The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study).

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

Effect of Medicinal Plant By-products Supplementation to Total Mixed Ration on Growth Performance, Carcass Characteristics and Economic Efficacy in the Late Fattening Period of Hanwoo Steers.

This study was conducted to evaluate the effect of medicinal plant by-products (MPB) supplementation to a total mixed ration (TMR) on growth, carcass characteristics and economic efficacy in the late fattening period of Hanwoo steers. Twenty seven steers (body weight [BW], 573±57 kg) were assigned to 3 treatment groups so that each treatment based on BW contained 9 animals. All groups received ad libitum TMR throughout the feeding trial until slaughter (from 24 to 30 months of age) and treatments were as follows: control, 1,000 g/kg TMR; treatment 1 (T1), 970 g/kg TMR and 30 g/kg MPB; treatment 2 (T2), 950 g/kg TMR and 50 g/kg MPB. Initial and final BW were not different among treatments. Resultant data were analyzed using general linear models of SAS. Average daily gain and feed efficiency were higher (p<0.05) for T1 than control, but there was no difference between control and T2. Plasma albumin showed low-, intermediate- and high-level (p<0.05) for control, T1 and T2, whereas non-esterified fatty acid was high-, intermediate- and high-level (p<0.05) for control, T1 and T2, respectively. Carcass weight, carcass rate, backfat thickness and rib eye muscle area were not affected by MPB supplementation, whereas quality and yield grades were highest (p<0.05) for T1 and T2, respectively. Daily feed costs were decreased by 0.5% and 0.8% and carcass prices were increased by 18.1% and 7.6% for T1 and T2 compared to control, resulting from substituting TMR with 30 and 50 g/kg MPB, respectively. In conclusion, the substituting TMR by 30 g/kg MPB may be a potential feed supplement approach to improve economic efficacy in the late fattening period of Hanwoo steers.

The association between the ratio of triglyceride to HDL-C and insulin resistance according to waist circumference in a rural Korean population.

BACKGROUND AND AIMS: This study aimed to examine the association between an increased ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) and insulin resistance as well as to investigate the interactive effect of TG/HDL-C and waist circumference on insulin resistance in a rural Korean population. METHODS AND RESULTS: This study, employing a cross-sectional design, included 8411 participants from the Korean Genomic Rural Cohort Study. Levels of fasting insulin, lipid profiles and anthropometric data were assessed for all participants. Insulin resistance was defined as a value greater than the 75th percentile on the homeostasis model assessment of insulin resistance (HOMA-IR). The TG/HDL-C ratio was positively correlated with waist circumference, total cholesterol, low-density lipoprotein cholesterol (LDL-C), TG and HOMA-IR, and negatively correlated with HDL-C when the calculations were controlled for gender. In comparison with the lowest quartile group of TG/HDL-C (≤1.92 in men, ≤1.63 in women), the odds ratios (ORs) (95% confidence interval) for insulin resistance in the highest quartile group of TG/HDL-C (>4.90 in men, >3.93 in women) were 2.33 (1.72-3.16) in men and 2.16 (1.73-2.71) in women, after adjusting for multiple covariates including waist circumference. Following stratification of waist circumference into quartiles, the effect of TG/HDL-C on insulin resistance remained significant irrespective of the waist circumference quartile. CONCLUSION: The TG/HDL-C ratio was linearly associated with insulin resistance in a rural Korean cohort independently of waist circumference in both genders, albeit not interactive.

Stimulation of epidermal calcium gradient loss increases the expression of hyaluronan and CD44 in mouse skin.

BACKGROUND: Hyaluronan (HA), a major extracellular matrix component in epidermis, has been found to accumulate in the epidermis after disruption of the epidermal barrier; however, the precise mechanisms underlying this process are not yet clear. Alterations in the epidermal calcium gradient are an important signal for permeability-barrier homeostasis. Thus, we hypothesized that epidermal calcium-ions might regulate HA expression. AIM: To investigate whether changes in the epidermal calcium gradient and subsequent induction of cytokines regulate HA, HA synthase (HAS) and HA receptor (CD44) expression in mouse epidermis, and to clarify the mechanisms of HA induction. METHODS: Sonophoresis of 1.5 mmol/L Ca(2+)-containing gel or Ca(2+)-free gel was performed to manipulate the epidermal Ca(2+) content without disrupting the permeability barrier. We also manipulated the Ca(2+) gradient by tape-stripping with or without 2 h immersion in 1.2 mmol/L Ca(2+)-containing solutions. Next we inhibited cytokine activity using tumour necrosis factor (TNF)-alpha or interleukin (IL)-1 inhibitors before sonophoresis. Six hours after each treatment, the expression of HA, HAS and CD44 were analysed using reverse transcription PCR and immunohistochemical stains. RESULTS: Sonophoresis of Ca(2+)-free gel significantly increased HA, HAS3 and CD44 expression in epidermis and in tape-stripped skin. However, the inhibition of Ca(2+) decrease in the upper epidermis by sonophoresis of Ca(2+)-containing gel or immersion of barrier-disrupted skin into a Ca(2+)-containing solution attenuated these inductions. Specific inhibitors of TNF-alpha and IL-1 specific inhibitors also abolished the sonophoresis-induced expression of HA, HAS3 and CD44. CONCLUSIONS: These results suggest that modulations in epidermal calcium regulate HA and CD44 expression directly or via induction of cytokines.

