Globular adiponectin acts as a melanogenic signal in human epidermal melanocytes.

BACKGROUND: Adiponectin is an adipocyte-derived cytokine that circulates as a full-length protein and a fragment containing the globular domain of adiponectin (gAd). A recent study has reported the antimelanogenic effects of full-length adiponectin. OBJECTIVES: To examine the involvement of gAd in melanogenesis and its mechanisms of action. METHODS: The effects of gAd on melanogenesis and its mechanisms of action were investigated in human epidermal melanocytes and reconstructed epidermis, including melanin content, cellular tyrosinase activity, cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activity, expression and phosphorylation of signalling molecules. RESULTS: Exogenous gAd increased melanin content, and the mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes TRP1, but not TRP2, were increased by gAd. However, cAMP production and PKA activity were not affected by gAd. Moreover, attempts to elucidate the underlying mechanism behind the gAd-mediated effect revealed that gAd could regulate melanogenesis by upregulating MITF through phosphorylation of the cAMP response element-binding protein (CREB). In addition, upregulation of MITF was mediated by activation of adenosine monophosphate-activated protein kinase (AMPK)-p38 mitogen-activated protein kinase (MAPK) signalling. Taken together, these findings indicate that promotion of melanogenesis by gAd occurs through increased expression of MITF, which is mediated by activation of the AMPK-p38 MAPK-CREB pathway. CONCLUSIONS: These findings suggest that gAd contributes to epidermal homeostasis via its effect on melanocyte biology, and products of adipose tissue could affect epidermal biology.

Effect of sodium chloride on the survival of Shigella flexneri in acidified laboratory media and cucumber puree.

AIMS: This study investigated the effects of sodium chloride (NaCl) and various acids, alone or in combination, on Shigella flexneri growth in laboratory medium and cucumber puree. METHODS AND RESULTS: Shigella flexneri was treated with various acids (acetic, citric, malic, tartaric, propionic, lactic and phosphoric acid) alone or with 3, 6 or 9% NaCl. Pronounced antagonistic effects were observed in Sh. flexneri treated with acetic or lactic acid in combination with 3% NaCl. Next, Sh. flexneri was pre-exposed to 3% NaCl and then treated with various acids; acid-stressed cells were then inoculated onto agar plates containing 3% NaCl. There was no significant difference in the reduction of Sh. flexneri, regardless of treatment (P > 0·05). Finally, Sh. flexneri was inoculated into cucumber puree to which various concentrations of acetic acid had been added with and without 3% NaCl. Antagonistic effects were observed with a treatment of either 0·5 or 1% acetic acid combined with 3% NaCl. CONCLUSIONS: Antagonistic effects were observed when Sh. flexneri was exposed to acetic or lactic acid with NaCl. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that depending on the type of acid, the addition of NaCl can increase the resistance of Sh. flexneri to acid treatments. This may provide useful information for developing methods of preserving acidified foods.

Association between coffee intake and gastroesophageal reflux disease: a meta-analysis.

Gastroesophageal reflux disease (GERD) is one of the most common diseases affecting patients worldwide, but its risk factors and causes are not clearly known. The aim of this study was to investigate the effect of coffee intake on GERD by a meta-analysis. We searched online published research databases such as PubMed, EMBASE, and Cochrane Library for studies that were published up to December 2012. These publications were reviewed by two independent authors, and studies that fulfilled the criteria were selected. Whenever there was a disagreement between the authors, a consensus was reached by discussion. Fifteen case-control studies were included in the final analysis. A meta-analysis showed that there was no significant association between coffee intake and GERD. The odds ratio was 1.06 (95% confidence interval, 0.94-1.19). In subgroup analyses in which the groups were subdivided based on the definition of GERD (diagnosed by endoscopy or by symptoms alone), only the endoscopy group showed a significantly higher odds ratio. In subgroup analyses in which the groups were subdivided based on the amount of coffee intake, quality of study, and assessment of exposure, there was no significant association between coffee intake and GERD.

