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The association between psoriasis and cardiovascular disease risk has been supported by recent epidemiological data. Patients with psoriasis have an increased adjusted relative risk for myocardial infarction. As such, the cardiovascular risk conferred by severe psoriasis may be comparable to what is seen with other well-established risk factors, such as diabetes mellitus. Previous studies demonstrated that low-density lipoprotein (LDL) plays critical roles during atherogenesis. It may be caused by the accumulation of macrophages and lipoprotein in the vessel wall. Oxidized LDL (ox-LDL) stimulates the expression of adhesion molecules, such as ICAM-1 and VCAM-1, on endothelial cells and increases the attachment of mononuclear cells and the endothelium. Even though previous evidence demonstrated that psoriasis patients have tortuous and dilated blood vessels in the dermis, which results in the leakage of ox-LDL, the leaked ox-LDL may increase the expression of adhesion molecules and cytokines, and disturb the static balance of osmosis. Therefore, exploration of the relationship between hyperlipidemia and psoriasis may be another novel treatment option for psoriasis and may represent the most promising strategy.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a well-known and novel class of oral antihyperglycaemic drugs. DPP-4 inhibition facilitates ulcer healing in patients with diabetes. However, the actual mechanisms, which are independent of lower blood glucose levels, are still unknown. Therefore, the aim of this study was to analyse the effect of the DPP-4 inhibitor sitagliptin on wound healing through a glucose-independent pathway. In this study, DPP-4 inhibitors facilitate keratinocyte differentiation and the proliferation, increase blood flow in the cutaneous of wounds in healthy C57BL/6 mice. Additionally, the administration of the DPP-4 inhibitor ameliorates wound healing and enhances adiponectin expression in healthy C57BL/6 mice. Taken together, our results reveal a protective role for the DPP-4 inhibitor sitagliptin in wound healing by regulating adiponectin and phospho-eNOS levels in keratinocytes. Based on these results, the DPP-4 inhibitor may have therapeutic potential for healing wounds through a diabetes-independent mechanism.

Mucocutaneous lesion appears in up to 40% of patients with primary systemic amyloidosis (AL amyloidosis). The cutaneous signs may be co-expressed with other organ involvement or even solely presented as the first clue. We reported a case of systemic AL amyloidosis who was initially presented as a solitary hemangioma with a purpuric halo. Excisional biopsy revealed a hemangioma with amyloid deposited in thickened vascular walls. Systemic AL amyloidosis was diagnosed after thorough survey. The stage of disease at the time of initial treatment is the greatest prognostic factor. To our knowledge, this is the first case of systemic AL amyloidosis initially presented as a purpuric halo around hemangioma in Taiwan. This target-like lesion should be linked to systemic AL amyloidosis and early diagnosis is extraordinary important.

Psoriasis is a chronic inflammatory skin disease. Even though scientists predict that abnormalities in lipid metabolism play an important role in the pathogenesis of psoriasis, the actual underlying mechanisms are still unclear. Therefore, understanding the possible relationship between mechanisms of the occurrence of psoriasis and dyslipidemia is an important issue that may lead to the development of effective therapies. Under this principle, we investigated the influences of hyperlipidemia in imiquimod (IMQ)-induced psoriasis-like B6.129S2-Apoetm1Unc/J mice and oxidized low-density lipoprotein (oxLDL) in tumor necrosis factor (TNF)-&alpha, stimulated Hacat cells. In our study, we showed that a high-cholesterol diet aggravated psoriasis-like phenomena in IMQ-treated B6.129S2-Apoetm1Unc/J mice. In vitro analysis showed that oxLDL increased keratinocyte migration and lectin-type oxLDL receptor 1 (LOX-1) expression. Evidence suggested that interleukin (IL)-23 was a main cytokine in the pathogenesis of psoriasis. High-cholesterol diet aggravated IL-23 expression in IMQ-treated B6.129S2-Apoetm1Unc/J mice, and oxLDL induced IL-23 expression mediated by LOX-1 in TNF-&alpha, stimulated Hacat cells. Therefore, it will be interesting to investigate the factors for the oxLDL induction of LOX-1 in psoriasis. LOX-1 receptor expression may be another novel treatment option for psoriasis and might represent the most promising strategy.