Imaging of the inflammatory response in reperfusion injury after transient cerebral ischemia in rats: correlation of superparamagnetic iron oxide-enhanced magnetic resonance imaging with histopathology.

BACKGROUND: Acute inflammatory responses have been thought to play a central role in ischemia-reperfusion injury after acute ischemic stroke. Superparamagnetic iron oxide (SPIO) particles have been known to enable in-vivo monitoring of macrophage infiltration by magnetic resonance imaging (MRI) in the experimental ischemic rat brain. PURPOSE: To determine whether the accumulation of macrophages could be seen in vivo in a reperfusion animal model after focal cerebral ischemia using SPIO-enhanced MRI. MATERIAL AND METHODS: Thirty-four adult male rats were enrolled in this study. SPIO particles were injected into the rats at different time points after 1-hour transient occlusion of the middle cerebral artery, and three-dimensional (3D) T2*-weighted magnetic resonance (MR) images with a gradient-echo sequence were performed 24 hours later. Histochemical iron staining was compared with T2* signal abnormalities. RESULTS: At days 3 and 4 post-reperfusion, focal areas of signal loss indicating local accumulation of SPIO particles appeared in a part of the damaged brain. Areas of signal loss corresponded to local accumulation of iron-laden macrophages in histologic sections, and SPIO-induced signal loss indicated active macrophage transmigration into the reperfused brain. CONCLUSION: SPIO-enhanced MRI demonstrated through in-vivo monitoring that macrophages participate in reperfusion injury at early stages of injury development. SPIO-enhanced MRI could be a useful tool to examine the inflammatory mechanisms involved in reperfusion brain injury.

The characterization of molecular organization of multilamellar emulsions containing pseudoceramide and type III synthetic ceramide.

To investigate the molecular organization and phase behavior of physiologic lipid mixtures that contain either newly synthesized pseudoceramide or type III synthetic ceramide, various analytical techniques were used. The phase transition temperatures detected in differential scanning calorimetry analysis were 51.19 and 50.52 for the pseudoceramide-containing physiologic lipid mixture and synthetic type III ceramide-containing lipid mixture, respectively. From the small angle XRD patterns, the multilamellar emulsion-pseudoceramide showed 11.5 nm and 7.61 nm lamellar phases, while the multilamellar emulsion-synthetic ceramide showed only a 7.61 nm lamellar phase. The nonceramide containing lipid mixture did not show any distinct repeat pattern. Lateral packing distances of multilamellar emulsion-pseudoceramide and multilamellar emulsion-synthetic ceramide were measured as 0.4119 and 0.4110 nm at 30, respectively, which indicated the presence of hexagonal lattice. On the contrary, non-multilamellar emulsion did not show any definite repeat pattern. Transmission electron microscopy observation showed nearly comparable lamellar structures in all of the tested emulsions compared to the structure of human stratum corneum intercellular lipid. Decrease of water contents resulted in phase transition into liquid phase for all the tested emulsions, whereas phase transition into orthorhombic phase was observed only in multilamellar emulsion-pseudoceramide. From these results, we concluded that the molecular organization of multilamellar emulsion-pseudoceramide was characterized as the lateral hexagonal phase and both the long and short periodicity lamellar phases, which showed structural similarity with the native human stratum corneum intercellular lipid.

The skin barrier state of aged hairless mice in a dry environment.