Effect of the G-protein ß3 subunit 825T allele on the change of body adiposity in obese female.

No clinical studies on the lipolytic effect of guanine nucleotide-binding protein ß3 subunit gene (GNB3) 825T polymorphism have been performed. This study was a subinvestigation of a 12-week randomized controlled trial (NCT01184560) for the additive effect of orlistat on sibutramine treatment. The analysis involved 101 obese females aged 18-49 years, genotyped at the GNB3 825 locus. To exclude any influence from potential confounders, we used an analysis of covariance model. After the intervention, fat mass proportion in total weight loss was significantly lower in subjects with a T allele than in those without a T allele (p = 0.034). GNB3 825T allele was associated with blunted fat mass reduction in obese females.

Efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers: a meta-analysis.

BACKGROUND: The efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers has not yet been established. OBJECTIVE: To investigate the efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers. SEARCH STRATEGY: A search was made of PubMed, Embase and CENTRAL in June 2011. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs and retrospective or prospective controlled studies were included. DATA COLLECTION AND ANALYSIS: The main analyses were designed to examine the efficacy of pharmacotherapy for smoking cessation among pregnant smokers based on the longest follow-up data available and from data obtained at the latest available time-point in pregnancy in each study. MAIN RESULTS: Of 74 articles identified from the databases, seven studies (five RCTs, one quasi-RCT and one prospective study) involving a total of 1386 pregnant smokers, 732 in the intervention groups and 654 in the control groups, were included in the final analyses. In a fixed-effects meta-analysis of all seven studies based on the longest follow-up data available, pharmacotherapy had a significant effect on smoking cessation (relative risk [RR] 1.80; 95% confidence interval [CI] 1.32-2.44). Subgroup meta-analysis by type of study design also showed similar findings for RCTs (RR 1.48; 95% CI 1.04-2.09) and other types of studies (RR 3.25; 95% CI 1.65-6.39). The abstinence rate at late pregnancy in the intervention ranged from 7 to 22.6% (mean abstinence rate 13.0%; 95% CI 10.9-15.2%). A few minor adverse effects and serious adverse effects were reported in several studies. AUTHOR'S CONCLUSIONS: This study indicates that there may be clinical evidence to support the use of pharmacotherapy for smoking cessation among pregnant smokers. Further RCTs are needed.

Analysis of patterns of three-phase bone scintigraphy for patients with complex regional pain syndrome diagnosed using the proposed research criteria (the 'Budapest Criteria').

BACKGROUND: Three-phase bone scintigraphy (TPBS) is an established objective diagnostic method for complex regional pain syndrome (CRPS), but its validity remains controversial. The aims of this study were: (i) to re-evaluate the diagnostic performance of TPBS, and (ii) to suggest new TPBS criteria based on the proposed research criteria for CPRS in Budapest (the 2003 Budapest research criteria). METHODS: The medical records of 228 consecutive patients, evaluated using the Budapest research criteria, were retrospectively analysed. Of these, 116 patients were included in the present study, and 69 of 116 were diagnosed to have CRPS based on these criteria. The diagnostic performance of TPBS was assessed by determining its sensitivity, specificity, and positive and negative likelihood ratios, and new criteria for TPBS were identified by pattern analysis using the Budapest research criteria. RESULTS: The sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of TPBS for the diagnosis of CRPS according to the Budapest research criteria were 40.0, 76.5, 1.73, and 0.78, respectively. Furthermore, D-D-D, D-D-S, and D-D-I patterns [i.e. according to decreased (D), symmetrical (S), or increased (I) tracer uptake during Phases I, II, and III] of TPBS were found to be positively predictive for CRPS. CONCLUSIONS: The diagnostic value of a positive TPBS for CRPS is low from the view point of the Budapest research criteria. Our findings suggest that a diagnosis of CRPS using the Budapest research criteria should be considered when decreased patterns of TPBS are observed during Phases I and II.

Aspirin use and risk for lung cancer: a meta-analysis.