Keloids is a fibroproliferative disease. The incidence of keloids among Asians has not been thoroughly studied. The objective of this study is to determine the incidence of keloids in Taiwan, which mainly consists of ethnic Chinese. Furthermore, we want to determine the comorbidity rate of other fibrosis-related diseases among keloid patients. This study was based on the National Health Insurance Research Database, which contains the data of 1 million randomly selected patients. Multivariate logistic regression analyses were employed to estimate the relative odds of keloids as a function of fibrosis-related diseases. The annual keloid incidence rate in Taiwan was 0.15 % for the general population. With a 1.33 ratio, women outnumbered men. Women with uterine leiomyoma have a 2.25-fold greater risk of keloids, compared with women without leiomyoma. We concluded that keloid incidence in Taiwan is approximately 0.15 %. Women with leiomyoma have a greater risk of keloids, this implicates that both diseases share a common etiopathological pathway.

Background Few studies have examined the association between autoimmune diseases and parkinsonism. Objective We sought to investigate the risk for parkinsonism during a 5-year follow-up period after a diagnosis of psoriasis using a population-based data set in Taiwan. Methods We identified 4885 patients with psoriasis for the study cohort and randomly selected 24,425 patients as a control cohort. Each subject was individually followed up for a 5-year period to identify those who subsequently developed parkinsonism. Results Stratified Cox proportional hazards regression showed that the adjusted hazard ratio for parkinsonism during the 5-year follow-up period for patients with psoriasis was 1.74 (95% confidence interval 1.35-2.20) that of control patients. Furthermore, the adjusted hazard ratios for parkinsonism within the 5-year follow-up period after the index date for subjects with psoriasis were similar between both sexes (1.78 and 1.66 for men and women, respectively). Limitation Our data set did not provide detailed information on the severity of psoriasis, or individual factors such as cigarette smoking, alcohol consumption, body mass index, and dietary patterns. Conclusion Patients with psoriasis were found to be at a significant risk of parkinsonism during a 5-year follow-up.

Background No prior study has investigated the possibility that scabies patients may be at an increased risk for developing pemphigoid. Objective To evaluate the risk of pemphigoid following scabies during a 3-year follow-up period using a Taiwanese population-based claims database and taking clinical and demographic characteristics into consideration. Methods This investigation consisted of a study group of 6793 subjects with a diagnosis of scabies and 33 965 randomly selected subjects used as a comparison group. Each patient was tracked for 3 years following their index dates to identify those who received a subsequent diagnosis of pemphigoid. Stratified Cox proportional hazards regressions were used to compute the hazard ratio (HR) of pemphigoid during the 3-year follow-up period. Results Of the 40 758 subjects, 52 (0.13%) had received a diagnosis of pemphigoid during the 3-year follow-up period; 33 (0.49% of the study group) were from the study group and 19 (0.06% of the comparison group) were from the comparison group. Compared to subjects without scabies, the HR for pemphigoid for subjects with scabies was 5.93 within the 3-year follow-up period following the index date after adjusting for monthly income, hypertension, diabetes, obesity, psoriasis, stroke, dementia, Parkinson's disease, coronary heart disease, schizophrenia or bipolar disorder, and after censoring those that died during the follow-up period. Conclusions This study detected an increased risk for pemphigoid among patients suffering from scabies. Physicians treating elderly patients with a history of scabies should be alert to the development of pemphigoid.

Background The most documented complication of scabies has been reported to be infection by group A streptococci, which has in turn been suggested to contribute to the development of glomerulonephritis. Objective This study aimed to investigate the risk of chronic kidney disease (CKD) subsequent to scabies utilizing a population-based dataset in Taiwan. Methods This retrospective matched-cohort study included 5071 subjects with scabies and 25 355 randomly selected comparison subjects. We individually tracked each subject for a 5-year period to identify those who subsequently received a diagnosis of CKD during the follow-up period. Stratified Cox proportional hazards regressions were performed to compute the hazard ratio (HR) of CKD during the 5-year follow-up period. Results The incidence rate of CKD during the 5-year follow-up period was 9.66 (8.51–10.93) per 1,000 person-years and 6.24 (5.82–6.69) per 1000 person-years for subjects with and without scabies respectively. The HR for CKD during the 5-year follow-up period for subjects with scabies was 1.34 (95% CI = 1.15–1.56) that of comparison subjects after adjusting for monthly income, hypertension, diabetes, obesity, stroke, coronary heart disease, chronic obstructive pulmonary disease, tobacco use disorder, hyperlipidemia and alcohol abuse during the 5-year follow-up period. Male subjects with scabies were 1.40 (95% CI = 1.14–1.71) times more likely than comparison subjects to suffer from subsequent CKD, and female study subjects were 1.27 (95% CI = 1.05–1.61) times more likely. Conclusions We concluded that there was an increased risk for CKD among patients suffering from scabies.

