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Sample records for repeated dermal toxicity

  1. Zinc oxide nanoparticles: a 90-day repeated-dose dermal toxicity study in rats

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    Ryu HJ

    2014-12-01

    Full Text Available Hwa Jung Ryu,1,* Mu Yeb Seo,2,* Sung Kyu Jung,1 Eun Ho Maeng,2 Seung-Young Lee,2 Dong-Hyouk Jang,2 Taek-Jin Lee,2 Ki-Yeon Jo,2 Yu-Ri Kim,3 Kyu-Bong Cho,4 Meyoung-Kon Kim,3 Beom Jun Lee,5 Sang Wook Son1 1Department of Dermatology, Korea University College of Medicine, Seoul, 2Korea Testing and Research Institute, Gyunggido, 3Department of Biochemistry and Molecular Biology, Korea University College of Medicine, Seoul, 4Department of Clinical Laboratory Science, Shinheung College, Uijeongbu, 5College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea *These authors contributed equally to this work and both should be considered first authors Abstract: Zinc oxide (ZnO works as a long-lasting, broad-spectrum physical sunblock, and can prevent skin cancer, sunburn, and photoaging. Nanosized ZnO particles are used often in sunscreens due to consumer preference over larger sizes, which appear opaque when dermally applied. Although the US Food and Drug Administration approved the use of nanoparticles (NPs in sunscreens in 1999, there are ongoing safety concerns. The aim of this study was to evaluate the subchronic toxicity of ZnO NPs after dermal application according to the Organization for Economic Cooperation and Development Test Guidelines 411 using Good Laboratory Practice. Sprague Dawley rats were randomly divided into eight (one control, one vehicle control, three experimental, and three recovery groups. Different concentrations of ZnO NPs were dermally applied to the rats in the experimental groups for 90 days. Clinical observations as well as weight and food consumption were measured and recorded daily. Hematology and biochemistry parameters were determined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. Analyses of tissue were undertaken to determine target organ tissue distribution. There was no increased mortality in the experimental group. Although there

  2. Use of a statistical model to predict the potential for repeated dose and developmental toxicity of dermally administered crude oil and relation to reproductive toxicity.

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    McKee, Richard H; Nicolich, Mark; Roy, Timothy; White, Russell; Daughtrey, Wayne C

    2014-01-01

    Petroleum (commonly called crude oil) is a complex substance primarily composed of hydrocarbon constituents. Based on the results of previous toxicological studies as well as occupational experience, the principal acute toxicological hazards are those associated with exposure by inhalation to volatile hydrocarbon constituents and hydrogen sulfide, and chronic hazards are associated with inhalation exposure to benzene and dermal exposure to polycyclic aromatic compounds. The current assessment was an attempt to characterize the potential for repeated dose and/or developmental effects of crude oils following dermal exposures and to generalize the conclusions across a broad range of crude oils from different sources. Statistical models were used to predict the potential for repeated dose and developmental toxicity from compositional information. The model predictions indicated that the empirical data from previously tested crude oils approximated a "worst case" situation, and that the data from previously tested crude oils could be used as a reasonable basis for characterizing the repeated dose and developmental toxicological hazards of crude oils in general.

  3. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA acute dermal toxicity. 799.9120 Section 799.9120 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES...) Preparations. Healthy young adult animals are acclimatized to the laboratory conditions for at least 5...

  4. 40 CFR 798.2250 - Dermal toxicity.

    Science.gov (United States)

    2010-07-01

    ... of lipids, hormones, acid/base balance, methemoglobin, and cholinesterase activity. Additional....2250 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT... its size, skin permeability, and extensive data base. Commonly used laboratory strains shall be...

  5. Acute and subchronic dermal toxicity of nanosilver in guinea pig

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    Arbabi Bidgoli S

    2011-04-01

    Full Text Available M Korani1, SM Rezayat1,2,4, K Gilani3, S Arbabi Bidgoli4, S Adeli11Department of Pharmacology, Faculty of Medicine, Tehran University of Medical Sciences; 2Department of Nanotechnology, Faculty of Advanced Sciences and Technology in Medicine, Tehran University of Medical Sciences; 3Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences; 4Department of Toxicology & Pharmacology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University (IAUPS, Tehran, IranAbstract: Silver has been used as an antimicrobial agent for a long time in different forms, but silver nanoparticles (nanosilver have recently been recognized as potent antimicrobial agents. Although nanosilver is finding diverse medical applications such as silver-based dressings and silver-coated medical devices, its dermal and systemic toxicity via dermal use has not yet been identified. In this study, we analyzed the potential toxicity of colloidal nanosilver in acute and subchronic guinea pigs. Before toxicity assessments, the size of colloidal nanosilver was recorded in sizes <100 nm by X-ray diffraction and transmission electron microscopy. For toxicological assessments, male guinea pigs weighing 350 to 400 g were exposed to two different concentrations of nanosilver (1000 and 10,000 µg/mL in an acute study and three concentrations of nanosilver (100, 1000, and 10,000 µg/mL in a subchronic study. Toxic responses were assessed by clinical and histopathologic parameters. In all experimental animals the sites of exposure were scored for any type of dermal toxicity and compared with negative control and positive control groups. In autopsy studies during the acute test, no significant changes in organ weight or major macroscopic changes were detected, but dose-dependent histopathologic abnormalities were seen in skin, liver, and spleen of all test groups. In addition, experimental animals subjected to subchronic tests showed greater

  6. ACUTE DERMAL TOXICITY STUDIES OF TROISTM IN NEWZEALAND WHITE RABBITS

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    Anurag Payasi

    2010-06-01

    Full Text Available The study was performed to assess the acute dermal toxicity of TroisTM in Newzealand white rabbit. Test substance was applied as such to the shaven skin of group of rabbits at the dose of 2000 mg/Kg body weight. Control group of animals were similarly treated but only with base. Following dosing up to 14 days the rabbits were observed for mortality and clinical sign of toxicity. No visible signs of toxicity after treatment were observed on the animals of both control and treated animals up to 14 days. Various haematological and biochemical parameters were evaluated and found to be in the normal limit, which indicates that no sign of toxicity in NewZealand white rabbits after 14 days treatment in respect to control group, proving safety of TroisTM in topical application.

  7. Toxicity of dermally applied alpha-cypermethrin in rats.

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    Luty, S; Latuszyńska, J; Halliop, J; Tochman, A; Obuchowska, D; Przylepa, E; Korczak, E

    1998-01-01

    The aim of the study was to assess the immunotoxic effect of dermally applied alpha-cypermethrin in rats based on phagocytic and bactericidal activity of neutrophils of peripheral blood, and the general toxic effect based on histological and ultrastructural examination of internal organs. The preparation was dermally applied in doses of 50 mg/kg and 250 mg/kg. It was administered to the tail skin of female Wistar rats, 4 hours daily for 28 days. After the experiment, the animals were anaesthetized and heart blood was taken in order to evaluate the activity of granulocyte system. The following organs were taken for histological examinations: brain, lung, heart, liver, spleen, kidneys, thymus and lymphatic nodes. Lung, liver, kidney and heart were used for ultrastructural studies. The results of the study showed that bactericidal and phagocytic activity of neutrophils was stimulated after administration of 50 mg/kg alpha-cypermethrin. Dermal application of the preparation resulted in slight histological changes in liver, kidney, lung and brain. Pathological changes in heart were observed only on the level of ultrastructure.

  8. A 13-week dermal repeat-dose neurotoxicity study of hydrodesulfurized kerosene in rats.

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    Breglia, Rudolph; Bui, Quang; Burnett, Donald; Koschier, Francis; Lapadula, Elizabeth; Podhasky, Paula; Schreiner, Ceinwen; White, Russell

    2014-01-01

    A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized (HDS) kerosene, a test material that also met the commercial specifications for aviation turbine fuel (jet A). The objectives were to assess the potential for target organ toxicity and neurotoxicity. The HDS kerosene was applied to the shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0 (vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or 495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the high-dose groups were held without treatment for 4 weeks to assess recovery. Standard parameters of toxicity were investigated during the in-life phase. At necropsy, organs were weighed and selected tissues were processed for microscopic evaluation. Neurobehavioral evaluations included tests of motor activity and functional observations that were conducted pretest, at intervals during the exposure period and after recovery. No test substance-related effects on mortality, clinical observations (except dermal irritation), body weight, or clinical chemistry values were observed. A dose-related increase in skin irritation, confirmed histologically as minimal, was evident at the dosing site. The only statistically significant change considered potentially treatment related was an increase in the neutrophil count in females at 13 weeks. No test article-related effects were observed in the neurobehavioral assessments or gross or microscopic findings in the peripheral or central nervous system tissues in any of the dose groups. Excluding skin irritation, the no observed adverse effect level value for all effects was considered 495 mg/kg/d.

  9. Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

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    Rennen, M.A.J.; Nordheim, K.; Houben, G.F.; Heer, C. de

    2002-01-01

    Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in

  10. Prediction of local irritant effects after repeated dermal and respiratory exposure to chemicals

    NARCIS (Netherlands)

    Rennen, M.A.J.; Nordheim, K.; Houben, G.F.; Heer, C. de

    2002-01-01

    Health risks resulting from occupational exposure to chemicals are controlled by the establishment of acceptable dermal and respiratory exposure levels. Due to a lack of route-specific toxicity data, acceptable levels are frequently established by means of route-to-route extrapolation. A pitfall in

  11. Novel System for Testing Dermal and Epidermal Toxicity in Vitro

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    1990-02-15

    months of this contract, we have been successful at establishing primary culture from 20 neonatal foreskin samples (from routine circumcisions ) and 6...objectives: 1. Established an inventory of neonatal and adult keratinocytes and fibroblasts. Modified the procedure for establishing and passing these...thymidine incorporation into adherent cell populations. Substrates utilized included neonatal fibroblast dermal equivalents (from foreskin) and adult

  12. Chronic Dermal Toxicity of Epoxy Resins I. Skin Carcinogenic Potency and General Toxicity

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    Holland, J.M.

    2001-01-16

    Epoxy resins are a diverse class of chemicals that differ in structure, physical properties, and, presumably, biological activity. The purpose of these experiments was to compare the chronic dermal toxicity and carcinogenicity of selected commercial epoxy resins and to determine the potential for positive synergistic carcinogenic interactions between different resins. This work is an extension and continuation of a Department of Energy sponsored program to evaluate epoxy resins for potential occupational health risks. The materials examined were chosen on the basis of their interest to the U.S. government. They are representative of the manufacturer's production at the time, and therefore the data are completely valid only for the specific production period. Results of the experimental exposures will be reported in two parts. This report describes the test materials, their chemical and physical characteristics and the experimental design. General (systemic) toxicity will be evaluated and the skin carcinogenicity of the materials compared. A subsequent report will provide morphological descriptions of skin and significant internal pathology induced by the various treatments.

  13. In-vitro methods for testing dermal absorption and penetration of toxic gases.

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    Gaskin, Sharyn; Pisaniello, Dino; Edwards, John W; Bromwich, David; Reed, Sue; Logan, Michael; Baxter, Christina

    2014-01-01

    This technical note provides details of an experimental technique for in-vitro skin studies with atmospheric chemical challenge. There appear to be major evidence gaps in relation to dermal exposure of gases. We describe a modification of standard OECD protocols for an atmospheric delivery system which can be used to understand interaction of toxic gases and the skin. The system can be used to examine the mechanisms by which skin uptake occurs. Auxiliary components which allow for parameter variation such as temperature and relative humidity are also described. Methodology presented in this technical note uses examples of gas challenges (ammonia, chlorine) to illustrate its application to gases of differing physicochemical properties. This adapted protocol can be applied in the context of HAZMAT scenarios involving atmospheric toxic chemical release and dermal absorption potential under variable exposure conditions.

  14. Oxidative stress and inflammatory response in dermal toxicity of single-walled carbon nanotubes.

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    Murray, A R; Kisin, E; Leonard, S S; Young, S H; Kommineni, C; Kagan, V E; Castranova, V; Shvedova, A A

    2009-03-29

    Single-walled carbon nanotubes (SWCNT) represent a novel material with unique electronic and mechanical properties. The extremely small size ( approximately 1 nm diameter) renders their chemical and physical properties unique. A variety of different techniques are available for the production of SWCNT; however, the most common is via the disproportionation of gaseous carbon molecules supported on catalytic iron particles (high-pressure CO conversion, HiPCO). The physical nature of SWCNT may lead to dermal penetration following deposition on exposed skin. This dermal deposition provides a route of exposure which is important to consider when evaluating SWCNT toxicity. The dermal effects of SWCNT are largely unknown. We hypothesize that SWCNT may be toxic to the skin. We further hypothesize that SWCNT toxicity may be dependent upon the metal (particularly iron) content of SWCNT via the metal's ability to interact with the skin, initiate oxidative stress, and induce redox-sensitive transcription factors thereby affecting/leading to inflammation. To test this hypothesis, the effects of SWCNT were assessed both in vitro and in vivo using EpiDerm FT engineered skin, murine epidermal cells (JB6 P+), and immune-competent hairless SKH-1 mice. Engineered skin exposed to SWCNT showed increased epidermal thickness and accumulation and activation of dermal fibroblasts which resulted in increased collagen as well as release of pro-inflammatory cytokines. Exposure of JB6 P+ cells to unpurified SWCNT (30% iron) resulted in the production of ESR detectable hydroxyl radicals and caused a significant dose-dependent activation of AP-1. No significant changes in AP-1 activation were detected when partially purified SWCNT (0.23% iron) were introduced to the cells. However, NFkappaB was activated in a dose-dependent fashion by exposure to both unpurified and partially purified SWCNT. Topical exposure of SKH-1 mice (5 days, with daily doses of 40 microg/mouse, 80 microg/mouse, or 160

  15. Developmental toxicity of Clarified Slurry Oil applied dermally to rats

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    Feuston, M.H.; Kerstetter, S.L.; Singer, E.J.; Mehlman, M.A. (Mobil Oil Corporation, Princeton, NJ (USA))

    1989-05-01

    Clarified Slurry Oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 pregnant rats at doses of 0, 4, 8, 30, 125, and 250 mg/kg/day. All groups received the test material on gestation days 0-19. CSO was applied undiluted and left uncovered on the skin; collars were placed on the rats to minimize ingestion of the test material. Signs of maternal toxicity, some of which were seen at dose levels as low as 8 mg/kg/day, included vaginal bleeding, decreased body weight gain, reduced food consumption, death, increased relative liver weights, atrophy of the thymus, and aberrant serum chemistry. The number of fetal resorptions/deaths was markedly increased and the number of viable offspring decreased by CSO at dosages of 30 mg/kg/day and above. The group receiving 250 mg/kg/day carried no viable offspring. Fetuses from pregnant females exposed to CSO at dose levels in excess of 8 mg/kg/day were smaller than those from control and 4 mg/kg/day groups, and their skeletons showed decreased ossification. Abnormal external development and visceral development were observed in living and dead fetuses exposed in utero to CSO at dose levels as low as 8 mg/kg/day. Based on these data, 4 mg/kg/day represents the No-Observed-Adverse-Effect-Level for both maternal and developmental toxicity.

  16. Dermal toxicity elicited by phthalates: evaluation of skin absorption, immunohistology, and functional proteomics.

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    Pan, Tai-Long; Wang, Pei-Wen; Aljuffali, Ibrahim A; Hung, Yi-Yun; Lin, Chwan-Fwu; Fang, Jia-You

    2014-03-01

    The toxicity of phthalates is an important concern in the fields of environmental health and toxicology. Dermal exposure via skin care products, soil, and dust is a main route for phthalate delivery. We had explored the effect of topically-applied phthalates on skin absorption and toxicity. Immunohistology, functional proteomics, and Western blotting were employed as methodologies for validating phthalate toxicity. Among 5 phthalates tested, di(2-ethylhexyl)phthalate (DEHP) showed the highest skin reservoir. Only diethyl phthalate (DEP) and dibutyl phthalate (DBP) could penetrate across skin. Strat-M(®) membrane could be used as permeation barrier for predicting phthalate penetration through skin. The accumulation of DEHP in hair follicles was ∼15nmol/cm(2), which was significantly greater than DBP and DEP. DBP induced apoptosis of keratinocytes and fibroblasts via caspase-3 activation. This result was confirmed by downregulation of 14-3-3 and immunohistology of TUNEL. On the other hand, the HSP60 overexpression and immunostaining of COX-2 suggested inflammatory response induced by DEP and DEHP. The proteomic profiling verified the role of calcium homeostasis on skin inflammation. Some proteins investigated in this study can be sensitive biomarkers for dermal toxicity of phthalates. These included HSPs, 14-3-3, and cytokeratin. This work provided novel platforms for examining phthalate toxicity on skin.

  17. The levels of kerosene components in biological samples after repeated dermal exposure to kerosene in rats.

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    Fujihara, Junko; Hieda, Yoko; Tsujino, Yoshio; Xue, Yuying; Takayama, Koji; Kimura, Kojiro; Dekio, Satoshi

    2004-04-01

    The current study was experimentally investigated using rats whether or not kerosene components are accumulated from daily repeated dermal exposure. Rats received daily 1h-exposure to kerosene for 5 days (5K), daily 1h-exposure for 4 days and left for 1 day (4KL), a single 1h-exposure (1K), a single 1h-exposure and left for 1 day (1KL), or a single 1h-exposure, sacrificed and left dead for 1 day (1KLD). Kerosene components, trimethylbenzenes (TMBs) and aliphatic hydrocarbons (AHCs) in blood and tissues were determined by GC-MS. In blood, almost the same concentrations of TMBs were detected in the rats sacrificed immediately after exposure (5K, 1K and 1KLD), and only trace levels were detected in the rats sacrificed 1 day after exposure (4 and 1KL). Almost the same levels of AHCs in blood were detected among groups except for the rats sacrificed 1 day after a single exposure (1KL), in which AHCs were slightly lower. These results suggest that (1) AHCs tend to be accumulated from daily exposure, while TMBs do not, (2) the proportions of detected kerosene components in blood can be an indicator of whether the last exposure occurred just before death or not, (3) the kerosene levels last at least 1 day without blood circulation.

  18. The margin of internal exposure (MOIE) concept for dermal risk assessment based on oral toxicity data - A case study with caffeine.

    Science.gov (United States)

    Bessems, Jos G M; Paini, Alicia; Gajewska, Monika; Worth, Andrew

    2017-03-10

    Route-to-route extrapolation is a common part of human risk assessment. Data from oral animal toxicity studies are commonly used to assess the safety of various but specific human dermal exposure scenarios. Using theoretical examples of various user scenarios, it was concluded that delineation of a generally applicable human dermal limit value is not a practicable approach, due to the wide variety of possible human exposure scenarios, including its consequences for internal exposure. This paper uses physiologically based kinetic (PBK) modelling approaches to predict animal as well as human internal exposure dose metrics and for the first time, introduces the concept of Margin of Internal Exposure (MOIE) based on these internal dose metrics. Caffeine was chosen to illustrate this approach. It is a substance that is often found in cosmetics and for which oral repeated dose toxicity data were available. A rat PBK model was constructed in order to convert the oral NOAEL to rat internal exposure dose metrics, i.e. the area under the curve (AUC) and the maximum concentration (Cmax), both in plasma. A human oral PBK model was constructed and calibrated using human volunteer data and adapted to accommodate dermal absorption following human dermal exposure. Use of the MOIE approach based on internal dose metrics predictions provides excellent opportunities to investigate the consequences of variations in human dermal exposure scenarios. It can accommodate within-day variation in plasma concentrations and is scientifically more robust than assuming just an exposure in mg/kg bw/day. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. protective effect of tetracycline against dermal toxicity induced by Jellyfish venom.

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    Changkeun Kang

    Full Text Available BACKGROUND: Previously, we have reported that most, if not all, of the Scyphozoan jellyfish venoms contain multiple components of metalloproteinases, which apparently linked to the venom toxicity. Further, it is also well known that there is a positive correlation between the inflammatory reaction of dermal tissues and their tissue metalloproteinase activity. Based on these, the use of metalloproteinase inhibitors appears to be a promising therapeutic alternative for the treatment of jellyfish envenomation. METHODOLOGY AND PRINCIPAL FINDINGS: Tetracycline (a metalloproteinase inhibitor has been examined for its activity to reduce or prevent the dermal toxicity induced by Nemopilema nomurai (Scyphozoa: Rhizostomeae jellyfish venom (NnV using in vitro and in vivo models. HaCaT (human keratinocyte and NIH3T3 (mouse fibroblast incubated with NnV showed decreases in cell viability, which is associated with the inductions of metalloproteinase-2 and -9. This result suggests that the use of metalloproteinase inhibitors, such as tetracycline, may prevent the jellyfish venom-mediated local tissue damage. In vivo experiments showed that comparing with NnV-alone treatment, tetracycline pre-mixed NnV demonstrated a significantly reduced progression of dermal toxicity upon the inoculation onto rabbit skin. CONCLUSIONS/SIGNIFICANCE: It is believed that there has been no previous report on the therapeutic agent of synthetic chemical origin for the treatment of jellyfish venom-induced dermonecrosis based on understanding its mechanism of action except the use of antivenom treatment. Furthermore, the current study, for the first time, has proposed a novel mechanism-based therapeutic intervention for skin damages caused by jellyfish stings.

  20. Acute, Multiple-Dose Dermal and Genetic Toxicity of Nu-3: A Novel Antimicrobial Agent

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    Juan Sun

    2010-01-01

    Full Text Available Nu-3 [butyl-phosphate-5-thymidine-3-phosphate-butyl] is a modified nucleotide that has been shown to have antimicrobial activity against a range of bacteria including Pseudomonas aeruginosa. However, data on the toxicological profile of Nu-3 are still lacking. In the present study, the toxicity of Nu-3 was evaluated by the following studies: acute oral toxicity, dermal and mucous membrane irritation, multiple-dose toxicity and genotoxicity in vivo and vitro. The acute oral toxicity test in mice showed that Nu-3 had an LD50 of 2001mg/kg body weight. The irritation tests on rats revealed that Nu-3 was not irritant, with an irritation scoring of 0. The multiple-dose toxicity study in rats showed that Nu-3 did not cause significant changes in histology, selected serum chemistry, and hematological parameters compared to the controls. Rats administrated with multiple-doses of Nu-3 showed no visible toxic symptoms. Both in vitro and in vivo, Nu-3 exhibited no notable genetic toxicity. Overall, the data suggest that Nu-3 is hypotoxic or nontoxic antimicrobial compound that warrants being further developed for treating Pseudomonas aeruginosa infection.

  1. Improving reptile ecological risk assessment: oral and dermal toxicity of pesticides to a common lizard species (Sceloporus occidentalis).

    Science.gov (United States)

    Weir, Scott M; Yu, Shuangying; Talent, Larry G; Maul, Jonathan D; Anderson, Todd A; Salice, Christopher J

    2015-08-01

    Reptiles have been understudied in ecotoxicology, which limits consideration in ecological risk assessments. The goals of the present study were 3-fold: to improve oral and dermal dosing methodologies for reptiles, to generate reptile toxicity data for pesticides, and to correlate reptile and avian toxicity. The authors first assessed the toxicity of different dosing vehicles: 100 μL of water, propylene glycol, and acetone were not toxic. The authors then assessed the oral and dermal toxicity of 4 pesticides following the up-and-down procedure. Neither brodifacoum nor chlorothalonil caused mortality at doses ≤ 1750 μg/g. Under the "neat pesticide" oral exposure, endosulfan (median lethal dose [LD50] = 9.8 μg/g) was more toxic than λ-cyhalothrin (LD50 = 916.5 μg/g). Neither chemical was toxic via dermal exposure. An acetone dosing vehicle increased λ-cyhalothrin toxicity (oral LD50 = 9.8 μg/g; dermal LD50 = 17.5 μg/g), but not endosulfan. Finally, changes in dosing method and husbandry significantly increased dermal λ-cyhalothrin LD50s, which highlights the importance of standardized methods. The authors combined data from the present study with other reptile LD50s to correlate with available avian data. When only definitive LD50s were used in the analysis, a strong correlation was found between avian and reptile toxicity. The results suggest it is possible to build predictive relationships between avian and reptile LD50s. More research is needed, however, to understand trends associated with chemical classes and modes of action.

  2. Evaluation of the dermal subchronic toxicity of phenoxyethyl isobutyrate in the rat.

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    Api, Anne Marie

    2004-02-01

    Phenoxyethyl isobutyrate (PEIB) is a fragrance and food ingredient that has been granted GRAS status and approved by the FDA for food use. The present studies investigated the dermal absorption parameters and subchronic toxicity of PEIB. For the absorption, distribution and elimination study, Sprague-Dawley rats received a dermal application of 2-[ring U 14C]-PEIB under occlusion for 6 h. PEIB was diluted in diethyl phthalate (DEP) to administer, a total application volume of 2 ml/kg, concentrations of 0.5, 5 and 50% ( congruent with 10, 100 and 1000 mg PEIB/kgBW). Approximately 61-69% of the applied dose was recovered from the dressing and skin surface washing procedure performed after 6-h exposure. By 72 h post dose, systemic elimination of radioactivity was congruent with 18 to 19% of the absorbed dose via the urine with small amounts also found in the feces (skin irritation, hematology, and blood chemistry, necropsy, and gross and histopathologic evaluation of tissues demonstrated no treatment-related effects. The local skin irritation and systemic toxicity no-observed-effect-levels (NOELs) for PEIB in this study were determined to be >1000 mg/kgBW/day.

  3. Evaluation of the dermal subchronic toxicity of diphenyl ether in the rat.

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    Api, A M; Ford, R A

    2003-02-01

    Diphenyl ether (DPE) was investigated to determine the dermal absorption parameters and subchronic toxicity of this fragrance ingredient. For the absorption, distribution and elimination study, Sprague-Dawley rats received a dermal application of [14C]DPE under a semi-occlusive dressing for 6 h. DPE was diluted in diethyl phthalate (DEP) to administer a total application volume of 2 ml/kg and concentrations of 0.5, 5 and 50% (approximately equal to 10, 100 and 1000 mg DPE/kg body weight). Approximately 17.7% of the administered dose was eliminated in the urine, with small amounts also found in the feces (1.18-3.79%). At 72 h post-dosing, approximately 0.2% of the applied dose was retained in the body with low levels also measured in the liver, kidney and gastrointestinal tract (approximately equal to 0.04, 0.02 and 0.3%, respectively). The 13-week subchronic toxicity study was performed with groups of 12 Sprague-Dawley rats/sex/dose that received semi-occluded daily dermal applications of DPE for 6 h/day. All groups were dosed at a constant 2 ml/kg body weight volume of DPE in the DEP vehicle at concentrations to administer 0, 100, 300 or 1000 mg DPE/kg body weight/day. At the high dose level, there was a slight reduction in body weight gain in males (13%), increase in albumin (5-6%) and phosphate (10-15%) levels in both sexes, a reduction of cholesterol in females (14%), an increase in kidney (17%) and brain (8%) weights in males, and an increase in liver weight (18-19%) in both sexes. No histopathological lesions were seen in any organ examined. At 300 mg/kg body weight/day, the only notable findings were an increase in liver weight (10%) in both sexes and a slight increase in albumin (5%) in females. In addition, skin irritation reactions at the site of application were observed in all DPE dose groups. The systemic no-observed-effect level (NOEL) in this study is 100 mg/kg body weight/day. Owing to mitigating factors, the systemic findings were judged to lack

  4. Dermal Exposure to Cumene Hydroperoxide: Assessing Its Toxic Relevance and Oxidant Potential.

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    Rider, Cynthia V; Chan, Po; Herbert, Ron A; Kissling, Grace E; Fomby, Laurene M; Hejtmancik, Milton R; Witt, Kristine L; Waidyanatha, Suramya; Travlos, Greg S; Kadiiska, Maria B

    2016-07-01

    Cumene hydroperoxide (CHP) is a high production volume chemical that is used to generate phenol and acetone. Dermal exposure to CHP was hypothesized to result in systemic tissue toxicity, production of free radicals, and consequent decrease in plasma antioxidant levels. To evaluate the hypothesis and characterize the toxicity of CHP, male and female B6C3F1/N mice and F344/N rats were exposed to varying doses of CHP applied topically for 14 or 90 days. No significant changes in survival or body weight of mice and rats were observed following 14 days of exposure. However, 90 days of CHP exposure at the high dose (12 mg/kg) triggered a significant decrease (-15%) in the body weight of the male rat group only. Irritation of the skin was observed at the site of application and was characterized by inflammation and epidermal hyperplasia. In treated animals, histology of liver tissue, free radical generation, and antioxidant levels in blood plasma were not significantly changed as compared to the corresponding controls. Consistent with the lack of systemic damage, no increase in micronucleated erythrocytes was seen in peripheral blood. In conclusion, topical CHP application caused skin damage only at the application site and did not cause systemic tissue impairment.

  5. Assessment of Acute Oral and Dermal Toxicity of 2 Ethyl-Carbamates with Activity against Rhipicephalus microplus in Rats

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    María Guadalupe Prado-Ochoa

    2014-01-01

    Full Text Available The acute oral and dermal toxicity of two new ethyl-carbamates (ethyl-4-bromophenyl-carbamate and ethyl-4-chlorophenyl-carbamate with ixodicide activity was determined in rats. The oral LD50 of each carbamate was 300 to 2000 mg/kg, and the dermal LD50 of each carbamate was >5000 mg/kg. Clinically, the surviving rats that had received oral doses of each carbamate showed decreased weight gain (P<0.05 and had slight nervous system manifestations. These clinical signs were evident from the 300 mg/kg dose and were reversible, whereas the 2000 mg/kg dose caused severe damage and either caused their death or was motive for euthanasia. At necropsy, these rats had dilated stomachs and cecums with diffuse congestion, as well as moderate congestion of the liver. Histologically, the liver showed slight degenerative lesions, binucleated hepatocytes, focal coagulative necrosis, and congestion areas; the severity of the lesions increased with dosage. Furthermore, an slight increase in gamma-glutamyltransferase, lactate dehydrogenase, and creatinine was observed in the plasma. The dermal application of the maximum dose (5000 mg/kg of each carbamate did not cause clinical manifestations or liver and skin alterations. This finding demonstrates that the carbamates under study have a low oral hazard and low acute dermal toxicity.

  6. Mitochondrial tolerance to single and repeat exposure to simulated sunlight in human epidermal and dermal skin cells.

    Science.gov (United States)

    Kelly, J; Murphy, J E J

    2016-12-01

    Sunlight represents the primary threat to mitochondrial integrity in skin given the unique nature of the mitochondrial genome and its proximity to the electron transport chain. The accumulation of mitochondrial DNA (mtDNA) mutations is a key factor in many human pathologies and this is linked to key roles of mitochondrial function in terms of energy production and cell regulation. The main objective of this study was to evaluate solar radiation induced changes in mitochondrial integrity, function and dynamics in human skin cells using a Q-Sun solar simulator to deliver a close match to the intensity of summer sunlight. Spontaneously immortalised human skin epidermal keratinocytes (HaCaT) and Human Dermal Fibroblasts (HDFn) were divided into two groups. Group A were irradiated once and Group B twice 7days apart and evaluated using cell survival, viability and mitochondrial membrane potential (MMP) and mass at 1, 4 and 7days post one exposure for Group A and 1, 4, 7 and 14days post second exposure for Group B. Viability and survival of HaCaT and HDFn cells decreased after repeat exposure to Simulated Sunlight Irradiation (SSI) with no recovery. HDFn cells showed no loss in MMP after one or two exposures to SSI compared to HaCaT cells which showed a periodic loss of MMP after one exposure with a repeat exposure causing a dramatic decrease from which cells did not recover. Mitochondrial Mass in exposed HDFn cells was consistent with control after one or two exposures to SSI; however mitochondrial mass was significantly decreased in HaCaT cells. Data presented here suggests that mitochondria in epidermal cells are more sensitive to sunlight damage compared to mitochondria in dermal cells, despite their origin, confirming a skin layer specific sensitivity to sunlight, but not as expected. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Evaluation of cationic polyamidoamine dendrimers' dermal toxicity in the rat skin model.

    Science.gov (United States)

    Winnicka, Katarzyna; Wroblewska, Magdalena; Sosnowska, Katarzyna; Car, Halina; Kasacka, Irena

    2015-01-01

    Polyamidoamine (PAMAM) dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL), skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with the concentration of PAMAM-NH2, but no significant differences in the cell proliferation activity in skin treated with PAMAM-NH2 generation 2 or generation 3 were observed. Significantly higher expression of PCNA extended throughout the skin layers might suggest abnormal cell proliferation, which, as a consequence, might even lead to neoplastic changes.

  8. Evaluation of cationic polyamidoamine dendrimers’ dermal toxicity in the rat skin model

    Science.gov (United States)

    Winnicka, Katarzyna; Wroblewska, Magdalena; Sosnowska, Katarzyna; Car, Halina; Kasacka, Irena

    2015-01-01

    Polyamidoamine (PAMAM) dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL), skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with the concentration of PAMAM-NH2, but no significant differences in the cell proliferation activity in skin treated with PAMAM-NH2 generation 2 or generation 3 were observed. Significantly higher expression of PCNA extended throughout the skin layers might suggest abnormal cell proliferation, which, as a consequence, might even lead to neoplastic changes. PMID:25834395

  9. Exposure to pesticides with dermal toxicity in farmers of Community of Valencia

    Directory of Open Access Journals (Sweden)

    Caterina Brandon Garcia

    2010-12-01

    Full Text Available Introduction: Dermal route has a toxicological importance, as well as substances such as entry, but by frequent local effects. In applications of pesticides by farmers is common and important the dermal exposure to pesticides, so the dermal route in this sector of activity could be of particular relevance. Objective: To determine the hazard of dermal exposure in farmers using pesticides and to propose specific preventive measures. Material and methods: A transversal descriptive study based on a questionnaire designed by the researchers, replying to the 238 attendees at the courses for pesticide handler card basic level Department of Health Xativa-Ontinyent (Valencia in 2009. Pesticides used were collected over the past 12 months and reviewed their R phrases (risk phrases looking for dermal effects. Results: 55 % of pesticides had some phrase R on skin problems. The phrase R38 "Irritating to skin" was found in 16 products, used by 59.05 % of respondents and the R43 "Possibility of sensitization by skin contact" at 7, used by 23.91 %. Conclusions: The skin irritation effect was related to more dermal exposure to these pesticides. It is necessary to emphasize the skin protection in the courses for workers who apply these products. Skin problems should be included damages for workplace exposure to pesticides.

  10. Evaluation of cationic polyamidoamine dendrimers’ dermal toxicity in the rat skin model

    Directory of Open Access Journals (Sweden)

    Winnicka K

    2015-03-01

    Full Text Available Katarzyna Winnicka,1 Magdalena Wroblewska,1 Katarzyna Sosnowska,1 Halina Car,2 Irena Kasacka3 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland; 2Department of Experimental Pharmacology, Faculty of Health Sciences, Medical University of Bialystok, Bialystok, Poland; 3Department of Histology and Cytophysiology, Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland Abstract: Polyamidoamine (PAMAM dendrimers are multi-branched, three-dimensional polymers with unique architecture, which makes these molecules attractive for medical and pharmaceutical applications. Using PAMAM as drug carriers for topical delivery might be beneficial as they only produce a transient effect without skin irritation. To evaluate the dermal toxicity of cationic PAMAM dendrimers generation 2 and generation 3, skin irritation studies were performed in vivo in the rat skin model. After 10 days topical application of various concentrations of PAMAM-NH2 (0.3 mg/mL, 3 mg/mL, 6 mg/mL, 30 mg/mL, 300 mg/mL, skin irritation was evaluated by visual, histopathological, and immunohistochemical examination. Microscopic assessment after hematoxylin-eosin staining revealed significant morphological changes of epidermal cells after application of PAMAM-NH2 at a concentration of ≥6 mg/mL. Morphological alterations of epidermal cells included cytoplasmic vacuolization of keratinocytes in the basal and spinous layers. Cytomorphological changes in keratinocytes, overall picture of the epidermis, and histopathological changes in the dermis were dose dependent. Detected alterations concerned hyperplasia of connective tissue fibers and leukocyte infiltration. Visible granulocyte infiltration in the upper dermis and sockets formed by necrotic, cornified cells in the hyperplastic foci of epithelium were also noted. Immunohistochemical analyses revealed that increased nuclear immunoreactivity to PCNA correlated with

  11. Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila.

    Science.gov (United States)

    Shieh, Shin-Yi; Bonini, Nancy M

    2011-12-15

    Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the disease in Drosophila. To provide insights into the nature of the RNA toxicity, we extracted brain-enriched RNA from flies expressing a toxic CAG-repeat mRNA (CAG100) and a non-toxic interrupted CAA/G mRNA repeat (CAA/G105) for microarray analysis. This approach identified 160 genes that are differentially expressed specifically in CAG100 flies. Functional annotation clustering analysis revealed several broad ontologies enriched in the CAG100 gene list, including iron ion binding and nucleotide binding. Intriguingly, transcripts for the Hsp70 genes, a powerful suppressor of polyQ and other human neurodegenerative diseases, were also upregulated. We therefore tested and showed that upregulation of heat shock protein 70 mitigates CAG-repeat RNA toxicity. We then assessed whether other modifiers of the pathogenic, expanded Ataxin-3 polyQ protein could also modify the CAG-repeat RNA toxicity. This approach identified the co-chaperone Tpr2, the transcriptional regulator Dpld, and the RNA-binding protein Orb2 as modifiers of both polyQ protein toxicity and CAG-repeat RNA-based toxicity. These findings suggest an overlap in the mechanisms of RNA and protein-based toxicity, providing insights into the pathogenicity of the RNA in polyQ disease.

  12. Role of surface modification in zinc oxide nanoparticles and its toxicity assessment toward human dermal fibroblast cells

    Directory of Open Access Journals (Sweden)

    Ramasamy M

    2014-08-01

    Full Text Available Mohankandhasamy Ramasamy,1 Minakshi Das,1 Seong Soo A An,1 Dong Kee Yi2 1Division of Bionanotechnology, Gachon University, Seongnam, 2Department of Chemistry, Myongji University, Yongin, South Korea Abstract: The wide-scale applications of zinc oxide (ZnO nanoparticles (NPs in ­photocatalysts, gas sensors, and cosmetics may cause toxicity to humans and environments. Therefore, the aim of the present study was to reduce the toxicity of ZnO NPs by coating them with a silica (SiO2 layer, which could be used in human applications, such as cosmetic preparations. The sol–gel method was used to synthesize core ZnO with SiO2-shelled NPs (SiO2/ZnO NPs with varying degrees of coating. Diverse studies were performed to analyze the toxicity of NPs against cells in a dose- and time-dependent manner. To ensure the decreased toxicity of the produced SiO2/ZnO NPs, cytotoxicity in membrane damage and/or intracellular reactive oxygen species (ROS were assessed by employing 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, lactate dehydrogenase, 2',7'-dichlorofluorescin, and lipid peroxide estimations. The cores of ZnO NPs exhibited cytotoxicity over time, regardless of shell thickness. Nevertheless, the thicker SiO2/ZnO NPs revealed reduced enzyme leakage, decreased peroxide production, and less oxidative stress than their bare ZnO NPs or thinner SiO2/ZnO NPs. Therefore, thicker SiO2/ZnO NPs moderated the toxicity of ZnO NPs by restricting free radical formation and the release of zinc ions, and decreasing surface contact with cells. Keywords: zinc oxide, silica coating, photostability, human dermal fibroblast, membrane damage, oxidative stress

  13. Dermal toxicity studies of technical polychlorinated biphenyls and fractions thereof in rabbits

    NARCIS (Netherlands)

    Vos, J.G.; Beems, R.B.

    1971-01-01

    A significant difference in toxicity between 3 polychlorinated biphenyl (PCB) preparations was found in a prior study: Clophen A 60 and Phenoclor DP6 showing the highest, Aroclor 1260 the lowest, toxicity (Vos and Koeman, 1970). A subsequent study revealed the presence of tetra- and pentachlorodiben

  14. Genes and pathways affected by CAG-repeat RNA-based toxicity in Drosophila

    OpenAIRE

    Shieh, Shin-Yi; Bonini, Nancy M.

    2011-01-01

    Spinocerebellar ataxia type 3 is one of the polyglutamine (polyQ) diseases, which are caused by a CAG-repeat expansion within the coding region of the associated genes. The CAG repeat specifies glutamine, and the expanded polyQ domain mutation confers dominant toxicity on the protein. Traditionally, studies have focused on protein toxicity in polyQ disease mechanisms. Recent findings, however, demonstrate that the CAG-repeat RNA, which encodes the toxic polyQ protein, also contributes to the ...

  15. Acute dermal toxicity: in vivo and in vitro comparisons in mice.

    Science.gov (United States)

    Helman, R G; Hall, J W; Kao, J Y

    1986-07-01

    Mouse skin was exposed topically to solutions of dinitrochlorobenzene (DNCB), croton oil (CO), epoxyethylbenzene (EEB), ethanolamine (EtNH2), or isopropylmyristate (IPM), and the histologic response evaluated 20 hr later with light microscopy. In a parallel series of experiments, discs of mouse skin were collected, exposed in vitro to the same chemicals and examined histologically after 20 hr in culture. Additionally, cellular enzyme leakage was determined in the culture medium. DNCB was the most toxic to the skin followed by CO and EEB. IPM and EtNH2 were toxic only at the highest concentration used (10%). There were good correlations between the magnitude of the skin lesions and the levels of enzyme activity in the culture medium. The results show that morphologic responses of skin maintained in organ culture are an indicator of in vitro skin toxicity. Moreover, enzyme leakage may provide a means for detecting sublethal cell injury which might not be observed histologically.

  16. Irritantcy potential and sub acute dermal toxicity study of Pistacia lentiscus fatty oil as a topical traditional remedy.

    Science.gov (United States)

    Djerrou, Zouhir; Djaalab, Hdria; Riachi, Foulla; Serakta, Mennouba; Chettoum, Aziez; Maameri, Zineb; Boutobza, Badaoui; Hamdi-Pacha, Youcef

    2013-01-01

    The current study was undertaken to assess safety of Pistacia lentiscus fruits fatty oil (PLFO) as a topical traditional remedy. A primary skin and eye irritation tests were conducted with New Zealand white rabbits to determine the potential for PLFO to produce irritation from a single application. In addition, a sub acute dermal toxicity study was performed on 18 NZW rabbits to evaluate possible adverse effect following application of PLFO for 28 days. Based on the results of the current study, PLFO is classified as slightly irritating to the skin and the eye of rabbits (Primary Irritation Index (P.I.I.) = 1.037; Ocular Irritation Index (O.I.I.) = 5.33 at 1 h). In the sub-acute toxicity test, PLFO produced neither mortality nor significant differences in the body and organ weights between control group and treated rabbits. However, a reversible irritant contact dermatitis was observed in the treated areas from the end of the second week of application until the end of experiment. This local phenomenon was accompanied by a significant skin thickening (P≤0.01) since the 12(th) day (ANOVA, F = 11, 07143, P = 0, 00765) which is confirmed with an inflammatory granuloma in histological study. Haematological analysis and blood chemistry values of the 2 groups showed no significant differences in any of the parameters examined. In summary, PLFO is minimally irritating to the eye and skin after a single exposure, but it may cause irritant contact dermatitis and a reversible thickening of skin after prolonged use.

  17. Comparison of the repeated dose toxicity of isomers of dinitrotoluene.

    Science.gov (United States)

    Lent, Emily May; Crouse, Lee C B; Quinn, Michael J; Wallace, Shannon M

    2012-03-01

    Dinitrotoluene (DNT) is a nitroaromatic explosive used in propellant mixtures and in the production of plastics. Isomers of DNT were administered daily via oral gavage to male Sprague-Dawley rats for 14 days to determine the subacute toxicity of individual isomers of DNT. The 3,5-DNT isomer was the most toxic isomer, inducing weight loss and mortality within 3 days. Cyanosis and anemia were observed for all isomers. Exposure to 2,4-, 2,6-, and 3,5-DNT resulted in decreased testes mass and degenerative histopathological changes. Increased splenic mass was observed for 2,4-, 2,6-, and 2,5-DNT. Extramedullary hematopoiesis of the spleen was noted for all isomers, while lymphoid hyperplasia of the spleen was noted for all isomers except 2,5-DNT. Increased liver mass was observed for 2,3-DNT and 3,4-DNT. Hepatocellular lesions were observed for 2,6-DNT and 2,4-DNT. Neurotoxic effects were noted for 3,4-DNT, 2,4-DNT, and 3,5-DNT.

  18. Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of “Zapote” Pouteria mammosa (L.) Cronquist

    Science.gov (United States)

    Dutok, Carlos M. S.; Berenguer-Rivas, Clara Azalea; Rodríguez-Leblanch, Elizabeth; Pérez-Jackson, Liliana; Chil-Nuñez, Idelsy; Escalona-Arranz, Julio César; Reyes-Tur, Bernardo; Queiroz, Margareth M. C.

    2015-01-01

    The common use of Pouteria mammosa (L.) Cronquist, “Mamey or Zapote,” in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25%) Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD). The aqueous extract was located in the following category: not classified as toxic (CTA 5), while hydroalcoholic extract at 25% was classified as dangerous (CTA 4). Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating. PMID:26273696

  19. 40 CFR 799.9305 - TSCA Repeated dose 28-day oral toxicity study in rodents.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 31 2010-07-01 2010-07-01 true TSCA Repeated dose 28-day oral toxicity study in rodents. 799.9305 Section 799.9305 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... strains of young healthy adult animals should be employed. The females should be nulliparous and...

  20. Distinct C9orf72-Associated Dipeptide Repeat Structures Correlate with Neuronal Toxicity

    Science.gov (United States)

    Krans, Amy; Sawaya, Michael R.; Paulson, Henry L.; Todd, Peter K.; Barmada, Sami J.; Ivanova, Magdalena I.

    2016-01-01

    Hexanucleotide repeat expansions in C9orf72 are the most common inherited cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The expansions elicit toxicity in part through repeat-associated non-AUG (RAN) translation of the intronic (GGGGCC)n sequence into dipeptide repeat-containing proteins (DPRs). Little is known, however, about the structural characteristics and aggregation propensities of the dipeptide units comprising DPRs. To address this question, we synthesized dipeptide units corresponding to the three sense-strand RAN translation products, analyzed their structures by circular dichroism, electron microscopy and dye binding assays, and assessed their relative toxicity when applied to primary cortical neurons. Short, glycine-arginine (GR)3 dipeptides formed spherical aggregates and selectively reduced neuronal survival compared to glycine-alanine (GA)3 and glycine-proline (GP)3 dipeptides. Doubling peptide length had little effect on the structure of GR or GP peptides, but (GA)6 peptides formed β-sheet rich aggregates that bound thioflavin T and Congo red yet lacked the typical fibrillar morphology of amyloids. Aging of (GA)6 dipeptides increased their β-sheet content and enhanced their toxicity when applied to neurons. We also observed that the relative toxicity of each tested dipeptide was proportional to peptide internalization. Our results demonstrate that different C9orf72-related dipeptides exhibit distinct structural properties that correlate with their relative toxicity. PMID:27776165

  1. Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulations.

    Science.gov (United States)

    Shende, Pravin; Kulkarni, Yogesh A; Gaud, R S; Deshmukh, Kiran; Cavalli, Roberta; Trotta, Francesco; Caldera, Fabrizio

    2015-05-01

    Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.

  2. 77 FR 43089 - Evaluation of an Up-and-Down Procedure for Acute Dermal Systemic Toxicity Testing: Request for...

    Science.gov (United States)

    2012-07-23

    ... Acute poisoning from chemicals and chemical products, including pharmaceuticals, is a significant public health problem. In 2009, 2.5 million human poisoning cases were reported to U.S. poison control centers (Bronstein et al., 2010). Dermal exposures were involved in 7.25% (179,832 cases) of the poisonings,...

  3. Evaluation of statistical tools used in short-term repeated dose administration toxicity studies with rodents.

    Science.gov (United States)

    Kobayashi, Katsumi; Pillai, K Sadasivan; Sakuratani, Yuki; Abe, Takemaru; Kamata, Eiichi; Hayashi, Makoto

    2008-02-01

    In order to know the different statistical tools used to analyze the data obtained from twenty-eight-day repeated dose oral toxicity studies with rodents and the impact of these statistical tools on interpretation of data obtained from the studies, study reports of 122 numbers of twenty-eight-day repeated dose oral toxicity studies conducted in rats were examined. It was found that both complex and easy routes of decision trees were followed for the analysis of the quantitative data. These tools include Scheffe's test, non-parametric type Dunnett's and Scheffe's tests with very low power. Few studies used the non-parametric Dunnett type test and Mann-Whitney's U test. Though Chi-square and Fisher's tests are widely used for analysis of qualitative data, their sensitivity to detect a treatment-related effect is questionable. Mann-Whitney's U test has better sensitivity to analyze qualitative data than the chi-square and Fisher's tests. We propose Dunnett's test for analysis of quantitative data obtained from twenty-eight-day repeated dose oral toxicity tests and for qualitative data, Mann-Whitney's U test. For both tests, one-sided test with p=0.05 may be applied.

  4. Evaluation of 90 day repeated dose oral toxicity and reproductive/developmental toxicity of 3'-hydroxypterostilbene in experimental animals.

    Science.gov (United States)

    Majeed, Muhammed; Bani, Sarang; Natarajan, Sankaran; Pandey, Anjali; S, Naveed

    2017-01-01

    3'-Hydroxypterostilbene (3'-HPT) is one of the active constituents of Sphaerophysa salsula and Pterocarpus marsupium. Despite many proposed therapeutic applications, the safety profile of 3'-HPT has not been established. The present work investigated 90 day repeated oral dose and reproductive (developmental) toxicity of 3'-HPT as a test substance in rats as per OECD guidelines. 90 day toxicity was conducted in sixty Sprague Dawley rats of each sex (120 rats), grouped into six dosage groups of 0 (control), 0 (control recovery), 20 (low dose), 80 (mid dose), 200 (high dose) and 200 (high dose recovery) mg/kg bwt/day (body weight/day) respectively. For the reproductive toxicity study forty Wistar rats of each sex (80 rats) divided into four dosage groups received 0 (vehicle control), 20 (low dose), 100 (mid dose) and 200 (high dose) mg/kg bwt/day of 3'-HPT respectively for a period of two weeks while pre-mating, mating, on the day before sacrifice, in females during pregnancy and four days of lactation period. Results showed no significant differences in body weight, food intake, absolute organ weight, haematology, with no adverse effects (toxicity) on biochemical values nor any abnormal clinical signs or behavioural changes were observed in any of the control/treatment groups, including reproductive and developmental parameters, gross and histopathological changes. In conclusion, the results suggested a No-Observed-Adverse-Effect-Level (NOAEL) of 200 mg/kg bwt/day in rats after oral administration, implying 3'-HPT did not exhibit any toxicity under the study conditions employed.

  5. Investigation of repeated dose (90 day oral toxicity, reproductive/developmental toxicity and mutagenic potential of ‘Calebin A’

    Directory of Open Access Journals (Sweden)

    Muhammed Majeed

    2015-01-01

    Full Text Available The present work investigated repeated dose and reproductive toxicity of Calebin A in Wistar rats. A study for assessing the mutagenic potential of Calebin A through an AMES test is also described. Calebin A was orally administered to groups of 10 male and/or 10 female Wistar rats each, assigned to three dose levels (20, 50 and 100 mg/kg/body weight once daily for 90 consecutive days. None of the animals in any of the treatment/control groups exhibited any abnormal clinical signs/behavioral changes, reproductive as well as developmental parameters, or gross and microscopic changes in both male and female rats. Calebin A was also evaluated for its ability to induce reverse mutations at selected loci of Salmonella typhimurium in the presence and absence of Aroclor 1254 induced rat liver S9 cell lines. In conclusion, 100 mg/kg/d of Calebin A is not likely to produce any significant toxic effects in male and female Wistar rats and no reproductive or developmental toxicity was observed at the same dose and hence Calebin A at 100 mg/kg was determined as “No Observed Adverse Effect Level (NOAEL” under the test conditions.

  6. Toxicological assessment of heavy straight run naphtha in a repeated dose/reproductive toxicity screening test.

    Science.gov (United States)

    McKee, Richard H; Steup, David; Schreiner, Ceinwen; Podhasky, Paula; Malley, Linda A; Roberts, Linda

    2014-01-01

    Gasoline blending stocks (naphthas) are comprised of normal, iso- and cycloparaffins and aromatic hydrocarbons with carbon numbers ranging from C4 to C12. Heavy straight run naphtha (HSRN, CAS number 64741-41-9) was selected for toxicity screening because substances of this type contain relatively high levels (28%) of cycloparaffins by comparison to other naphtha streams and the data complement toxicity information on other gasoline blending streams. Rats were exposed by inhalation to wholly vaporized material at levels of approximately 100, 500, or 3000 parts per million (ppm) daily to screen the potential for systemic toxicity, neurotoxicity, reproductive toxicity, and developmental effects to postnatal day 4. All animals survived the treatment period. Principal effects of repeated exposure included increased liver weights in males and females, increased kidney weights in males, and histological changes in the thyroid, secondary to liver enzyme induction. These changes were not considered to be toxicologically meaningful and are not relevant to humans. There were no treatment-related effects in functional observation tests or motor activity; no significant reductions in fertility or changes in other reproductive parameters; and no evidence of developmental toxicity in offspring. The overall no observed adverse effect concentration was 3000 ppm (approximately 13, 600 mg/m(3)). In conclusion the HSRN effects on liver and kidney are consistent with the results of other studies of volatile fractions or other naphthas or formulated gasoline, and there were no HSRN effects on neurological developmental or reproductive parameters.

  7. Strengths and limitations of using repeat-dose toxicity studies to predict effects on fertility.

    Science.gov (United States)

    Dent, M P

    2007-08-01

    The upcoming European chemicals legislation REACH (Registration, Evaluation, and Authorisation of Chemicals) will require the risk assessment of many thousands of chemicals. It is therefore necessary to develop intelligent testing strategies to ensure that chemicals of concern are identified whilst minimising the testing of chemicals using animals. Xenobiotics may perturb the reproductive cycle, and for this reason several reproductive studies are recommended under REACH. One of the endpoints assessed in this battery of tests is mating performance and fertility. Animal tests that address this endpoint use a relatively large number of animals and are also costly in terms of resource, time, and money. If it can be shown that data from non-reproductive studies such as in-vitro or repeat-dose toxicity tests are capable of generating reliable alerts for effects on fertility then some animal testing may be avoided. Available rat sub-chronic and fertility data for 44 chemicals that have been classified by the European Union as toxic to fertility were therefore analysed for concordance of effects. Because it was considered appropriate to read across data for some chemicals these data sets were considered relevant for 73 of the 102 chemicals currently classified as toxic to reproduction (fertility) under this system. For all but 5 of these chemicals it was considered that a well-performed sub-chronic toxicity study would have detected pathology in the male, and in some cases, the female reproductive tract. Three showed evidence of direct interaction with oestrogen or androgen receptors (linuron, nonylphenol, and fenarimol). The remaining chemicals (quinomethionate and azafenidin) act by modes of action that do not require direct interaction with steroid receptors. However, both these materials caused in-utero deaths in pre-natal developmental toxicity studies, and the relatively low NOAELs and the nature of the hazard identified in the sub-chronic tests provides an alert

  8. Stages and conformations of the Tau repeat domain during aggregation and its effect on neuronal toxicity.

    Science.gov (United States)

    Kumar, Satish; Tepper, Katharina; Kaniyappan, Senthilvelrajan; Biernat, Jacek; Wegmann, Susanne; Mandelkow, Eva-Maria; Müller, Daniel J; Mandelkow, Eckhard

    2014-07-18

    Several neurodegenerative diseases are characterized by the aggregation and posttranslational modifications of Tau protein. Its "repeat domain" (TauRD) is mainly responsible for the aggregation properties, and oligomeric forms are thought to dominate the toxic effects of Tau. Here we investigated the conformational transitions of this domain during oligomerization and aggregation in different states of β-propensity and pseudo-phosphorylation, using several complementary imaging and spectroscopic methods. Although the repeat domain generally aggregates more readily than full-length Tau, its aggregation was greatly slowed down by phosphorylation or pseudo-phosphorylation at the KXGS motifs, concomitant with an extended phase of oligomerization. Analogous effects were observed with pro-aggregant variants of TauRD. Oligomers became most evident in the case of the pro-aggregant mutant TauRDΔK280, as monitored by atomic force microscopy, and the fluorescence lifetime of Alexa-labeled Tau (time-correlated single photon counting (TCSPC)), consistent with its pronounced toxicity in mouse models. In cell models or primary neurons, neither oligomers nor fibrils of TauRD or TauRDΔK280 had a toxic effect, as seen by assays with lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, respectively. However, oligomers of pro-aggregant TauRDΔK280 specifically caused a loss of spine density in differentiated neurons, indicating a locally restricted impairment of function. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Stages and Conformations of the Tau Repeat Domain during Aggregation and Its Effect on Neuronal Toxicity*

    Science.gov (United States)

    Kumar, Satish; Tepper, Katharina; Kaniyappan, Senthilvelrajan; Biernat, Jacek; Wegmann, Susanne; Mandelkow, Eva-Maria; Müller, Daniel J.; Mandelkow, Eckhard

    2014-01-01

    Several neurodegenerative diseases are characterized by the aggregation and posttranslational modifications of Tau protein. Its “repeat domain” (TauRD) is mainly responsible for the aggregation properties, and oligomeric forms are thought to dominate the toxic effects of Tau. Here we investigated the conformational transitions of this domain during oligomerization and aggregation in different states of β-propensity and pseudo-phosphorylation, using several complementary imaging and spectroscopic methods. Although the repeat domain generally aggregates more readily than full-length Tau, its aggregation was greatly slowed down by phosphorylation or pseudo-phosphorylation at the KXGS motifs, concomitant with an extended phase of oligomerization. Analogous effects were observed with pro-aggregant variants of TauRD. Oligomers became most evident in the case of the pro-aggregant mutant TauRDΔK280, as monitored by atomic force microscopy, and the fluorescence lifetime of Alexa-labeled Tau (time-correlated single photon counting (TCSPC)), consistent with its pronounced toxicity in mouse models. In cell models or primary neurons, neither oligomers nor fibrils of TauRD or TauRDΔK280 had a toxic effect, as seen by assays with lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, respectively. However, oligomers of pro-aggregant TauRDΔK280 specifically caused a loss of spine density in differentiated neurons, indicating a locally restricted impairment of function. PMID:24825901

  10. Renal Toxicity of Nickel,Sodium Lauryl Sulphate and Their Combination after Dermal Application in Guinea Pigs

    Institute of Scientific and Technical Information of China (English)

    A.K.MATHUR; B.N.GUPTA; 等

    1993-01-01

    The guinea pigs were dermally exposed to nickel(Ni).sodium lauryl sulphate(SLS)and in their combination for 7 and 14 days.The exposure to Ni and SLS produced changes in enzymes and lipid peroxidation in kidney.The exposure to Ni or SLS epicted slight changes while combined exposure to Ni plus SLS exhibited more degenerative changes in kidney.The result of the study suggests that industrial workers and/or populations exposed simultaneously to Ni and SLS produces more damage to kidney.

  11. [Twenty-eight days repeated dose toxicity test of N-(fluorodichloromethylthio)phthalimide in rats].

    Science.gov (United States)

    Matsushima, Y; Tsuda, M; Naito, K; Saitoh, M; Isama, K; Ikarashi, Y; Kawasaki, Y; Momma, J; Kitajima, S; Kaniwa, M

    1995-01-01

    N-(Fluorodichloromethylthio)phthalimide (Fluor-folpet) has been widely used as an anti-mold and anti-bacterial agent. In this study, 28 days repeated-dose oral toxicity study of fluor-folpet was carried out in Slc:Wistar rats. An oral toxicity study for fluor-folpet, the twenty-eight days test, repeated-dose, oral administration, was performed as follows: Five week-old rats, male and female, 10 rats, each/group, were treated with intragastric administration of fluor-folpet with a dose of 0 (1% Sodium CMC, control), 20, 80 and 320 mg/kg, body weight. Recovery test, for 14 days after the last treatment, was examined for the control and the 320 mg/kg groups. The 320 mg/kg groups, both males and females, showed significantly reduced their body-weight gain compared with the control group. In the 320 mg/kg group, five out of 20 male rats and four out of 20 female rats died from dyspnea during the treatment period. In the female rats in the 320 mg/kg group, serum ChE level was decreased to 50% of control level and gamma-GT was increased in a dose-dependent manner, but these serum levels recovered after 14 days non-treatment period. No histopathological change, relating to the treatment, in liver was observed. Increased weight of the kidney and vacuolation in renal tubules were found in both sexes of 320 mg/kg group. Hyperkeratosis and hyperplasia of the stomach epithelium were observed at the dose more than 80 mg/kg in male, and more than 20 mg/kg in female. A supplemental study, repeated-dose, oral administration in rats carried out to examine the dyspnea revealed that severe acute toxic damages in epithelium of nasal cavity and meatus nasopharyngeus were induced by intragastric administration of fluor-folpet. Fluor-folpet is shown to be cytotoxic. In conclusion, the no-observed-effect level (NOEL) for fluor-folpet was not found under the experimental conditions employed in this repeated-dose toxicity study.

  12. Investigation of the toxicity of some organophosphorus pesticides in a repeated dose study in rats.

    Science.gov (United States)

    Baconi, Daniela Luiza; Bârcă, Maria; Manda, Gina; Ciobanu, Anne Marie; Bălălău, C

    2013-01-01

    The study aimed to the investigation of the toxicity of organophosphorus pesticides malathion (MLT) and diazinon (DZN) in Wistar rats in a repeated dose study for 35 days. MLT and DZN in corn oil vehicle were oral administered. Body and organs weights, plasma and brain cholinesterase activities, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, histopathological changes in liver and kidney, and some parameters of the immune function, such as leukocyte formula, spleen weight and cellularity, spleen lymphocytes proliferation in response to concanavalin A (Con A) were investigated; the potential oxidative stress (malondialdehyde in plasma and brain, and blood catalase activity) was also evaluated. No clinical toxicity signs attributed to pesticides were noted; no significant changes in the organ weights have been found. Body weight tends slightly to increase, predominantly in DZN treated rats. The results suggest that plasma cholinesterase is more susceptible than brain cholinesterase to the inhibitory effect of DZN and MLT. Other serum biochemical parameters showed no significant difference. DZN produced a marked increase of the number of spleen lymphocytes without a significant gain of the relative spleen weight. The both pesticides produced an increase of the number of mononuclear cells÷weight spleen. The splenic lymphocyte proliferation has not been influenced by MLT or DZN treatment. Histopathological observations identified some changes (vasodilatation, microvacuoles, and granular dystrophy) in the liver, with MLT, inducing macrovacuolar steatosis. The study indicates that repeated exposure, at subclinical doses, to organophosphorus MLT and DZN causes some biochemical, histopathological and immune alterations in rats.