BACKGROUND: Aspirin has received increasing attention owing to its potential as a chemopreventive agent against lung cancer. Previous observational studies have reported inconsistent findings on this issue. We investigated the association between aspirin use and risk for lung cancer by conducting a meta-analysis. PATIENTS AND METHODS: Relevant studies were identified by searching Medline, EMBASE, and Cochrane Library to December 2009. We also reviewed relevant bibliographies from the retrieved articles. Two authors independently extracted data and assessed study quality. Disagreements were resolved by consensus. RESULTS: Fifteen studies (six case-control studies and nine prospective cohort studies) were included in the final meta-analysis. When all studies were pooled, the odds ratio (OR) of aspirin use for lung cancer risk was 0.86 [95% confidence interval (CI) 0.76-0.98]. In subgroup meta-analyses, there was no association between aspirin use and lung cancer risk among cohort studies (relative risk, 0.97; 95% CI 0.87-1.08), while there was a significant association among case-control studies (OR, 0.74; 95% CI 0.57-0.99). In a subgroup meta-analysis by quality of study methodology, a significant protective effect of aspirin use on lung cancer was observed only among eight low-quality studies (OR, 0.82; 95% CI 0.68-0.99), but not among seven high-quality studies (OR, 0.90; 95% CI 0.76-1.07). CONCLUSIONS: Overall, the findings of this meta-analysis support that there was no association between aspirin use and lung cancer risk. Our findings should be confirmed in future prospective cohort studies or randomized, controlled trials.

Microbial contamination of food products consumed by infants and babies in Korea.

AIMS: The objectives of this study were to investigate the microbiological safety of various foods intended for consumption by infants and babies. METHODS AND RESULTS: The incidence of Cronobacter spp. and Enterobacteriaceae from powdered infant formula (PIF, n = 75) and baby soy milk (n = 10) was examined. Additionally, aerobic plate count, coliforms and the prevalence of foodborne pathogens were investigated in 230 samples from a variety of infant and baby foods, including cereal-based follow-up formulas (FUF), liquid FUF and other infant foods. High APCs were observed in nutrient supplements and cereal-based FUF. Coliforms were found in 6 (2·6%) products, and Cronobacter spp. was isolated in 10 (4·4%) samples, including four PIF and six cereal-based FUF. Bacillus cereus was detected in 48 (20·9%) samples: cereal-based FUF items (23·0%), rice soups (20·6%), honey samples (40·0%), biscuits (40·0%) and liquid FUF (7·4%). CONCLUSIONS: New safety criteria, along with hygienic control measures and consumer education strategies, are essential to improve the microbiological safety of infant or baby foods. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides comprehensive information about the prevalence and level of contamination of infant and baby food products by Cronobacter spp. and other major foodborne pathogens.

Synthesis of poly(methyl urethane) acrylate oligomer using 2-isocyanatoethyl methacrylate for UV curable coating.

The poly(methyl urethane) acrylate oligomer was obtained by the reaction of methyl acrylate oligomer and 2-isocyanatoethyl methacrylate. Synthesis of poly(methyl urethane) acrylate oligomer was done with 2-mercaptoethanol (2-MEOH), methyl acrylate, 2,2'-azobisisobutyronitrile (AIBN, initiator) and dibutyltin dilaurate as a catalyst. Then 2-MEOH was used for functional chain transfer agent. The structure and property of the synthesized oligomers were characterized by FT-IR, FT-NMR, rheometer, and DSC. In this study, by synthetic method including the addition of 2-isocyanatoethyl methacrylate, thermal behavior of synthesized material was improved more than that reported in the previous study. Poly(methyl urethane) oligomer can be used for UV curable coatings, inks and adhesives. UV curable coating have high resistance against weather, ozone, aging, frictional wear, and heat. Besides they can absorb the shock and resist rust according to the thickness of film. It is used as an adhesive, paint, optical fiber coating agent, and waterproof agent because of these advantages at the present time.

Effect of heat treatment on Cronobacter spp. in reconstituted, dried infant formula: preparation guidelines for manufacturers.