BACKGROUND: Many elderly people have chronic xerosis, and frequently experience an exacerbation during winter. OBJECTIVES: To investigate the barrier state of aged murine skin with or without barrier disruption in a dry environment. METHODS: Aged and young hairless mice were kept separately in dry and normal conditions for 9 days. Acetone treatment was used to perturb the skin barrier. Skin barrier function was measured as transepidermal water loss (TEWL), and morphological changes in the epidermis were studied by electron microscopy. RESULTS: The baseline TEWL was not higher in the dry environment. The number of stratum corneum (SC) layers and the epidermal thickness of aged mice increased in the dry environment. The recovery rate of the aged skin barrier was neither accelerated nor delayed in the dry environment. In the normal environment, aged mice recovered more slowly than young mice. After barrier perturbation in the aged mice, changes in SC layers and in epidermal thickness were similar in the two environments. The secretion and number of lamellar bodies did not differ between the two environments. CONCLUSIONS: We confirmed that a dry environment induces epidermal proliferation and scaling in both aged and young mice. However, no remarkable difference was found in the skin barrier recovery of aged hairless mice in a dry environment.

Complications of eyelash and eyebrow tattooing: reports of 2 cases of pigment fanning.

Eyelash and eyebrow tattooing are commonly performed procedures that have a very low rate of reported complications. We describe one case of infraorbital pigmentation after eyelash tattooing and another of periorbital pigmentation after eyebrow tattooing. Although most complications related to eyelash and eyebrow tattooing, including pigment fanning, have been reported by ophthalmologists, pigment fanning is also of concern to dermatologists.

Functional and structural changes of the epidermal barrier induced by various types of insults in hairless mice.

Acute barrier disruption, regardless of the method of induction, depletes the stratum corneum intercellular lipids and this stimulates a series of lipid/ DNA synthesis activities which lead to barrier recovery. After barrier disruption by tape stripping, occlusion with a water vapor-impermeable membrane inhibits barrier repair. In this study, we investigated the changes in the murine epidermis after barrier perturbation by tape stripping and three different types of surfactants (Emalex NP-12, ENP-12; sodium dodecyl sulfate, SDS; benzalkonium chloride, BKC). To examine the effect of an artificial barrier, we covered the animals with a water vapor-impermeable membrane for 3 days following barrier disruption and then exposed them to the air for 2 days. The histological findings after occlusion or air exposure were similar. However, after air exposure for 2 days, the thickness of the epidermis including the stratum corneum and the stratum granulosum layers decreased to about half that of the epidermis after occlusion. Ultrastructural examination revealed obvious distortion of the lamellar bilayers within the stratum corneum interstices immediately after barrier disruption. After 3 days of occlusion, extensive disorganization was evident in the intercellular domain of the stratum corneum, whereas 2 days after removal of the occlusion, the normal basic unit structure of the lamellar bilayers had partially reappeared. Our findings provide evidence that the kinetic pattern of barrier repair and the morphological changes are similar after occlusion following barrier disruption regardless of the mechanism of disruption.

The effects of famciclovir and epidural block in the treatment of herpes zoster.

In our previous study, we concluded that an epidural blockade combined with intravenous acyclovir is very effective in treating the acute pain in herpes zoster and postherpetic neuralgia. We evaluated the efficacy of oral famciclovir and epidural blockade on the pain of herpes zoster, compared to acyclovir administered intravenously and epidural blockade. For this purpose, we examined a new group treated with famciclovir and epidural blockade to compare with the group treated with acyclovir and epidural blockade in our previously study. The changes in the intensity of pain, the number of days required for relief of pain, and the total duration of pain were checked. We compared the days required for relief of pain (DRP) and the total duration of pain (TDP) of this group with those of the previous studied group treated with acyclovir and epidural blockade. DRP was significantly less, but TDP was similar. DRP and TDP were significantly lower, if the patients were treated within 7 days of symptom onset. The patients had a shorter DRP regardless of pain type than the previously studied group treated with acycolvir and epidural blockade. For the severe and moderate pain grades, there was a shorter DRP from 100 to 10. TDP was not significantly different for the groups regardless of pain type or grade. We believe that famciclovir and epidural blockade are very effective in treating the pain of herpes zoster, with a view to shortening the period of acute pain, providing similar effects on the prevention of postherpetic neuralgia, and being convenient to administer, compared to intravenous acyclovir and epidural blockade in our previous study.

Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity.

