The mixture effect of propyl paraben and bisphenol A on the uterotrophic response in the ovariectomized rats after oral administration.

Recent studies reported bisphenol A (BPA) and propyl paraben (PrP) are found in human urine, blood, and breast milk samples as well as in food, packaging, socks, and clothes. This means that the two chemicals co-exist in consumer products, and humans are exposed simultaneously to the mixture chemicals. However, the studies on the mixture effects of the two chemicals on human health are not enough. This study was designed to elucidate the effects of orally administered PrP, BPA, and their mixture effects on the uterotrophic response using ovariectomized rats. In addition, the correlation between the uterotrophic response and tissue concentrations of the two chemicals was studied to investigate whether one chemical has any effect on the absorption, distribution, or excretion of the other chemical. Histopathology, hematology, and plasma biochemistry analysis were also performed to evaluate the chemicals' toxicological effects in the treated rats. Although a significant increase in uterus weight (absolute and relative) was observed in the positive chemical (17ß-estradiol) treated group, there were no statistical differences in the uterus weight between the vehicle control and the chemical-treated groups. However, a slight increase in the endometrial glands and a change in the cuboidal to columnar epithelium of the endometrial epithelium were observed in the mixture-treated group. There was no significant toxicity in all treated groups by the hematology and plasma biochemistry analysis results. The results of tissue distribution showed that BPA was mostly detected in the liver while PrP was not detected in most tissues, and the BPA level was higher when the rats were treated with PrP than without PrP, suggesting that PrP may increase the absorption of BPA after oral administration.

Probabilistic risk assessment of preservatives in dishwashing detergents and wet wipes for Korean consumers.

Preservatives are essential additives in dishwashing detergents and wet wipes. Ensuring the safe use of preservatives in products is important for public health, as some preservatives are associated with health issues. In this study, the content of 12 preservatives in 105 dishwashing detergents and 105 wet wipes was determined, where these compounds are commonly found, among consumer products. A realistic exposure estimation was considered by using Korean consumer-specific exposure parameters for adults and babies. A probabilistic risk assessment was conducted by applying the Monte Carlo simulation method. Benzoic acid (41%) and cetylpyridinium chloride (30%) were the most commonly used preservatives in dishwashing detergents and wet wipes, respectively, although their content in different products (benzoic acid: 0.28-19.4 mg/g in dishwashing detergents; cetylpyridinium chloride: 0.003-0.64 mg/g in wet wipes) varied widely. The calculated median and upper-limit margin of safety (MOS) values related to systemic health effects and skin sensitization from exposure to preservatives largely exceeded the target MOS, which confirmed the safety of the products. Exposure to preservatives from wet wipes was several times higher in babies than in adults. Sensitivity analysis revealed that the amount of the product used, frequency of use, and weight fraction of the preservative were the major contributors to the exposure to preservatives from dishwashing detergents and wet wipes.

Development of a Method for Simultaneous Analysis of Allergenic Flavoring Agents in Cigarettes and Quantitative Risk Assessment for Consumer Safety.

Flavoring agents are added to cigarettes to improve taste. There are mostly permitted food additives, but some of them are restricted for use in food, cosmetics, and toys, since they can cause allergic reactions. Previous studies have investigated the levels of flavoring agents in tobacco but none has focused on their content in filter tips and capsules. Moreover, no studies have assessed the risk of adding allergenic flavoring agents in cigarettes. Here, we developed and validated a simultaneous analysis method for 25 allergenic flavoring agents and menthol with gas chromatography-tandem mass spectrometry to determine levels of flavoring agents in the tobacco, filter tips, and capsules of 54 commercial cigarettes in Korea. All cigarettes contained at least one allergenic flavoring agent regardless of the inclusion of flavoring capsules. Importantly, the filter tips and the capsules contained higher levels of flavoring agents than tobacco, highlighting the importance of the quantification of flavoring agents in these parts of cigarettes. Nevertheless, the risk assessment based on their levels in cigarettes suggested that their exposure was maintained at a safe level. However, the risk assessed from maximum menthol, linalool, and cinnamaldehyde exceeded one-tenth of derived no-effect levels, suggesting the need for further studies on their risk to human health.

