S-methyl-(L)-methionine (SMM), also known as vitamin U, is commercially available as skin care cosmetic products for its wound healing and photoprotective effects. However, the low skin permeation expected of SMM due to its hydrophilic nature with a log P value of −3.3, has not been thoroughly addressed. The purpose of this study thus was to evaluate the effect of skin permeation enhancers on the skin permeation/deposition of SMM. Among the enhancers tested for the in vitro skin permeation and deposition of SMM, oleic acid showed the most significant enhancing effect. Moreover, the combination of oleic acid and ethanol further enhanced in vitro permeation and deposition of SMM through hairless mouse skin. Furthermore, the combination of oleic acid and ethanol significantly increased the in vivo deposition of SMM in the epidermis/dermis for 12 hr, which was high enough to exert a therapeutic effect. Therefore, based on the in vitro and in vivo studies, the combination of oleic acid and ethanol was shown to be effective in improving the topical skin delivery of SMM, which may be applied in the cosmetic production process for SMM.
Animals ; Ethanol ; In Vitro Techniques* ; Mice ; Mice, Hairless ; Oleic Acid ; Skin Care ; Skin* ; Vitamin U ; Wound Healing

BACKGROUND: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. METHODS: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) were measured in BALF. Nuclear factor kappaB (NF-kappaB), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. RESULTS: TNF-alpha and IL-1beta concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5+/-2.8 nmol/mL vs. 16.5+/-1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4+/-1.8 unit/g vs. 11.2+/-6.3 unit/g, tissue) (p<0.048). The concentration of NF-kappaB in NAC treatment group was significantly lower than that of LPS group (0.3+/-0.1 ng/microL vs. 0.4+/-0.2 ng/microL) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. CONCLUSION: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-kappaB activation.
Acetylcysteine ; Acute Lung Injury ; Animals ; Antioxidants ; Humans ; Interleukin-1beta ; Lipid Peroxidation ; Lung ; Lung Injury ; Male ; NF-kappa B ; Peroxidase ; Rats ; Rats, Sprague-Dawley ; Therapeutic Irrigation ; Tumor Necrosis Factor-alpha ; Veins

BACKGROUND: Oxidation plays an important role in acute lung injury. This study was conducted in order to elucidate the effect of repetitive post-treatment of N-acetylcysteine (NAC) in lipopolysaccaride (LPS)-induced acute lung injury (ALI) of rats. METHODS: Six-week-old male Sprague-Dawley rats were divided into 4 groups. LPS (Escherichia coli 5 mg/kg) was administered intravenously via the tail vein. NAC (20 mg/kg) was injected intraperitoneally 3, 6, and 12 hours after LPS injection. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the ALI at 24 hours after LPS injection. The concentration of tumor necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) were measured in BALF. Nuclear factor kappaB (NF-kappaB), lipid peroxidation (LPO), and myeloperoxidase (MPO) were measured using lung tissues. Micro-computed tomography (micro-CT) images were examined in each group at 72 hours apart from the main experiments in order to observe the delayed effects of NAC. RESULTS: TNF-alpha and IL-1beta concentration in BALF were not different between LPS and NAC treatment groups. The concentration of LPO in NAC treatment group was significantly lower than that of LPS group (5.5+/-2.8 nmol/mL vs. 16.5+/-1.6 nmol/mL) (p=0.001). The activity of MPO in NAC treatment group was significantly lower than that of LPS group (6.4+/-1.8 unit/g vs. 11.2+/-6.3 unit/g, tissue) (p<0.048). The concentration of NF-kappaB in NAC treatment group was significantly lower than that of LPS group (0.3+/-0.1 ng/microL vs. 0.4+/-0.2 ng/microL) (p=0.0001). Micro-CT showed less extent of lung injury in NAC treatment than LPS group. CONCLUSION: After induction of ALI with lipopolysaccharide, the therapeutic administration of NAC partially attenuated the extent of ALI through the inhibition of NF-kappaB activation.
Acetylcysteine ; Acute Lung Injury ; Animals ; Antioxidants ; Humans ; Interleukin-1beta ; Lipid Peroxidation ; Lung ; Lung Injury ; Male ; NF-kappa B ; Peroxidase ; Rats ; Rats, Sprague-Dawley ; Therapeutic Irrigation ; Tumor Necrosis Factor-alpha ; Veins