There is evidence that the "acid mantle" of the stratum corneum is important for both permeability barrier formation and cutaneous antimicrobial defense. The origin of the acidic pH of the stratum corneum remains conjectural, however. Both passive (e.g., eccrine/sebaceous secretions, proteolytic) and active (e.g., proton pumps) mechanisms have been proposed. We assessed here whether the free fatty acid pool, which is derived from phospholipase-mediated hydrolysis of phospholipids during cornification, contributes to stratum corneum acidification and function. Topical applications of two chemically unrelated secretory phospholipase sPLA2 inhibitors, bromphenacylbromide and 1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol, for 3 d produced an increase in the pH of murine skin surface that was paralleled not only by a permeability barrier abnormality but also altered stratum corneum integrity (number of strippings required to break the barrier) and decreased stratum corneum cohesion (protein weight removed per stripping). Not only stratum corneum pH but also all of the functional abnormalities normalized when either palmitic, stearic, or linoleic acids were coapplied with the inhibitors. Moreover, exposure of intact murine stratum corneum to a neutral pH for as little as 3 h produced comparable abnormalities in stratum corneum integrity and cohesion, and further amplified the inhibitor-induced functional alterations. Furthermore, short-term applications of an acidic pH buffer to inhibitor-treated skin also reversed the abnormalities in stratum corneum integrity and cohesion, despite the ongoing decrease in free fatty acid levels. Finally, the secretory-phospholipase-inhibitor-induced alterations in integrity/cohesion were in accordance with premature dissolution of desmosomes, demonstrated both by electron microscopy and by reduced desmoglein 1 levels in the stratum corneum (shown by immunofluorescence staining and visualized by confocal microscopy). Together, these results demonstrate: (i) the importance of phospholipid-to-free-fatty-acid processing for normal stratum corneum acidification; and (ii) the potentially important role of this pathway not only for barrier homeostasis but also for the dual functions of stratum corneum integrity and cohesion.

Basis of occlusive therapy in psoriasis: correcting defects in permeability barrier and calcium gradient.

BACKGROUND: Although occlusive dressings have great potential in the management of psoriasis vulgaris, the therapeutic mechanism is not completely understood. Occlusion artificially restores and corrects the defective barrier in psoriasis plaques. Additionally, occlusion is know to normalize the epidermal calcium gradients in hyperproliferative murine skin models. METHODS: To investigate the basis of the therapeutic effect of occlusion on psoriatic plaques, we investigated the ultrastructural morphology of intercorneocyte lipid layers, lamellar bodies, and calcium gradient in chronic plaque-type psoriasis after occlusion with a water vapor-impermeable membrane. The specimens were processed for electron microscopy using: (i) ruthenium tetroxide postfixation; and (ii) ion-capture cytochemistry for calcium localization. RESULTS: Occlusion for 7 days resulted in a nearly mature pattern of intercellular multilamellar structures, re-establishment of the near-normal epidermal calcium gradient, and disappearance of calcium precipitates from the stratum corneum interstices. CONCLUSIONS: The normalization of the permeability barrier and epidermal calcium gradient may play important roles in the therapeutic effects of occlusive dressings in chronic plaque-type psoriasis.

Studies on the changes of c-fos protein in spinal cord and neurotransmitter in dorsal root ganglion of the rat with an experimental peripheral neuropathy.

Animal models for human chronic pain syndromes have been developed and widely used for pain research. One of these neuropathic pain models by Kim and Chung (1992) has many advantages for operation and pain elicitation. In this neuropathic model we have examined the c-fos protein, substance P, CGRP immunoreactivity in dorsal root ganglia and dorsal horn. 50 Sprague-Dawley rats were used for this study. L5 and L6 spinal nerves were ligated tightly to produce the neuropathic pain model. After 2, 4, 8, 16, and 24 hours and 1 week of surgery, rats were anesthetized and sacrificed by perfusion. After confirmation of the roots transected by the surgery, the L5 and L6 dorsal root ganglions and spinal cord were removed and processed for immunohistochemistry. All tissue sections were immunohistochemically stained for substance P, CGRP and c-fos using the peroxidase-antiperoxidase (PAP) method. The number of immunostained substance P and CGRP dorsal root ganglion cells and c-fos immunoreactive dorsal horn cells were counted and analyzed statistically with Mann-Whitney U test. The results are as follows. The number of c-fos protein immunoreactive neurons in the superficial layer of dorsal horn were increased markedly 2 hours after operation, and gradually decreased to normal level 1 week after operation. The number of c-fos protein immunoreactive neurons in the deep layer of the dorsal horn gradually increased to a peak 24 hours after operation, then decreased to the normal level 1 week after operation. The number of substance P and CGRP immunoreactive L5 and L6 dorsal root ganglion neurons were decreased markedly 1 week after the pain model operation. In conclusion, after neuropathic pain model operation, c-fos proteins were immediately expressed in the superficial layer of spinal dorsal horn, thereafter c-fos proteins in the deep layer of spinal dorsal horn were expressed. CGRP and substance P immunoreactive neurons in DRG were decreased markedly 1 week after neuropathic pain model operation. These decrements do not coincide with the other chronic pain models, which show great increases in these pain transmitting substances. Therefore, the relationship between pain and c-fos, SP and CGRP should be investigated further.

