Allergy testing for Cremophor in a patient with cervical cancer with infusion reactions to paclitaxel and docetaxel.

A woman in her 30s with cervical cancer underwent postoperative chemotherapy and showed allergic reactions to multiple taxanes. As the patient had infusion reactions to both paclitaxel and docetaxel, a prick test with Cremophor was conducted. In the absence of an allergic reaction to etoposide, we determined that the patient was allergic to pure taxane compounds. Among infusion reactions caused by taxanes, Cremophor allergy is reported in 3% of cases. Therefore, a prick test with Cremophor performed on a taxane infusion reaction will be useful in diagnosing allergy. In addition, allergy due to docetaxel may be managed by adequate premedication and continuous intravenous chlorpheniramine administration.

Enhancement of Ultraviolet B-Induced Apoptosis and Elimination of DNA Damage by Pre-Irradiation with Infrared Radiation A Does Not Depend on DNA Damage Repair.

BACKGROUND: We previously reported that pre-irradiation with infrared radiation A (IRA) eliminated ultraviolet B (UVB) -induced cyclobutane pyrimidine dimers (CPDs). Accelerated elimination of CPDs could have resulted from enhanced DNA repair and/or enhanced induction of apoptosis. Using Xpa knockout (KO) mice, which are deficient in DNA repair, we examined whether IRA accelerated elimination of CPDs by enhancing DNA repair. METHODS: We have already generated mice harboring epidermal melanocytes that produce only eumelanin and dominant pheomelanin, and no melanin. To obtain such mice with impaired DNA repair ability, we backcrossed them with Xpa KO mice. Three hours before UVB irradiation, the mice were irradiated with IRA, and CPDs and apoptotic cells were examined. RESULTS: Pre-irradiation of Xpa KO mice with IRA before UVB irradiation accelerated removal of CPDs and enhanced apoptotic changes. CONCLUSION: These results indicate that enhancement of UVB-induced apoptosis and acceleration of removal of CPDs by pre-irradiation with IRA does not depend on DNA damage repair.

Dietary Habits in Japanese Patients with Alopecia Areata.

PURPOSE: Alopecia areata (AA) is characterized by non-scarring, patchy hair loss caused by autoimmune reactions to anagen hair follicles. The pathogenesis of AA may be affected by the diet. However, the dietary habits of patients with AA have not been precisely examined. Therefore, the aim of this study was to investigate the dietary habits of patients with AA in comparison to those of healthy controls. PATIENTS AND METHODS: We evaluated the dietary habits of 70 adult Japanese patients with AA using a brief-type self-administered diet history questionnaire and compared them to the habits of age- and sex-matched healthy controls. RESULTS: Japanese patients with AA had a higher body mass index (BMI) and higher intakes of vitamin C and fruit than the controls. Logistic regression analysis showed that AA was associated with BMI. Retinol intake was positively correlated with severity of alopecia tool (SALT) score, and linear regression analysis revealed that retinol intake was a predictor of SALT score. Retinol intake among patients with moderate to severe AA (ie, a SALT score >25) was higher than that in patients with mild AA (a SALT score ≤25). The mean age of AA patients with atopic dermatitis (AD) was lower than that of AA patients without AD; however, there were no differences in nutrient or food intake between these two groups. Logistic regression analysis showed that the comorbidity AD was negatively associated with age. CONCLUSION: AA was associated with a high BMI, and high retinol intake was a predictor of SALT score. Further studies should be conducted to clarify whether dietary intervention to reduce BMI or limit retinol intake can alter the development or severity of AA.

Dietary habits in Japanese patients with palmoplantar pustulosis.

Palmoplantar pustulosis (PPP) is a chronic dermatitis characterized by sterile intra-epidermal pustules associated with erythema and scales on the palms and soles. Tumor necrosis factor (TNF)-α/interleukin (IL)-23/IL-17 inflammatory pathway may be involved in the pathogenesis of PPP, and the skin lesions manifest the enhanced expression of IL-8 in keratinocytes and increased levels of antimicrobial peptide cathelicidin, leucine leucine-37 in vesicles/pustules. Some PPP patients are associated with arthro-osteitis, called pustulotic arthro-osteitis (PAO). Dietary habits may modulate the pathogenesis of PPP, however, have not been investigated in PPP patients. We evaluated dietary habits in adult Japanese PPP patients, using a validated, brief-type self-administered diet history questionnaire, and compared their results to those of age- and sex-matched healthy controls. The results in PPP patients with PAO were compared to those in the patients without. Japanese PPP patients showed higher body mass indices (BMIs), higher intakes of pulses and sugar/sweeteners, and lower intake of vitamin A, compared to those of healthy controls. The bivariate and multivariable logistic regression analysis showed that PPP was associated with high BMI, high intake of pulses, and low intake of vitamin A. The sodium intake and BMI were positively correlated with palmoplantar pustulosis area and severity index (PPPASI). The linear multivariate regression analysis revealed that sodium intake and BMI were predictors of PPPASI. The age and sodium intake in the patients with PAO were lower than those in the patients without. The bivariate and multivariable logistic regression analysis showed that PAO was negatively associated with age and sodium intake. This is the first study showing the dietary habits in patients with PPP. Further studies should clarify if the dietary intervention to correct the BMI and sodium intake will alter the progress of PPP.