Typical cutaneous non-tuberculous mycobacteria (NTM) infections show a histopathology pattern of granulomas with admixed Langhans giant cells, and abscesses may be observed in acute lesions. Herein, we describe a patient carrying a high titer of autoantibodies to interferon (IFN)-γ with disseminated Mycobacterium kansasii infection presenting with emperipolesis and Rosai-Dorfman disease (RDD)-like histopathological features characterized by remarkable, large, pale-staining "RD cells", which were CD68 and S100 positive and CD1a negative. The patient was misdiagnosed with RDD initially, but exhibited a poor response to all interventions. A re-biopsy revealed Langhans-type multinucleated giant cells; multiple definite acid-fast bacilli were also found. M. kansasii was isolated from cultured tissues. Anti-NTM treatment was initiated. After treatment, all lesions resolved almost completely within the following month. High-titer anti-IFN-γ autoantibodies were detected during follow up, leading to the diagnosis of adult-onset immunodeficiency syndrome. In conclusion, patients carrying high-titer autoantibodies to IFN-γ who also have a disseminated cutaneous M. kansasii infection may present with RDD-like histopathological features, which may be a pitfall in the diagnosis of disseminated cutaneous NTM infections.

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an unusual entity with variable clinical manifestations and histopathological features. It is associated with a variety of immune-mediated systemic diseases, most commonly in rheumatoid arthritis. We report a 42-year-old female with a long-standing history of rheumatoid arthritis, presenting with multiple pruritic erythematous papules and nodules on the lower legs 1 month after beginning treatment with etanercept. Microscopic examination of a fully developed lesion showed a diffuse dense interstitial lymphohistiocytic infiltrate interspersed with palisaded granulomas consisting of epithelioid histiocytes and multinucleated giant cells surrounding central zones of degenerated collagen, neutrophils and leukocytoclastic debris. A diagnosis of PNGD was made on the basis of typical histopathologic features. Withdrawal of etanercept led to gradual resolution of the skin lesions, with no new skin lesions appearing afterwards. Although the correlation between the use of tumor necrosis factor-α (TNF-α) antagonists and the development of PNGD remains controversial and warrants further investigation, PNGD should be considered in the differential diagnosis of skin eruptions within a setting of anti-TNF-α therapy.

Necrobiosis lipoidica (NL) is a granulomatous disease with unknown etiology and pathogenesis. Clinically, it is characterized by yellow-brown atrophic plaques with inflammatory rims on shins. Histologically, it shows diffused palisade and interstitial granulomatous dermatitis with focal connective tissue degeneration (necrobiosis). We described three non-diabetic NL cases with unusual histologic features. All patients presented erythematous to brownish plaque(s) on the shin(s). In Case 1, in addition to the characteristics of NL, the biopsy showed dense perineural infiltration, which may explain the pathogenesis of the anesthesia of NL lesions. In Case 2, well-formed tuberculoid granulomas were of special interest. In Case 3, there was conspicuous lobular panniculitis. These histologic features present difficulties in the diagnosis and represent the broad spectrum of NL lesions, histologically.

Due to the rapid advance of technology, manufacturers’ marketing models and quickly changing consumer tastes, products such as apparel, clothing accessories and consumer electronics are likely to face the problem of short product life cycles. This study deals with the problem of determining order quantity and multi-discount selling prices for these types of gradually obsolescent products, in which two novel proposals are presented as follows: (1) without considering any exogenous factors that could affect demand, we develop a time-dependent demand model that appropriately portrays an integrated demand behavior associated with the characteristic of obsolescence; (2) we then treat the selling price as an exogenous factor influencing demand and, referring to the linear demand D = α − βp , the effect that “the increase of demand due to price change is linearly correlated with the difference between two consecutive selling prices” is incorporated, so as to make the demand model be a function of both time and selling price. Afterwards, optimization models are hereby formulated to predetermine pricing strategy with a limited number of price changes by maximizing retailer’s profit. As a result, numerical examples illustrate that the multi-discount model indeed provides higher total profit than a single discount one. This is presented along with the result analysis conducted to gain some managerial insights.

