBJECTIVE: To explore patient and caregiver perspectives regarding their experience with AD. METHODS: Patients and caregivers of patients with AD completed a pre-meeting survey and were invited to join an advisory board meeting in their country (China, Hong Kong, Ireland, Japan and Lebanon) to discuss the survey results. Data were analyzed descriptively. RESULTS: The survey included 31 participants (patients and caregivers) from Hong Kong (n = 7), China (n = 7), Ireland (n = 6), Japan (n = 6) and Lebanon (n = 5). The most challenging factors in the AD journey were management of symptoms before a confirmed diagnosis (68%), sudden recurrence of flares or worsening of symptoms (68%) and lifestyle changes (52%). In terms of overall AD management, 35% of participants indicated that AD was managed well, 23% had a clear treatment plan and 19% were generally satisfied with disease management. A collaborative relationship with healthcare professionals was favored. CONCLUSION: A holistic assessment of AD includes understanding patient and caregiver preferences, needs, experiences and disease perceptions. Addressing the identified gaps may improve the management of AD.

Palmitate induces apoptosis and inhibits osteogenic differentiation of human periodontal ligament stem cells.

OBJECTIVE: The aim of the present study was to investigate the effect of palmitate on human periodontal ligament stem cells (PDLSCs). DESIGN: PDLSCs were isolated from the third molars of healthy adult donors, and cultured in normal or osteogenic medium supplemented with palmitate (0, 100, or 250 µM) for 21 days. Cell proliferation was evaluated by measuring the amount of formazan at 6, 24, 48, and 72 h. Apoptosis was detected by ELISA and terminal deoxynucleotidyl transferase dUTP nick end labeling assay at days 3 and 7. Osteogenic differentiation was evaluated by measuring the alkaline phosphatase (ALP) activity, production of procollagen type I C-peptide and osteocalcin, mineralization, and mRNA expression of Runx2 at days 3, 7, 14, and 21. In addition, mRNA expression of IL-6 and IL-8 was measured at day 3. RESULTS: Palmitate inhibited the proliferation, ALP activity, production of procollagen type I C-peptide and osteocalcin, mineralization, and mRNA expression of Runx2 in the cultured PDLSCs. Palmitate also induced apoptosis and mRNA expression of IL-6 and IL-8 in the PDLSCs. CONCLUSIONS: The results of the present study demonstrate that palmitate induces apoptosis and inhibits osteogenic differentiation of PDLSCs. These findings may help clarify the relationship between palmitate and periodontal tissue regeneration.

Oral administration of ß-carotene or lycopene prevents atopic dermatitis-like dermatitis in HR-1 mice.

Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease. Certain populations of patients are resistant to standard therapies with topical steroids and/or calcineurin inhibitors, and require systemic medication, such as immunosuppressants. Recently, several reports have shed light on the anti-allergic effects of carotenoids. Therefore, we investigated the effect of p.o. administration of ß-carotene or lycopene on AD-like symptoms of HR-1 hairless mice fed with a low zinc/magnesium diet. Mice were divided into four groups: (i) fed with a standard diet (Co group); (ii) low zinc/magnesium diet (HR group); (iii) low zinc/magnesium and ß-carotene diet (HR-C group); and (iv) low zinc/magnesium and lycopene diet (HR-L group). They were then fed these diets for 8 weeks. Severities of dermatitis were assessed by their appearance, and histopathological and hematological observations. Mice in the HR group developed AD-like dermatitis both clinically and histologically. HR-C and HR-L group mice also developed xerosis and wrinkle-like skin changes, but they were milder than those of HR group mice. Histological analysis revealed that epidermis thickening and inflammatory cell infiltration in the skin of the HR-C and HR-L groups were both statistically less than those of the HR group. The concentration of thymus and activation regulated chemokine in the skin of the HR-L group and the concentration of CCL27 in the skin of the HR-C group were significantly lower than those of the HR group, respectively. In conclusion, p.o. administration of ß-carotene or lycopene prevents AD-like symptoms in association with a suppression of T-helper 2 chemokines in a murine model. Ingestion of carotenoids may be beneficial for patients with AD.

Evaluation of recombinant MGL_1304 produced by Pichia pastoris for clinical application to sweat allergy.