Local Toxicity of Biocides after Direct and Aerosol Exposure on the Human Skin Epidermis and Airway Tissue Models.

Biocides are commonly used as spray- or trigger-type formulations, thus dermal and respiratory exposure to biocide aerosol is unavoidable. However, little is known about the impact of aerosolization on the local toxicity of biocides on the skin or the airway. We compared the local toxicity of biocides after direct or aerosol exposure on reconstructed human skin epidermis and upper airway models. Three biocides, 1,2-benzisothiazol-3(2H)-one (BIT), 2-phenoxyethanol (PE), and 2-phenylphenol (OPP), most widely used in the market were selected. When the biocide was treated in aerosols, toxicity to the skin epidermis and upper airway tissue became significantly attenuated compared with the direct application as determined by the higher tissue viabilities. This was further confirmed in histological examination, wherein the tissue damages were less pronounced. LC-MS/MS and GC/MS analysis revealed that concentrations of biocides decreased during aerosolization. Importantly, the toxicity of biocides treated in 3 µm (median mass aerodynamic diameter (MMAD)) aerosols was stronger than that of 5 µm aerosol, suggesting that the aerosol particle size may affect biocide toxicity. Collectively, we demonstrated that aerosolization could affect the local toxicity of biocides on the skin epidermis and the upper airway.

Development of a 68 Ga-labelled PET tracer for carbonic anhydrase IX-overexpressed tumors using the artificial sweetener saccharin.

In this study, we developed a saccharin (SAC)-based radiopharmaceutical (68 Ga-NOTA-SAC) and evaluated the possibility of its application as a PET tracer in the diagnosis of carbonic anhydrase IX (CA IX)-overexpressed tumors. We did a water-soluble tetrazolium assay and flow cytometry analysis to identify the cell viability decrease by SAC. The radiochemical purity and stability of 68 Ga- NOTA-SAC in human and mouse serum was greater than 98%. The small animal PET image-based radioactivity distribution of all organs decreased over time.68 Ga-NOTA-SAC presented the highest tumor-to-muscle ratio at 90 min post injection (p.i). The growth rates of tumor-to-muscle ratios of 68 Ga-NOTA-SAC were 88% at 60 min and 220% at 90 min, compared to 30 min p.i. The potential of 68 Ga-NOTA-SAC as a PET tracer is expected to contribute to the diagnostic research on CA IX-overexpressed tumors with the advantages of a relatively simple synthesis method.

Determination of toxic metal release from metallic kitchen utensils and their health risks.

The effect of simulants, repeated use, washing, and oiling on the release of toxic metals from metallic kitchen utensils was investigated. The release of As, Cd, Cr, Ni, and Pb from kitchen utensils composed of stainless steel, aluminum, copper alloy, and cast iron into food simulants was quantified using inductively coupled plasma-mass spectrometry. The results show that this release of toxic metals was highly dependent on pH. Generally, the release of toxic metals tended to decrease with repeated use, and the release of Cr and Ni from stainless steel samples was significantly higher in the first test, compared to the third test. The washing conditions affected the release of As and Cr, whose release levels were higher when washing only with water and with a steel wool pad, respectively. Furthermore, oiling cast iron cookware reduced the release of As, Cd, Cr, and Ni into acidic simulants by 66%, 83%, 71%, and 15%, respectively. The margin of exposure (MOE) was calculated for each toxic metal; the calculated MOE values indicated that it is improbable that the current level of exposure from metallic kitchen utensils would pose a health risk in Korea.

Survey of characteristics of exposure to mainstream cigarette smoke using discarded cigarette butts from Korean smokers.