Background No previous study has investigated the incidence or risk of acute myocardial infarction (AMI) developing after the diagnosis of psoriasis in Asian populations. Objective We sought to evaluate the association between psoriasis and subsequent AMI during a 5-year follow-up period, using a nationwide Taiwanese population-based claims database, and taking clinical and demographic characteristics into consideration. Methods Our study cohort consisted of all patients with a first recorded diagnosis of psoriasis (N = 4752) between 1999 and 2001 and of patients without a diagnosis of psoriasis (N = 23,760) who were matched by age and sex (1:5) to the patients with psoriasis. Each patient was tracked using hospitalization data from 2001 until the end of 2006. Stratified Cox proportional hazard regressions (stratified by age and sex) were performed as a means of computing the 5-year AMI-free survivals after adjusting for possible confounding factors. Results Of the total sample, 70 patients (0.2%) had AMIs during the 5-year follow-up period: 22 (0.5% of the patients with psoriasis) from the study cohort and 48 (0.2%) from the comparison cohort. After adjusting for other factors, the hazard of AMI during the 5-year follow-up period was 2.10 times greater (95% confidence interval 1.27-3.43, P = .004) for patients with psoriasis than for comparison patients. Limitations We could not take into account some known risk factors for AMI, such as smoking and body mass index. Conclusions Psoriasis may confer an independent risk of AMI in Asian populations. We suggest that patients with psoriasis be made aware of the increased risk of AMI.

This paper extends the problem in Ouyang, Chen and Chuang [13] and Huang and Goyal [10] to new product introduction, under which demand is assumed to be the ramp type function of time, and supplier off ers retailer a full and partial deferral of payment to choose from. Ultimately, the determination of optimal order quantity and optimal payment policy minimizing total cost per unit time is explored. Six possible cases occur here, among which one of the most commonly seen will be mathematically analyzed, while the others are presented by numerical examples.

Cholesterol embolism (CE) is characterized by emboli containing cholesterol crystal in the arterioles, most commonly found in the skin and the kidney. The skin presentations of CE include livedo reticularis, blue toe syndrome, ulceration and gangrene. Cutaneous reactive angiomatosis (CRA) is a recently proposed term to describe a group of reactive vascular proliferation in skin caused by various diseases. Its occurrence in association with CE is extremely uncommon. An 82-year-old man with a history of cerebral infarction and on long-term warfarin therapy developed progressive, multiple violaceous papules and nodules on the dorsal feet, soles and toes, simulating Kaposi's sarcoma. Skin biopsy showed marked vascular endothelial cell proliferations characteristic of CRA affecting the full thickness of dermis. In addition, cholesterol crystal emboli were found in dermal arterioles. The skin lesions improved after the warfarin dose was reduced. We emphasize the possible presence of CE in a patient presented with CRA, especially in those with a pre-existing atherosclerotic disease, on anticoagulation therapy, or having a prior history of invasive vascular procedure. Yang Y-W, Chen C-L, Ho W-T, Wang K-H. Cutaneous reactive angiomatosis associated with cholesterol embolism.

In a highly competitive market, no matter for classical retailers or for mail order retailers, offering a return policy to entice customers to purchase items has become an inevitable strategy. This paper aims to investigate the problem of jointly determining order size, selling price and selling period of an inventory management for deteriorating items with resalable returns, in which we restrict the assumptions made by Vlachos and Dekker [9] and Mostard et al. [6] as follows: (1) returns are allowed only within a certain time frame, thereafter, no return is accepted; (2) money is fully reimbursed by retailer; (3) returns can be resold and returned several times per period. In addition, both the effects of deterioration and holding cost are incorporated to make our proposed model more realistic and pragmatic with regard to retail sales. Meanwhile, as proposed by Vlachosand Dekker [9], we defined return rate in terms of percentage of demand, and hence an average distribution approach to model inventory beh...

Clear cell fibrous papule (FP) is a rare variant of FP. We report a 39-year-old female patient who presented with a dome-shaped papule on the nose. The diagnosis of clear cell FP was made based on histological and immunohistochemical studies. Interestingly, scattered S-100 cells were admixed within the lesion, a finding hitherto not reported. The S-100 positivity may be misleading and should be cautiously interpreted.