  13. Review of dermal effects and uptake of petroleum hydrocarbons

    Energy Technology Data Exchange (ETDEWEB)

    Kezic, S.; Kruse, J. [Coronel Institute of Occupational Health, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Jakasa, I. [University of Zagreb, Zagreb (Croatia)

    2010-12-15

    This report serves as an update to and an extension of a previous CONCAWE report on dermal absorption of petroleum hydrocarbons (Petroleum hydrocarbons: their absorption through and effects on the skin, CONCAWE Report 84/54, 1984). To contribute to health risk assessments associated with dermal exposure, this report evaluates experimental data to determine the extent to which petroleum hydrocarbons pass through the skin. These data strongly suggest that dermal exposure to petroleum hydrocarbons, even following long-term exposures such as in occupational settings, will not cause systemic toxicity under normal working conditions and assuming an intact skin barrier. Skin contact with some petroleum products may cause skin irritation, leading to dermatitis, particularly after repeated or prolonged exposure. In addition to these irritating effects, the skin barrier function may be affected following repeated contact with petroleum hydrocarbons, making the skin potentially more susceptible to other irritants, sensitizing agents, and bacteria. In addition, the impaired skin barrier may lead to increased dermal penetration of hydrocarbons and other substances. To avoid this there is a need to minimise skin contact.

  14. An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Scala, R.A.; Bevan, C.; Beyer, B.K. (Exxon Biomedical Sciences, Inc., East Millstone, NJ (United States))

    1992-08-01

    A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.

  15. Precise small-molecule recognition of a toxic CUG RNA repeat expansion.

    Science.gov (United States)

    Rzuczek, Suzanne G; Colgan, Lesley A; Nakai, Yoshio; Cameron, Michael D; Furling, Denis; Yasuda, Ryohei; Disney, Matthew D

    2017-02-01

    Excluding the ribosome and riboswitches, developing small molecules that selectively target RNA is a longstanding problem in chemical biology. A typical cellular RNA is difficult to target because it has little tertiary, but abundant secondary structure. We designed allele-selective compounds that target such an RNA, the toxic noncoding repeat expansion (r(CUG)(exp)) that causes myotonic dystrophy type 1 (DM1). We developed several strategies to generate allele-selective small molecules, including non-covalent binding, covalent binding, cleavage and on-site probe synthesis. Covalent binding and cleavage enabled target profiling in cells derived from individuals with DM1, showing precise recognition of r(CUG)(exp). In the on-site probe synthesis approach, small molecules bound adjacent sites in r(CUG)(exp) and reacted to afford picomolar inhibitors via a proximity-based click reaction only in DM1-affected cells. We expanded this approach to image r(CUG)(exp) in its natural context.

  16. Respiratory toxicity of repeated exposure to particles produced by traffic and sugar cane burning.

    Science.gov (United States)

    Mazzoli-Rocha, Flavia; Carvalho, Giovanna M C; Lanzetti, Manuella; Valença, Samuel S; Silva, Luiz F F; Saldiva, Paulo H N; Zin, Walter A; Faffe, Débora S

    2014-01-15

    We compared the toxicity of subchronic exposure to equivalent masses of particles from sugar cane burning and traffic. BALB/c mice received 3 intranasal instillations/week during 1, 2 or 4 weeks of either distilled water (C1, C2, C4) or particles (15μg) from traffic (UP1, UP2, UP4) or biomass burning (BP1, BP2, BP4). Lung mechanics, histology and oxidative stress were analyzed 24h after the last instillation. In all instances UP and BP groups presented worse pulmonary elastance, airway and tissue resistance, alveolar collapse, bronchoconstriction and macrophage influx into the lungs than controls. UP4, BP2 and BP4 presented more alveolar collapse than UP1 and BP1, respectively. UP and BP had worse bronchial and alveolar lesion scores than their controls; BP4 had greater bronchial lesion scores than UP4. Catalase was higher in UP4 and BP4 than in C4. In conclusion, biomass particles were more toxic than those from traffic after repeated exposures.

  17. Repeated exposure to iron oxide nanoparticles causes testicular toxicity in mice.

    Science.gov (United States)

    Sundarraj, Kiruthika; Manickam, Vijayprakash; Raghunath, Azhwar; Periyasamy, Madhivadhani; Viswanathan, Mangala Priya; Perumal, Ekambaram

    2017-02-01

    The aim of this study was to determine whether repeated exposure to iron oxide nanoparticles (Fe2 O3 -NPs) could be toxic to mice testis. Fe2 O3 -NPs (25 and 50 mg/kg) were intraperitoneally administered into mice once a week for 4 weeks. Our study showed that Fe2 O3 -NPs have the ability to cross the blood-testis barrier to get into the testis. The findings showed that exposure resulted in the accumulation of Fe2 O3 -NPs which was evidenced from the iron content and accumulation in the testis. Furthermore, 25 and 50 mg/kg Fe2 O3 -NPs administration increased the reactive oxygen species, lipid peroxidation, protein carbonyl content, glutathione peroxidase activity, and nitric oxide levels with a concomitant decrease in the levels of antioxidants-superoxide dismutase, catalase, glutathione, and vitamin C. Increased expression of Bax, cleaved-caspase-3, and cleaved-PARP confirms apoptosis. Serum testosterone levels increased with increased concentration of Fe2 O3 -NPs exposure. In addition, the histopathological lesions like vacuolization, detachment, and sloughing of germ cells were also observed in response to Fe2 O3 -NPs treatment. The data from our study entailed that testicular toxicity caused by Fe2 O3 -NPs exposure may be associated with Fe2 O3 -NPs accumulation leading to oxidative stress and apoptosis. Therefore, precautions should be taken in the safe use of Fe2 O3 -NPs to avoid complications in the fertility of males. Further research will unravel the possible molecular mechanisms on testicular toxicity of Fe2 O3 -NPs. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 594-608, 2017.

  18. Study of four week repeated dose toxic test of Sweet Bee Venom in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Jae-Seuk Park

    2010-12-01

    Full Text Available Objectives: This study was performed to analyse four week repeated dose toxicity of Sweet Bee Venom(Sweet BV extracted from the bee venom in Beagle dogs. Methods: All experiments were conducted under the regulations of Good Laboratory Practice (GLP at Biotoxtech Company, a non-clinical study authorized institution. Male and female Beagle dogs of 5-6 months old were chosen for the pilot study of four week repeated dose toxicity of Sweet BV which was administered at the level of 0.56㎎/㎏ body weight which is eighty times higher than the clinical application dosage as the high dosage, followed by 0.28 and 0.14㎎/㎏ as midium and low dosage, respectively. Equal amount of excipient(normal saline to the Sweet BV experiment groups was administered as the control group every day for four weeks. Results: 1. No mortality was witnessed in all of the experiment groups. 2. All experiment groups were appealed pain sense in the treating time compared to the control group, and hyperemia and movement disorder were observed around the area of administration in all experiment groups, and higher occurrence in the higher dosage treatment. 3. For weight measurement, Neither male nor female groups showed significant changes. 4. In the urine analysis, CBC and biochemistry didn't show any significant changes in the experiment groups compared with control group. 5. For weight measurement of organs, experiment groups didn't show any significant changes compared with control group. 6. To verify abnormalities of organs and tissues, thigh muscle which treated with Sweet BV, cerebrum, liver, lung, kidney, and spinal cords were removed and conducted histologocal observation with H-E staining. In the histologocal observation of thigh muscle, cell infiltration, inflammatory, degeneration, necrosis of muscle fiber, and fibrosis were found in both thigh tissue. And the changes were depend on the dose of Sweet BV. But another organs were not detected in any abnormalities. 7

  19. Repeat length and RNA expression level are not primary determinants in CUG expansion toxicity in Drosophila models.

    Directory of Open Access Journals (Sweden)

    Gwenn Le Mée

    Full Text Available Evidence for an RNA gain-of-function toxicity has now been provided for an increasing number of human pathologies. Myotonic dystrophies (DM belong to a class of RNA-dominant diseases that result from RNA repeat expansion toxicity. Specifically, DM of type 1 (DM1, is caused by an expansion of CUG repeats in the 3'UTR of the DMPK protein kinase mRNA, while DM of type 2 (DM2 is linked to an expansion of CCUG repeats in an intron of the ZNF9 transcript (ZNF9 encodes a zinc finger protein. In both pathologies the mutant RNA forms nuclear foci. The mechanisms that underlie the RNA pathogenicity seem to be rather complex and not yet completely understood. Here, we describe Drosophila models that might help unravelling the molecular mechanisms of DM1-associated CUG expansion toxicity. We generated transgenic flies that express inducible repeats of different type (CUG or CAG and length (16, 240, 480 repeats and then analyzed transgene localization, RNA expression and toxicity as assessed by induced lethality and eye neurodegeneration. The only line that expressed a toxic RNA has a (CTG(240 insertion. Moreover our analysis shows that its level of expression cannot account for its toxicity. In this line, (CTG(240.4, the expansion inserted in the first intron of CG9650, a zinc finger protein encoding gene. Interestingly, CG9650 and (CUG(240.4 expansion RNAs were found in the same nuclear foci. In conclusion, we suggest that the insertion context is the primary determinant for expansion toxicity in Drosophila models. This finding should contribute to the still open debate on the role of the expansions per se in Drosophila and in human pathogenesis of RNA-dominant diseases.

  20. Corneal epithelial toxicity of antiglaucoma formulations: in vitro study of repeated applications

    Directory of Open Access Journals (Sweden)

    Meloni M

    2012-09-01

    Timogel. Expression of OCLN, a sign of epithelial barrier impairment, was only significantly upregulated at 24 hours by BAK 0.01%, suggesting a toxic reaction at the ocular surface. OCLN was also overexpressed after repeated application of Nyogel and Timogel.Conclusion: Overall, the multiple endpoint analysis approach allows classification of these products according to decreasing order of irritation potential as follows: BAK 0.01%, Timoptol, Nyogel, Timogel, and Timolabak.Keywords: occludin, gene expression, interleukin-1α, eye compatibility, human corneal epithelium

  1. Correlation of inter-locus polyglutamine toxicity with CAG•CTG triplet repeat expandability and flanking genomic DNA GC content.

    Directory of Open Access Journals (Sweden)

    Colm E Nestor

    Full Text Available Dynamic expansions of toxic polyglutamine (polyQ-encoding CAG repeats in ubiquitously expressed, but otherwise unrelated, genes cause a number of late-onset progressive neurodegenerative disorders, including Huntington disease and the spinocerebellar ataxias. As polyQ toxicity in these disorders increases with repeat length, the intergenerational expansion of unstable CAG repeats leads to anticipation, an earlier age-at-onset in successive generations. Crucially, disease associated alleles are also somatically unstable and continue to expand throughout the lifetime of the individual. Interestingly, the inherited polyQ length mediating a specific age-at-onset of symptoms varies markedly between disorders. It is widely assumed that these inter-locus differences in polyQ toxicity are mediated by protein context effects. Previously, we demonstrated that the tendency of expanded CAG•CTG repeats to undergo further intergenerational expansion (their 'expandability' also differs between disorders and these effects are strongly correlated with the GC content of the genomic flanking DNA. Here we show that the inter-locus toxicity of the expanded polyQ tracts of these disorders also correlates with both the expandability of the underlying CAG repeat and the GC content of the genomic DNA flanking sequences. Inter-locus polyQ toxicity does not correlate with properties of the mRNA or protein sequences, with polyQ location within the gene or protein, or steady state transcript levels in the brain. These data suggest that the observed inter-locus differences in polyQ toxicity are not mediated solely by protein context effects, but that genomic context is also important, an effect that may be mediated by modifying the rate at which somatic expansion of the DNA delivers proteins to their cytotoxic state.

  2. Repeat associated non-ATG translation initiation: one DNA, two transcripts, seven reading frames, potentially nine toxic entities!

    Directory of Open Access Journals (Sweden)

    Christopher E Pearson

    2011-03-01

    Full Text Available Diseases associated with unstable repetitive elements in the DNA, RNA, and amino acids have consistently revealed scientific surprises. Most diseases are caused by expansions of trinucleotide repeats, which ultimately lead to diseases like Huntington's disease, myotonic dystrophy, fragile X syndrome, and a series of spinocerebellar ataxias. These repeat mutations are dynamic, changing through generations and within an individual, and the repeats can be bi-directionally transcribed. Unsuspected modes of pathogenesis involve aberrant loss of protein expression; aberrant over-expression of non-mutant proteins; toxic-gain-of-protein function through expanded polyglutamine tracts that are encoded by expanded CAG tracts; and RNA-toxic-gain-of-function caused by transcripts harboring expanded CUG, CAG, or CGG tracts. A recent advance reveals that RNA transcripts with expanded CAG repeats can be translated in the complete absence of a starting ATG, and this Repeat Associated Non-ATG translation (RAN-translation occurs across expanded CAG repeats in all reading frames (CAG, AGC, and GCA to produce homopolymeric proteins of long polyglutamine, polyserine, and polyalanine tracts. Expanded CTG tracts expressing CUG transcripts also show RAN-translation occurring in all three frames (CUG, UGC, and GCU, to produce polyleucine, polycysteine, and polyalanine. These RAN-translation products can be toxic. Thus, one unstable (CAG•(CTG DNA can produce two expanded repeat transcripts and homopolymeric proteins with reading frames (the AUG-directed polyGln and six RAN-translation proteins, yielding a total of potentially nine toxic entities. The occurrence of RAN-translation in patient tissues expands our horizons of modes of disease pathogenesis. Moreover, since RAN-translation counters the canonical requirements of translation initiation, many new questions are now posed that must be addressed. This review covers RAN-translation and some of the pertinent

  3. Mammalian Toxicity of Munitions Compounds. Phase I. Acute Oral Toxicity, Primary Skin and Eye Irritation, Dermal Sensitization, Disposition and Metabolism and Ames Tests of Additional Compounds

    Science.gov (United States)

    1978-12-08

    Assay of 300 Chemicals, Proc. Nat. Acad. Sci., 72:5135-5139, 1975. 17. Wang, C. Y., K. Muraoka, and G. T. Bryan, Yatagenicity of Nitrofurans ...L. H. DiSalvo, and J. Ng, Toxicity and Mutagenicity of 2,4,6-Trinitrotoluene and Its Microbial Metabolites , Appl. Environ. Microbiol., 31:576-580

  4. The OSIRIS Weight of Evidence approach: ITS for the endpoints repeated-dose toxicity (RepDose ITS)

    NARCIS (Netherlands)

    Tluczkiewicz, I.; Batke, M.; Kroese, D.; Buist, H.; Aldenberg, T.; Pauné, E.; Grimm, H.; Kühne, R.; Schüürmann, G.; Mangelsdorf, I.; Escher, S.E.

    2013-01-01

    In the FP6 European project OSIRIS, Integrated Testing Strategies (ITSs) for relevant toxicological endpoints were developed to avoid new animal testing and thus to reduce time and costs. The present paper describes the development of an ITS for repeated-dose toxicity called RepDose ITS which evalua

  5. Alteration in metabolism and toxicity of acetaminophen upon repeated administration in rats.

    Science.gov (United States)

    Kim, Sun J; Lee, Min Y; Kwon, Do Y; Kim, Sung Y; Kim, Young C

    2009-10-01

    Our previous studies showed that administration of a subtoxic dose of acetaminophen (APAP) to female rats increased generation of carbon monoxide from dichloromethane, a metabolic reaction catalyzed mainly by cytochrome P450 (CYP) 2E1. In this study we examined the changes in metabolism and toxicity of APAP upon repeated administration. An intraperitoneal dose of APAP (500 mg/kg) alone did not increase aspartate aminotransferase, alanine aminotransferase, or sorbitol dehydrogenase activity in serum, but was significantly hepatotoxic when the rats had been pretreated with an identical dose of APAP 18 h earlier. The concentrations and disappearance of APAP and its metabolites in plasma were monitored for 8 h after the treatment. APAP pretreatment reduced the elevation of APAP-sulfate, but increased APAP-cysteine concentrations in plasma. APAP or APAP-glucuronide concentrations were not altered. Administration of a single dose of APAP 18 h before sacrifice increased microsomal CYP activities measured with p-nitrophenol, p-nitroanisole, and aminopyrine as probes. Expression of CYP2E1, CYP3A, and CYP1A proteins in the liver was also elevated significantly. The results suggest that administration of APAP at a subtoxic dose may result in an induction of hepatic CYP enzymes, thereby altering metabolism and toxicological consequences of various chemical substances that are substrates for the same enzyme system.

  6. Estimation of acute oral toxicity using the No Observed Adverse Effect Level (NOAEL) from the 28 day repeated dose toxicity studies in rats.

    Science.gov (United States)

    Bulgheroni, Anna; Kinsner-Ovaskainen, Agnieszka; Hoffmann, Sebastian; Hartung, Thomas; Prieto, Pilar

    2009-02-01

    Acute systemic toxicity is one of the areas of particular concern due to the 2009 deadline set by the 7th Amendment of the Cosmetics Directive (76/768/EEC), which introduces a testing and marketing ban of cosmetic products with ingredients tested on animals. The scientific community is putting considerable effort into developing and validating non-animal alternatives in this area. However, it is unlikely that validated and regulatory accepted alternative methods and/or strategies will be available in March 2009. Following the initiatives undertaken in the pharmaceutical industry to waive the acute oral toxicity testing before going to clinical studies by using information from other in vivo studies, we proposed an approach to identify non-toxic compounds (LD50>2000mg/kg) using information from 28 days repeated dose toxicity studies. Taking into account the high prevalence of non-toxic substances (87%) in the New Chemicals Database, it was possible to set a NOAEL threshold of 200mg/kg that allowed the correct identification of 63% of non-toxic compounds, while testing of cosmetic ingredients.

  7. Problems and solutions for the analysis of somatic CAG repeat expansion and their relationship to Huntington's disease toxicity.

    Science.gov (United States)

    Budworth, Helen; McMurray, Cynthia T

    2016-01-01

    Huntington's Disease is caused by inheritance of a single disease-length allele harboring an expanded CAG repeat, which continues to expand in somatic tissues with age. Whether somatic expansion contributed to toxicity was unknown. From extensive work from multiple laboratories, it has been made clear that toxicity depended on length of the inherited allele, but whether preventing or delaying somatic repeat expansion in vivo would be beneficial was unknown, since the inherited disease allele was still expressed. In Budworth et al., we provided definitive evidence that suppressing the somatic expansion in mice substantially delays disease onset in littermates that inherit the same disease-length allele. This key discovery opens the door for therapeutic approaches targeted at stopping or shortening the CAG tract during life. The analysis was difficult and, at times, non-standard. Here, we take the opportunity to discuss the challenges, the analytical solutions, and to address some controversial issues with respect to expansion biology.

  8. Effect of silver/copper and copper oxide nanoparticle powder on growth of Gram-negative and Gram-positive bacteria and their toxicity against the normal human dermal fibroblasts

    Science.gov (United States)

    Peszke, Jerzy; Nowak, Anna; Szade, Jacek; Szurko, Agnieszka; Zygadło, Dorota; Michałowska, Marlena; Krzyściak, Paweł; Zygoń, Patrycja; Ratuszna, Alicja; Ostafin, Marek M.

    2016-12-01

    Engineered nanomaterials, especially metallic nanoparticles, are the most popular system applied in daily life products. The study of their biological and toxicity properties seems to be indispensable. In this paper, we present results of biological activity of Ag/Cu nanoparticles. These nanoparticles show more promising killing/inhibiting properties on Gram-negative bacteria than for Gram-positive ones. The Gram-negative bacteria show strong effect already at the concentration of 1 ppm after 15 min of incubation. Moreover, in vitro tests of toxicity made on normal human dermal fibroblast cultures showed that after 72 h of incubation with Ag/Cu nanoparticles, they are less toxic then Cu2O/CuO nanoparticles.

  9. Repeated-Doses Toxicity Study of the Essential Oil of Hyptis martiusii Benth. (Lamiaceae in Swiss Mice

    Directory of Open Access Journals (Sweden)

    Germana Freire Rocha Caldas

    2013-01-01

    Full Text Available Hyptis martiusii Benth. (Lamiaceae is found in abundance in Northeastern Brazil where it is used in traditional medicine to treat gastric disorders. Since there are no studies reporting the toxicity and safety profile of this species, we investigated repeated-doses toxicity of the essential oil of Hyptis martiusii (EOHM. Swiss mice of both sexes were orally treated with EOHM (100 and 500 mg/kg for 30 days, and biochemical, hematological, and morphological parameters were determined. No toxicity signs or deaths were recorded during the treatment with EOHM. The body weight gain was not affected, but there was an occasional variation in water and food consumption among mice of both sexes treated with both doses. The hematological and biochemical profiles did not show significant differences except for a decrease in the MCV and an increase in albumin, but these variations are within the limits described for the species. The microscopic analysis showed changes in liver, kidneys, lungs, and spleen; however, these changes do not have clinical relevance since they varied among the groups, including the control group. The results indicate that the treatment of repeated-doses with the essential oil of Hyptis martiusii showed low toxicity in mice.

  10. Repeated measures dose-finding design with time-trend detection in the presence of correlated toxicity data.

    Science.gov (United States)

    Yin, Jun; Paoletti, Xavier; Sargent, Daniel J; Mandrekar, Sumithra J

    2017-08-01

    Phase I trials are designed to determine the safety, tolerability, and recommended phase 2 dose of therapeutic agents for subsequent testing. The dose-finding paradigm has thus traditionally focused on identifying the maximum tolerable dose of an agent or combination therapy under the assumption that there is a non-decreasing relationship between dose-toxicity and dose-efficacy. The dose is typically determined based on the probability of severe toxicity observed during the first treatment cycle. A novel endpoint, the total toxicity profile, was previously developed to account for the multiple toxicity types and grades experienced in the first cycle. More recently, this was extended to a repeated measures design based on the total toxicity profile to account for longitudinal toxicities over multiple treatment cycles in the absence of within-patient correlation. In this work, we propose to extend the design in the presence of within-patient correlation. Furthermore, we provide a framework to detect a toxicity time trend (toxicity increasing, decreasing, or stable) over multiple treatment cycles. We utilize a linear mixed model in the Bayesian framework, with the addition of Bayesian risk functions for decision-making in dose assignment. The performance of this design was evaluated using simulation studies and real data from a phase I trial. We demonstrated that using available toxicity data from all cycles of treatment improves the accuracy of maximum tolerated dose identification and allows for the detection of a time trend. The performance is consistent regardless of the strength of the within-patient correlation. In addition, the use of a quasi-continuous total toxicity profile score significantly increased the power to detect time trends compared to when binary data only were used. The increased interest in molecularly targeted agents and immunotherapies in oncology necessitates innovative phase I study designs. Our proposed framework provides a tool to tackle

  11. Changes of lead speciation and microbial toxicity in soil treated with repeated Pb exposure in the presence of BDE209.

    Science.gov (United States)

    Zhang, Rong; Zhang, Wei; Liu, Gao; Lin, Kuangfei; Fu, Rongbing

    2016-03-01

    Lead (Pb) and decabromodiphenyl ether (BDE209) are main pollutants at electric waste (e-waste) recycling sites (EWRSs), and their joint toxicological effects have received extensive attention. Frequently, soil pollution at EWRSs usually results from the occurrence of repeated single or multiple pollution events, with continuous impacts on soil microorganisms. Therefore, a laboratory incubation study was conducted to determine Pb bioavailability and microbial toxicity in repeated Pb-polluted soil in the presence of BDE209 for the first time. We evaluated the impacts of repetitive exposure trials on chemical fractions of Pb, and the results showed that repeated single Pb pollution event resulted in an increase of carbonates fraction of Pb, which was different from one-off single Pb exposure. Moreover, one-off Pb-treated groups exhibited higher I R (reduced partition index) values on day 30 and all treatments remained the same I R level at the end of incubation period. The parameters of microbial toxicity were well reflected by soil enzymes. During the entire incubation, the dehydrogenase and urease activities were significantly inhibited by Pb (P soil enzymes were clearly observed (P < 0.05 or 0.01). Such observations would provide useful information for ecological effects of Pb and BDE209 at EWRSs.

  12. The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing.

    Science.gov (United States)

    Kohonen, Pekka; Benfenati, Emilio; Bower, David; Ceder, Rebecca; Crump, Michael; Cross, Kevin; Grafström, Roland C; Healy, Lyn; Helma, Christoph; Jeliazkova, Nina; Jeliazkov, Vedrin; Maggioni, Silvia; Miller, Scott; Myatt, Glenn; Rautenberg, Michael; Stacey, Glyn; Willighagen, Egon; Wiseman, Jeff; Hardy, Barry

    2013-01-01

    The aim of the SEURAT-1 (Safety Evaluation Ultimately Replacing Animal Testing-1) research cluster, comprised of seven EU FP7 Health projects co-financed by Cosmetics Europe, is to generate a proof-of-concept to show how the latest technologies, systems toxicology and toxicogenomics can be combined to deliver a test replacement for repeated dose systemic toxicity testing on animals. The SEURAT-1 strategy is to adopt a mode-of-action framework to describe repeated dose toxicity, combining in vitro and in silico methods to derive predictions of in vivo toxicity responses. ToxBank is the cross-cluster infrastructure project whose activities include the development of a data warehouse to provide a web-accessible shared repository of research data and protocols, a physical compounds repository, reference or "gold compounds" for use across the cluster (available via wiki.toxbank.net), and a reference resource for biomaterials. Core technologies used in the data warehouse include the ISA-Tab universal data exchange format, REpresentational State Transfer (REST) web services, the W3C Resource Description Framework (RDF) and the OpenTox standards. We describe the design of the data warehouse based on cluster requirements, the implementation based on open standards, and finally the underlying concepts and initial results of a data analysis utilizing public data related to the gold compounds. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. The OSIRIS Weight of Evidence approach: ITS for the endpoints repeated-dose toxicity (RepDose ITS).

    Science.gov (United States)

    Tluczkiewicz, Inga; Batke, Monika; Kroese, Dinant; Buist, Harrie; Aldenberg, Tom; Pauné, Eduard; Grimm, Helvi; Kühne, Ralph; Schüürmann, Gerrit; Mangelsdorf, Inge; Escher, Sylvia E

    2013-11-01

    In the FP6 European project OSIRIS, Integrated Testing Strategies (ITSs) for relevant toxicological endpoints were developed to avoid new animal testing and thus to reduce time and costs. The present paper describes the development of an ITS for repeated-dose toxicity called RepDose ITS which evaluates the conditions under which in vivo non-guideline studies are reliable. In a tiered approach three aspects of these "non-guideline" studies are assessed: the documentation of the study (reliability), the quality of the study design (adequacy) and the scope of examination (validity). The reliability is addressed by the method "Knock-out criteria", which consists of four essential criteria for repeated-dose toxicity studies. A second tool, termed QUANTOS (Quality Assessment of Non-guideline Toxicity Studies), evaluates and weights the adequacy of the study by using intra-criterion and inter-criteria weighting. Finally, the Coverage approach calculates a probability that the detected Lowest-Observed-Effect-Level (LOEL) is similar to the LOEL of a guideline study dependent on the examined targets and organs of the non-guideline study. If the validity and adequacy of the non-guideline study are insufficient for risk assessment, the ITS proposes to apply category approach or the Threshold of Toxicological Concern (TTC) concept, and only as a last resort new animal-testing.

  14. Evaluation of electric arc furnace-processed steel slag for dermal corrosion, irritation, and sensitization from dermal contact.

    Science.gov (United States)

    Suh, Mina; Troese, Matthew J; Hall, Debra A; Yasso, Blair; Yzenas, John J; Proctor, Debora M

    2014-12-01

    Electric arc furnace (EAF) steel slag is alkaline (pH of ~11-12) and contains metals, most notably chromium and nickel, and thus has potential to cause dermal irritation and sensitization at sufficient dose. Dermal contact with EAF slag occurs in many occupational and environmental settings because it is used widely in construction and other industrial sectors for various applications including asphaltic paving, road bases, construction fill, and as feed for cement kilns construction. However, no published study has characterized the potential for dermal effects associated with EAF slag. To assess dermal irritation, corrosion and sensitizing potential of EAF slag, in vitro and in vivo dermal toxicity assays were conducted based on the Organisation for Economic Co-operation and Development (OECD) guidelines. In vitro dermal corrosion and irritation testing (OECD 431 and 439) of EAF slag was conducted using the reconstructed human epidermal (RHE) tissue model. In vivo dermal toxicity and delayed contact sensitization testing (OECD 404 and 406) were conducted in rabbits and guinea pigs, respectively. EAF slag was not corrosive and not irritating in any tests. The results of the delayed contact dermal sensitization test indicate that EAF slag is not a dermal sensitizer. These findings are supported by the observation that metals in EAF slag occur as oxides of low solubility with leachates that are well below toxicity characteristic leaching procedure (TCLP) limits. Based on these results and in accordance to the OECD guidelines, EAF slag is not considered a dermal sensitizer, corrosive or irritant.

  15. Toxic PR poly-dipeptides encoded by the C9orf72 repeat expansion target LC domain polymers

    Science.gov (United States)

    Lin, Yi; Mori, Eiichiro; Kato, Masato; Xiang, Siheng; Wu, Leeju; Kwon, Ilmin; McKnight, Steven L.

    2016-01-01

    Summary Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding, and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene to message to protein. PMID:27768897

  16. Toxic PR Poly-Dipeptides Encoded by the C9orf72 Repeat Expansion Target LC Domain Polymers.

    Science.gov (United States)

    Lin, Yi; Mori, Eiichiro; Kato, Masato; Xiang, Siheng; Wu, Leeju; Kwon, Ilmin; McKnight, Steven L

    2016-10-20

    Two complementary approaches were used in search of the intracellular targets of the toxic PR poly-dipeptide encoded by the repeat sequences expanded in the C9orf72 form of amyotrophic lateral sclerosis. The top categories of PRn-bound proteins include constituents of non-membrane invested cellular organelles and intermediate filaments. PRn targets are enriched for the inclusion of low complexity (LC) sequences. Evidence is presented indicating that LC sequences represent the direct target of PRn binding and that interaction between the PRn poly-dipeptide and LC domains is polymer-dependent. These studies indicate that PRn-mediated toxicity may result from broad impediments to the dynamics of cell structure and information flow from gene to message to protein.

  17. The genomic landscape of rapid, repeated evolutionary rescue from toxic pollution in wild fish

    Science.gov (United States)

    Several populations of Atlantic killifish (Fundulus heteroclitus) in contaminated Atlantic coast estuaries have evolved resistance to the toxic effects of PCBs, dioxins, and PAHs. However, the genetic mechanisms of resistance and whether they are shared among populations is not known. We sequenced t...

  18. Dermal uptake of petroleum substances.

    Science.gov (United States)

    Jakasa, Ivone; Kezic, Sanja; Boogaard, Peter J

    2015-06-01

    Petroleum products are complex substances comprising varying amounts of linear and branched alkanes, alkenes, cycloalkanes, and aromatics which may penetrate the skin at different rates. For proper interpretation of toxic hazard data, understanding their percutaneous absorption is of paramount importance. The extent and significance of dermal absorption of eight petroleum substances, representing different classes of hydrocarbons, was evaluated. Literature data on the steady-state flux and permeability coefficient of these substances were evaluated and compared to those predicted by mathematical models. Reported results spanned over 5-6 orders of magnitude and were largely dependent on experimental conditions in particular on the type of the vehicle used. In general, aromatic hydrocarbons showed higher dermal absorption than more lipophilic aliphatics with similar molecular weight. The results showed high variation and were largely influenced by experimental conditions emphasizing the need of performing the experiments under "in use" scenario. The predictive models overestimated experimental absorption. The overall conclusion is that, based on the observed percutaneous penetration data, dermal exposure to petroleum hydrocarbons, even of aromatics with highest dermal absorption is limited and highly unlikely to be associated with health risks under real use scenarios. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  19. Toxicity from repeated doses of acetaminophen in children: assessment of causality and dose in reported cases.

    Science.gov (United States)

    Heard, Kennon; Bui, Alison; Mlynarchek, Sara L; Green, Jody L; Bond, G Randall; Clark, Richard F; Kozer, Eran; Koff, Raymond S; Dart, Richard C

    2014-01-01

    Liver injury has been reported in children treated with repeated doses of acetaminophen. The objective of this study was to identify and validate reports of liver injury or death in children younger than 6 years who were administered repeated therapeutic doses of acetaminophen. We reviewed US Poison Center data, peer-reviewed literature, US Food and Drug Administration Adverse Event Reports, and US Manufacturer Safety Reports describing adverse effects after acetaminophen administration. Reports that described hepatic abnormalities (description of liver injury or abnormal laboratory testing) or death after acetaminophen administration to children younger than 6 years were included. The identified reports were double abstracted and then reviewed by an expert panel to determine if the hepatic injury was related to acetaminophen and whether the dose of acetaminophen was therapeutic (≤75 mg/kg) or supratherapeutic. Our search yielded 2531 reports of adverse events associated with acetaminophen use. From these cases, we identified 76 cases of hepatic injury and 26 deaths associated with repeated acetaminophen administration. There were 6 cases of hepatic abnormalities and no deaths associated with what our panel determined to be therapeutic doses. A large proportion of cases could not be fully evaluated due to incomplete case reporting. Although we identified numerous examples of liver injury and death after repeated doses of acetaminophen, all the deaths and all but 6 cases of hepatic abnormalities involved doses more than 75 mg/kg per day. This study suggests that the doses of less than 75 mg/kg per day of acetaminophen are safe for children younger than 6 years.

  20. Repeated dose oral toxicity of inorganic mercury in wistar rats: biochemical and morphological alterations

    Directory of Open Access Journals (Sweden)

    M. D. Jegoda

    2013-06-01

    Full Text Available Aim: The study was conducted to find out the possible toxic effect of mercuric chloride (HgCl2 at the histological, biochemical, and haematological levels in the wistar rats for 28 days. Materials and Methods: The biochemical and hematological alteration were estimated in four groups of rat (each group contain ten animals, which were treated with 0 (control, 2, 4, and 8 mg/kg body weight of HgCl2 through oral gavage. At the end of study all rats were sacrificed and subjected for histopathology. Result: A significantly (P < 0.05 higher level of serum alanine amino transferase (ALT, gamma Glutamyle Transferase, and creatinine were recorded in treatment groups, while the level of alkaline phosphtase (ALP was significantly decreased as compared to the control group. The toxic effect on hematoclogical parameter was characterized by significant decrease in hemoglobin, packed cell volume, total erythrocytes count, and total leukocyte count. Gross morphological changes include congestion, severe haemorrhage, necrosis, degenerative changes in kidneys, depletion of lymphocyte in spleen, decrease in concentration of mature spermatocyte, and edema in testis. It was notable that kidney was the most affected organ. Conclusion: Mercuric chloride (HgCl caused dose-dependent toxic effects on blood parameters and kidney. [Vet World 2013; 6(8.000: 563-567

  1. Evaluation of arecoline hydrobromide toxicity after a 14-day repeated oral administration in Wistar rats.

    Directory of Open Access Journals (Sweden)

    Xiaojuan Wei

    Full Text Available A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah, to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg, medium-dose group (200 mg/kg, low-dose group (100mg/kg and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05 with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions.

  2. Evaluation of arecoline hydrobromide toxicity after a 14-day repeated oral administration in Wistar rats.

    Science.gov (United States)

    Wei, Xiaojuan; Zhang, Jiyu; Niu, Jianrong; Zhou, Xuzheng; Li, Jianyong; Li, Bing

    2015-01-01

    A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah), to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg), medium-dose group (200 mg/kg), low-dose group (100mg/kg) and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05) with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions.

  3. Toxicity evaluation of zinc aluminium levodopa nanocomposite via oral route in repeated dose study

    Science.gov (United States)

    Kura, Aminu Umar; Cheah, Pike-See; Hussein, Mohd Zobir; Hassan, Zurina; Tengku Azmi, Tengku Ibrahim; Hussein, Nor Fuzina; Fakurazi, Sharida

    2014-05-01

    Nanotechnology, through nanomedicine, allowed drugs to be manipulated into nanoscale sizes for delivery to the different parts of the body, at the same time, retaining the valuable pharmacological properties of the drugs. However, efficient drug delivery and excellent release potential of these delivery systems may be hindered by possible untoward side effects. In this study, the sub-acute toxicity of oral zinc aluminium nanocomposite with and without levodopa was assessed using the Organization for Economic Co-operation and Development guidelines. No sign or symptom of toxicity was observed in orally treated rats with the nanocomposite at 5 and 500 mg/kg concentrations. Body weight gain, feeding, water intake, general survival and organosomatic index were not significantly different between control and treatment groups. Aspartate aminotransferase (AST) in 500 mg/kg levodopa nanocomposite (169 ± 30 U/L), 5 mg/kg levodopa nanocomposite (172 ± 49 U/L), and 500 mg/kg layered double hydroxides (LDH) nanocomposite (175 ± 25 U/L) were notably elevated compared to controls (143 ± 05 U/L); but the difference were not significant ( p > 0.05). However, the differences in aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio of 500 mg/kg levodopa nanocomposite (0.32 ± 0.12) and 500 mg/kg LDH nanocomposite (0.34 ± 0.12) were statistically significant ( p brain was found to be of similar morphology in both control and experimental groups. The kidneys of 500-mg/kg-treated rats with levodopa nanocomposite and LDH nanocomposite were found to have slight inflammatory changes, notably leukocyte infiltration around the glomeruli. The ultra-structure of the neurons from the substantia nigra of nanocomposite-exposed group was similar to those receiving only normal saline. The observed result has suggested possible liver and renal toxicity in orally administered levodopa intercalated nanocomposite; it is also dose-dependent that needs further assessment.

  4. Metal availability and soil toxicity after repeated croppings of Thlaspi caerulescens in metal contaminated soils

    Energy Technology Data Exchange (ETDEWEB)

    Keller, Catherine; Hammer, Daniel

    2004-09-01

    Metal phytoextraction with hyperaccumulating plants could be a useful method to decontaminate soils, but it is not fully validated yet. In order to quantify the efficiency of Cd and Zn extraction from a calcareous soil with and without Fe amendment and an acidic soil, we performed a pot experiment with three successive croppings of Thlaspi caerulescens followed by 3 months without plant and 7 weeks with lettuce. We used a combined approach to assess total extraction efficiency (2 M HNO{sub 3}-extractable metals), changes in metal bio/availability (0.1 M NaNO{sub 3}-extractable metals and lettuce uptake) and toxicity (lettuce biomass and the BIOMETreg] biosensor). The soil solution was monitored over the whole experiment. In the calcareous soil large Cu concentrations were probably responsible for chlorosis symptoms observed on T. caerulescens. When this soil was treated with Fe, the amount of extracted metal by T. caerulescens increased and metal availability and soil toxicity decreased when compared to the untreated soil. In the acidic soil, T. caerulescens was most efficient: Cd and Zn concentrations in plants were in the range of hyperaccumulation and HNO{sub 3}-extractable Cd and Zn, metal bio/availability, soil toxicity, and Cd and Zn concentrations in the soil solution decreased significantly. However, a reduced Cd concentration measured in the third T. caerulescens cropping indicated a decrease in metal availability below a critical threshold, whereas the increase of dissolved Cd and Zn concentrations after the third cropping may be the early sign of soil re-equilibration. This indicates that phytoextraction efficiency must be assessed by different approaches in order not to overlook any potential hazard and that an efficient phytoextraction scheme will have to take into account the different dynamics of the soil-plant system.

  5. Drosophila melanogaster As a Model Organism to Study RNA Toxicity of Repeat Expansion-Associated Neurodegenerative and Neuromuscular Diseases

    Science.gov (United States)

    Koon, Alex C.; Chan, Ho Yin Edwin

    2017-01-01

    For nearly a century, the fruit fly, Drosophila melanogaster, has proven to be a valuable tool in our understanding of fundamental biological processes, and has empowered our discoveries, particularly in the field of neuroscience. In recent years, Drosophila has emerged as a model organism for human neurodegenerative and neuromuscular disorders. In this review, we highlight a number of recent studies that utilized the Drosophila model to study repeat-expansion associated diseases (READs), such as polyglutamine diseases, fragile X-associated tremor/ataxia syndrome (FXTAS), myotonic dystrophy type 1 (DM1) and type 2 (DM2), and C9ORF72-associated amyotrophic lateral sclerosis/frontotemporal dementia (C9-ALS/FTD). Discoveries regarding the possible mechanisms of RNA toxicity will be focused here. These studies demonstrate Drosophila as an excellent in vivo model system that can reveal novel mechanistic insights into human disorders, providing the foundation for translational research and therapeutic development. PMID:28377694

  6. Screening of repeated dose toxicity data present in SCC(NF)P/SCCS safety evaluations of cosmetic ingredients.

    Science.gov (United States)

    Vinken, Mathieu; Pauwels, Marleen; Ates, Gamze; Vivier, Manon; Vanhaecke, Tamara; Rogiers, Vera

    2012-03-01

    Alternative methods, replacing animal testing, are urgently needed in view of the European regulatory changes in the field of cosmetic products and their ingredients. In this context, a joint research initiative called SEURAT was recently raised by the European Commission and COLIPA, representing the European cosmetics industry, with the overall goal of developing an animal-free repeated dose toxicity testing strategy for human safety assessment purposes. Although cosmetic ingredients are usually harmless for the consumer, one of the initial tasks of this research consortium included the identification of organs that could potentially be affected by cosmetic ingredients upon systemic exposure. The strategy that was followed hereof is described in the present paper and relies on the systematic evaluation, by using a self-generated electronic databank, of published reports issued by the scientific committee of DG SANCO responsible for the safety of cosmetic ingredients. By screening of the repeated dose toxicity studies present in these reports, it was found that the liver is potentially the most frequently targeted organ by cosmetic ingredients when orally administered to experimental animals, followed by the kidney and the spleen. Combined listing of altered morphological, histopathological, and biochemical parameters subsequently indicated the possible occurrence of hepatotoxicity, including steatosis and cholestasis, triggered by a limited number of cosmetic compounds. These findings are not only of relevance for the in vitro modeling efforts and choice of compounds to be tested in the SEURAT project cluster, but also demonstrate the importance of using previously generated toxicological data through an electronic databank for addressing specific questions regarding the safety evaluation of cosmetic ingredients.

  7. Complications of Dermal Filling

    Directory of Open Access Journals (Sweden)

    Sajad Ahmad Salati

    2011-11-01

    Full Text Available Dermal fillers have globally become sought after drugs due to the desire of aging population to regain the youthful looks without any surgical operations. But like other procedures, dermal filling can become complicated. Besides the profitability have introduced the factor of malpractice which can bring in misery rather than beauty and youthful body contours. This article briefly reviews the common adverse effects of dermal fillers.

  8. Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

    Science.gov (United States)

    Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

    2015-04-01

    Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

  9. Unique evolutionary trajectories in repeated adaptation to hydrogen sulphide-toxic habitats of a neotropical fish (Poecilia mexicana).

    Science.gov (United States)

    Pfenninger, Markus; Patel, Simit; Arias-Rodriguez, Lenin; Feldmeyer, Barbara; Riesch, Rüdiger; Plath, Martin

    2015-11-01

    Replicated ecological gradients are prime systems to study processes of molecular evolution underlying ecological divergence. Here, we investigated the repeated adaptation of the neotropical fish Poecilia mexicana to habitats containing toxic hydrogen sulphide (H2 S) and compared two population pairs of sulphide-adapted and ancestral fish by sequencing population pools of >200 individuals (Pool-Seq). We inferred the evolutionary processes shaping divergence and tested the hypothesis of increase of parallelism from SNPs to molecular pathways. Coalescence analyses showed that the divergence occurred in the face of substantial bidirectional gene flow. Population divergence involved many short, widely dispersed regions across the genome. Analyses of allele frequency spectra suggest that differentiation at most loci was driven by divergent selection, followed by a selection-mediated reduction of gene flow. Reconstructing allelic state changes suggested that selection acted mainly upon de novo mutations in the sulphide-adapted populations. Using a corrected Jaccard index to quantify parallel evolution, we found a negligible proportion of statistically significant parallel evolution of Jcorr  = 0.0032 at the level of SNPs, divergent genome regions (Jcorr  = 0.0061) and genes therein (Jcorr  = 0.0091). At the level of metabolic pathways, the overlap was Jcorr  = 0.2545, indicating increasing parallelism with increasing level of biological integration. The majority of pathways contained positively selected genes in both sulphide populations. Hence, adaptation to sulphidic habitats necessitated adjustments throughout the genome. The largely unique evolutionary trajectories may be explained by a high proportion of de novo mutations driving the divergence. Our findings favour Gould's view that evolution is often the unrepeatable result of stochastic events with highly contingent effects.

  10. Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF Pharmacopuncture in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Yoo-min Choi

    2015-03-01

    Full Text Available Objectives: Water-soluble carthami flos (WCF is a new mixture of Carthami flos (CF pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS. Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.

  11. Neurobehavioral toxicity of a repeated exposure (14 days to the airborne polycyclic aromatic hydrocarbon fluorene in adult Wistar male rats.

    Directory of Open Access Journals (Sweden)

    Julie Peiffer

    Full Text Available Fluorene is one of the most abundant polycyclic aromatic hydrocarbons in air and may contribute to the neurobehavioral alterations induced by the environmental exposure of humans to PAHs. Since no data are available on fluorene neurotoxicity, this study was conducted in adult rats to assess the behavioral toxicity of repeated fluorene inhalation exposure. Male rats (n = 18/group were exposed nose-only to 1.5 or 150 ppb of fluorene 6 hours/day for 14 consecutive days, whereas the control animals were exposed to non-contaminated air. At the end of the exposure, animals were tested for activity and anxiety in an open-field and in an elevated-plus maze, for short-term memory in a Y-maze, and for spatial learning in an eight-arm maze. The results showed that the locomotor activity and the learning performances of the animals were unaffected by fluorene. In parallel, the fluorene-exposed rats showed a lower level of anxiety than controls in the open-field, but not in the elevated-plus maze, which is probably due to a possible difference in the aversive feature of the two mazes. In the same animals, increasing blood and brain levels of fluorene monohydroxylated metabolites (especially the 2-OH fluorene were detected at both concentrations (1.5 and 150 ppb, demonstrating the exposure of the animals to the pollutant and showing the ability of this compound to be metabolized and to reach the cerebral compartment. The present study highlights the possibility for a 14-day fluorene exposure to induce some specific anxiety-related behavioral disturbances, and argues in favor of the susceptibility of the adult brain when exposed to volatile fluorene.

  12. Twenty-eight-day repeated inhalation toxicity study of nano-sized lanthanum oxide in male sprague-dawley rats.

    Science.gov (United States)

    Shin, Seo-Ho; Lim, Cheol-Hong; Kim, Yong-Soon; Lee, Yong-Hoon; Kim, Sung-Hwan; Kim, Jong-Choon

    2017-04-01

    Although the use of lanthanum has increased in field of high-tech industry worldwide, potential adverse effects to human health and to the environment are largely unknown. The present study aimed to investigate the potential toxicity of nano-sized lanthanum oxide (La2 O3 ) following repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed nose-only to nano-sized La2 O3 for 28 days (5 days/week) at doses of 0, 0.5, 2.5, and 10 mg/m(3) . In the experimental period, we evaluated treatment-related changes including clinical signs, body weight, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology findings. We also analyzed lanthanum distribution in the major organs and in the blood, bronchoalveolar lavage fluids (BALF), and oxidative stress in lung tissues. Lanthanum level was highest in lung tissues and showed a dose-dependent relation. Alveolar proteinosis was observed in all treatment groups and was accompanied by an increase in lung weight; moreover, lung inflammation was observed in the 2.5 mg/m(3) and higher dose groups and was accompanied by an increase in white blood cells. In the BALF, total cell counts including macrophages and neutrophils, lactate dehydrogenase, albumin, nitric oxide, and tumor necrosis factor-alpha increased significantly in all treatment groups. Furthermore, these changes tended to deteriorate in the 10 mg/m(3) group at the end of the recovery period. In the present experimental conditions, we found that the lowest-observed-adverse-effect level of nano-sized La2 O3 was 0.5 mg/m(3) in male rats, and the target organ was the lung. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1226-1240, 2017. © 2016 Wiley Periodicals, Inc.

  13. Gain of Toxicity from ALS/FTD-Linked Repeat Expansions in C9ORF72 Is Alleviated by Antisense Oligonucleotides Targeting GGGGCC-Containing RNAs.

    Science.gov (United States)

    Jiang, Jie; Zhu, Qiang; Gendron, Tania F; Saberi, Shahram; McAlonis-Downes, Melissa; Seelman, Amanda; Stauffer, Jennifer E; Jafar-Nejad, Paymaan; Drenner, Kevin; Schulte, Derek; Chun, Seung; Sun, Shuying; Ling, Shuo-Chien; Myers, Brian; Engelhardt, Jeffery; Katz, Melanie; Baughn, Michael; Platoshyn, Oleksandr; Marsala, Martin; Watt, Andy; Heyser, Charles J; Ard, M Colin; De Muynck, Louis; Daughrity, Lillian M; Swing, Deborah A; Tessarollo, Lino; Jung, Chris J; Delpoux, Arnaud; Utzschneider, Daniel T; Hedrick, Stephen M; de Jong, Pieter J; Edbauer, Dieter; Van Damme, Philip; Petrucelli, Leonard; Shaw, Christopher E; Bennett, C Frank; Da Cruz, Sandrine; Ravits, John; Rigo, Frank; Cleveland, Don W; Lagier-Tourenne, Clotilde

    2016-05-04

    Hexanucleotide expansions in C9ORF72 are the most frequent genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Disease mechanisms were evaluated in mice expressing C9ORF72 RNAs with up to 450 GGGGCC repeats or with one or both C9orf72 alleles inactivated. Chronic 50% reduction of C9ORF72 did not provoke disease, while its absence produced splenomegaly, enlarged lymph nodes, and mild social interaction deficits, but not motor dysfunction. Hexanucleotide expansions caused age-, repeat-length-, and expression-level-dependent accumulation of RNA foci and dipeptide-repeat proteins synthesized by AUG-independent translation, accompanied by loss of hippocampal neurons, increased anxiety, and impaired cognitive function. Single-dose injection of antisense oligonucleotides (ASOs) that target repeat-containing RNAs but preserve levels of mRNAs encoding C9ORF72 produced sustained reductions in RNA foci and dipeptide-repeat proteins, and ameliorated behavioral deficits. These efforts identify gain of toxicity as a central disease mechanism caused by repeat-expanded C9ORF72 and establish the feasibility of ASO-mediated therapy.

  14. Collaborative work on evaluation of ovarian toxicity. 2) Two- or four-week repeated dose studies and fertility study of mifepristone in female rats.

    Science.gov (United States)

    Tamura, Toru; Yokoi, Ryohei; Okuhara, Yuji; Harada, Chiho; Terashima, Yukari; Hayashi, Morimichi; Nagasawa, Tatsuya; Onozato, Tomoya; Kobayashi, Kazuo; Kuroda, Junji; Kusama, Hiroshi

    2009-01-01

    In order to assess ovarian pathological changes and their relationship to changes in female fertility parameters, mifepristone, a progesterone receptor antagonist, was selected as the test article and was administered orally to female rats at dose levels of 0, 0.8, 4, 20 and 100 mg/kg for 2 or 4 weeks in repeated dose-toxicity studies and in a female fertility study at dose levels of 0, 0.8, 4 and 20 mg/kg from > 2 weeks before copulation to postcoital day 7. In the repeated dose toxicity studies, persistent estrus was seen in the vaginal smears, and multiple cysts in the ovaries at necropsy, increases in luteinized cysts and hypertrophy of previously formed corpora lutea were observed in the histopathological examination of ovaries in rats receiving 20 mg/kg or more for 2 or 4 weeks. In female fertility studies, persistent vaginal cornification was also observed at 20 mg/kg and the precoital interval was significantly shortened. All of the animals were completely infertile when dosed with 20 mg/kg during the post-coital period. An increase in pre-implantation losses was observed in the animals treated with 20 mg/kg during the pre-coital phase, while treatment with 4 mg/kg mifepristone during the post-coital phase induced an increase in post-implantation losses. These results suggested that a 2-week administration period would be sufficient to detect the ovarian toxicity of mifepristone in repeated dose toxicity study and the pathological findings in the ovaries would reflect the alterations in female reproductive endpoints in the female fertility study.

  15. Collaborative work on evaluation of ovarian toxicity. 17) Two- or four-week repeated-dose studies and fertility study of sulpiride in female rats.

    Science.gov (United States)

    Ishii, Shun-ichiro; Ube, Masayuki; Okada, Miyoko; Adachi, Tamiko; Sugimoto, Jiro; Inoue, Yoshimi; Uno, Yoshifumi; Mutai, Mamoru

    2009-01-01

    To find the appropriate dosing period to detect ovarian toxicity, sulpiride, a D2 antagonist was orally dosed to female rats at dose levels of 1, 10, and 100 mg/kg/day daily for 2 or 4 weeks in repeated-dose toxicity studies. In addition, sulpiride at the same dose levels was given to female rats daily during the pre-mating period, mating period, and Days 0-7 of gestation to assess its effect on fertility. In ovarian histology in the 2-week study, increases in atretic follicle were seen at 1 mg/kg or more and increases in follicular cysts at 10 mg/kg or more. In the 4-week study, these findings were seen at 1 mg/kg or more, and a decrease in large follicles was seen at 10 mg/kg or more. Increased body weight gain was observed at 10 mg/kg or more in the 2- and 4-week studies. The females in these groups exhibited development of mammary alveolus by sulpiride-induced hyperprolactinemia. In the fertility study, sulpiride-treated females showing persistent diestrus resulted in successful mating, and almost all females got pregnant. However, increased implantation loss was observed at 10 mg/kg or more, which was considered to be caused by the adverse effect of sulpiride on oocyte development. From these results, sulpiride-induced ovarian toxicity was seen at 1 mg/kg or more in the 2- and 4-week repeated-dose toxicity studies, and the observed ovarian changes were considered to be related to adverse effects on female fertility.

  16. Nutrient and toxic element soil concentrations during repeated mineral and compost fertilization treatments in a Mediterranean agricultural soil.

    Science.gov (United States)

    Baldantoni, Daniela; Morra, Luigi; Saviello, Giovanni; Alfani, Anna

    2016-12-01

    Agricultural soils of semi-arid Mediterranean areas are often subjected to depletion of their chemical, physical, and biological properties. In this context, organic fertilization, in addition to providing nutrients for a longer time in respect to mineral fertilization, improves many other characteristics related to soil fertility. Moreover, the combined use of organic and mineral fertilizers may promote a more sustainable crop production. However, a concern on the long-term use of organic fertilizers arises in relation to the possible accumulation of toxic elements in soil and their transfer to human beings. For this reason, a long-term study on nutrient and toxic element total concentrations and availabilities during fertilization treatments was carried out. In particular, mineral NPK fertilized soils, soils amended with biowaste compost, soils amended with biowaste compost plus mineral nitrogen, and unfertilized soils were analyzed for 11 chemical elements. The results highlighted that temporal variations in total and bioavailable concentrations of both nutrients and toxic elements, occurring also in unfertilized soils, are wider than those related to fertilization treatments. Anyway, soil amendments with biowaste compost, alone or in combination with mineral fertilizers, reduce Cu bioavailability but improve K, Fe, Mn, and Zn availabilities, excluding at the same time a long-term accumulation in soil. Total and bioavailable toxic element concentrations (apart from available Cd) do not vary in relation to fertilization treatments.

  17. (1)H NMR-based metabolomics study on repeat dose toxicity of fine particulate matter in rats after intratracheal instillation.

    Science.gov (United States)

    Zhang, Yannan; Hu, Hejing; Shi, Yanfeng; Yang, Xiaozhe; Cao, Lige; Wu, Jing; Asweto, Collins Otieno; Feng, Lin; Duan, Junchao; Sun, Zhiwei

    2017-07-01

    Systemic metabolic effects and toxicity mechanisms of ambient fine particulate matter (PM2.5) remain uncertain. In order to investigate the mechanisms in PM2.5 toxicity, we explored the endogenous metabolic changes and possible influenced metabolic pathways in rats after intratracheal instillation of PM2.5 by using a (1)H nuclear magnetic resonance (NMR)-based metabolomics approach. Liver and kidney histopathology examinations were also performed. Chemical characterization demonstrated that PM2.5 was a complex mixture of elements. Histopathology showed cellular edema in liver and glomerulus atrophy of the PM2.5 treated rats. We systematically analyzed the metabolites changes of serum and urine in rats using (1)H NMR techniques in combination with multivariate statistical analysis. Significantly reduced levels of lactate, alanine, dimethylglycine, creatine, glycine and histidine in serum, together with increased levels of citrate, arginine, hippurate, allantoin and decreased levels of allthreonine, lactate, alanine, acetate, succinate, trimethylamine, formate in urine were observed of PM2.5 treated rats. The mainly affected metabolic pathways by PM2.5 were glycine, serine and threonine metabolism, glyoxylate and dicarboxylate metabolism, citrate cycle (TCA cycle), nitrogen metabolism and methane metabolism. Our study provided important information on assessing the toxicity of PM2.5 and demonstrated that metabolomics approach can be employed as a tool to understand the toxicity mechanism of complicated environmental pollutants. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Construction of the Database of Rat Repeated-dose Toxicity Tests of Pesticides for the Toxicological Characterization of Hepatocyte Hypertrophy.

    Science.gov (United States)

    Masuda, Akane; Masuda, Miyabi; Kawano, Takuya; Kitsunai, Yoko; Nakayama, Haruka; Nakajima, Hiroyuki; Kojima, Hiroyuki; Kitamura, Shigeyuki; Uramaru, Naoto; Hosaka, Takuomi; Sasaki, Takamitsu; Yoshinari, Kouichi

    2017-01-01

     Liver and hepatocyte hypertrophy can be induced by exposure to chemical compounds, but the mechanisms and toxicological characteristics of these phenomena have not yet been investigated extensively. In particular, it remains unclear whether the hepatocyte hypertrophy induced by chemical compounds should be judged as an adaptive response or an adverse effect. Thus, understanding of the toxicological characteristics of hepatocyte hypertrophy is of great importance to the safety evaluation of pesticides and other chemical compounds. To this end, we have constructed a database of potentially toxic pesticides. Using risk assessment reports of pesticides that are publicly available from the Food Safety Commission of Japan, we extracted all observations/findings that were based on 90-day subacute toxicity tests and 2-year chronic toxicity and carcinogenicity tests in rats. Analysis of the database revealed that hepatocyte hypertrophy was observed for 37-47% of the pesticides investigated (varying depending on sex and testing period), and that centrilobular hepatocyte hypertrophy was the most frequent among the various types of hepatocyte hypertrophy in both the 90-day and 2-year studies. The database constructed in this study enables us to investigate the relationships between hepatocyte hypertrophy and other toxicological observations/findings, and thus will be useful for characterizing hepatocyte hypertrophy.

  19. Toxicity assessment of repeated intravenous injections of arginine–glycine–aspartic acid peptide conjugated CdSeTe/ZnS quantum dots in mice

    Directory of Open Access Journals (Sweden)

    Wang YW

    2014-10-01

    Full Text Available You-Wei Wang, Kai Yang, Hong Tang, Dan Chen, Yun-Long Bai Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: Nanotechnology-based near-infrared quantum dots (NIR QDs have many excellent optical properties, such as high fluorescence intensity, good fluorescence stability, and strong tissue-penetrating ability. Integrin αvß3 is highly and specifically expressed in tumor angiogenic vessel endothelial cells of almost all carcinomas. Recent studies have shown that NIR QDs linked to peptides containing the arginine–glycine–aspartic acid (RGD sequence (NIR QDs-RGD can specifically target integrin αvß3 expressed in endothelial cells of tumor angiogenic vessels in vivo, and they offer great potential for early cancer diagnosis, in vivo tumor imaging, and tumor individualized therapy. However, the toxicity profile of NIR QDs-RGD has not been reported. This study was conducted to investigate the toxicity of NIR QDs-RGD when intravenously administered to mice singly and repeatedly at the dose required for successful tumor imaging in vivo.Materials and methods: A NIR QDs-RGD probe was prepared by linking NIR QDs with the maximum emission wavelength of 800 nm (QD800 to the RGD peptide (QD800-RGD. QD800-RGD was intravenously injected to BALB/C mice once or twice (200 pmol equivalent of QD800 for each injection. phosphate-buffered saline solution was used as control. Fourteen days postinjection, toxicity tests were performed, including complete blood count (white blood cell, red blood cell, hemoglobin, platelets, lymphocytes, and neutrophils and serum biochemical analysis (total protein, albumin, albumin/globulin, aspartate aminotransferase, alanine aminotransferase, and blood urea nitrogen. The coefficients of liver, spleen, kidney, and lung weight to body weight were measured, as well as their oxidation and antioxidation indicators, including

  20. Use of lanthanum to detect changes in the permeability barrier of rat skin after dermal exposure to organic chemicals

    Energy Technology Data Exchange (ETDEWEB)

    Mattie, D.R.; McDougal, J.N.; Chase, M.R.; Hixson, C.J.

    1987-01-01

    Occupational dermal exposures to organic solvents are of importance due to local effects in the skin and systematic toxicity if penetration occurs through the skin. Repeated or prolonged contact with organic solvents have been shown to penetrate the skin; little information is available however, concerning effects on the barrier properties of skin after dermal exposure to solvents. This investigation examines the ultrastructural changes in rat skin after exposure of 3 organic chemicals and to correlate changes with the location of an electron-dense tracer, lanthanum, which is normally excluded by the permeability barrier in the stratum corneum. Male rats were exposed for 24 h to sterile saline, trichloroethylene (TCE), perchloroethylene (PERC), or toluene using dermal-exposure cells developed in this laboratory. Rat skin exposed to saline for 24 h appeared normal. Rat skin exposed to neat TCE, PERC or toluene for 24 h caused acute, coagulative necrosis of the epidermis and upper 1/2 to 1/3 of the dermis.

  1. Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

    Science.gov (United States)

    Funabashi, H; Fujioka, M; Kohchi, M; Tateishi, Y; Matsuoka, N

    2000-10-01

    The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

  2. Genetics Home Reference: focal dermal hypoplasia

    Science.gov (United States)

    ... Home Health Conditions focal dermal hypoplasia focal dermal hypoplasia Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Focal dermal hypoplasia is a genetic disorder that primarily affects the ...

  3. Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.

    Science.gov (United States)

    Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah

    2012-04-10

    Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.