A Case of Autoimmune Hepatitis/Primary Biliary Cholangitis Overlap Syndrome during Treatment with Brodalumab for Generalized Pustular Psoriasis.

Psoriasis is a chronic inflammatory skin disease characterized by accelerated tumor necrosis factor-α (TNF-α) /interleukin (IL) -23/IL-17 axis, epidermal hyperproliferation, and dysregulated differentiation. Psoriasis is occasionally associated with autoimmune liver diseases such as autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC), caused by autoimmunity against hepatocyte- or cholangiocyte-specific autoantigens, respectively. Overlap syndrome is a condition in which patients have features of both AIH and PBC. It has been reported that AIH, PBC, or the overlap syndrome can be triggered by certain drug therapies. A 65-year-old Japanese man developed increased serum levels of aspartate and alanine aminotransferases, and positive anti-nuclear and anti-mitochondrial M2 antibodies, along with neutropenia, at 4 weeks of treatment with an anti-IL-17 receptor A antibody brodalumab for generalized pustular psoriasis. Histological evaluation of the liver revealed interface hepatitis and non-suppurative destructive cholangitis, which is compatible with the overlap syndrome of AIH and PBC. This is the first case of AIH/PBC overlap syndrome during treatment with brodalumab for generalized pustular psoriasis. The relationship between brodalumab and AIH/PBC overlap syndrome should be further elucidated. The risk of autoimmune liver diseases in patients with psoriasis treated with brodalumab should be carefully considered.

Dietary habits in Japanese patients with chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is defined as the spontaneously appearing weals and/or angioedema for more than 6 weeks. Dietary habits can modulate the pathogenesis of CSU. However, dietary intakes of nutrients or food in CSU patients, compared with healthy controls, have not been examined in quality and quantity. METHODS: We evaluated dietary habits in adult Japanese patients with chronic spontaneous urticaria using a validated, brief-type self-administered diet history questionnaire and compared the results to those of age- and sex-matched healthy controls. The severity of CSU was evaluated using the Urticaria Control Test. RESULTS: Japanese CSU patients showed higher body mass indices, higher intakes of eggs, vegetables other than green/yellow vegetables/mushrooms/algae, cholesterol, folic acid, dietary fibres, vitamin D, vitamin K, Cu, Fe, Pi, Ca, Mg, Na and salt, and lower intake of alcohol, compared to controls. The logistic regression analysis showed that CSU was associated with high body mass index and high intake of eggs. The intake of beverages was higher in uncontrolled CSU patients (Urticaria Control Test ≦11 points) than in controlled patients. The logistic regression analysis showed that uncontrolled CSU was associated with high intake of beverages. The intake of coffee, caffeine-rich and non-alcohol beverage, in uncontrolled CSU patients was higher than that in controlled patients. CONCLUSIONS: Chronic spontaneous urticaria was associated with high body mass index and high intake of eggs. Uncontrolled CSU was associated with high intake of beverages. Further studies should elucidate the relationships of these results with the development or exacerbation of CSU.

Dietary habits in Japanese patients with psoriasis and psoriatic arthritis: Low intake of meat in psoriasis and high intake of vitamin A in psoriatic arthritis.

Psoriasis is characterized by T-helper 17 cell-dominant abnormal immunity, and hyperproliferation and abnormal differentiation of epidermal keratinocytes. Some patients are associated with arthritis. Dietary habits can modulate the pathogenesis of psoriasis. Previous studies in Western countries showed higher body mass indices, higher intake of fat and lower intake of fish or vegetables in psoriatic patients compared with the reference groups. We evaluated dietary habits in adult Japanese psoriatic patients, using a validated brief-type self-administered dietary history questionnaire, and compared the results to those of age- and sex-matched healthy controls. The results in psoriatic patients with arthritis were compared with those in the patients without. Japanese psoriatic patients showed higher body mass indices, higher intake of fish/shellfish, pulses, sugar/sweeteners, vitamin B12 and vitamin D, and lower intake of meat, compared with those of healthy controls. The logistic regression analysis showed that psoriasis was associated with high body mass index and low intake of meat. The intake of confection in patients with high Psoriasis Area and Severity Index was higher than that in those with low index. The intake of ß-carotene, vitamin A and green/yellow vegetables in psoriatic patients with arthritis were higher than those in the patients without. The dietary habits in Japanese psoriatic patients are rather different from those in Western patients. This is the first study showing the differences in dietary habits between psoriatic patients with arthritis and those without. Further studies should elucidate the relationships of these results with skin and joint lesions in psoriatic patients.

