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Purpose: To investigate the prevalence and clinical features of acquired lower eyelid epiblepharon in Korean patients with thyroid-associated ophthalmopathy (TAO) and compare the pathogenic features of acquired and congenital epiblepharon., Design: Retrospective, nonrandomized, comparative case series, cross-sectional study., Participants: A total of 494 Korean patients with TAO and 845 Korean patients with congenital lower eyelid epiblepharon., Methods: The medical records were reviewed, and the presence, location, and extent of epiblepharon were identified. Clinical features of TAO (lower eyelid retraction, exophthalmos, and elevation limitation) were compared between patients with TAO with and without epiblepharon. Acquired epiblepharon was classified into 3 types according to the location and extent. The prevalence of epiblepharon types was determined and evaluated for associations with TAO clinical features. Comparisons were made between the prevalence of epiblepharon types in acquired and congenital epiblepharon., Main Outcome Measures: Prevalence, location, and extent of epiblepharon; association with clinical features of TAO; and difference from congenital epiblepharon., Results: An acquired lower eyelid epiblepharon was found in 42 (8.5%) of 494 patients with TAO. The mean age of patients with TAO with epiblepharon (34.2±13.5 years) was significantly lower than that of patients with TAO without epiblepharon (46.5±14.1 years) (P = 0.000). Lower eyelid retraction (0.78±1.11 mm) was more severe in patients with TAO with epiblepharon than in patients without epiblepharon (0.30±0.73 mm) (P = 0.000). Lower eyelid retraction was more severe in diffuse-type acquired epiblepharon than in central-type epiblepharon (P = 0.012). Elevation limitation was more severe in central-type acquired epiblepharon than in medial-type epiblepharon (P = 0.001). The occurrence of central-type epiblepharon was higher in TAO-associated acquired epiblepharon (20 eyelids, 30.8%) than in congenital epiblepharon (27 eyelids, 1.9%, P = 0.000)., Conclusions: Acquired lower eyelid epiblepharon is one of the clinical features of patients with TAO. The association between lower eyelid retraction and acquired epiblepharon may lead to a better understanding of the cause of acquired epiblepharon in patients with TAO., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

In this study, we investigated whether single nucleotide polymorphisms (SNPs) of the interleukin-1 beta (IL-1B) were associated with papillary thyroid carcinoma (PTC). We also assessed the relationships between IL-1B SNPs and the clinicopathologic characteristics of PTC patients. Ninety-three PTC patients and 324 controls were recruited. The patients with PTC were dichotomized and compared with respect to the clinicopathologic characteristics of PTC. Seven SNPs in the IL-1B gene were selected and genotyped using direct sequencing. Four SNPs (rs1143627, rs3136558, rs1143633, and rs1143643) in the IL-1B gene were significantly associated with PTC (p < 0.05). In clinicopathologic features, 3 SNPs (rs1143630, rs1143633, and rs1143643) showed a strong relationship with lymph node metastasis of PTC. The genotype and allele frequencies of rs1143630 and rs1143643 remained significantly associated with lymph node metastasis after Bonferroni correction for multiple testing. In haplotype analysis, two linkage disequilibrium blocks (block 1 consisted of rs1143627, rs3917356, and rs1143630; block 2 consisted of rs1143633 and rs1143643) also revealed significant associations with lymph node metastasis. Our results suggest that IL-1B polymorphisms may be associated with the risk of PTC in the Korean population. Especially, IL-1B polymorphisms might be a predictive factor for lymph node metastasis of PTC patients.