  4. Toxicity of 100 nm zinc oxide nanoparticles: a report of 90-day repeated oral administration in Sprague Dawley rats

    Directory of Open Access Journals (Sweden)

    Kim YR

    2014-12-01

    Full Text Available Yu-Ri Kim,1,* Jong-Il Park,2,* Eun Jeong Lee,1 Sung Ha Park,3 Nak-won Seong,2 Jun-Ho Kim,2 Geon-Yong Kim,2 Eun-Ho Meang,2 Jeong-Sup Hong,2 Su-Hyon Kim,2 Sang-Bum Koh,2 Min-Seok Kim,2 Cheol-Su Kim,4 Soo-Ki Kim,4 Sang Wook Son,5 Young Rok Seo,6 Boo Hyon Kang,7 Beom Seok Han,8 Seong Soo A An,9 Hyo-In Yun,9 Meyoung-Kon Kim1 1Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 2General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 3Department of Biochemistry, University of Bath, Bath, UK; 4Department of Microbiology, Wonju College of Medicine, Yonsei University, Wonju-si, Gangwon, Korea; 5Department of Life Science, Institute of Environmental Medicine for Green Chemistry, Dongguk University, Seoul, Korea; 6Nonclinical Research Institute, Chemon Inc., Yongin, Gyeonggi, Korea; 7Toxicological Research Center, Hoseo University, Ansan, Chungnam, Korea; 8Department of Bionanotechnology, Gachon University, Seongnam, Gyeonggi, Korea; 9College of Veterinary Medicine, Chungnam National University, Daejon, Korea  *These authors contributed equally to this work Abstract: Nanoparticles (NPs are used commercially in health and fitness fields, but information about the toxicity and mechanisms underlying the toxic effects of NPs is still very limited. The aim of this study is to investigate the toxic effect(s of 100 nm negatively (ZnOAE100[-] or positively (ZnOAE100[+] charged zinc oxide (ZnO NPs administered by gavage in Sprague Dawley rats, to establish a no observed adverse effect level, and to identify target organ(s. After verification of the primary particle size, morphology, hydrodynamic size, and zeta potential of each test article, we performed a 90-day study according to Organisation for Economic Co-operation and Development test guideline 408. For the 90-day study, the high dose was set at 500 mg/kg and the middle and low doses were set at 125 mg/kg and 31.25 mg

  5. Dermal route in systemic exposure

    NARCIS (Netherlands)

    Benford, D.J.; Cocker, J.; Sartorelli, P.; Schneider, T.; Hemmen, J. van; Firth, J.G.

    1999-01-01

    To evaluate risk from dermal exposure, the amount of material on the skin must first be measured. The potential for dermal uptake must then be assessed for the potential health effects from systemic exposure. No standard methods exist for studying these processes, and published data are not comparab

  6. Hyaluronic acid dermal fillers: can adjunctive lidocaine improve patient satisfaction without decreasing efficacy or duration?

    Directory of Open Access Journals (Sweden)

    Lynnelle Smith

    2011-03-01

    Full Text Available Lynnelle Smith1, Kimberly Cockerham21Ophthalmology Department, Loma Linda University, Loma Linda, CA, USA; 2Ophthalmology Department, Stanford University, Palo Alto, CA, USAAbstract: Hyaluronic acid (HA dermal fillers are the most widely used injectables to augment facial volume without surgery. HA dermal fillers are popular because of their ease of administration, predictable effectiveness, good safety profile, and quick patient recovery. The most common patient complaint is pain. Our goal is to review the current literature on HA fillers and compare outcomes with and without lidocaine. We found adjunctive lidocaine significantly decreases pain during injection and postinjection with corresponding increased patient satisfaction. The efficacy and safety profile appears unchanged. Rare complications with HA fillers and those associated with constituents of the product, contaminants, and lidocaine are reviewed. The corrective effects of HA fillers are temporary; repeat treatment is required to maintain results. Minimizing pain is crucial to optimize patient satisfaction.Keywords: hyaluronic acid, lidocaine, drug toxicity, hypersensitivity, collagen, herpes simplex

  7. Mathematical analysis of dermal absorption rate of heavy metals.

    Science.gov (United States)

    Batkin, Izmail; Bolic, Miodrag

    2015-08-01

    Presently 90 - 95% of children in the US wear disposable diapers before completing their toilet training at average age of 30 months. The diaper absorbs urine and liquid component from feces contaminated with excreted toxicants. In this initial study, we posit that the long contact between the diaper and the skin leads to increased dermal reabsorption of excreted body toxicants, mainly heavy metals, which are statistically associated with autism and neurodevelopmental disorder. We developed a mathematical model to analyse the increase of the level of toxicants due to dermal reabsorption after excretion. This simple kinetic model gives us the average reabsorbtion factor in the range of 1.6 to 5. The limitation of this work is that only mathematical model has been considered and it has not been verified experimentally.

  8. Generalized mid dermal elastolysis

    Directory of Open Access Journals (Sweden)

    Maria João Cruz

    2011-12-01

    Full Text Available Mid-dermal elastolysis (MDE is a rare skin disorder clinically characterized by the appearance of diffuse fine wrinkling, most often of the trunk and arms. This entity is distinguished from other elastolytic disorders by its characteristic selective loss of elastic fibers of the mid dermis. The aetiopathogenesis of the disease is still unclear as well as the effective treatment. Half of the cases described in the literature are associated with ultraviolet radiation exposure. Other reported triggering conditions such as urticaria, eczema and granuloma annulare suggests different eliciting inflammatory pathways. The authors describe the case of a 38-year-old woman who developed an urticarial eruption during months which progressed to generalized and severe fine wrinkling.

  9. Prediction of the carcinogenic potential of human pharmaceuticals using repeated dose toxicity data and their pharmacological properties

    Directory of Open Access Journals (Sweden)

    Jan Willem Van Der Laan

    2016-10-01

    Full Text Available In an exercise designed to reduce animal use, we analysed the results of rat sub-chronic toxicity studies from 289 pharmaceutical compounds with the aim to predict the tumour outcome of carcinogenicity studies in this species. The results were obtained from the assessment reports available at the Medicines Evaluation Board of the Netherlands for 289 pharmaceutical compounds that had been shown to be non-genotoxic. One hundred and forty-three of the 239 compounds not inducing putative preneoplastic lesions in the sub-chronic study did not induce tumours in the carcinogenicity study (True Negatives - TN, whereas 96 compounds were categorised as False Negatives (FN, because tumours were observed in the carcinogenicity study. For the remaining 50 compounds, 31 showed preneoplastic lesions in the subchronic study and tumours in the carcinogenicity study (True positives - TP, and 19 only showed preneoplastic lesions in subchronic studies but no tumours in the carcinogenicity study (False positives - FP. In addition, we then re-assessed the prediction of the tumour outcome by integrating the pharmacological properties of these compounds. These pharmacological properties were evaluated with respect to the presence or absence of a direct or indirect proliferative action. We found support for the absence of cellular proliferation for 204 compounds (TN. For 67 compounds the presence of cellular hyperplasia as evidence for proliferative action could be found (TP. Therefore, this approach resulted in an ability to predict non-carcinogens at a success rate of 92 % and the ability to detect carcinogens at 98 %. The combined evaluation of pharmacological and histopathological endpoints eventually led to only 18 unknown outcomes (17 categorised as FN. 1 as FP, thereby enhancing both the negative and positive predictivity of an evaluation based upon histopathological evaluation only. The data show the added value of a consideration of the pharmacological

  10. Repeated-Dose and Reproductive/Developmental Toxicity of NTO (3-Nitro-1,2,4-Triazol-5-One) in the Rat

    Science.gov (United States)

    2014-03-21

    than 5000 milligrams per kilogram (mg/kg) . In addition, NTO was reported to be a mild skin and eye irritant but was not a dermal sensitizer (Los...pancreas; testes; uterus; aorta; esophagus; stomach; duodenum; jejunum; ileum; caecum; colon ; rectum; urinary bladder; representative lymph node...adrenals; pancreas; testes; uterus; aorta; esophagus; stomach; duodenum; jejunum; ileum; cecum; colon ; rectum; urinary bladder; representative lymph

  11. Exposure to pesticides with dermal toxicity in farmers of Community of Valencia Exposición a plaguicidas con toxicidad dérmica en agricultores de la Comunitat Valenciana

    Directory of Open Access Journals (Sweden)

    Caterina Brandon Garcia

    2010-12-01

    Full Text Available Introduction: Dermal route has a toxicological importance, as well as substances such as entry, but by frequent local effects. In applications of pesticides by farmers is common and important the dermal exposure to pesticides, so the dermal route in this sector of activity could be of particular relevance. Objective: To determine the hazard of dermal exposure in farmers using pesticides and to propose specific preventive measures. Material and methods: A transversal descriptive study based on a questionnaire designed by the researchers, replying to the 238 attendees at the courses for pesticide handler card basic level Department of Health Xativa-Ontinyent (Valencia in 2009. Pesticides used were collected over the past 12 months and reviewed their R phrases (risk phrases looking for dermal effects. Results: 55 % of pesticides had some phrase R on skin problems. The phrase R38 "Irritating to skin" was found in 16 products, used by 59.05 % of respondents and the R43 "Possibility of sensitization by skin contact" at 7, used by 23.91 %. Conclusions: The skin irritation effect was related to more dermal exposure to these pesticides. It is necessary to emphasize the skin protection in the courses for workers who apply these products. Skin problems should be included damages for workplace exposure to pesticides.Introducción: La vía dérmica tiene importancia toxicológica, además de como entrada de sustancias, por los frecuentes efectos locales. En aplicaciones de plaguicidas realizadas por agricultores resulta habitual e importante la exposición dérmica a plaguicidas, por lo que la vía dérmica en este sector de actividad puede resultar de especial relevancia. Objetivo: Conocer los riesgos cutáneos de los agricultores que utilizan plaguicidas, para poder así proponer medidas preventivas específicas. Material y métodos: Se realizó un estudio descriptivo transversal basado en un cuestionario diseñado por los investigadores, contestando al

  12. Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry, histopathology and NMR-based metabonomic approach.

    Science.gov (United States)

    Benourad, Fouzia; Kahvecioglu, Zehra; Youcef-Benkada, Mokhtar; Colet, Jean-Marie

    2014-10-01

    In the field of natural extracts, research generally focuses on the study of their biological activities for food, cosmetic, or pharmacological purposes. The evaluation of their adverse effects is often overlooked. In this study, the extracts of Thymus vulgaris L. were obtained by two different extraction methods. Intraperitoneal injections of both extracts were given daily for four days to male Wistar Han rats, at two different doses for each extract. The evaluation of the potential toxic effects included histopathological examination of liver, kidney, and lung tissues, as well as serum biochemistry of liver and kidney parameters, and (1)H-NMR-based metabonomic profiles of urine. The results showed that no histopathological changes were observed in the liver and kidney in rats treated with both extracts of thyme. Serum biochemical investigations revealed significant increases in blood urea nitrogen, creatinine, and uric acid in animals treated with polyphenolic extract at both doses. In these latter groups, metabonomic analysis revealed alterations in a number of urine metabolites involved in the energy metabolism in liver mitochondria. Indeed, the results showed alterations of glycolysis, Krebs cycle, and β-oxidative pathways as evidenced by increases in lactate and ketone bodies, and decreases in citrate, α-ketoglutarate, creatinine, hippurate, dimethylglycine, and dimethyalanine. In conclusion, this work showed that i.p. injection of repeated doses of thyme extracts causes some disturbances of intermediary metabolism in rats. The metabonomic study revealed interesting data which could be further used to determine the cellular pathways affected by such treatments.

  13. Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Merilin Al Sharif

    2014-01-01

    Full Text Available Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools. The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD are of specific interest, due to its increasing incidence in the modern society. Growing evidence stresses on the PPARγ ligand-dependent dysregulation as a key molecular initiating event (MIE for this adverse effect. The aim of this work was to analyze and systematize the numerous scientific data about the steatogenic role of PPARγ. Over 300 papers were ranked according to preliminary defined criteria and used as reliable and significant sources of data about the PPARγ-dependent prosteatotic MoA. A detailed analysis was performed regarding proteins which PPARγ-mediated expression changes had been confirmed to be prosteatotic by most experimental evidence. Two probable toxicological MoAs from PPARγ ligand binding to NAFLD were described according to the Organisation for Economic Cooperation and Development (OECD concepts: (i PPARγ activation in hepatocytes and (ii PPARγ inhibition in adipocytes. The possible events at different levels of biological organization starting from the MIE to the organ response and the connections between them were described in details.

  14. 26-week repeated oral dose toxicity study of UP446, a combination of defined extracts of Scutellaria baicalensis and Acacia catechu, in beagle dogs.

    Science.gov (United States)

    Yimam, Mesfin; Lee, Young Chul; Jia, Qi

    2016-07-01

    The needs for relatively safe botanical alternatives to relieve symptoms associated to arthritis have continued to grow in parallel with the ageing population. UP446, a standardized bioflavonoid composition from the roots of Scutellaria baicalensis and the heartwoods of Acacia catechu, has been used as over the counter joint care dietary supplements and a prescription medical food. Significant safety data have been documented in rodents and human for this composition. Here we evaluated the potential adverse effects of orally administered UP446 in beagle dogs following a 26-week repeated oral dose toxicity study. UP446 at doses of 250, 500 and 1000 mg/kg/day were administered orally to beagle dogs for 26 weeks. A 4-week recovery group from the high dose (1000 mg/kg) and vehicle treated groups were included. No morbidity or mortality was observed for the duration of the study. No significant differences between groups in body weights, food consumption, ophthalmological examinations, electrocardiograms, urinalysis, hematology, clinical chemistry, organ weights, gross pathology and histopathology were documented. Emesis, loose feces and diarrhea were noted in both genders at the 1000 mg/kg treatment groups. These clinical signs were considered to be reversible as they were not evident in the recovery period. In conclusion, the no-observed-adverse-effect-level (NOAEL) of UP446 was considered to be 500 mg/kg/day both in male and female beagle dogs.

  15. Influence of coefficient of variation in determining significant difference of quantitative values obtained from 28-day repeated-dose toxicity studies in rats.

    Science.gov (United States)

    Kobayashi, Katsumi; Sakuratani, Yuki; Abe, Takemaru; Yamazaki, Kazuko; Nishikawa, Satoshi; Yamada, Jun; Hirose, Akihiko; Kamata, Eiichi; Hayashi, Makoto

    2011-01-01

    In order to understand the influence of coefficient of variation (CV) in determining significant difference of quantitative values of 28-day repeated-dose toxicity studies, we examined 59 parameters of 153 studies conducted in accordance with Chemical Substance Control Law in 12 test facilities. Sex difference was observed in 12 parameters and 10 parameters showed large CV in females. The minimum CV was 0.74% for sodium. CV of electrolytes was comparatively small, whereas enzymes had large CV. Large differences in CV were observed for major parameters among 7-8 test facilities. The changes in CV were grossly classified into 11. Our study revealed that a statistical significant difference is usually detected if there is a difference of 7% in mean values between the groups and the groups have a CV of about 7%. A parameter with a CV as high as 30% may be significantly different, if the difference of the mean between the groups is 30%. It would be ideal to use median value to assess the treatment-related effect, rather than mean, when the CV is very high. We recommend using CV of the body weight as a standard to judge the adverse effect level.

  16. 氟氯氰菊酯亚急性吸入毒性实验研究%Inhalation toxicity of cyfluthrin for 28-day repeated dose in rats

    Institute of Scientific and Technical Information of China (English)

    秦珩; 乔善磊; 顾军; 钟义红; 杨洪宝; 王玉邦; 施爱民

    2012-01-01

    Objective To determine the inhalation toxicity and find the non -observed adverse effect level (NOAEL) of cyfluthrin for a 28-day repeated dose in rats. Methods Clean-grade SD rats were randomly divided into 5 groups with 5 females and 5 males in each. The animals inhaled DMSO or cyfluthrin at the concentration of 0, 7. 81 , 9. 05 and 18. 98 mg/m for 4 weeks (6 h/d, 5 d/w). At the end of inhalation , all the animals were kindly sacrificed. Their organs were collected for histopathological examination . Blood samples were collected for analysis of complete blood count , biochemistry and coagulation. Results The animals in 18. 98 mg/m3 group were found scratching repeatedly around the mouth, listless, fidgeting, trembling, discharging blood around the mouth and nose . However, symptoms in females were less serious than in males. Furthermore , the body mass , feed efficiency , weight of kidney of animals in this dose male group were found decreased compared with the control group . Biochemistry detection revealed that serum AST was elevated markedly in both genders of 18. 98 mg/m3 group and in males of 9. 05 mg/m3 group. No obvious abnormity was found in 7.81 mg/m3 group or control group. Conclusion Based on the results above, the non-observed adverse effect level (NOAEL) of cyfluthrin in SD rats is 7. 81 mg/m3 for 28 d repeated inhalation in this study.%目的 观察氟氯氰菊酯染毒大鼠亚急性吸入毒性.方法 7周龄清洁级SD大鼠随机分成5组,每组雌雄各5只,分别吸入氟氯氰菊酯0,7.81,9.05,18.98 mg/m3及溶剂二甲亚砜,每天6 h,每周5 d,共28 d.实验结束时取血液做常规生化指标、血细胞指标、血凝学指标检测.取心、肝、脾等8种主要脏器称重并做病理组织学检查.结果 18.98 mg/m3组动物在染毒中呈现反复抓挠口周、烦躁不安、鼻有血性分泌物、颤抖,染毒结束后呈现萎靡、蜂腰、四肢无力的体征.雌性动物的毒性表现较雄性低.与溶剂对照组相

  17. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster

    DEFF Research Database (Denmark)

    Langkilde, Søren; Mandimika, T.; Schrøder, Malene

    2009-01-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanum tuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine...... to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity...... of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios...

  18. Effect of microemulsions on cell viability of human dermal fibroblasts

    Science.gov (United States)

    Li, Juyi; Mironava, Tatsiana; Simon, Marcia; Rafailovich, Miriam; Garti, Nissim

    Microemulsions are optically clear, thermostable and isotropic mixture consisting of water, oil and surfactants. Their advantages of ease preparation, spontaneous formation, long-term stability and enhanced solubility of bioactive materials make them great potentials as vehicles in food and pharmaceutical applications. In this study, comparative in vitro cytotoxicity tests were performed to select a best formulation of microemulsion with the least toxicity for human dermal fibroblasts. Three different kinds of oils and six different kinds of surfactants were used to form microemulsions by different ratios. The effect of oil type and surfactant type as well as their proportions on cell proliferation and viability were tested.

  19. A 28-day repeat dose toxicity study of steroidal glycoalkaloids a-solanine and a-chaconine in the Syrian Golden Hamster

    NARCIS (Netherlands)

    Langkilde, S.; Mandimika, T.; Schroder, M.; Meyer, O.; Slob, W.; Peijnenburg, A.A.C.M.; Poulsen, M.

    2009-01-01

    Glycoalkaloids ¿-solanine and ¿-chaconine are naturally present toxicants in the potato plant (Solanum tuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of ¿-solanine to ¿-chaconine m

  20. Dermal absorption of chlorpyrifos in human volunteers

    NARCIS (Netherlands)

    Meuling, W.J.; Ravensberg, L.C.; Roza, L.; Hemmen, J.J. van

    2005-01-01

    Objective: The methods and results are described of a study on the dermal absorption of chlorpyrifos (CPF) in humans established via urinary excretion of the metabolite 3,5,6-trichloro-2-pyridinol (TCP). Methods: Two dermal, single, doses of CPF were applied in two study groups (A and B) each

  1. Biomechanical properties of four dermal substitutes

    Institute of Scientific and Technical Information of China (English)

    ZHANG Guo-an; NING Fang-gang; ZHAO Nan-ming

    2007-01-01

    @@ Many kinds of cell-free dermal substitutes have been developed during the past several years, however,their biomechanical properties, including hysteresis,stress relaxation, creep, and non-linear stress-strain, are still unknown. In this study, we tested these biomechanical characteristics of four dermal substitutes,and compared them with those of fresh human skin (FHS).

  2. From dermal exposure to internal dose

    NARCIS (Netherlands)

    Sandt, J.J.M. van de; Dellarco, M.; Hemmen, J.J. van

    2007-01-01

    Exposure scenarios form an essential basis for chemical risk assessment reports under the new EU chemicals regulation REACH (Registration, Evaluation, Authorisation and restriction of Chemicals). In case the dermal route of exposure is predominant, information on both exposure and dermal bioavailabi

  3. Oxime silanes: structure/toxicity relationships.

    Science.gov (United States)

    Derelanko, Michael J; Rusch, George M

    2008-01-01

    Acute and repeated oral and dermal rat toxicology studies of standard designs were conducted on four methyl ethyl ketoxime (MEKO) silanes and four methyl isobutyl ketoxime (MIBKO) silanes. Each compound contained either MEKO or MIBKO groups (but not both) and either a single methyl, vinyl, or phenyl group (trifunctional oxime silane), two methyl groups or a methyl and vinyl group (difunctional oxime silane), or no nonoxime group (tetrafunctional oxime silane) attached to the central silicon atom. All compounds caused transient narcosis and anemia, with oral exposure associated with the hydrolyzed oxime groups. Difunctional oxime silanes, containing both a methyl and a vinyl group, caused degeneration of the seminiferous tubules of the testes following oral administration. Serial testicular histopathology indicated the effect originated at the level of the spermatocyte, resulting in a wave of cellular depletion of later maturation stages of spermatogenesis. Spermatogenesis gradually recovered but function was not evaluated. Tetrafunctional oxime silanes, trifunctional oxime silanes, including those containing a single methyl or vinyl group, or difunctional oxime silane containing two methyl groups did not affect the testes, indicating that both a methyl and vinyl group needs to be present on the oxime silane molecule for testicular toxicity. The testicular toxicity appears to be associated with the methyl/vinyl silane portion and not the oxime portion of the oxime silane molecule. With the exception of the methyl/vinyl difunctional oxime silanes, the silane portion of oxime silanes does not appear to contribute any significant toxicity to these compounds.

  4. A 28-day repeat dose toxicity study of steroidal glycoalkaloids, alpha-solanine and alpha-chaconine in the Syrian Golden hamster.

    Science.gov (United States)

    Langkilde, Søren; Mandimika, Tafadzwa; Schrøder, Malene; Meyer, Otto; Slob, Wout; Peijnenburg, Ad; Poulsen, Morten

    2009-06-01

    Glycoalkaloids alpha-solanine and alpha-chaconine are naturally present toxicants in the potato plant (Solanumtuberosum). Human intake of high doses of glycoalkaloids has led to acute intoxication, in severe cases coma and death. Previous studies have indicated that the ratio of alpha-solanine to alpha-chaconine may determine the degree and nature of the glycoalkaloid toxicity in potatoes, as the toxicity of the two alkaloids act synergistically. The aim of the present study was to investigate whether an altered ratio of alpha-solanine and alpha-chaconine would reduce the toxicity of the glycoalkaloids. The Syrian Golden hamster was given daily doses of alpha-solanine and alpha-chaconine by gavage for 28 days. Doses of up to 33.3 mg total glycoalkaloids/kg body weight were applied in ratios of 1:3.7 and 1:70 (alpha-solanine:alpha-chaconine). Administration of the highest doses of both ratios resulted in distended and fluid filled small intestines and stomach. Animals receiving the ratio with the reduced content of alpha-solanine were less affected compared to those receiving the other ratio. Gene expression profiling experiments were conducted using RNA from epithelial scrapings from the small intestines of the hamsters administered the highest doses of the glycoalkaloid treatments. In general, more differential gene expression was observed in the epithelial scrapings of the hamsters fed the ratio of 1:3.7. Mostly, pathways involved in lipid and energy metabolism were affected by the ratio of 1:3.7.

  5. Evaluation of 90-day Repeated Dose Oral Toxicity, Glycometabolism, Learning and Memory Ability, and Related Enzyme of Chromium Malate Supplementation in Sprague-Dawley Rats.

    Science.gov (United States)

    Feng, Weiwei; Wu, Huiyu; Li, Qian; Zhou, Zhaoxiang; Chen, Yao; Zhao, Ting; Feng, Yun; Mao, Guanghua; Li, Fang; Yang, Liuqing; Wu, Xiangyang

    2015-11-01

    Our previous study showed that chromium malate improved the regulation of blood glucose in mice with alloxan-induced diabetes. The present study was designed to evaluate the 90-day oral toxicity of chromium malate in Sprague-Dawley rats. The present study inspected the effect of chromium malate on glycometabolism, glycometabolism-related enzymes, lipid metabolism, and learning and memory ability in metabolically healthy Sprague-Dawley rats. The results showed that all rats survived and pathological, toxic, feces, and urine changes were not observed. Chromium malate did not cause measurable damage on liver, brain, and kidney. The fasting blood glucose, serum insulin, insulin resistance index, C-peptide, hepatic glycogen, glucose-6-phosphate dehydrogenase, glucokinase, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels of normal rats in chromium malate groups had no significant change when compared with control group and chromium picolinate group under physiologically relevant conditions. The serum and organ content of Cr in chromium malate groups had no significant change compared with control group. No significant changes were found in morris water maze test and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and true choline esterase (TChE) activity. The results indicated that supplementation with chromium malate did not cause measurable toxicity and has no obvious effect on glycometabolism and related enzymes, learning and memory ability, and related enzymes and lipid metabolism of female and male rats. The results of this study suggest that chromium malate is safe for human consumption.

  6. Evaluation of a repeated dose liver micronucleus assay in rats treated with two genotoxic hepatocarcinogens, dimethylnitrosamine and 2-acetylaminofluorene: the possibility of integrating micronucleus tests with multiple tissues into a repeated dose general toxicity study.

    Science.gov (United States)

    Takashima, Rie; Takasawa, Hironao; Kawasako, Kazufumi; Ohyama, Wakako; Okada, Emiko; Narumi, Kazunori; Fujiishi, Yohei; Wako, Yumi; Yasunaga, Katsuaki; Hattori, Akiko; Kawabata, Masayoshi; Nakadate, Kiyoko; Nakagawa, Munehiro; Hamada, Shuichi

    2015-03-01

    As part of a collaborative study by the Collaborative Study Group for Micronucleus Test (CSGMT) of the Mammalian Mutagenicity Study Group (MMS) in the Japanese Environmental Mutagen Society (JEMS), the present study evaluated the effectiveness of the repeated dose liver micronucleus (RDLMN) assay. Two genotoxic hepatocarcinogens, dimethylnitrosamine (DMN) and 2-acetylaminofluorene (2-AAF), were administered orally to male rats (6 weeks old at the initial dosing) once daily for 14 and 28 days to evaluate the micronucleus (MN) inducibility in the liver. In addition, these chemicals were evaluated for MN inducibility in the bone marrow (BM) and gastrointestinal (GI) tract, i.e. glandular stomach and colon of the same animals used in the RDLMN assay. As a result, both chemicals produced positive results in the liver, although a weak positive response was given by 2-AAF. DMN gave negative results in the tissues other than the liver. 2-AAF produced positive responses in the BM and glandular stomach, and a prominent response was particularly observed in the glandular stomach, which is directly exposed to the test chemicals by gavage. The present results suggest that the RDLMN assay is a useful method for detecting genotoxic hepatocarcinogens, and that it is especially effective for evaluating test chemicals, such as DMN, undetectable by the BM and GI tract MN assay. Moreover, the results in this investigation indicate that the use of multiple tissues in the study integrating the MN tests is more effective than using a single tissue, for detection of the MN induction produced by chemical exposure to rats, and helps to determine the characteristics of the test chemicals.

  7. Clinical and Microscopic Characteristics of Canine Toxic Epidermal Necrolysis

    National Research Council Canada - National Science Library

    Banovic, F; Olivry, T; Bazzle, L; Tobias, J. R; Atlee, B; Zabel, S; Hensel, N; Linder, K. E

    2015-01-01

    Canine toxic epidermal necrosis (TEN), a rare and life-threatening cutaneous drug reaction, traditionally has been described as full-thickness devitalization of the epidermis with minimal dermal inflammation...

  8. Decreased level of Nurr1 in heterozygous young adult mice leads to exacerbated acute and long-term toxicity after repeated methamphetamine exposure.

    Directory of Open Access Journals (Sweden)

    Yu Luo

    Full Text Available The abuse of psychostimulants, such as methamphetamine (METH, is prevalent in young adults and could lead to long-term adaptations in the midbrain dopamine system in abstinent human METH abusers. Nurr1 is a gene that is critical for the survival and maintenance of dopaminergic neurons and has been implicated in dopaminergic neuron related disorders. In this study, we examined the synergistic effects of repeated early exposure to methamphetamine in adolescence and reduction in Nurr1 gene levels. METH binge exposure in adolescence led to greater damage in the nigrostrial dopaminergic system when mice were exposed to METH binge later in life, suggesting a long-term adverse effect on the dopaminergic system. Compared to naïve mice that received METH binge treatment for the first time, mice pretreated with METH in adolescence showed a greater loss of tyrosine hydroxylase (TH immunoreactivity in striatum, loss of THir fibers in the substantia nigra reticulata (SNr as well as decreased dopamine transporter (DAT level and compromised DA clearance in striatum. These effects were further exacerbated in Nurr1 heterozygous mice. Our data suggest that a prolonged adverse effect exists following adolescent METH binge exposure which may lead to greater damage to the dopaminergic system when exposed to repeated METH later in life. Furthermore, our data support that Nurr1 mutations or deficiency could be a potential genetic predisposition which may lead to higher vulnerability in some individuals.

  9. An antisense CAG repeat transcript at JPH3 locus mediates expanded polyglutamine protein toxicity in Huntington's disease-like 2 mice.

    Science.gov (United States)

    Wilburn, Brian; Rudnicki, Dobrila D; Zhao, Jing; Weitz, Tara Murphy; Cheng, Yin; Gu, Xiaofeng; Greiner, Erin; Park, Chang Sin; Wang, Nan; Sopher, Bryce L; La Spada, Albert R; Osmand, Alex; Margolis, Russell L; Sun, Yi E; Yang, X William

    2011-05-12

    Huntington's disease-like-2 (HDL2) is a phenocopy of Huntington's disease caused by CTG/CAG repeat expansion at the Junctophilin-3 (JPH3) locus. The mechanisms underlying HDL2 pathogenesis remain unclear. Here we developed a BAC transgenic mouse model of HDL2 (BAC-HDL2) that exhibits progressive motor deficits, selective neurodegenerative pathology, and ubiquitin-positive nuclear inclusions (NIs). Molecular analyses reveal a promoter at the transgene locus driving the expression of a CAG repeat transcript (HDL2-CAG) from the strand antisense to JPH3, which encodes an expanded polyglutamine (polyQ) protein. Importantly, BAC-HDL2 mice, but not control BAC mice, accumulate polyQ-containing NIs in a pattern strikingly similar to those in the patients. Furthermore, BAC mice with genetic silencing of the expanded CUG transcript still express HDL2-CAG transcript and manifest polyQ pathogenesis. Finally, studies of HDL2 mice and patients revealed CBP sequestration into NIs and evidence for interference of CBP-mediated transcriptional activation. These results suggest overlapping polyQ-mediated pathogenic mechanisms in HD and HDL2.

  10. Dermal benefits of topical D-ribose

    Directory of Open Access Journals (Sweden)

    Linda M Shecterle

    2009-09-01

    Full Text Available Linda M Shecterle, John A St. CyrJacqmar, Inc., Minneapolis, MN, USAAbstract: Our aging skin undergoes changes with reductions in collagenous and elastic fibers, fibroblasts, mast cells, and macrophages with free radical production, which can result in reduced skin tone and wrinkle formation. Fibroblasts are important for dermal integrity and function with a decrease in function producing less skin tone, thinning, and wrinkle formation. Dermal levels of adenosine triphosphate (ATP decline with aging, potentially altering dermal function. Supplemental D-ribose, a natural occurring carbohydrate, enhances ATP regeneration. D-ribosebased studies demonstrated benefits in both cell culture fibroblastic activities and a subsequent clinical study in women with decreased skin tone with wrinkles. Supplemental D-ribose may offer this needed cellular benefit.Keywords: dermal, fibroblast, ATP, aging, wrinkles

  11. Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

    Science.gov (United States)

    Milán, Aroha Belen Sánchez; Campmany, Ana C Calpena; Naveros, Beatriz Clares

    2017-02-22

    Melatonin (MLT) is emerging as a promising therapeutic agent, mainly due to its role as antioxidant. Substantial evidences show that melatonin is potentially effective on a variety of diseases as cancer, inflammation and neurodegenerative diseases. The excellent antioxidant capacity with pharmacokinetics characteristics and the emerging search for new pharmaceutical nanotechnology based systems, make it particularly attractive to elaborate nanoplatforms based on MLT for biomedical or cosmetic dermal applications. Different nanosystems for dermal delivery have been investigated. These nanosystems are expected to play a significant role in the protection of therapeutic functions of MLT, enhanced transdermal permeability and dermal delivery profiles. These nanocarriers not only transport MLT, but also increase the solubility, bioavailability, half-life and antioxidant activity. In the current review, we will focus on nanocarrier production strategies, dermal MLT application and delivery advances in vivo and in vitro. Equally, future perspectives of this assisted MLT delivery will be also discussed.

  12. Dermal administration of manganese porphyrin by iontophoresis.

    Science.gov (United States)

    Ito, Fuminori; Imamura, Shinya; Asayama, Shoichiro; Kanamura, Kiyoshi; Kawakami, Hiroyoshi

    2014-08-01

    The present study describes a technique for dermal administration of cationic manganese porphyrin (Mn-porphyrin), an antioxidant with superoxide dismutase (SOD) activity, in hairless mouse. In general, the stratum corneum on the surface of the skin represents a barrier to passive diffusion of therapeutic agents by standard dermal administration. The present study investigated whether, dermal administration of Mn-porphyrin solution using iontophoresis, the electrical dermal administration technique, could overcome this barrier. We visually confirmed that Mn-porphyrin had penetrated to the reverse side of the hairless mouse skin after iontophoresis for a short period. With prolonged iontophoresis, the ratio of detectable Mn-porphyrin solution on the reverse side of the hairless mouse skin increased. In the future, this technique could provide an innovative approach for delivery of this antioxidant in intractable disease.

  13. Pengujian Toksisitas Akut Oral Dan Dermal pada Biolarvasida Metarhizium anisopliae terhadap Tikus Putih Spraque Dawley

    Directory of Open Access Journals (Sweden)

    Deni Zulfiana

    2016-03-01

    Full Text Available Acute oral and dermal toxicity test against white rats was conducted to determine the toxicity and side effects of bio-larvacide (Metarhizium anisopliae crude extract on humans. In the oral test used a maximum dose 5000 mg/kg and dermal testing used a maximum dose of 2000 mg/kg. Dose treatment and control tested to 5 Spraque Dawley male rats. The results showed that oral treatment with a dose of 5000 mg/kg did not cause mortality and did not cause changes in anatomic pathology of viceral organs. In the dermal treatment with a dose of 2000 mg/kg did not cause mortality and did not cause changes in anatomic pathology of viceral organs. Based on these results LD50 acute oral M. anisopliae biolarvacide above 5000 mg/kg and the acute dermal is above 2000 mg/kg. It was therefore concluded that the formulation of Metarhizium anisopliae biolarvasida classified as not hazardous when used in accordance with the recommendation of the class I (WHO, 2003.

  14. Teratogenicity study of N-methylpyrrolidone after dermal application to Sprague-Dawley rats.

    Science.gov (United States)

    Becci, P J; Knickerbocker, M J; Reagan, E L; Parent, R A; Burnette, L W

    1982-01-01

    Teratogenicity studies were performed in rats given N-methylpyrrolidone, a solvent used in chemical processing. Dosages of 75,237 and 750 mg of N-methylpyrrolidone/kg body weight/day were administered dermally to groups of 25 pregnant Sprague-Dawley rats on days 6 through 15 of gestation. Additionally, the study used a positive dermal control. Hexafluoroacetone, was chosen based on its dermal teratogenic activity. An oral positive control, aspirin, was included in order to add significance to the data generated in the experimental positive dermal control group. All animals were killed and subjected to uterine examination on day 20 of gestation. Maternal toxicity was indicated at 750 mg of N-methylpyrrolidone/kg by reduced body weight gain during gestation. Treatment with N-methylpyrrolidone resulted in dose-dependent brightly colored yellow urine and dry skin. Treatment at the high dosage level resulted in fewer live fetuses per dam, an increase in the percentage of resorption sites and skeletal abnormalities. These effects could be the result of maternal toxicity. There was no evidence of teratogenic effects nor effects on the dams at 75 and 237 mg/kg of body weight.

  15. Statistical tools for analysing the data obtained from repeated dose toxicity studies with rodents: a comparison of the statistical tools used in Japan with that of used in other countries.

    Science.gov (United States)

    Kobayashi, Katsumi; Pillai, K Sadasivan; Guhatakurta, Soma; Cherian, K M; Ohnishi, Mariko

    2011-01-01

    In the present study, an attempt was made to compare the statistical tools used for analysing the data of repeated dose toxicity studies with rodents conducted in 45 countries, with that of Japan. The study revealed that there was no congruence among the countries in the use of statistical tools for analysing the data obtained from the above studies. For example, to analyse the data obtained from repeated dose toxicity studies with rodents, Scheffé's multiple range and Dunnett type (joint type Dunnett) tests are commonly used in Japan, but in other countries use of these statistical tools is not so common. However, statistical techniques used for testing the above data for homogeneity of variance and inter-group comparisons do not differ much between Japan and other countries. In Japan, the data are generally not tested for normality and the same is true with the most of the countries investigated. In the present investigation, out of 127 studies examined, data of only 6 studies were analysed for both homogeneity of variance and normal distribution. For examining homogeneity of variance, we propose Levene's test, since the commonly used Bartlett's test may show heterogeneity in variance in all the groups, if a slight heterogeneity in variance is seen any one of the groups. We suggest the data may be examined for both homogeneity of variance and normal distribution. For the data of the groups that do not show heterogeneity of variance, to find the significant difference among the groups, we recommend Dunnett's test, and for those show heterogeneity of variance, we recommend Steel's test.

  16. Systemic and immunotoxicity of pristine and PEGylated multi-walled carbon nanotubes in an intravenous 28 days repeated dose toxicity study

    Science.gov (United States)

    Zhang, Ting; Tang, Meng; Zhang, Shanshan; Hu, Yuanyuan; Li, Han; Zhang, Tao; Xue, Yuying; Pu, Yuepu

    2017-01-01

    The numerous increasing use of carbon nanotubes (CNTs) derived from nanotechnology has raised concerns about their biosafety and potential toxicity. CNTs cause immunologic dysfunction and limit the application of CNTs in biomedicine. The immunological responses induced by pristine multi-walled carbon nanotubes (p-MWCNTs) and PEGylated multi-walled carbon nanotubes (MWCNTs-PEG) on BALB/c mice via an intravenous administration were investigated. The results reflect that the p-MWCNTs induced significant increases in spleen, thymus, and lung weight. Mice treated with p-MWCNTs showed altered lymphocyte populations (CD3+, CD4+, CD8+, and CD19+) in peripheral blood and increased serum IgM and IgG levels, and splenic macrophage ultrastructure indicated mitochondria swelling. p-MWCNTs inhibited humoral and cellular immunity function and were associated with decreased immune responses against sheep erythrocytes and serum hemolysis level. Natural killer (NK) activity was not modified by two types of MWCNTs. In comparison with two types of MWCNTs, for a same dose, p-MWCNTs caused higher levels of inflammation and immunosuppression than MWCNTs-PEG. The results of immunological function suggested that after intravenous administration with p-MWCNTs caused more damage to systemic immunity than MWCNTs-PEG. Here, we demonstrated that a surface functional modification on MWCNTs reduces their immune perturbations in vivo. The chemistry-modified MWCNTs change their preferred immune response in vivo and reduce the immunotoxicity of p-MWCNTs. PMID:28280324

  17. Comparative 28-day repeated oral toxicity of Longdan Xieganwan, Akebia trifoliate (Thunb.) koidz., Akebia quinata (Thunb.) Decne. and Caulis aristolochiae manshuriensis in mice.

    Science.gov (United States)

    Xue, Xiang; Xiao, Ying; Gong, Likun; Guan, Shuhong; Liu, Yongzhen; Lu, Henglei; Qi, Xinming; Zhang, Yunhai; Li, Yan; Wu, Xiongfei; Ren, Jin

    2008-09-02

    Longdan Xieganwan, which contains Aristolochia species, is a traditional Chinese prescription. It has been used for thousands of years to "enhance liver". However, many cases of Longdan Xieganwan induced nephropathy were reported recently. This study was designed to compare the possible toxic effects of Longdan Xieganwan and three different Aristolochia species, i.e. Akebia trifoliate (Thunb.) koid (Akebia trifoliate), Akebia quinata (Thunb.) Decne. (Akebia quinata) and Caulis aristolochiae manshuriensis (Aristolochia manshuriensis). Mice were orally administered these drugs for 28 days. Clinical signs, body weights, serum biochemistry, organ weights and histopathology were examined. Significantly decreased body weights and obvious nephropathy were noticed in the Aristolochia manshuriensis groups at doses higher than 0.24 g/kg/d. A few endothelial cell degenerations in renal glomerulus were observed in the Akebia trifoliate group at a high-dose of 2.00 g/kg/d. No significant changes were observed in the other groups. The no-observed-adverse-effect levels (NOAELs) for Aristolochia manshuriensis, Akebia trifoliate, Akebia quinata and Longdan Xieganwan in this study for mice were 0.06 g/kg/d, 0.40 g/kg/d, higher than 3.00 g/kg/d and higher than 10.00 g/kg/d, which were equivalent to 0.25 times, 5 times, 25 times and 10 times of normal human dose in clinical prescription, respectively.

  18. Evaluation of the cytotoxicity of cell free dermal substitutes using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method

    Institute of Scientific and Technical Information of China (English)

    NING Fang-gang; ZHANG Guo-an

    2010-01-01

    Background The cytotoxicity of dermal substitutes may be increased by the very processes used to deplete the cells. The present research aimed to investigate the method for monitoring the cytotoxicity of cell-free dermal substitutes using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method.Methods The cytotoxicity of four dermal substitutes was evaluated using the MTT method according to the standards set by the Chinese State Food and Drug Administration (SFDA). Swine acellular dermal matrix (SADM) and goat acellular dermal matrix (GADM) were produced using a repeated freeze-thaw method. Human dermal matrix glutaraldehyde composite (HADM-G) and SADM cross-linked with glutaraldehyde (SADM-G) were produced using conventional methods. Results The cytotoxicity of all dermal substitutes ranged from Grade 0 to Grade 1, meeting the standards of the Chinese FDA. The OD_(490) of both SADM and GADM was higher than that of either HADM-G or SADM-G (P<0.05). Conclusion Dermal substitutes produced by the freeze-thaw method are less cytotoxic than those produced using conventional methods.

  19. 40 CFR 799.9325 - TSCA 90-day dermal toxicity.

    Science.gov (United States)

    2010-07-01

    ... measured. Measurements of additional enzymes (of hepatic or other origin) and bile acids, may also be... latency period for development (e.g., carcinogenicity and life shortening). Extrapolation from the results... the test animal's life span. Target organ is any organ of a test animal showing evidence of an effect...

  20. Acute Dermal Toxicity of Trimethylolethane Trinitrate (TMETN) in Rabbits

    Science.gov (United States)

    1989-07-01

    and lateral sections of the animals (surface area approximately 300 cm 2 ) were close-clipped with electric clippers (Oster® Model A5, Size 40 blade...13 Nov 84 Cause: Unknown Syndrome : None Gross Comments: All lesions including the liver lesion were considered as incidental findings and not

  1. Polymethylmethacrylate dermal fillers: evaluation of the systemic toxicity in rats.

    Science.gov (United States)

    Medeiros, C C G; Borghetti, R L; Nicoletti, N; da Silva, V D; Cherubini, K; Salum, F G; de Figueiredo, M A Z

    2014-01-01

    This study evaluated local and systemic reactions after an intravascular injection of polymethylmethacrylate (PMMA) at two concentrations in a murine model. Thirty rats were divided equally into three groups: 2% PMMA, 30% PMMA, and a control group (normal saline only injection). The filler was injected into the ranine vein. The rats were sedated at 7 and 90 days and a clinical evaluation performed. After euthanasia, the right lung, liver, and right kidney were removed, weighed, and microscopically analyzed. The submandibular lymph nodes and tongue were removed and examined microscopically. Serum was subjected to liver and kidney function tests. No groups showed clinical alterations. Microspheres were not observed at any distant organ. Two samples from the 2% PMMA group showed a local inflammatory response at day 7 and another two samples from the 30% PMMA group at day 90. The group injected with 30% PMMA presented higher levels of alanine aminotransferase (P = 0.047) after 90 days when compared with the other groups. The data obtained in this study demonstrate that intravascular injections of PMMA fillers show potential health risks such as chronic inflammation at the implantation site.

  2. Repeated high-dose (5 × 10(8) TCID50) toxicity study of a third generation smallpox vaccine (IMVAMUNE) in New Zealand white rabbits.

    Science.gov (United States)

    Tree, Julia A; Hall, Graham; Rees, Peter; Vipond, Julia; Funnell, Simon G P; Roberts, Allen D

    2016-07-01

    Concern over the release of variola virus as an agent of bioterrorism remains high and a rapid vaccination regimen is desirable for use in the event of a confirmed release of virus. A single, high-dose (5×10(8) TCID50) of Bavarian Nordic's IMVAMUNE was tested in a Phase-II clinical trial, in humans, as a substitute for the standard (1×10(8) TCID50), using a 2-dose, 28-days apart regimen. Prior to this clinical trial taking place a Good Laboratory Practice, repeated high-dose, toxicology study was performed using IMVAMUNE, in New Zealand white rabbits and the results are reported here. Male and female rabbits were dosed twice, subcutaneously, with 5×10(8) TCID50 of IMVAMUNE (test) or saline (control), 7-days apart. The clinical condition, body-weight, food consumption, haematology, blood chemistry, immunogenicity, organ-weight, and macroscopic and microscopic pathology were investigated. Haematological investigations indicated changes within the white blood cell profile that were attributed to treatment with IMVAMUNE; these comprised slight increases in neutrophil and monocyte numbers, on study days 1-3 and a marginal increase in lymphocyte numbers on day 10. Macroscopic pathology revealed reddening at the sites of administration and thickened skin in IMVAMUNE, treated animals. After the second dose of IMVAMUNE 9/10 rabbits seroconverted, as detected by antibody ELISA on day 10, by day 21, 10/10 rabbits seroconverted. Treatment-related changes were not detected in other parameters. In conclusion, the subcutaneous injection of 2 high-doses of IMVAMUNE, to rabbits, was well tolerated producing only minor changes at the site of administration. Vaccinia-specific antibodies were raised in IMVAMUNE-vaccinated rabbits only.

  3. Assessment of the safety of hydrogenated resistant maltodextrin: reverse mutation assay, acute and 90-day subchronic repeated oral toxicity in rats, and acute no-effect level for diarrhea in humans.

    Science.gov (United States)

    Yoshikawa, Yuko; Kishimoto, Yuka; Tagami, Hiroyuki; Kanahori, Sumiko

    2013-01-01

    A series of safety assessments were performed on hydrogenated resistant maltodextrin prepared by converting the reducing terminal glucose of resistant maltodextrin into sorbitol. The reverse mutation assay did not show mutagenicity. Acute and 90-day subchronic oral toxicity studies in rats showed no death was observed in any groups, including the group receiving the highest single dose of 10 g/kg body weight or the highest dose of 5 g/kg body weight per day for 90 days. Mucous or watery stools were observed in the hydrogenated resistant maltodextrin treatment group on the acute study, which were transient and were associated with the osmotic pressure caused by intake of the high concentrations. Subchronic study showed dose-dependent increases in the weights of cecum alone, cecal contents alone, and cecum with cecal contents as well as hypertrophy of the cecal mucosal epithelium, which are considered to be common physiological responses after intake of indigestible carbohydrates. These results indicated that the no observed adverse effect level (NOAEL) of hydrogenated resistant maltodextrin was 10 g/kg body weight or more on the acute oral toxicity study and 5.0 g/kg body weight/day or more on the 90-day subchronic repeated oral toxicity study in rats. Further study performed in healthy adult humans showed that the acute no-effect level of hydrogenated resistant maltodextrin for diarrhea was 0.8 g/kg body weight for men and more than 1.0 g/kg body weight for women. The results of the current safety assessment studies suggest that hydrogenated resistant maltodextrin is safe for human consumption.

  4. Methods for assessing risks of dermal exposures in the workplace.

    Science.gov (United States)

    McDougal, James N; Boeniger, Mark F

    2002-07-01

    The skin as a route of entry for toxic chemicals has caused increasing concern over the last decade. The assessment of systemic hazards from dermal exposures has evolved over time, often limited by the amount of experimental data available. The result is that there are many methods being used to assess safety of chemicals in the workplace. The process of assessing hazards of skin contact includes estimating the amount of substance that may end up on the skin and estimating the amount that might reach internal organs. Most times, toxicology studies by the dermal route are not available and extrapolations from other exposure routes are necessary. The hazards of particular chemicals can be expressed as "skin notations", actual exposure levels, or safe exposure times. Characterizing the risk of a specific procedure in the workplace involves determining the ratio of exposure standards to an expected exposure. The purpose of this review is to address each of the steps in the process and describe the assumptions that are part of the process. Methods are compared by describing their strengths and weaknesses. Recommendations for research in this area are also included.

  5. Pulmonary toxicity of polyvinyl chloride particles after repeated intratracheal instillations in rats. Elevated CD4/CD8 lymphocyte ratio in bronchoalveolar lavage.

    Science.gov (United States)

    Xu, Haiyan; Vanhooren, Hadewijch M; Verbeken, Erik; Yu, Lisong; Lin, Yuan; Nemery, Benoit; Hoet, Peter H M

    2004-01-15

    Occupational exposure to polyvinyl chloride (PVC) particles has been associated with interstitial lung disease. Our previous study showed that a single intratracheal instillation of emulsion PVC particles, with or without residual additives, induces acute but transient alveolitis in a dose-dependent manner in rats. The aim of the present study was to investigate the pulmonary response after the administration of the same PVC particles (PVC-E3 and PVC-W3) given in the same cumulative doses (10 and 50 mg/kg BW), but fractionated as seven intratracheal instillations (7 x 1.4 and 7 x 7.1 mg/kg BW) in the course of 3 weeks (day 0 to day 21). Pulmonary response was characterized by analysis of lung weight, bronchoalveolar lavage (BAL) fluid for lactate dehydrogenase (LDH), total protein, and cell cytology, and a microscopic evaluation of lung tissue. BAL T lymphocyte phenotypes (CD3 + CD4 +, CD3 + CD8+) were analyzed by flow cytometry. On day 28, lung weights, BAL-LDH, cell numbers in BAL, and CD4/CD8 ratios in BAL T lymphocytes were higher in rats that had received the high dose of PVC-E3 or PVC-W3 than in rats that had received the low dose of PVC particles and control rats. On day 90, the pulmonary response had partially regressed towards control values, but there were still microscopically evident lesions in the lungs and greater CD4/CD8 ratio in the high dose groups. There were significant positive correlations between the CD4/CD8 ratio and a histopathology score of the lung (r = 0.36, P = 0.038 on day 28, and r = 0.46, P = 0.006 on day 90). In conclusion, repeated intratracheal instillations of PVC particles yielded similar results as single instillations. The examined PVC particles have the potential of inducing a limited and transient acute inflammatory reaction in the lung, and possibly a more persistent alteration of pulmonary T lymphocyte subsets towards a high CD4/CD8 ratio.

  6. Serial non-invasive measurements of dermal carotenoid concentrations in dairy cows following recovery from abomasal displacement.

    Directory of Open Access Journals (Sweden)

    Julian Klein

    Full Text Available Maintaining the health of farm animals forms the basis for a sustainable and profitable production of food from animal origin. Recently, the effects of carotenoids on the oxidative status as well as on reproductive and immune functions in cattle have been demonstrated. The present study aimed at investigating dermal carotenoid levels in cattle recovering from abomasal displacement. For this purpose, serial in vivo measurements were undertaken using a miniaturized scanner system that relies on reflection spectroscopy (Opsolution GmbH, Kassel, Germany. In a first trial, repeated measurements of dermal carotenoid concentrations were performed on the udder skin of healthy non-lactating cattle (n = 6 for one month in weekly intervals. In a second trial, in vivo dermal carotenoid concentrations were determined in intervals in 23 cows following surgical treatment of abomasal displacement. The results show that dermal carotenoid concentrations, determined on a weekly basis over a period of one month, showed variations of up to 18% in the healthy individuals kept under constant conditions with respect to housing and nutrition. Repeated measurements during the recovery period following surgical treatment of abomasal displacement resulted in an increase in dermal carotenoid concentrations in 18 of 20 animals with a favourable outcome when compared with results obtained within 12 hours following surgery. The mean increase in dermal carotenoid concentrations in subsequent measurements was 53 ± 44%, whereas levels decreased (mean 31 ± 27% in cattle with a fatal outcome.These results indicate potential applications for reflection spectroscopy for non-invasive early detection of changes in the dermal carotenoid concentrations as a reflection of the antioxidant status in an animal.

  7. Site-specific rectocele repair with dermal graft augmentation: comparison of porcine dermal xenograft (Pelvicol) and human dermal allograft.

    Science.gov (United States)

    Biehl, Roger C; Moore, Robert D; Miklos, John R; Kohli, Neeraj; Anand, Indu S; Mattox, T Fleming

    2008-01-01

    This study is a retrospective chart review comparing 195 women who underwent rectocele repair with either a porcine dermal xenograft or human allogenic cadaveric dermal graft augmentation over a two year period. A site-specific defect repair was completed prior to augmentation with the graft. Examinations were performed preoperatively and postoperatively using the pelvic organ prolapse quantification system. Questionnaires were used to assess constipation and dyspareunia. De novo dyspareunia and cure rates for constipation and dyspareunia were not statistically different between the two groups. Site-specific fascial rectocele repairs with xenograft or allograft augmentation were found to have similar complication rates as well as objective and subjective cure rates.

  8. Assessment of ZnO and SiO2 nanoparticle permeability through and toxicity to the blood-brain barrier using Evans blue and TEM.

    Science.gov (United States)

    Shim, Kyu Hwan; Jeong, Kyeong-Hoon; Bae, Sun Oh; Kang, Min O; Maeng, Eun Ho; Choi, Cheol Soo; Kim, Yu-Ri; Hulme, John; Lee, Eun Kyu; Kim, Meyoung-Kon; An, Seong Soo A

    2014-01-01

    As increasing variants of nanoparticles (NPs) are being used in various products, it has become apparent that size alone can no longer adequately explain the variety of generated toxic profiles. Recent studies with NPs have suggested that various sizes of NPs could determine in vitro toxicity. In an attempt to address concerns regarding neurotoxicity of zinc oxide (ZnO) and silica (SiO2) NPs, these were examined after exposing them via oral, dermal, and intravenous administrations of NPs and their toxicological effects on the brain over a prescribed period of time were assessed. After 28 days of repeated oral administrations of ZnO or SiO2 independently, possibly due to damages to the blood brain barrier (BBB), neurotoxicity, were investigated by Evans blue technique. Next, in order to assess whether ZnO NPs could compromise the BBB, ZnO NPs were intravenously injected on day 0, 7, 14, 21 and 28 no further treatment was administered for 62 days. Deposition of SiO2 in brain from repeated dermal and oral administrations for 90 days were evaluated by transmission electron microscopy coupled with scanning energy-dispersive X-ray spectroscopy. Physiochemical profiles were principally determined on particle size at the beginning of the current toxicity investigations on ZnO and SiO2 NPs. The BBB was found to be intact after independent repeated oral administrations of ZnO or SiO2 NPs for 28 days, suggesting no significant damage. Neuronal death was also not observed after the intravenous administrations of ZnO NPs. After 90 days of repeated dermal and oral administration of SiO2 NPs, no deposition of NPs was observed in hippocampus, striatum, and cerebellum regions using transmission electron microscope analyses. These observations suggest that the BBB was not compromised and was able to block penetration of ZnO and SiO2 NPs, resulting in significant neurotoxic effects. Moreover, absence of SiO2 in three regions of brain after dermal and oral administrations for 90 days

  9. Improved epidermal barrier formation in human skin models by chitosan modulated dermal matrices

    Science.gov (United States)

    Mieremet, Arnout; Rietveld, Marion; Absalah, Samira; van Smeden, Jeroen

    2017-01-01

    Full thickness human skin models (FTMs) contain an epidermal and a dermal equivalent. The latter is composed of a collagen dermal matrix which harbours fibroblasts. Current epidermal barrier properties of FTMs do not fully resemble that of native human skin (NHS), which makes these human skin models less suitable for barrier related studies. To further enhance the resemblance of NHS for epidermal morphogenesis and barrier formation, we modulated the collagen dermal matrix with the biocompatible polymer chitosan. Herein, we report that these collagen-chitosan FTMs (CC-FTMs) possess a well-organized epidermis and maintain both the early and late differentiation programs as in FTMs. Distinctively, the epidermal cell activation is reduced in CC-FTMs to levels observed in NHS. Dermal-epidermal interactions are functional in both FTM types, based on the formation of the basement membrane. Evaluation of the barrier structure by the organization of the extracellular lipid matrix of the stratum corneum revealed an elongated repeat distance of the long periodicity phase. The ceramide composition exhibited a higher resemblance of the NHS, based on the carbon chain-length distribution and subclass profile. The inside-out barrier functionality indicated by the transepidermal water loss is significantly improved in the CC-FTMs. The expression of epidermal barrier lipid processing enzymes is marginally affected, although more restricted to a single granular layer. The novel CC-FTM resembles the NHS more closely, which makes them a promising tool for epidermal barrier related studies. PMID:28333992

  10. Deployment Repeatability

    Science.gov (United States)

    2016-04-01

    controlled to great precision, but in a Cubesat , there may be no attitude determination at all. Such a Cubesat might treat sun angle and tumbling rates as...could be sensitive to small differences in motor controller timing. In these cases, the analyst might choose to model the entire deployment path, with...knowledge of the material damage model or motor controller timing precision. On the other hand, if many repeated and environmentally representative

  11. New in vitro dermal absorption database and the prediction of dermal absorption under finite conditions for risk assessment purposes

    NARCIS (Netherlands)

    Buist, H.E.; Burgsteden, J.A. van; Freidig, A.P.; Maas, W.J.M.; Sandt, J.J.M. van de

    2010-01-01

    Most QSARs for dermal absorption predict the permeability coefficient, Kp, of a molecule, which is valid for infinite dose conditions. In practice, dermal exposure mostly occurs under finite dose conditions. Therefore, a simple model to predict finite dose dermal absorption from infinite

  12. Assessment of dermal exposure to chemicals

    NARCIS (Netherlands)

    Hemmen, J.J. van; Brouwer, D.H.

    1995-01-01

    The methods for the dermal exposure assessment vary in their complexity and are in some sense complementary to each other. The most easy-to-use methods involve a pseudo-skin-approach, such as gloves and removal by washing. In some cases generic modelling appears to be possible. The experimental

  13. Focal dermal hypoplasia: A rare case report

    Directory of Open Access Journals (Sweden)

    Sahana M Srinivas

    2015-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem disorder primarily involving the skin, skeletal system, eyes, and face. We report the case of an eight-month-old female child who presented with multiple hypopigmented atrophic macules along the lines of blaschko, skeletal anomalies, umbilical hernia, developmental delay, hypoplastic nails, syndactyly, and lobster claw deformity characteristic of Goltz syndrome.

  14. Assessment of dermal exposure to chemicals

    NARCIS (Netherlands)

    Hemmen, J.J. van; Brouwer, D.H.

    1995-01-01

    The methods for the dermal exposure assessment vary in their complexity and are in some sense complementary to each other. The most easy-to-use methods involve a pseudo-skin-approach, such as gloves and removal by washing. In some cases generic modelling appears to be possible. The experimental meth

  15. Acellular Dermal Matrix in Postmastectomy Breast Reconstruction

    NARCIS (Netherlands)

    A.M.S. Ibrahim (Ahmed)

    2014-01-01

    markdownabstract__Abstract__ Over the last decade the use of acellular dermal matrix (ADM) in reconstructive breast surgery has been transformative. Some authors have gone as far as to suggest that it is the single most important advancement in prosthetic breast reconstruction. ADMs are able

  16. Dermal permeation of biocides and aromatic chemicals in three generic formulations of metalworking fluids.

    Science.gov (United States)

    Vijay, Vikrant; White, Eugene M; Kaminski, Michael D; Riviere, Jim E; Baynes, Ronald E

    2009-01-01

    Metalworking fluids (MWF) are complex mixtures consisting of a variety of components and additives. A lack of scientific data exists regarding the dermal permeation of its components, particularly biocides. The aim of this study was to evaluate the dermal permeation of biocides and other aromatic chemicals in water and in three generic soluble oil, semi-synthetic, and synthetic MWF types in order to evaluate any differences in their permeation profiles. An in vitro flow-through diffusion cell study was performed to determine dermal permeation. An infinite dose of different groups of chemicals (6 biocides and 29 aromatic chemicals) was applied to porcine skin, with perfusate samples being collected over an 8-h period. Perfusate samples were analyzed by gas chromatography/mass spectrometry (GC-MS) and ultra-performance liquid chromatography/mass spectroscopy (UPLC-MS), and permeability was calculated from the analysis of the permeated chemical concentration-time profile. In general, the permeation of chemicals was highest in aqueous solution, followed by synthetic, semi-synthetic, and soluble oil MWF. The absorption profiles of most of the chemicals including six biocides were statistically different among the synthetic and soluble oil MWF formulations, with reduced permeation occurring in oily formulations. Permeation of almost all chemicals was statistically different between aqueous and three MWF formulation types. Data from this study show that permeation of chemicals is higher in a generic synthetic MWF when compared to a soluble oil MWF. This indicates that a soluble oil MWF may be safer than a synthetic MWF in regard to dermal permeation of chemicals to allow for an increased potential of systemic toxicity. Therefore, one may conclude that a synthetic type of formulation has more potential to produce contact dermatitis and induce systemic toxicological effects. The dilution of these MWF formulations with water may increase dermal permeability of biocides

  17. Hyaluronic acid dermal fillers: can adjunctive lidocaine improve patient satisfaction without decreasing efficacy or duration?

    Science.gov (United States)

    Smith, Lynnelle; Cockerham, Kimberly

    2011-03-14

    Hyaluronic acid (HA) dermal fillers are the most widely used injectables to augment facial volume without surgery. HA dermal fillers are popular because of their ease of administration, predictable effectiveness, good safety profile, and quick patient recovery. The most common patient complaint is pain. Our goal is to review the current literature on HA fillers and compare outcomes with and without lidocaine. We found adjunctive lidocaine significantly decreases pain during injection and postinjection with corresponding increased patient satisfaction. The efficacy and safety profile appears unchanged. Rare complications with HA fillers and those associated with constituents of the product, contaminants, and lidocaine are reviewed. The corrective effects of HA fillers are temporary; repeat treatment is required to maintain results. Minimizing pain is crucial to optimize patient satisfaction.