Angioma serpiginosum is an uncommon, acquired vascular nevoid disorder with capillary dilation and proliferation in the papillary dermis. The eruptions are asymptomatic and characterized by grouped, erythematous to violaceous, serpiginous and punctate macules. The condition usually appears in females during adolescence on unilateral lower extremities and the buttocks. We report a rare case with a late onset and atypical distribution of lesions in a 48-year-old female patient who had groups of punctate lesions on her left foot for four to five years. Histopathological examination showed hyperkeratosis and multiple dilated and proliferated capillaries in the papillary dermis. Inflammation and extravasation of red blood cells were not found. According to the clinical and pathological findings, we established a diagnosis of angioma serpiginosum. She was treated with a pulsed dye laser, and the angiomatous lesions subsequently improved.

Summary Background An uncommon histiocytosis primarily involving the lymph nodes, Rosai–Dorfman disease (RDD, originally called sinus histiocytosis with massive lymphadenopathy) involves extranodal sites in 43% of cases; cutaneous RDD (C-RDD) is a rare form of RDD limited to the skin. The clinicopathological diagnosis of C-RDD may sometimes be difficult, with different clinical profiles from those of its nodal counterpart, and occasionally misleading histological pictures. There have been few multipatient studies of C-RDD and documentation of its histological spectrum is rare. Objectives To identify the clinical and histopathological profiles, associated features, and the chronological changes of this rare histiocytosis. Methods From 1991 to 2002, patients diagnosed as having C-RDD were collected in four academic hospitals. Clinical presentations, treatments, and courses of each case were documented. In total, 21 biopsy specimens obtained from these patients were re-evaluated and scored microscopically with attention to the uncommon patterns and chronological evolution both clinically and histologically. Results We examined six patients with C-RDD, three men and three women. The mean age at the first visit was 43·7 years. The clinical presentations were mostly papules, nodules and plaques, varying with the duration and depth of lesions. Although the anatomical distribution was wide, the face was most commonly involved. Evolutional changes were identified clinically, as the lesions typically began with papules or plaques and grew to form nodules with satellite lesions and resolved with fibrotic plaques before complete remission. No patient had lymphadenopathy or extracutaneous lesions during follow-up (mean 50·5 months). At the end of follow-up, the lesions in four patients had completely resolved irrespective of treatment; two patients had persistent lesions. The histopathological pattern of the main infiltrate, the components of cells and the stromal responses showed dynamic changes according to the duration of lesions. The characteristic Rosai–Dorfman cells (RD cells) were found in association with a nodular or diffuse infiltrate in 15 lesions (71%). Four lesions (19%) demonstrated a patchy/interstitial pattern. One lesion (5%) assumed the pattern of a suppurative granuloma. RD cells were less readily found in these atypical patterns. Conspicuous proliferation of histiocytes associated with RD cells was found in three lesions, including xanthoma, localized Langerhans cell histiocytosis and xanthogranuloma. Along with lymphocytes, plasma cells were present in all lesions, often in large numbers with occasional binucleated or trinucleated cells. Variably found in the lesions were neutrophils (nine lesions, 43%) and eosinophils (13 lesions, 62%). The former occasionally formed microabscesses, while the latter were often few in number. Vascular proliferation was a relatively constant feature (90%). Fibrosis was found in 10 lesions (48%). Conclusions Our study further confirms that C-RDD is a distinct entity with different age and possibly race distributions from RDD. Compared with its nodal counterpart, C-RDD demonstrates a wider histopathological spectrum with different clinicopathological phases depending on duration of the lesions. Awareness of these features is helpful in making a correct diagnosis. The associations of C-RDD with other histiocytoses may have important implications for the pathogenesis of this rare histiocytosis.

Background. Topical 5-fluorouracil (5-FU) is a standard treatment for Bowen's disease. However, its efficacy may be limited by the presence of stratum corneum. The Er:YAG laser has shown a dramatic enhancement effect on the delivery of 5-FU in vitro by ablation of the stratum corneum. The efficacy of laser-assisted delivery of 5-FU has not been tested in human. Objective. To see whether Er:YAG laser pretreatment can improve the efficacy of topical 5-FU in the treatment of Bowen's disease. Methods. Three target lesions from a patient with multiple Bowen's disease were selected for a half-side comparison study. The Er:YAG laser was used to remove the cornified layer on one side of each lesion, followed by twice-daily application of 5-FU cream to both sides. Clinical and histologic responses were compared. Results. Lesions pretreated with the Er:YAG laser showed more rapid clinical and histologic responses to topical 5-FU than those treated with 5-FU alone. Evaluation at 9 months after treatment showed no recurrences of lesions on both sides. Conclusions. Our preliminary study demonstrates that this Er:YAG laser-assisted modality is effective and shows accelerated clinical response and shortened treatment time compared with topical 5-FU as a single treatment.