BACKGROUND: We previously identified MGL_1304 secreted by Malassezia globosa as a sweat antigen for patients with atopic dermatitis (AD) and cholinergic urticaria (ChU). However, purifying native MGL_1304 from human sweat or culture supernatant of M. globosa (sup-MGL_1304) is costly and time-consuming. Moreover, recombinant MGL_1304 expressed by using Escherichia coli (TF-rMGL_1304) needs a large chaperon protein and lacks the original glycosylation of yeasts. Thus, we generated a recombinant MGL_1304 by Pichia pastoris (P-rMGL_1304) and investigated its characteristic features. METHODS: Recombinant MGL_1304 proteins expressed by E. coli and P. pastoris were generated. Properties of these recombinants and native antigens were compared by western blot analysis, histamine release tests (HRT) of patients with AD and ChU, and ß-hexosaminidase release tests with RBL-48 cells. P-rMGL_1304-specific IgE in sera of patients with AD were measured by sandwich ELISA. RESULTS: Western blot analysis revealed that IgE of patients with AD bound to all MGL_1304 recombinants and native antigens. The histamine releasing ability of P-rMGL_1304 was 100 times higher than that of TF-rMGL_1304, and was comparable to that of sup-MGL_1304. Degranulation rates of RBL-48 cells, sensitized with sera of patients with AD in response to the stimulation of P-rMGL_1304, were comparable to those of sup-MGL_1304, whereas those of TF-rMGL_1304 were relatively weak. The levels of P-rMGL_1304-specific IgE in sera of patients with AD were correlated with their disease severities. CONCLUSIONS: P-rMGL_1304 has an antigenicity comparable to the native antigen, and is more useful than TF-rMGL_1304, especially in HRT and degranulation assay of RBL-48 cells.

[Pneumococcal meningitis with accompanying severe hearing loss: 3D-FLAIR imaging of the inner ear and treatment].

A 66-year-old man was admitted to our hospital because of unconsciousness. He was diagnosed with pneumococcal meningitis and treated with a combination of antibiotics (meropenem hydrate), dexamethasone, and intravenous immunoglobulin. Although he gradually regained consciousness, he started showing signs of hearing disturbance. Measurement of auditory brainstem response revealed severe sensorineural hearing loss. The patient then underwent three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging, which revealed increased signals in the cochlea and the vestibuum, and their enhancement after gadolinium administration. This enhancement was still observed on images of the inner ear acquired on the 52nd hospital day. These findings suggested that the change of content in the lymph and the damage to the blood-labyrinth barrier was caused and aggravated by an immune response. Recent studies have shown that an MyD88-dependent immune response contributes to hearing loss in an experimental mouse model of pneumococcal meningitis. The patient was administered steroid pulse and hyperbaric oxygen therapies for improving the hearing deficit, but these therapies were discontinued because of the aggravation of hepatitis B and diabetes mellitus, which he had developed previously.

[A case of large carcinoma of the tongue and mouth floor, in which chemotherapy using a combination of nedaplatin and 5-FU was effective].

We encountered a case of extensive squamous cell carcinoma ranging from the tongue to the mouth floor, in which chemotherapy using a combination of nedaplatin and 5-FU was effective. The patient was a 46-year-old male, who noticed a small mass in the mouth floor in September 2000, and visited the department of oral and maxillofacial surgery at a hospital on October 12, 2000. A 27 x 15 mm tumor with erosion was noted on the mouth floor, which was diagnosed as squamous cell carcinoma by biopsy, and the patient was referred to our department for treatment on November 16, 2000. Intra-oral findings included a healthy-colored induration with a bulge in the area ranging from the apex of the tongue posteriorly for 30 mm, and from the right lateral edge of the tongue to the left side exceeding the median area of the tongue by approximately 7 mm. MRI detected a tumor of approximately 2 cm in diameter in the area ranging from the median area of the tongue to the right ventral side of the tongue, which protruded on the mouth floor side. Two courses of combination chemotherapy using nedaplatin and 5-FU were performed. Nedaplatin (90 mg/m2, total 143 mg) and 5-FU (700 mg/m2, total 1,113 mg) were administered in a first course during December 15-19, 2000, and in the same amounts in a second course during January 23-27, 2001. Adverse effects of gastralgia and stomatitis occurred, but they gradually disappeared with time. The tumor with erosion in the tongue and mouth floor and induration disappeared 2 weeks after administration. Tongue was recovered, so that tongue movement was almost normal. Postoperative MR showed no abnormal signals in T2-weighed images, suggesting that the tumor in the right mouth floor had almost disappeared. External irradiation (40 Gy/20 times/28 days, 2 Gy/day, opposing bilateral portal irradiation) between March 13 and April 9, 2001, and micro-selection high dose fractionated interstitial irradiation (42 Gy/7 times/6 days, 6 Gy/1 time) April 18-23, 2001 were performed as booster therapy. Outpatient observation has shown a good clinical course without recurrence.