  18. Assessment of dermal exposure and histopathologic changes of different sized nano-silver in healthy adult rabbits

    Energy Technology Data Exchange (ETDEWEB)

    Koohi, Mohammad kazem; Hejazy, Marzie [Toxicology division, Basic science department, Faculty of Veterinary Medicine, University of Tehran, Qareeb Street, Azadi Av. PO Box: 14155-6453, Tehran (Iran, Islamic Republic of); Asadi, Farzad [Biochemistry division, Basic science department, Faculty of Veterinary Medicine, University of Tehran, Qareeb Street, Azadi Av. PO Box: 14155-6453, Tehran (Iran, Islamic Republic of); Asadian, Peyman, E-mail: mkkoohi@ut.ac.ir [Clinical pathology department, Faculty of Veterinary Medicine, University of Khorramabad (Iran, Islamic Republic of)

    2011-07-06

    The purpose of this study is to evaluate the dermal toxicity (Irritation/Corrosion) of three sizes of nanosilver particles (10, 20 and 30 nm) during 3 min, 1 and 4 hours according to the OECD/OCDE guideline Histopathological effects in secondary organs from liver, kidney, heart, spleen and brain 14 day post dermal administration are also reported. 10 and 20 nm Ag nanoparticles treated group showed well defined dermal erythema and oedema. Histopathological findings of 10 and 20 nm (4 hours exposure) on 14-day post dermal administration showed hyperkeratosis, acanthosis, hair-filled follicles and papillomatosis in an irregular epidermis, fibrosis, hyperemia, erythema, intracellular oedema and hyalinisation of collagen in dermis of skin. Liver revealed midzonal and periacinar necrosis, portal mononuclear infiltration, liver fatty change, liver congestion and hyperemic central vein. Splenic red pulp congestion and white pulp hyperreactivity, splenic trabeculae and sinusoidal congestion and hyaline change were found in spleen. Fatty degeneration in some cardiovascular cells and subendocardial hemorrhage without inflammation was perceived. Picnotic appearance of pyramidal neurons in the brain cortex, gliosis and mild perineuronal oedema ischemic cell change and hyperemic meninges was observed in brain. Our research concluded that dermal exposure to lesser sizes of silver nanoparticles is more disastrous than greater ones.

  19. Dermal fillers for tissue augmentation: an overview

    Directory of Open Access Journals (Sweden)

    Zeplin, Philip H.

    2014-06-01

    Full Text Available [english] Treatments with dermal fillers for tissue augmentation constitute the majority of all non-surgical procedures in plastic surgery. Newly developed products get launched and the market grows continuously, but the “ideal” substance has yet not been found. The substances used these days are high molecular compounds. They have substantial differences in their physicochemical properties and are suspended in complex matrices. This overview describes the latest history of dermal fillers and the commonly used substances of different origin and formalizes the need for the development of systematic procedures of standardized pre-clinical tests with subsequent certification as well as the establishment of interdisciplinary clinical guidelines to ensure custumer’s safety.

  20. Chemical sterilization of allograft dermal tissues.

    Science.gov (United States)

    Phipps, Abigail; Vaynshteyn, Edward; Kowalski, John B; Ngo, Manh-Dan; Merritt, Karen; Osborne, Joel; Chnari, Evangelia

    2017-08-10

    Common terminal sterilization methods are known to alter the natural structure and properties of soft tissues. One approach to providing safe grafts with preserved biological properties is the combination of a validated chemical sterilization process followed by an aseptic packaging process. This combination of processes is an accepted method for production of sterile healthcare products as described in ANSI/AAMI ST67:2011. This article describes the validation of the peracetic acid and ethanol-based (PAAE) chemical sterilization process for allograft dermal tissues at the Musculoskeletal Transplant Foundation (MTF, Edison, NJ). The sterilization capability of the PAAE solution used during routine production of aseptically processed dermal tissue forms was determined based on requirements of relevant ISO standards, ISO 14161:2009 and ISO 14937:2009. The resistance of spores of Bacillus subtilis, Clostridium sporogenes, Mycobacterium terrae, Pseudomonas aeruginosa, Enterococcus faecium, and Staphylococcus aureus to the chemical sterilization process employed by MTF was determined. Using a worst-case scenario testing strategy, the D value was calculated for the most resistant microorganism, Bacillus. The 12D time parameter determined the minimum time required to achieve a SAL of 10(-6). Microbiological performance qualification demonstrated a complete kill of 10(6) spores at just a quarter of the full cycle time. The validation demonstrated that the PAAE sterilization process is robust, achieves sterilization of allograft dermal tissue to a SAL 10(-6), and that in combination with aseptic processing secures the microbiological safety of allograft dermal tissue while avoiding structural and biochemical tissue damage previously observed with other sterilization methods such as ionizing irradiation.

  1. Dermal mass aspirate from a Persian cat.

    Science.gov (United States)

    Zimmerman, Kurt; Feldman, Bernard; Robertson, John; Herring, Erin S; Manning, Thomas

    2003-01-01

    A 1-year-old spayed female Persian cat with alopecia and weight loss had numerous variably ulcerated dermal nodules. Cytologic examination of an aspirate of one of the nodules revealed pyogranulomatous inflammation along with septate hyphae and basophilic round bodies, 0.5-1.0 microm in diameter, surrounded by a thin clear halo (arthrospores). The cytologic diagnosis was dermatophytic pseudomycetoma. Histologically, there were dermal granulomas containing poorly staining, septate hyphae with bulbous spores embedded within abundant amorphous eosinophilic material (Splendore-Hoeppli reaction), and the histologic diagnosis was pseudomycetoma-associated chronic multifocal severe granulomatous dermatitis with lymphocytic perifolliculitis and furunculosis. Microsporum canis was cultured from the lesion. Pseudomycetomas are distinguished from fungal mycetomas, or eumycotic mycetomas, by the findings of multiple lesions, lack of a history of skin trauma, an association with dermatophytes, most commonly Microsporum canis, and, histologically, lack of true cement material and a more abundant Splendore-Hoeppli reaction in pseudomycetomas. Additionally, pseudomycetomas differ from dermatophytosis, in which lesions are restricted to epidermal structures. Persian cats have a high incidence of pseudomycetoma formation, suggesting a heritable predisposition. The prognosis is fair with systemic antifungal therapy. When examining cytologic specimens from Persian cats with single or multiple dermal nodules, especially if pyogranulomatous inflammation is present, a diagnosis of pseudomycetoma should be suspected and is warranted if arthrospores and refractile septate hyphae are present.

  2. Posterior repair with perforated porcine dermal graft

    Directory of Open Access Journals (Sweden)

    G. Bernard Taylor

    2008-02-01

    Full Text Available OBJECTIVE: To compare postoperative vaginal incision separation and healing in patients undergoing posterior repair with perforated porcine dermal grafts with those that received grafts without perforations. Secondarily, the tensile properties of the perforated and non-perforated grafts were measured and compared. MATERIALS AND METHODS: This was a non-randomized retrospective cohort analysis of women with stage II or greater rectoceles who underwent posterior repair with perforated and non-perforated porcine dermal grafts (PelvicolTM CR Bard Covington, GA USA. The incidence of postoperative vaginal incision separation (dehiscence was compared. A secondary analysis to assess graft tensile strength, suture pull out strength, and flexibility after perforation was performed using standard test method TM 0133 and ASTM bending and resistance protocols. RESULTS: Seventeen percent of patients (21/127 who received grafts without perforations developed vaginal incision dehiscence compared to 7% (5/71 of patients who received perforated grafts (p = 0.078. Four patients with vaginal incision dehiscence with non-perforated grafts required surgical revision to facilitate healing. Neither tensile strength or suture pull out strength were significantly different between perforated and non-perforated grafts (p = 0.81, p = 0.29, respectively. There was no difference in the flexibility of the two grafts (p = 0.20. CONCLUSION: Perforated porcine dermal grafts retain their tensile properties and are associated with fewer vaginal incision dehiscences.

  3. Evaluation of cytochrome P450 activity in vitro, using dermal and hepatic microsomes from four species and two keratinocyte cell lines in culture.

    Science.gov (United States)

    Rolsted, Kamilla; Kissmeyer, Anne-Marie; Rist, Gerda Marie; Hansen, Steen Honoré

    2008-01-01

    The Cytochrome P450 (CYP450) enzymes are expressed in the skin, and despite a low activity, as compared to the hepatic counterpart, a role during transdermal delivery of a drug cannot be excluded. Additionally, the enzymes may play a role in local toxicity, and further knowledge of dermal CYP450 activity can contribute to elucidate this issue. To achieve this, a cocktail of six selective CYP450 probe substrates were incubated with dermal and hepatic microsomes isolated from mouse, rat, minipig and man. Different species were used to evaluate if a reliable substitute for human tissue was possible. Further, the hepatic microsomes were included in this study, to estimate if the hepatic CYP450 activity is predictive of dermal CYP450 activity. The CYP450 activity was determined in two keratinocyte cell lines as well, as this in vitro model is desirable due to the ease in handling, among other factors. Overall, the metabolism found in the dermal microsomes was very low, and major differences were observed between species. When comparing the activities in dermal and hepatic microsomes, the qualitative pattern was to some extent similar within species, but also a number of differences were observed. The CYP450 metabolic activity in the two keratinocyte cell lines was not comparable to metabolism in the human dermal microsomes.

  4. Dermal uptake of polycyclic aromatic hydrocarbons after hairwash with coal-tar shampoo

    Energy Technology Data Exchange (ETDEWEB)

    Schooten, F.-J. van; Moonen, E.J.C.; Rhijnsburger, E.; Agen, B. van; Thijssen, H.H.W.; Kleinjans, J.C.S. [University of Limburg, Maastricht (Netherlands). Dept. of Health Risk Analysis and Toxicology

    1994-11-26

    Describes an experiment to assess the dermal uptake of polycyclic aromatic hydrocarbons (PAHs) after hairwashing with coal tar antidandruff shampoo. The urinary excretion of 1-hydroxypyrene (1-OH-P), a PAH metabolile was used to assess internal dose of PAH. A single use of coal tar shampoo resulted in increased 1-OH-P excretion in all members of the experimental group compared with the control group using a non-coal tar antidandruff shampoo. It is suggested that repeated use of coal tar shampoo would result in a high internal dose of carcinogenic PAH. 5 refs., 1 fig.

  5. Low-Dose UVA Radiation-Induced Adaptive Response in Cultured Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Zhongrong Liu

    2012-01-01

    Full Text Available Objective. To investigate the mechanism of the adaptive response induced by low-dose ultraviolet A (UVA radiation. Methods. Cultured dermal fibroblasts were irradiated by a lethal dose of UVA (86.4 J/cm2 with preirradiation of single or repetitive low dose of UVA (7.2 J/cm2. Alterations of cellular morphology were observed by light microscope and electron microscope. Cell cycle and cellular apoptosis were assayed by flow cytometer. The extent of DNA damage was determined by single-cell gel electrophoresis (SCGE. Results. The cultured dermal fibroblasts, with pretreatment of single or repetitive irradiation of 7.2 J/cm2 UVA relieved toxic reaction of cellular morphology and arrest of cell cycle, decreased apoptosis ratio, reduced DNA chain breakage, and accelerated DNA repair caused by subsequent 86.4 J/cm2 UVA irradiation. Compared with nonpretreatment groups, all those differences were significant (P<0.01 or P<0.05. Conclusions. The adaptation reaction might depend on the accumulated dose of low-dose UVA irradiation. Low-dose UVA radiation might induce adaptive response that may protect cultured dermal fibroblasts from the subsequent challenged dose of UVA damage. The duration and protective capability of the adaptive reaction might be related to the accumulated dose of low-dose UVA Irradiation.

  6. New E-beam-initiated hyaluronan acrylate cryogels support growth and matrix deposition by dermal fibroblasts.

    Science.gov (United States)

    Thönes, S; Kutz, L M; Oehmichen, S; Becher, J; Heymann, K; Saalbach, A; Knolle, W; Schnabelrauch, M; Reichelt, S; Anderegg, U

    2017-01-01

    Cryogels made of components of natural extracellular matrix components are potent biomaterials for bioengineering and regenerative medicine. Human dermal fibroblasts are key cells for tissue replacement during wound healing. Thus, any biomaterial for wound healing applications should enable growth, differentiation and matrix synthesis by these cells. Cryogels are highly porous scaffolds consisting of a network of interconnected pores. Here, we used a novel group of cryogels generated from acrylated hyaluronan where the polymerization was initiated by accelerated electrons (E-beam). This novel procedure omits any toxic polymerization initiators and results in sterile, highly elastic scaffolds with adjustable pore size, excellent swelling and low flow resistance properties. We show that these cryogels are effective 3D-substrates for long-term cultures of human dermal fibroblasts in vitro. The cells proliferate for at least 28days throughout the cryogels and deposit their own matrix in the pores. Moreover, key modulators of dermal fibroblasts during wound healing like TGFβ and PDGF efficiently stimulated the expression of wound healing-relevant genes. In conclusion, electron beam initiated cryogels of acrylated hyaluronan represent a functional and cell compatible biomaterial that could be adapted for special wound healing applications by further functionalization. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. File list: Unc.Epd.50.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Epd.50.AllAg.Dermal_fibroblasts mm9 Unclassified Epidermis Dermal fibroblasts h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Epd.50.AllAg.Dermal_fibroblasts.bed ...

  8. File list: Unc.Epd.20.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Epd.20.AllAg.Dermal_fibroblasts mm9 Unclassified Epidermis Dermal fibroblasts h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Epd.20.AllAg.Dermal_fibroblasts.bed ...

  9. Evaluation of lymphangiogenesis in acellular dermal matrix

    Directory of Open Access Journals (Sweden)

    Mario Cherubino

    2014-01-01

    Full Text Available Introduction: Much attention has been directed towards understanding the phenomena of angiogenesis and lymphangiogenesis in wound healing. Thanks to the manifold dermal substitute available nowadays, wound treatment has improved greatly. Many studies have been published about angiogenesis and cell invasion in INTEGRA® . On the other hand, the development of the lymphatic network in acellular dermal matrix (ADM is a more obscure matter. In this article, we aim to characterize the different phases of host cell invasion in ADM. Special attention was given to lymphangiogenic aspects. Materials and Methods: Among 57 rats selected to analyse the role of ADM in lymphangiogenesis, we created four groups. We performed an excision procedure on both thighs of these rats: On the left one we did not perform any action except repairing the borders of the wound; while on the right one we used INTEGRA® implant. The excision biopsy was performed at four different times: First group after 7 days, second after 14 days, third after 21 days and fourth after 28 days. For our microscopic evaluation, we used the classical staining technique of haematoxylin and eosin and a semi-quantitative method in order to evaluate cellularity counts. To assess angiogenesis and lymphangiogenesis development we employed PROX-1 Ab and CD31/PECAM for immunohistochemical analysis. Results: We found remarkable wound contraction in defects that healed by secondary intention while minor wound contraction was observed in defects treated with ADM. At day 7, optical microscopy revealed a more plentiful cellularity in the granulation tissue compared with the dermal regeneration matrix. The immunohistochemical process highlighted vascular and lymphatic cells in both groups. After 14 days a high grade of fibrosis was noticeable in the non-treated group. At day 21, both lymphatic and vascular endothelial cells were better developed in the group with a dermal matrix application. At day 28

  10. Quantification of chemical mixture interactions modulating dermal absorption using a multiple membrane fiber array.

    Science.gov (United States)

    Baynes, Ronald E; Xia, Xin Rui; Imran, Mudassar; Riviere, Jim E

    2008-03-01

    Dermal exposures to chemical mixtures can potentially increase or decrease systemic bioavailability of toxicants in the mixture. Changes in dermal permeability can be attributed to changes in physicochemical interactions between the mixture, the skin, and the solute of interest. These physicochemical interactions can be described as changes in system coefficients associated with molecular descriptors described by Abraham's linear solvation energy relationship (LSER). This study evaluated the effects of chemical mixtures containing either a solvent (ethanol) or a surfactant (sodium lauryl sulfate, SLS) on solute permeability and partitioning by quantifying changes in system coefficients in skin and a three-membrane-coated fiber (MCF) system, respectively. Regression analysis demonstrated that changes in system coefficients in skin were strongly correlated ( R2 = 0.89-0.98) to changes in system coefficients in the three-membrane MCF array with mixtures containing either 1% SLS or 50% ethanol. The PDMS fiber appeared to play a significant role (R2 = 0.84-0.85) in the MCF array in predicting changes in solute permeability, while the WAX fiber appeared to contribute less (R2 = 0.59-0.77) to the array than the other two fibers. On the basis of changes in system coefficients that are part of a LSER, these experiments were able to link physicochemical interactions in the MCF with those interactions in skin when either system is exposed to 1% SLS or 50% ethanol. These experiments further demonstrated the utility of a MCF array to adequately predict changes in dermal permeability when skin is exposed to mixtures containing either a surfactant or a solvent and provide some insight into the nature of the physiochemical interactions that modulate dermal absorptions.

  11. Dermal pharmacokinetics of microemulsion formulations determined by in vivo microdialysis

    DEFF Research Database (Denmark)

    Kreilgaard, Mads

    2001-01-01

    To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data.......To investigate the potential of improving dermal drug delivery of hydrophilic and lipophilic substances by formulation in microemulsion vehicles and to establish a reliable pharmacokinetic model to analyze cutaneous microdialysis data....

  12. Spectrum of PORCN mutations in Focal Dermal Hypoplasia

    Science.gov (United States)

    Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome (OMIM 305600), is a genetic disorder that affects multiple organ systems early in development. Features of FDH include skin abnormalities, (hypoplasia, atrophy, linear pigmentation, and herniation of fat through dermal defects); papillomas...

  13. Lipid nanoparticles for dermal drug delivery.

    Science.gov (United States)

    Kakadia, Pratibha G; Conway, Barbara R

    2015-01-01

    Lipid based drug delivery systems have been widely studied and reported over the past decade and offer a useful alternative to other colloidal drug delivery systems. Skin is a popular route of drug delivery for locally and systemically acting drugs and nanoparticles are reported as a potential formulation strategy for dermal delivery. Although the skin acts as a natural physical barrier against penetration of foreign materials, including particulates, opportunities exist for the delivery of therapeutic nanoparticles, especially in diseased and damaged skin and via appendageal routes such as the openings of hair follicles. The extent and ability of nanoparticles to penetrate into the underlying viable tissue is still the subject of debate although recent studies have identified the follicular route as the most likely route of entry; this influences the potential applications of these dosage forms as a drug delivery strategy. This paper reviews present state of art of lipid-based nanocarriers focussing on solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions, their production methods, potential advantages and applications in dermal drug delivery.

  14. Novel PORCN mutations in focal dermal hypoplasia.

    Science.gov (United States)

    Froyen, G; Govaerts, K; Van Esch, H; Verbeeck, J; Tuomi, M-L; Heikkilä, H; Torniainen, S; Devriendt, K; Fryns, J-P; Marynen, P; Järvelä, I; Ala-Mello, S

    2009-12-01

    Focal dermal hypoplasia (FDH), Goltz or Goltz-Gorlin syndrome, is an X-linked dominant multisystem disorder characterized primarily by involvement of the skin, skeletal system and eyes. We screened for mutations in the PORCN gene in eight patients of Belgian and Finnish origin with firm clinical suspicion of FDH. First, we performed quantitative PCR (qPCR) analysis to define the copy number at this locus. Next, we sequenced the coding regions and flanking intronic sequences of the PORCN gene. Three de novo mutations were identified in our patients with FDH: a 150-kb deletion removing six genes including PORCN, as defined by qPCR and X-array-CGH, and two heterozygous missense mutations; c.992T>G (p.L331R) in exon 11 and c.1094G>A (p.R365Q) in exon 13 of the gene. Both point mutations changed highly conserved amino acids and were not found in 300 control X chromosomes. The three patients in whom mutations were identified all present with characteristic dermal findings together with limb manifestations, which were not seen in our mutation-negative patients. The clinical characteristics of our patients with PORCN mutations were compared with the previously reported mutation-positive cases. In this report, we summarize the literature on PORCN mutations and associated phenotypes.

  15. [Cerebellar abscesses secondary to infection of an occipital dermal sinus].

    Science.gov (United States)

    García Galera, A; Martínez León, M I; Pérez da Rosa, S; Ros López, B

    2013-09-01

    A dermal sinus is a congenital defect arising from a closure failure of the neural tube that results in different degrees of communication between the skin and the central nervous system. A dermal sinus can occur anywhere from the root of the nose to the conus medullaris, and the occipital location is the second most common. Dermal sinuses are often found in association with dermoid or epidermoid cysts and less frequently with teratomas. Patients with an occipital dermoid cyst associated with a dermal sinus can develop meningitis and/or abscesses as the first clinical manifestation of the disease due to the dermoid cyst itself becoming abscessed or to the formation of secondary abscesses; few cases of the formation of secondary abscesses have been reported. We present a case of a dermoid cyst associated with an infected dermal sinus and posterior development of cerebellar abscesses and hydrocephalus.

  16. Late-onset Ito's nevus: an uncommon acquired dermal melanocytosis.

    Science.gov (United States)

    Mataix, Javier; López, Norberto; Haro, Rosario; González, Elena; Angulo, Jorge; Requena, Luis

    2007-08-01

    Dermal melanocytoses comprise a variety of congenital and acquired conditions characterized by a sparse population of intradermal dendritic, variably pigmented, spindle-shaped melanocytes. While Mongolian spot, Ota's and Ito's nevi are usually present at birth or appear around puberty; acquired dermal melanocytoses that appear in adult life are extremely rare. They include the facial lesions of acquired bilateral nevus of Ota-like macules, also named Hori's nevus, and the acquired unilateral nevus of Ota, also known as Sun's nevus. Uncommon extrafacial examples of acquired dermal melanocytoses include lesions involving upper extremities, wrist, back, lower extremities and dorsal aspects of the hands and feet. They are more prevalent among Asian women. In general, dermal melanocytoses are rare lesions in Caucasian patients and acquired variants are exceedingly uncommon. We report a rare example of acquired Ito's nevus that appeared in a Caucasian elderly woman and review the literature about acquired dermal melanocytoses.

  17. Human dermal exposure to galaxolide from personal care products.

    Science.gov (United States)

    Correia, P; Cruz, A; Santos, L; Alves, A

    2013-06-01

    Musks are synthetic fragrances applied on personal care and household products as fixatives, by retarding the release of other fragrances with higher volatility. Galaxolide is the most used polycyclic musk since the 90th decade, and it has been detected in several environmental and biological matrices, particularly in human tissues and fluids. For exposure assessment purposes, large-monitoring data need to be obtained and rapid but reliable analytical techniques are requested. The main objective of this study is to develop and validate a new and fast analytical methodology to quantify galaxolide in personal care products and to apply this method to real matrices like skin care products (creams and lotions), shower products (soap bar), hair care products (shampoo and hair conditioner) and oral care products (toothpaste), to evaluate the human dermal exposure risk. A dispersive solid-phase extraction is proposed, using QuEChERS methodology, followed by HPLC with fluorescence detection. Some extraction parameters were studied, like the ratio of sample/solvent amounts, the homogenization time, the salt addition effect and the used sorbents. The validation parameters of the developed method were the following: a linearity range of 0.005-1.002 mg kg⁻¹ sample, a limit of detection of 0.001 mg kg⁻¹ sample, repeatability between 0.7% and 11.3% (variation coefficient of six standard injections), an intermediate precision of 2.5% (variation coefficient of six independent analysis of the same sample), mean recoveries ranging from 65% (soap bar) to 95% (body cream) and 3% of global uncertainty in most of the working range. The time of analysis, including the extraction steps, is 60 min, allowing a throughput of 4 samples h⁻¹ . Galaxolide was detected in all of the seven analysed products in concentrations ranging from 0.04 ± 0.01 mg kg⁻¹ sample (toothpaste) to 280.78 ± 8.19 mg kg⁻¹ sample (perfumed body cream), which may correspond to a significant estimated

  18. Hypocellular Plaque-Like CD34-Positive Dermal Fibroma (Medallion-Like Dermal Dendrocyte Hamartoma) Presenting as a Skin-Colored Dermal Nodule.

    Science.gov (United States)

    Mutgi, Krishna A J; Chitgopeker, Pooja; Ciliberto, Heather; Stone, Mary S

    2016-01-01

    Plaque-like CD34-positive dermal fibromas, also known as medallion-like dermal dendrocyte hamartomas (MDDHs), are a recently recognized group of congenital and acquired spindle cell neoplasms that may appear histologically similar to dermatofibrosarcoma protuberans. Recognizing the clinical heterogeneity of this neoplasm and the subtle pathologic differences are crucial to making the correct diagnosis and avoiding the aggressive surgical intervention required to treat a dermatofibrosarcoma protuberans. We present the case of a 9-year-old girl with an acquired variant of a plaque-like CD34-positive dermal fibroma without clinical epidermal change. Our case expands the clinical spectrum to include an acquired variant of a plaque-like CD34-positive dermal fibroma without clinical epidermal change. Examination of more cases is needed to determine whether all clinical variants are truly subtypes of the same neoplasm or represent distinct CD34-positive spindle cell proliferations.

  19. 注射用右旋雷贝拉唑钠大鼠13周重复给药毒性研究%Study on Repeated Dose Toxicity of Dexrabeprazole Sodium Injection in Rats for 13 Weeks

    Institute of Scientific and Technical Information of China (English)

    戴晓莉; 戴学栋; 郭峰; 胡建庭; 马玉奎

    2016-01-01

    目的:研究SD大鼠连续静脉给予注射用右旋雷贝拉唑钠13周的毒性作用。方法选取SD大鼠190只,雌性各半,分为溶媒对照组、注射用雷贝拉唑钠市售对照80 mg·kg-1组、注射用右旋雷贝拉唑钠80、20、5 mg·kg-1组及注射用雷贝拉唑钠、注射用右旋雷贝拉唑钠各剂量毒代卫星组,每天给药1次,连续给药13周,停药恢复4周。试验期间,全部动物每周称量体重和摄食量,给药13周及停药恢复4周时腹主动脉取血进行血液相关指标检测,剖检摘取脏器进行组织病理学检查;卫星组动物分别于首次和末次给药后颈静脉采血进行毒代动力学检测。结果注射用右旋雷贝拉唑钠80、20 mg·kg-1剂量下可导致大鼠出现呼吸急促、步态不稳、俯卧不动等症状,血液中RBC、HGB、HCT含量降低、甲状腺出现小滤泡形成增多,停药4周后血液学异常指标均恢复正常,但甲状腺病理学改变未能完全恢复。结论重复静脉注射给予注射用右旋雷贝拉唑钠80、20 mg·kg-1剂量下可导致SD大鼠红细胞相关指标可逆性改变、甲状腺病理改变。%Objective To observe the toxicity damage of dexrabeprazole sodium injection in rats for 13 Weeks.Methods One hundred and ninety rats(female half)were randomly divided into vehicle control group, rabeprazole sodium injection control group, three dexrabeprazole sodium injection groups with different dosages (80, 20 and 5 mg·kg-1), in addition, rabeprazole sodium injection and dexrabeprazole sodium injection satellite group. Then the group should be given the injection once a day for 13 weeks, after that, stopped to recovery for 4 weeks. During the test, all the animals should weigh weight and food intake. When stopped injection and ifnishing recovery, blood taken from abdominal aorta, organ coefifcient and histopathology were measured for the overall toxicity assessment. Respectively, Satellite animals were

  20. "The blood pressure and dermal sensitivity effects of Nylon hollow fiber releasing Glycerin Trinitrate in vivo "

    Directory of Open Access Journals (Sweden)

    "Ostad SN

    2002-09-01

    Full Text Available In order to improve patient's compliance in taking glycerine trinitrate (GTN nylon hollow fiber which has been successfully used for release of chlorhexidine diacetate and levonorgestrel was employed to make nylon hollow fiber releasing GTN. Hollow nylon fibres of external diameter 0.63 mm, 75 mm long with an internal capacity of 16 μl, were filled with GTN (190 mg/ml in 70% ethanol (v/v or vehicle alone and the ends were heat-sealed. The fibers were then immersed in 10 ml of 0.9% (w/v saline in a separating funnel. The GTN release pattern from fiber, the effect of the product on blood pressure and its potential dermal toxicity were assessed. The release of GTN from the fibres was approximately 2.7 μg/min when the fibres contained 16 mg of drug. The results showed that the amount of GTN within the single fibre was enough to reduce blood pressure significantly, while it did not show significant dermal toxicity. It is concluded that GTN fiber, if used as monofilament, is not an alternative method for GTN delivery.

  1. Investigation of the Dermal Absorption and Irritation Potential of Sertaconazole Nitrate Anhydrous Gel

    Directory of Open Access Journals (Sweden)

    Mahima Manian

    2016-07-01

    Full Text Available Effective topical therapy of cutaneous fungal diseases requires the delivery of the active agent to the target site in adequate concentrations to produce a pharmacological effect and inhibit the growth of the pathogen. In addition, it is important to determine the concentration of the drug in the skin in order to evaluate the subsequent efficacy and potential toxicity for topical formulations. For this purpose, an anhydrous gel containing sertaconazole nitrate as a model drug was formulated and the amount of the drug in the skin was determined by in vitro tape stripping. The apparent diffusivity and partition coefficients were then calculated by a mathematical model describing the dermal absorption as passive diffusion through a pseudo-homogenous membrane. The skin irritation potential of the formulation was also assessed by using the in vitro Epiderm™ model. An estimation of the dermal absorption parameters allowed us to evaluate drug transport across the stratum corneum following topical application. The estimated concentration for the formulation was found to be higher than the MIC100 at the target site which suggested its potential efficacy for treating fungal infections. The skin irritation test showed the formulation to be non-irritating in nature. Thus, in vitro techniques can be used for laying the groundwork in developing efficient and non-toxic topical products.

  2. Phenytoin silver: a new nanocompound for promoting dermal wound healing via comprehensive pharmacological action

    Science.gov (United States)

    Ai, Xiao-yu; Liu, Hui-juan; Lu, Cheng; Liang, Cai-li; Sun, Yan; Chen, Shuang; Sun, Bo; Li, Yang; Liu, Yan-rong; Zhang, Qiang; Liu, Xue-qiang; Xiao, Ting; Jing, Xue-shuang; Sun, Tao; Zhou, Hong-gang; Yang, Cheng

    2017-01-01

    Phenytoin, an antiepileptic drug, has been widely used for wound healing. Inspired by previous studies, phenytoin silver (PnAg), a sparingly soluble silver nanocompound, was synthesized which exhibited good therapeutic efficacy in tissue repair with low toxicity (LD50 >5 g/kg). In vivo studies showed that PnAg could accelerate dermal wound healing and strong inflammation control in Sprague-Dawley rats (SD rat) and Bama minipigs. Due to its low solubility, PnAg led to low toxicity and blood enrichment in animals. Furthermore, PnAg could upregulate the promoter activity of Jak, Stat3, and Stat3 downstream proteins. Therefore, PnAg may serve as an effective therapeutic compound for wound healing through regulating the gp130/Jak/Stat3 signaling pathway.

  3. Reactive skin decontamination lotion (RSDL) for the decontamination of chemical warfare agent (CWA) dermal exposure.

    Science.gov (United States)

    Schwartz, M D; Hurst, C G; Kirk, M A; Reedy, S J D; Braue, E H

    2012-08-01

    Rapid decontamination of the skin is the single most important action to prevent dermal absorption of chemical contaminants in persons exposed to chemical warfare agents (CWA) and toxic industrial chemicals (TICs) as a result of accidental or intentional release. Chemicals on the skin may be removed by mechanical means through the use of dry sorbents or water. Recent interest in decontamination systems which both partition contaminants away from the skin and actively neutralize the chemical has led to the development of several reactive decontamination solutions. This article will review the recently FDA-approved Reactive Skin Decontamination Lotion (RSDL) and will summarize the toxicity and efficacy studies conducted to date. Evidence of RSDL's superior performance against vesicant and organophosphorus chemical warfare agents compared to water, bleach, and dry sorbents, suggests that RSDL may have a role in mass human exposure chemical decontamination in both the military and civilian arenas.

  4. Dermal graft correction of extraordinary chordee.

    Science.gov (United States)

    Kogan, S J; Reda, E F; Smey, P L; Levitt, S B

    1983-11-01

    Severe degrees of primary chordee and persistent or recurrent chordee following previous surgical attempts at correction present a challenging problem. Inadequate resection of involved tissues, which may involve all layers of the penile investiture, or recurrent scarring of the ventral skin, Buck's fascia and tunica albuginea is usually the cause. Reoperation to achieve penile straightening often is unsuccessful unless all chordee-bearing tissue is resected extensively. Excision of large segments of tunica albuginea or wide separation of the margins creates a defect that tends to heal by dense scarring unless the defect is bridged by a graft. Various autogenous materials have been used, including blood vessel, fascia, free fat graft, dermis and tunica albuginea, as well as prosthestic materials, such as polytetrafluoroethylene, with varying results. A series of patients with extensive chordee is presented in whom tunical resection was necessary to achieve penile straightening. The results of free dermal graft replacement of the tunica are reported.

  5. Prenatal Diagnosis of Congenital Dermal Sinus

    Directory of Open Access Journals (Sweden)

    Sharif Sakr

    2015-04-01

    Full Text Available Background - Congenital dermal sinus (CDS is an uncommon form of spinal dysraphism. Although postdelivery identification in the neonate is aided by several associated physical examination findings, establishing this diagnosis prenatally has proven to be elusive. Case Report - We present a case of CDS where the prenatal findings at 20 weeks gestation led to the diagnosis, which was confirmed postnatally. The associated protrusion of fibrotic membranes through the sinus tract helped in the identification of this lesion prenatally, but created confusion with a more common type of lesion, an open neural tube defect. This is the first case report in the literature describing prenatal diagnosis of fetal CDS. Conclusion - Prenatal diagnosis with postnatal confirmation of CDS leads to early intervention, better long-term outcomes, and lesser complications.

  6. Dermal and Ophthalmic Findings in Pseudohypoaldosteronism

    Science.gov (United States)

    Korkut, Sabriye; Gökalp, Emir; Özdemir, Ahmet; Kurtoğlu, Selim; Demirtaş, Şafak; Gül, Ülkü; Baştuğ, Osman

    2015-01-01

    Pseudohypoaldosteronism (PHA) is defined as a state of resistance to aldosterone, a hormone crucial for electrolyte equilibrium. The genetically transmitted type of PHA is primary hypoaldosteronism. Secondary hypoaldosteronism develops as a result of hydronephrosis or hydroureter. PHA patients suffer from severe hyponatremia and a severe clinical condition due to severe loss of salt can be encountered in the neonatal period. Dermal findings in the form of miliaria rubra can also develop in these patients. With the loss of salt, abnormal accumulation of sebum in the eye due to a defect in the sodium channels can also occur. In this paper, a case of PHA in a newborn showing typical dermatological and ophthalmological findings is presented. PMID:26316441

  7. Naphthalene toxicity and antioxidant nutrients.

    Science.gov (United States)

    Stohs, Sidney J; Ohia, Sunny; Bagchi, Debasis

    2002-10-30

    Naphthalene is a bicyclic aromatic compound that has wide industrial and commercial applications. It is used as the starting material for the synthesis of other compounds, as a moth repellent, soil fumigant and lavatory deodorant. Most exposure occurs through low dose chronic inhalation, dermal contact or ingestion through the food chain. The lungs and eyes appear to be most susceptible to toxicity, although biochemical markers of toxicity can be demonstrated in other tissues, such as the kidney, brain and liver. In addition to lens opacification (cataracts) and histological changes associated with pneumotoxicity, other biomarkers of toxic effects include glutathione depletion, lipid peroxidation, DNA fragmentation and the production of the active oxygen species as superoxide anion and hydroxyl radical. In addition, the urinary excretion of lipid metabolites occurs. A role for the tumor suppressor gene p53 has been demonstrated. Toxic manifestations of naphthalene are associated with its oxidative metabolism to various products including quinones. The ability to protect against the toxic effects of naphthalene by using various antioxidants and free radical scavengers has been demonstrated. Studies have been conducted with vitamin E, vitamin E succinate, melatonin, curcumin, various L-cysteine prodrugs, several aldose reductase inhibitors and spin-trapping agents. The ability to prevent the toxic manifestations of naphthalene is dependent on the pharmacokinetic properties of the agents, which have been studied. The appropriate selection of chemoprotectants can be useful in preventing naphthalene toxicity.

  8. [Generalized granuloma annulare or diffuse dermal histiocytosis?].

    Science.gov (United States)

    Kretzschmar, L; Biel, K; Luger, T A; Goerdt, S

    1995-08-01

    Generalized granuloma annulare is a rare variant of granuloma annulare affecting the trunk and extremities with a multitude of lesions. In contrast to localized granuloma annulare, generalized granuloma annulare occurs in older patients, shows a stronger association with diabetes, and is characteristically chronic. Like our 55-year-old patient, most patients present with papules and annular plaques; less often, macular or non-annular lesions may be encountered. Histology often fails to show necrobiotic or necrotic connective tissue changes demarcated by a palisading granuloma. Instead, there are diffuse dermal, band-like or nodular aggregations of histiocytes intermingled with some multinucleated giant cells and a predominantly lymphocytic infiltrate in the periphery. Because of its special characteristics, it has been suggested that generalized granuloma annulare might constitute a separate disease entity and that it should be classed among the primary cutaneous histiocytoses as a diffuse dermal histiocytosis. Using immunohistochemistry to determine the macrophage phenotype of the lesional histiocytes, we have shown that generalized granuloma annulare is not a cutaneous histiocytosis. Neither MS-1 high-molecular-weight protein, a new specific marker for cutaneous non-Langerhans cell histiocytoses, nor CD1a, the well-known marker for Langerhans cells and Langerhans cell histiocytoses, is expressed by the lesional histiocytes of our patient. In contrast, the antigen expression pattern was diagnostic for non-infectious granulomas and was highly similar to that in localized granuloma annulare. In contrast to the successful treatment of localized granuloma annulare reported with intralesional interferon beta-1, systemic treatment with interferon alpha-2b (9 x 10(6) units three times a week) was ineffective.

  9. Repeat-until-success quantum repeaters

    Science.gov (United States)

    Bruschi, David Edward; Barlow, Thomas M.; Razavi, Mohsen; Beige, Almut

    2014-09-01

    We propose a repeat-until-success protocol to improve the performance of probabilistic quantum repeaters. Conventionally, these rely on passive static linear-optics elements and photodetectors to perform Bell-state measurements (BSMs) with a maximum success rate of 50%. This is a strong impediment for entanglement swapping between distant quantum memories. Every time a BSM fails, entanglement needs to be redistributed between the corresponding memories in the repeater link. The key ingredients of our scheme are repeatable BSMs. Under ideal conditions, these turn probabilistic quantum repeaters into deterministic ones. Under realistic conditions, our protocol too might fail. However, using additional threshold detectors now allows us to improve the entanglement generation rate by almost orders of magnitude, at a nominal distance of 1000 km, compared to schemes that rely on conventional BSMs. This improvement is sufficient to make the performance of our scheme comparable to the expected performance of some deterministic quantum repeaters.

  10. Methods of acute biological assays in guinea-pigs for the study of toxicity and innocuity of drugs and chemicals

    OpenAIRE

    2010-01-01

    In this study, 602 samples were tested by the following assays performed at the animal facilities (Cedeme) of the Federal University of São Paulo (UNIFESP): 385 for dermal irritability, 90 for ocular irritability (discontinued in 1995), 31 for systemic toxicity by injection, 26 for oral acute toxicity, 15 for toxicity by intracutaneous injection, 15 for skin sensitization, 15 for toxicity of serum and vaccines for human use, 14 for toxicity by intramuscular implantation, 7 for pyrogens, 2 for...

  11. Butachlor-induced acute toxic hepatitis.

    Science.gov (United States)

    Daryani, Nasser Ebrahimi; Hosseini, Parviz; Bashashati, Mohammad; Haidarali, Mona; Sayyah, Alireza

    2007-01-01

    Butachlor is a highly effective herbicidal substance widely used by farmers. We report a 60-year-old man with exfoliative dermatitis, jaundice, increase in liver enzymes and eosinophilia one day after accidental dermal exposure to butachlor toxin. The diagnostic workup showed no other cause and liver histology was consistent with substance-induced toxic hepatitis. Within two weeks of conservative therapy, his liver function tests returned to normal.

  12. Dermal grafts for correction of severe chordee associated with hypospadias.

    Science.gov (United States)

    Horton, C E; Gearhart, J P; Jeffs, R D

    1993-08-01

    We report on 24 patients with hypospadias and severe chordee that could not be straightened with conventional techniques. We used small dermal grafts to augment the ventral tunica albuginea, which resulted in a completely straight, normal appearing erection in all patients. Subsequent urethroplasty was not complicated by the presence of the dermal graft. This procedure is technically straightforward and consistently results in a completely straight penis. Although required only rarely in hypospadias surgery, we recommend the dermal graft technique of tunica albuginea augmentation for cases of refractory chordee.

  13. Genotoxicity assessment of reactive and disperse textile dyes using human dermal equivalent (3D cell culture system).

    Science.gov (United States)

    Leme, Daniela Morais; Primo, Fernando Lucas; Gobo, Graciely Gomides; da Costa, Cleber Rafael Vieira; Tedesco, Antonio Claudio; de Oliveira, Danielle Palma

    2015-01-01

    Thousands of dyes are marketed daily for different purposes, including textile dyeing. However, there are several studies reporting attributing to dyes deleterious human effects such as DNA damage. Humans may be exposed to toxic dyes through either ingestion of contaminated waters or dermal contact with colored garments. With respect to dermal exposure, human skin equivalents are promising tools to assess in vitro genotoxicity of dermally applied chemicals using a three-dimensional (3D) model to mimic tissue behavior. This study investigated the sensitivity of an in-house human dermal equivalent (DE) for detecting genotoxicity of textile dyes. Two azo (reactive green 19 [RG19] and disperse red 1[DR1]) dyes and one anthraquinone (reactive blue 2 [RB2]) dye were analyzed. RG19 was genotoxic for DE in a dose-responsive manner, whereas RB2 and DR1 were nongenotoxic under the conditions tested. These findings are not in agreement with previous genotoxicological assessment of these dyes carried out using two-dimensional (2D) cell cultures, which showed that DR1 was genotoxic in human hepatoma cells (HepG2) and RG19 was nongenotoxic for normal human dermal fibroblasts (NHDF). These discrepant results probably may be due to differences between metabolic activities of each cell type (organ-specific genotoxicity, HepG2 and fibroblasts) and the test setup systems used in each study (fibroblasts cultured at 2D and three-dimensional [3D] culture systems). Genotoxicological assessment of textile dyes in context of organ-specific genotoxicity and using in vitro models that more closely resemble in vivo tissue architecture and physiology may provide more reliable estimates of genotoxic potential of these chemicals.

  14. 经皮反复给予玉红膏对大鼠器官毒性的研究%Organ toxicity of Yuhong Ointment(玉红膏) after repeated transdermal administration in rats

    Institute of Scientific and Technical Information of China (English)

    胡小靖; 孙新民; 黄雯; 邱恒; 牟稷征; 王丽霞; 王旗

    2013-01-01

    1.6% calomel group were significantly higher than that in the matrix control group (P < 0.05) on 28 days after treatment and 28 days after drug withdrawal.The differences of coefficients of heart,brain,liver,and spleen of rats in different groups were not statistically significant (all P > 0.05).There were no obvious morphological changes in liver,kidney and spleen in different groups 28 days after treatment.Conclusions No obvious toxic reactions were observed in rats after transdermal administration of Yuhong Ointment repeatedly.The high concentrations of Yuhong Ointment maybe bring reversible kidney injury.The kidney function of patient who received large volume of Yuhong Ointment for long-term should be monitored.%目的 观察经皮反复给予玉红膏对大鼠肝、肾功能及心、脑、肝、肾、脾等主要脏器组织形态学的影响,为临床安全用药提供实验数据.方法 SPF级SD大鼠100只,体重200 g,雌雄各半.用抽签法随机分为基质对照组、1倍浓度玉红膏组(轻粉含量0.4%)、2倍浓度玉红膏组(轻粉含量0.8%)、4倍浓度玉红膏组(轻粉含量1.6%)和1.6%轻粉组,每组20只.制备大鼠皮肤破损模型,经破损皮肤涂抹不同浓度玉红膏,1次/d,连续28 d.分别于给药前、给药14、28 d和停药28 d测定各组大鼠血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、尿素氮(BUN)、肌酐(Cr)和N-乙酰-β-D氨基葡萄糖苷酶(NAG)水平;给药28 d和停药28 d时每组各处死10只大鼠,取心、脑、肝、肾、脾等脏器称重,计算脏器系数,并取肝、肾、脾组织观察形态学改变.结果 不同浓度玉红膏组和1.6%轻粉组大鼠ALT、AST、BUN、Cr和NAG水平与同期基质对照组比较差异无统计学意义(均P>0.05);停药28 d时,1.6%轻粉组大鼠血清Cr含量高于基质对照组(P<0.05).给药28 d与停药28d时,2和4倍浓度玉红膏组、1.6%轻粉组大鼠的肾脏系数均明显高于基质对照组(均P<0.05).

  15. Dermal reflectivity determined by optical coherence tomography is an indicator of epidermal hyperplasia and dermal edema within inflamed skin

    Science.gov (United States)

    Phillips, Kevin G.; Wang, Yun; Levitz, David; Choudhury, Niloy; Swanzey, Emily; Lagowski, James; Kulesz-Martin, Molly; Jacques, Steven L.

    2011-04-01

    Psoriasis is a common inflammatory skin disease resulting from genetic and environmental alterations of cutaneous immune responses. While numerous therapeutic targets involved in the immunopathogenesis of psoriasis have been identified, the in vivo dynamics of inflammation in psoriasis remain unclear. We undertook in vivo time course focus-tracked optical coherence tomography (OCT) imaging to noninvasively document cutaneous alterations in mouse skin treated topically with Imiquimod (IMQ), an established model of a psoriasis-like disease. Quantitative appraisal of dermal architectural changes was achieved through a two parameter fit of OCT axial scans in the dermis of the form A(x, y, z) = ρ(x, y)exp [ - μ(x, y)z]. Ensemble averaging over 2000 axial scans per mouse in each treatment arm revealed no significant changes in the average dermal attenuation rate, , however the average local dermal reflectivity , decreased significantly following 1, 3, and 6 days of IMQ treatment (p collagen fiber bundle enlargement, occur prior to epidermal thickness changes due to hyperplasia and dermal thickness changes due to edema. Dermal reflectivity positively correlated with epidermal hyperplasia (repi2 = 0.78) and dermal edema (rderm2 = 0.86). Our results suggest that dermal reflectivity as measured by OCT can be utilized to quantify a psoriasis-like disease in mice, and thus has the potential to aid in the quantitative assessment of psoriasis in humans.

  16. Efficacy of skin wash on dermal absorption: an in vitro study on four model compounds of varying solubility

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo

    2010-01-01

    that percutaneous penetration continues after end of exposure due to the reservoir present in the skin. However, penetration rate will decrease significantly, and it is evident that simple hand-wash after end of exposure not only reduces the amount of residue present in the upper skin compartment but also......PURPOSE: Following dermal exposure to chemicals causing systemic toxicity, the general advice to avoid further systemic exposure is to wash the skin. The present study uses four model compounds (benzoic acid, glyphosat, caffeine, malathion) with varying size and solubility to substantiate...... this advice and quantify the effect of skin wash following 6 h dermal exposure on subsequent extent of skin penetration and deposition within the skin compartment. METHOD: Percutaneous penetration through human skin is studied in an in vitro model with static diffusion cells. RESULTS: The study demonstrates...

  17. Focal dermal hypoplasia: Unusual presentation in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Awadh Alamri

    2016-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem characterized by multiple abnormalities of ectodermal and mesodermal origin. It is found predominantly in females. We report a case of a two month-old baby girl who had dermal hypoplasia, atrophic skin lesions with telangiectasia in a linear pattern, fat herniations, papillomas and cleft of the upper lip, ectrodactyly, claw hands, microphthalmia and unusual association of gastrointestinal omphalocele.

  18. Acquired ichthyosis and impaired dermal lipogenesis in Hodgkin's disease.

    Science.gov (United States)

    Cooper, M F; Wilson, P D; Hartop, P J; Shuster, S

    1980-06-01

    Epidermal lipid biosynthesis was normal in patients with mild ichthyosis due to Hodgkin's disease, but greatly reduced in one patient with severe ichthyosis. Dermal (sebaceous) lipid synthesis was decreased in all patients with Hodgkin's disease, whether or not they had ichthyosis, and was greatly reduced in the patient with severe ichthyosis. Neither the mechanism nor the possible relationship between the dermal and epidermal changes is understood.

  19. Evaluation of dermal fillers with noncontact optical coherence elastography

    Science.gov (United States)

    Singh, Manmohan; Wang, Shang; Yee, Richard W.; Han, Zhaolong; Aglyamov, Salavat R.; Larin, Kirill V.

    2017-02-01

    Over 2 million dermal filler procedures are performed each year in the USA alone, and this figure is only expected to increase as the aging population continues to grow. Dermal filler treatments can last from a few months to years depending on the type of filler and its placement. Although adverse reactions are rare, they can be quite severe due to ischemic events and filler migration. Previously, techniques such as ultrasound or magnetic resonance imaging have been used to evaluate the filler injections. However, these techniques are not practical for real-time filler injection guidance due to limitations such as the physical presence of the transducer. In this work, we propose the use of optical coherence tomography (OCT) for image-guided dermal filler injections due to the high spatial and temporal resolution of OCT. In addition, we utilize a noncontact optical coherence elastography (OCE) technique, to evaluate the efficacy of the dermal filler injection. A grid of air-pulse OCE measurements was taken, and the dynamic response of the skin to the air-pulse was translated to the Young's modulus and shear viscosity. Our results show that OCT was able to visualize the dermal filler injection process, and that OCE was able to localize the dermal filler injection sites. Combined with functional techniques such as optical microangiography, and recent advanced in OCT hardware, OCT may be able to provide real-time injection guidance in 3D by visualizing blood vessels to prevent ischemic events.

  20. Microneedle technologies for (trans)dermal drug and vaccine delivery.

    Science.gov (United States)

    van der Maaden, Koen; Jiskoot, Wim; Bouwstra, Joke

    2012-07-20

    Microneedles have been used for the dermal and transdermal delivery of a broad range of drugs, such as small molecular weight drugs, oligonucleotides, DNA, peptides, proteins and inactivated viruses. However, until now there are no microneedle-based (trans)dermal drug delivery systems on the market. In the past decade various types of microneedles have been developed by a number of production processes. Numerous geometries of microneedles have been designed from various materials. These microneedles have been used for different approaches of microneedle-based (trans)dermal drug delivery. Following a brief introduction about dermal and transdermal drug delivery, this review describes different production methods for solid and hollow microneedles as well as conditions that influence skin penetration. Besides, the four microneedle-based (trans)dermal drug delivery approaches are discussed: "poke and flow", "poke and patch", "poke and release", and "coat and poke". A separate section of this review is devoted to the use of microneedles for the delivery of therapeutic proteins and vaccines. Finally, we give our view on research and development that is needed to render microneedle-based (trans)dermal drug delivery technologies clinically useful in the near future.

  1. Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients.

    Science.gov (United States)

    Api, Anne Marie; Basketter, David A; Cadby, Peter A; Cano, Marie-France; Ellis, Graham; Gerberick, G Frank; Griem, Peter; McNamee, Pauline M; Ryan, Cindy A; Safford, Robert

    2008-10-01

    Based on chemical, cellular, and molecular understanding of dermal sensitization, an exposure-based quantitative risk assessment (QRA) can be conducted to determine safe use levels of fragrance ingredients in different consumer product types. The key steps are: (1) determination of benchmarks (no expected sensitization induction level (NESIL)); (2) application of sensitization assessment factors (SAF); and (3) consumer exposure (CEL) calculation through product use. Using these parameters, an acceptable exposure level (AEL) can be calculated and compared with the CEL. The ratio of AEL to CEL must be favorable to support safe use of the potential skin sensitizer. This ratio must be calculated for the fragrance ingredient in each product type. Based on the Research Institute for Fragrance Materials, Inc. (RIFM) Expert Panel's recommendation, RIFM and the International Fragrance Association (IFRA) have adopted the dermal sensitization QRA approach described in this review for fragrance ingredients identified as potential dermal sensitizers. This now forms the fragrance industry's core strategy for primary prevention of dermal sensitization to these materials in consumer products. This methodology is used to determine global fragrance industry product management practices (IFRA Standards) for fragrance ingredients that are potential dermal sensitizers. This paper describes the principles of the recommended approach, provides detailed review of all the information used in the dermal sensitization QRA approach for fragrance ingredients and presents key conclusions for its use now and refinement in the future.

  2. Long-Term Followup of Dermal Substitution with Acellular Dermal Implant in Burns and Postburn Scar Corrections

    OpenAIRE

    Juhasz, I.; Kiss, B.; Lukacs, L.; Erdei, I.; Peter, Z.; Remenyik, E.

    2010-01-01

    Full-thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the impl...

  3. Fine needle aspiration cytology of dermal cylindroma

    Directory of Open Access Journals (Sweden)

    Parikshaa Gupta

    2014-01-01

    Full Text Available In this paper, we have described fine needle aspiration cytology (FNAC of a rare case of dermal cylindroma. A 40-year-old female presented with a lateral mid-cervical swelling fixed to the skin. FNAC smears showed multiple clusters of small, round to oval cells with hyperchromatic nuclei, inconspicuous nucleoli and scant cytoplasm. In addition, the background showed deposits of basement membrane type material. This was dark magenta colored pinkish globular material. The globules were occasionally surrounded by the basal type of cells. Occasional cells with elongated nuclei were also noted. Cytological diagnosis of skin adnexal tumor possibly cylindroma was offered. Subsequent histopathology of the swelling showed sheets and clusters of cells in a jigsaw puzzle-like fashion. Deposition of abundant basement membrane-like material was noted in between the tumor cells. A diagnosis of cylindorma was offered. FNAC along with the subcutaneous location of the tumor and absence of primary salivary gland tumor may help to diagnose such rare case.

  4. Dermal factors influencing measurement of skin autofluorescence.

    Science.gov (United States)

    Noordzij, Margaretha J; Lefrandt, Joop D; Graaff, Reindert; Smit, Andries J

    2011-02-01

    Skin autofluorescence (SAF) is a noninvasive marker of accumulation of advanced glycation end products. It predicts cardiovascular complications and mortality in diabetes and renal failure. We assessed the influence of potential common confounders in SAF measurement, by determining the effects of endogenous and exogenous local dermal changes by body creams, hyperemia, vasoconstriction, and hydration. SAF was measured before and after local administration of body lotion, day cream, sunscreen, or self-browning cream and after attempts to remove these effects with alcohol swabs and washing. SAF was measured before and during three hyperemia maneuvers: vasoconstriction and on a dry and wet skin. The body lotion increased SAF by 18%. Day cream, sunscreen, and self-browning cream gave an increase of >100%. Except for body lotion, subsequent cleaning with alcohol swabs and washing with soap did not return SAF to baseline values. The effect of self-browning cream persisted for 2 weeks and that of sunscreen for 4 days. Hyperemia caused by a hot bath, capsicum cream, or postocclusive reactive hyperemia gave a decrease in SAF of, respectively, 18%, 22%, and 2.3%. Vasoconstriction caused by immersing the arm in cold water gave a 10% increase. Hydration state did not influence SAF. Measurement of SAF is strongly affected by several skin creams. This effect was often not fully corrected by alcohol swabs and washing with soap and may persist for many days. Marked hyperemia and vasoconstriction also influence SAF. We advise avoiding these potential error sources.

  5. ABCB5 Identifies Immunoregulatory Dermal Cells

    Directory of Open Access Journals (Sweden)

    Tobias Schatton

    2015-09-01

    Full Text Available Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5 identifies dermal immunoregulatory cells (DIRCs capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1. Purified Abcb5+ DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5+ DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.

  6. ABCB5 identifies immunoregulatory dermal cells

    Science.gov (United States)

    Schatton, Tobias; Yang, Jun; Kleffel, Sonja; Uehara, Mayuko; Barthel, Steven R.; Schlapbach, Christoph; Zhan, Qian; Dudeney, Stephen; Mueller, Hansgeorg; Lee, Nayoung; de Vries, Juliane C.; Meier, Barbara; Vander Beken, Seppe; Kluth, Mark A.; Ganss, Christoph; Sharpe, Arlene H.; Waaga-Gasser, Ana Maria; Sayegh, Mohamed H.; Abdi, Reza; Scharffetter-Kochanek, Karin; Murphy, George F.; Kupper, Thomas S.; Frank, Natasha Y.; Frank, Markus H.

    2015-01-01

    Summary Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly-defined immunomodulatory cell populations poses a barrier to this field. Here we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5+ DIRCs suppressed T-cell proliferation, evaded immune rejection, homed to recipient immune tissues and induced Tregs in vivo. In fully MHC-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T-cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5+ DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy. PMID:26321644

  7. Emotional intelligence and electro-dermal activity.

    Science.gov (United States)

    Zysberg, Leehu

    2012-09-01

    Emotional intelligence (EI) is a promising concept in our understanding of emotional regulation, related behaviors and pathologies. However, research linking EI to underlying physiological and biological structure and responses is meager. This study explored potential associations of EI with electro-dermal activity (EDA) responses to emotionally arousing visual stimuli. It was hypothesized that higher levels of EI will associate with more efficient emotional regulation as reflected by EDA. Eighty-four healthy participants were exposed to stimuli consisting of a series of 12 images designed to evoke positive or negative emotional responses, presented in a counterbalanced order. A self-report questionnaire and a computer based test of EI were administered along with a demographic questionnaire. EDA measures were taken during the exposure to the above stimuli using BIOPACK MP150. EI test scores (Beta = .35, .32; p self-report measure of EI and other demographics (e.g., gender. ethnicity) did not show any associations with the outcome measures. The results support the relevance of the concept to our understanding of emotional responses and regulation. The findings are briefly discussed within the context of underlying mechanisms of EI as well as measure validity and relevance.

  8. Topically applied vitamin C increases the density of dermal papillae in aged human skin

    Directory of Open Access Journals (Sweden)

    Koop Urte

    2004-09-01

    Full Text Available Abstract Background The influence of ageing on the density of the functional entities of the papillae containing nutritive capillaries, here in terms as the papillary index, and the effect of topically applied vitamin C were investigated by confocal laser scanning microscopy (CLSM in vivo. Methods The age dependency of the papillary index was determined by CLSM on 3 different age groups. Additionally, we determined the effect of a topical cream containing 3% vitamin C against the vehicle alone using daily applications for four months on the volar forearm of 33 women. Results There were significant decreases in the papillary index showing a clear dependency on age. Topical vitamin C resulted in a significant increase of the density of dermal papillae from 4 weeks onward compared to its vehicle. Reproducibility was determined in repeated studies. Conclusions Vitamin C has the potential to enhance the density of dermal papillae, perhaps through the mechanism of angiogenesis. Topical vitamin C may have therapeutical effects for partial corrections of the regressive structural changes associated with the aging process.

  9. Asphalt fume dermal carcinogenicity potential: I. dermal carcinogenicity evaluation of asphalt (bitumen) fume condensates.

    Science.gov (United States)

    Clark, Charles R; Burnett, Donald M; Parker, Craig M; Arp, Earl W; Swanson, Mark S; Minsavage, Gary D; Kriech, Anthony J; Osborn, Linda V; Freeman, James J; Barter, Robert A; Newton, Paul E; Beazley, Shelley L; Stewart, Christopher W

    2011-10-01

    Asphalt (bitumen) fume condensates collected from the headspace above paving and Type III built up roofing asphalt (BURA) tanks were evaluated in two-year dermal carcinogenicity assays in male C3H/HeNCrl mice. A third sample was generated from the BURA using a NIOSH laboratory generation method. Similar to earlier NIOSH studies, the BURA fume condensates were applied dermally in mineral oil twice per week; the paving sample was applied 7 days/week for a total weekly dose of 50 mg/wk in both studies. A single benign papilloma was observed in a group of 80 mice exposed to paving fume condensate at the end of the two-year study and only mild skin irritation was observed. The lab generated BURA fume condensate resulted in statistically significant (P<0.0001) increases in squamous cell carcinomas (35 animals or 55% of animals at risk). The field-matched BURA condensate showed a weaker but significant (P=0.0063) increase (8 carcinomas or 13% of animals) and a longer average latency (90 weeks vs. 76 for the lab fume). Significant irritation was observed in both BURA condensates. It is concluded that the paving fume condensate was not carcinogenic under the test conditions and that the field-matched BURA fume condensate produced a weak tumor response compared to the lab generated sample.

  10. Human Dermal Stem/Progenitor Cell-Derived Conditioned Medium Improves Senescent Human Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Ji-Yong Jung

    2015-08-01

    Full Text Available Adult skin stem cells are recognized as potential therapeutics to rejuvenate aged skin. We previously demonstrated that human dermal stem/progenitor cells (hDSPCs with multipotent capacity could be enriched from human dermal fibroblasts using collagen type IV. However, the effects of hDSPCs on cellular senescence remain to be elucidated. In the present study, we investigated whether conditioned medium (CM collected from hDSPC cultures (hDSPC-CM exhibits beneficial effects on senescent fibroblasts. We found that hDSPC-CM promoted proliferation and decreased the expression level of senescence-associated β-galactosidase in senescent fibroblasts. In addition, p53 phosphorylation and p21 expression were significantly reduced in senescent fibroblasts treated with hDSPC-CM. hDSPC-CM restored the expression levels of collagen type I, collagen type III, and tissue inhibitor of metalloproteinase, and antagonized the increase of matrix metalloproteinase 1 expression. Finally, we demonstrated that hDSPC-CM significantly reduced reactive oxygen species levels by specifically up-regulating the expression level of superoxide dismutase 2. Taken together, these data suggest that hDSPC-CM can be applied as a potential therapeutic agent for improving human aged skin.