PURPOSE: We sought to identify asthma-related genes and to examine the potential of these genes to predict asthma, based on expression levels. METHODS: The subjects were 42 asthmatics and 10 normal healthy controls. PBMC RNA was subjected to microarray analysis using a 35K array; t-tests were used to identify genes that were expressed differentially between the two groups. A multiple logistic regression analysis was applied to the differentially expressed genes, and area under the curve (AUC) values from receiver operating characteristic (ROC) curves were obtained. RESULTS: In total, 170 genes were selected using the following criteria: P< or =0.001 and > or =2-fold change. Among these genes, 57 were up-regulated and 113 were down-regulated in asthmatics versus normal controls. A multiple logistic regression analysis was done using more stringent criteria (P< or =0.001 and > or =5-fold change), and eight genes were selected as candidate asthma biomarkers. Using these genes, 255 models (2(8)-1) were generated. Among them, only 85 showed P< or =0.05 by multiple logistic regression analysis. Based on the AUCs from ROC curves for the 85 models, we found that the best model consisted of the genes MEPE, MLSTD1, and TRIM37. The model showed 0.9928 of the AUC with 98% sensitivity and 80% specificity. CONCLUSIONS: MEPE, MLSTD1, and TRIM37 may be useful biomarkers for asthma.
Area Under Curve ; Asthma ; Biomarkers ; Gene Expression ; Gene Expression Profiling ; Genetic Markers ; Logistic Models ; Microarray Analysis ; RNA ; ROC Curve

PURPOSE: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARgamma regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. METHODS: Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). RESULTS: Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). CONCLUSIONS: The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.
Alleles ; Aspirin ; Asthma ; Cytokines ; Eosinophils ; Haplotypes ; Humans ; Hypersensitivity ; Inflammation ; Ligands ; Logistic Models ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; Polymorphism, Single Nucleotide ; PPAR gamma

PURPOSE: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors activated by ligands of the nuclear hormone receptor superfamily. The activation of PPARgamma regulates inflammation by downregulating the production of Th2 type cytokines and eosinophil function. In addition, a range of natural substances, including arachidonate pathway metabolites such as 15-hydroxyeicosatetranoic acid (15-HETE), strongly promote PPARG expression. Therefore, genetic variants of the PPARG gene may be associated with the development of aspirin-intolerant asthma (AIA). We investigated the relationship between single nucleotide polymorphism (SNP) of the PPARG gene and AIA. METHODS: Based on the results of an oral aspirin challenge, asthmatics (n=403) were categorized into two groups: those with a decrease in FEV1 of 15% or greater (AIA) or less than 15% (aspirin-tolerant asthma, ATA). We genotyped two single nucleotide polymorphisms in the PPARG gene from Korean asthmatics and normal controls (n=449): +34C>G (Pro12Ala) and +82466C>T (His449His). RESULTS: Logistic regression analysis showed that +82466C>T and haplotype 1 (CC) were associated with the development of aspirin hypersensitivity in asthmatics (P=0.04). The frequency of the rare allele of +82466C>T was significantly higher in AIA patients than in ATA patients in the recessive model [P=0.04, OR=3.97 (1.08-14.53)]. In addition, the frequency of PPARG haplotype 1 was significantly lower in AIA patients than in ATA patients in the dominant model (OR=0.25, P=0.04). CONCLUSIONS: The +82466C>T polymorphism and haplotype 1 of the PPARG gene may be linked to increased risk for aspirin hypersensitivity in asthma.
Alleles ; Aspirin ; Asthma ; Cytokines ; Eosinophils ; Haplotypes ; Humans ; Hypersensitivity ; Inflammation ; Ligands ; Logistic Models ; Peroxisome Proliferator-Activated Receptors ; Peroxisomes ; Polymorphism, Single Nucleotide ; PPAR gamma

PURPOSE: There has been increased the number of early gastric cancer and laparoscopy-assisted gastrectomy (LAG), due to early detection through mass screening program. We started the LAG in April 2004 and performed 119 cases of gastric cancer in 2005, so we report a surgical outcome compared with that of open gastrectomy (OG). MATERIALS AND METHODS: 119 patients underwent LAG in 2005, and for open group, 126 patiens of early gastric cancer were selected sequentially from January 2005 to March 2005. We compared clinicopathologic characteristics, postoperative courses and complications between two groups. RESULTS: There was no significant difference between age, a length of hospital stay, distal resection margin and a number of retrived lymph nodes. The operation time was longer in LAG group (239.2 vs 123.3 mins, P < 0.001) and a diet progression was faster in LAG group (first flatus: 3.05 vs 3.70 days, SOW: 2.86 vs 3.22 days, liquid diet: 3.87 vs 4.19 days ,soft diet: 4.84 vs 5.26 days, P < 0.001). But there was no difference statistically in postoperative discharge date (7.73 vs 8.25 days, P=0.229). The additional requirement of analgesic injection was less frequent in LAG group (2.97 vs 4.92 times, P < 0.001). The harvested lymph nodes were similar in both groups (23.9 vs 23.1, P=0.563). A complication rate was lower in LAG group (4.9% vs 9.5%), but there was no statistical significance (P=0.179). There was no mortality in both groups and no conversion to open gastrectomy in the LAG group. CONCLUSION: LAG can be performed safely and accepted in view of curative procedure in treatment of early gastric cancer. But we need the follow up of long-term period to evaluate the survival rate and recurrence, and a prospective randomized controlled study should be done to establish that LAG will be a standard operation for early gastric cancer.
Diet ; Flatulence ; Follow-Up Studies ; Gastrectomy* ; Humans ; Length of Stay ; Lymph Nodes ; Mass Screening ; Mortality ; Recurrence ; Stomach Neoplasms ; Survival Rate