Evaluating the characteristics of exposure to mainstream cigarette smoke is an essential field in tobacco research because of the large risk burden among smokers. Detailed evaluation of the complex factors pertaining to the exposure of smokers to mainstream cigarette smoke was attempted by analysis of discarded cigarette butts. A total of 5475 samples of discarded cigarette butts was collected to investigate the exposure characteristics in relation to Korean smokers. The basic physico-chemical characteristics of cigarettes, including the filter length, filter type, menthol addition, and nicotine and tar content, were determined and the manufacturer and cigarette size were identified. The tobacco-burned percentage (TBP)) and tar staining were used as physical markers, and actual human exposure to cigarette smoke was determined using the part filter method. Multiple linear regression analyses and generalized ordinal logistic regression analysis were conducted to identify the relationship between the socio-demographic factors and the physico-chemical characteristics of the cigarettes themselves and the exposure characteristics. Significant associations were observed between the TBP and age group, occupational group, manufacturer, tar staining, ISO tar content, and filter length. Increased odds of smoking with a heavier tar stain among Korean smokers were associated with blue collar workers vs. other workers, manufacturer B vs. other manufacturers, recess filter vs. other filter types, ISO tar content, and TBP. Finally, significant associations between the log-transformed human-smoked tar and nicotine yields and occupational group, the TBP, tar staining, and physico-chemical properties of cigarettes were found and were used to propose models for predicting the actual exposure to tar and nicotine. The proposed models account for 60-61% and 47-49% of the variance of human exposure to tar and nicotine, respectively. This analysis of discarded cigarette butts revealed that various factors, including socio-demographic factors such as age group and occupational group, as well as the physico-chemical properties of cigarette products such as the filter type and length, cigarette size, ISO tar and nicotine content, and mentholation, affect the characteristics of exposure of Korean smokers to mainstream cigarette smoke.

Potential for short-term migration of mineral oil hydrocarbons from coated and uncoated food contact paper and board into a fatty food simulant.

Mineral oil hydrocarbons (MOH) are widely used in the food industry for applications such as printing inks, additives, adhesives, and processing aids for food additives. Recently, the migration of MOH from food contact paper and board into foods has raised public health concerns. In this study, a total of 110 food contact paper and board samples, including baking and cooking paper (23), baking cups (28), food packaging bags (22), lunch boxes (8), party plates (26), and straws (3) were evaluated to quantify the content and short-term migration levels of MOH. The MOH were separated into mineral oil saturated hydrocarbons (MOSH)/polyolefin oligomeric saturated hydrocarbons (POSH) and mineral oil aromatic hydrocarbons (MOAH) via a validated on-line liquid chromatography-gas chromatography-flame ionisation detection (LC-GC-FID) technique. The coating materials of the sample products comprised polyethylene, polypropylene, polyethylene terephthalate, and silicone. The effects of the coating materials on the content and migration of MOH/POSH were evaluated. Quantitative analysis of the MOH in the samples showed that the MOSH/POSH and MOAH content varied widely, ranging from 16 to 5626 mg kg-1 for MOH, regardless of the coating materials. Short-term migration of MOSH/POSH was observed only in samples with polyolefinic coatings, such as polyethylene and polypropylene, in experiments conducted at 25 °C for 10 min, although the extent of MOAH migration for all samples was at the trace level. The migration of MOSH/POSH was detected within the range of 0.93 to 62.3 µg L-1 in 22 samples, and the migration of MOAH was detected within the range of 0.80 to 2.6 µg L-1 in only 4 samples. These results demonstrate that although the short-term migration potential of MOH is generally negligible, the migration of MOSH/POSH into wet fatty foods can be accelerated by polyolefinic coatings, even within a very short time.

An optimised method for the rapid analysis of condensed phosphates in fishery and processed marine food products using ion chromatography and microwave sample processing.