  11. In vivo and in vitro studies of borate based glass micro-fibers for dermal repairing.

    Science.gov (United States)

    Zhou, Jie; Wang, Hui; Zhao, Shichang; Zhou, Nai; Li, Le; Huang, Wenhai; Wang, Deping; Zhang, Changqing

    2016-03-01

    Full-thickness skin defects represent urgent clinical problem nowadays. Wound dressing materials are hotly needed to induce dermal reconstruction or to treat serious skin defects. In this study, the borate bioactive glass (BG) micro-fibers were fabricated and compared with the traditional material 45S5 Bioglass(®) (SiG) micro-fibers. The morphology, biodegradation and bioactivity of BG and SiG micro-fibers were investigated in vitro. The wound size reduction and angiogenic effects of BG and SiG micro-fibers were evaluated by the rat full-thickness skin defect model and Microfil technique in vivo. Results indicated that the BG micro-fibers showed thinner fiber diameter (1 μm) and better bioactivity than the SiG micro-fibers did. The ionic extracts of BG and SiG micro-fibers were not toxic to human umbilical vein endothelial cells (HUVECs). In vivo, the BG micro-fiber wound dressings obviously enhanced the formation of blood vessel, and resulted in a much faster wound size reduction than the SiG micro-fibers, or than the control groups, after 9 days application. The good skin defect reconstruction ability of BG micro-fibers contributed to the B element in the composition, which results in the better bioactivity and angiogenesis. As shown above, the novel bioactive borate glass micro-fibers are expected to provide a promising therapeutic alternative for dermal reconstruction or skin defect repair.

  12. Unraveling the relative importance of oral and dermal contaminant exposure in reptiles: insights from studies using the western fence lizard (Sceloporus occidentalis).

    Science.gov (United States)

    Weir, Scott M; Talent, Larry G; Anderson, Todd A; Salice, Christopher J

    2014-01-01

    Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals.

  13. Unraveling the Relative Importance of Oral and Dermal Contaminant Exposure in Reptiles: Insights from Studies Using the Western Fence Lizard (Sceloporus occidentalis)

    Science.gov (United States)

    Weir, Scott M.; Talent, Larry G.; Anderson, Todd A.; Salice, Christopher J.

    2014-01-01

    Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage) and dermal (ventral skin application) exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP]) were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP) were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples), suggesting that lipophilicity (log Kow>2) is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue), but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals. PMID

  14. Unraveling the relative importance of oral and dermal contaminant exposure in reptiles: insights from studies using the western fence lizard (Sceloporus occidentalis.

    Directory of Open Access Journals (Sweden)

    Scott M Weir

    Full Text Available Despite widespread recognition of significant data deficiencies, reptiles remain a relatively understudied taxon in ecotoxicology. To conduct ecological risk assessments on reptiles frequently requires using surrogate taxa such as birds, but recent research suggests that reptiles have significantly different exposure profiles and toxicant sensitivity. We exposed western fence lizards, Sceloporus occidentalis, to the same quantities of three model chemicals via oral (gavage and dermal (ventral skin application exposure for either 24 or 48 hours. Three phthalate esters (di-methyl phthalate [DMP], di-iso-butyl phthalate [DIBP], and di-n-octyl phthalate [DNOP] were chosen as model chemicals because they represent a gradient of lipophilicity but are otherwise structurally similar. Overall, the more lipophilic phthalates (DIBP and DNOP were found to have higher concentrations in tissues than the less lipophilic DMP. Significant differences in tissue concentrations between DIBP and DNOP were tissue-dependent, suggesting that delivery to a site of action following exposure is not only a simple function of lipophilicity. In dermal treatments, DMP usually had fewer detections (except in ventral skin samples, suggesting that lipophilicity (log Kow>2 is a requirement for uptake across the skin. In general, tissue residues were greater in oral treatments than dermal treatments (significant in adipose and liver tissue, but differences were driven strongly by differences in DMP which did not appear to be absorbed well across skin. When differences in tissue residue concentrations between oral and dermal exposure did occur, the difference was not drastic. Taken together these results suggest that dermal exposure should be considered in risk assessments for reptilian receptors. Dermal exposure may be an especially important route for reptiles as their ectothermic physiology translates to lower energetic demands and dietary exposure compared to birds and mammals.

  15. Antibacterial and dermal toxicological profiles of ethyl acetate extract from Crassocephalum bauchiense (Hutch. Milne-Redh (Asteraceae

    Directory of Open Access Journals (Sweden)

    Njateng Guy SS

    2011-05-01

    Full Text Available Abstract Background The emergence in recent years of numerous resistant strains of pathogenic bacteria to a range of formerly efficient antibiotics constitutes a serious threat to public health. Crassocephalum bauchiense, a medicinal herb found in the West Region of Cameroon is used to treat gastrointestinal infections as well as liver disorders. The ethyl acetate extract from the leaves of C. bauchiense was evaluated for its antibacterial activity as well as acute and sub-acute toxicities. Methods The plant extract was prepared by maceration in ethyl acetate. Its phytochemical screening was done by standard methods. The broth microdilution method was used to evaluate the in vitro antibacterial activity. The in vivo antibacterial activity of a gel formulation (0.05, 1 and 2% w/v of this extract was evaluated using a Staphylococcus aureus-induced dermatitis in a murine model. Selected haematological and biochemical parameters were used to evaluate the dermal sub-acute toxicity of the extract in rats. Results Phytochemical screening of the C. bauchiense extract revealed the presence of alkaloids, phenols, tannins and sterols. In vitro antibacterial activities were observed against all the tested microorganisms (MIC = 0.04-6.25 mg/ml. Formulated extract-gel (2% w/v and gentamycin (reference drug eradicated the microbial infection after five days of treatment. A single dermal dose of this extract up to 32 g/kg body weight (bw did not produce any visible sign of toxicity. Also, daily dermal application of the C. bauchiense extract gel formulation for 28 days did not show any negative effect, instead some biochemical parameters such as alanine aminotransferase (ALT and AST, low density lipoprotein (LDL, high density lipoprotein (HDL and triglycerides were significantly (p Conclusion These results indicate that the C. bauchiense ethyl acetate extract can be used safely for the treatment of some bacterial infections.

  16. The toxicity of refrigerants

    Energy Technology Data Exchange (ETDEWEB)

    Calm, J.M.

    1996-07-01

    This paper presents toxicity data and exposure limits for refrigerants. The data address both acute (short-term, single exposure) and chronic (long-term, repeated exposure) effects, with emphasis on the former. The refrigerants covered include those in common use for the last decade, those used as components in alternatives, and selected candidates for future replacements. The paper also reviews the toxicity indicators used in both safety standards and building, mechanical, and fire codes. It then outlines current classification methods for refrigerant safety and relates them to standard and code usage.

  17. Dermal absorption and toxicological risk assessment

    NARCIS (Netherlands)

    Buist, H.

    2016-01-01

    Absorption of toxic substances via the skin is an important phenomenon in the assessment of the risk of exposure to these substances. People are exposed to a variety of substances and products via the skin, either directly or indirectly, while at work, at home or in public space. Pesticides, organic

  18. Dermal absorption and toxicological risk assessment

    NARCIS (Netherlands)

    Buist, H.

    2016-01-01

    Absorption of toxic substances via the skin is an important phenomenon in the assessment of the risk of exposure to these substances. People are exposed to a variety of substances and products via the skin, either directly or indirectly, while at work, at home or in public space. Pesticides, organic

  19. Allergic inflammation in the upper respiratory tract of the rat upon repeated inhalation exposure to the contact allergen dinitrochlorobenzene (DNCB).

    NARCIS (Netherlands)

    Triel, J.J. van; Arts, J.H.; Muijser, H.; Kuper, C.F.

    2010-01-01

    Previously, the contact allergen dinitrochlorobenzene (DNCB) was identified as a sensitizer by inhalation in BALB/c mice; in addition, DNCB induced a lymphocytic infiltrate in the larynx of dermally sensitized Th1-prone Wistar rats upon a single inhalation challenge. In the present study, repeated

  20. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeate

  1. Effects of single and repeated exposure to biocidal active substances on the barrier function of the skin in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Sandt, J.J.M. van de; Burgsteden, J.A. van; Heer, C. de

    2005-01-01

    The dermal route of exposure is important in worker exposure to biocidal products. Many biocidal active substances which are used on a daily basis may decrease the barrier function of the skin to a larger extent than current risk assessment practice addresses, due to possible skin effects of repeate

  2. Allergic inflammation in the upper respiratory tract of the rat upon repeated inhalation exposure to the contact allergen dinitrochlorobenzene (DNCB).

    NARCIS (Netherlands)

    Triel, J.J. van; Arts, J.H.; Muijser, H.; Kuper, C.F.

    2010-01-01

    Previously, the contact allergen dinitrochlorobenzene (DNCB) was identified as a sensitizer by inhalation in BALB/c mice; in addition, DNCB induced a lymphocytic infiltrate in the larynx of dermally sensitized Th1-prone Wistar rats upon a single inhalation challenge. In the present study, repeated i

  3. Alteration of Skin Properties with Autologous Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Rajesh L. Thangapazham

    2014-05-01

    Full Text Available Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.

  4. Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.

    Directory of Open Access Journals (Sweden)

    Peter C Cook

    2011-03-01

    Full Text Available Infection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S products. Here, we show that multiple (4x exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4(+ cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x, dermal cells from multiply infected mice (4x, were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80(+MHC-II(-, but they did not impact the ability of antigen presenting cells (APC to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1(+, Ym-1(+ alternatively activated macrophage-like cells, and the second are functionally compromised MHC-II(hi cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development.

  5. Carbodiimide crosslinked collagen from porcine dermal matrix for high-strength tissue engineering scaffold.

    Science.gov (United States)

    Li, Jianhua; Ren, Na; Qiu, Jichuan; Jiang, Huaidong; Zhao, Hongshi; Wang, Guancong; Boughton, Robert I; Wang, Yingjun; Liu, Hong

    2013-10-01

    Naturally-derived collagens for tissue engineering are limited by low mechanical strength and rapid degradation. In this study, carbodiimide is used to chemically modify the collagen derived from porcine acellular dermal matrix (PADM). The results show that the strength and resistance of PADM to enzymatic digestion can be adjusted by the reconnection of free amino and carboxyl groups of the collagen fibers. The cytocompatibility of the crosslinked PADM was evaluated by cell adhesion and proliferation assays. The cell culture studies on crosslinked and uncrosslinked PADM showed that the modification does not affect the scaffold's biocompatibility. These results demonstrate that the PADM collagen materials can be strengthened through a low-cost, non-toxic crosslinking method for potential use in biomedical applications.

  6. Pesticides re-entry dermal exposure of workers in greenhouses.

    Science.gov (United States)

    Caffarelli, V; Conte, E; Correnti, A; Gatti, R; Musmeci, F; Morali, G; Spagnoli, G; Tranfo, G; Triolo, L; Vita, M; Zappa, G

    2004-01-01

    This research has the aim to evaluate the risk of pesticide dermal exposure for workers in greenhouses. We considered the following crops: tomato, cucumber and strawberry, largely spread in Bracciano lake district. The pesticides monitored were: tetradifon on strawberry: metalaxyl, azoxystrobin and fenarimol on cucumber; acrinathrin, azoxystrobin and chlorpyrifos ethyl on tomato. The dermal exposure was evaluated by Dislodgeable Foliar Residue (DFR) measurements employing transfer coefficients got from literature. For risk evaluation, we have compared the dermal exposures with Acceptable Operator Exposure Levels (AOEL). The re-entry time were obtained intercepting the dose decay curves with AOEL values. The re-entry times result higher than two days in the cases of chlorpyrifos on tomato (re-entry time: 3 days), azoxystrobin on tomato (4 days), and tetradifon on strawberry (8 days). The need of measuring specific transfer coefficients is pointed out.

  7. Proliferation kinetics of the dermal infiltrate in cutaneous malignant lymphomas

    Energy Technology Data Exchange (ETDEWEB)

    Sterry, W.; Pullmann, H.; Steigleder, G.K.

    1981-01-01

    To obtain information about the role of local proliferation in the pathogenesis of dermal infiltrate in malignant cutaneous lymphomas, we determined the percentage of /sup 3/H-thymidine-labeled infiltrating cells (/sup 3/H-index). A linear correlation was found between proliferative activity and clinical stage in mycosis fungoides, i.e., the /sup 3/H-index is moderately elevated in stage I and high in stage III. The /sup 3/H-index is within normal range in dermal infiltrate of Sezary syndrome, diffuse lymphocytic lymphoma, as well as in lymphocytoma benigna cutis. In parapsoriasis en plaques two groups can be distinguished: in the small plaque variant (chronic superficial dermatitis) the /sup 3/H-index is low, whereas the large-plaque variant (prereticulotic poikiloderma) shows strong proliferative activity. Thus, determination of proliferative activity seems to give new insights into the pathogenesis of dermal infiltrate in cutaneous lymphomas.

  8. Efficacy of liposomal amphotericin B (AmBisome) in the treatment of persistent post-kala-azar dermal leishmaniasis (PKDL).

    Science.gov (United States)

    Musa, A M; Khalil, E A G; Mahgoub, F A; Hamad, S; Elkadaru, A M Y; El Hassan, A M

    2005-09-01

    A dermatosis commonly known as post-kala-azar dermal leishmaniasis (PKDL) may develop following the treatment of human visceral leishmaniasis (VL). In about 15% of PKDL cases the disfiguring lesions persist, sometimes for many years. Such persistent lesions currently require daily injections of sodium stibogluconate (SSG) for 2-4 months and even then treatment may not be successful. Alternative, quicker and cheaper treatment options that cause less toxicity are being explored. Immuno-chemotherapeutic regimens (based on leishmaniasis candidate vaccines/BCG with SSG) are still experimental but treatment with liposomal amphotericin B (AmBisome) has already been found effective, albeit in a small number of patients. AmBisome is considered less nephrotoxic than non-liposomal amphotericin B because it specifically targets the macrophages in which the Leishmania parasites develop. The aim of the present study was to evaluate further the usefulness of AmBisome in the treatment of persistent PKDL, in Sudan. The 12 subjects, all of whom gave their informed consent, had each had PKDL lesions for >6 months and shown no improvement after repeated injections of SSG. During the study period, they were hospitalized and regularly screened, haematologically and biochemically, for adverse effects. The AmBisome, given intravenously at 2.5 mg/kg.day for 20 days, completely cleared the skin rash of 10 (83%) of the patients and caused no detectable adverse effects. In the 10 patients who responded well to the treatment, the papular lesions regressed and became flat while the hypopigmented lesions darkened (continuing to do so even after the last AmBisome injections). Treatment outcome appeared to be unaffected by the age or gender of the patient (P = 0.7 for each) but the time taken for the PKDL lesions to heal was correlated with the age of the lesions (P = 0.009). The macular lesions healed more slowly than the papular (P = 0.02). In conclusion, Ambisome appears suitable for the

  9. Blaschko Linear Enamel Defects - A Marker for Focal Dermal Hypoplasia: Case Report of Focal Dermal Hypoplasia

    Directory of Open Access Journals (Sweden)

    Stefan Gysin

    2015-05-01

    Full Text Available Focal dermal hypoplasia (FDH is a rare genetic skin disorder. The inheritance of FDH or Goltz-Gorlin syndrome is X-linked dominant and the disease is associated with a PORCN gene mutation. This gene plays a key role in the Wnt pathway, which has an impact on embryonic development. Every tissue derived from meso- and ectoderm can be affected. Patients suffer from cutaneous, ocular, osseous, oral and dental defects. The skin and dental alterations manifest along the Blaschko lines. We present a woman (born in 1962 suffering from FDH with congenital skin changes and Blaschko linear enamel defects. Typical symptoms (e.g. fat herniations, scoliosis, syndactyly, microphthalmia, caries and alopecia plus vertical grooving of all teeth gave a first indication. Molecular genetic testing confirmed the definitive diagnosis of FDH. We hypothesize that, in the context of typical skin changes, visible Blaschko lines on the teeth in the form of vertical grooves are almost pathognomonic for FDH.

  10. Dermal Exposure during Filling, Loading and Brushing with Products Containing 2-(2-Butoxyethoxy)ethanol

    NARCIS (Netherlands)

    Gijsbers, J.H.J.; Tielemans, E.; Brouwer, D.H.; Hemmen, J.J. van

    2004-01-01

    Introduction: Limited quantitative information is available on dermal exposure to chemicals during various industrial activities. Therefore, within the scope of the EU-funded RISKOFDERM project, potential dermal exposure was measured during three different tasks: filling, loading and brushing. DEGBE

  11. Successful breast reconstruction using acellular dermal matrix can be recommended in healthy non-smoking patients

    DEFF Research Database (Denmark)

    Gunnarsson, Gudjon Leifur; Børsen-Koch, Mikkel; Arffmann, Susanne

    2013-01-01

    We present Scandinavia's first series of immediate alloplastic breast reconstructions with an acellular dermal matrix.......We present Scandinavia's first series of immediate alloplastic breast reconstructions with an acellular dermal matrix....

  12. Quantum repeated games revisited

    CERN Document Server

    Frackiewicz, Piotr

    2011-01-01

    We present a scheme for playing quantum repeated 2x2 games based on the Marinatto and Weber's approach to quantum games. As a potential application, we study twice repeated Prisoner's Dilemma game. We show that results not available in classical game can be obtained when the game is played in the quantum way. Before we present our idea, we comment on the previous scheme of playing quantum repeated games.

  13. Dermal Toxicity Evaluation of Neutralized Chemical Agent Identification Sets (CAIS) with an Overview of the Dermal Toxicity of Vesicant Agents and their Degradation Products.

    Science.gov (United States)

    1996-10-01

    chloroform, nitrogen mustard (HN-l) (10%) in chloroform, or lewisite (5%) in chloroform; and " Sniff Set" containing sulfur mustard, nitrogen mustard...Exposure) Species LC,, (mg/m 3 ) Exposure Duration (Min) Mouse 120 (10) Rat 80 (10) Guinea Pig 170 (10) Rabbit 90 (10) Dog 60 (10) Goat 190 (10) Monkey 80...Carcinogenicity/Tumorigenicitv: Chronic exposure to sulfur mustard can cause cancer of the respiratory tract, skin and blood forming tissues. Sulfur mustard has

  14. [Exploratory study on the micro-remodeling of dermal tissue].

    Science.gov (United States)

    Jiang, Yu-zhi; Ding, Gui-fu; Lu, Shu-liang

    2009-10-01

    To explore the effect of three-dimensional structure of dermal matrix on biological behavior of fibroblasts (Fb) in the microcosmic perspective. The three-dimensional structure of dermal tissue was analyzed by plane geometric and trigonometric function. Microdots structure array with cell adhesion effect was designed by computer-assisted design software according to the adhesive and non-adhesive components of dermal tissue. Four sizes (8 microm x 3 microm, space 6 microm; 16 microm x 3 microm, space 6 microm; 16 microm x 5 microm, space 8 microm; 20 microm x 3 microm, space 2 microm) of micropier grid used for cell culture (MPGCC) with cell-adhesive microdots, built up with micro-pattern printing and molecule self-assembly method were used to culture dermal Fb. Fb cultured with cell culture matrix without micropier grid was set up as control. The expression of skeleton protein (alpha-SMA) of Fb, cell viability and cell secretion were detected with immunohistochemistry, fluorescent immunohistochemistry, MTT test and the hydroxyproline content assay. The three-dimensional structure of dermal tissue could be simulated by MPGCC as shown in arithmetic analysis. Compared with those of control group [(12 +/- 3)% and (0.53 +/- 0.03) microg/mg, (0.35 +/- 0.04)], the expression of alpha-SMA [(49 +/- 3)%, (61 +/- 3)%, (47 +/- 4)%, (51 +/- 3)%] and the content of hydroxyproline [(0.95 +/- 0.04), (0.87 +/- 0.03), (0.81 +/- 0.03), (0.77 +/- 0.03) microg/mg] were increased significantly (P cell viability of Fb (0.12 +/- 0.03, 0.13 +/- 0.04, 0.14 +/- 0.03, 0.19 +/- 0.03) cultured in MPGCC was decreased significantly (P cell viability and the content of hydroxyproline of Fb cultured in four sizes of MPGCC were also significantly changed as compared with one another (P < 0.05). MPGCC may be the basic functional unit of dermal template, or unit of dermal template to call. Different three-dimensional circumstances for dermal tissue can result in different template effect and wound

  15. File list: InP.Epd.10.AllAg.Dermal_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Epd.10.AllAg.Dermal_fibroblast hg19 Input control Epidermis Dermal fibroblast S...,SRX447386,SRX666594,SRX447389,SRX200051,SRX864096,SRX200053 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Epd.10.AllAg.Dermal_fibroblast.bed ...

  16. File list: NoD.Epd.05.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Epd.05.AllAg.Dermal_fibroblasts mm9 No description Epidermis Dermal fibroblasts... http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Epd.05.AllAg.Dermal_fibroblasts.bed ...

  17. File list: ALL.Epd.20.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Epd.20.AllAg.Dermal_fibroblasts mm9 All antigens Epidermis Dermal fibroblasts S...26,SRX310225,SRX310224,SRX388187 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Epd.20.AllAg.Dermal_fibroblasts.bed ...

  18. File list: InP.Epd.50.AllAg.Dermal_fibroblast [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Epd.50.AllAg.Dermal_fibroblast hg19 Input control Epidermis Dermal fibroblast S...,SRX200045,SRX864096,SRX200053,SRX200051,SRX447389,SRX447386 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/InP.Epd.50.AllAg.Dermal_fibroblast.bed ...

  19. File list: Oth.Epd.20.AllAg.Dermal_fibroblasts [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Epd.20.AllAg.Dermal_fibroblasts mm9 TFs and others Epidermis Dermal fibroblasts... SRX247302,SRX382120,SRX247301,SRX247303,SRX382119,SRX310229,SRX310227,SRX310225 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Epd.20.AllAg.Dermal_fibroblasts.bed ...

  20. Validation of the dermal exposure model in ECETOC TRA.

    Science.gov (United States)

    Marquart, Hans; Franken, Remy; Goede, Henk; Fransman, Wouter; Schinkel, Jody

    2017-08-01

    The ECETOC TRA model (presently version 3.1) is often used to estimate worker inhalation and dermal exposure in regulatory risk assessment. The dermal model in ECETOC TRA has not yet been validated by comparison with independent measured exposure levels. This was the goal of the present study. Measured exposure levels and relevant contextual information were gathered via literature search, websites of relevant occupational health institutes and direct requests for data to industry. Exposure data were clustered in so-called exposure cases, which are sets of data from one data source that are expected to have the same values for input parameters in the ECETOC TRA dermal exposure model. For each exposure case, the 75th percentile of measured values was calculated, because the model intends to estimate these values. The input values for the parameters in ECETOC TRA were assigned by an expert elicitation and consensus building process, based on descriptions of relevant contextual information.From more than 35 data sources, 106 useful exposure cases were derived, that were used for direct comparison with the model estimates. The exposure cases covered a large part of the ECETOC TRA dermal exposure model. The model explained 37% of the variance in the 75th percentiles of measured values. In around 80% of the exposure cases, the model estimate was higher than the 75th percentile of measured values. In the remaining exposure cases, the model estimate may not be sufficiently conservative.The model was shown to have a clear bias towards (severe) overestimation of dermal exposure at low measured exposure values, while all cases of apparent underestimation by the ECETOC TRA dermal exposure model occurred at high measured exposure values. This can be partly explained by a built-in bias in the effect of concentration of substance in product used, duration of exposure and the use of protective gloves in the model. The effect of protective gloves was calculated to be on average a

  1. Toxic Elements

    DEFF Research Database (Denmark)

    Hajeb, Parvaneh; Shakibazadeh, Shahram; Sloth, Jens Jørgen

    2016-01-01

    Food is considered the main source of toxic element (arsenic, cadmium, lead, and mercury) exposure to humans, and they can cause major public health effects. In this chapter, we discuss the most important sources for toxic element in food and the foodstuffs which are significant contributors...... to human exposure. The occurrence of each element in food classes from different regions is presented. Some of the current toxicological risk assessments on toxic elements, the human health effect of each toxic element, and their contents in the food legislations are presented. An overview of analytical...... techniques and challenges for determination of toxic elements in food is also given....

  2. Cause Analysis of the Repeated Occurrence of Toxic and Hazardous Food Events%有毒有害食品事件屡次发生的原因分析

    Institute of Scientific and Technical Information of China (English)

    康国定; 杨莉; 焦亚波; 周秀慧

    2011-01-01

    人民群众餐桌安全、生命健康安全是维护社会稳定的头等大事之一,关乎群众切身利益、群众反映强烈的有毒有害食品已引起政府和全社会的高度重视.本文针对若干有毒有害食品事件进行分析,结果表明导致这类事件屡次发生的原因主要有:①政府和相关职能部门的管理和监督缺乏力度,至今还没有建立完全可靠的食品安全控制体系.②一些商家经营的规范和诚信责任不强,一些员工职业道德缺失和食品安全知识匮乏.③消费者维护食品安全意识薄弱.只有政府相关职能部门切实实施有效管理和监督,食品企业切实履行经营规范、诚信责任和员工职业道德教育及食品安全知识的培训,所有消费者切实提高认识和识别能力来维护食品安全,只有这样才能使人们的饮食健康能够得到保障.%The food table safety and the life and health safety of people is one of the cardinal issues to maintain social stability. The toxic and hazardous food that related to the vital interests of the masses has caused the government and the whole society's attention. In this paper, a number of toxic and hazardous food events are analyzed. The results showe that the main reasons include: ① The management and supervision of the government and relevant functional departments is lack of intensity, and it has not established a fully reliable food safety control system so far. ② The norms of some business operations are not standard and their fiduciary duty are not strong, and some of the staff is lack of professional ethics and the knowledge of food safety. ③ The consumer's awareness of food safety maintenance is weak. So the government agencies should effectively implement effective management and supervision, the food business should effectively implement operator norms and conduct the training of the integrity responsibilities, professional ethics and food safety knowledge for staff, and

  3. Dermal Lipogenesis Inhibits Adiponectin Production in Human Dermal Fibroblasts while Exogenous Adiponectin Administration Prevents against UVA-Induced Dermal Matrix Degradation in Human Skin.

    Science.gov (United States)

    Fang, Chien-Liang; Huang, Ling-Hung; Tsai, Hung-Yueh; Chang, Hsin-I

    2016-07-14

    Adiponectin is one of the most abundant adipokines from the subcutaneous fat, and regulates multiple activities through endocrine, paracrine, or autocrine mechanisms. However, its expression in adipogenic induced fibroblasts, and the potential role in photoaging has not been determined. Here, human dermal fibroblasts, Hs68, were presented as a cell model of dermal lipogenesis through stimulation of adipogenic differentiation medium (ADM). Similar to other studies in murine pre-adipocyte models (i.e., 3T3-L1), Hs68 fibroblasts showed a tendency to lipogenesis based on lipid accumulation, triglyceride formation, and the expressions of PPAR-γ, lipoprotein lipase (LPL), and FABP4 mRNA. As expected, ADM-treated fibroblasts displayed a reduction on adiponectin expression. Next, we emphasized the photoprotective effects of adiponectin against UVA-induced damage in Hs68 fibroblasts. UVA radiation can downregulate cell adhesion strength and elastic modulus of Hs68 fibroblasts. Moreover, UVA radiation could induce the mRNA expressions of epidermal growth factor receptor (EGFR), adiponectin receptor 1 (AdipoR1), matrix metalloproteinase-1 (MMP-1), MMP-3, and cyclooxygenase-2 (COX-2), but downregulate the mRNA expressions of type I and type III collagen. On the other hand, post-treatment of adiponectin can partially overcome UVA-induced reduction in the cell adhesion strength of Hs68 fibroblasts through the activation of AdipoR1 and the suppression of EGF-R. In addition, post-treatment of adiponectin indicated the increase of type III collagen and elastin mRNA expression and the decrease of MMP-1 and MMP-3 mRNA expression, but a limited degree of recovery of elastic modulus on UVA-irradiated Hs68 fibroblasts. Overall, these results suggest that dermal lipogenesis may inhibit the expression of adiponectin while exogenous adiponectin administration prevents against UVA-induced dermal matrix degradation in Hs68 fibroblasts.

  4. Task-based dermal exposure models for regulatory risk assessment

    NARCIS (Netherlands)

    Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of ne

  5. Crosslinking of dermal sheep collagen using hexamethylene diisocyanate

    NARCIS (Netherlands)

    Olde Damink, L.H.H.; Dijkstra, P.J.; Luyn, van M.J.A.; Wachem, van P.B.; Nieuwenhuis, P.; Feijen, J.

    1995-01-01

    The use of hexamethylene diisocyanate (HMDIC) as a crosslinking agent for dermal sheep collagen (DSC) was studied. Because HMDIC is only slightly water soluble, a surfactant was used to obtain a clear and micellar crosslinking solution and to promote the penetration of HMDIC in the DSC matrix. Using

  6. Differential Apoptosis in Mucosal and Dermal Wound Healing

    Science.gov (United States)

    Johnson, Ariel; Francis, Marybeth; DiPietro, Luisa Ann

    2014-01-01

    Objectives: Dermal and mucosal healing are mechanistically similar. However, scarring and closure rates are dramatically improved in mucosal healing, possibly due to differences in apoptosis. Apoptosis, nature's preprogrammed form of cell death, occurs via two major pathways, extrinsic and intrinsic, which intersect at caspase3 (Casp3) cleavage and activation. The purpose of this experiment was to identify the predominant pathways of apoptosis in mucosal and dermal wound healing. Approach: Wounds (1 mm biopsy punch) were made in the dorsal skin (n=3) or tongue (n=3) of female Balb/C mice aged 6 weeks. Wounds were harvested at 6 h, 24 h, day 3 (D3), D5, D7, and D10. RNA was isolated and analyzed using real time reverse transcriptase–polymerase chain reaction. Expression levels for genes in the intrinsic and extrinsic apoptotic pathways were compared in dermal and mucosal wounds. Results: Compared to mucosal healing, dermal wounds exhibited significantly higher expression of Casp3 (at D5; pwound healing compared to skin. Conclusion: Expression patterns of key regulators of apoptosis in wound healing indicate that apoptosis occurs predominantly through the intrinsic pathway in the healing mucosa, but predominantly through the extrinsic pathway in the healing skin. The identification of differences in the apoptotic pathways in skin and mucosal wounds may allow the development of therapeutics to improve skin healing. PMID:25493209

  7. Dermal Uptake of Organic Vapors Commonly Found in Indoor Air

    DEFF Research Database (Denmark)

    Weschler, Charles J.; Nazaroff, William W

    2014-01-01

    . In this group are common parabens, lower molecular weight phthalates, o-phenylphenol, Texanol, ethylene glycol, and α-terpineol. For other compounds, estimated dermal uptakes are small compared to inhalation. Examples include aliphatic hydrocarbons, single ring aromatics, terpenes, chlorinated solvents...

  8. CROSS-LINKING OF DERMAL SHEEP COLLAGEN USING HEXAMETHYLENE DIISOCYANATE

    NARCIS (Netherlands)

    DAMINK, LHHO; DIJKSTRA, PJ; VANLUYN, MJA; VANWACHEM, PB; NIEUWENHUIS, P; FEIJEN, J

    1995-01-01

    The use of hexamethylene diisocyanate (HMDIC) as a crosslinking agent for dermal sheep collagen (DSC) was studied. Because HMDIC is on ly slightly water soluble, a surfactant was used to obtain a clear and micellar crosslinking solution and to promote the penetration of HMDIC in the DSC matrix. Usin

  9. The Effect of Gynostemma pentaphyllum Extract on Mouse Dermal Fibroblasts.

    Science.gov (United States)

    Lobo, Sara Nadia; Qi, Yu Qing; Liu, Quan Zhong

    2014-01-01

    Background. The objective of this paper is to demonstrate the effect of Gynostemma pentaphyllum extract on mouse dermal fibroblasts. Recent studies have shown that this plant may possess great antioxidant properties, which can be very beneficial in combating oxidative stress. Methods. Gynostemma pentaphyllum extract was prepared and mouse dermal fibroblasts were obtained and cultured as per our laboratory protocols. Twelve samples of cells were cultured under the same conditions and both negative and positive controls were established. Induction of oxidative stress was carried out using ultraviolet C (UVC) light. Viable cell count was carried out, using microscopy. The analysis of the overall results was processed using SPSS version 16.0. Results. Statistical analysis showed strong positive correlation between the concentration of Gynostemma pentaphyllum and the mean duration of cell viability (rs = 1), with a high level of statistical significance (P Gynostemma pentaphyllum extract prolongs viability of mouse dermal fibroblasts damaged by UVC light-induced oxidative stress. The results show the potential benefits of this extract on dermal cell aging.

  10. PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES

    Science.gov (United States)

    PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATESM.J.K. Selgrade, E.H. Boykin, N.H. Coates, D.L. Doerfler, S.H. GavettExperimental Toxicology Div., National Health and Environmental Research Laboratory, Office of Research and Developmen...

  11. Cerebellair abces door een occipitale dermale sinus bij een zuigeling

    NARCIS (Netherlands)

    Groen, R J; van Ouwerkerk, W J

    1994-01-01

    A 7.5-month-old girl was admitted with the clinical signs and symptoms of raised intracranial pressure. This was caused by an obstructive hydrocephalus, due to cerebellar abscesses induced by an infected contiguous complete occipital dermal sinus. Staphylococcus aureus was cultured. The patient was

  12. Task-based dermal exposure models for regulatory risk assessment

    NARCIS (Netherlands)

    Warren, N.D.; Marquart, H.; Christopher, Y.; Laitinen, J.; Hemmen, J.J. van

    2006-01-01

    The regulatory risk assessment of chemicals requires the estimation of occupational dermal exposure. Until recently, the models used were either based on limited data or were specific to a particular class of chemical or application. The EU project RISKOFDERM has gathered a considerable number of

  13. In vivo dermal absorption of pyrethroid pesticides in the rat.

    Science.gov (United States)

    The potential for exposure to pyrethroid pesticides has risen recently because of their increased use. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin and permethrin in the rat. Hair on the dorsal side of anesthetized adult m...

  14. Defense against dermal exposures is only skin deep

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm

    2007-01-01

    substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present...

  15. Inhalation and dermal exposure among asphalt paving workers.

    Science.gov (United States)

    McClean, M D; Rinehart, R D; Ngo, L; Eisen, E A; Kelsey, K T; Herrick, R F

    2004-11-01

    The primary objective of this study was to identify determinants of inhalation and dermal exposure to polycyclic aromatic compounds (PACs) among asphalt paving workers. The study population included three groups of highway construction workers: 20 asphalt paving workers, as well as 12 millers and 6 roadside construction workers who did not work with hot-mix asphalt. During multiple consecutive work shifts, personal air samples were collected from each worker's breathing zone using a Teflon filter and cassette holder connected in series with an XAD-2 sorbent tube, while dermal patch samples were collected from the underside of each worker's wrist. All exposure samples were analyzed for PACs, pyrene and benzo[a]pyrene. Inhalation and dermal PAC exposures were highest among asphalt paving workers. Among paving workers, inhalation and dermal PAC exposures varied significantly by task, crew, recycled asphalt product (RAP) and work rate (inhalation only). Asphalt mix containing high RAP was associated with a 5-fold increase in inhalation PAC exposures and a 2-fold increase in dermal PAC exposure, compared with low RAP mix. The inhalation PAC exposures were consistent with the workers' proximity to the primary source of asphalt fume (paver operators > screedmen > rakers > roller operators), such that the adjusted mean exposures among paver operators (5.0 microg/m3, low RAP; 24 microg/m3, high RAP) were 12 times higher than among roller operators (0.4 microg/m3, low RAP; 2.0 microg/m3, high RAP). The dermal PAC exposures were consistent with the degree to which the workers have actual contact with asphalt-contaminated surfaces (rakers > screedmen > paver operators > roller operators), such that the adjusted mean exposures among rakers (175 ng/cm2, low RAP; 417 ng/cm2, high RAP) were approximately 6 times higher than among roller operators (27 ng/cm2, low RAP; 65 ng/cm2, high RAP). Paving task, RAP content and crew were also found to be significant determinants of

  16. Dermal exposure and urinary 1-hydroxypyrene among asphalt roofing workers.

    Science.gov (United States)

    McClean, M D; Rinehart, R D; Sapkota, A; Cavallari, J M; Herrick, R F

    2007-01-01

    The primary objective of this study was to identify significant determinants of dermal exposure to polycyclic aromatic compounds (PACs) among asphalt roofing workers and use urinary 1-hydroxyprene (1-OHP) measurements to evaluate the effect of dermal exposure on total absorbed dose. The study population included 26 asphalt roofing workers who performed three primary tasks: tearing off old roofs (tear-off), putting down new roofs (put-down), and operating the kettle at ground level (kettle). During multiple consecutive work shifts (90 workerdays), dermal patch samples were collected from the underside of each worker's wrists and were analyzed for PACs, pyrene, and benzo(a)pyrene (BAP). During the same work week, urine samples were collected at pre-shift, post-shift, and bedtime each day and were analyzed for 1-OHP (205 urine samples). Linear mixed effects models were used to evaluate the dermal measurements for the purpose of identifying important determinants of exposure, and to evaluate urinary 1-OHP measurements for the purpose of identifying important determinants of total absorbed dose. Dermal exposures to PAC, pyrene, and BAP were found to vary significantly by roofing task (tear-off > put-down > kettle) and by the presence of an old coal tar pitch roof (pitch > no pitch). For each of the three analytes, the adjusted mean dermal exposures associated with tear-off (812 ng PAC/cm2, 14.9 ng pyrene/cm2, 4.5 ng BAP/cm2) were approximately four times higher than exposures associated with operating the kettle (181 ng PAC/cm2, 4.1 ng pyrene/cm2, 1.1 ng BAP/cm2). Exposure to coal tar pitch was associated with a 6-fold increase in PAC exposure (p = 0.0005), an 8-fold increase in pyrene exposure (p pitch roof was removed, accounting for a 3.7-fold difference at pre-shift (p = 0.01), a 5.0-fold difference at post-shift (p = 0.004), and a 7.2-fold difference at bedtime (p = 0.002). The pyrene measurements obtained during the work shift were found to be strongly correlated

  17. Reconfigurable multiport EPON repeater

    Science.gov (United States)

    Oishi, Masayuki; Inohara, Ryo; Agata, Akira; Horiuchi, Yukio

    2009-11-01

    An extended reach EPON repeater is one of the solutions to effectively expand FTTH service areas. In this paper, we propose a reconfigurable multi-port EPON repeater for effective accommodation of multiple ODNs with a single OLT line card. The proposed repeater, which has multi-ports in both OLT and ODN sides, consists of TRs, BTRs with the CDR function and a reconfigurable electrical matrix switch, can accommodate multiple ODNs to a single OLT line card by controlling the connection of the matrix switch. Although conventional EPON repeaters require full OLT line cards to accommodate subscribers from the initial installation stage, the proposed repeater can dramatically reduce the number of required line cards especially when the number of subscribers is less than a half of the maximum registerable users per OLT. Numerical calculation results show that the extended reach EPON system with the proposed EPON repeater can save 17.5% of the initial installation cost compared with a conventional repeater, and can be less expensive than conventional systems up to the maximum subscribers especially when the percentage of ODNs in lightly-populated areas is higher.

  18. Revisiting the TALE repeat.

    Science.gov (United States)

    Deng, Dong; Yan, Chuangye; Wu, Jianping; Pan, Xiaojing; Yan, Nieng

    2014-04-01

    Transcription activator-like (TAL) effectors specifically bind to double stranded (ds) DNA through a central domain of tandem repeats. Each TAL effector (TALE) repeat comprises 33-35 amino acids and recognizes one specific DNA base through a highly variable residue at a fixed position in the repeat. Structural studies have revealed the molecular basis of DNA recognition by TALE repeats. Examination of the overall structure reveals that the basic building block of TALE protein, namely a helical hairpin, is one-helix shifted from the previously defined TALE motif. Here we wish to suggest a structure-based re-demarcation of the TALE repeat which starts with the residues that bind to the DNA backbone phosphate and concludes with the base-recognition hyper-variable residue. This new numbering system is consistent with the α-solenoid superfamily to which TALE belongs, and reflects the structural integrity of TAL effectors. In addition, it confers integral number of TALE repeats that matches the number of bound DNA bases. We then present fifteen crystal structures of engineered dHax3 variants in complex with target DNA molecules, which elucidate the structural basis for the recognition of bases adenine (A) and guanine (G) by reported or uncharacterized TALE codes. Finally, we analyzed the sequence-structure correlation of the amino acid residues within a TALE repeat. The structural analyses reported here may advance the mechanistic understanding of TALE proteins and facilitate the design of TALEN with improved affinity and specificity.

  19. Toxicity Studies on "840 Biologic Pesticide"

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    [Objective] "840 Biologic Pesticide" is a very effective biologic pesticide. It consists of Abamectin and celastrus angulatus. Toxicity study was aimed to provide scientific toxicological basis. [Methods] The acute toxicity test,Ames test,micronucleus test and testicle chromosome aberration test were done. [Results] The acute toxicity of single dose of "840 Biologic Pesticide" showed that acute oral LD50 for female and male rats are 4 300 and 4 280 mg/kg,and for female and male mice are 2 330 and 5 110 mg/kg,respectively. The dermal LD50 was >2 000 mg/kg for female and male rats. The mutagenesis studies indicated that Ames test,micronucleus test and testicle chromosome aberration test were negative. [Conclusion] Tested pesticidc belongs to low toticity grade.

  20. Enhanced dermal delivery of acyclovir using solid lipid nanoparticles.

    Science.gov (United States)

    Jain, Sanyog; Mistry, Meghal A; Swarnakar, Nitin K

    2011-10-01

    The present investigation was enthused by the possibility to develop solid lipid nanoparticles (SLNs) of hydrophilic drug acyclovir (ACV) and evaluate their potential as the carrier for dermal delivery. ACV-loaded SLNs (ACV-SLNs) were prepared by the optimized double emulsion process using Compritol 888 ATO as solid lipid. The prepared SLNs were smooth and spherical in shape with average diameter, polydispersity index, and entrapment efficiency of 262 ± 13 nm, 0.280 ± 0.01, and 40.08 ± 4.39% at 10% (w/w) theoretical drug loading with respect to Compritol 888 ATO content. Differential scanning calorimetry and powder X-ray diffraction pattern revealed that ACV was present in the amorphous state inside the SLNs. In vitro skin permeation studies on human cadaver and Sprague-Dawley rat skin revealed 17.65 and 15.17 times higher accumulation of ACV-SLNs in the dermal tissues in comparison to commercially available ACV cream after 24 h. Mechanism of topical permeation and dermal distribution was studied qualitatively using confocal laser scanning microscopy. While free dye (calcein) failed to penetrate skin barrier, the same encapsulated in SLNs penetrated deeply into the dermal tissue suggesting that pilosebaceous route was followed by SLNs for skin penetration. Histological examination and transdermal epidermal water loss measurement suggested that no major morphological changes occurred on rat skin surface due to the application of SLNs. Overall, it was concluded that ACV-loaded SLNs might be beneficial in improving dermal delivery of antiviral agent(s) for the treatment of topical herpes simplex infection.

  1. Applications of acellular dermal matrix in revision breast reconstruction surgery.

    Science.gov (United States)

    Spear, Scott L; Sher, Sarah R; Al-Attar, Ali; Pittman, Troy

    2014-01-01

    Acellular dermal matrix has been used for over a decade in primary breast reconstruction. Few articles have specifically examined its use in revision breast reconstruction for fold malposition, capsular contracture, rippling, and symmastia. One hundred thirty-five revision breast reconstructive procedures using acellular dermal matrix (AlloDerm) in 118 patients (154 breasts) over a 5-year period were reviewed. Most procedures were revisions or part of the second stage of previous mastectomy reconstructions; three were revisions after reconstruction of congenital chest wall deformities. Fifty-seven revisions (37 percent) were for inferior fold malposition, followed by 40 (25.9 percent) for inferior pole support, 42 (27.2 percent) for capsular contracture, 10 (6.4 percent) for rippling, and five (3.2 percent) for symmastia. The overall complication rate was 5 percent. Revisions with acellular dermal matrix were successful in 147 of 154 breasts (95.5 percent). The most common complication was capsular contracture, occurring in five breasts (3.2 percent). There was one infection (0.6 percent), failure to lower the inframammary fold in one breast (0.6 percent), and one persistence of rippling (0.6 percent). The mean follow-up was 207 days. Acellular dermal matrix has proven to be a reliable tool for managing some of the most common and challenging problems in implant-based breast reconstruction. Although there are few published data on the success of more conventional solutions to fold malposition, lower pole support, and capsular contracture, the addition of acellular dermal matrix to buttress these repairs has been shown to provide a high likelihood of success with a low risk of complications.

  2. Modulatory Effect of Baphia Nitida Dye in Toluene Induced Cytogenotoxicity, Hematotoxicity and Histopathology in Dermal Exposed Wistar Rats

    Directory of Open Access Journals (Sweden)

    Chibuisi Gideon Alimba

    2015-03-01

    Full Text Available Background: There is unprecedented increase in the processing and packaging of many plant materials into food supplements, herbal medicine, skincare and cosmetic products for human needs. Baphia nitida is used for topical skincare products. Toluene, a toxic aromatic solvent, is increasingly being used in the production of these skincare and cosmetic products in many industries. This study assessed toluene toxicological profile and the ability of Baphia nitida dye to ameliorate toluene induced cytogenotoxicity, hematotoxicity and histopathological effects in rats. Methods: Rats were treated with various concentrations; 0, 1000, 2000 and 5000 mg of the aqueous, ethanol and toluene processed B. nitida dye via dermal exposure for acute and sub-lethal toxicity. 96 h acute toxicity was assessed for the solvents. Micronuclei induction, alterations in hematological indices and erythrocyte morphology and skin histology were assessed after sub-lethal treatment. Results: 96 h LD50 of B. nitida processed dye for the three solvents were indeterminate. There was insignificant (p>0.05 alterations in the hematological indices and erythrocyte morphology, induction of micronucleated polychromatic erythrocyte and polychromatic and normochromatic erythrocyte ratio in the aqueous and ethanol processed B. nitida treated rats compared to their corresponding controls. Toluene induced significant (p<0.05 decrease in erythrocytes count, hematocrit and leucocytes, increased micronucleated PCE, decreased PCE/NCE ratio and induced necrosis, thick dermal layer and dispersed areolar tissues in treated rats. But, these effects were ameliorated by the B. nitida dye. Conclusion: Camwood dye protects against toluene induced toxicity in rats. This suggests its relative safety in topical cosmetic and skincare production.

  3. Recursive quantum repeater networks

    CERN Document Server

    Van Meter, Rodney; Horsman, Clare

    2011-01-01

    Internet-scale quantum repeater networks will be heterogeneous in physical technology, repeater functionality, and management. The classical control necessary to use the network will therefore face similar issues as Internet data transmission. Many scalability and management problems that arose during the development of the Internet might have been solved in a more uniform fashion, improving flexibility and reducing redundant engineering effort. Quantum repeater network development is currently at the stage where we risk similar duplication when separate systems are combined. We propose a unifying framework that can be used with all existing repeater designs. We introduce the notion of a Quantum Recursive Network Architecture, developed from the emerging classical concept of 'recursive networks', extending recursive mechanisms from a focus on data forwarding to a more general distributed computing request framework. Recursion abstracts independent transit networks as single relay nodes, unifies software layer...

  4. Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Kanae [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Shishido, Mayumi [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Fujimoto, Keiko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan); Hirota, Yuko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Yo, Kazuyuki; Gomi, Takamasa [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Tanaka, Yoshitaka, E-mail: tanakay@bioc.phar.kyushu-u.ac.jp [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan)

    2014-01-03

    Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

  5. Repeat Gamma Knife Radiosurgery for Trigeminal Neuralgia

    Energy Technology Data Exchange (ETDEWEB)

    Aubuchon, Adam C., E-mail: acaubuchon@gmail.com [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Chan, Michael D. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Lovato, James F. [Department of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC (United States); Balamucki, Christopher J. [Department of Radiation Oncology, University of Florida, Gainesville, FL (United States); Ellis, Thomas L.; Tatter, Stephen B. [Department of Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, NC (United States); McMullen, Kevin P.; Munley, Michael T.; Deguzman, Allan F.; Ekstrand, Kenneth E.; Bourland, J. Daniel; Shaw, Edward G. [Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC (United States)

    2011-11-15

    Purpose: Repeat gamma knife stereotactic radiosurgery (GKRS) for recurrent or persistent trigeminal neuralgia induces an additional response but at the expense of an increased incidence of facial numbness. The present series summarized the results of a repeat treatment series at Wake Forest University Baptist Medical Center, including a multivariate analysis of the data to identify the prognostic factors for treatment success and toxicity. Methods and Materials: Between January 1999 and December 2007, 37 patients underwent a second GKRS application because of treatment failure after a first GKRS treatment. The mean initial dose in the series was 87.3 Gy (range, 80-90). The mean retreatment dose was 84.4 Gy (range, 60-90). The dosimetric variables recorded included the dorsal root entry zone dose, pons surface dose, and dose to the distal nerve. Results: Of the 37 patients, 81% achieved a >50% pain relief response to repeat GKRS, and 57% experienced some form of trigeminal dysfunction after repeat GKRS. Two patients (5%) experienced clinically significant toxicity: one with bothersome numbness and one with corneal dryness requiring tarsorraphy. A dorsal root entry zone dose at repeat treatment of >26.6 Gy predicted for treatment success (61% vs. 32%, p = .0716). A cumulative dorsal root entry zone dose of >84.3 Gy (72% vs. 44%, p = .091) and a cumulative pons surface dose of >108.5 Gy (78% vs. 44%, p = .018) predicted for post-GKRS numbness. The presence of any post-GKRS numbness predicted for a >50% decrease in pain intensity (100% vs. 60%, p = .0015). Conclusion: Repeat GKRS is a viable treatment option for recurrent trigeminal neuralgia, although the patient assumes a greater risk of nerve dysfunction to achieve maximal pain relief.

  6. In Vitro Toxicity of Aluminum Nanoparticles in Human Keratinocytes

    Science.gov (United States)

    2008-03-01

    absorption of aluminum has been reported after application of underarm deodorant (Becaria, 2002:311). Two adult volunteers were dermally exposed to one...NPs can be classified as a sensitizer agent. Since sensitization has been identified in persons exposed to aluminum in deodorant , vaccines, and...IN VITRO TOXICITY OF ALUMINUM NANOPARTICLES IN HUMAN KERATINOCYTES THESIS Stephanie McCormack-Brown, Major, USAF, BSC AFIT/GIH/ENV

  7. Toxic Hazards Research Unit. Annual Technical Report. 1978

    Science.gov (United States)

    1978-08-01

    AFB, OH Histologic examination revealed a low grade adenocarcinoma. Sub- sequent examination resulted in a change in diagnosis to rectal polyps. All...remarkable changes noted in the higher exposure level group. Kidney injury was seen in both exposed groups of male rats con- sisting of nephropathy ...Sanford Clinical Diagnosis by Laboratory Methods, 14th Edition, Saunders Company, p. 149-152. Draize, J. H., (1959), "Dermal Toxicity," in Appraisal of the

  8. Dermal quercetin smartCrystals®: Formulation development, antioxidant activity and cellular safety.

    Science.gov (United States)

    Hatahet, T; Morille, M; Hommoss, A; Dorandeu, C; Müller, R H; Bégu, S

    2016-05-01

    Flavonoids are natural plant pigments, which possess high antioxidative and antiradical activities. However, their poor water solubility led to a limited bioavailability. To overcome this major hurdle, quercetin nanocrystals were produced implementing smartCrystals® technology. This process combines bead milling and subsequent high-pressure homogenization at relatively low pressure (300bar). To test the possibility to develop a dermal formulation from quercetin smartCrystals®, quercetin nanosuspensions were admixed to Lutrol® F127 and hydroxythylcellulose nonionic gels. The physicochemical properties (morphology, size and charge), saturation solubility, dissolution velocity and the antioxidant properties (DPPH assay) as well as the cellular interaction of the produced quercetin smartCrystals® were studied and compared to crude quercetin powder. Quercetin smartCrystals® showed a strong increase in the saturation solubility and the dissolution velocity (7.6 fold). SmartCrystals® loaded or not into gels proved to be physically stable over a period of three months at 25°C. Interestingly, in vitro DPPH assay confirmed the preservation of quercetin antioxidative properties after nanonization. In parallel, the nanocrystalline form did not display cellular toxicity, even at high concentration (50μg/ml), as assayed on an epithelial cell line (VERO cells). In addition, the nanocrystalline form confirmed a protective activity for VERO cells against hydrogen peroxide induced toxicity in vitro. This new formulation presents a promising approach to deliver quercetin efficiently to skin in well-tolerated formulations.

  9. Development of anti-migraine therapeutics using the capsaicin-induced dermal blood flow model.

    Science.gov (United States)

    Buntinx, Linde; Vermeersch, Steve; de Hoon, Jan

    2015-11-01

    The efficacy of calcitonin gene-related peptide (receptor) (CGRP-(R)) blocking therapeutics in the treatment of acute migraine headache provided proof-of-concept for the involvement of CGRP in the pathophysiology of this disorder. One of the major hurdles for the development of any class of drugs, including CGRP blocking therapeutics, is the early clinical development process during which toxic and inefficacious compounds need to be eliminated as early as possible in order to focus on the most promising molecules. At this stage, human models providing proof of target engagement, combined with safety and tolerability studies, are extremely valuable in focusing on those therapeutics that have the highest engagement from the lowest exposure. They guide the go/no-go decision making, establish confidence in the candidate molecule by de-risking toxicity and safety issues and thereby speed up the early clinical development. In this review the focus is on the so called 'capsaicin model' as a typical example of a target engagement biomarker used as a human model for the development of CGRP blocking therapeutics. By applying capsaicin onto the skin, TRPV1 channels are activated and a CGRP-mediated increase in dermal blood flow can be quantified with laser Doppler perfusion imaging. Effective CGRP blocking therapeutics in turn, display blockade of this response. The translation of this biomarker model from animals to humans is discussed as well as the limitations of the assay in predicting the efficacy of anti-migraine drugs.

  10. Efek Pemberian Suntikan Subkutan Vitamin C Terhadap Luka Insisi Dermal

    Directory of Open Access Journals (Sweden)

    Surya Darma

    2013-09-01

    Full Text Available Abstrak Vitamin C berfungsi sebagai kofaktor enzyme prolil dan lysil hydroxilase. Enzym tersebut berfungsi dalam proses hidroksilasi yang membentuk ikatan hidroksiprolin dan hidroksilisin pada fibroblast dalam membentuk kolagen. Selain itu Vitaimin C juga berfungsi meregulasi dan menstabilkan trankripsi gen mRNA prokolagen pada proses pembentukan kolagen di dermis. Berdasarkan hal tersebut diatas, peneliti tertarik untuk membuktikan apakah pemberian vitamin C subkutan disekitar luka insisi dermal berefek pada pembentukan kolagen yang lebih padat dalam proses penyembuhan luka. Metode: Penelitian eksperimental ini menggunakan tikus Wistar sebanyak 32 ekor, yang dibagi menjadi 2 kelompok yaitu 16 ekor sebagai kontrol dan 16 ekor lagi sebagai perlakuan. Pada kedua kelompok dilakukan insisi di punggung sepanjang 2 cm. Kelompok perlakuan diberi suntikan vitamin C subkutan disekitar luka insisi dermal sebanyak 9 mg (0,09ml, sedangkan kelompokkontrol tidak diberikan.Pada hari kelima dilakukan pengambilan jaringan luka pada kedua sampel untuk pemeriksaan kepadatan kolagen secara mikroskopik. Hasil:Kepadatan kolagen pada hari kelimamenunjukkan perbedaan yang bermakna dari efek penyuntikan vitamin C subkutan terhadap kepadatan kolagen (χ2 = 5,833; P<0,05. Kesimpulan: Penyuntikan vitamin C subkutan disekitar luka insisi dermal efektif dalam meeningkatan kepadatan kolagen. Kata kunci: suntikan vitamin C subkutan, kepadatan kolagen. Abstract Vitamin C functions as enzyme co-factor for prolyl and hidroxylase lysil. The enzyme functions in hydroxylase process that builds hydroxyproline and hydroxylysine bondsin fibroblast in the synthesis of collagen. Besides that, vitamin C also functions in regulating and stabilizing procollagen mRNA gen transcription in dermal collagen synthesis. Based on the facts above, researchers are interested to prove whether subcutaneous injection of vitamin C around dermal insisional wound would result in more compact collagen

  11. Efek Pemberian Suntikan Subkutan Vitamin C Terhadap Luka Insisi Dermal

    Directory of Open Access Journals (Sweden)

    Surya Darma

    2014-09-01

    Full Text Available Abstrak Vitamin C berfungsi sebagai kofaktor enzyme prolil dan lysil hydroxilase. Enzym tersebut berfungsi dalam proses hidroksilasi yang membentuk ikatan hidroksiprolin dan hidroksilisin pada fibroblast dalam membentuk kolagen. Selain itu Vitaimin C juga berfungsi meregulasi dan menstabilkan trankripsi gen mRNA prokolagen pada proses pembentukan kolagen di dermis. Berdasarkan hal tersebut diatas, peneliti tertarik untuk membuktikan apakah pemberian vitamin C subkutan disekitar luka insisi dermal berefek pada pembentukan kolagen yang lebih padat dalam proses penyembuhan luka. Metode: Penelitian eksperimental ini menggunakan tikus Wistar sebanyak 32 ekor, yang dibagi menjadi 2 kelompok yaitu 16 ekor sebagai kontrol dan 16 ekor lagi sebagai perlakuan. Pada kedua kelompok dilakukan insisi di punggung sepanjang 2 cm. Kelompok perlakuan diberi suntikan vitamin C subkutan disekitar luka insisi dermal sebanyak 9 mg (0,09ml, sedangkan kelompokkontrol tidak diberikan.Pada hari kelima dilakukan pengambilan jaringan luka pada kedua sampel untuk pemeriksaan kepadatan kolagen secara mikroskopik. Hasil:Kepadatan kolagen pada hari kelimamenunjukkan perbedaan yang bermakna dari efek penyuntikan vitamin C subkutan terhadap kepadatan kolagen (χ2 = 5,833; P<0,05. Kesimpulan: Penyuntikan vitamin C subkutan disekitar luka insisi dermal efektif dalam meeningkatan kepadatan kolagen. Kata kunci: suntikan vitamin C subkutan, kepadatan kolagen.Abstract Vitamin C functions as enzyme co-factor for prolyl and hidroxylase lysil. The enzyme functions in hydroxylase process that builds hydroxyproline and hydroxylysine bondsin fibroblast in the synthesis of collagen. Besides that, vitamin C also functions in regulating and stabilizing procollagen mRNA gen transcription in dermal collagen synthesis. Based on the facts above, researchers are interested to prove whether subcutaneous injection of vitamin C around dermal insisional wound would result in more compact collagen

  12. Enhancing dermal and bone regeneration in calvarial defect surgery

    Directory of Open Access Journals (Sweden)

    Bruno Zanotti

    2014-01-01

    Full Text Available Introduction: To optimize the functional and esthetic result of cranioplasty, it is necessary to choose appropriate materials and take steps to preserve and support tissue vitality. As far as materials are concerned, custom-made porous hydroxyapatite implants are biomimetic, and therefore, provide good biological interaction and biointegration. However, before it is fully integrated, this material has relatively low mechanical resistance. Therefore, to reduce the risk of postoperative implant fracture, it would be desirable to accelerate regeneration of the tissues around and within the graft. Objectives: The objective was to determine whether integrating growth-factor-rich platelet gel or supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate bone remodeling and promote soft tissue regeneration, respectively. Materials and Methods: The investigation was performed on cranioplasty patients fitted with hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet gel was applied to the bone/prosthesis interface during surgery, and in a further 5 patients, characterized by thin, hypotrophic skin coverage of the cranial lacuna, a sheet of dermal matrix was applied between the prosthesis and the overlying soft tissue. In several of the former groups, platelet gel mixed with hydroxyapatite granules was used to fill small gaps between the skull and the implant. To confirm osteointegration, cranial computed tomography (CT scans were taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI was used to confirm dermal integrity. Results: Clinical examination performed a few weeks after surgery revealed good dermal regeneration, with thicker, healthier skin, apparently with a better blood supply, which was confirmed by MRI at 3-6 months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite granules were

  13. Enhancing dermal and bone regeneration in calvarial defect surgery.

    Science.gov (United States)

    Zanotti, Bruno; Zingaretti, Nicola; Almesberger, Daria; Verlicchi, Angela; Stefini, Roberto; Ragonese, Mauro; Guarneri, Gianni Franco; Parodi, Pier Camillo

    2014-01-01

    To optimize the functional and esthetic result of cranioplasty, it is necessary to choose appropriate materials and take steps to preserve and support tissue vitality. As far as materials are concerned, custom-made porous hydroxyapatite implants are biomimetic, and therefore, provide good biological interaction and biointegration. However, before it is fully integrated, this material has relatively low mechanical resistance. Therefore, to reduce the risk of postoperative implant fracture, it would be desirable to accelerate regeneration of the tissues around and within the graft. The objective was to determine whether integrating growth-factor-rich platelet gel or supportive dermal matrix into hydroxyapatite implant cranioplasty can accelerate bone remodeling and promote soft tissue regeneration, respectively. The investigation was performed on cranioplasty patients fitted with hydroxyapatite cranial implants between 2004 and 2010. In 7 patients, platelet gel was applied to the bone/prosthesis interface during surgery, and in a further 5 patients, characterized by thin, hypotrophic skin coverage of the cranial lacuna, a sheet of dermal matrix was applied between the prosthesis and the overlying soft tissue. In several of the former groups, platelet gel mixed with hydroxyapatite granules was used to fill small gaps between the skull and the implant. To confirm osteointegration, cranial computed tomography (CT) scans were taken at 3-6 month intervals for 1-year, and magnetic resonance imaging (MRI) was used to confirm dermal integrity. Clinical examination performed a few weeks after surgery revealed good dermal regeneration, with thicker, healthier skin, apparently with a better blood supply, which was confirmed by MRI at 3-6 months. Furthermore, at 3-6 months, CT showed good biomimetism of the porous hydroxyapatite scaffold. Locations at which platelet gel and hydroxyapatite granules were used to fill gaps between the implant and skull appeared to show more rapid

  14. Inhalational and dermal exposures during spray application of biocides.

    Science.gov (United States)

    Berger-Preiss, Edith; Boehncke, Andrea; Könnecker, Gustav; Mangelsdorf, Inge; Holthenrich, Dagmar; Koch, Wolfgang

    2005-01-01

    Data on inhalational and potential dermal exposures during spray application of liquid biocidal products were generated. On the one hand, model experiments with different spraying devices using fluorescent tracers were carried out to investigate the influence of parameters relevant to the exposure (e.g. spraying equipment, nozzle size, direction of application). On the other hand, measurements were performed at selected workplaces (during disinfection operations in food and feed areas; pest control operations for private, public and veterinary hygiene; wood protection and antifouling applications) after application of biocidal products such as Empire 20, Responsar SC, Omexan-forte, Actellic, Perma-forte; Fendona SC, Pyrethrum mist; CBM 8, Aldekol Des 03, TAD CID, Basileum, Basilit. The measurements taken in the model rooms demonstrated dependence of the inhalation exposure on the type of spraying device used, in the following order: "spraying with low pressure" < "airless spraying" < "fogging" indicating that the particle diameter of the released spray droplets is the most important parameter. In addition inhalation exposure was lowest when the spraying direction was downward. Also for the potential dermal exposure, the spraying direction was of particular importance: overhead spraying caused the highest contamination of body surfaces. The data of inhalational and potential dermal exposures gained through workplace measurements showed considerable variation. During spraying procedures with low-pressure equipments, dose rates of active substances inhaled by the operators ranged from 7 to 230 microg active substance (a.s.)/h. An increase in inhaled dose rates (6-33 mg a.s./h) was observed after use of high application volumes/time unit during wood protection applications indoors. Spraying in the veterinary sector using medium-pressure sprayers led to inhaled dose rates between 2 and 24mga.s./h. The highest inhaled dose rates were measured during fogging (114 mg a

  15. Tungsten toxicity.

    Science.gov (United States)

    Witten, Mark L; Sheppard, Paul R; Witten, Brandon L

    2012-04-05

    There is emerging evidence that tungsten has toxic health effects. We summarize the recent tungsten toxicity research in this short review. Tungsten is widely used in many commercial and military applications because it has the second highest melting temperature of any element. Consequently, it is important to elucidate the potential health effects of tungsten.