Receptor interacting protein 140 (RIP140) is a coregulator for numerous nuclear receptors and transcription factors and primarily exerts gene-repressive activities on various target genes. We previously identified a spectrum of posttranslational modifications on RIP140 that augment its property and biological activity. In T(3)-triggered biphasic regulation of cellular retinoic acid binding protein 1 (Crabp1) gene along the course of fibroblast-adipocyte differentiation, we found TRAP220(MED1) critical for T(3)-activated chromatin remodeling whereas RIP140 essential for T(3)-repressive chromatin remodeling of this gene promoter. In this current study, we aim to examine whether and how RIP140 replaces TRAP220(MED1) on the CrabpI promoter in differentiating adipocyte cultures. We find increasing recruitment of RIP140 to this promoter, with corresponding reduction in TRAP220(MED1) recruitment during the T(3)-repressive phase. We also uncover direct interaction of RIP140 with cyclin-dependent kinase (CDK)8 through the amino terminus of RIP140, which is stimulated by lysine acetylation on RIP140. We further validate the biological activity of lysine acetylation-mimetic RIP140, which elicits a stronger repressive effect and more efficiently recruits CDK8 and confirm CDK8's function in recruiting repressive components, such as G9a, to the RIP140 complex on this promoter. This underlies the T(3)-triggered repression of CrabpI gene. This study illustrates a new gene-repressive mechanism of RIP140 that can affect the transcription machinery by directly interacting with CDK8.

Background: During neurosurgical procedures, patients are often exposed to hypoxic and ischemic brain damage. Cerebral ischemia leads to neuronal cell death and eventually causes neurological impairments. Remifentanil is a new ultra-short acting phenylpiperidine opioid analgesic. In this study, we evaluated remifentanil to determine if it exerts an anti-apoptotic effect in the hippocampal dentate gyrus following transient global ischemia in gerbils., Methods: Step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemical staining for caspase-3 were performed., Results: The numbers of TUNEL-positive cells and caspase-3-positive cells in the dentate gyrus were increased by ransient global ischemia. Latency in the step-down avoidance task was increased by transient global ischemia. Results revealed that apoptotic cell death in the dentate gyrus was increased significantly following transient global ischemia, resulting in memory impairment. However, treatment with remifentanil suppressed ischemia-induced apoptosis in the dentate gyrus, thereby alleviating the memory impairment that was induced by ischemic cerebral injury., Conclusions: These results indicate that remifentanil may exert a neuroprotective effect on ischemic brain damage during surgery.

Background: Atrichia with papular lesions (APL) is a rare inherited disease characterized by early onset of total hair loss, followed by papular lesions over the extensor areas of the body. Recently, mutations in the human hairless (HR) gene have been implicated in its pathogenesis. The identification of mutations in the HR gene is important for differentiating between APL and alopecia universalis (AU)., Objective: We compared the HR genes of patients with presumed AU who showed minimal or no response to treatment with the HR genes of healthy controls., Methods: The subjects were 11 patients with presumed AU who had not responded to treatments. Fifty healthy people were included as controls for molecular analysis. To screen for mutations, polymerase chain reaction was performed., Results: DNA analysis identified a novel heterozygous G-to-A transition at nucleotide position 191 in exon 5. The mutation was not found in the controls, other AU patients, or any unaffected family members except for the patients' mother and maternal grandfather, who were heterozygous HR gene carriers., Conclusion: Our study identifies a novel missense mutation in exon 5 of the HR gene in a Korean APL patient previously diagnosed as AU.

Objectives: Consultation difficulty occurs in hospitals located in many countries, and it is understood that strategies to improve the emergency department (ED) consultation process are needed. The authors constructed a computerized consultation management system in the ED of a tertiary care teaching hospital to improve the consultation process and evaluate the influence of the consultation management system on ED length of stay (LOS) and the throughput process., Methods: Consultation management system software was developed and integrated into the hospital information system. The development process took place between June 2008 and May 2009. Before the development of the consultation system, ED personnel contacted on-call physicians of the specialty department, who are usually residents, by cellular phones. After the system had been developed, ED personnel selected the department and on-call physician in the specialty department using the consultation management software and activated the automatic consultation process when specialty consultation was necessary. If the treatment plan had not been registered for 3 hours, all of the residents in the specific department are notified of the delay in the treatment plan with a short message service (SMS) message. If an admission or discharge order had not been made in 6 hours, all of the residents and faculty staff in the specific department receive SMS messages stating the delay in disposition. ED patient data were collected from the hospital information system for 40 days before the system was developed (June 1, 2008, to July 10, 2008) and 40 days after the system was implemented (June 1, 2009, to July 10, 2009)., Results: The median ED LOS decreased significantly, from 417.5 minutes (interquartile range [IQR] = 178.8-1,247.5 minutes) in the presystem period to 311.0 minutes (IQR = 128.0-817.3 minutes) in the postsystem period (p < 0.001). Also, the median time to disposition order decreased significantly, from 336.0 minutes (IQR = 145.0-943.0 minutes) to 235.0 minutes (IQR = 103.0-21.5; p = 0.001). No significant reduction was observed in the interval between the time of disposition decision and the time when the patients left the ED. Significant reductions of ED LOS were observed after implementing the system (p < 0.001) regardless of whether the visit occurred during the weekday daytime (09:00-17:00 hours), holiday and weekend daytime (09:00-17:00 hours), or nighttime (17:00-09:00 hours next day)., Conclusions: This study found decreased ED LOS by implementation of a computerized consultation management system in a tertiary care teaching hospital. The automated consultation and monitoring process formalized communication between physicians providing ED patient care in the academic ED with high consultation and admission rates., (© 2011 by the Society for Academic Emergency Medicine.)