The effects of topical alpha-hydroxyacids on the normal skin barrier of hairless mice.

BACKGROUND: alpha-hydroxyacids (AHA), such as glycolic acid and lactic acid, have recently been used in cosmetic and dermatological formulations. However, the mechanisms of action of these substances have not been well documented. OBJECTIVES: This study was done to investigate the effects of AHA on the skin barrier of hairless mice and to clarify the contribution of AHA to the formation and secretion of the lamellar bodies (LB), which are known to be the critical structure for barrier function in the epidermis. METHODS: 5% Lactic acid and 5% glycolic acid were applied to normal skin of the mice daily for 14 days. RESULTS: Changes in transepidermal water loss (TEWL), capacitance and electron microscopic findings of the epidermis of hairless mice were compared with those in which only the vehicle was applied. CONCLUSIONS: There were no significant differences in TEWL, capacitance or epidermal thickness between the epidermis of the mice to which AHA or vehicle only had been applied. On electron micrographs, the normal epidermis to which AHA had been applied showed an increase in the number and secretion of LB and a decrease in the number of stratum corneum (SC) layers in comparison with the epidermis to which the vehicle only had been applied. The lipid layers of the SC intercellular spaces and calcium gradient in both the epidermis with application of AHA and that with vehicle only were normal. These results suggest that AHA, in low concentration (5%), may improve the skin barrier in hairless mice by inducing enhanced desquamation, and by increasing the number and secretion of LB without increasing TEWL.

Tuberculous cellulitis.

We report a case of cutaneous tuberculosis presenting as cellulitis. The patient was a 63-year-old Korean woman who also had diabetes mellitus and a 20-year-history of oral corticosteroid medication prescribed for arthralgia. In addition, she had had pulmonary tuberculosis 20-year previously for which she received systemic treatment for 1 year. Her clinical cellulitis failed to respond to antibiotic therapy. Subsequent investigations, using histopathology and polymerase chain reaction, established an alternative diagnosis of cutaneous tuberculosis. The skin eruption cleared after treatment with isoniazid, rifampicin, ethambutol and pyrazinamide. This case represents a most unusual presentation of tuberculosis in the skin. The atypical features may reflect the patient's general medical state.

Apocrine poroma with sebaceous differentiation.

Poromas have been classified as eccrine neoplasms, but several recent reports of poroid tumors with sebaceous, follicular, and apocrine differentiation have challenged this concept. We report a case of apocrine poroma with sebaceous differentiation. A 69-year-old man presented with an asymptomatic elevated erythematous plaque. Histopathology revealed cellular nests composed of cuboidal poroid cells and sebocytes. The nests varied in size and were entirely intraepidermally arranged in a growth pattern similar to that of hidroacanthoma simplex. Given the common embryologic origin of folliculosebaceous and apocrine units, we believe that this lesion represents an apocrine poroma with sebaceous differentiation.

Structural and functional effects of oleic acid and iontophoresis on hairless mouse stratum corneum.

The aim of this study was to assess the effects of chemical and electrical modes of percutaneous penetration enhancement on the intercellular lipid lamellae of the stratum corneum. Hairless mice were treated with either oleic acid/propylene glycol and iontophoresis separately or together. Permeability barrier function was evaluated by measuring transepidermal water loss and correlated with the structure of stratum corneum intercellular lamellae, as evaluated by electron microscopy, using ruthenium tetroxide postfixation. Transepidermal water loss levels did not change following 1 h iontophoresis alone. In contrast, topical applications of 0.3 M oleic acid in propylene glycol for 1 h increased transepidermal water loss significantly. Moreover, the combined use of iontophoresis plus 0.3 M oleic acid for 1 h further increased transepidermal water loss at equivalent time points. Ultrastructural observations demonstrated both marked disorganization of the intercellular lipid lamellae, as well as the presence of distended lacunae within the stratum corneum in oleic acid/propylene glycol plus or minus iontophoresis-treated stratum corneum. This study provides direct evidence that the oleic acid/propylene glycol system can disrupt the stratum corneum lipid lamellar structures, and that coapplications of oleic acid with iontophoresis further enhance the effects of oleic acid. The synergy between chemical and physical enhancement may afford a new approach to promote transdermal drug delivery.

Design and synthesis of highly potent fumagillin analogues from homology modeling for a human MetAP-2.

New fumagillin analogues were designed through structure-based molecular modeling with a human methionine aminopeptidase-2. Among the fumagillin analogues, cinnamic acid ester derivative CKD-731 showed 1000-fold more potent proliferation inhibitory activity on endothelial cell than TNP-470.