  16. 啮齿类动物28天重复剂量经口毒性改良试验简介与进展%Introduction and progress on the enhancement of repeated dose 28-day oral toxicity study in rodents

    Institute of Scientific and Technical Information of China (English)

    王恒娟; 刘兆平

    2012-01-01

    Repeated dose 28-day oral toxicity study in rodents ( OECD Test Guidelines 407) is widely used to evaluate the general toxicity of chemicals. In 1998, the Organization for Economic Co-operation and Development (OECD) enhanced existing TG 407 to develop new Test Guidelines for screening and testing potential endocrine disruptors. This procedure has been verified by an extensive international validation program. To provide reference for developing endocrine disruptor evaluation system in China, the enhanced TG 407, its progress and its advantages and disadvantages were summarized in this paper.%经济合作与发展组织(Organization for Economic Co-operation and Development,OECD)推荐的啮齿类动物28天重复剂量经口毒性试验( OECD TG 407)是一种广泛用于评价化学物一般毒性的毒理学试验方案.OECD在1998年对其进行改良后,建立TG 407改良试验并经世界多国实验室验证,用于检测化学物的内分泌干扰作用.本文简要介绍了OECD TG 407改良试验指南,并对其进展情况以及优缺点进行综述,以期为我国的内分泌干扰物的评价体系提供参考.

  17. Dermal fat graft from simultaneous abdominoplasty as an adjunct to revision aesthetic and reconstructive breast surgery: A poor man's acellular dermal matrix?

    Directory of Open Access Journals (Sweden)

    F. Xie

    2014-01-01

    CONCLUSION: We herein report the use of free dermal fat graft in revision aesthetic and reconstructive surgery in a manner akin to recent acellular dermal matrix use. The comparable enhanced aesthetic outcomes, minimal complication rate and substantial cost savings merit dissemination to a global audience and encourage surgeons to consider this economic alternative.

  18. A toxicological review of the ethylene glycol series: Commonalities and differences in toxicity and modes of action.

    Science.gov (United States)

    Fowles, Jeff; Banton, Marcy; Klapacz, Joanna; Shen, Hua

    2017-08-15

    This review summarizes the hazards, exposure and risk that are associated with ethylene glycols (EGs) in their intended applications. Ethylene glycol (EG; CAS RN 107-21-1) and its related oligomers include mono-, di-, tri-, tetra-, and penta-EG. All of the EGs are quickly and extensively absorbed following ingestion and inhalation, but not by the dermal route. Metabolism involves oxidation to the mono- and dicarboxylic acids. Elimination is primarily through the urine as the parent compound or the monoacid, and, in the case of EG, also as exhaled carbon dioxide. All EGs exert acute toxicity in a similar manner, characterized by CNS depression and metabolic acidosis in humans and rodents; the larger molecules being proportionally less acutely toxic on a strict mg/kg basis. Species differences exist in the metabolism and distribution of toxic metabolites, particularly with the formation of glycolic acids and oxalates (OX) from EG and diethylene glycol (DEG); OX are not formed to a significant degree in higher ethylene glycols. Among rodents, rats are more sensitive than mice, and males more sensitive than females to the acute and repeated-dose toxicity of EG. The metabolic formation of glycolic acid (GA), diglycolic acid (DGA), and OX are associated with nephrotoxicity in humans and rodents following single and repeated exposures. However, physiological and metabolic differences in the rate of formation of GA, DGA and OX and their distribution result in EG and DEG causing embryotoxicity in rats, but not rabbits. This rodent-specific sensitivity indicates that EG and its higher oligomers are not anticipated to be embryotoxic in humans at environmentally relevant doses. None of the compounds present developmental toxicity concerns at doses that do not also cause significant maternal toxicity, nor do any of the EGs cause adverse effects on fertility. The EGs are neither genotoxic nor carcinogenic. A read-across matrix is presented, which considers the common and

  19. Dermal versus total uptake of benzene from mineral spirits solvent during parts washing.

    Science.gov (United States)

    Bogen, Kenneth T; Sheehan, Patrick J

    2014-07-01

    Quantitative approaches to assessing exposure to, and associated risk from, benzene in mineral spirits solvent (MSS), used widely in parts washing and degreasing operations, have focused primarily on the respiratory pathway. The dermal contribution to total benzene uptake from such operations remains uncertain because measuring in vivo experimental dermal uptake of this volatile human carcinogen is difficult. Unprotected dermal uptake involves simultaneous sustained immersion events and transient splash/wipe events, each yielding residues subject to evaporation as well as dermal uptake. A two-process dermal exposure framework to assess dermal uptake to normal and damaged skin was applied to estimate potential daily dermal benzene dose (Dskin ) to workers who used historical or current formulations of recycled MSS in manual parts washers. Measures of evaporation and absorption of MSS dermally applied to human subjects were modeled to estimate in vivo dermal uptake of benzene in MSS. Uncertainty and interindividual variability in Dskin was characterized by Monte Carlo simulation, conditioned on uncertainty and/or variability estimated for each model input. Dermal exposures are estimated to average 33% of total (inhalation + dermal) benzene parts washing dose, with approximately equal predicted portions of dermal dose due to splash/wipe and to continuous contact with MSS. The estimated median (95th percentile) dermal and total daily benzene doses from parts washing are: 0.0069 (0.024) and 0.025 (0.18) mg/day using current, and 0.027 (0.085) and 0.098 (0.69) mg/day using historical, MSS solvents, respectively. © 2014 Society for Risk Analysis.

  20. A metabolically active dermal replacement (Dermagraft) for vestibuloplasty.

    Science.gov (United States)

    Raguse, J D; Gath, H J

    2005-05-01

    This article describes the use of tissue-engineered dermal replacement in the vestibular extension instead of palatal donor tissue or (split-thickness) skin graft. In three patients the living human-derived fibroblast skin substitute (Dermagraft) was implanted on the wound surface after mucogingival junction and supraperiosteal dissection. Following application of Dermagraft, epithelial closure starting from the resection margins of the defect was observed, obviating further surgical treatment. Vestibular depth was increased and no scarring or frena occurred. Tissue-engineered dermal replacement consisting of living human fibroblasts appears to be a useful substitute for autogenous grafts in pre-prosthetic surgery, offering the advantages of unlimited availability, good colour match and no donor site morbidity.

  1. Focal dermal hypoplasia: ultrastructural abnormalities of the connective tissue.

    Science.gov (United States)

    del Carmen Boente, María; Asial, Raúl A; Winik, Beatriz C

    2007-02-01

    We followed over 10 years three girls with focal dermal hypoplasia syndrome. The histopathological changes demonstrated at the optical level an hypoplastic dermis with thin and scarce collagen bundles and a marked diminution of elastic fibers. Mature adipose tissue was found scattered within the papillary and reticular dermis. No alterations in the basal membrane were observed by immunocytochemical or ultrastructural techniques. Ultrastructurally, in the skin-affected areas, loosely arranged collagen bundles composed of few fibrils were seen scattered in the extracellular matrix. Scarce elastic fibers of normal morphology were also observed. Fibroblasts were smaller, oval-shaped, and diminished in number with a poorly developed cytoplasm. In these fibroblasts, the most conspicuous feature was a remarkable and irregular thickening of the nuclear fibrous lamina. Taking into account that a common link between all laminopaties may be a failure of stem cells to regenerate mesenchymal tissue, this failure would induce the dermal hypoplasia observed in our patients presenting Goltz syndrome.

  2. Clinical, pathological, and etiologic aspects of acquired dermal melanocytosis.

    Science.gov (United States)

    Mizoguchi, M; Murakami, F; Ito, M; Asano, M; Baba, T; Kawa, Y; Kubota, Y

    1997-06-01

    To study the pathogenesis of acquired dermal melanocytosis (ADM), we reviewed the clinical, immunohistochemical, and ultrastructural features of 34 cases (female, 33, and male, 1) of ADM. The patients' ages at onset ranged from 8 to 51 years and averaged 26.8 +/- 12.7 years. There was a positive family history. Gray-brown macules were mostly recognized on the face. Not only active dermal melanocytes but also non-pigmented c-KIT- and TRP-2-positive immature melanocytes were detected in the dermis. Taken together those clinical and histological findings, activation of pre-existing immature melanocytes by sunlight, estrogen, and/or progesterone, and some other factors, may be the most likely mode of the development of ADM. Moreover, using cultured murine neural crest cells as a model of c-KIT-positive immature melanocytes, we confirmed that endothelin-1, which is produced and secreted by keratinocytes after UV-irradiation, affects melanocytes and accelerated melanogenesis.

  3. The Pentapeptide Repeat Proteins

    Energy Technology Data Exchange (ETDEWEB)

    Vetting,M.; Hegde, S.; Fajardo, J.; Fiser, A.; Roderick, S.; Takiff, H.; Blanchard, J.

    2006-01-01

    The Pentapeptide Repeat Protein (PRP) family has over 500 members in the prokaryotic and eukaryotic kingdoms. These proteins are composed of, or contain domains composed of, tandemly repeated amino acid sequences with a consensus sequence of [S, T,A, V][D, N][L, F]-[S, T,R][G]. The biochemical function of the vast majority of PRP family members is unknown. The three-dimensional structure of the first member of the PRP family was determined for the fluoroquinolone resistance protein (MfpA) from Mycobacterium tuberculosis. The structure revealed that the pentapeptide repeats encode the folding of a novel right-handed quadrilateral {beta}-helix. MfpA binds to DNA gyrase and inhibits its activity. The rod-shaped, dimeric protein exhibits remarkable size, shape and electrostatic similarity to DNA.

  4. Mycobacterium chelonae Facial Infections Following Injection of Dermal Filler

    OpenAIRE

    Rodriguez, Jan M.; Xie, Yingda L.; Winthrop, Kevin L; Schafer, Sean; Sehdev, Paul; Solomon, Joel; Jensen, Bette; Toney, Nadege C.; Lewis, Paul F.

    2013-01-01

    A cluster of 3 facial Mycobacterium chelonae infections occurred after cosmetic dermal filler injections at a plastic surgery clinic. Pulsed-field gel electrophoresis showed that M chelonae isolated from the clinic tap water were identical to the patient wound isolates. Review of injection procedures identified application of nonsterile ice to the skin prior to injection as a possible source of M chelonae. Surveys of regional laboratories and a national plastic surgery listserv identified no ...

  5. Dermal tolerance of Sterillium, a propanol-based hand rub.

    Science.gov (United States)

    Kampf, G; Muscatiello, M

    2003-12-01

    Alcohol-based hand rubs have been used for hygienic hand disinfection in hospitals for decades. In order to achieve good compliance with hand hygiene practices in the healthcare setting, dermal tolerance of a hand rub product is crucial. Sterillium, which is used in many European countries for hygienic hand disinfection, is based on iso-propanol, n-propanol and mecetronium etilsulphate. The potential for dermal irritation and sensitization of commercially available propanol-based hand rubs containing emollients has not been studied systematically. We therefore studied the dermal tolerance of Sterillium in a repetitive occlusive patch test on 55 subjects. Sterillium was applied to one site on the back under an occlusive patch during an induction phase (total of nine applications over a three-week period) and two weeks later to a virgin site on the back during a challenge phase (one application). Twenty-four hours after removal of the patches (induction phase and challenge phase), and in addition, after 48 and 72 h (challenge phase), the sites were graded for skin reactions using a standardized scoring scale. In the induction phase, two of the 55 subjects had a barely perceptible minimal erythema at one of nine time points. The remaining 53 subjects had no skin reaction at any time. In the challenge phase, all 55 subjects had no skin reaction at all. The absence of significant reactions with respect to severity and frequency demonstrates the favourable dermal tolerance of the hand rub product. The lack of irritation or sensitization potential could enhance compliance with hand hygiene among healthcare workers.

  6. Generation of human induced pluripotent stem cells from dermal fibroblasts

    OpenAIRE

    2008-01-01

    The generation of patient-specific pluripotent stem cells has the potential to accelerate the implementation of stem cells for clinical treatment of degenerative diseases. Technologies including somatic cell nuclear transfer and cell fusion might generate such cells but are hindered by issues that might prevent them from being used clinically. Here, we describe methods to use dermal fibroblasts easily obtained from an individual human to generate human induced pluripotent stem (iPS) cells by ...

  7. Dermal type I collagen assessment by digital image analysis*

    OpenAIRE

    Brianezi, Gabrielli; Grandi, Fabrizio; Bagatin, Ediléia; Enokihara, Mílvia Maria S. S.; Miot, Hélio Amante [UNESP

    2015-01-01

    Type I collagen is the main dermal component, and its evaluation is relevant to quantitative studies in dermatopathology. However, visual gradation (0 to 4+) has low precision and high subjectivity levels. This study aimed to develop and validate a digital morphometric analysis technique to estimate type I collagen levels in the papillary dermis. Four evaluators visually quantified (0 to 4+) the density of type I collagen in 63 images of forearm skin biopsies marked by immunohistochemistry an...

  8. Immune Suppression by Dermal Application of JP-8 Jet Fuel

    Science.gov (United States)

    2008-10-13

    transmitting the immunosuppressive signal from the skin to the immune system ( Limon -Flores, et al., Mast Cells mediate the Immune suppression Induced by...human and murine data. Nat Rev Immunol 7, 93-104. Byrne, S. N., Limon -Flores, A. Y. and Ullrich, S. E. (2008). Mast cell migration from the skin to...Ramos, G., Limon -Flores, A. Y. and Ullrich, S. E. (2007). Dermal exposure to jet fuel suppresses delayed-type hypersensitivity: a critical role

  9. Repeating the Past

    Science.gov (United States)

    Moore, John W.

    1998-05-01

    As part of the celebration of the Journal 's 75th year, we are scanning each Journal issue from 25, 50, and 74 years ago. Many of the ideas and practices described are so similar to present-day "innovations" that George Santayana's adage (1) "Those who cannot remember the past are condemned to repeat it" comes to mind. But perhaps "condemned" is too strong - sometimes it may be valuable to repeat something that was done long ago. One example comes from the earliest days of the Division of Chemical Education and of the Journal.

  10. Dopamine regulates angiogenesis in normal dermal wound tissues.

    Directory of Open Access Journals (Sweden)

    Saurav Shome

    Full Text Available Cutaneous wound healing is a normal physiological process and comprises different phases. Among these phases, angiogenesis or new blood vessel formation in wound tissue plays an important role. Skin is richly supplied by sympathetic nerves and evidences indicate the significant role of the sympathetic nervous system in cutaneous wound healing. Dopamine (DA is an important catecholamine neurotransmitter released by the sympathetic nerve endings and recent studies have demonstrated the potent anti-angiogenic action of DA, which is mediated through its D(2 DA receptors. We therefore postulate that this endogenous catecholamine neurotransmitter may have a role in the neovascularization of dermal wound tissues and subsequently in the process of wound healing. In the present study, the therapeutic efficacy of D(2 DA receptor antagonist has been investigated for faster wound healing in a murine model of full thickness dermal wound. Our results indicate that treatment with specific D(2 DA receptor antagonist significantly expedites the process of full thickness normal dermal wound healing in mice by inducing angiogenesis in wound tissues. The underlined mechanisms have been attributed to the up-regulation of homeobox transcription factor HoxD3 and its target α5β1 integrin, which play a pivotal role in wound angiogenesis. Since D(2 DA receptor antagonists are already in clinical use for other disorders, these results have significant translational value from the bench to the bedside for efficient wound management along with other conventional treatment modalities.

  11. Dermal insecticide residues from birds inhabiting an orchard

    Science.gov (United States)

    Vyas, N.B.; Spann, J.W.; Hulse, C.S.; Gentry, S.; Borges, S.L.

    2007-01-01

    The US Environmental Protection Agency conducts risk assessments of insecticide applications to wild birds using a model that is limited to the dietary route of exposure. However, free-flying birds are also exposed to insecticides via the inhalation and dermal routes. We measured azinphos-methyl residues on the skin plus feathers and the feet of brown-headed cowbirds (Molothrus ater) in order to quantify dermal exposure to songbirds that entered and inhabited an apple (Malus x domestica) orchard following an insecticide application. Exposure to azinphos-methyl was measured by sampling birds from an aviary that was built around an apple tree. Birds sampled at 36 h and 7-day post-application were placed in the aviary within 1 h after the application whereas birds exposed for 3 days were released into the aviary 4-day post-application. Residues on vegetation and soil were also measured. Azinphos-methyl residues were detected from the skin plus feathers and the feet from all exposure periods. Our results underscore the importance of incorporating dermal exposure into avian pesticide risk assessments.

  12. Citral: identifying a threshold for induction of dermal sensitization.

    Science.gov (United States)

    Lalko, Jon; Api, Anne Marie

    2008-10-01

    Citral [CAS# 5392-40-5; EINECS# 226-394-6; RIFM # 116; cis- and trans-3,7-dimethyl-2,6-Octadienal] is an important fragrance ingredient appreciated for its powerful lemon-aroma. It is widely used in fragrance formulations and incorporated into numerous consumer products. A comprehensive review of the dermal sensitization data available for citral was undertaken with the goal of identifying a threshold for the induction of dermal sensitization. In 2007, a complete literature search was conducted. On-line databases that were surveyed included Chemical Abstract Services and the National Library of Medicine. In addition, the toxicologic database of the Research Institute for Fragrance materials, Inc. (RIFM) was searched, which includes numerous unpublished reports. Based on a weight of evidence approach, the data from this survey demonstrate that the human NOEL (No Observed Effect Level) for induction of dermal sensitization to citral is 1400 microg/cm(2). The identification of this induction threshold will allow for risk assessments to focus on primary prevention of contact allergy to citral based on a new Quantitative Risk Assessment (QRA) paradigm. This subsequent assessment will form the basis of a risk management approach; specifically a new IFRA (International Fragrance Association) standard on the use of citral in consumer products.

  13. Human acellular dermal wound matrix: evidence and experience.

    Science.gov (United States)

    Kirsner, Robert S; Bohn, Greg; Driver, Vickie R; Mills, Joseph L; Nanney, Lillian B; Williams, Marie L; Wu, Stephanie C

    2015-12-01

    A chronic wound fails to complete an orderly and timely reparative process and places patients at increased risk for wound complications that negatively impact quality of life and require greater health care expenditure. The role of extracellular matrix (ECM) is critical in normal and chronic wound repair. Not only is ECM the largest component of the dermal skin layer, but also ECM proteins provide structure and cell signalling that are necessary for successful tissue repair. Chronic wounds are characterised by their inflammatory and proteolytic environment, which degrades the ECM. Human acellular dermal matrices, which provide an ECM scaffold, therefore, are being used to treat chronic wounds. The ideal human acellular dermal wound matrix (HADWM) would support regenerative healing, providing a structure that could be repopulated by the body's cells. Experienced wound care investigators and clinicians discussed the function of ECM, the evidence related to a specific HADWM (Graftjacket(®) regenerative tissue matrix, Wright Medical Technology, Inc., licensed by KCI USA, Inc., San Antonio, TX), and their clinical experience with this scaffold. This article distills these discussions into an evidence-based and practical overview for treating chronic lower extremity wounds with this HADWM. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

  14. Amorphous cyclosporin A nanoparticles for enhanced dermal bioavailability.

    Science.gov (United States)

    Romero, Gregori B; Arntjen, Anja; Keck, Cornelia M; Müller, Rainer H

    2016-02-10

    Cylosporin A (CyA) was formulated as amorphous nanoparticle suspension to increase dermal penetration, e.g. applicable in psoriasis. The suspension consisted of 5% CyA in water, stabilized with vitamin E polyethylene glycol succinate (TPGS, Kolliphor TPGS) and was produced by bead milling. The diameter of the bulk population was about 350 nm, laser diffraction diameter 99% was 690 nm. The suspension was physically stable over one year of storage at room temperature, and most important the amorphous state also remained stable. Despite the high dispersitivity and related large surface area in contact with water, the drug content reduced only by 5% over 1 year of storage. i.e. the formulation is feasible as commercial product with expiry date. The CyA nanoparticles and μm-sized CyA particles were incorporated into hydroxypropylcellulose (HPC) gels and the penetration studied into fresh pig ear skin applying the tape stripping method. At tape number 30, the penetrated cumulative amount of CyA from nanoparticles was 6.3 fold higher compared to the μm-sized raw drug powder (450.1 μg/cm(2) vs. 71.3 μg/cm(2)). A theoretical mechanism is presented to explain the observed superiority in penetration. Based on amorphous CyA nanoparticles, dermal formulations for improved dermal CyA delivery seem to be feasible. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Tabebuia avellanedae naphthoquinones: activity against methicillin-resistant staphylococcal strains, cytotoxic activity and in vivo dermal irritability analysis

    Directory of Open Access Journals (Sweden)

    Giambiagi-deMarval Marcia

    2006-03-01

    Full Text Available Abstract Background Methicillin-resistant Staphylococcus aureus (MRSA and coagulase-negative staphylococcus infections are a worldwide concern. Currently, these isolates have also shown resistance to vancomycin, the last therapy used in these cases. It has been observed that quinones and other related compounds exhibit antibacterial activity. This study evaluated the antibacterial activity, toxicity and in vivo dermal irritability of lapachol extracted from Tabebuia avellanedae and derivatives against methicillin-resistant staphylococcal isolates. In addition, its mechanism of action was also analyzed. Methods The compounds β-lapachone, 3-hydroxy β N lapachone and α-lapachone were tested to determine the MIC values against methicillin-resistant S. aureus, S. epidermidis and S. haemolyticus strains, being the two last ones hetero-resistant to vancomycin. Experiments of protein synthesis analysis to investigate the naphthoquinones action were assessed. In vitro toxicity to eukaryotic BSC-40 African Green Monkey Kidney cell cultures and in vivo primary dermal irritability in healthy rabbits were also performed. Results The compounds tested showed antibacterial activity (MICs of 8, 4/8 and 64/128 μg/mL to β-lapachone, 3-hydroxy β N lapachone and α-lapachone, respectively, but no bactericidal activity was observed (MBC > 512 μg/mL for all compounds. Although it has been observed toxic effect in eukaryotic cells, the compounds were shown to be atoxic when applied as topic preparations in healthy rabbits. No inhibition of proteins synthesis was observed. Conclusion Our results suggest that quinones could be used in topic preparations against wound infections caused by staphylococci, after major investigation of the pharmacological properties of the compounds. Studies about the use of these compounds on tumoral cells could be carried on, due to their effect in eukaryotic cells metabolism.

  16. Embryonic dermal condensation and adult dermal papilla induce hair follicles in adult glabrous epidermis through different mechanisms

    OpenAIRE

    2006-01-01

    Hair induction in the adult glabrous epidermis by the embryonic dermis was compared with that by the adult dermis. Recombinant skin, composed of the adult sole epidermis and the embryonic dermis containing dermal condensations (DC), was transplanted onto the back of nude mice. The epidermis of transplants formed hairs. Histology on the induction process demonstrated the formation of placode-like tissues, indicating that the transplant produces hair follicles through a mechanism similar to tha...

  17. All-optical repeater.

    Science.gov (United States)

    Silberberg, Y

    1986-06-01

    An all-optical device containing saturable gain, saturable loss, and unsaturable loss is shown to transform weak, distorted optical pulses into uniform standard-shape pulses. The proposed device performs thresholding, amplification, and pulse shaping as required from an optical repeater. It is shown that such a device could be realized by existing semiconductor technology.

  18. Bidirectional Manchester repeater

    Science.gov (United States)

    Ferguson, J.

    1980-01-01

    Bidirectional Manchester repeater is inserted at periodic intervals along single bidirectional twisted pair transmission line to detect, amplify, and transmit bidirectional Manchester 11 code signals. Requiring only 18 TTL 7400 series IC's, some line receivers and drivers, and handful of passive components, circuit is simple and relatively inexpensive to build.

  19. Significant chemical burns associated with dermal exposure to laundry pod detergent.

    Science.gov (United States)

    Russell, Jason L; Wiles, Devin A; Kenney, Brian; Spiller, Henry A

    2014-09-01

    Concentrated laundry pods have been reported to cause significant clinical effects including oropharyngeal burns and respiratory distress requiring intubation. Dermal burns have been reported, but no incidents of serious isolated dermal injury have been published. We report a case of significant, isolated dermal injury as a result of dermal exposure to a concentrated laundry detergent pod. Total body surface area partial thickness burns in this case were estimated at approximately 2 % with an additional 4-5 % of total body surface area (TBSA) displaying superficial burns/chemical dermatitis. Health-care providers should be aware of this complication and should perform thorough dermal decontamination in the event of an exposure. Parents should be educated regarding the dangers associated with dermal exposure to laundry pod compounds and the need to secure these items away from children as well as proper decontamination techniques should an exposure occur.

  20. Long-Term Followup of Dermal Substitution with Acellular Dermal Implant in Burns and Postburn Scar Corrections

    Directory of Open Access Journals (Sweden)

    I. Juhasz

    2010-01-01

    Full Text Available Full-thickness burn and other types of deep skin loss will result in scar formation. For at least partial replacement of the lost dermal layer, there are several options to use biotechnologically derived extracellular matrix components or tissue scaffolds of cadaver skin origin. In a survey, we have collected data on 18 pts who have previously received acellular dermal implant Alloderm. The age of these patients at the injury varied between 16 months and 84 years. The average area of the implants was 185 cm2. Among those, 15 implant sites of 14 patients were assessed at an average of 50 months after surgery. The scar function was assessed by using the modified Vancouver Scar Scale. We have found that the overall scar quality and function was significantly better over the implanted areas than over the surrounding skin. Also these areas received a better score for scar height and pliability. Our findings suggest that acellular dermal implants are especially useful tools in the treatment of full-thickness burns as well as postburn scar contractures.

  1. Epidermal Vascular Endothelial Growth Factor Production Is Required for Permeability Barrier Homeostasis, Dermal Angiogenesis, and the Development of Epidermal Hyperplasia

    Science.gov (United States)

    Elias, Peter M.; Arbiser, Jack; Brown, Barbara E.; Rossiter, Heidemarie; Man, Mao-Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R.

    2008-01-01

    Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf−/− mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis. PMID:18688025

  2. A TRILAYER DERMAL EQUIVALENT CONTAINING SILVER NANOPARTICLES WITH ENHANCED ANTIBACTERIAL PROPERTY

    Institute of Scientific and Technical Information of China (English)

    马列; 高长有

    2009-01-01

    A dermal equivalent having a trilayered structure was designed by combining a silver nanoparticles incorporated chitosan film with a bilayer collagen-chitosan/silicon membrane dermal equivalent(BDE).The silver nanoparticles prepared at different conditions were characterized by UV-Vis and transmission electron microscopy(TEM).The macroscopic sharp and the microstructure of the trilayer dermal equivalent(TDE) were also studied.Then,the in vitro antibacterial property of TDE was evaluated by the antibacter...

  3. The characterization, replication and testing of dermal denticles of Scyliorhinus canicula for physical mechanisms of biofouling prevention

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, Timothy; Regan, Fiona, E-mail: fiona.regan@dcu.ie [Marine and Environmental Sensing Technology Hub (MESTECH), National Centre for Sensor Research, School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9 (Ireland)

    2011-12-15

    There is a current need to develop novel non-toxic antifouling materials. The mechanisms utilized by marine organisms to prevent fouling of external surfaces are of interest in this regard. Biomimicry of these mechanisms and the ability to transfer the antifouling characteristics of these surfaces to artificial surfaces are a highly attractive prospect to those developing antifouling technologies. In order to achieve this, the mechanisms responsible for any antifouling ability must be elucidated from the study of the natural organism and the critical surface parameters responsible for fouling reduction. Dermal denticles of members of the shark family have been speculated to possess some natural, as yet unidentified antifouling mechanism related to the physical presence of denticles. In this study, the dermal denticles of one particular member of the slow-swimming sharks, Scyliorhinus canicula were characterized and it was found that a significant natural variation in denticle dimensions exists in this species. The degree of denticle surface contamination was quantified on denticles at various locations and it was determined that the degree of contamination of the dorsal surface of denticles varies with the position on the shark body. In addition, we successfully produced synthetic sharkskin samples using the real skin as a template. Testing of the produced synthetic skin in field conditions resulted in significant differences in material attachment on surfaces exhibiting denticles of different dimensions.

  4. Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis.

    Science.gov (United States)

    Driskell, Ryan R; Giangreco, Adam; Jensen, Kim B; Mulder, Klaas W; Watt, Fiona M

    2009-08-01

    The dermal papilla comprises the specialised mesenchymal cells at the base of the hair follicle. Communication between dermal papilla cells and the overlying epithelium is essential for differentiation of the hair follicle lineages. We report that Sox2 is expressed in all dermal papillae at E16.5, but from E18.5 onwards expression is confined to a subset of dermal papillae. In postnatal skin, Sox2 is only expressed in the dermal papillae of guard/awl/auchene follicles, whereas CD133 is expressed both in guard/awl/auchene and in zigzag dermal papillae. Using transgenic mice that express GFP under the control of the Sox2 promoter, we isolated Sox2(+) (GFP(+)) CD133(+) cells and compared them with Sox2(-) (GFP(-)) CD133(+) dermal papilla cells. In addition to the 'core' dermal papilla gene signature, each subpopulation expressed distinct sets of genes. GFP(+) CD133(+) cells had upregulated Wnt, FGF and BMP pathways and expressed neural crest markers. In GFP(-) CD133(+) cells, the hedgehog, IGF, Notch and integrin pathways were prominent. In skin reconstitution assays, hair follicles failed to form when dermis was depleted of both GFP(+) CD133(+) and GFP(-) CD133(+) cells. In the absence of GFP(+) CD133(+) cells, awl/auchene hairs failed to form and only zigzag hairs were found. We have thus demonstrated a previously unrecognised heterogeneity in dermal papilla cells and shown that Sox2-positive cells specify particular hair follicle types.

  5. Duct Leakage Repeatability Testing

    Energy Technology Data Exchange (ETDEWEB)

    Walker, Iain [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sherman, Max [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2014-01-01

    Duct leakage often needs to be measured to demonstrate compliance with requirements or to determine energy or Indoor Air Quality (IAQ) impacts. Testing is often done using standards such as ASTM E1554 (ASTM 2013) or California Title 24 (California Energy Commission 2013 & 2013b), but there are several choices of methods available within the accepted standards. Determining which method to use or not use requires an evaluation of those methods in the context of the particular needs. Three factors that are important considerations are the cost of the measurement, the accuracy of the measurement and the repeatability of the measurement. The purpose of this report is to evaluate the repeatability of the three most significant measurement techniques using data from the literature and recently obtained field data. We will also briefly discuss the first two factors. The main question to be answered by this study is to determine if differences in the repeatability of these tests methods is sufficient to indicate that any of these methods is so poor that it should be excluded from consideration as an allowed procedure in codes and standards.

  6. Safety of Repeated Yttrium-90 Radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G. E. H.; Louie, John D. [Stanford University School of Medicine, Division of Interventional Radiology (United States); Iagaru, Andrei H.; Goris, Michael L. [Stanford University School of Medicine, Division of Nuclear Medicine (United States); Sze, Daniel Y., E-mail: dansze@stanford.edu [Stanford University School of Medicine, Division of Interventional Radiology (United States)

    2013-10-15

    Purpose: Repeated radioembolization (RE) treatments carry theoretically higher risk of radiation-induced hepatic injury because of the liver's cumulative memory of previous exposure. We performed a retrospective safety analysis on patients who underwent repeated RE. Methods: From 2004 to 2011, a total of 247 patients were treated by RE. Eight patients (5 men, 3 women, age range 51-71 years) underwent repeated treatment of a targeted territory, all with resin microspheres (SIR-Spheres; Sirtex, Lane Cove, Australia). Adverse events were graded during a standardized follow-up. In addition, the correlation between the occurrence of RE-induced liver disease (REILD) and multiple variables was investigated in univariate and multivariate analyses in all 247 patients who received RE. Results: Two patients died shortly after the second treatment (at 84 and 107 days) with signs and symptoms of REILD. Both patients underwent whole liver treatment twice (cumulative doses 3.08 and 2.66 GBq). The other 6 patients demonstrated only minor toxicities after receiving cumulative doses ranging from 2.41 to 3.88 GBq. All patients experienced objective tumor responses. In the whole population, multifactorial analysis identified three risk factors associated with REILD: repeated RE (p = 0.036), baseline serum total bilirubin (p = 0.048), and baseline serum aspartate aminotransferase (p = 0.043). Repeated RE proved to be the only independent risk factor for REILD in multivariate analysis (odds ratio 9.6; p = 0.002). Additionally, the administered activity per target volume (in GBq/L) was found to be an independent risk factor for REILD, but only in whole liver treatments (p = 0.033). Conclusion: The risk of REILD appears to be elevated for repeated RE. Objective tumor responses were observed, but establishment of safety limits will require improvement in dosimetric measurement and prediction.

  7. Acute Dermal Irritation Study of Six Jet Fuels in New Zealand White Rabbits: Comparison of Four Bio-Based Jet Fuels with Two Petroleum JP-8 Fuels

    Science.gov (United States)

    2014-02-01

    alternative fuel, ReadiJet, refers to a Renewable, Aromatic, Drop-in (abbreviated Readi) fuel produced from plant oils or animal fats through a catalytic...camelina plant, tallow, animal fats and oils , algae) were tested in this assay by Mattie et al. (2013) and Sterner et al. (2014). HEFA-SPKs were...Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Dermal Toxicity , pp. 46-59. Assoc. of Food and Drug Officials of the U.S., Topeka

  8. The pharmacokinetics and metabolism of 14C/13C-labeled ortho-phenylphenol formation following dermal application to human volunteers.

    Science.gov (United States)

    Timchalk, C; Selim, S; Sangha, G; Bartels, M J

    1998-08-01

    1. The pharmacokinetics and metabolism of uniformly labeled 14C/13C-ortho-phenylphenol (OPP) were followed in six human male volunteers given a single 8 h dermal dose of 6 microg OPP/kg body weight formulated as a 0.4% (w/v) solution in isopropyl alcohol. The application site was covered with a non-occlusive dome allowing free movement of air, but preventing the loss of radioactivity due to physical contact. At 8 h post-exposure the non-occlusive dome was removed, the dose site was wiped with isopropyl alcohol containing swabs and the skin surface repeatedly stripped with tape. Blood specimens, urine, and feces were collected from each volunteer over a 5 day post-exposure period and were analyzed for radioactivity and metabolites (urine only). 2. Following dermal application, peak plasma levels of radioactivity were obtained within 4 h post-exposure and rapidly declined with virtually all of the absorbed dose rapidly excreted into the urine within 24 h post-exposure. A one-compartment pharmacokinetic model was used to describe the time-course of OPP absorption and clearance in male human volunteers. Approximately 43% of the dermally applied dose was absorbed through the skin with an average absorption half-life of 10 h. Once absorbed the renal clearance of OPP was rapid with an average half-life of 0.8 h. The rate limiting step for renal clearance was the relatively slower rate of dermal absorption; therefore the pharmacokinetics of OPP in humans was described by a 'flip-flop' single compartment model. Overall, the pharmacokinetics were similar between individuals, and the model parameters were in excellent agreement with the experimental data. 3. Approximately 73% of the total urinary radioactivity was accounted for as free OPP, OPP-sulfate and OPP-glucuronide conjugates. The sulfate conjugate was the major metabolite (approximately 69%). Therefore, total urinary OPP equivalents (acid-labile conjugates+free OPP) can be used to estimate the systemically absorbed

  9. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    . The first section of this chapter outlines the complete cause-effect pathway, from emissions of toxic substances to intake by the population up to damages in terms of human health effects. Section 2 outlines the framework for assessing human toxicity in LCIA. Section 3 discusses the contributing substances......This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... – demonstrates the importance to account for both outdoor and indoor exposure, including consumer products. Analysing the variations in intake fraction (the fraction of the emitted or applied chemical that is taken in by the consumer and the general population), effect factor and characterisation factor across...

  10. Dermal echogenicity: a biological indicator of individual cumulative UVR exposure?

    Science.gov (United States)

    Sandby-Møller, Jane; Thieden, Elisabeth; Philipsen, Peter Alshede; Schmidt, Grethe; Wulf, Hans Christian

    2004-04-01

    Dermal alterations due to chronic UVR exposure may influence dermal ultrasound echogenicity, and a subepidermal low-echogenic band has been proposed as a marker of photoaging. The aim of this study was to determine whether dermal echogenicity could be used as a biological UVR dosimeter. We included 201 subjects (138 healthy volunteers, 31 patients with basal cell carcinoma, and 32 patients with cutaneous malignant melanoma). The number of low-echogenic pixels in the upper dermis relative to the lower dermis (LEP(u/l)) was determined in sun-exposed and sun-protected skin. Individual UVR exposure data were collected retrospectively and prospectively using a questionnaire and electronic personal UVR dosimeters. Age, but not sex, skin type, constitutive pigmentation or smoking, correlated significantly with LEP(u/l) at all body sites. Different measures of individual UVR exposure were significantly positively correlated with LEP(u/l) (together r(2)=0.39, dorsal forearm), but separately the correlations were poor ( r(2)=0.04-0.19). LEP(u/l) was higher in the dorsal forearm in a group with high UVR exposure compared to a low-exposure group ( P=0.007). Skin cancer patients in general had a lower LEP(u/l) than healthy subjects. The results indicate that the age-related increase in LEP(u/l) might be attributed mainly to UVR exposure, and that the methods used to obtain the UVR exposure data might not be sufficiently sensitive or specific. Genetic factors might also influence LEP(u/l). We consider LEP(u/l) to be a sensitive and specific marker for UVR exposure at the dorsal aspect of the forearm in healthy subjects.

  11. Abdominal wall repair with human acellular dermal autograft

    Directory of Open Access Journals (Sweden)

    Roel E. Genders

    2011-12-01

    Full Text Available Repair of abdominal wall defects in the presence of contamination or infection is a significant problem. The loss of tissue warrants enforcement of the abdominal wall, preferably by autologous material. However, autologous repair often requires extensive surgery. This paper presents a review of available literature of placement of an acellular human dermis to repair an abdominal fascia defect, in contaminated as well as in non-contaminated surgical fields. It is illustrated with a case report that describes the successful reconstruction of an infected abdominal wall defect with a human acellular dermis allograft. A systematic literature review was undertaken with searches performed in the Pubmed and Cochrane databases for the period up till March 2009, using the search terms Alloderm [Substance Name], Hernia [Mesh] and the key words acellular dermis, acellular dermal matrix, human acellular dermal allograft and abdominal wall defect. To assess methodological quality, each article was subjected to a modification of the methodological index for non-randomized studies (MINORS according to Slim et al. Two items from the original index were not included because none of the studies selected had an unbiased assessment of the study end points and in none of the studies was a prospective calculation of the study size performed. Seventeen studies were included in the review. Data were extracted regarding study design, number of patients, surgical technique, followup period, contaminated or non-contaminated area of the fascia defect, mortality and morbidity (hemorrhage, seroma, wound dehiscence, infection of the operative procedure, the longterm results (removal of the graft, reherniation and bulging and level of evidencey. A total of 169 short-term complications and 151 longterm complications occurred after 643 surgical procedures reconstructing both contaminated and clean abdominal wall defects by implantation of an HADA. Human acellular dermal allograft

  12. Patterns of 1-hydroxypyrene excretion in volunteers exposed to pyrene by the dermal route

    Energy Technology Data Exchange (ETDEWEB)

    Viau, C.; Vyskocil, A. [University of Montreal, Montreal, PQ (Canada)

    1995-02-24

    The urinary excretion profiles following exposure to pyrene were established in one psoriasic patient under treatment with a coal tar-based shampoo and in two other volunteers exposed to a single dose of 100{mu}1 creosote and, in a separate experiment, to five consecutive daily dermal applications of 500{mu}g pyrene on 200 cm{sup 2} of the inner face of the forearms. Timed micturitions were collected for up to 48 h following exposure. Both in the psoriasic patient and in the volunteers exposed to creosote, the excretion peaks between 10 and 15 h after application and first-order apparent half lives of 11.5-15 h can be calculated for the elimination phase. Compatible with these observations, repeated exposure to pyrene in the volunteers causes an increase in peak and trough urinary 1-hydroxypyrene (1-OHP) values for the first few days following the first exposure. These results suggest that the difference between beginning-of-shift/beginning of work week and beginning-of-shift/end of work week 1-OHP excretion should reflect the average exposure of the week in workers having a constant exposure to pyrene. The difference between the beginning and end-of-shift excretion values of a given day should reflect the exposure of that day but the maximum excretion would be attained a few hours after termination of exposure.

  13. Cataractogenesis after Repeat Laser in situ Keratomileusis

    Directory of Open Access Journals (Sweden)

    Ahmad M. Mansour

    2012-08-01

    Full Text Available There has been the unsubstantiated clinical impression that laser refractive surgery accelerates cataract development along with solid experimental data about the cataractogenic effects of excimer laser treatment. We present the first documented case of significant cataract formation in a young myope after repeat excimer laser ablation necessitating phacoemulsification with a posterior chamber implant. Proposed explanations include focusing of the ablation wave on the posterior capsule (acoustic wave lens epithelial damage, photooxidative stress of the lens (ultraviolet and inflammatory oxidative stress, and corticosteroid-induced cataract (lens toxicity.

  14. Experimental Studies of Toxicity on HNIW and Its Intermediates

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ying; CHEN Shu-sen; JIN Shao-hua; CUI Zhao-kuan

    2006-01-01

    The polycyclic nitramine hexanitrohexaazaisowurtane(HNIW) is a compound of high energy density. HNIW can replace 1, 3, 5-trinitro-1, 3, 5-triazacyclohexane(RDX)or HMX, but its toxicity is unknown. In this paper,HNIW, hexabenzylhexaazaisowurtzitane ( HBIW ), tetraacetyldibenzulhexaazaisowurtzitane ( TADBIW ), tetraacetyldiformylhexaazaisowurtzitane(TADFIW) and tetraacetylhexaazaisowurtzitane(TAIW), which are intermediates of the synthesis of the HNIW, were selected as the tested objects in acute toxicity test, acute eye stimulation test and skin irritation test according to the standards of "chemical product testing method-401: acute oral toxicity test", "chemical product testing means-405: acute eye irritation/corrosion test" and "chemical product testing means-404: acute dermal irritation/corrosion test" of National Circumstance Protect Bureau. The results show that all of the five objects have no toxicity, no stimulation to eye and skin under the tested conditions.

  15. Toxic myopathies.

    Science.gov (United States)

    Pasnoor, Mamatha; Barohn, Richard J; Dimachkie, Mazen M

    2014-08-01

    Muscle tissue is highly sensitive to many substances. Early recognition of toxic myopathies is important, because they potentially are reversible on removal of the offending drug or toxin, with greater likelihood of complete resolution the sooner this is achieved. Clinical features range from mild muscle pain and cramps to severe weakness with rhabdomyolysis, renal failure, and even death. The pathogenic bases can be multifactorial. This article reviews some of the common toxic myopathies and their clinical presentation, histopathologic features, and possible underlying cellular mechanisms.

  16. Soft tissue augmentation - Use of hyaluronic acid as dermal filler

    Directory of Open Access Journals (Sweden)

    Vedamurthy Maya

    2004-01-01

    Full Text Available Soft tissue augmentation has revolutionized the treatment of the aging face. It is a technique in which a substance is injected under the skin. The concept of utilizing materials for soft tissue augmentation actually began around 1950 with the use of fluid silicone. Today we have a large armamentarium of implant materials to delay the tell tale signs of aging. Filling has replaced conventional surgery in facial rejuvenation. In this article, the emphasis will be on hyaluronic acid as this substance is easily available in India and ranks among the most widely used dermal fillers.

  17. Dermal exposure from transfer of lubricants and fuels by consumers.

    Science.gov (United States)

    Galea, Karen S; Davis, Alice; Todd, Davis; MacCalman, Laura; McGonagle, Carolyn; Cherrie, John W

    2014-11-01

    Consumer uses of fuels and lubricants in Europe are subject to the Registration, Evaluation, Authorization and restriction of CHemicals (REACH) legislation. Ten volunteers completed a series of exposure situations to simulate filling a vehicle fuel tank with diesel (ES1 Diesel), adding lubricant to a car engine (two situations, one filling point easier to reach (ES2 Easy) than the other (ES3 Hard)) and lubricating a bicycle chain (ES4 Bike). Dermal exposure to the hands and forearms was assessed using a wipe sampling method. A high proportion of samples was less than the limit of detection (ES1=38%, ES3=60%, ES2 and 4, both 78%). In ES1 Diesel, dermal exposure to the hands and forearms ranged from <0.25 μg/cm(2) to 96.21 μg/cm(2). Significantly higher dermal exposure was observed when a lower level of care was taken to complete the task. In ES2 Easy and ES3 Hard, the hand and forearm results ranged from <0.1 μg/cm(2) to 3.33 μg/cm(2) and from <0.1 μg/cm(2) to 3.54 μg/cm(2), respectively. In ES4 Bike, the hand and forearm exposures ranged from <0.35 μg/cm(2) to 5.25 μg/cm(2). Not all volunteers fully complied with the ES4 instructions, thus highlighting that this situation may have more variability in consumer behaviour. The ratio of the amount measured on the hands and forearms to the amount of product handled for ES1 Diesel, ES2 Easy and ES3 Hard was less than 0.0001%, for ES4 Bike it was 0.04%. Mixed effect models showed that the between and within volunteer variations are small for all except ES1 Diesel, where the within volunteer variation was relatively large (likely due to the few high measurements). This study reports dermal exposure measurement data, which will be of value when updating REACH and other exposure assessments for these, and similar, petroleum products.

  18. Dermal tunneling: a proposed treatment for depressed scars*

    Science.gov (United States)

    Lima, Emerson Vasconcelos de Andrade

    2016-01-01

    Depressed facial scars are still a challenge in medical literature, despite the wide range of proposed treatments. Subcision is a technique that is frequently performed to improve this type of lesions. This article proposes a new method to release depressed scars, reported and named by the author as dermal tunneling. This study presents a simple and didactic manner to perform this method. The results in 17 patients with facial scars were considered promising. Thus, the technique was deemed to be safe and reproducible. PMID:27828658

  19. Photocytotoxicity in human dermal fibroblasts elicited by permanent makeup inks containing titanium dioxide.

    Science.gov (United States)

    Wamer, Wayne G; Yin, Jun-Jie

    2011-01-01

    Titanium dioxide (TiO2) is a pigment widely used in decorative tattoo and permanent makeup inks. However, little is known about the risks associated with its presence in these products. We have developed an in vitro assay to identify inks containing TiO2 that are cytotoxic and/or photocytotoxic. The presence of TiO2 in ten permanent makeup inks was established by X-ray fluorescence. Using X-ray diffraction, we found that seven inks contained predominately TiO2 (anatase), the more photocatalytically active crystalline form of TiO2. The remaining inks contained predominately TiO2 (rutile). To identify cytotoxic and/or photocytotoxic inks, human dermal fibroblasts were incubated for 18 h in media containing inks or pigments isolated from inks. Fibroblasts were then irradiated with 10 J/cm2 UVA radiation combined with 45 J/cm2 visible light for determining photocytotoxicity, or kept in the dark for determining cytotoxicity. Toxicity was assessed as inhibition of colony formation. No inks were cytotoxic. However eight inks, and the pigments isolated from these inks, were photocytotoxic. Using ESR, we found that most pigments from photocytotoxic inks generated hydroxyl radicals when photoexcited with UV radiation. Therefore, the possibility of photocytotoxicity should be considered when evaluating the safety of permanent makeup inks containing TiO2.

  20. Acute oral and percutaneous toxicity of pesticides to mallards: Correlations with mammalian toxicity data

    Science.gov (United States)

    Hudson, R.H.; Haegele, M.A.; Tucker, R.K.

    1979-01-01

    Acute oral (po) and 24-hr percutaneous (perc) LD50 values for 21 common pesticides (19 anticholinesterases, of which 18 were organophosphates, and one was a carbamate; one was an organochlorine central nervous system stimulant; and one was an organonitrogen pneumotoxicant) were determined in mallards (Anas platyrhynchos). Three of the pesticides tested were more toxic percutaneously than orally. An index to the percutaneous hazard of a pesticide, the dermal toxicity index (DTI = po LD50/perc LD50 ? 100), was also calculated for each pesticide. These toxicity values in mallards were compared with toxicity data for rats from the literature. Significant positive correlations were found between log po and log percutaneous LD50 values in mallards (r = 0.65, p 0.10). Variations in percutaneous methodologies are discussed with reference to interspecies variation in toxicity values. It is recommended that a mammalian DTI value approaching 30 be used as a guideline for the initiation of percutaneous toxicity studies in birds, when the po LD50 and/or projected percutaneous LD50 are less than expected field exposure levels.

  1. Toxic synovitis

    Science.gov (United States)

    ... Names Synovitis - toxic; Transient synovitis References Horowitz R. Pediatric orthopedic emergencies. In: Adams JG, ed. Emergency Medicine: Clinical ... JW III, Schor NF, eds. Nelson Textbook of Pediatrics . 20th ed. Philadelphia, PA: Elsevier; 2016:chap ... Shoulder Service, UCSF Department of Orthopaedic Surgery, San Francisco, CA. Also reviewed by David ...

  2. Genotoxic exposure and biological effects in the rubber manufacturing industry. Relevance of the dermal route

    NARCIS (Netherlands)

    Vermeulen, R.

    2001-01-01

    This thesis describes an industry wide survey on genotoxic exposure and biological effects in the rubber manifacturing industry. Chapters are devoted to long-term trends in inhalable and dermal contamination levels, identification of dermal exposure pathways and the assessment of mutagenic

  3. Shh maintains dermal papilla identity and hair morphogenesis via a Noggin-Shh regulatory loop.

    Science.gov (United States)

    Woo, Wei-Meng; Zhen, Hanson H; Oro, Anthony E

    2012-06-01

    During hair follicle morphogenesis, dermal papillae (DPs) function as mesenchymal signaling centers that cross-talk with overlying epithelium to regulate morphogenesis. While the DP regulates hair follicle formation, relatively little is known about the molecular basis of DP formation. The morphogen Sonic hedgehog (Shh) is known for regulating hair follicle epithelial growth, with excessive signaling resulting in basal cell carcinomas. Here, we investigate how dermal-specific Shh signaling contributes to DP formation and hair growth. Using a Cre-lox genetic model and RNAi in hair follicle reconstitution assays, we demonstrate that dermal Smoothened (Smo) loss of function results in the loss of the DP precursor, the dermal condensate, and a stage 2 hair follicle arrest phenotype reminiscent of Shh(-/-) skin. Surprisingly, dermal Smo does not regulate cell survival or epithelial proliferation. Rather, molecular screening and immunostaining studies reveal that dermal Shh signaling controls the expression of a subset of DP-specific signature genes. Using a hairpin/cDNA lentiviral system, we show that overexpression of the Shh-dependent gene Noggin, but not Sox2 or Sox18, can partially rescue the dermal Smo knockdown hair follicle phenotype by increasing the expression of epithelial Shh. Our findings suggest that dermal Shh signaling regulates specific DP signatures to maintain DP maturation while maintaining a reciprocal Shh-Noggin signaling loop to drive hair follicle morphogenesis.

  4. High matrix metalloproteinase levels are associated with dermal graft failure in diabetic foot ulcers.

    Science.gov (United States)

    Izzo, Valentina; Meloni, Marco; Vainieri, Erika; Giurato, Laura; Ruotolo, Valeria; Uccioli, Luigi

    2014-09-01

    The aim of our study is to analyze factors, including matrix metalloproteinase (MMP) levels, that could influence the integration of dermal grafts in diabetic foot ulcers. From September 2012 to September 2013, 35 diabetic patients with IIA lesion (Texas Wound Classification) and an extensive foot tissue loss were considered suitable for dermal graft. Before the enrollment we ensured the best local conditions: adequate blood supply, control of infection, and offloading. The MMP level of each lesion was evaluated blindly before the application of dermal substitutes. At 1-month follow-up, we analyzed the correlation between clinical patient characteristics, local wound features including MMP levels, dermal substitute applied, and the outcome expressed in terms of dermal graft integration. We observed dermal graft integration in 28/35 patients (80% of our population). In multivariate analysis high MMP level was the only negative predictor for dermal graft integration (P < .0007). In addition, we divided the patients into 2 groups according to MMP levels: group 1 with low protease activity (24 patients) and group 2 with elevated protease activity (11 patients). The integration of the dermal graft was 100% in group 1 (n = 24 patients) and 36.4% in group 2 (n = 4patients), P < .0001. According to our data, the evaluation of MMP levels may be useful to choose the right strategy to get the best results in terms of clinical success and cost saving. However, further studies are necessary to confirm these findings.

  5. A new model for preclinical testing of dermal substitutes for human skin reconstruction.

    Science.gov (United States)

    Hartmann-Fritsch, Fabienne; Biedermann, Thomas; Braziulis, Erik; Meuli, Martin; Reichmann, Ernst

    2013-05-01

    Currently, acellular dermal substitutes used for skin reconstruction are usually covered with split-thickness skin grafts. The goal of this study was to develop an animal model in which such dermal substitutes can be tested under standardized conditions using a bioengineered dermo-epidermal skin graft for coverage. Bioengineered grafts consisting of collagen type I hydrogels with incorporated human fibroblasts and human keratinocytes seeded on these gels were produced. Two different dermal substitutes, namely Matriderm(®), and an acellular collagen type I hydrogel, were applied onto full-thickness skin wounds created on the back of immuno-incompetent rats. As control, no dermal substitute was used. As coverage for the dermal substitutes either the bioengineered grafts were used, or, as controls, human split-thickness skin or neonatal rat epidermis were used. Grafts were excised 21 days post-transplantation. Histology and immunofluorescence was performed to investigate survival, epidermis formation, and vascularization of the grafts. The bioengineered grafts survived on all tested dermal substitutes. Epidermis formation and vascularization were comparable to the controls. We could successfully use human bioengineered grafts to test different dermal substitutes. This novel model can be used to investigate newly designed dermal substitutes in detail and in a standardized way.

  6. Dermal exposure assessment to benzene and toluene using charcoal cloth pads

    NARCIS (Netherlands)

    Wendel de Joode, B. van; Tielemans, E.; Vermeulen, R.; Wegh, H.; Kromhout, H.

    2005-01-01

    Charcoal cloth pads have been used to assess volatile chemicals on the skin in a laboratory setting; however, they have not yet been applied to measure dermal exposure in occupational settings. This study aimed at evaluating whether charcoal pads can be used to assess dermal exposure to benzene and

  7. Patterns of Dermal Exposure to Hazardous Substances in European Union Workplaces

    NARCIS (Netherlands)

    Rajan-Sithamparanadarajah, R.; Roff, M.; Delgado, P.; Eriksson, K.; Fransman, W.; Gijsbers, J.H.J.; Hughson, G.; Mäkinen, M.; Hemmen, J.J. van

    2004-01-01

    Workplace dermal exposure assessment is a complex task that aims to understand the dynamic interaction between the skin and the hazardous substances present in the surrounding environment. A European project known as RISKOFDERM gathered dermal exposure data in 85 workplaces (industrial and other typ

  8. Harmonization of future needs for dermal exposure assessment and modeling : a workshop report

    NARCIS (Netherlands)

    Marquart, H.; Maidment, S.; Mcclaflin, J.L.; Fehrenbacher, M.C.

    2001-01-01

    Dermal exposure assessment and modeling is still in early phases of development. This article presents the results of a workshop organized to harmonize the future needs in this field. Methods for dermal exposure assessment either assess the mass of contaminant that is transferred to the skin, or the

  9. Classification of Dermal Exposure Modifiers and Assignment of Values for a Risk Assessment Toolkit

    NARCIS (Netherlands)

    Goede, H.A.; Tijssen, S.C.H.A.; Schipper, H.J.; Warren, N.; Oppl, R.; Kalberlah, F.; Hemmen, J.J. van

    2003-01-01

    This paper describes how default dermal exposure values can be adjusted with modifier values for specific work situations. The work presented here is supplementary to a toolkit developed for the EU RISKOFDERM project. This toolkit is intended for the assessment and management of dermal risks in smal

  10. Patterns of Dermal Exposure to Hazardous Substances in European Union Workplaces

    NARCIS (Netherlands)

    Rajan-Sithamparanadarajah, R.; Roff, M.; Delgado, P.; Eriksson, K.; Fransman, W.; Gijsbers, J.H.J.; Hughson, G.; Mäkinen, M.; Hemmen, J.J. van

    2004-01-01

    Workplace dermal exposure assessment is a complex task that aims to understand the dynamic interaction between the skin and the hazardous substances present in the surrounding environment. A European project known as RISKOFDERM gathered dermal exposure data in 85 workplaces (industrial and other

  11. Variability of Task-based Dermal Exposure Measurements from a Variety of Workplaces

    NARCIS (Netherlands)

    Kromhout, H.; Fransman, W.; Vermeulen, R.; Roff, M.; Hemmen, J.J. van

    2004-01-01

    Introduction: The RISKOFDERM project collected task-based estimates of potential dermal exposure from a wide range of industries and services from around Europe. A formal statistical analysis was carried out to explore the main components of variability in dermal exposure levels. The central

  12. A dermal model for spray painters, part I : subjective exposure modelling of spray paint deposition

    NARCIS (Netherlands)

    Brouwer, D.H.; Semple, S.; Marquart, J.; Cherrie, J.W.

    2001-01-01

    The discriminative power of existing dermal exposure models is limited. Most models only allow occupational hygienists to rank workers between and within workplaces according to broad bands of dermal exposure. No allowance is made for the work practices of different individuals. In this study a

  13. Variability of Task-based Dermal Exposure Measurements from a Variety of Workplaces

    NARCIS (Netherlands)

    Kromhout, H.; Fransman, W.; Vermeulen, R.; Roff, M.; Hemmen, J.J. van

    2004-01-01

    Introduction: The RISKOFDERM project collected task-based estimates of potential dermal exposure from a wide range of industries and services from around Europe. A formal statistical analysis was carried out to explore the main components of variability in dermal exposure levels. The central researc

  14. Repeatability of Cryogenic Multilayer Insulation

    Science.gov (United States)

    Johnson, W. L.; Vanderlaan, M.; Wood, J. J.; Rhys, N. O.; Guo, W.; Van Sciver, S.; Chato, D. J.

    2017-01-01

    Due to the variety of requirements across aerospace platforms, and one off projects, the repeatability of cryogenic multilayer insulation has never been fully established. The objective of this test program is to provide a more basic understanding of the thermal performance repeatability of MLI systems that are applicable to large scale tanks. There are several different types of repeatability that can be accounted for: these include repeatability between multiple identical blankets, repeatability of installation of the same blanket, and repeatability of a test apparatus. The focus of the work in this report is on the first two types of repeatability. Statistically, repeatability can mean many different things. In simplest form, it refers to the range of performance that a population exhibits and the average of the population. However, as more and more identical components are made (i.e. the population of concern grows), the simple range morphs into a standard deviation from an average performance. Initial repeatability testing on MLI blankets has been completed at Florida State University. Repeatability of five GRC provided coupons with 25 layers was shown to be +/- 8.4 whereas repeatability of repeatedly installing a single coupon was shown to be +/- 8.0. A second group of 10 coupons have been fabricated by Yetispace and tested by Florida State University, through the first 4 tests, the repeatability has been shown to be +/- 16. Based on detailed statistical analysis, the data has been shown to be statistically significant.

  15. Modeling repeated measurement data for occupational exposure assessment and epidemiology

    NARCIS (Netherlands)

    Peretz, Chava

    2004-01-01

    Repeated measurements designs, occur frequently in the assessment of exposure to toxic chemicals. This thesis deals with the possibilities of using mixed effects models for occupational exposure assessment and in the analysis of exposure response relationships. The model enables simultaneous estima

  16. Dermal and transdermal delivery of pharmaceutically relevant macromolecules.

    Science.gov (United States)

    Münch, S; Wohlrab, J; Neubert, R H H

    2017-10-01

    The skin offers an attractive way for dermal and transdermal drug delivery that is why the drug still needs certain qualities to transcend the outermost layer of the skin, the stratum corneum. The requirements are: drugs with a maximum molecular weight of 1kDa, high lipophilicity and a certain polarity. This would restrict the use of a transdermal delivery of macromolecules, which would make the drug more effective in therapeutic administration. Various studies have shown that macromolecules without support do not penetrate the human skin. This effect can be achieved using physical and chemical methods, as well as biological peptides. The most popular physical method is the use of microneedles to create micropores in the skin and release the active agent in different sections. But also, other methods have been tested. Microjets, lasers, electroporation, sonophoresis and iontophoresis are also promising methods to successfully deliver dermal and transdermal macromolecules. Additionally, there are different penetration enhancer groups and biological peptides, which are also considered to be interesting approaches of enabling macromolecules to travel along the skin. All these methods will be described and evaluated in this review article. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. The dermal carcinogenic potential of unrefined and hydrotreated lubricating oils.

    Science.gov (United States)

    McKee, R H; Daughtrey, W C; Freeman, J J; Federici, T M; Phillips, R D; Plutnick, R T

    1989-08-01

    Unrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method. The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyrene), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice-weekly aliquots to the backs of 40 male C3H mice. In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non-carcinogenic products.

  18. Complications caused by injection of dermal filler in Danish patients

    DEFF Research Database (Denmark)

    Uth, Charlotte Caspara; Elberg, Jens Jørgen; Zachariae, Claus

    2016-01-01

    Background: The usage of dermal fillers has increased significantly in recent years. Soft tissue augmentation with fillers helps to diminish the facial lines and to restore volume and fullness in the face at a relatively low cost. With the increasing number of treatments, the number of complicati......Background: The usage of dermal fillers has increased significantly in recent years. Soft tissue augmentation with fillers helps to diminish the facial lines and to restore volume and fullness in the face at a relatively low cost. With the increasing number of treatments, the number...... of complications is likely to increase as well.  Methods: A total of 37 patients with complications were collected retrospectively during a period of 13 years using original data files. Information on the type, date, number and location of the injections, type and date of complications, treatment, bacteria...... and complications was 2 years (range 1 day–8 years). The most common reported complications were edema (81 %), noduli (67.7 %), infections (54.1 %), discoloration (51.4 %), and granuloma formation (48.6 %). Surgical removal of the filler material was attempted in four patients.  Conclusions: With the increased use...