Promyelocytic leukemia (Pml) protein is required for Oct4 gene expression and the maintenance of its open chromatin conformation in stem cells. In proliferating stem cells, Pml-nuclear body, along with transcription factors TR2, steroidogenic factor 1 (SF1) and Sp1, and Brg1-dependent chromatin remodeling complex (BRGC), associates with conserved region 1 (CR1) of this promoter to maintain a nucleosome-free region for gene activity. Retinoic acid (RA) rapidly downregulates Pml, resulting in the replacement of BRGC with Brm-containing remodeling complex, disassociation of SF1 and Sp1, retaining of TR2, recruitment of receptor-interaction protein 140, G9a and HP1γ, and sequential insertion of two nucleosomes on CR1 that progressively displays repressive heterochromatin marks. This study demonstrates a functional role for Pml in maintaining a specific open chromatin conformation of the Oct4 promoter region for its constant expression in stem cells; and illustrates the mechanism underlying RA-induced chromatin remodeling of Oct4 gene in differentiating cells, in which Pml plays a critical role. The study also demonstrates a novel mode of chromatin remodeling, which occurs by repositioning and sequentially inserting nucleosomes into a specific region of the gene promoter to compact the chromatin in differentiating cells., (Copyright © 2011 AlphaMed Press.)

Background: Various maneuvers are commonly used to achieve the ideal operative field necessary for successful endoscopic sinus surgery (ESS). There are a few contradictory reports on this subject and the consensus is that propofol anesthesia results in a better or similar surgical field and less or similar amount of bleeding than volatile anesthesia. The aim of this study was to compare the surgical field in patients in whom intravenous anesthesia is used as opposed to balanced general anesthesia., Methods: SIXTY PATIENTS UNDERGOING ESS WERE RANDOMLY ASSIGNED INTO THREE GROUPS, EACH OF WHICH USED A DIFFERENT TYPE OF ANESTHESIA: propofol/remifentanil (PRO/REM) group, sevoflurane/remifentanil (SEV/REM) group, and desflurane/remifentanil (DES/REM) group. We aimed to maintain the intraoperative mean blood pressure (MBP) at 65 mmHg and the heartrate (HR) at about 75 beats per minute. The quality of visibility of the surgical field was graded, using a validated scoring system, 60 minutes after the start of the operation., Results: All groups had a similar MBP and mean HR at 60 minutes after the operation started. There was no significant differences among the three groups for surgical grade score (P = 0.83)., Conclusions: In this comparative study of three anesthetic combinations (PRO/REM, SEV/REM, and DES/REM) in patients undergoing ESS with controlled BP and HR, we did not observe any significant differences in the surgical grade scores.

We routinely have performed arthroscopic shoulder surgery under general anesthesia in the beach chair position using epinephrine (0.33 mg/L) saline irrigation. At a 2-week interval, two patients, a 19-year-old man scheduled to undergo an arthroscopic Bankart repair for left traumatic anterior instability and a 49-year-old woman scheduled for an arthroscopic rotator cuff repair for a left rotator cuff tear, were resuscitated by chest compression and defibrillation due to a sudden developed cardiogenic shock following ventricular tachycardia at the time of arthroscopic shoulder surgery. They were transferred to the intensive care unit because their emergent echocardiogram showed significantly decreased cardiac functions. They were fully recovered and then discharged. Epinephrine was considered to be the cause of ventricular tachycardia because the two patients showed no anaphylactic reaction to drugs or symptoms of air embolism related to the beach chair position. In addition, according to our observation of epinephrine flow patterns, it was more likely that highly concentrated epinephrine was rapidly infused into the body. This complication is very rare. However, thorough understanding of the side effects and their development of epinephrine during arthroscopic shoulder surgery should neither be overemphasized nor disregarded.