Condensed phosphates are deliberately added to the fishery and processed marine food products on purpose to increase the weight of products. However, excessive intake overwhelming bodily homoeostasis can result in phosphate toxicity such as mineral and bone disorders, associated with chronic kidney diseases, and cardiovascular events. Rapid analysis for condensed phosphates is required to detect the illegal adulteration of processed marine products. We optimised an analytical method using ion chromatography for the rapid and selective detection of condensed phosphates in various kinds of fishery and processed marine products. We compared the performance of three columns (IonPac AS11, AS11-HC, and AS16) for the detection of condensed phosphates with respect to time of analysis and sensitivity. The IonPac AS11 column exhibited the shortest retention time for the major condensed phosphates (pyro-, tri-, and trimetaphosphate), the highest sensitivity for trimetaphosphate, and good repeatability and precision. Microwave and boiling processing were examined as methods to prevent hydrolysis of condensed phosphates into orthophosphate, which is critical in distinguishing intentionally added condensed phosphates from naturally occurring orthophosphate. Microwave treatment was determined to be the more effective method to suppress hydrolysis of condensed phosphates to orthophosphate. Furthermore, microwave processing could be used for thawing the frozen samples, saving extra effort and time. We confirmed that the method exhibits good recovery (80% or more) and precision (%RSD < 10%) for samples with various matrices. With the method, 14 kinds of fishery and processed marine food products were successfully analysed for condensed phosphates. Especially, we identified that phosphate levels in the processed shrimp and dried shredded squid samples exceeded the maximum allowable levels specified in the CODEX standard. We believe that our method would be useful for the rapid analysis of condensed phosphates in various types of fishery and processed marine food products.

Risk assessment of toxicants on WHO TobReg priority list in mainstream cigarette smoke using human-smoked yields of Korean smokers.

Recently, the World Health Organization Study Group on Tobacco Product Regulation (WHO TobReg) announced a priority list of 38 toxicants among the more than 7000 chemicals found in cigarette smoke, building upon previous lists of toxicants in cigarette smoke. Here, we conducted a comprehensive study on the quantitative exposure and risk characterization of these priority toxicants in mainstream cigarette smoke listed by the WHO TobReg. The human-smoked toxicant yields estimated from spent cigarette butts of a total of 361 smokers using the part-filter method (PFM) were applied to current exposure and risk estimation for the first time. The PFM can estimate human-smoked yields of toxicants using smokers' maximum mouth-level exposure. The human-smoked yield of each toxicant was converted to systemic uptake by considering bioavailability. Risk indicators-including the incremental lifetime cancer risk (ILCR), cumulative ILCR, hazard quotient (HQ), hazard indices (HIs), and margin of exposure (MOE)-were estimated from the systemic uptake of toxicants combined with Korean exposure factors by gender and age group as well as for total smokers. It was demonstrated that cigarette smoking results in significant cancer and non-cancer health risks. A sensitivity analysis showed that the human-smoked toxicant yield is one of the most important contributors to risk level variations. Our risk estimation suggested that previous risk assessments might have ignored or underestimated the uncertainty of risk assessment. In conclusion, we assessed the risk level of the 38 toxicants on the priority list developed by the WHO TobReg and provided a Korean-specific priority list for the regulations on the emission of cigarette smoke.

Exposure to cigarette smoke via respiratory system may induce abnormal alterations of reproductive organs in female diabetic rats.