  19. Distribution of kerosene components in rats following dermal exposure.

    Science.gov (United States)

    Tsujino, Y; Hieda, Y; Kimura, K; Eto, H; Yakabe, T; Takayama, K; Dekio, S

    2002-08-01

    The systemic distribution of kerosene components in blood and tissues was analysed in rats following dermal exposure. Four types of trimethylbenzenes (TMBs) and aliphatic hydrocarbons (AHCs) with carbon numbers 9-16 (C(9)-C(16)) were analysed as major kerosene components by capillary gas chromatography/mass spectrometry (GC/MS). The kerosene components were detected in blood and all tissues after a small piece of cotton soaked with kerosene was applied to the abdominal skin. The amounts of TMBs detected were higher than those of AHCs. Greater increases in TMB levels were found in adipose tissue in an exposure duration-dependent manner. The amounts of TMBs detected were only at trace levels following post-mortem dermal exposure to kerosene. These findings suggest that kerosene components were absorbed percutaneously and distributed to various organs via the blood circulation. Post-mortem or ante-mortem exposure to kerosene could be distinguished when the exposure duration was relatively long. Adipose tissue would seem to be the most useful for estimating the degree of kerosene exposure.

  20. Nanofeatured silk fibroin membranes for dermal wound healing applications.

    Science.gov (United States)

    Karahaliloğlu, Zeynep; Ercan, Batur; Denkbaş, Emir B; Webster, Thomas J

    2015-01-01

    As an effort to create the next generation of improved skin graft materials, in this study, we modified the surfaces of a previously investigated material, silk fibroin, using a NaOH alkaline treatment to obtain a biologically inspired nanofeatured surface morphology. Such surfaces were characterized for roughness, energy, and chemistry. In addition, keratinocyte (skin-forming cells) adhesion and proliferation on such nanofeatured silk fibroin wound dressings were studied in an initial attempt to determine the promotion of an epidermal cover on the wound bed to form a new epidermal barrier. Dermal fibroblast adhesion and proliferation were also studied to assess the ability of nanostructured silk fibroin to replace damaged dermal tissue in chronic wounds (i.e., for diabetic foot ulcers). Results demonstrated for the first time that keratinocyte and fibroblast cell density was greater on nanofeatured silk fibroin membranes compared with non-treated silk fibroin surfaces. The enhancement in cellular functions was correlated with an increase in silk surface nanotopography, wettability and change in chemistry after NaOH treatment. Due to the present promising results, the newly developed nanofeatured silk fibroin membranes are exciting alternative skin graft materials which should be further studied for various skin patch and wound dressing applications.

  1. A study of uniaxial tension on the superficial dermal microvasculature.

    Science.gov (United States)

    Barnhill, R L; Bader, D L; Ryan, T J

    1984-05-01

    A spring-loaded apparatus was designed to apply uniaxial tension to forearm skin in 17 human subjects--10 normals, 6 psoriatics, and 1 patient with scleroderma. Simultaneously, the effects of stretching on the upper dermal vasculature were observed stereomicroscopically. Progressive changes (collapse) in the superficial microvasculature--vertical capillary loops and horizontal subpapillary plexus--with increasing tension were photographed. Force and strains were recorded at the points of disappearance of virtually all vessels. An average force of 11.9 newtons (N), accompanied by a mean strain of 10.3%, resulted in occlusion of all vessels. A much higher force (18.5 N) was necessary to occlude blood flow in the 1 patient with scleroderma. In summary, we have described a new technique for the study of mechanical forces on the blood supply of the epidermis. The data have shown that uniaxial tension has important effects on the superficial dermal microvasculature, resulting in impedance and obliteration of blood flow at relatively low magnitudes.

  2. Acellular dermal matrix based nipple reconstruction: A modified technique

    Directory of Open Access Journals (Sweden)

    Raghavan Vidya

    2017-09-01

    Full Text Available Nipple areolar reconstruction (NAR has evolved with the advancement in breast reconstruction and can improve self-esteem and, consequently, patient satisfaction. Although a variety of reconstruction techniques have been described in the literature varying from nipple sharing, local flaps to alloplastic and allograft augmentation, over time, loss of nipple projection remains a major problem. Acellular dermal matrices (ADM have revolutionised breast reconstruction more recently. We discuss the use of ADM to act as a base plate and strut to give support to the base and offer nipple bulk and projection in a primary procedure of NAR with a local clover shaped dermal flap in 5 breasts (4 patients. We used 5-point Likert scales (1 = highly unsatisfied, 5 = highly satisfied to assess patient satisfaction. Median age was 46 years (range: 38–55 years. Nipple projection of 8 mm, 7 mm, and 7 mms were achieved in the unilateral cases and 6 mm in the bilateral case over a median 18 month period. All patients reported at least a 4 on the Likert scale. We had no post-operative complications. It seems that nipple areolar reconstruction [NAR] using ADM can achieve nipple projection which is considered aesthetically pleasing for patients.

  3. Effect of Arctium lappa (burdock) extract on canine dermal fibroblasts.

    Science.gov (United States)

    Pomari, Elena; Stefanon, Bruno; Colitti, Monica

    2013-12-15

    Although the biological activities of Arctium lappa (burdock) have been already investigated in human and other species, data evaluating the molecular mechanisms have not been reported in the dog. In this study we analyzed for the first time the effect of a root extract of burdock on molecular responses in canine dermal fibroblasts with H2O2 stimulation (H group), with burdock treatment (B group) and with H2O2 stimulation and burdock treatment (BH group), using RNAseq technology. Differentially expressed genes (P<0.05) of H, B and BH groups in comparison to the untreated sample (negative control, C group) were identified with MeV software and were functional annotated and monitored for signaling pathways and candidate biomarkers using the Ingenuity Pathways Analysis (IPA). The expression profile of canine dermal fibroblasts treated with burdock extract with or without H2O2 stimulation, showed an up-regulation of mitochondrial superoxide dismutase (SOD2), disheveled 3 (DVL3) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (CSGALNACT2). The data suggested that burdock has implications in cell adhesion and gene expression with the modulation of Wnt/β catenin signaling and Chondroitin Sulphate Biosynthesis that are particularly important for the wound healing process.

  4. The Use of Dermal Autograft for Fascial Repair of TRAM Flap Donor Sites

    Directory of Open Access Journals (Sweden)

    Ali Arab Kheradmand

    2010-03-01

    Full Text Available Closure of fascia after transverse rectus abdominis musculocutaneous (TRAM flap has usually been performed with direct closure or synthetic material. The dermal autograft was removed from zone IV of flap was an alternative to reinforce fascial closure. The dermal autograft was used in 34 patients after TRAM harvest for breast, head and neck reconstruction and Prolene mesh was used in 42 other patients for closure of fascial defect. All patients were followed by physical examinations. Average follow-up in the dermal autograft group was 27.3 versus 20.7 months in the second group. In the dermal autograft group, one patient complained of bulging of the anterior abdominal wall; one developed a wound infection. In the second group, one patients experienced true hernia. Dermal autografts are a useful alternative to mesh repair of fascial defects after TRAM flap harvest.

  5. Hanford Tank Ventilation System Condensates and Headspace Vapors: An Assessment of Potential Dermal Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Huckaby, James L.; Springer, David L.

    2006-04-24

    This study considers the question of whether potential dermal exposures to Hanford high-level radioactive waste tank headspace vapors and their condensates could result in significant exposure to workers. Three types of potential exposures were evaluated; dermal contact with aqueous condensate, organic condensate, and direct contact with head space vapors. The dermal absorption rates from aqueous and organic condensates were estimated for selected chemicals using a model described by EPA (1992) with a modified correlation for dermal permeability suggested by Wilschut et al. (1995). Dermal absorption rates of vapors were estimated using a model given by AIHA (2000). Results were compared to an ''equivalent inhalation dose'' calculated by multiplying the inhalation occupational exposure limit by a nominal daily inhalation rate. The results should provide guidance for industrial hygienists to prepare specific recommendations based on specific scenarios.

  6. Deriving Default Dermal Exposure Values for Use in a Risk Assessment Toolkit for Small and Medium-sized Enterprises

    NARCIS (Netherlands)

    Warren, N.; Goede, H.A.; Tijssen, S.C.H.A.; Oppl, R.; Schipper, H.J.; Hemmen, J.J. van

    2003-01-01

    This paper describes the derivation of default task-based dermal exposure values for use in a risk assessment toolkit for small and medium-sized enterprises (SMEs). A set of separately determined dermal exposure modifiers have been applied to published studies of dermal exposure to obtain 'normalize

  7. Assessment of dermal exposure to bitumen condensate among road paving and mastic crews with an observational method

    NARCIS (Netherlands)

    Agostini, M.; Fransman, W.; Vocht, F.D.; Joode, B.V.W.D.; Kromhout, H.

    2011-01-01

    Objective: To assess dermal exposure to bitumen condensate among road pavers and indoor mastic workers in multiple crews using a semi-quantitative observational method [DeRmal Exposure Assessment Method (DREAM)].Methods: Two skilled observers assessed dermal exposure to bitumen condensate among 85 a

  8. Evaluation of dermal substitute in a novel co-transplantation model with autologous epidermal sheet.

    Directory of Open Access Journals (Sweden)

    Guofeng Huang

    Full Text Available The development of more and more new dermal substitutes requires a reliable and effective animal model to evaluate their safety and efficacy. In this study we constructed a novel animal model using co-transplantation of autologous epidermal sheets with dermal substitutes to repair full-thickness skin defects. Autologous epidermal sheets were obtained by digesting the basement membrane (BM and dermal components from rat split-thickness skins in Dispase II solution (1.2 u/ml at 4 °C for 8, 10 and 12 h. H&E, immunohistochemical and live/dead staining showed that the epidermal sheet preserved an intact epidermis without any BM or dermal components, and a high percentage of viable cells (92.10 ± 4.19% and P63 positive cells (67.43 ± 4.21% under an optimized condition. Porcine acellular dermal matrixes were co-transplanted with the autologous epidermal sheets to repair full-thickness skin defects in Sprague-Dawley rats. The epidermal sheets survived and completely re-covered the wounds within 3 weeks. Histological staining showed that the newly formed stratified epidermis attached directly onto the dermal matrix. Inflammatory cell infiltration and vascularization of the dermal matrix were not significantly different from those in the subcutaneous implantation model. Collagen IV and laminin distributed continuously at the epidermis and dermal matrix junction 4 weeks after transplantation. Transmission electron microscopy further confirmed the presence of continuous lamina densa and hemidesmosome structures. This novel animal model can be used not only to observe the biocompatibility of dermal substitutes, but also to evaluate their effects on new epidermis and BM formation. Therefore, it is a simple and reliable model for evaluating the safety and efficacy of dermal substitutes.

  9. Cytotoxicity and Proliferation Studies with Arsenic in Established Human Cell Lines: Keratinocytes, Melanocytes, Dendritic Cells, Dermal Fibroblasts, Microvascular Endothelial Cells, Monocytes and T-Cells

    Directory of Open Access Journals (Sweden)

    Hari H. P. Cohly

    2003-01-01

    Full Text Available Abstract: Based on the hypothesis that arsenic exposure results in toxicity and mitogenecity, this study examined the dose-response of arsenic in established human cell lines of keratinocytes (HaCaT, melanocytes (1675, dendritic cells (THP-1/A23187, dermal fibroblasts (CRL1904, microvascular endothelial cells (HMEC, monocytes (THP-1, and T cells (Jurkat. Cytotoxicity was determined by incubating THP-1, THP-1+ A23187 and JKT cells in RPMI 1640, 1675 in Vitacell, HMEC in EBM, and dermal fibroblasts and HaCaT in DMEM with 10% fetal bovine serum, 1% streptomycin and penicillin for 72 hrs in 96-well microtiter plates, at 37oC in a 5% CO2 incubator with different concentrations of arsenic using fluorescein diacetate (FDA. Cell proliferation in 96-well plates was determined in cultured cells starved by prior incubation for 24 hrs in 1% FBS and exposed for 72 hours, using the 96 cell titer proliferation solution (Promega assay. Cytotoxicity assays yielded LD50s of 9 μg/mL for HaCaT, 1.5 μg/mL for CRL 1675, 1.5 μg/mL for dendritic cells, 37 μg/mL for dermal fibroblasts, 0.48 μg/mL for HMEC, 50 μg/mL for THP-1 cells and 50 μg/mL for JKT-T cells. The peak proliferation was observed at 6 μg/mL for HaCaT and THP-1 cells, 0.19 μg/mL for CRL 1675, dendritic cells, and HMEC, and 1.5 μg/mL for dermal fibroblasts and Jurkat T cells. These results show that arsenic is toxic at high doses to keratinocytes, fibroblasts, monocytes and T cells, and toxic at lower doses to melanocytes, microvascular endothelial cells and dendritic cells. Proliferation studies showed sub-lethal doses of arsenic to be mitogenic.

  10. Human Toxicity

    DEFF Research Database (Denmark)

    Jolliet, Olivier; Fantke, Peter

    2015-01-01

    This chapter reviews the human toxicological impacts of chemicals and how to assess these impacts in life cycle impact assessment (LCIA), in order to identify key processes and pollutants. The complete cause-effect pathway – from emissions of toxic substances up to damages on human health...... on characterisation factors means that results should by default be reported and interpreted in log scales when comparing scenarios or substance contribution! We conclude by outlining future trends in human toxicity modelling for LCIA, with promising developments for (a) better estimates of degradation halflives, (b......) the inclusion of ionization of chemicals in human exposure including bioaccumulation, (c) metal speciation, (d) spatialised models to differentiate the variability associated with spatialisation from the uncertainty, and (e) the assessment of chemical exposure via consumer products and occupational settings...

  11. Dermal adipocytes and hair cycling: is spatial heterogeneity a characteristic feature of the dermal adipose tissue depot?

    Science.gov (United States)

    Kruglikov, Ilja L; Scherer, Philipp E

    2016-04-01

    Adipocytes are widely distributed in the dermis, in a unique fat depot referred to as dermal white adipose tissue (dWAT). In rodents, dWAT is present as widespread thin layers, whereas in pigs and humans, it is present in clusters referred to as 'dermal cones' around the pilosebaceous units. This distinct layer of fat cells located above the subcutaneous white adipose tissue is important for proper hair follicle (HF) cycling in rodents. Murine HFs produce spatially restricted synchronous patches after their second postnatal cycle which correlates with the spatial heterogeneity of murine dWAT. Similarly, the cycling of HFs in humans may also be related to the spatial distribution of dWAT, making the difference between murine and human HF cycling of more quantitative than of qualitative nature. This should allow the production of small spatially correlated HF patches in human skin, and we propose that this process can be regulated by paracrine signalling involving a number of signalling modules, including the hedgehog pathway. This pathway is an established player in HF cycling, but is also involved in the regulation of adipogenesis and may therefore be a key regulator of the process across species. We also suggest that the spatial heterogeneity of dWAT is connected not only to HF cycling, but may also be related to other physiological and pathological processes in the skin.

  12. RAN translation at CGG repeats induces ubiquitin proteasome system impairment in models of fragile X-associated tremor ataxia syndrome

    OpenAIRE

    Oh, Seok Yoon; He, Fang; Krans, Amy; Frazer, Michelle; Taylor, J. Paul; Paulson, Henry L.; Todd, Peter K

    2015-01-01

    Fragile X-associated tremor ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a CGG trinucleotide repeat expansion in the 5′ UTR of the Fragile X gene, FMR1. FXTAS is thought to arise primarily from an RNA gain-of-function toxicity mechanism. However, recent studies demonstrate that the repeat also elicits production of a toxic polyglycine protein, FMRpolyG, via repeat-associated non-AUG (RAN)-initiated translation. Pathologically, FXTAS is characterized by ubiquitin-positive ...

  13. Acute toxicity testing of chemicals-Opportunities to avoid redundant testing and use alternative approaches.

    Science.gov (United States)

    Creton, Stuart; Dewhurst, Ian C; Earl, Lesley K; Gehen, Sean C; Guest, Robert L; Hotchkiss, Jon A; Indans, Ian; Woolhiser, Michael R; Billington, Richard

    2010-01-01

    Assessment of the acute systemic oral, dermal, and inhalation toxicities, skin and eye irritancy, and skin sensitisation potential of chemicals is required under regulatory schemes worldwide. In vivo studies conducted to assess these endpoints can sometimes be associated with substantial adverse effects in the test animals, and their use should always be scientifically justified. It has been argued that while information obtained from such acute tests provides data needed to meet classification and labelling regulations, it is of limited value for hazard and risk assessments. Inconsistent application of in vitro replacements, protocol requirements across regions, and bridging principles also contribute to unnecessary and redundant animal testing. Assessment of data from acute oral and dermal toxicity testing demonstrates that acute dermal testing rarely provides value for hazard assessment purposes when an acute oral study has been conducted. Options to waive requirements for acute oral and inhalation toxicity testing should be employed to avoid unnecessary in vivo studies. In vitro irritation models should receive wider adoption and be used to meet regulatory needs. Global requirements for sensitisation testing need continued harmonisation for both substance and mixture assessments. This paper highlights where alternative approaches or elimination of tests can reduce and refine animal use for acute toxicity requirements.

  14. Androgen receptor accelerates premature senescence of human dermal papilla cells in association with DNA damage.

    Directory of Open Access Journals (Sweden)

    Yi-Chien Yang

    Full Text Available The dermal papilla, located in the hair follicle, expresses androgen receptor and plays an important role in hair growth. Androgen/Androgen receptor actions have been implicated in the pathogenesis of androgenetic alopecia, but the exact mechanism is not well known. Recent studies suggest that balding dermal papilla cells exhibit premature senescence, upregulation of p16(INK4a, and nuclear expression of DNA damage markers. To investigate whether androgen/AR signaling influences the premature senescence of dermal papilla cells, we first compared frontal scalp dermal papilla cells of androgenetic alopecia patients with matched normal controls and observed that premature senescence is more prominent in the dermal papilla cells of androgenetic alopecia patients. Exposure of androgen induced premature senescence in dermal papilla cells from non-balding frontal and transitional zone of balding scalp follicles but not in beard follicles. Overexpression of the AR promoted androgen-induced premature senescence in association with p16(INK4a upregulation, whereas knockdown of the androgen receptor diminished the effects of androgen. An analysis of γ-H2AX expression in response to androgen/androgen receptor signaling suggested that DNA damage contributes to androgen/androgen receptor-accelerated premature senescence. These results define androgen/androgen receptor signaling as an accelerator of premature senescence in dermal papilla cells and suggest that the androgen/androgen receptor-mediated DNA damage-p16(INK4a axis is a potential therapeutic target in the treatment of androgenetic alopecia.

  15. Thermal Stress and Toxicity

    Science.gov (United States)

    Elevating ambient temperature above thermoneutrality exacerbates toxicity of most air pollutants, insecticides, and other toxic chemicals. On the other hand, safety and toxicity testing of toxicants and drugs is usually performed in mice and rats maintained at subthermoneutral te...

  16. Dermal lesions after post mortem petrol-exposure.

    Science.gov (United States)

    Bux, R; Stengel, P D; Schnabel, A

    2006-11-10

    The effect of post mortem contact of the skin with petrol was investigated in 18 corpses with exposure times between 10 min and 24 h. The earliest onset of skin changes was observed within 2 h of exposure. They consisted of swelling and wrinkling with detachment of the upper layers of the skin (positive Nikolski's sign). Histologically the lesions appeared as non-vital acantholyses located in the prickle-cell layer with formation of intra-epidermal bullae. An influence of age and sex could be excluded, the earlier onset of lesions at 22 degrees C than at 4 degrees C was not statistically significant. These findings prove that post mortem petrol exposure may lead to dermal lesions.

  17. Bioactives from probiotics for dermal health: functions and benefits.

    Science.gov (United States)

    Lew, L-C; Liong, M-T

    2013-05-01

    Probiotics have been extensively reviewed for decades, emphasizing on improving general gut health. Recently, more studies showed that probiotics may exert other health-promoting effects beyond gut well-being, attributed to the rise of the gut-brain axis correlations. Some of these new benefits include skin health such as improving atopic eczema, atopic dermatitis, healing of burn and scars, skin-rejuvenating properties and improving skin innate immunity. Increasing evidence has also showed that bacterial compounds such as cell wall fragments, their metabolites and dead bacteria can elicit certain immune responses on the skin and improve skin barrier functions. This review aimed to underline the mechanisms or the exact compounds underlying the benefits of bacterial extract on the skin based on evidences from in vivo and in vitro studies. This review could be of help in screening of probiotic strains with potential dermal enhancing properties for topical applications.

  18. Complex wound management utilizing an artificial dermal matrix.

    Science.gov (United States)

    Muangman, Pornprom; Engrav, Loren H; Heimbach, David M; Harunari, Nobuyuki; Honari, Shari; Gibran, Nicole S; Klein, Matthew B

    2006-08-01

    The benefits of the Integra Dermal Regeneration Template in the management of extensive burn injuries have been well documented. Integra can reduce donor- and graft-site scarring and has been reported to be capable of vascularizing over small areas of exposed bone and tendon. Given these potential advantages, we have used Integra for a variety of other reconstruction applications. We performed a retrospective review of patients with complex wounds treated with Integra at our burn center. Integra was used in the management of a variety of wounds, including necrotizing fasciitis, extremity degloving injury, meningococcemia, Marjolin ulcer, postburn lip reconstruction, and fourth-degree burns with exposed bone or tendon. Engraftment rates of Integra and autograft were 98% +/- 4% and 97% +/- 4%, respectively. All areas of graft loss healed without need for regrafting. The benefits of Integra in the management of acute burn wounds can be extended to other traumatic and complex wounds.

  19. Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

    Science.gov (United States)

    Cohen, Brandon E; Bashey, Sameer; Cole, Christine; Abraham, Jerrold L; Ragsdale, Bruce; Ngo, Binh

    2016-12-01

    Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

  20. Post-kala-azar dermal leishmaniasis associated with AIDS

    Directory of Open Access Journals (Sweden)

    Bittencourt Achiléa

    2003-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

  1. Post-kala-azar dermal leishmaniasis associated with AIDS

    Directory of Open Access Journals (Sweden)

    Bittencourt Achiléa

    2002-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is rarely reported in South America. In spite of the fact that there are many reports about the association of visceral leishmaniasis and AIDS, PKDL is very uncommon in HIV-positive patients, and so far only four cases have been documented in the literature. We present another case with unusual clinicopathological aspects. The patient, a 28-year-old male, from Salvador, Bahia (an endemic area presented with clinical manifestations of visceral leishmaniasis three years after the diagnosis of AIDS. During treatment for visceral leishmaniasis he developed disseminated miliary papules. Microscopically, the skin biopsy showed a "saw-tooth" pattern with a lichenoid mononuclear infiltrate simulating lichen planus. The histopathological diagnosis was achieved through the finding of amastigotes. The authors discuss the clinicopathological aspects of this case based on a review of the specific literature.

  2. Acute concentrated phenol dermal burns: Complications and management

    Directory of Open Access Journals (Sweden)

    Tapan Jayantilal Parikh

    2015-01-01

    Full Text Available Phenol burns can result in multiple organ failure. This is a case report of acute severe phenol dermal burn after accidental splash of 94% phenol on 35-year-old patient′s body who was brought to hospital after 90 min of exposure. Decontamination was done with high-density water and glycerol. Early complications in form of metabolic acidosis and acute renal failure required hemodialysis. Extensive protein denaturation was managed with IV albumin and high protein diet. Patient also developed pleural effusion and acute respiratory distress syndrome, but these were successfully managed by intercostal drain tube insertion and noninvasive ventilation. The patient survived after multiple organ failures and widespread burns despite the fact that it has been observed that outcome of phenol burns with >60 2 inches of skin affected or two or more organs failure involving renal system is nearly fatal.

  3. Sonographic Appearance of Dermal and Subcutaneous Sarcoidosis: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ja Yoon; Bae, Young A; Hong, Hyeok Jin; Kwon, Kye Won [Dept. of Radiology, Bundang Jesaeng General Hospital, Seongnam (Korea, Republic of)

    2012-08-15

    Sarcoidosis is a systemic granulomatous disease of unknown origin that mainly involves lung and skin, but rarely involves subcutaneous tissue. While some studies have reported on CT or MR imaging findings of subcutaneous sarcoidosis, there is only one report on sonographic findings of subcutaneous sarcoidosis, recently published in the US. Familiarity with ultrasonographic findings of subcutaneous sarcoidosis might be helpful for the early diagnosis in patient with palpable nodules and image follow-up for subcutaneous sarcoidosis. Here we report on the sonographic appearance of subcutaneous sarcoidosis involving dermal and subcutaneous tissue over axilla and sole, a case diagnosed as sarcoidosis and improved by steroid treatment, along with a review of the relevant literature.

  4. Defense against dermal exposures is only skin deep

    DEFF Research Database (Denmark)

    Nielsen, Jesper Bo; Nielsen, Flemming; Sørensen, Jens Ahm

    2007-01-01

    The OECD guideline for studies on percutaneous penetration to be used in hazard and risk evaluations prescribes experimental conditions with optimal barrier integrity of the skin, which in many occupational settings probably is not true. Thus, workers may have compromised skin due to chemical...... or mechanical damage, due to different medical conditions (eczema, dermatitis, skin irritation) or related to occupational scenarios involving prolonged wet work. The present study used the OECD guideline procedures to study the in vitro percutaneous penetration through human skin of a number of model...... substances (glyphosat, caffeine, benzoic acid, malathion) covering a range of solubilities. Further, we studied the extent to which a slightly damaged skin would change the rate, the amount absorbed during dermal exposure and the distribution of chemical deposition between epidermis and dermis. The present...

  5. Lycopene from tomatoes: vesicular nanocarrier formulations for dermal delivery.

    Science.gov (United States)

    Ascenso, Andreia; Pinho, Sónia; Eleutério, Carla; Praça, Fabíola Garcia; Bentley, Maria Vitória Lopes Badra; Oliveira, Helena; Santos, Conceição; Silva, Olga; Simões, Sandra

    2013-07-31

    This experimental work aimed to develop a simple, fast, economic, and environmentally friendly process for the extraction of lycopene from tomato and incorporate this lycopene-rich extract into ultradeformable vesicular nanocarriers suitable for topical application. Lycopene extraction was conducted without a cosolvent for 30 min. The extracts were analyzed and incorporated in transfersomes and ethosomes. These formulations were characterized, and the cellular uptake was observed by confocal microscopy. Dermal delivery of lycopene formulations was tested under in vitro and in vivo conditions. Lycopene extraction proved to be quite safe and selective. The vesicular formulation was taken up by the cells, being more concentrated around the nucleus. Epicutaneous application of lycopene formulations decreased the level of anthralin-induced ear swelling by 97 and 87%, in a manner nonstatistically different from the positive control. These results support the idea that the lycopene-rich extract may be a good alternative to the expensive commercial lycopene for incorporation into advanced topical delivery systems.

  6. [Assessment of predictive dermal exposure to chemicals in the work environment].

    Science.gov (United States)

    Jankowska, Agnieszka; Czerczak, Sławomir; Kupczewska-Dobecka, Małgorzata

    2017-06-27

    Assessment of dermal exposure to chemicals in the work environment is problematic, mainly as a result of the lack of measurement data on occupational exposure to chemicals. Due to common prevalence of occupational skin exposure and its health consequences it is necessary to look for efficient solutions allowing for reliable exposure assessment. The aim of the study is to present predictive models used to assess non-measured dermal exposure, as well as to acquaint Polish users with the principles of the selected model functioning. This paper presents examples of models to assist the employer in the the assessment of occupational exposure associated with the skin contact with chemicals, developed in European Union (EU) countries, as well as in countries outside the EU. Based on the literature data dermal exposure models EASE (Estimation and Assessment of Substance Exposure), COSHH Essentials (Control of Substances Hazardous to Health Regulations), DREAM (Dermal Exposure Assessment Method), Stoffenmanager , ECETOC TRA (European Centre for Ecotoxicology and Toxicology of Chemicals Targeted Risk Assessment), MEASE (Metal's EASE), PHED (Pesticide Handlers Exposure Database), DERM (Dermal Exposure Ranking Method) and RISKOFDERM (Risk Assessment of Occupational Dermal Exposure to Chemicals) were briefly described. Moreover the characteristics of RISKOFDERM, guidelines for its use, information on input and output data were further detailed. Problem of full work shift dermal exposure assessment is described. An example of exposure assessment using RISKOFDERM and effectiveness evaluation to date were also presented. When no measurements are available, RISKOFDERM allows dermal exposure assessment and thus can improve the risk assessment quality and effectiveness of dermal risk management. Med Pr 2017;68(4):557-569. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

  7. CTRP6 inhibits fibrogenesis in TGF-β1-stimulated human dermal fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Fan, Rong-hui, E-mail: fan_ronghuixa@163.com [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Zhu, Xiu-mei; Sun, Yao-wen [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China); Peng, Hui-zi [Department of Cosmetology Plastic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061 (China); Wu, Hang-li; Gao, Wen-jie [Department of Burn and Plastic Surgery, Shaanxi Provincial People’s Hospital, Xi’an 710068 (China)

    2016-07-08

    Skin fibrosis is characterized by excessive proliferation of fibroblasts and overproduction of extracellular matrix (ECM). C1q/tumor necrosis factor-related protein 6 (CTRP6), a member of CTRPs, has been involved in the development of cardiac fibrosis. However, the function and detailed regulatory mechanism of CTRP6 in skin fibrosis remain unclear. The aim of this study was to investigate the effect of CTRP6 on the activation of human dermal fibroblasts. Our results showed that CTRP6 was lowly expressed in scar tissues and transforming growth factor-β1 (TGF-β1)-treated dermal fibroblasts. CTRP6 overexpression significantly inhibited the proliferation of dermal fibroblasts, as well as suppressed the expression of ECM in TGF-β1-treated dermal fibroblasts. Furthermore, CTRP6 overexpression markedly inhibited TGF-β1-induced phosphorylation of Smad3 in dermal fibroblasts. In conclusion, the data reported here demonstrate that CTRP6 is able to inhibit the proliferation and ECM expression in human dermal fibroblasts through suppressing the TGF-β1/Smad3 signaling pathway. These findings suggest that CTRP6 may be a potential therapeutic target for the prevention of skin fibrosis. -- Highlights: •CTRP6 expression was decreased in scar tissues and TGF-β1-treated dermal fibroblasts. •CTRP6 inhibits TGF-β1-induced the proliferation of dermal fibroblasts. •CTRP6 inhibits expression of collagen type I and α-SMA. •CTRP6 inhibits the activation of TGF-β1/Smad3 signaling pathway in dermal fibroblasts.

  8. Sirtinol treatment reduces inflammation in human dermal microvascular endothelial cells.

    Directory of Open Access Journals (Sweden)

    Angela Orecchia

    Full Text Available Histone deacetylases (HDAC are key enzymes in the epigenetic control of gene expression. Recently, inhibitors of class I and class II HDAC have been successfully employed for the treatment of different inflammatory diseases such as rheumatoid arthritis, colitis, airway inflammation and asthma. So far, little is known so far about a similar therapeutic effect of inhibitors specifically directed against sirtuins, the class III HDAC. In this study, we investigated the expression and localization of endogenous sirtuins in primary human dermal microvascular endothelial cells (HDMEC, a cell type playing a key role in the development and maintenance of skin inflammation. We then examined the biological activity of sirtinol, a specific sirtuin inhibitor, in HDMEC response to pro-inflammatory cytokines. We found that, even though sirtinol treatment alone affected only long-term cell proliferation, it diminishes HDMEC inflammatory responses to tumor necrosis factor (TNFα and interleukin (IL-1β. In fact, sirtinol significantly reduced membrane expression of adhesion molecules in TNFã- or IL-1β-stimulated cells, as well as the amount of CXCL10 and CCL2 released by HDMEC following TNFα treatment. Notably, sirtinol drastically decreased monocyte adhesion on activated HDMEC. Using selective inhibitors for Sirt1 and Sirt2, we showed a predominant involvement of Sirt1 inhibition in the modulation of adhesion molecule expression and monocyte adhesion on activated HDMEC. Finally, we demonstrated the in vivo expression of Sirt1 in the dermal vessels of normal and psoriatic skin. Altogether, these findings indicated that sirtuins may represent a promising therapeutic target for the treatment of inflammatory skin diseases characterized by a prominent microvessel involvement.

  9. In vitro dermal penetration study of carbofuran, carbosulfan, and furathiocarb

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Kwang-Hyeon [Department of Pharmacology, Inje University, College of Medicine, 614-735, Busan (Korea); Kim, Jeong-Han [School of Agricultural Biotechnology, Seoul National University, 441-744, Suwon (Korea)

    2003-05-01

    In this study, the dermal penetration rate of carbofuran, carbosulfan, and furathiocarb has been measured with rat abdominal skin using the static diffusion cell. The technical grades of three compounds were applied at different doses on skin surface mounted in static diffusion cell and incubated at 32 C for 48 h with shaking. The same procedures were carried out with furathiocarb EC (emulsifiable concentrate) and WP (wettable powder). At regular intervals, the receptor fluid in cell was sampled and analyzed by HPLC. Only carbofuran was found in carbosulfan- or furathiocarb-treated samples, suggesting they converted into carbofuran while passing through the skin layer. The quantity of insecticide penetrating skin increased with time and applied dose. The skin penetration rate increased with the water solubility of insecticides. The dermal penetration rates of carbofuran, furathiocarb, and carbosulfan were determined as 1.05 {mu}g/cm{sup 2} per h (r{sup 2}=0.991), 0.46 {mu}g/cm{sup 2} per h (r{sup 2}=0.984) and 0.14 {mu}g/cm{sup 2} per h (r{sup 2}=0.967), respectively. There was no significant difference in rate of skin penetration between furathiocarb EC (1.42 {mu}g/cm{sup 2} per h, r{sup 2}=0.988) and WP (1.35 {mu}g/cm{sup 2} per h, r{sup 2}=0.982), while furathiocarb technical grade showed a lower skin penetration rate. In vitro models may be used to predict percutaneous absorption and are useful in selecting safer formulations for field application of pesticide. (orig.)

  10. Toxicokinetics of captan and folpet biomarkers in dermally exposed volunteers.

    Science.gov (United States)

    Berthet, Aurélie; Bouchard, Michèle; Vernez, David

    2012-03-01

    To better assess biomonitoring data in workers exposed to captan and folpet, the kinetics of ring metabolites [tetrahydrophthalimide (THPI), phthalimide (PI) and phthalic acid] were determined in urine and plasma of dermally exposed volunteers. A 10  mg kg(-1) dose of each fungicide was applied on 80  cm(2) of the forearm and left without occlusion or washing for 24  h. Blood samples were withdrawn at fixed time periods over the 72  h following application and complete urine voids were collected over 96  h post-dosing, for metabolite analysis. In the hours following treatment, a progressive increase in plasma levels of THPI and PI was observed, with peak levels being reached at 24  h for THPI and 10  h for PI. The ensuing elimination phase appeared monophasic with a mean elimination half-life (t(½) ) of 24.7 and 29.7 h for THPI and PI, respectively. In urine, time courses PI and phthalic acid excretion rate rapidly evolved in parallel, and a mean elimination t(½) of 28.8 and 29.6  h, respectively, was calculated from these curves. THPI was eliminated slightly faster, with a mean t(½) of 18.7  h. Over the 96  h period post-application, metabolites were almost completely excreted, and on average 0.02% of captan dose was recovered in urine as THPI while 1.8% of the folpet dose was excreted as phthalic acid and 0.002% as PI, suggesting a low dermal absorption fraction for both fungicides. This study showed the potential use of THPI, PI and phthalic acid as key biomarkers of exposure to captan and folpet.

  11. Measurements of dermal uptake of nicotine directly from air and clothing

    DEFF Research Database (Denmark)

    Bekö, Gabriel; Morrison, Glenn C.; Weschler, Charles J.

    2016-01-01

    Dermal uptake directly from air is a significant contributor to total exposure for certain organic compounds, and has been recently experimentally verified for two phthalates. The objective of the current study was to investigate whether airborne nicotine can be dermally absorbed. Two bare...... a shirt previously exposed to tobacco smoke. Urine samples were subsequently analyzed for nicotine and two of its metabolites. The results demonstrate that nicotine can be dermally absorbed directly from air at rates comparable to passive smoking. Wearing clean clothes significantly decreases uptake...

  12. Histologic fate of dermal grafts following implantation for temporomandibular joint meniscal perforation: a preliminary study.

    Science.gov (United States)

    Stewart, H M; Hann, J R; DeTomasi, D C; Neville, B W; DeChamplain, R W

    1986-11-01

    A study was carried out to evaluate the histologic changes of meniscus perforation repair associated with dermal grafts to the temporomandibular joint of cynomolgus monkeys (Macaca fascicularis) following surgical perforation of the meniscus. Dermal grafts were studied histologically at 3-week, 6-week, 3-month, and 6-month intervals. Results showed early attachment of the dermal graft to the meniscus, followed by gradual incorporation of the graft into the meniscus and subsequent return of the meniscal-graft complex to a normal meniscal architecture.

  13. Molecular mechanisms of acrolein toxicity: relevance to human disease.

    Science.gov (United States)

    Moghe, Akshata; Ghare, Smita; Lamoreau, Bryan; Mohammad, Mohammad; Barve, Shirish; McClain, Craig; Joshi-Barve, Swati

    2015-02-01

    Acrolein, a highly reactive unsaturated aldehyde, is a ubiquitous environmental pollutant and its potential as a serious environmental health threat is beginning to be recognized. Humans are exposed to acrolein per oral (food and water), respiratory (cigarette smoke, automobile exhaust, and biocide use) and dermal routes, in addition to endogenous generation (metabolism and lipid peroxidation). Acrolein has been suggested to play a role in several disease states including spinal cord injury, multiple sclerosis, Alzheimer's disease, cardiovascular disease, diabetes mellitus, and neuro-, hepato-, and nephro-toxicity. On the cellular level, acrolein exposure has diverse toxic effects, including DNA and protein adduction, oxidative stress, mitochondrial disruption, membrane damage, endoplasmic reticulum stress, and immune dysfunction. This review addresses our current understanding of each pathogenic mechanism of acrolein toxicity, with emphasis on the known and anticipated contribution to clinical disease, and potential therapies.

  14. Expansion of protein domain repeats.

    Directory of Open Access Journals (Sweden)

    Asa K Björklund

    2006-08-01

    Full Text Available Many proteins, especially in eukaryotes, contain tandem repeats of several domains from the same family. These repeats have a variety of binding properties and are involved in protein-protein interactions as well as binding to other ligands such as DNA and RNA. The rapid expansion of protein domain repeats is assumed to have evolved through internal tandem duplications. However, the exact mechanisms behind these tandem duplications are not well-understood. Here, we have studied the evolution, function, protein structure, gene structure, and phylogenetic distribution of domain repeats. For this purpose we have assigned Pfam-A domain families to 24 proteomes with more sensitive domain assignments in the repeat regions. These assignments confirmed previous findings that eukaryotes, and in particular vertebrates, contain a much higher fraction of proteins with repeats compared with prokaryotes. The internal sequence similarity in each protein revealed that the domain repeats are often expanded through duplications of several domains at a time, while the duplication of one domain is less common. Many of the repeats appear to have been duplicated in the middle of the repeat region. This is in strong contrast to the evolution of other proteins that mainly works through additions of single domains at either terminus. Further, we found that some domain families show distinct duplication patterns, e.g., nebulin domains have mainly been expanded with a unit of seven domains at a time, while duplications of other domain families involve varying numbers of domains. Finally, no common mechanism for the expansion of all repeats could be detected. We found that the duplication patterns show no dependence on the size of the domains. Further, repeat expansion in some families can possibly be explained by shuffling of exons. However, exon shuffling could not have created all repeats.

  15. DWI Repeaters and Non-Repeaters: A Comparison.

    Science.gov (United States)

    Weeber, Stan

    1981-01-01

    Discussed how driving-while-intoxicated (DWI) repeaters differed signigicantly from nonrepeaters on 4 of 23 variables tested. Repeaters were more likely to have zero or two dependent children, attend church frequently, drink occasionally and have one or more arrests for public intoxication. (Author)

  16. To Repeat or Not to Repeat a Course

    Science.gov (United States)

    Armstrong, Michael J.; Biktimirov, Ernest N.

    2013-01-01

    The difficult transition from high school to university means that many students need to repeat (retake) 1 or more of their university courses. The authors examine the performance of students repeating first-year core courses in an undergraduate business program. They used data from university records for 116 students who took a total of 232…

  17. The incorporation of Brazilian propolis into collagen-based dressing films improves dermal burn healing.

    Science.gov (United States)

    de Almeida, Enrik Barbosa; Cordeiro Cardoso, Juliana; Karla de Lima, Adriana; de Oliveira, Nívia Lucas; de Pontes-Filho, Nicodemos Teles; Oliveira Lima, Sônia; Leal Souza, Isana Carla; de Albuquerque-Júnior, Ricardo Luiz Cavalcanti

    2013-05-20

    Hydroalcoholic solutions of propolis, a resinous product produced by bees, have been currently employed in improving the cicatricial repair. Biological activity of propolis might be related to its antimicrobial, anti-inflammatory and immunomudalatory properties. Investigate the suitability of the collagen-based films containing hydroalcoholic extracts of two different varieties of Brazilian propolis (green and red ones) on the dermal burn healing in rodent model. The hydroalcoholic extracts of red propolis (RP) or Green propolis (GP) were incorporated into collagen-based dressing films (COL). Burn wounds were performed in the dorsum of Wistar rats and dressing with COL, COL+GPa (0.5%), COL+GPb (1,0%) or COL+RP (0.5%). A control group (CTR) was performed keeping the wound undressed. The histological analyses were carried out after 3, 7, 14, 21 and 30 days for histological assessment of the inflammatory response, epithelization rates (ER), myofibroblastic count (MC) and collagenization pattern. GPa, GPb and RP provided significant decrease of the inflammatory severity, improved the ER in GPa in 7 (p=0.000), 14 (p=0.000), 21 (p=0.005) and 30 days (p=0.015), and induced earlier replacement of type-III for type-I collagen (ppropolis improved the biological events associated to burn healing without toxic effects, but the red variety provided the best results. Therefore, these collagen-based containing natural apicultural products films may be considered a promising new dressing for wound occlusion and tissue repairing. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  18. Delisting toxicity evaluation of HTH and oxone(trade name) decontaminated VX. Final report, July 1989-March 1990

    Energy Technology Data Exchange (ETDEWEB)

    Manthei, J.H.; Heitkamp, D.H.; Buettner, L.C.; Lawrence-Beckett, E.M.; Samuel, J.B.

    1992-07-01

    The acute percutaneous (bare skin) LD50 was determined for EA 2192 in the rabbit. Also established were the effective doses (ED50s) for the major toxic signs observed. Dermal, Department of Transportation (DOT), tests with rabbits indicated that VX/HTH decontaminated waste is a Class B poison after being aged only 24 hr following initiation of the decontamination procedure. The same reaction, when allowed to age through about 2 half-lives (28-30 days), was no longer a Class B poison and was nonhazardous by Code of Maryland Regulations (COMAR) toxicity criteria. The DOT tests with OXONE decontaminated/neutralized VX showed this solution to be less than a Class B poison by all three routes of administration (rat oral, rat inhalation, and rabbit dermal) after only 24-hr aging and a nonhazardous material by COMAR toxicity criteria.... vx, Rat, Half-life, ED50, EA 2192, Rabbit, COMAR, Decontaminated/Neutralized, HTH, OXONE, LD50.

  19. TISSUE INTERACTIONS WITH DERMAL SHEEP COLLAGEN IMPLANTS - A TRANSMISSION ELECTRON-MICROSCOPIC EVALUATION

    NARCIS (Netherlands)

    VANWACHEM, PB; VANLUYN, MJA; DAMINK, LO; FEIJEN, J; NIEUWENHUIS, P

    1991-01-01

    Tissue interactions with discs of dermal sheep collagen (DSC), subcutaneously implanted in rats, were evaluated using transmission electron microscopy. DSC cross-linked with hexamethylenediisocyanate (HDSC) had already been tested previously. In the present study, we compared tissue interactions of

  20. The Effectiveness of Porcine Dermal Collagen (Permacol®) on Wound Healing in the Rat Model

    National Research Council Canada - National Science Library

    Kalin, Murat; Kuru, Serdar; Kismet, Kemal; Barlas, Aziz Mutlu; Akgun, Yusuf Akif; Astarci, Hesna Muzeyyen; Ustun, Huseyin; Ertas, Ertugrul

    2015-01-01

    Porcine acellular dermal collagen (PDC), which is a biological material derived from processing porcine dermis, has already been used for urologic, gynecologic, plastic, and general surgery procedures up to now...

  1. Influence of ethylene oxide gas treatment on the in vitro degradation behaviour of dermal sheep collagen

    NARCIS (Netherlands)

    Olde damink, L.H.H.; Olde Damink, L.H.H.; Dijkstra, Pieter J.; van Luyn, M.J.A.; van Wachem, P.B.; Nieuwenhuis, P.; Feijen, Jan

    1995-01-01

    The influence of ethylene oxide gas treatment on the in vitro degradation behavior of noncrosslinked, glutaraldehyde crosslinked or hexamethylene diisocyanate crosslinked dermal sheep collagen (DSC) using bacterial collagenase is described. The results obtained were compared with the degradation

  2. In vitro dermal absorption of decabromodiphenyl ethane in rat and human skin

    Data.gov (United States)

    U.S. Environmental Protection Agency — In vitro dermal absorption of decabromodiphenyl ethane in rat and human skin. This dataset is associated with the following publication: Knudsen, G., J.M. Sanders,...

  3. In vitro bioaccessibility of copper azole following simulated dermal transfer from pressure-treated wood

    Data.gov (United States)

    U.S. Environmental Protection Agency — In vitro bioaccessibility of copper azole following simulated dermal transfer from pressure-treated wood. This dataset is associated with the following publication:...

  4. Tissue immunostaining for factor XIIIa in dermal dendrocytes of pityriasis alba skin lesions

    National Research Council Canada - National Science Library

    Carneiro, Francisca Regina Oliveira; Amaral, Gabriela Borborema do; Mendes, Maiana Darwich; Quaresma, Juarez Antônio Simões

    2014-01-01

    .... However, its etiology remains uncertain. OBJECTIVE: The objective of the present study was to evaluate the immunoexpression of factor XIIIa in dermal dendrocytes of skin lesions of pityriasis alba. METHOD...

  5. Osteopathia striata: a characteristic X-ray finding in focal dermal hypoplasia (Goltz-Gorlin syndrome)

    Energy Technology Data Exchange (ETDEWEB)

    Barthels, W.; Boepple, D.; Petzel, H.

    1982-12-01

    Two cases of the very rare Goltz-Gorlin syndrome are presented. The relationship of osteopathia striata and focal dermal hypoplasia is discussed, and it is concluded that the osteopathia striata represents the characteristic picture of this ectopic mesodermal abnormality.

  6. Influence of ethylene oxide gas treatment on the in vitro degradation behavior of dermal sheep collagen

    NARCIS (Netherlands)

    Olde Damink, L.H.H.; Dijkstra, P.J.; Luyn, van M.J.A.; Wachem, van P.B.; Nieuwenhuis, P.; Feijen, J.

    1995-01-01

    The influence of ethylene oxide gas treatment on the in vitro degradation behavior of noncrosslinked, glutaraldehyde crosslinked or hexamethylene diisocyanate crosslinked dermal sheep collagen (DSC) using bacterial collagenase is described. The results obtained were compared with the degradation beh

  7. Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

    DEFF Research Database (Denmark)

    Grimbaldeston, Michele A; Skov, Lone; Finlay-Jones, John J;

    2002-01-01

    Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise......, display variations in dermal mast cell prevalence. In a study of Danish and South Australian BCC patients and control subjects, one 4-mm punch biopsy of non-sun-exposed buttock skin was sampled from each participant. This skin site was investigated to avoid any changes in mast cell prevalence caused...... dermal area (expressed as mast cells per square millimeter). This technique enabled us to detect heterogeneity of dermal mast cell prevalence in buttock skin between individuals and provided evidence of an association between high dermal mast cell prevalence and BCC development in two diverse populations...

  8. Functional trade-off between strength and thermal capacity of dermal armor: Insights from girdled lizards.

    Science.gov (United States)

    Broeckhoven, Chris; du Plessis, Anton; Hui, Cang

    2017-10-01

    The presence of dermal armor is often unambiguously considered the result of an evolutionary predator-prey arms-race. Recent studies focusing predominantly on osteoderms - mineralized elements embedded in the dermis layer of various extant and extinct vertebrates - have instead proposed that dermal armor might exhibit additional functionalities besides protection. Multiple divergent functionalities could impose conflicting demands on a phenotype, yet, functional trade-offs in dermal armor have rarely been investigated. Here, we use high-resolution micro-computed tomography and voxel-based simulations to test for a trade-off between the strength and thermal capacity of osteoderms using two armored cordylid lizards as model organisms. We demonstrate that high vascularization, associated with improved thermal capacity might limit the strength of osteoderms. These results call for a holistic, cautionary future approach to studies investigating dermal armor, especially those aiming to inspire artificial protective materials. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY IN MICE AFTER DERMAL AND INTRATRACHAEL (IT) EXPOSURES

    Science.gov (United States)

    ABSTRACT for 2001 DMS213TRIMELLITIC ANHYDRIDE (TMA) HYPERSENSITIVITY INMICE AFTER DERMAL AND INTRATRACHEAL (IT) EXPOSURES. E Boykin, M Ward, MJ Selgrade, and D Sailstad. NHEERL, ORD, US EPA, RTP, NC, USA.TMA causes respiratory hypersensitivity (RH) responses. W...

  10. A Fibrocontractive Mechanochemical Model of Dermal Wound Closure Incorporating Realistic Growth Factor Kinetics

    KAUST Repository

    Murphy, Kelly E.

    2012-01-13

    Fibroblasts and their activated phenotype, myofibroblasts, are the primary cell types involved in the contraction associated with dermal wound healing. Recent experimental evidence indicates that the transformation from fibroblasts to myofibroblasts involves two distinct processes: The cells are stimulated to change phenotype by the combined actions of transforming growth factor β (TGFβ) and mechanical tension. This observation indicates a need for a detailed exploration of the effect of the strong interactions between the mechanical changes and growth factors in dermal wound healing. We review the experimental findings in detail and develop a model of dermal wound healing that incorporates these phenomena. Our model includes the interactions between TGFβ and collagenase, providing a more biologically realistic form for the growth factor kinetics than those included in previous mechanochemical descriptions. A comparison is made between the model predictions and experimental data on human dermal wound healing and all the essential features are well matched. © 2012 Society for Mathematical Biology.

  11. Bovine versus Porcine Acellular Dermal Matrix: A Comparison of Mechanical Properties

    Directory of Open Access Journals (Sweden)

    David M. Adelman, MD, PhD, FACS

    2014-05-01

    Conclusions: Before implantation, BADM is inherently stronger than PADM at equivalent thicknesses and considerably stronger at increased thicknesses. These results corroborate clinical data from a previous study in which PADM was associated with a higher intraoperative device failure rate. Although numerous properties of acellular dermal matrix contribute to clinical outcomes, surgeons should consider initial mechanical strength properties when choosing acellular dermal matrices for load-bearing applications such as hernia repair.

  12. Laser-induced transepidermal elimination of dermal content by fractional photothermolysis.

    Science.gov (United States)

    Hantash, Basil M; Bedi, Vikramaditya P; Sudireddy, Vasanthi; Struck, Steven K; Herron, G Scott; Chan, Kin Foong

    2006-01-01

    The wound healing process in skin is studied in human subjects treated with fractional photothermolysis. In-vivo histological evaluation of vacuoles formed over microthermal zones (MTZs) and their content is undertaken. A 30-W, 1550-nm single-mode fiber laser system delivers an array of 60 microm or 140 microm 1e2 incidence microbeam spot size at variable pulse energy and density. Treatments span from 6 to 20 mJ with skin excisions performed 1-day post-treatment. Staining with hematoxylin and eosin demonstrates an intact stratum corneum with vacuolar formation within the epidermis. The re-epithelialization process with repopulation of melanocytes and keratinocytes at the basal layer is apparent by 1-day post-treatment. The dermal-epidermal (DE) junction is weakened and separated just above zones of dermal coagulation. Complete loss of dermal cell viability is noted within the confines of the MTZs 1-day post-treatment, as assessed by lactate dehydrogenase. All cells falling outside the irradiation field remain viable. Content within the epidermal vacuoles stain positively with Gomori trichrome, suggesting a dermal origin. However, the positive staining could be due to loss of specificity after thermal alteration. Nevertheless, this dermal extrusion hypothesis is supported by very specific positive staining with an antihuman elastin antibody. Fractional photothermolysis creates microthermal lesions that allow transport and extrusion of dermal content through a compromised DE junction. Some dermal material is incorporated into the microepidermal necrotic debris and shuttled up the epidermis to eventually be exfoliated through the stratum corneum. This is the first report of a nonablative laser-induced transport mechanism by which dermal content can be predictably extruded biologically through the epidermis. Thus, treatment with the 1550-nm fiber laser may provide the first therapeutic option for clinical indications, including pigmentary disorders such as medically

  13. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    OpenAIRE

    Quan, Taihao; Fisher, Gary J.

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin d...

  14. Tissue immunostaining for factor XIIIa in dermal dendrocytes of pityriasis alba skin lesions

    OpenAIRE

    Carneiro, Francisca Regina Oliveira; Amaral,Gabriela Borborema do; Mendes,Maiana Darwich; Quaresma,Juarez Antônio Simões

    2014-01-01

    BACKGROUND: Pityriasis alba affects 1% of the world population and about 9.9% of the children in Brazil. However, its etiology remains uncertain. OBJECTIVE: The objective of the present study was to evaluate the immunoexpression of factor XIIIa in dermal dendrocytes of skin lesions of pityriasis alba. METHOD: Twenty patients with pityriasis alba and 20 patients with atopic dermatitis underwent biopsy. The dermal dendrocytes marked by factor XIIIa were counted by means of immunohistochemic...

  15. Hyaluronic acid dermal fillers: can adjunctive lidocaine improve patient satisfaction without decreasing efficacy or duration?

    OpenAIRE

    Lynnelle Smith; Kimberly Cockerham

    2011-01-01

    Lynnelle Smith1, Kimberly Cockerham21Ophthalmology Department, Loma Linda University, Loma Linda, CA, USA; 2Ophthalmology Department, Stanford University, Palo Alto, CA, USAAbstract: Hyaluronic acid (HA) dermal fillers are the most widely used injectables to augment facial volume without surgery. HA dermal fillers are popular because of their ease of administration, predictable effectiveness, good safety profile, and quick patient recovery. The most common patient complaint is pain. Our goal ...

  16. Characterization and evolution of dermal filaments from patients with Morgellons disease

    OpenAIRE

    Middelveen MJ; Mayne PJ; Kahn DG; Stricker RB

    2013-01-01

    Marianne J Middelveen,1 Peter J Mayne,1 Douglas G Kahn,2 Raphael B Stricker11International Lyme and Associated Diseases Society, Bethesda, MD, USA; 2Department of Pathology, Olive View–UCLA Medical Center, Sylmar, CA, USAAbstract: Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either s...

  17. Metabolism of pesticides after dermal exposure to amphibians

    Science.gov (United States)

    Understanding how pesticide exposure to non-target species influences toxicity is necessary to accurately assess the ecological risks these compounds pose. Aquatic, terrestrial, and arboreal amphibians are often exposed to pesticides during their agricultural application resultin...

  18. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  19. Nifty Nines and Repeating Decimals

    Science.gov (United States)

    Brown, Scott A.

    2016-01-01

    The traditional technique for converting repeating decimals to common fractions can be found in nearly every algebra textbook that has been published, as well as in many precalculus texts. However, students generally encounter repeating decimal numerals earlier than high school when they study rational numbers in prealgebra classes. Therefore, how…

  20. All-photonic quantum repeaters

    Science.gov (United States)

    Azuma, Koji; Tamaki, Kiyoshi; Lo, Hoi-Kwong

    2015-01-01

    Quantum communication holds promise for unconditionally secure transmission of secret messages and faithful transfer of unknown quantum states. Photons appear to be the medium of choice for quantum communication. Owing to photon losses, robust quantum communication over long lossy channels requires quantum repeaters. It is widely believed that a necessary and highly demanding requirement for quantum repeaters is the existence of matter quantum memories. Here we show that such a requirement is, in fact, unnecessary by introducing the concept of all-photonic quantum repeaters based on flying qubits. In particular, we present a protocol based on photonic cluster-state machine guns and a loss-tolerant measurement equipped with local high-speed active feedforwards. We show that, with such all-photonic quantum repeaters, the communication efficiency scales polynomially with the channel distance. Our result paves a new route towards quantum repeaters with efficient single-photon sources rather than matter quantum memories. PMID:25873153

  1. The determinants of dermal exposure ranking method (DERM): a pesticide exposure assessment approach for developing countries.

    Science.gov (United States)

    Blanco, Luis E; Aragón, Aurora; Lundberg, Ingvar; Wesseling, Catharina; Nise, Gun

    2008-08-01

    A new method for assessment of dermal exposure to pesticides in subsistence farmers by use of determinants of dermal exposure is described. The method, called the determinants of dermal exposure ranking method (DERM), is a combination of checklists and expert rating assessment. Thus, determinants are listed in a form, which is used to check their presence and to assess them using a simple algorithm based on two factors, the type of transport process (T value) and the area of body surface exposed (A value). In addition, the type of clothing worn during applications is included as a protection factor. We applied the DERM to real pesticide applications, characterizing dermal exposure and comparing DERM estimates with earlier developed semiquantitative visual scores based on fluorescent tracer, the total visual score (TVS) and contaminated body area (CBA). DERM showed a very good level of agreement with both the TVS (r = 0.69; P = 0.000) and the CBA (r = 0.67; P = 0.000). DERM allowed identification of the determinants that had the highest effect on exposure and the farmers with the highest exposure. In conclusion, DERM provided information on the determinants responsible for dermal exposure in a group of subsistence farmers. This can be useful to design monitoring and preventive programs, define priorities for intervention and prioritize and select most adequate measurement strategies. DERM promises to be a low-cost easy-to-use method to assess dermal exposure to pesticides in developing country conditions.

  2. Collagen/chitosan based two-compartment and bi-functional dermal scaffolds for skin regeneration

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Feng [Department of Plastic Surgery and Burns, Shenzhen Second People' s Hospital, Shenzhen 518035 (China); Wang, Mingbo [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); She, Zhending [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shenzhen Lando Biomaterials Co., Ltd., Shenzhen 518057 (China); Fan, Kunwu; Xu, Cheng [Department of Plastic Surgery and Burns, Shenzhen Second People' s Hospital, Shenzhen 518035 (China); Chu, Bin; Chen, Changsheng [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shi, Shengjun, E-mail: shengjunshi@yahoo.com [The Burns Department of Zhujiang Hospital, Southern Medical University, Guangzhou 510280 (China); Tan, Rongwei, E-mail: tanrw@landobiom.com [Key Laboratory of Biomedical Materials and Implants, Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057 (China); Shenzhen Lando Biomaterials Co., Ltd., Shenzhen 518057 (China)

    2015-07-01

    Inspired from the sophisticated bilayer structures of natural dermis, here, we reported collagen/chitosan based two-compartment and bi-functional dermal scaffolds. Two functions refer to mediating rapid angiogenesis based on recombinant human vascular endothelial growth factor (rhVEGF) and antibacterial from gentamicin, which were encapsulated in PLGA microspheres. The gentamicin and rhVEGF encapsulated PLGA microspheres were further combined with collagen/chitosan mixtures in low (lower layer) and high (upper layer) concentrations, and molded to generate the two-compartment and bi-functional scaffolds. Based on morphology and pore structure analyses, it was found that the scaffold has a distinct double layered porous and connective structure with PLGA microspheres encapsulated. Statistical analysis indicated that the pores in the upper layer and in the lower layer have great variations in diameter, indicative of a two-compartment structure. The release profiles of gentamicin and rhVEGF exceeded 28 and 49 days, respectively. In vitro culture of mouse fibroblasts showed that the scaffold can facilitate cell adhesion and proliferation. Moreover, the scaffold can obviously inhibit proliferation of Staphylococcus aureus and Serratia marcescens, exhibiting its unique antibacterial effect. The two-compartment and bi-functional dermal scaffolds can be a promising candidate for skin regeneration. - Highlights: • The dermal scaffold is inspired from the bilayer structures of natural dermis. • The dermal scaffold has two-compartment structures. • The dermal scaffold containing VEGF and gentamicin encapsulated PLGA microspheres • The dermal scaffold can facilitate cell adhesion and proliferation.

  3. Optical coherence tomography for image-guided dermal filler injection and biomechanical evaluation

    Science.gov (United States)

    Singh, Manmohan; Wang, Shang; Yee, Richard W.; Han, Zhaolong; Aglyamov, Salavat R.; Larin, Kirill V.

    2017-02-01

    Dermal fillers are a very popular anti-ag ing treatment with estimated sales in the billions of dollars and millions of procedures performed. As the aging population continues to grow, these figures are only e xpected to increase. Dermal fillers have various compositions depending on their intended applicati on. Reactions to dermal fillers can be severe, such as ischemic events and filler migration to the eyes. Howe ver, these adverse reactions are rare. Nevertheless, the capability to perform imag e-guided filler injections would minimize th e risk of such reacti ons. In addition, the biomechanical properties of various fillers have been evalua ted, but there has been no investigation on the effects of filler on the biomechanical properties of skin. In this work, we utilize optical cohe rence tomography (OCT) for visualizing dermal filler injections with micrometer-scale sp atial resolution. In addition, we utilize noncontact optical coherence elastography (OCE) to quantify the changes in the biomechan ical properties of pig skin after the dermal filler injections. OCT was successfully able to visualize the dermal filler injecti on process, and OCE showed that the viscoelasticity of the pig skin was increased locally at the filler injection sites. OCT may be able to provide real-time image guidance in 3D, and when combined with functional OCT techniques such as optical microangiography, could be used to avoid blood vessels during the injection.

  4. Characterization of dermal plates from armored catfish Pterygoplichthys pardalis reveals sandwich-like nanocomposite structure.