AIM: To explore safe guidelines for manufacturers and consumers to prepare, handle and store dry infant formula (DIF) to protect infants against Cronobacter spp. METHODS AND RESULTS: Selected strains (2.45, FSM 293, ATCC-12868, FSM-271) screened from 68 strains of Cronobacter spp. were used to study growth and survival in commercial DIF. Prototype growth patterns in Enterobacteriaceae enrichment broth (EEB) containing a cocktail comprised of ATCC 12868, ATCC 29004, ATCC 29544 and ATCC 51329 showed a rapid increase in cell count (2.0 log(10) to 6.2 log(10) CFU ml(-1)). Infant formula provided a better protective environment for the cells of Cronobacter strains than did buffered peptone water. Experiments on survival in inoculated (10(4)-10(6) CFU ml(-1)) reconstituted infant formula (RIF), preparation temperature, the effect of preparation volume (one-serving or two-serving) and effect of storage at room temperature for up to 10 h provided information to develop consumer guidelines for DIF preparation and handling. CONCLUSIONS: Reconstituted DIF in water at >70 degrees C in larger volumes, minimizing storage time before feeding and storing unused reconstituted formulate at <4 degrees C, may reduce the risk of Cronobacter infection in infants. SIGNIFICANCE AND IMPACT OF THE STUDY: Meningitis, necrotizing enterocolitis and bacteremia in premature babies has been linked to contaminated milk powder and DIF; better handling practices may improve the safety of these foods for neonates.

A model of the effect of temperature on the growth of pathogenic and nonpathogenic Vibrio parahaemolyticus isolated from oysters in Korea.

Vibrio parahaemolyticus is recognized as the leading cause of human gastroenteritis associated with the consumption of seafood. The objective of this study was to model the growth kinetics of pathogenic and nonpathogenic V. parahaemolyticus in broth and oyster slurry. Primary growth models of V. parahaemolyticus in broth and oyster slurry fit well to a modified Gomperz equation (broth R(2)=0.99; oyster slurry R(2)=0.96). The lag time (LT), specific growth rate (SGR), and maximum population density (MPD) of each primary model were compared. The growth of nonpathogenic V. parahaemolyticus was found to be more rapid than that of pathogenic V. parahaemolyticus, regardless of the model medium. In addition, significant (P<0.05) differences in the growth kinetics between pathogenic and nonpathogenic V. parahaemolyticus in broth were observed at 10 degrees C. When compared to growth in broth, the growth of V. parahaemolyticus was delayed in oyster slurry, and growth was not observed at 10 or 15 degrees C. The Davey and square root models were identified as appropriate secondary models for predicting the LT and SGR, respectively. For the broth model, the average B(f) and A(f) values for LT were found to be 0.97 and 1.3, respectively, whereas the average B(f) and A(f) values for SGR were 1.05 and 1.11, respectively. The model generated in this study predicted an LT that was shorter and an SGR that was similar to those that were actually observed, which indicates that these models provide a reliable and safe prediction of V. parahaemolyticus growth.

The Drosophila homolog of the human tumor suppressor gene BHD interacts with the JAK-STAT and Dpp signaling pathways in regulating male germline stem cell maintenance.

Birt-Hogg-Dubé syndrome (BHD) is a rare, inherited genodermatosis characterized by hair follicle hamartomas, kidney tumors and spontaneous pneumothorax. The BHD locus was mapped to chromosome 17p11.2 by linkage analysis, and germline mutations in a novel gene (BHD) were identified in a panel of BHD families. Using RNA interference to decrease expression of the Drosophila BHD homolog (DBHD), we have demonstrated that DBHD is required for male germline stem cell (GSC) maintenance in the fly testis. Reduction of DBHD gene activity suppresses the GSC overproliferation phenotype associated with overexpression of either unpaired (upd) or decapentaplegic (dpp). Further genetic interaction experiments suggest that DBHD regulates GSC maintenance downstream or in parallel of the JAK/STAT and Dpp signal-transduction pathways. These findings suggest that the BHD protein may regulate tumorigenesis through modulating stem cells in human.