Cigarette smoke (CS) has harmful effects on human fertility, reproduction, and development as well as on patients suffering from metabolic diseases such as diabetes than on healthy individuals. This study was conducted to investigate the relationship between CS exposure and histological alterations of reproductive organs in female diabetic rats. We evaluated the histology of uteruses and ovaries obtained from female rats exposed to smoke from standard cigarettes for 4 weeks (28 hours a week). After CS exposure, tissue slides were made from uterine and ovarian samples and examined after hematoxylin and eosin staining. Immunohistochemistry was used for detection of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), and estrogen receptor (ER)α in the uterus and ovary. MMP9 is an inflammatory biomarker that increases during progression to endometriosis. As a chemokine receptor, CXCR4 is involved in development of the inner wall of the uterus and cell adhesion. In the uterus, the occurrence of MMP9, CXCR4, and ERα and the number of endometrial glands were increased by CS exposure, while in the ovary, occurrence of MMP9, CXCR4, ERα, proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Collectively, this study indicates that CS induced abnormal development of the uterus and ovary under induced diabetes, leading to adverse effects on normal function of reproductive organs in female rats. HIGHLIGHTS: Cigarette smoke (CS) exposure adversely affected reproductive organs of diabetic female rats. In the uterus, expression of matrix metallopeptidase 9 (MMP9), C-X-C chemokine receptor type 4 (CXCR4), estrogen receptor (ER)α, and the number of endometrial glands were increased by CS exposure, In the ovary, the expression of MMP9, CXCR4, ERα, and proliferating cell nuclear antigen and the number of corpus lutea or cyst follicles were increased by CS exposure. Exposure to CS via the respiratory system exerted a harmful impact on the uterus and ovary in female rats with diabetes.

The cigarette smoke components induced the cell proliferation and epithelial to mesenchymal transition via production of reactive oxygen species in endometrial adenocarcinoma cells.

Cigarette smoke (CS) causes about 480,000 deaths each year worldwide and is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. In the present study, the effects of acrylonitrile (AN), benzo(a)pyrene (B(a)P), formaldehyde (FOR), isoprene (ISO), nicotine-derived nitrosamine ketone (NNK), which are the main components of CS, on the proliferation, invasion, and the epithelial-mesenchymal transition (EMT) process of human Ishikawa endometrial adenocarcinoma cells were investigated. Treating Ishikawa cells with CS components resulted in increased cell growth and altered expression of cell cycle-related genes: the protein expression of cyclin D & E increased, while the levels of p21 & p27 were reduced following treatment of these five CS components. In addition, CS components increased the invasion capacity of Ishikawa cells. The expression of the epithelial markers, E-cadherin and occludin, were significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by CS components. In dichloro-dihydro-fluorescein diacetate (H2DCF-DA) assay, ROS production increased by treatment of CS components. The CS components activated the ROS-p38 MAPK-EMT pathway by increasing the level of phosphorylated p38 MAPK and p44/42 (ERK1/2), and by up-regulating Snail and Slug, the transcription factors for EMT. Taken together, these results indicate that CS components can promote progression of endometrial adenocarcinoma via increasing cell proliferation and the ROS-mediated EMT process.

Mixture risk assessment of selected mainstream cigarette smoke constituents generated from low-yield cigarettes in South Korean smokers.

A total of 38 hazardous constituents in mainstream cigarette smoke of low-yield cigarettes sold in Korea were selected and analyzed using established methods. Risk calculations were performed using risk algorithms employed in previous studies and Korean population-based exposure parameters. The median cumulative incremental lifetime cancer risk of male smokers could vary from 828 × 10-6 to 2510 × 10-6, and that of female smokers could range from 440 × 10-6 to 1300 × 10-6, depending on the smoking regimens. The median hazard index as the sum of hazard quotients of male smokers varied from 367 to 1,225, and that of female smokers varied from 289 to 970, depending on the smoking regimens. The sensitivity analysis for this risk assessment indicated that the constituent yields in mainstream cigarette smoke, average number of cigarettes smoked per day or year, and mouth-spill rate are the main risk factors. Statistical positive correlations between the average daily dose calculated by the exposure algorithm used in this study for individual smokers and biomarkers verified the reliability of this assessment. It could be concluded that inhalation of the constituents present in the mainstream of low-yield cigarettes has significant cancer and non-cancer health risks, although its effect on risk reduction is still unknown under the fixed machine-smoking conditions.

Quantitative analysis of menthol and identification of other flavoring ingredients in capsule cigarettes marketed in Korea.