Objectives: To find new biomarkers by stimulating acupuncture point GB34 (Yangneungcheon) which has neuroprotective effect on the mouse model of Parkinson's disease, analysis of cDNA microarray on mRNAs of the substantia nigra was performed., Methods: Male C57BL/6 mice were divided into two groups: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated mice (MPTP group, n=3); 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and acupuncture (GB34)-treated mice (MPTP + ACU group, n=3). The mice received an intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) once daily for 3 consecutive days. Manual acupuncture was performed 2 hours after every injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The total RNA in the substantia nigra of each mouse was isolated on 3 days after the last 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. Agilent mouse whole genome 44K chip was used for microarray analysis and the hybridization image was analysed by GenePix Pro 6.0. Data normalization and analysis were performed using GeneSpring GX 7.3.1 program., Results: The acupuncture stimulation revealed 799 genes (424 up- and 375 down-regulated) of which expression levels were changed more than two-folds in the MPTP + ACU group, compared to the MPTP group. The genes selected were classified into several categories based on their functions using DAVID Bioinformatics Resources 2008 (http://david.abcc.ncifcrf.gov/) and KEGG PATHWAY Database (http://www.genome.jp/kegg/pathway.html)., Discussion: Biomarkers in response to acupuncture stimulation to GB34 were identified in a mouse model for Parkinson's disease. These biomarkers might provide a promising clue for understanding the neuroprotective effect of acupuncture in Parkinson's disease.

Objectives: Early stressors can influence the development of biological and neurological systems. Maternal separation (social isolation) in early life may increase vulnerability to neurodegenerative diseases and neuropsychiatric disorders over the lifespan. To identify new proteins on acupuncture effects in maternally separated rats, an animal model for study of early environmental insults, proteomic approach on the expression of the hypothalamic proteins was performed., Methods: On post-natal day 14, rat pups were randomly divided into four groups: pups kept with their mothers for 7 days; pups kept with their mothers with acupuncture daily to HT8 (Sobu); maternally separated pups; maternally separated pups with acupuncture. The hypothalamic proteins were analysed by two-dimensional electrophoresis coupled with matrix assisted laser desorption/ionization time-of-flight mass spectrometer., Results: The results showed that 27 spots were differentially and commonly expressed. Of 27 spots, 21 spots were identified while six spots were not, and 15 proteins were known proteins. In maternally separated group, the expressions of 14 proteins were down-regulated, compared to control group. In group of maternally separation with acupuncture, five proteins were down-regulated and nine were up-regulated, compared to the maternally separated group. Among nine proteins up-regulated by acupuncture treatment, we found four proteins (dihydropyrimidinase-like 2, dystrophin-related protein 2, tubulin, alpha 1a and syntaxin 1b) related to neurodevelopment., Discussion: The result suggests that acupuncture to HT8 may affect neurodevelopment, and acupuncture may be a possible therapy for neurodevelopmental disorders.

Cellular retinoic acid binding protein 1 (Crabp1) gene is biphasically (proliferation versus differentiation) regulated by thyroid hormone (T3) in 3T3-L1 cells. This study examines T3-repression of Crabp1 gene during adipocyte differentiation. T3 repression of Crabp1 requires receptor interacting protein 140 (RIP140). During differentiation, the juxtaposed chromatin configuration of Crabp1 promoter with its upstream region is maintained, but the 6-nucleosomes spanning thyroid hormone response element to transcription initiation site slide bi-directionally, with the third nucleosome remaining at the same position throughout differentiation. On the basal promoter, RIP140 replaces coactivators GRIP1 and PCAF and forms a repressive complex with CtBP1, HDAC3 and G9a. Initially active chromatin marks on this promoter, histone modifications H3-Ac and H3K4-me3, are weakened whereas repressive chromatin marks, H3K9-me3 and H3K27-me3 modification and recruitment of G9a, HP1alpha, HP1gamma and H1, are intensified. This is the first study to examine chromatin remodeling, during the phase of hormone repression, of a bi-directionally regulated hormone target gene, and provides evidence for a functional role of RIP140 in chromatin remodeling to repress hormone target gene expression.