Background Methotrexate-induced epidermal necrosis (MEN) is a rare but life-threatening cutaneous reaction that mimics Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Objectives To investigate the clinicopathology, risk factors, and prognostic factors of MEN. Methods We enrolled 24 patients with MEN and 150 controls and analyzed the demographics, pathology, and plasma concentrations of methotrexate (MTX). Results Patients with MEN showed extensive skin necrosis (mean, 33.2% total body surface area) but no target lesions. The histopathology displayed keratinocyte dystrophy. Early signs of MEN included painful skin erosions, oral ulcers, and leukopenia/thrombocytopenia. Although 79.2% patients received leucovorin treatment, there was 16.7% mortality. Risk factors for MEN included older age (>60 years), chronic kidney disease, and high initial dosage of MTX without folic acid supplementation. Renal insufficiency delayed MTX clearance. Severe renal disease and leukopenia predicted poor prognosis in MEN, but none of the SCORe of Toxic Epidermal Necrosis criteria were associated with mortality of MEN. Limitations The study was limited by the small sample size. Conclusion MEN exhibited distinct clinicopathologic features from SJS/TEN. Recognition of the early signs and prognostic factors is important, because the rapid institution of leucovorin may be helpful. To reduce the risk of MEN, physicians should avoid prescribing MTX to high-risk patients and titrate the dosage slowly upward with folic acid supplementation.

SummaryBackground Although psoriasis is seldom life threatening, very few studies have compared differences in health care service use between patients with and without psoriasis. Objectives To investigate differences in health care service use between patients with and without psoriasis. Methods Patient details and data on their use of health services were retrieved from the Taiwan Longitudinal Health Insurance Database 2000. We included 3649 patients with psoriasis and 3649 without it. Each patient was followed for a 1-year period to estimate their utilization of health care resources. Student t-tests were used to compare differences in health care services use between patients with and without psoriasis. Results For dermatology services, patients with psoriasis had significantly more outpatient visits (3·5 vs. 0·9), and higher outpatient and total costs (US$148·00 vs. US$12·20 and US$581·60 vs. US$347·20, respectively) than those without psoriasis. For nondermatology services, patients with psoriasis had more outpatient visits (21·3 vs. 17·6), and higher outpatient and total costs (US$904·60 vs. US$663·50 and US$1335·50 vs. US$998·30, respectively) than those without psoriasis. For overall health care service use, patients with psoriasis had significantly more outpatient visits (24·8 vs. 18·5; P

Hesperidin is present in the traditional Chinese medicine, “Chen Pi,” and recently was reported to have anti-inflammatory effects. Therefore, we were interested in comparing the effects of hesperidin and hesperidin-3′-O-methylether on phosphodiesterase inhibition and airway hyperresponsiveness (AHR) in a murine model of asthma. In the present results, hesperidin-3′-O-methylether, but not hesperidin, at 30 μmol/kg (p.o.) significantly attenuated the enhanced pause (Penh) value, suppressed the increases in numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and BALF, and enhanced the level of totalIgG2ain the serum of sensitized and challenged mice, suggesting that hesperidin-3′-O-methylether is more potent than hesperidin in suppression of AHR and immunoregulation. The different potency between them may be due to their aglycons, because these two flavanone glycosides should be hydrolyzed byβ-glucosidase after oral administration. Neither influenced xylazine/ketamine-induced anesthesia, suggesting that they may have few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, hesperidin-3′-O-methylether is more potent in phosphodiesterase inhibition and suppression of AHR and has higher therapeutic (PDE4H/PDE4L) ratio than hesperidin. Thus, hesperidin-3′-O-methylether may have more potential for use in treating allergic asthma and chronic obstructive pulmonary disease.

Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, “Chen Pi.” Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4H/PDE4L) ratio of >11. Hesperetin (10 ~ 30 μmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation.