Currently, capsule cigarettes have been introduced by tobacco industries and their sales have increased exponentially. However, the capsule flavoring ingredients and their safety are still unknown. Although the contents of menthol and other ingredients directly added to cigarettes have been determined extensively, no analogous study exists for menthol-containing cigarette capsules. Basic physical properties of capsules in all 31 different capsule cigarettes commercially available in Korea were investigated, and their menthol contents were determined in this study. Other ingredients in these capsules were also qualitatively analyzed; methyl octanoate, menthone and isopulegol as well as menthol were detected in all the capsules. There is considerable variability in basic physical properties and menthol contents of cigarette capsules depending on their brand styles. The menthol contents of capsules and whole cigarettes are similar or higher than those previously reported for conventional menthol cigarettes. This is the first report on the physical properties of capsules and the fact that a wide range of menthol contents in capsule cigarettes, regardless of flavor types, allows smokers to select menthol content to their liking.

Investigation of dermal toxicity of ionic liquids in monolayer-cultured skin cells and 3D reconstructed human skin models.

Ionic liquids have gained increasing attention in the chemical industry as potential green substitutes for traditional solvents. However, little is known about toxicity of ionic liquids on the skin, a major exposure portal to toxic substances. Here, we evaluated dermal toxicity of ionic liquids using human keratinocyte and fibroblast cell line, 3D reconstructed human epidermis, and full-thickness model to investigate underlying mechanisms. Cytotoxicity of ionic liquids was evaluated for representative anions, [TFSI], [PF6], [BF4], and [DCA], as well as for cations, [EMIM], [BMPY], [TBA] and [Zn], in human keratinocyte cell line, HaCaT, and human dermal fibroblasts. In our results, significant cytotoxicity was induced by ionic liquids with [TFSI] in both cell lines. Notably, cytotoxicity of [TFSI] containing ionic liquids was comparable to xylene, a toxic conventional organic solvent. Fluorescent and flow cytometric analysis revealed that [TFSI]-exposed cells underwent necrotic cell death. Reactive oxygen species (ROS) was increased while the amount of glutathione was decreased by [TFSI] in dose-dependent manner, which was reversed by antioxidant, N-acetylcysteine. In 3D reconstructed human epidermis and full-thickness model, a single application of [TFSI] induced toxicity although it was minimal and largely limited to epidermal layer. Collectively, these results demonstrated potential dermal toxicity of ionic liquids.

Three components of cigarette smoke altered the growth and apoptosis of metastatic colon cancer cells via inducing the synthesis of reactive oxygen species and endoplasmic reticulum stress.

Cigarette smoke (CS) is a well-known risk factor for carcinogenesis and has been found to be related to the occurrence and development of colon cancer. In this study, the effect of formaldehyde (FA), benzene (Bz), and isoprene (IP), which are included in main components of CS, on cell viability and apoptosis of SW620 colorectal cancer cells was examined to identify the connection between CS components and colon cancer. In cell viability assay, FA, Bz, and IP decreased cell viability of SW620 cells in a dose dependent manner. In Western blot assay, the protein expression of cell cycle related genes, cyclin D1 & E1, was decreased by FA, Bz, and IP, which corresponded to their inhibitory effect on cell viability. In addition, FA, Bz, and IP increased the protein expression of pro-apoptotic genes, C/EBP homologous protein (CHOP) and Bax, and reduced the protein expression of anti-apoptotic gene, Bcl-2. In reactive oxygen species (ROS) assay using dichlorofluorescin diacetate (DCFH-DA), FA, Bz, and IP increased the ROS production in SW620 cells. In the measurement of apoptotic cells, the numbers of apoptotic cells were increased by the treatment of FA, Bz, and IP. As CHOP is an endoplasmic reticulum (ER)-stress related apoptosis marker of which production is induced by ROS, it was considered that these CS components induce apoptosis of SW620 cells by increasing ROS synthesis and ER-stress. Taken together, these results showed that CS components, i.e., FA, Bz, and IP, inhibited the cell viability of SW620 cells by down-regulating the protein expression of cyclin D1 & E1 and induced apoptosis of SW620 cells by increasing ROS production and simultaneously activating ER-stress.