Purpose: The aim of this study was to compare the change in body temperature between the cotton blanket group and forced-air warming blanket group during arthroscopic shoulder surgery. In both groups irrigation fluid at room temperature (22 degrees C) was used., Methods: We randomly assigned 44 American Society of Anesthesiologists physical status I and II patients scheduled for elective shoulder arthroscopic surgery to receive 1 cotton blanket (group I, n = 22) or a forced-air warming blanket (group II, n = 22). Body temperatures were measured with an esophageal stethoscope, which was inserted immediately after intubation., Results: A significant difference in body temperatures was observed at 60 minutes after induction (P = .0192), 90 minutes after induction (P = .0004), 120 minutes after induction (P = .0003), and 150 minutes after induction (P = .0228). Shivering on arrival in the postanesthesia care unit was found in 15 patients in group I (68.1%) and only 1 patient in group II (4.5%)., Conclusions: We conclude that forced-air warming is significantly more efficient than a cotton blanket alone at maintaining perioperative normothermia during arthroscopic shoulder surgery., Level of Evidence: Level I, randomized controlled trial.

Background: Tourniquet deflation during lower extremity surgery affects the hemodynamics and metabolism of the patient, which can affect brain activity. This study examined the changes in brain activity during tourniquet deflation by measuring the bispectral index (BIS)., Methods: The BIS was measured during surgery in forty patients who had received knee arthroscopic surgery under general anaesthesia. The BIS was measured 5 minutes before deflation (DB5) and 5 minutes after deflation (DA5)., Results: The BIS at DB5 and DA5 was 50.2 +/- 9.9 and 44.4 +/- 10.4, respectively. The BIS of DA5 was significantly lower than that of DB5 (P < 0.05)., Conclusions: Tourniquet deflation during lower extremity surgery decreases the BIS associated with hemodynamic and metabolic changes. However, its clinical significance in neurologically critical patients, such as geriatric or neurologically disabled patients, remains to be clarified.

Pigmentary anomalies display a variety of different patterns. The phylloid pattern is characterized by a leaf-shaped arrangement reminiscent of floral ornaments. We describe a 20-year-old Korean man with hyperpigmented oblong patches and atypically short, thick hairs in a phylloid pattern on the face, the left shoulder, and the left side of the trunk. Associated musculoskeletal anomalies included equinovarus deformities, bilateral club foot, lumbar lordosis, spina bifida, and relative hypertrophy of the right thigh muscles.

Background: The use of CO2 for pneumoperitoneum during laparoscopic surgery provokes a decrement in the gastric pH. Since the incidence rate of PONV increases after laparoscopic surgery, the possibility of lung aspiration of gastric juice with a low pH during a postanesthetic emergence may increase and this could be fatal for the patient. We conducted this study to determine the effects of esomeprazole premedication on inhibiting the decrement of the gastric pH during laparoscopic surgery., Methods: 40 adult patients with no underlying diseases were chosen and 20 patients each were grouped as C (the control group) and E (the esomeprazole group). In both group, 0.2 mg glycopyrrolate was given intramuscularly 30 minutes prior to the surgery. In group E, esomeprazole was given orally 2 hours prior to the surgery. The pH, PaCO2, and PETCO2 were measured via pH probe, an ABGA and an capnogram at preinsufflation and 15, 30 and 60 minutes after the CO2 insufflation and right before CO2 exhaustion (predeflation)., Results: Comparing the measurements of the gastric pH between group E and group C, all the results showed a significant increase in group E (P < 0.05). The difference of the PaCO2 and PETCO2 in the two groups was not significance., Conclusions: In contrast to the decrease in the gastric pH as the PaCO2 and PETCO2 increased in group C, the gastric pH in group E remained high until the end of the surgery despite the increase in the PaCO2 and PETCO2. Esomeprazole premedication seem to have an effect for inhibiting the gastric pH decrement regardless of the increase in the PaCO2 and PETCO2 during laparoscopic surgery.