Membrane cytoskeleton: PIP(2) pulls the strings.

A recent application of optical tweezers has shown that plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)) levels control adhesion of the membrane bilayer to the underlying cytoskeleton, by regulated direct binding of PIP(2) to cytoskeletal proteins and/or indirect effects on cytoskeleton structure.

Reduction of Oxygen-Induced CSF Hyperintensity on FLAIR MR Images in Sedated Children: Usefulness of Magnetization-Prepared FLAIR Imaging.

BACKGROUND AND PURPOSE: Oxygen-induced CSF hyperintensity on FLAIR MR imaging is often observed in sedated children. This phenomenon can mimic leptomeningeal pathology and lead to a misdiagnosis. The purpose of this study was to investigate whether magnetization-prepared FLAIR MR imaging can reduce oxygen-induced CSF hyperintensity and improve image quality compared with conventional (non-magnetization-prepared) FLAIR MR imaging. MATERIALS AND METHODS: Bloch simulation for magnetization-prepared and non-magnetization-prepared FLAIR sequences was performed for tissue contrast. We retrospectively reviewed 85 children with epilepsy who underwent MR imaging under general anesthesia with supplemental oxygen (41 with non-magnetization-prepared FLAIR and 44 with magnetization-prepared FLAIR). CSF hyperintensity was scored from 0 to 3 points according to the degree of CSF signal intensity and was compared between the 2 sequences. The contrast-to-noise ratios among GM, WM, and CSF were evaluated to assess general image quality from both sequences. To assess the diagnostic accuracy for hemorrhage, we reviewed an additional 25 patients with hemorrhage. RESULTS: Bloch simulation demonstrated that CSF hyperintensity can be reduced on magnetization-prepared FLAIR compared with non-magnetization-prepared FLAIR. CSF hyperintensity scores were significantly lower in magnetization-prepared FLAIR than in non-magnetization-prepared FLAIR (P < .01). The contrast-to-noise ratios for GM-WM, GM-CSF, and WM-CSF were significantly higher in magnetization-prepared FLAIR than in non-magnetization-prepared FLAIR (P < .05). Hemorrhage was clearly demarcated from CSF hyperintensity in the magnetization-prepared group (100%, 12/12) and non-magnetization-prepared group (38%, 5/13). CONCLUSIONS: Magnetization-prepared 3D-FLAIR MR imaging can significantly reduce oxygen-induced CSF artifacts and increase the tissue contrast-to-noise ratio beyond the levels achieved with conventional non-magnetization-prepared 3D-FLAIR MR imaging.

Effect of sodium intake on renin level: Analysis of general population and meta-analysis of randomized controlled trials.

BACKGROUND: We evaluated the association between sodium intake and plasma renin levels in the cross sectional study and meta-analysis of randomized controlled trials, whether there is a persistent elevation of plasma renin by longer-term sodium intake restriction. METHODS: Plasma renin activity (PRA) and 24-h urine sodium (24HUNa) excretion were measured from individuals randomly selected from a community. Simple and multiple linear regression analyses adjusted for age, 24-h systolic blood pressure, 24-h average heart rate, fasting blood glucose and gender were performed. For meta-analysis, 74 studies published from 1975 to mid-2014 were identified in a systematic literature search using EMBASE, CINAHL, and MEDLINE. Random effects meta-analyses and a meta-regression analysis were performed. RESULTS: Among the 496 participants recruited, 210 normotensive and 87 untreated hypertensive subjects were included in the analysis. There was no significant association between PRA and 24HUNa in the total population, or hypertensive and normotensive individuals. In the meta-analysis, the standard mean difference (SMD) of renin level by sodium intake reduction was 1.26 (95% CI: 1.08 to 1.44, Z=12.80, P<0.001, I(2)=87%). In the meta-regression analysis, an increase in a day of intervention was associated with a fall in SMD by -0.04 (95% CI: -0.05 to -0.02, Z=-5.27, P<0.001, I(2)=86%), indicating that longer duration of reduced sodium intake would lead to lesser SMD of renin level. CONCLUSIONS: The present population based cross-sectional study and meta-analysis suggests that prolonged reduction in sodium intake is very unlikely associated with elevation of plasma renin levels.