Rhododenol and raspberry ketone impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45.

Rhododenol or rhododendrol (RD, 4-(4-hydroxyphenyl)-2-butanol) occurs naturally in many plants along with raspberry ketone (RK, 4-(4-hydroxyphenyl)-2-butanone), a ketone derivative, which include Nikko maple tree (Acer nikoense) and white birch (Betula platyphylla). De-pigmenting activity of RD was discovered and it was used as a brightening ingredient for the skin whitening cosmetics. Recently, cosmetics containing RD were withdrawn from the market because a number of consumers developed leukoderma, inflammation and erythema on their face, neck and hands. Here, we explored the mechanism underlying the toxicity of RD and RK against melanocytes using B16F10 murine melanoma cells and human primary epidermal melanocytes. Treatment with RD or RK resulted in the decreased cell viability in a dose-dependent manner which appeared from cell growth arrest. Consistently, ROS generation was significantly increased by RD or RK as determined by DCF-enhanced fluorescence. An antioxidant enzyme, glutathione peroxidase was depleted as well. In line with ROS generation, oxidative damages and the arrest of normal cell proliferation, GADD genes (Growth Arrest and DNA Damage) that include GADD45 and GADD153, were significantly up-regulated. Prevention of ROS generation with an anti-oxidant, N-acetylcysteine (NAC) significantly rescued RD and RK-suppressed melanocyte proliferation. Consistently, up-regulation of GADD45 and GADD153 was significantly attenuated by NAC, suggesting that increased ROS and the resultant growth arrest of melanocytes may contribute to RD and RK-induced leukoderma.

Novel anti-melanogenic hexapeptoids, PAL-10 and PAL-12.

Diverse compound sources are being explored for de-pigmentation activities to develop novel therapeutic agents or functional cosmetic ingredients for hyper-pigmentation disorders. Peptoids are a class of peptidomimetics whose side chains are appended to the nitrogen atom of the peptide backbone, instead of α-carbon. Peptoids are more durable against proteolysis and are being actively investigated in drug discovery, but rarely studied as cosmetic ingredients. Here, we demonstrated that new hexa-peptoids, PAL-10 and PAL-12, can inhibit melanogenesis in B16F10 melanoma cells, a 3D pigmented human skin model (Neoderm(®)-ME, Tegoscience Co) and zebrafish. Anti-melanogenic effects of PAL-10 or PAL-12 as compared with arbutin, a positive control in B16F10 cells, Neoderm(®)-ME and zebrafish were statistically significant and concentration-dependent anti-melanogenic effects were manifested as determined by image, histology, and melanin contents. Anti-melanogenic effects of PAL-10 appeared to be from enzymatic inhibition of tyrosinase while mRNA expression of melanogenic enzymes was not affected. In conclusion, we demonstrated that PAL-10 and PAL-12 can be used as a new cosmetic ingredient with strong brightening efficacies.

Diagnostic recognition of Escherichia coli septicemia in in vivo vascular blood.

A method of detecting Escherichia coli (EC) in in vivo blood with septicemia was sought using a handmade macro three-electrode (ME) system. Towards this end, an analytical ME probe was prepared using mercury immobilized on a carbon nanotube working electrode, and two graphite pencils were used as counter and reference electrodes instead of the expensive Ag/AgCl standard and Pt counter electrode. Under the optimum conditions, the cyclic potential was obtained at a 0.05 V anodic, then the square-wave stripping working range was obtained at 0.5-3.5 ml (3x10(2)~4x10(2)CFU/1ml) EC. Also under the optimum conditions, the statistic stability was examined in 1 ml EC 15(th) repeat anodic, with a relative standard deviation of RSD=0.98x10(-2). The developed method was applied to non treated blood, using only one drop. The patient blood with septicemia had a fast accumulation time (30 sec). A diagnostic detection limit of 0.06 ml EC was obtained. The recognition methods can be applied to in vivo vascular blood and real organic fluids, and can be used for poisoning control.