Background: L-Ascorbic acid is used to treat melasma; however, it is quickly oxidized in aqueous solutions. Thus, C'ensil, a formulation containing 25% l-ascorbic acid and a chemical penetration enhancer, was created to promote the penetration of l-ascorbic acid into the skin., Objective: To evaluate the efficacy of C'ensil in patients with melasma., Methods: Forty subjects with melasma were treated with C'ensil during an open-label trial over a period of 16 weeks. Each subject's skin pigmentation was assessed every 4 weeks using the Melasma Area and Severity Index (MASI) and mexameter score. In addition, transepidermal water loss, skin dryness and irritation, and quality of life (Melasma Quality of Life Scale [MelasQoL]) were evaluated., Results: After 16 weeks, a significant decrease was noted in the degree of pigmentation based on the patients' MASI and mexameter scores. MelasQoL scores also decreased, indicating an increase in the subjects' quality of life., Conclusion: Our data indicate that C'ensil is an effective treatment modality for melasma.

A 43-year-old male was admitted for reconstruction surgery to repair posterolateral rotatory instability of the knee. At the request of the surgeon, ranitidine was slowly administered intravenously immediately before the patient was transferred to the operating room to reduce the incidence of acid reflux. A few minutes later, during the transfer of the patient, anaphylaxis developed with hypotension, nausea, dyspnea, change in consciousness and urticaria. The patient had no previous history of any allergic tendency. After appropriate management, he recovered without complication. Following surgery, an allergic skin prick test was performed to determine if the patient was allergic to any of the drugs used during the surgery. According to the results, only ranitidine showed a positive reaction.

We previously reported an intricate mechanism underlying the homeostasis of Oct4 expression in normally proliferating stem cell culture of P19, mediated by SUMOylation of orphan nuclear receptor TR2. In the present study, we identify a signaling pathway initiated from the nongenomic activity of all-trans retinoic acid (atRA) to stimulate complex formation of extracellular signal-regulated kinase 2 (ERK2) with its upstream kinase, mitogen-activated protein kinase kinase (MEK). The activated ERK2 phosphorylates threonine-210 (Thr-210) of TR2, stimulating its subsequent SUMOylation. Dephosphorylated TR2 recruits coactivator PCAF and functions as an activator for its target gene Oct4. Upon phosphorylation at Thr-210, TR2 increasingly associates with promyelocytic leukemia (PML) nuclear bodies, becomes SUMOylated, and recruits corepressor RIP140 to act as a repressor for its target, Oct4. To normally proliferating P19 stem cell culture, exposure to a physiological concentration of atRA triggers a rapid nongenomic signaling cascade to suppress Oct4 gene and regulate cell proliferation.

Deep depth peeling using phenol is one of the most effective chemical peeling methods. However, it has been rarely used on Asian people because of side-effects, especially hypopigmentation. In order to reduce side-effects, a number of modified phenol peeling formulas were developed. Exoderm, a modified phenol peel, has shown reduced side-effects such as arrhythmia, long-lasting erythema, hypopigmentation, hypertrophic scar and keloid. In the present study, our aim was to evaluate the effectiveness of Exoderm on wrinkles, acne scars, and melasma and its safety for Asian patients. Forty-six patients were treated with Exoderm. Twenty-eight patients (61%) were treated for wrinkles and 11 patients (24%) for acne scars. Clinical improvement and side-effects were evaluated and the degree of improvement was graded into four stages. The overall average improvement scores were 3.39 and 3.30 out of 4.00 as evaluated by the doctor and patient, respectively. Forty-one patients (89%) showed 51% or more improvement. All patients with wrinkles improved 51% or more and their average improvement score was 3.64 out of 4.00. Seven of 11 patients (64%) with acne scars improved 51% or more and their average improvement score was 2.73 out of 4.00. The most frequent side-effect was postinflammatory hyperpigmentation (74%). Prolonged erythema, keloid and milia were observed temporarily, however, hypopigmentation persisted for 6 months in the follow-up period. All side-effects were tolerable and reversible except for one complication of hypopigmentation. We conclude that Exoderm is very effective for treating the facial wrinkles and acne scars of Asian patients.