Dietary habits in adult Japanese patients with atopic dermatitis.

Dietary habits can modulate the pathogenesis of atopic dermatitis. We evaluated these habits in adult Japanese patients with atopic dermatitis using a validated, brief-type self-administered diet history questionnaire and compared the results to those of age- and sex-matched healthy controls. Patients with atopic dermatitis showed higher intakes of carbohydrate and potatoes and lower intakes of alcohol, niacin, meat and oils/fats compared with those of the healthy controls. The results of logistic regression analysis showed that the intake of alcohol was negatively associated with atopic dermatitis (odds ratio, 0.905; 95% confidence interval, 0.832-0.983; P = 0.0181). The intakes of vitamin B6 and fruit were positively correlated with the severity scoring of atopic dermatitis. Multiple regression analysis revealed that vitamin B6 intake was a predictor of the severity scoring of atopic dermatitis (ß = 26.98508709, t = 2.3995292, P = 0.01933781). The intakes of vegetable fat, n-6 polyunsaturated fatty acid, and confections were lower in the severe atopic dermatitis group (severity scoring of atopic dermatitis, ≥33) than those in the mild group. Atopic dermatitis is negatively associated with alcohol intake, and intake of vitamin B6 is a predictor of severity scoring of atopic dermatitis. The intake of n-6 polyunsaturated fatty acid is lower in the severe atopic dermatitis group than that in the mild group. Further study is warranted on the relationships of these results with abnormal immune responses, impaired skin barrier or pruritus in atopic dermatitis.

Effect of infrared radiation A on photoaged hairless mice harboring eumelanin and pheomelanin in the epidermis.

Infrared radiation A (IRA) is absorbed by melanin and generates heat. Therefore, the effect of IRA could be well analyzed using skin, which contains melanin in the epidermis. Hairless mice harboring epidermal melanocytes that produce eumelanin, pheomelanin, or non-melanin were generated by backcrossing K14-stem cell factor mice, recessive yellow mice, and then albino hairless mice. High-dose IRA was irradiated over 18 weeks after the establishment of photoaged mice by irradiation with ultraviolet B (UVB) three times a week for 14 weeks. Tumor formation was assessed every week. The formation of cyclobutane pyrimidine dimer and apoptotic cells by the irradiation of IRA and UVB was evaluated. Repetitive irradiation of IRA did not promote tumor formation in all types of mice. Pre-irradiation of IRA to UVB, but not post-irradiation, accelerated the elimination of cyclobutane pyrimidine dimers and enhanced apoptosis; these effects were most obvious in eumelanin-producing mice. Real-time polymerase chain reaction analysis showed downregulation of FLICE (cellular caspase 8)-like inhibitory protein and B-cell lymphoma-extra large and upregulation of Bcl-2-associated X protein by UVB, but further enhancement of these molecules by pre-irradiation of IRA was not observed. These results indicate that IRA does not confer the promotion of UVB-induced carcinogenesis in photoaged mice harboring epidermal melanocytes and that photochemical reaction between IRA and melanin might be involved in the induction of apoptosis and the elimination of cyclobutane pyrimidine dimers by UVB. The enhancement of apoptosis by pre-irradiation of IRA to UVB might be induced by mechanisms other than the modification of the mRNA expression of FLICE (cellular caspase 8)-like inhibitory protein, B-cell lymphoma-extra large, and Bcl-2-associated X.

TRPV4 regulates the integrity of the blood-cerebrospinal fluid barrier and modulates transepithelial protein transport.

The diffusion of materials from systemic circulation to the central nervous system (CNS) is restricted by the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). Choroid plexus epithelial cells (CPECs) of the brain ventricles constitute the BCSFB and regulate the infiltration of plasma proteins as well as immune cells into the interstitium of the CNS. The barrier function is altered in pathologic conditions. However, the regulatory mechanism of BCSFB is not fully understood. Here, we investigated the function of transient receptor potential vanilloid 4 (TRPV4), a polymodally gated divalent cation channel that is highly expressed in CPECs. TRPV4 was localized broadly on the apical membrane in swine CPECs, in contrast with an intense ciliary localization found on other cell types. Treatment with the TRPV4-specific agonist, GSK1016790A (GSK; EC50 34 nM), induced a robust calcium influx and an immediate serine/threonine protein phosphorylation. The agonist treatment induced a marked decrease in the amount of filamentous actin and disintegrated the cell junctions in 10-20 minutes. In contrast, inhibition of the basal TRPV4 activity with the TRPV4-specific antagonist, HC067047 (HC; IC50 74 nM), reduced the basolateral-to-apical transport of α-2-macroglobulin (A2M). Overall, this study demonstrated a novel physiologic function of TRPV4 in the regulation of BCSFB permeability.