Construction of a human full-length cDNA bank.

We aimed to construct a full-length cDNA bank from an entire set of human genes and to analyze the function of a protein encoded by each cDNA. To achieve this purpose, a multifunctional phagemid shuttle vector, pKA1, was constructed for preparing a high-quality cDNA library composed of full-length cDNA clones which can be sequenced and expressed in vitro and in mammalian cells without subcloning the cDNA fragment into other vectors. Using this as a vector primer, we have prepared a prototype of the bank composed of full-length cDNAs encoding 236 human proteins whose amino acid sequences are identical or similar to known proteins. Most cDNAs contain a putative cap site sequence, some of which show a pyrimidine-rich conserved sequence exhibiting polymorphism. It was confirmed that the vector permits efficient in vitro translation, expression in mammalian cells and the preparation of nested deletion mutants.

Detection of genetic alterations in the human gastric cancer cell lines by two-dimensional analysis of genomic DNA.

We examined genomic DNA from each of three human-derived gastric cancer cell lines, using the technique of restriction landmark genomic scanning (RLGS) which allows monitoring of approximately 2, 000 NotI landmarks. The resulting DNA spots from cancer cell DNA were compared with those in normal mucosa or gastric primary tumor. In all, 9 intense spots were detected from two of the three cancer cell lines. Two highly intensified spots were common in the two cancer cell lines and proven to be originated from DNA region containing the human c-myc proto-oncogene on chromosome 8. The degree of amplification of c-myc DNA was similar to each other and was estimated to be 60-fold as compared to those from normal mucosa DNA. On the basis of chromosome-assigned RLGS (CA-RLGS), other spots were assigned to each chromosome, such as one on chromosome 8, two each from chromosome 20, and three on one of chromosome 9-12. The remaining spot seems to be due to demethylation of a repetitive element. Twenty-four spot that were lost due to either homozygous deletion or methylation on corresponding NotI cleavage sites were commonly observed in all cancer cells. These spots were also assigned to each chromosome: one each from chromosome 2, 6, 7, 13, 14, 16, and 20, two each from chromosome 3 and 5, and nine from chromosome 9-12 by CA-RLGS. Many of the multi-copy spots corresponding to ribosomal RNA genes were greatly decreased due mainly to methylation on CpG islands along with minor rDNA variants, indicating that only minor rRNA genes may be silenced in these cancer cells. These results show that the present alterations detected by RLGS might be useful for identification of candidate genes inactivated or expressed unexpectedly in tumor development and tumor progression in the stomach.

An N-methyl-D-aspartate antagonist, MK-801, preferentially reduces electroconvulsive shock-induced phosphorylation of p38 mitogen-activated protein kinase in the rat hippocampus.

Electroconvulsive shock (ECS) activates the mitogen-activated protein kinase (MAPK) family in the rat hippocampus, but the signaling pathways for this activation are not well understood. We investigated whether N-methyl-D-aspartate (NMDA) receptor mediated signaling is involved in the phosphorylation-activation of the MAPK family. The NMDA receptor antagonist, MK-801, dose-dependently reduced ECS-induced phosphorylation of p38 and its upstream kinase MKK6 up to 1 mg/kg. MK-801 also reduced the phosphorylation of ERK1/2 and MEK1, but only at high dosage, 2 mg/kg. Moreover, the reduction in the phosphorylation of p38 and MKK6 was greater than that of ERK1/2 and MEK1. Our results suggest that ECS activates p38 and ERK1/2 partly through an NMDA receptor-mediated signaling system in the rat hippocampus and that NMDA receptor mediated signaling is more responsible for the activation of the MKK6-p38 pathway than the MEK1-ERK pathway.