Orphan nuclear receptor TR2 is a preadipocyte proliferator. Knockdown of TR2 in 3T3-L1 preadipocytes reduced their proliferation efficiency, whereas specific elevation of TR2 in these cells facilitated their proliferation. All-trans retinoic acid (RA) stimulates cellular proliferation in 3T3-L1 preadipocytes by activating TR2 through an IR0-type RA response element, which further activates c-Myc expression. In post-differentiated adipocytes, RA becomes a repressive signal for TR2 and rapidly down-regulates its expression. The biphasic effect of RA on TR2 expression in 3T3-L1 is mediated by differential RA-dependent coregulator recruitment to the receptor/Glucocorticoid Receptor-Interacting Protein 1 (GRIP1) complex that binds IR0 on the TR2 promoter. RA induces the recruitment of histone acetyl transferase-containing/GRIP1/p300/CBP-associated factor (PCAF) complex to the TR2 promoter in undifferentiated cells, whereas it triggers recruitment of histone deacetylase-containing/GRIP1/receptor-interacting protein 140 (RIP140) complex in differentiated cells. GRIP1 directly interacts with RIP140 through its carboxyl terminal AD2 domain. GRIP1 interacts with PCAF and RIP140 directly and differentially, functioning as a platform molecule to mediate differential RA-induced coregulator recruitment to TR2 promoter target. This results in a biphasic effect of RA on the expression of TR2 in undifferentiated and differentiated cells, which is required for RA-stimulated preadipocyte proliferation.

Background: Axillary osmidrosis and hyperhidrosis are distressing social problems, particularly in Asian societies. Various treatment methods have been developed for removal of the apocrine and eccrine glands. But conventional surgical methods often lead to significant scarring and frequent recurrence., Objective: To evaluate the effect of liposuction with curettage using a new device, the Fatemi cannula, in the treatment of axillary osmidrosis and hyperhidrosis., Methods: From August 2003 through December 2004, 25 patients (15 women and 10 men) with axillary osmidrosis or hyperhidrosis were treated by tumescent liposuction and curettage. The results of malodor elimination were graded by the patients as excellent, good, fair, and poor. Changes in axillary sweating and hair growth, postoperative scarring, patient satisfaction degree, and complications were also evaluated. Biopsies of the axillary skin were performed in 14 patients., Results: Of the 50 axillae, 38 (76.0%) were graded as excellent results, 11 (22.0%) were good, and one (2.0%) was fair. No serious complications were noted except temporary ecchymosis and local infection in minor cases. The preoperative histologic examinations showed large and numerous apocrine glands and postoperative significant decrease and degeneration of them., Conclusion: Tumescent liposuction with dermal curettage using the Fatemi cannula is an effective and safe method in the treatment of axillary osmidrosis and hyperhidrosis.

Receptor interacting protein (RIP140) is a versatile coregulator for many nuclear receptors and transcription factors. Analysis by liqid chromatography tandem mass spectroscopy led to the identification of 11 phosphopeptides from tryptic digests of His6-RIP140 purified from Sf21 insect cells. No phosphopeptides were detected on RIP140 expressed in E. coli in a parallel experiment, suggesting that RIP140 phosphorylation occurred specifically only in eukaryotic cells. The tandem mass spectra of the precursor ions of the phosphopeptides were analyzed to map the exact phosphorylation sites on RIP140. All the phosphopeptides displayed intact phosphate containing y- or b-ion signals along with their beta-eliminated product ions, due to neutral loss of phosphoric acid. Phosphorylation occurred specifically on nine serine and a single threonine residues, including Ser-104, Thr-207, Ser-358, Ser-380, Ser-488, Ser-519, Ser-531, Ser-543, Ser-672, and Ser-1003. No tyrosine phosphorylation was found. These data suggested that the central region of RIP140, one major repressive domain, was extensively modified by phosphorylation. These phosphorylation sites can be the targets in future studies addressing post-translational modification of RIP140 with regards to its biological activities.