Background Systemic inflammation and dysregulated immune function in chronic obstructive pulmonary disease (COPD) is hypothesized to predispose patients to development of herpes zoster. However, the risk of herpes zoster among patients with COPD is undocumented. We therefore aimed to investigate the risk of herpes zoster among patients with COPD. Methods We conducted a cohort study using data from the Taiwan Longitudinal Health Insurance Database. We performed Cox regressions to compare the hazard ratio (HR) of herpes zoster in the COPD cohort and in an age- and sex-matched comparison cohort. We divided the patients with COPD into three groups according to use of steroid medications and performed a further analysis to examine the risk of herpes zoster. Results The study included 8486 patients with COPD and 33 944 matched control patients. After adjustment for potential confounding factors, patients with COPD were more likely to have incidents of herpes zoster (adjusted HR 1.68, 95% confidence interval [CI] 1.45-1.95). When compared with the comparison cohort, the adjusted HR of herpes zoster was 1.67 (95% CI 1.43-1.96) for patients with COPD not taking steroid medications. The adjusted HR of herpes zoster was slightly greater for patients with COPD using inhaled corticosteroids only (adjusted HR 2.09, 95% CI 1.38-3.16) and was greatest for patients with COPD using oral steroids (adjusted HR 3.00, 95% CI 2.40-3.75). Interpretation Patients with COPD were at increased risk of herpes zoster relative to the general population. The relative risk of herpes zoster was greatest for patients with COPD using oral steroids.

Plasma-cell cheilitis is a rare inflammatory disorder of the lip characterized histologically by a band-like infiltrate of plasma cells in the upper dermis. It is considered an oral counterpart of plasma-cell balanitis. Clinically, it presents as a circumscribed, flat to slightly raised, eroded area of the lip. The cause of plasma-cell cheilitis is unknown, and the treatment is often disappointing. We describe a 55-year-old woman who had a long-lasting painful, swollen, and eroded area on her lips, which responded poorly to various topical treatments. Biopsy showed a band-like infiltrate composed mainly of mature plasma cells in the dermis. A diagnosis of plasma-cell cheilitis was made after excluding contact dermatitis, lichen planus, bacterial, fungal and spirochaete infections, and an extramedullary plasmacytoma. Dramatic improvements were observed after intralesional injections of corticosteroids. The lesion cleared up after two treatments, and there has been no recurrence in 1 year of follow-up.

Eruptive melanocytic nevi (EMN) is a rare phenomenon with an unclear pathogenesis. Mutation on a molecular basis has been proposed, but insufficient data are available to confirm this hypothesis. Theoretically, the possibility of malignant transformation is high, but no previous definite cases had been reported. Herein, we report the first case of a patient with EMN in whom hypopharyngeal low-grade melanocytic malignancies were detected using a fibrolaryngoscope. BRAF activation and p16 mutations were discovered through real-time polymerase chain reaction and immunohistochemical staining on EMN tissue samples, respectively. The significance of these findings has yet to be determined.

BackgroundHesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4). While hesperetin-7,3'-O-dimethylether (HDME) is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs)in vitro, and its effects on ovalbumin-induced airway hyperresponsivenessin vivo, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD).MethodsPDE1~5 activities were measured using a two-step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [3H]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th)1/Th2 cytokine CBA kits, and total immunoglobulin (Ig)E or IgG2alevels were done using ELISA method. Xylazine (10 mg/kg)/ketamine (70 mg/kg)-induced anesthesia was performed.ResultsHDME revealed selective phosphodiesterase 4 (PDE4) inhibition with a therapeutic (PDE4H/PDE4L) ratio of 35.5in vitro.In vivo, HDME (3~30 μmol/kg, orally (p.o.)) dose-dependently and significantly attenuated the airway resistance (RL) and increased lung dynamic compliance (Cdyn), and decreased enhanced pause (Penh) values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) of these mice. In addition, HDME (3~30 μmol/kg, p.o.) dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (Ig)E levels in the BALF and serum, and enhanced IgG2alevel in the serum of these mice.ConclusionsHDME exerted anti-inflammatory effects, including suppression of AHR, and reduced expressions of inflammatory cells and cytokines in this murine model, which appears to be suitable for studying the effects of drugs on atypical asthma and COPD, and for screening those on typical asthma. However, HDME did not influnce xylazine/ketamine-induced anesthesia. Thus HDME may have the potential for use in treating typical and atypical asthma, and COPD.