Idiopathic fibrosing mediastinitis is, an uncommon cause of pulmonary hypertension this is characterized by excessive fibrosis of the mediastinum with an unknown etiology. Steroid therapy has been suggested for individuals with progressive symptoms, bu there is littlet data demonstrating the efficacy of such therapy are lacking. We present a case of pulmonary hypertension secondary to a compression of a main pulmonary artery by fibrosing mediastinitis which was confirmed by a biopsy with a thoracotomy. The chest CT scan and 2D echocardiography performed before and after a trial of steroid therapy demonstrated improvement after steroid therapy.
Biopsy ; Echocardiography ; Fibrosis ; Hypertension, Pulmonary* ; Mediastinitis* ; Mediastinum ; Pulmonary Artery ; Thoracotomy ; Tomography, X-Ray Computed

RUNX1, a member of the runt domain gene family of transcription factors, encodes a heterodimeric transcription factor and regulates the expression of various genes related to hematopoiesis and myeloid differentiation. RUNX1 has been one of the target genes for research into various autoimmune diseases due to its properties as a transcription factor and functional distribution for chromosomal translocation. In an effort to identify additional gene polymorphisms in which variants have been implicated in asthma, we investigated the genetic polymorphisms in RUNX1 to evaluate it as a potential candidate gene for a host genetic study of asthma and IgE production. We identified 19 sequence variants by direct DNA sequencing in 24 individuals of which four common variants were selected for genotyping in our asthma cohort (1,055 asthmatic patients, 384 normal controls). Using logistic regression analysis for association with the risk of asthma, while controlling for age, gender, and smoking status as covariates, no significant associations with the risk of asthma were detected. However, two polymorphisms in the promoter region (-2084G>C and -1282G>A) showed a marginal association with total IgE levels (0.03 and 0.03 in recessive models, respectively). Our findings suggest that polymorphisms in RUNX1 might be one of the genetic factors for the regulation of IgE production.
Sequence Analysis, DNA ; Risk Factors ; Polymorphism, Single Nucleotide ; *Polymorphism, Genetic ; Middle Aged ; Male ; Korea ; Immunoglobulin E/*blood ; Humans ; Female ; Data Collection ; Core Binding Factor Alpha 2 Subunit/*genetics ; Cohort Studies ; Child, Preschool ; Child ; Asthma/epidemiology/genetics ; Aged, 80 and over ; Aged ; Adult ; Adolescent

PURPOSE: The laparoscopy assisted gastrectomy has been increasingly reported as the treatment of choice for early gastric cancer. However, expert surgeons, who have performed a conventional open gastrectomy for a long time, tend to have a negative attitude toward laparoscopic procedures. The aim of this study was to determine the learning curve of a laparoscopy assisted distal gastrectomy (LADG) for a surgeon expert in performing an open gastrectomy and to analyze the factors that have an effect on a LADG. MATERIALS AND METHODS: Between April 2005 and March 2006, 62 patients underwent a LADG with D1+beta lymph-node dissection. The 62 patients were divided into 10 sequential groups with 6 cases in each group (the last group was 8 cases), and the time required to reach the plateau of the learning curve was determined by examining the average operative times of these 10 groups. Other factors, such as sex, BMI, complications, transfusion requirements, the number of retrieved lymph nodes, and change of postoperative hemoglobin level, were also analyzed. RESULTS: With the 5th group (after 30 cases), the operative time reached a plateau (average: 170 min/operation). The differences between before the 30th case and after the 31st case with respect to changes in the postoperative hemoglobin level, the number of retrieved lymph nodes, the transfusion requirements, and the complications rate were not significant. CONCLUSION: According to an analysis of the operative time, experience with 30 LADGs in patients with early gastric cancer is the point at which the plateau of the learning curve (7 months) is reached. Abundant experience with a conventional open gastrectomy and a well-organized laparoscopic surgery team are important factors in overcoming the learning curve earlier.
Gastrectomy* ; Humans ; Laparoscopy* ; Learning Curve* ; Learning* ; Lymph Nodes ; Operative Time ; Stomach Neoplasms