Modulation of the spontaneous activity of rat medial vestibular nuclear neurons by nitric oxide was investigated using the whole-cell patch-clamp technique. The spike frequency was increased by sodium nitroprusside (SNP), a nitric oxide liberating agent, and it was also increased by another nitric oxide liberating agent, sodium-nitroso-N-acetylpenicillamine. L-Arginine, the substrate of nitric oxide synthase, increased the firing of the neurons. The increased SNP-induced firing was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ), a specific inhibitor of guanylate cyclase. These results suggest that nitric oxide increases the neuronal excitability of the neurons by a cGMP-dependent mechanism.

Nitric oxide (NO) may regulate gene expression by directly modifying redox state-sensitive residues of transcription factors. Here we show that the NO donor, sodium nitroprusside (SNP), rapidly represses c-myc gene transcription in a protein synthesis-independent manner in P19 embryonal carcinoma cells by inactivation of NF-kappa B. SNP treatment reduces the DNA binding ability of the constitutively active NF-kappa B heterodimer, p65/p50, and its consequent transactivation of the c-myc promoter. Repression can be blocked by the peroxynitrite scavenger, deferoxamine, but not by dithiothreitol, which triggers reduction of S-nitrosylated residues. In HEK293 cells, where tumor necrosis factor-alpha can activate NF-kappa B, SNP likewise suppresses the binding of the active NF-kappa B complex, restoring the binding of the repressive p50/p50 homodimer complex. This effect of SNP in HEK293 cells is also blocked by deferoxamine. Chromatin immunoprecipitation analysis of SNP-treated P19 cells reveals reduced association of p65, but not of p50, with the promoter region of the endogenous c-myc gene. SNP-induced p65 dissociation was associated with the recruitment of histone deacetylase 1 and 2 to the endogenous c-myc gene promoter and the subsequent deacetylation of its chromatin histone. This study is the first to demonstrate that NO modulates the transcriptional activity of the c-myc gene promoter by dissociating the active form of NF-kappa B and replacing it with a repressive NF-kappa B complex, correlated with the recruitment of gene-silencing histone deacetylases. In light of findings that NF-kappa B stimulates Myc oncoprotein expression in cancers, our findings suggest that NO should be investigated as a prospective therapeutic cancer agent.

Nitric oxide (NO) suppressed the transcription of the mouse kappa opioid receptor (KOR) gene, mediated by a rapid downregulation of c-myc gene expression. KOR was constitutively expressed in postnatal day 19 (P19) embryonal carcinoma stem cells and is suppressed by NO donors [sodium nitroprusside (SNP), 3-morpholinosydnonimine-1, and S-nitrosoglutathione] in P19 stem cells within 4 hr. The suppression was reversed by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, an NO scavenger, but could not be blocked by dithiothreitol, ruling out S-nitrosylation as the underlying mechanism. The suppressive effect of NO on KOR occurred at the level of gene transcription, mediated by E boxes located in promoters I and II of this gene. Protein-DNA complexes that formed on these E boxes contained c-myc; c-myc expression was suppressed by NO in P19 stem cells within 2 hr of treatment. Furthermore, chromatin immunoprecipitation demonstrated reduced c-myc binding to the E boxes and hypoacetylation of histone H3 on the chromatin of endogenous KOR promoters in P19 stem cells treated with SNP. It is proposed that NO regulates KOR at the level of gene transcription, mediated by a rapid suppression of c-myc gene expression and its binding to KOR promoters, and followed by chromatin hypoacetylation of and reduced transcription from KOR promoters in P19 stem cells. A novel pathway mediating the potential interplay between NO and opioid systems is discussed.

Background: Treatment of coup de sabre must remain conservative until the disease is no longer in an active state. When activity has ceased, some operative intervention is safe and effective for the correction of deformity. While hair transplantation showed high survival rates for the correction of cicatricial alopecia, it has not yet been reported to be performed for the correction of coup de sabre., Objective: To examine the therapeutic possibility of hair transplantation for the correction of coup de sabre., Methods: Follicular units consisting of two to three hairs from the patient's occipital scalp were transplanted using Choi hair transplanters., Results: Ten-month follow-up studies showed an 86.5% survival rate and 10-14 cm (mean 12 cm) length of the transplanted hairs., Conclusion: When coup de sabre is no longer in an active state, hair transplantation is a useful method for cosmetic improvement of the alopecia.