    Science.gov (United States)

    Ebenstein, Donna; Calderon, Carlos; Troncoso, Omar P; Torres, Fernando G

    2015-05-01

    Dermal plates from armored catfish are bony structures that cover their body. In this paper we characterized structural, chemical, and nanomechanical properties of the dermal plates from the Amazonian fish Pterygoplichthys pardalis. Analysis of the morphology of the plates using scanning electron microscopy (SEM) revealed that the dermal plates have a sandwich-like structure composed of an inner porous matrix surrounded by two external dense layers. This is different from the plywood-like laminated structure of elasmoid fish scales but similar to the structure of osteoderms found in the dermal armour of some reptiles and mammals. Chemical analysis performed using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results revealed similarities between the composition of P. pardalis plates and the elasmoid fish scales of Arapaima gigas. Reduced moduli of P. pardalis plates measured using nanoindentation were also consistent with reported values for A. gigas scales, but further revealed that the dermal plate is an anisotropic and heterogeneous material, similar to many other fish scales and osteoderms. It is postulated that the sandwich-like structure of the dermal plates provides a lightweight and tough protective layer.

  5. The application of dermal papillary rings in dermatology by in vivo confocal laser scanning microscopy

    Science.gov (United States)

    Xiang, W. Z.; Xu, A. E.; Xu, J.; Bi, Z. G.; Shang, Y. B.; Ren, Q. S.

    2010-08-01

    Confocal laser scanning microscopy (CLSM) allows noninvasive visualization of human skin in vivo, without needing to fix or section the tissue. Melanocytes and pigmented keratinocytes at the level of the basal layer form bright dermal papillary rings which are readily amenable to identify in confocal images. Our purpose was to explore the role of dermal papillary rings in assessment of lesion location, the diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. Seventy-one patients were imaged with the VivaScope 1500 reflectance confocal microscope provided by Lucid, Inc. The results indicate that dermal papillary rings can assess the location of lesion; the application of dermal papillary rings can provide diagnostic support and differential diagnosis for vitiligo, nevus depigmentosus, tinea versicolor, halo nevus, common nevi, and assess the therapeutic efficacy of NBUVB phototherapy plus topical 0.1 percent tacrolimus ointment for vitiligo. In conclusion, our findings indicate that the dermal papillary rings play an important role in the assessment the location of lesion, diagnosis, differential diagnosis of lesions and assessment of therapeutic efficacy by in vivo CLSM. CLSM may be a promising tool for noninvasive examination in dermatology. However, larger studies are needed to expand the application of dermal papillary rings in dermatology.

  6. Sexual dimorphisms in the dermal denticles of the lesser-spotted catshark, Scyliorhinus canicula (Linnaeus, 1758.

    Directory of Open Access Journals (Sweden)

    Neil Crooks

    Full Text Available The dermal layers of several elasmobranch species have been shown to be sexually dimorphic. Generally, when this occurs the females have thicker dermal layers compared to those of males. This sexual dimorphism has been suggested to occur as a response to male biting during mating. Although male biting as a copulatory behaviour in Scyliorhinus canicula has been widely speculated to occur, only relatively recently has this behaviour been observed. Male S. canicula use their mouths to bite the female's pectoral and caudal fins as part of their pre-copulatory behaviour and to grasp females during copulation. Previous work has shown that female S. canicula have a thicker epidermis compared to that of males. The structure of the dermal denticles in females may also differ from that of males in order to protect against male biting or to provide a greater degree of friction in order to allow the male more purchase. This study reveals that the length, width and density of the dermal denticles of mature male and female S. canicula are sexually dimorphic across the integument in areas where males have been observed to bite and wrap themselves around females (pectoral fin, area posterior to the pectoral fin, caudal fin, and pelvic girdle. No significant differences in the dermal denticle dimensions were found in other body areas examined (head, dorsal skin and caudal peduncle. Sexually dimorphic dermal denticles in mature S. canicula could be a response to male biting/wrapping as part of the copulatory process.

  7. Human toxicity potentials for life-cycle assessment and toxics release inventory risk screening.

    Science.gov (United States)

    Hertwich, E G; Mateles, S F; Pease, W S; McKone, T E

    2001-04-01

    The human toxicity potential (HTP), a calculated index that reflects the potential harm of a unit of chemical released into the environment, is based on both the inherent toxicity of a compound and its potential dose. It is used to weight emissions inventoried as part of a life-cycle assessment (LCA) or in the toxics release inventory (TRI) and to aggregate emissions in terms of a reference compound. Total emissions can be evaluated in terms of benzene equivalence (carcinogens) and toluene equivalents (noncarcinogens). The potential dose is calculated using a generic fate and exposure model, CalTOX, which determines the distribution of a chemical in a model environment and accounts for a number of exposure routes, including inhalation, ingestion of produce, fish, and meat, and dermal contact with water and soil. Toxicity is represented by the cancer potency q1* for carcinogens and the safe dose (RfD, RfC) for noncarcinogens. This article presents cancer and noncancer HTP values for air and surface-water emissions of 330 compounds. This list covers 258 chemicals listed in U.S. Environmental Protection Agency TRI, or 79 weight-% of the TRI releases to air reported in 1997.

  8. An evaluation of acute toxicity of colloidal silver nanoparticles.

    Science.gov (United States)

    Maneewattanapinyo, Pattwat; Banlunara, Wijit; Thammacharoen, Chuchaat; Ekgasit, Sanong; Kaewamatawong, Theerayuth

    2011-11-01

    Tests for acute oral toxicity, eye irritation, corrosion and dermal toxicity of colloidal silver nanoparticles (AgNPs) were conducted in laboratory animals following OECD guidelines. Oral administration of AgNPs at a limited dose of 5,000 mg/kg produced neither mortality nor acute toxic signs throughout the observation period. Percentage of body weight gain of the mice showed no significant difference between control and treatment groups. In the hematological analysis, there was no significant difference between mice treated with AgNPs and controls. Blood chemistry analysis also showed no differences in any of the parameter examined. There was neither any gross lesion nor histopathological change observed in various organs. The results indicated that the LD(50) of colloidal AgNPs is greater than 5,000 mg/kg body weight. In acute eye irritation and corrosion study, no mortality and toxic signs were observed when various doses of colloidal AgNPs were instilled in guinea pig eyes during 72 hr observation period. However, the instillation of AgNPs at 5,000 ppm produced transient eye irritation during early 24 hr observation time. No any gross abnormality was noted in the skins of the guinea pigs exposed to various doses of colloidal AgNPs. In addition, no significant AgNPs exposure relating to dermal tissue changes was observed microscopically. In summary, these findings of all toxicity tests in this study suggest that colloidal AgNPs could be relatively safe when administered to oral, eye and skin of the animal models for short periods of time.

  9. HYALURONIC ACID IN DERMAL REJUVENATION: AN IN VITRO STUDY.

    Science.gov (United States)

    Avantaggiato, A; Pascali, M; Lauritano, D; Cura, F; Pezzetti, F; Palmieri, A

    2015-01-01

    The purpose of this paper is to evaluate the role of hyaluronic acid in bio-revitalization by testing several extracellular matrix biological parameters in cultured dermal fibroblasts. To this aim, fibroblastic expressed genes after exposition to three hyaluronic acid medical devices were evaluated. Cells were seeded on a layer of three different medical devices containing 6.2, 10 and 20 mg/ml of hyaluronic acid for 24 h. Real Time Polymerase Chain Reaction was performed to investigate gene expressions. Genes encoding hyaluronic acid synthesis and degradation, Metalloproteinases 2 and 3 and Desmoplakin production as well as GDF6, and IGF1 were activated by hyaluronic acid products. The in vitro study showed similar effects on tested genes despite a different concentration of hyaluronic acid contained in the medical devices and the simultaneous presence of other additives. Based on the reported data, gene activations are an aspect of metabolic modulation of signalling pathways rather than the proportional production of a specific connective tissue molecule. Indeed different hyaluronic acid concentration and the presence of other additives did not change the overall effect on the studied genes. We believe that the optimization of extracellular matrix micro-environment, obtained by enhanced structural support with hyaluronic acid, leads to functional and metabolic improvement.

  10. Inheritance of hereditary equine regional dermal asthenia in Quarter Horses.

    Science.gov (United States)

    Tryon, Robert C; White, Stephen D; Famula, Thomas R; Schultheiss, Patricia C; Hamar, Dwayne W; Bannasch, Danika L

    2005-03-01

    To assess heritability and mode of inheritance for hereditary equine regional dermal asthenia (HERDA) in Quarter Horses. 1,295 horses with Quarter Horse bloodlines, including 58 horses affected with HERDA. Horses were classified as affected or unaffected or as undetermined when data were insufficient to assess phenotype. Pedigree data were analyzed to determine the probable mode of inheritance. Heritability was estimated by use of Bayesian statistical methods. Heritability (mean+/-SD) of HERDA was estimated to be 0.38+/-0.13, with both sexes having an equal probability of being affected. Results for evaluation of the pedigrees were consistent with a single Mendelian autosomal recessive mode of inheritance. HERDA in Quarter Horses is an inherited disease, and affected horses are more likely to produce affected offspring. An autosomal recessive mode of inheritance should be considered by people making breeding decisions involving Quarter Horses when a first-degree relative has been confirmed with HERDA or has produced affected offspring. In addition, breeders whose horses have produced affected offspring can reduce the likelihood of producing affected horses in the future by avoiding inbreeding.

  11. Evaluation of dermal symptoms in hypothyroidism and hyperthyroidism.

    Science.gov (United States)

    Razi, Ahad; Golforoushan, Farideh; Nejad, Amir Bahrami Shahla Babaee; Goldust, Mohamad

    2013-06-01

    Many symptoms arise in thyroid diseases. The aim of this study was to evaluate the dermal symptoms in hypothyroidism and hyperthyroidism. In this cross sectional study, 120 patients with hyperthyroidism and 50 patients suffering from hypothyroidism were studied. Cutaneous, hair and nail clinical symptoms were studied and registered in a special questionnaire. Mean age of patients suffering from hypothyroidism and hyperthyroidism were 38.24 +/- 14.45 and 25.86 +/- 14.69 years old. Dry and Coarse/rough skin were the most prevalent manifestations in the skin involvement in hypothyroidism since softness was the most prevalent ones in hyperthyroidism. Fragileness was the most prevalent symptom in patients with nail involvement in hypothyroidism since soft skin was the most prevalent ones in hyperthyroidism. Coarse/rough skin was observed more in patients with hair involvement in hypothyroidism since the most prevalent ones was separation of nail from its bed in hyperthyroidism. High prevalence of skin, hair and nail symptoms in thyroid patients, early diagnosis of the signs may be helpful in premature diagnosis and treatment of thyroid diseases.

  12. Optical coherence tomography: imaging architect for dermal microdialysis in psoriasis

    Science.gov (United States)

    O'Connell, M.-L.; O'Connor, W.; Ramsay, B.; Guihen, E.; Ho, W. L.; Leahy, M. J.

    2011-03-01

    Optical coherence tomography (OCT) has been used as part of a ground breaking translational study to shed some light on one of the worlds most prevalent autoimmune diseases; psoriasis. The work successfully integrates the fields of optical imaging, biochemistry and dermatology in conducting a dermal microdialysis (DMD) trial for quantitative histamine assessment amongst a group of psoriasis sufferers. The DMD process involves temporary insertion of microscopic hollow tubes into a layer of skin to measure the levels of histamine and other important biological molecules in psoriasis. For comparison purposes, DMD catheters were implanted into healthy, peri-lesional and lesional skin regions. The catheters' entry and exit points and their precise locations in the epidermal layer of the skin were confirmed using OCT thus obtaining high resolution, wide-field images of the affected skin as well as catheter placement whilst local microdialysis enabled a tissue chemistry profile to be obtained from these three skin regions including histamine, a local immune system activator known to contribute towards itch and inflammation. Together these tools offer a synergistic approach in the clinical assessment of the disease. In addition, OCT delivered a non-invasive and rapid method for analyzing the affected skin architecture.

  13. Oral phenotype and variation in focal dermal hypoplasia.

    Science.gov (United States)

    Wright, John Timothy; Puranik, Chaitanya P; Farrington, Frank

    2016-03-01

    Focal dermal hypoplasia (FDH) or Goltz Syndrome (OMIM# 305600) is an X-linked dominant ectodermal dysplasia caused by mutations in the PORCN gene. This gene encodes an endoplasmic reticulum transmembrane protein that is involved in processing the embryonically critical WNT signaling proteins. Individuals diagnosed with FDH were recruited to participate in the study through the National Foundation for Ectodermal Dysplasia. Individuals were evaluated to characterize the FDH phenotype. Each participant completed a brief dental survey and oral evaluation using artificial light. To identify the oral soft and hard tissue findings 19 individuals (16 female and 3 male) participated with a median age of 10 years (range 2-56 years). Soft and hard tissue defects were present in 68% (13) and 94% (18) of the patients, respectively. Dental anomalies were highly prevalent with 68% (13) demonstrating vertical enamel grooving, 52% (10) having peg shaped tooth deformities, and 78% (15) having enamel hypoplasia with or without discoloration. Cleft lip and cleft palate presented in 15% (3) of the participants. Other findings included 57% (11) having intra-oral lipoma or papilloma with no site predilection. Dental malocclusions were common with 63% (12) having some degree of malocclusion with 15% (3) of participants having class III malocclusion with an anterior dental cross bite. Participants frequently reported speech problems or difficulty with chewing (73%; N = 14). This study shows there is marked variation in the oral phenotype of individuals with FDH and underscores the important role of WNT signaling in oro-facial development.

  14. Misdiagnosis and Mistreatment of Post-Kala-Azar Dermal Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Ahmed Mohamed El Hassan

    2013-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is a known complication of visceral leishmaniasis (VL caused by L. donovani. It is rare in VL caused by L. infantum and L. chagasi. In Sudan, it occurs with a frequency of 58% among successfully treated VL patients. In the majority of cases, PKDL can be diagnosed on the basis of clinical appearance, distribution of the lesions, and past history of treated VL. The ideal diagnostic method is to demonstrate the parasite in smears, by culture or PCR. Diagnosis is particularly difficult in patients who develop PKDL in the absence of previous history of visceral leishmaniasis. We describe a case of cutaneous leishmaniasis misdiagnosed as PKDL and 3 cases of PKDL who were either misdiagnosed or mistreated as other dermatoses. This caused exacerbation of their disease leading to high parasite loads in the lesions and dissemination to internal organs in one of the patients, who was also diabetic. The latter patient had L. major infection. A fourth patient with papulonodular lesions on the face and arms of 17-year duration and who was misdiagnosed as having PKDL is also described. He turned out to have cutaneous leishmaniasis due to L. major. Fortunately, he was not treated with steroids. He was cured with intravenous sodium stibogluconate.

  15. Verification of somatic CAG repeat expansion by pre-PCR fractionation.

    Science.gov (United States)

    Hunter, Jesse M; Crouse, Andrew B; Lesort, Mathieu; Johnson, Gail V W; Detloff, Peter J

    2005-05-15

    The inheritance of a long CAG repeat causes several late onset neurological disorders including Huntington's disease (HD). Longer CAG repeats correlate with earlier onset of HD suggesting an increased toxicity for the products of long repeat alleles. PCR based data has been used to show that HD CAG repeat expansion beyond the inherited length occurs in affected tissues indicating a possible role for somatic instability in the disease process. PCR, however, is prone to artifacts resulting from expansion of repeat sequences during amplification. We describe a method to distinguish between CAG repeat expansions that exist in vivo and those that potentially occur during PCR. The method involves size fractionation of genomic restriction fragments containing the expanded repeats followed by PCR amplification. The application of this method confirms the presence of somatic expansions in the brains of a knock-in mouse model of HD.

  16. Toxic Amblyopia (Nutritional Amblyopia)

    Science.gov (United States)

    ... Finds Additional Content Medical News Toxic Amblyopia (Nutritional Amblyopia) By James Garrity, MD, Whitney and Betty MacMillan ... Neuropathies) Ischemic Optic Neuropathy Optic Neuritis Papilledema Toxic Amblyopia Toxic amblyopia is damage to the optic nerve ...

  17. Acute and 28-day repeated oral toxicological evaluation of Kuruthi Azhal Chooranam – a Siddha preparation on rodents

    OpenAIRE

    Marimuthu Kannadasana; Ganesan Sumathy; Palanivel Thirusangu Sangeetha; Chidambaram Saravanababu; Kathirvelu Baskar

    2016-01-01

    Objective: To determine the effect of phytochemicals in acute and repeated dose of 28-day oral toxicity of Kuruthi Azhal Chooranam (KAC) in Sprague Dawley rats of both sexes. Methods: Acute oral toxicity was conducted with 2000 mg/kg body weight of KAC orally and the treated animals were observed for signs of toxicity at 30 min, 1, 2, 4 and 24 h and for up to 14 days. In repeated 28-day oral toxicity study, the KAC formulation was administered orally with 600, 900 and 1200 mg/k...

  18. Epidermal vascular endothelial growth factor production is required for permeability barrier homeostasis, dermal angiogenesis, and the development of epidermal hyperplasia: implications for the pathogenesis of psoriasis.

    Science.gov (United States)

    Elias, Peter M; Arbiser, Jack; Brown, Barbara E; Rossiter, Heidemarie; Man, Mao-Qiang; Cerimele, Francesca; Crumrine, Debra; Gunathilake, Roshan; Choi, Eung Ho; Uchida, Yoshikazu; Tschachler, Erwin; Feingold, Kenneth R

    2008-09-01

    Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf(-/-) mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis.

  19. Dermal dendritic cells” comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages

    OpenAIRE

    Ochoa,Maria Teresa; Loncaric, Anya; Krutzik, Stephan R.; Becker, Todd C.; Modlin, Robert L.

    2008-01-01

    A key cell type of the resident skin immune system is the dendritic cell, which in normal skin is located in two distinct microanatomical compartments: Langerhans cells (LC) mainly in the epidermis and dermal dendritic cells (DDC) in the dermis. Here, the lineage of dermal dendritic cells was investigated using monoclonal antibodies and immunohistology. We provide evidence that “dermal dendritic cells” comprise at least two major phenotypic populations of dendritic appearing cells: immature D...

  20. Analysis of repeated measures data

    CERN Document Server

    Islam, M Ataharul

    2017-01-01

    This book presents a broad range of statistical techniques to address emerging needs in the field of repeated measures. It also provides a comprehensive overview of extensions of generalized linear models for the bivariate exponential family of distributions, which represent a new development in analysing repeated measures data. The demand for statistical models for correlated outcomes has grown rapidly recently, mainly due to presence of two types of underlying associations: associations between outcomes, and associations between explanatory variables and outcomes. The book systematically addresses key problems arising in the modelling of repeated measures data, bearing in mind those factors that play a major role in estimating the underlying relationships between covariates and outcome variables for correlated outcome data. In addition, it presents new approaches to addressing current challenges in the field of repeated measures and models based on conditional and joint probabilities. Markov models of first...

  1. Optimal Concentrations and Synergistic Effects of Some Herbal Extracts on Viability of Dermal Fibroblasts

    Directory of Open Access Journals (Sweden)

    Zandi

    2016-08-01

    Full Text Available Background Many studies examine the antibacterial effects of medicinal plants; however, little research is done to evaluate their effects on different cell types, especially dermal fibroblasts. Objectives The current study aimed to study the effect of different concentrations of Aloe Vera, henna, chamomile, myrtle, mint, licorice, cinnamon, ginger and cedar extracts and their synergistic effects on the viability of dermal fibroblasts. Methods To evaluate the performance of herbal extracts on dermal fibroblasts, in the first experiment different concentrations (6.25, 12.5, 25, 50, 100, 250, 500 and 1000 µg/mL of the extracts were evaluated by the MTT cell proliferation assay. In the second experiment, the minimum effective concentrations of the plant extracts in triple combination were evaluated in the cells under study. Results The minimum effective concentrations of henna, chamomile, myrtle, mint, cinnamon, ginger and cedar were 12.5, 6.25, 6.25, 6.25, 6.25, 12.5 and 12.5µg/mL, respectively. Results showed that, by comparing the minimum effective concentration of herbal extracts, the viability of dermal fibroblasts significantly increased by cedar extract (P < 0.05. Combination of Aloe Vera, licorice and mint extracts significantly increased the viability of dermal fibroblasts (P < 0.05. Conclusions Based on the results of the current study, it was concluded that Aloe vera, licorice and mint extracts had synergistic effects on the viability of dermal fibroblasts; in addition, the combination of Aloe vera and licorice with either henna or myrtle, and Aloe vera and mint with either cedar or ginger resulted in synergistic effects on viability of dermal fibroblasts. The third category of triple combinations of herbal extracts with synergistic effects on the cells under study was the combination of Aloe Vera and mint with either chamomile or cinnamon and also Aloe vera and licorice with either myrtle or cedar.

  2. Dermal penetration of [14C]captan in young and adult rats.

    Science.gov (United States)

    Fisher, H L; Hall, L L; Sumler, M R; Shah, P V

    1992-07-01

    Age dependence in dermal absorption has been a major concern in risk assessment. Captan, a chloroalkyl thio heterocyclic fungicide, was selected for study of age dependence as representative of this class of pesticides. Dermal penetration of [14C]captan applied at 0.286 mumol/cm2 was determined in young (33-d-old) and adult (82-d-old) female Fischer 344 rats in vivo and by two in vitro methods. Dermal penetration in vivo at 72 h was about 9% of the recovered dose in both young and adult rats. The percentage penetration was found to increase as dosage (0.1, 0.5, 2.7 mumol/cm2) decreased. Two in vitro methods gave variable dermal penetration values compared with in vivo results. A static system yielded twofold higher dermal penetration values compared with in vivo results for both young and adult rats. A flow system yielded higher dermal penetration values in young rats and lower penetration values in adults compared with in vivo results. Concentration in body, kidney, and liver was less in young than in adult rats given the same absorbed dosage. A physiological pharmacokinetic model was developed having a dual compartment for the treated skin and appeared to describe dermal absorption and disposition well. From this model, tissue/blood ratios of captan-derived radioactivity for organs were found to range from 0.35 to 3.4, indicating no large uptake or binding preferences by any organ. This preliminary pharmacokinetic model summarizes the experimental findings and could provide impetus for more complex and realistic models.

  3. Interaction of New-Developed TiO2-Based Photocatalytic Nanoparticles with Pathogenic Microorganisms and Human Dermal and Pulmonary Fibroblasts

    Science.gov (United States)

    Nica, Ionela Cristina; Stan, Miruna Silvia; Popa, Marcela; Chifiriuc, Mariana Carmen; Lazar, Veronica; Pircalabioru, Gratiela G.; Dumitrescu, Iuliana; Ignat, Madalina; Feder, Marcel; Tanase, Liviu Cristian; Mercioniu, Ionel; Diamandescu, Lucian; Dinischiotu, Anca

    2017-01-01

    TiO2-based photocatalysts were obtained during previous years in order to limit pollution and to ease human daily living conditions due to their special properties. However, obtaining biocompatible photocatalysts is still a key problem, and the mechanism of their toxicity recently received increased attention. Two types of TiO2 nanoparticles co-doped with 1% of iron and nitrogen (TiO2-1% Fe–N) atoms were synthesized in hydrothermal conditions at pH of 8.5 (HT1) and 5.5 (HT2), and their antimicrobial activity and cytotoxic effects exerted on human pulmonary and dermal fibroblasts were assessed. These particles exhibited significant microbicidal and anti-biofilm activity, suggesting their potential application for microbial decontamination of different environments. In addition, our results demonstrated the biocompatibility of TiO2-1% Fe–N nanoparticles at low doses on lung and dermal cells, which may initiate oxidative stress through dose accumulation. Although no significant changes were observed between the two tested photocatalysts, the biological response was cell type specific and time- and dose-dependent; the lung cells proved to be more sensitive to nanoparticle exposure. Taken together, these experimental data provide useful information for future photocatalytic applications in the industrial, food, pharmaceutical, and medical fields. PMID:28125053

  4. Distributed Structure Searchable Toxicity

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Distributed Structure Searchable Toxicity (DSSTox) online resource provides high quality chemical structures and annotations in association with toxicity data....

  5. Salicylate Toxicity from Genital Exposure to a Methylsalicylate-Containing Rubefacient

    Directory of Open Access Journals (Sweden)

    Trevonne M. Thompson, MD

    2016-03-01

    Full Text Available Methylsalicylate-containing rubefacients have been reported to cause salicylate poisoning after ingestion, topical application to abnormal skin, and inappropriate topical application to normal skin. Many over-the-counter products contain methylsalicylate. Topical salicylates rarely produce systemic toxicity when used appropriately; however, methylsaliclyate can be absorbed through intact skin. Scrotal skin can have up to 40-fold greater absorption compared to other dermal regions. We report a unique case of salicylate poisoning resulting from the use of a methylsalicylate-containing rubefacient to facilitate masturbation in a male teenager. Saliclyate toxicity has not previously been reported from the genital exposure to methylsaliclyate.

  6. In vitro dermal absorption rate testing of certain chemicals of interest to the Occupational Safety and Health Administration: summary and evaluation of USEPA's mandated testing.

    Science.gov (United States)

    Fasano, William J; McDougal, James N

    2008-07-01

    water or neat, respectively, were comparable to measured values at both 10 and 60min. Kp data for chemicals applied in water and the flux values for neat chemicals will be useful for making estimates of skin absorption in occupational settings. Kp measurements for chemicals applied in IPM vehicle are not envisioned to provide useful data for estimating the risk from dermal exposure to chemicals in the workplace. When available, in vitro dermal flux measurements should be combined with toxicity information in order to improve the utility of chemical skin notations.

  7. Effects of dihydrotestosterone on rat dermal papilla cells in vitro.

    Science.gov (United States)

    Kang, Jung-Il; Kim, Sang-Cheol; Kim, Min-Kyoung; Boo, Hye-Jin; Kim, Eun-Ji; Im, Guang-Jin; Kim, Young Ho; Hyun, Jin-Won; Kang, Ji-Hoon; Koh, Young-Sang; Park, Deok-Bae; Yoo, Eun-Sook; Kang, Hee-Kyoung

    2015-06-15

    Androgenetic alopecia involves the action of dihydrotestosterone (DHT) on dermal papilla cells (DPCs) that line the base of the hair follicle. However, the mechanism of DHT action is not completely understood. The effects of DHT on DPCs, regulatory cells that function in follicle growth and the hair cycle, were examined in immortalized cells derived from rat vibrissa follicles. DHT did not affect the proliferation of immortalized DPCs. However, flow cytometry analysis revealed that DHT increased cell-cycle arrest in these cells, which was accompanied by an increase in the p27(kip1) level and by decreases in cyclin E, cyclin D1, and cyclin-dependent kinase 2 levels. DHT treatment resulted in the phosphorylation and nuclear translocation of Smad2/3, a mediator of the transforming growth factor-β (TGF-β) signaling pathway, which leads to the catagen phase of the hair cycle. DHT also induced the phosphorylation and nuclear translocation of heat shock protein 27 (HSP27). Moreover, DHT decreased the levels of total and nuclear β-catenin, an important regulator of hair growth and proliferation, while lithium chloride, a glycogen synthase kinase-3β inhibitor, attenuated the DHT-induced downregulation of the β-catenin level. On the other hand, DHT increased the phosphorylation of mammalian target of rapamycin (mTOR), a regulator of proliferation, in immortalized DPCs. These results illustrate that DHT could shorten the duration of the hair growth cycle by initiating cell-cycle arrest, downregulating the β-catenin level, and upregulating the TGF-β/Smad and HSP27 level, whereas activation of mTOR by DHT could attenuate the inhibition of hair growth cycle in immortalized DPCs. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Generation of human induced pluripotent stem cells from dermal fibroblasts.

    Science.gov (United States)

    Lowry, W E; Richter, L; Yachechko, R; Pyle, A D; Tchieu, J; Sridharan, R; Clark, A T; Plath, K

    2008-02-26

    The generation of patient-specific pluripotent stem cells has the potential to accelerate the implementation of stem cells for clinical treatment of degenerative diseases. Technologies including somatic cell nuclear transfer and cell fusion might generate such cells but are hindered by issues that might prevent them from being used clinically. Here, we describe methods to use dermal fibroblasts easily obtained from an individual human to generate human induced pluripotent stem (iPS) cells by ectopic expression of the defined transcription factors KLF4, OCT4, SOX2, and C-MYC. The resultant cell lines are morphologically indistinguishable from human embryonic stem cells (HESC) generated from the inner cell mass of a human preimplantation embryo. Consistent with these observations, human iPS cells share a nearly identical gene-expression profile with two established HESC lines. Importantly, DNA fingerprinting indicates that the human iPS cells were derived from the donor material and are not a result of contamination. Karyotypic analyses demonstrate that reprogramming of human cells by defined factors does not induce, or require, chromosomal abnormalities. Finally, we provide evidence that human iPS cells can be induced to differentiate along lineages representative of the three embryonic germ layers indicating the pluripotency of these cells. Our findings are an important step toward manipulating somatic human cells to generate an unlimited supply of patient-specific pluripotent stem cells. In the future, the use of defined factors to change cell fate may be the key to routine nuclear reprogramming of human somatic cells.

  9. Dermatologic findings of focal dermal hypoplasia (Goltz syndrome).

    Science.gov (United States)

    Bree, Alanna F; Grange, Dorothy K; Hicks, M John; Goltz, Robert W

    2016-03-01

    Goltz syndrome, caused by mutations in PORCN, is an X-linked dominant ectodermal dysplasia which is also known as focal dermal hypoplasia. This name is derived from the predominant pathologic skin findings of the syndrome. Nineteen Goltz-affected participants attended a multidisciplinary scientific and clinical conference convened by the National Foundation for Ectodermal Dysplasia which allowed further characterization of the features of this very rare condition. At birth, the affected areas of skin are typically erythematous and fragile. The hallmark cutaneous features, which vary widely due to mosacism and X-inactivation, include the previously described skin changes of asymmetric Blaschko-linear and reticulated atrophy, pigmentary changes, and telangectasias. Lipomatous changes and papillomas as characteristically defined were reported in the majority of patients. A newly recognized skin finding was progressive hyperpigmented freckling that occurred within the hypopigmented areas which were noted to be photosensitive. Many patients also had a pebbly texture to the central face, dorsal hands and feet. Punctate erosions within the atrophic areas and hypohidrosis were also common. Most had patchy alopecia and many had diffusely thin hair. Scanning electron microscopy of the hair shafts revealed abnormalities in the majority of participants with several different features identified, including atrophic hairs with reduced diameters, markedly flattened hairs as noted in cross-sectional views, trichorrhexis nodosa, pili torti, and pili trianguli et canaliculi. Nail changes included V-nicking and longitudinal ridging of the nail plate, in addition to micronychia. Early recognition of the dermatologic features, in addition to the variable but universal limb anomalies, of Goltz syndrome will allow early and accurate diagnosis without the need for extensive diagnostic studies, while also allowing for accurate prognosis and appropriate genetic counseling.

  10. Nurses with dermal exposure to antineoplastic drugs: Reproductive outcomes

    NARCIS (Netherlands)

    Fransman, W.; Roeleveld, N.; Peelen, S.; Kort, W.de; Kromhout, H.; Heederik, D.

    2007-01-01

    BACKGROUND: Nurses and other hospital workers are exposed to antineoplastic drugs during daily activities. Previous studies suggest that antineoplastic drugs at occupational exposure levels may be toxic to reproduction, but these studies are not consistent or conclusive. METHODS: Self-administered

  11. Nurses with dermal exposure to antineoplastic drugs: reproductive outcomes.

    NARCIS (Netherlands)

    Fransman, W.; Roeleveld, N.; Peelen, S.J.M.; Kort, W. de; Kromhout, H.; Heederik, D.

    2007-01-01

    BACKGROUND: Nurses and other hospital workers are exposed to antineoplastic drugs during daily activities. Previous studies suggest that antineoplastic drugs at occupational exposure levels may be toxic to reproduction, but these studies are not consistent or conclusive. METHODS: Self-administered

  12. Characterization and assessment of dermal and inhalable nickel exposures in nickel production and primary user industries.

    Science.gov (United States)

    Hughson, G W; Galea, K S; Heim, K E

    2010-01-01

    The aim of this study was to measure the levels of nickel in the skin contaminant layer of workers involved in specific processes and tasks within the primary nickel production and primary nickel user industries. Dermal exposure samples were collected using moist wipes to recover surface contamination from defined areas of skin. These were analysed for soluble and insoluble nickel species. Personal samples of inhalable dust were also collected to determine the corresponding inhalable nickel exposures. The air samples were analysed for total inhalable dust and then for soluble, sulfidic, metallic, and oxidic nickel species. The workplace surveys were carried out in five different workplaces, including three nickel refineries, a stainless steel plant, and a powder metallurgy plant, all of which were located in Europe. Nickel refinery workers involved with electrolytic nickel recovery processes had soluble dermal nickel exposure of 0.34 microg cm(-2) [geometric mean (GM)] to the hands and forearms. The GM of soluble dermal nickel exposure for workers involved in packing nickel salts (nickel chloride hexahydrate, nickel sulphate hexahydrate, and nickel hydroxycarbonate) was 0.61 microg cm(-2). Refinery workers involved in packing nickel metal powders and end-user powder operatives in magnet production had the highest dermal exposure (GM = 2.59 microg cm(-2) soluble nickel). The hands, forearms, face, and neck of these workers all received greater dermal nickel exposure compared with the other jobs included in this study. The soluble nickel dermal exposures for stainless steel production workers were at or slightly above the limit of detection (0.02 microg cm(-2) soluble nickel). The highest inhalable nickel concentrations were observed for the workers involved in nickel powder packing (GM = 0.77 mg m(-3)), although the soluble component comprised only 2% of the total nickel content. The highest airborne soluble nickel exposures were associated with refineries using

  13. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

    Directory of Open Access Journals (Sweden)

    Peipei Zhang

    2014-10-01

    Full Text Available Alopecia is an exceedingly prevalent problem effecting men and women of all ages. The standard of care for alopecia involves either transplanting existing hair follicles to bald areas or attempting to stimulate existing follicles with topical and/or oral medication. Yet, these treatment options are fraught with problems of cost, side effects, and, most importantly, inadequate long-term hair coverage. Innovative cell-based therapies have focused on the dermal papilla cell as a way to grow new hair in previously bald areas. However, despite this attention, many obstacles exist, including retention of dermal papilla inducing ability and maintenance of dermal papilla productivity after several passages of culture. The use of adipocyte lineage cells, including adipose-derived stem cells, has shown promise as a cell-based solution to regulate hair regeneration and may help in maintaining or increasing dermal papilla cells inducing hair ability. In this review, we highlight recent advances in the understanding of the cellular contribution and regulation of dermal papilla cells and summarize adipocyte lineage cells in hair regeneration.

  14. Urinary excretion of tetrahydrophtalimide in fruit growers with dermal exposure to captan.

    Science.gov (United States)

    de Cock, J; Heederik, D; Hoek, F; Boleij, J; Kromhout, H

    1995-08-01

    The relation between dermal and respiratory exposure and uptake into the body of captan, measured as 24 hr cumulative tetrahydrophtalimide (THPI) dose, was studied among 14 male fruit growers applying pesticides in orchards in the Netherlands. No contribution of respiratory exposure was observed on THPI in the urine. Dermal exposure, measured with skin pads, showed a clear relation with THPI in urine when exposure was estimated from exposure on skin pads of ankles and neck. No relation was found for total dermal exposure, calculated from measured exposure on skin pads of representative skin areas according to models described in the literature. Determinants of exposure such as use of a cabin on the tractor, use of gloves during mixing and loading, and use of rubber boots also explained THPI in urine very well. This finding corroborated the findings on measured dermal exposure. Results indicate that more attention should be paid to skin areas which are suspected to be most permeable for a chemical under study. It was concluded that dermal exposure data can be linked better to biological monitoring based on empirical findings as gathered in a pilot study on exposure of specific body areas than on estimations of total skin dose.

  15. The Role of Dermal Matrices in Treating Inflammatory and Diabetic Wounds.

    Science.gov (United States)

    Climov, Mihail; Bayer, Lauren R; Moscoso, Andrea V; Matsumine, Hajime; Orgill, Dennis P

    2016-09-01

    Dermal matrices are used to improve healing in both acute and chronic wounds including diabetic and lower extremity wounds, burns, trauma, and surgical reconstruction. The use of dermal matrices for the closure of inflammatory ulcerations is less frequent but growing. Currently available products include decellularized dermis and semisynthetic matrices. A review of the published literature was performed to identify reports that use acellular dermal matrices in diabetic and inflammatory wounds. Studies were evaluated for quality and outcomes, and a level of evidence was assigned according to the American Society of Plastic Surgeons' Rating Levels of Evidence. Case studies from the authors' experience are also presented. Seventeen primary studies evaluating the use of dermal matrices in diabetic ulcers were identified with 2 based on level I data. There are no prospective clinical trial reports of their use in atypical or inflammatory wounds, but there are several case studies. Treatment of diabetic and inflammatory wounds may include both medical and surgical modalities. The use of dermal matrices can be a useful adjunct, but their optimal use will require future clinical studies.

  16. Penile Reconstruction with Skin Grafts and Dermal Matrices: Indications and Management.

    Science.gov (United States)

    Triana Junco, Paloma; Dore, Mariela; Nuñez Cerezo, Vanesa; Jimenez Gomez, Javier; Miguel Ferrero, Miriam; Díaz González, Mercedes; Lopez-Pereira, Pedro; Lopez-Gutierrez, Juan Carlos

    2017-01-01

    Introduction  The penis eventually needs specific cutaneous coverage in the context of reconstructive procedures following trauma or congenital anomalies. Local flaps are the first choice but are not always available after multiple previous procedures. In these cases, skin graft and dermal matrices should be considered. Materials and Methods  This study was a retrospective review of the past 4 years of four patients with severe loss of penile shaft skin who underwent skin reconstruction. Dermal matrices and skin grafts were utilized. Dermal matrices were placed for a median of 4.5 weeks (3.0-6.0 weeks). The skin graft was harvested from the inner thigh region for split-thickness skin graft (STSG) and the inguinal region for full-thickness skin graft (FTSG). Results  The four patients presented with complete loss of skin in the penile shaft. One patient had a vesical exstrophy, one had a buried penis with only one corpus cavernosum, one had a wide congenital lymphedema of the genitalia, and one had a lack of skin following circumcision at home. They underwent reconstruction with three patients undergoing split-thickness skin graft; two dermal matrices; and one full-thickness graft, respectively, thereby achieving a good cosmetic and functional result. There were no complications, and all the patients successfully accepted the graft. Conclusion  Dermal matrices and skin grafts may serve as effective tools in the management of severe penile skin defects unable to be covered with local flaps.

  17. Management of gingival recession with acellular dermal matrix graft: A clinical study

    Directory of Open Access Journals (Sweden)

    V R Balaji

    2016-01-01

    Full Text Available Aims and Objectives: Obtaining root coverage has become an important part of periodontal therapy. The aims of this studyare to evaluate the clinical efficacy of acellular dermal matrix graft in the coverage of denuded roots and also to examine the change in the width of keratinized gingiva. Materials and Methods: A total of 20 sites with more than or equal to 2 mm of recession depth were taken into the study, for treatment with acellular dermal matrix graft. The clinical parameters such as recession depth, recession width, width of keratinized gingiva, probing pocket depth (PD, and clinical attachment level (CAL were measured at the baseline, 8th week, and at the end of the study (16th week. The defects were treated with a coronally positioned pedicle graft combined with acellular dermal matrix graft. Results: Out of 20 sites treated with acellular dermal matrix graft, seven sites showed complete root coverage (100%, and the mean root coverage obtained was 73.39%. There was a statistically significant reduction in recession depth, recession width, and probing PD. There was also a statistically significant increase in width of keratinized gingiva and also gain in CAL. The postoperative results were both clinically and statistically significant (P < 0.0001. Conclusion: The results of this study were esthetically acceptable to the patients and clinically acceptable in all cases. From this study, it may be concluded that acellular dermal matrix graft is an excellent substitute for autogenous graft in coverage of denuded roots.

  18. The Effectiveness of Porcine Dermal Collagen (Permacol(®)) on Wound Healing in the Rat Model.

    Science.gov (United States)

    Kalin, Murat; Kuru, Serdar; Kismet, Kemal; Barlas, Aziz Mutlu; Akgun, Yusuf Akif; Astarci, Hesna Muzeyyen; Ustun, Huseyin; Ertas, Ertugrul

    2015-12-01

    Porcine acellular dermal collagen (PDC), which is a biological material derived from processing porcine dermis, has already been used for urologic, gynecologic, plastic, and general surgery procedures up to now. The aim of this study is to investigate the effectiveness of PDC on wound healing as a dermal substitute in the rat model. Twenty Wistar albino rats were divided into two groups. Standard full-thickness skin defects were created on the back of the rats. In the control group (Group 1), the dressings moisturized with saline were changed daily. In the study group (Group 2), porcine dermal collagen was implanted onto each wound and fixed with 4-0 polypropylene sutures. Contraction percentages of wound areas were calculated on the third, seventh, tenth, and fourteenth days by using the planimetric program. On fourteenth day, the wound areas were excised for histopathological examination, inflammatory scoring, and evaluation of collagen deposition. The study group was superior to the control group in terms of inflammatory scoring, type I/type III collagen ratio, and wound contraction rates. Porcine dermal collagen may be used effectively and safely on full-thickness wounds as a current dermal substitute.

  19. Understanding the toxicity of carbon nanotubes.

    Science.gov (United States)

    Liu, Ying; Zhao, Yuliang; Sun, Baoyun; Chen, Chunying

    2013-03-19

    Because of their unique physical, chemical, electrical, and mechanical properties, carbon nanotubes (CNTs) have attracted a great deal of research interest and have many potential applications. As large-scale production and application of CNTs increases, the general population is more likely to be exposed to CNTs either directly or indirectly, which has prompted considerable attention about human health and safety issues related to CNTs. Although considerable experimental data related to CNT toxicity at the molecular, cellular, and whole animal levels have been published, the results are often conflicting. Therefore, a systematic understanding of CNT toxicity is needed but has not yet been developed. In this Account, we highlight recent investigations into the basis of CNT toxicity carried out by our team and by other laboratories. We focus on several important factors that explain the disparities in the experimental results of nanotoxicity, such as impurities, amorphous carbon, surface charge, shape, length, agglomeration, and layer numbers. The exposure routes, including inhalation, intravenous injection, or dermal or oral exposure, can also influence the in vivo behavior and fate of CNTs. The underlying mechanisms of CNT toxicity include oxidative stress, inflammatory responses, malignant transformation, DNA damage and mutation (errors in chromosome number as well as disruption of the mitotic spindle), the formation of granulomas, and interstitial fibrosis. These findings provide useful insights for de novo design and safe application of carbon nanotubes and their risk assessment to human health. To obtain reproducible and accurate results, researchers must establish standards and reliable detection methods, use standard CNT samples as a reference control, and study the impact of various factors systematically. In addition, researchers need to examine multiple types of CNTs, different cell lines and animal species, multidimensional evaluation methods, and

  20. Proposal for the assessment of quantitative dermal exposure limits in occupational environments: Part 2. Feasibility study for application in an exposure scenario for MDA by two different dermal exposure sampling methods

    NARCIS (Netherlands)

    Bos, P.M.J.; Brouwer, D.H.; Stevenson, H.; Hoogendoorn, L.; Boogaard, P.J.; Kort, W.L.A.M. de; Hemmen, J.J. van

    1998-01-01

    Objective. To evaluate two different techniques for assessing dermal exposure to 4,4'-methylene dianiline (MDA) in a field study. The results were used to test the applicability of a recently proposed quantitative dermal occupational exposure limit (DOEL) for MDA in a workplace scenario. Methods. Fo

  1. Glycyrrhizic acid (GA), a triterpenoid saponin glycoside alleviates ultraviolet-B irradiation-induced photoaging in human dermal fibroblasts.

    Science.gov (United States)

    Afnan, Quadri; Adil, Mushtaq Dar; Nissar-Ul, Ashraf; Rafiq, Ahmad Rather; Amir, Hussian Faridi; Kaiser, Peerzada; Gupta, Vijay Kumar; Vishwakarma, Ram; Tasduq, Sheikh Abdullah

    2012-05-15

    Glycyrrhizic acid (GA), a triterpenoid saponin glycoside from the roots and rhizomes of licorice is used in traditional and modern medicine for the treatment of numerous medical conditions including skin diseases and beauty care product. In the present study, we investigated the effect of GA against ultraviolet B (UVB) irradiation-induced photoaging in human dermal fibroblasts (HDFs) and its possible mechanism of action. HDFs were subjected to photoaging by sub-toxic dose of UVB (10 mj/cm(2)) irradiation. Cell viability, matrix metalloproteinase 1 (MMP1), pro-collagen 1, cellular and nuclear morphology, cell cycle, intracellular reactive oxygen species (ROS), caspase 3 and hyaluronidase inhibition assays were performed. Western blotting was used to evaluate the expression of NF-kappa B (NF-κB) and cytochrome-C proteins. GA treatment significantly inhibited photoaging. It achieved this by reducing ROS, NF-κB, cytochrome c, caspase 3 levels and inhibiting hyaluronidase enzyme. The main mechanism seems to be, most likely by blocking MMP1 activation by modulating NF-κB signaling. These findings may be useful for development of natural and safe photoprotective agents against UVB irradiation. Copyright © 2012 Elsevier GmbH. All rights reserved.

  2. Treatment-Based Strategy for the Management of Post-Kala-Azar Dermal Leishmaniasis Patients in the Sudan

    Directory of Open Access Journals (Sweden)

    A. M. Musa

    2013-01-01

    Full Text Available Post-kala-azar dermal leishmaniasis (PKDL is a dermatosis that affects more than 50% of successfully treated visceral leishmaniasis (VL patients in Sudan. PKDL is considered an important reservoir for the parasite and its treatment may help in the control of VL. Currently, treatment is mainly with sodium stibogluconate (SSG, an expensive and fairly toxic drug and without universally in treatment protocols used. A literature review, a consensus of a panel of experts, and unpublished data formed the basis for the development of guidelines for the treatment of PKDL in the Sudan. Six treatment modalities were evaluated. Experts were asked to justify their choices based on their experience regarding of drug safety, efficacy, availability, and cost. The consensus was defined by assigning a categorical rank (first line, second line, third line to each option. Regarding the use of AmBisome the presence of the drug in the skin was confirmed in smears from PKDL lesions. Recommendations: AmBisome at 2.5 mg/kg/day/20 days or SSG at 20 mg/kg/day/40 days plus four/weekly intradermal injection of alum-precipitated autoclave L. major vaccine are suggested as first- and second-treatment options for PKDL in the Sudan, respectively. SSG at 20 mg/Kg/day/60 or more days can be used if other options are not available.

  3. Limitations on quantum key repeaters.

    Science.gov (United States)

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  4. Hysteresis of magnetostructural transitions: Repeatable and non-repeatable processes

    Energy Technology Data Exchange (ETDEWEB)

    Provenzano, Virgil [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Della Torre, Edward; Bennett, Lawrence H. [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States); ElBidweihy, Hatem, E-mail: Hatem@gwmail.gwu.edu [Department of Electrical and Computer Engineering, The George Washington University, Washington, DC 20052 (United States)

    2014-02-15

    The Gd{sub 5}Ge{sub 2}Si{sub 2} alloy and the off-stoichiometric Ni{sub 50}Mn{sub 35}In{sub 15} Heusler alloy belong to a special class of metallic materials that exhibit first-order magnetostructural transitions near room temperature. The magnetic properties of this class of materials have been extensively studied due to their interesting magnetic behavior and their potential for a number of technological applications such as refrigerants for near-room-temperature magnetic refrigeration. The thermally driven first-order transitions in these materials can be field-induced in the reverse order by applying a strong enough field. The field-induced transitions are typically accompanied by the presence of large magnetic hysteresis, the characteristics of which are a complicated function of temperature, field, and magneto-thermal history. In this study we show that the virgin curve, the major loop, and sequentially measured MH loops are the results of both repeatable and non-repeatable processes, in which the starting magnetostructural state, prior to the cycling of field, plays a major role. Using the Gd{sub 5}Ge{sub 2}Si{sub 2} and Ni{sub 50}Mn{sub 35}In{sub 15} alloys, as model materials, we show that a starting single phase state results in fully repeatable processes and large magnetic hysteresis, whereas a mixed phase starting state results in non-repeatable processes and smaller hysteresis.

  5. Measuring the strength of dermal fibroblast attachment to functionalized titanium alloys in vitro.

    Science.gov (United States)

    Pendegrass, Catherine J; Middleton, Claire A; Gordon, David; Jacob, Josh; Blunn, Gordon W

    2010-03-01

    The success of intraosseous transcutaneous amputation prostheses (ITAP) relies on soft tissue attachment to prevent infection which leads to implant failure. Fibronectin (Fn) has been shown to enhance dermal fibroblast attachment in vitro, however measurement of cell attachment strength has been indirect; using cell area and immunolocalization of focal adhesion components. In this study, we have developed a flow apparatus to assess the biophysical strength of cell attachment to biomaterials used in ITAP. We have demonstrated that dermal fibroblast attachment strength increases significantly up to 96 h and that data from direct and indirect methods of assessing cell attachment strength have a significant positive correlation. Additionally, we have used direct and indirect assessment methods to demonstrate that dermal fibroblast attachment strength is significantly greater on fibronectin-coated titanium alloy compared with uncoated controls at 1, 4, and 24 hours.

  6. Changes in dermal matrix in the absence of Rac1 in keratinocytes

    DEFF Research Database (Denmark)

    Stanley, Alanna; Pedersen, Esben; Brakebusch, Cord

    2016-01-01

    Keratinocytes, in response to irritants, secrete pro-inflammatory mediators which recruit and activate immune and mesenchymal cells, including fibroblasts, to repair the skin. Fibroblasts respond by synthesising collagen and promoting the crosslinking extracellular matrix (ECM). We recently showed...... of ICD on the tissue localisation and arrangements of dermal collagen. Qualitative analysis did not reveal evidence for the formation of pathologies in the dermis. However, quantitative analysis did reveal some perturbations in the dermal matrix, namely that only the combination of the lack of Rac1...... and ICD affects the architectural organisation of the dermal collagen, and that a higher inflammatory state in the tissue (i.e. when Rac1 is deleted in the keratinocytes or ICD is induced in the skin, or a combination of both) influences the diameter of the collagen fibrils. It is proposed...

  7. Clinical evaluation of an acellular dermal allograft for increasing the zone of attached gingiva.

    Science.gov (United States)

    Shulman, J

    1996-03-01

    Grafting with autogenous tissue or freeze-dried skin is the generally accepted method for increasing and/or restoring the width of attached gingiva. This article describes the periodontal use of an acellular dermal allograft previously available for treating burn patients. When used as a gingival graft, this new dermal allograft has major potential advantages over the previously available periodontal graft materials, including improved color and contour match, elimination of multiple surgeries, and unlimited availability. The technique and results of acellular dermal grafting are presented and discussed. The learning objective of this article is to describe the principles and the clinical procedure of this technique. Several cases are used to illustrate this technique.

  8. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    Science.gov (United States)

    Quan, Taihao; Fisher, Gary J

    2015-01-01

    Human skin is largely composed of a collagen-rich connective tissue, which provides structural and functional support. The collagen-rich connective tissue is produced, organized, and maintained by dermal fibroblasts. During aging, dermal collagen fibrils undergo progressive loss and fragmentation, leading to thin and structurally weakened skin. Age-related alterations of collagen fibrils impairs skin structure and function and creates a tissue microenvironment that promotes age-related skin diseases, such as delayed wound healing and skin cancer development. This review describes cellular mechanisms that give rise to self-perpetuating, collagen fibril fragmentation that creates an age-associated dermal microenvironment (AADM), which contributes to decline of human skin function. PMID:25660807

  9. Attachment of IgG to dermal extracellular matrix in patients with fibromyalgia.

    Science.gov (United States)

    Eneström, S; Bengtson, A; Lindström, F; Johan, K

    1990-01-01

    Deposits of IgG localized to collagen bundles/extracellular matrix components occurred in skin biopsies from patients with primary fibromyalgia (PF). None of these patients demonstrated a positive lupus band test. Control skin biopsies from healthy controls were negative but showed intense reactivity for IgG after collagenase treatment. PF-skin attached both homologous and heterologous serum IgG in indirect immunofluorescence, which may point to a qualitative alteration of dermal matrix components in PF. Skin from patients with systemic lupus erythematosus and rheumatoid arthritis showed a lower dermal fluorescence intensity than in PF patients. The cause of the presence of IgG in dermal tissue from PF patients is unclear. It may be caused by a non-specific attachment of IgG to the extracellular matrix related, for example, to tissue hypoxia and/or increased capillary leakage due to an increased number of mast cells in the PF-skin.

  10. A TRILAYER DERMAL EQUIVALENT CONTAINING SILVER NANOPARTICLES WITH ENHANCED ANTIBACTERIAL PROPERTY

    Institute of Scientific and Technical Information of China (English)

    Ai-bin Huang; Shao-jun Xu; Guo-yang Wei; Lie Ma; Chang-you Gao

    2009-01-01

    A dermal equivalent having a trilayered structure was designed by combining a silver nanoparticles incorporated chitosan film with a bilayer collagen-chitosan/silicon membrane dermal equivalent (BDE). The silver nanoparticles prepared at different conditions were characterized by UV-Vis and transmission electron microscopy (TEM). The macroscopic sharp and the microstructure of the trilayer dermal equivalent (TDE) were also studied. Then, the in vitro antibacterial property of TDE was evaluated by the antibacterial zone test. The effect of the incorporated silver nanoparticles on the resistance of wound infection was further studied by the in vivo animal test. The results prove that the silver nanoparticles incorporated TDE has a better antibacterial property, thus may be potentially applied to a broader field in skin repair such as full thickness defect and burn.

  11. Characterization and evolution of dermal filaments from patients with Morgellons disease.

    Science.gov (United States)

    Middelveen, Marianne J; Mayne, Peter J; Kahn, Douglas G; Stricker, Raphael B

    2013-01-01

    Morgellons disease is an emerging skin disease characterized by formation of dermal filaments associated with multisystemic symptoms and tick-borne illness. Some clinicians hypothesize that these often colorful dermal filaments are textile fibers, either self-implanted by patients or accidentally adhering to lesions, and conclude that patients with this disease have delusions of infestation. We present histological observations and electron microscopic imaging from representative Morgellons disease samples revealing that dermal filaments in these cases are keratin and collagen in composition and result from proliferation and activation of keratinocytes and fibroblasts in the epidermis. Spirochetes were detected in the dermatological specimens from our study patients, providing evidence that Morgellons disease is associated with an infectious process.

  12. Correction of tear trough deformity with novel porcine collagen dermal filler (Dermicol-P35).

    Science.gov (United States)

    Goldberg, David J

    2009-01-01

    Deformity of the tear trough region, which can occur during the aging process, can result in dark shadows under the eyes and a fatigued appearance. Augmentation of the tear trough is challenging because of the thin skin and lack of fat in the region. Adding volume to the tear trough region with a dermal filler is a nonsurgical procedure with minimal discomfort to the patient. Dermicol-P35 (Evolence; Ortho Dermatologics, Skillman, NJ) is a new, ribose crosslinked, highly purified, porcine-based collagen filler that does not require prior skin testing and has shown improved persistence compared with bovine collagen-based dermal fillers. In this article, we present the clinical outcomes of patients who have received treatment with a novel ribose crosslinked porcine collagen dermal filler for the correction of tear trough deformity.

  13. Long tract of untranslated CAG repeats is deleterious in transgenic mice.

    Directory of Open Access Journals (Sweden)

    Ren-Jun Hsu

    Full Text Available The most frequent trinucleotide repeat found in human disorders is the CAG sequence. Expansion of CAG repeats is mostly found in coding regions and is thought to cause diseases through a protein mechanism. Recently, expanded CAG repeats were shown to induce toxicity at the RNA level in Drosophila and C. elegans. These findings raise the possibility that CAG repeats may trigger RNA-mediated pathogenesis in mammals. Here, we demonstrate that transgenic mice expressing EGFP transcripts with long CAG repeats in the 3' untranslated region develop pathogenic features. Expression of the transgene was directed to the muscle in order to compare the resulting phenotype to that caused by the CUG expansion, as occurs in myotonic dystrophy. Transgenic mice expressing 200, but not those expressing 0 or 23 CAG repeats, showed alterations in muscle morphology, histochemistry and electrophysiology, as well as abnormal behavioral phenotypes. Expression of the expanded CAG repeats in testes resulted in reduced fertility due to defective sperm motility. The production of EGFP protein was significantly reduced by the 200 CAG repeats, and no polyglutamine-containing product was detected, which argues against a protein mechanism. Moreover, nuclear RNA foci were detected for the long CAG repeats. These data support the notion that expanded CAG repeat RNA can cause deleterious effects in mammals. They also suggest the possible involvement of an RNA mechanism in human diseases with long CAG repeats.

  14. Immunohistochemical analysis of radiation-induced non-healing dermal wounds of the head and neck.

    Science.gov (United States)

    Riedel, Frank; Philipp, Katrin; Sadick, Haneen; Goessler, Ullrich; Hörmann, Karl; Verse, Thomas

    2005-01-01

    Persistent, poorly healing wounds are a significant clinical problem in patients who have had previous irradiation. The pathology of chronic dermal ulcers is characterised by excessive proteolytic activity which degrades the extracellular matrix (required for cell migration) and growth factors and their receptors. Interestingly, the molecular basis of radiation-induced dermal wounds is poorly understood. The aim of this study was to investigate, by immunohistochemistry, the expression of the endothelial marker vWF, of angiogenic bFGF, VEGF and IL-8, of collagenases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2, in tissue samples from radiation-induced chronic dermal wounds and healthy control skin. Performing immunohistochemical detection of microvessels, an equivalent density of microvessels was observed within tissue samples from normal healthy skin and from radiation-induced non-healing cutaneous wounds. Investigation of angiogenic bFGF and VEGF demonstrated a decreased expression of both factors in the radiation-induced dermal wounds. The expression of angiogenic IL-8 was weak in both the healthy skin samples and the radiation-induced wounds. In addition, an increased expression of collagenases MMP-2 and MMP-9 protein within the radiation-induced wounds was demonstrated. While the expression of TIMP-1 showed no difference of expression between normal control skin and tissue samples from radiation-induced wounds, TIMP-2 expression was slightly increased compared to healthy controls. Our data suggest that radiation-induced dermal injuries often fail to heal because of decreased angiogenesis and persistently high concentrations of MMPs with an imbalance of their tissue inhibitors. The basic mechanisms of wound healing in radiation-induced dermal wounds at the molecular level need to be understood further for the development of innovative treatment strategies.

  15. Review of data on the dermal penetration of mineral oils and waxes used in cosmetic applications.

    Science.gov (United States)

    Petry, T; Bury, D; Fautz, R; Hauser, M; Huber, B; Markowetz, A; Mishra, S; Rettinger, K; Schuh, W; Teichert, T

    2017-10-05

    Mineral oils and waxes used in cosmetic products, also referred to as "personal care products" outside the European Union, are mixtures of predominantly saturated hydrocarbons consisting of straight-chain, branched and ring structures with carbon chain lengths greater than C16. They are used in skin and lip care cosmetic products due to their excellent skin tolerance as well as their high protecting and cleansing performance and broad viscosity options. Recently, concerns have been raised regarding potential adverse health effects of mineral oils and waxes from dermal application of cosmetics. In order to be able to assess the risk for the consumer the dermal penetration potential of these ingredients has to be evaluated. The scope and objective of this review are to identify and summarize publicly available literature on the dermal penetration of mineral oils and waxes as used in cosmetic products. For this purpose, a comprehensive literature search was conducted. A total of 13 in vivo (human, animal) and in vitro studies investigating the dermal penetration of mineral oils and waxes has been identified and analysed. The majority of the substances were dermally adsorbed to the stratum corneum and only a minor fraction reached deeper skin layers. Overall, there is no evidence from the various studies that mineral oils and waxes are percutaneously absorbed and become systemically available. Thus, given the absence of dermal uptake, mineral oils and waxes as used in cosmetic products do not present a risk to the health of the consumer. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Histology of the heterostracan dermal skeleton: Insight into the origin of the vertebrate mineralised skeleton.

    Science.gov (United States)

    Keating, Joseph N; Marquart, Chloe L; Donoghue, Philip C J

    2015-06-01

    Living vertebrates are divided into those that possess a fully formed and fully mineralised skeleton (gnathostomes) versus those that possess only unmineralised cartilaginous rudiments (cyclostomes). As such, extinct phylogenetic intermediates of these living lineages afford unique insights into the evolutionary assembly of the vertebrate mineralised skeleton and its canonical tissue types. Extinct jawless and jawed fishes assigned to the gnathostome stem evidence the piecemeal assembly of skeletal systems, revealing that the dermal skeleton is the earliest manifestation of a homologous mineralised skeleton. Yet the nature of the primitive dermal skeleton, itself, is poorly understood. This is principally because previous histological studies of early vertebrates lacked a phylogenetic framework required to derive evolutionary hypotheses. Nowhere is this more apparent than within Heterostraci, a diverse clade of primitive jawless vertebrates. To this end, we surveyed the dermal skeletal histology of heterostracans, inferred the plesiomorphic heterostracan skeleton and, through histological comparison to other skeletonising vertebrate clades, deduced the ancestral nature of the vertebrate dermal skeleton. Heterostracans primitively possess a four-layered skeleton, comprising a superficial layer of odontodes composed of dentine and enameloid; a compact layer of acellular parallel-fibred bone containing a network of vascular canals that supply the pulp canals (L1); a trabecular layer consisting of intersecting radial walls composed of acellular parallel-fibred bone, showing osteon-like development (L2); and a basal layer of isopedin (L3). A three layered skeleton, equivalent to the superficial layer L2 and L3 and composed of enameloid, dentine and acellular bone, is possessed by the ancestor of heterostracans + jawed vertebrates. We conclude that an osteogenic component is plesiomorphic with respect to the vertebrate dermal skeleton. Consequently, we interpret the

  17. Protective effect of oat bran extracts on human dermal fibroblast injury induced by hydrogen peroxide

    Institute of Scientific and Technical Information of China (English)

    Bing FENG; Lai-ji MA; Jin-jing YAO; Yun FANG; Yan-ai MEI; Shao-min WEI

    2013-01-01

    Oat contains different components that possess antioxidant properties;no study to date has addressed the antioxidant effect of the extract of oat bran on the cellular level.Therefore,the present study focuses on the investigation of the protective effect of oat bran extract by enzymatic hydrolysates on human dermal fibroblast injury induced by hydrogen peroxide(H2O2).Kjeldahl determination,phenol-sulfuric acid method,and high-performance liquid chromatography(HPLC)analysis indicated that the enzymatic products of oat bran contain a protein amount of 71.93%,of which 97.43% are peptides with a molecular range from 438.56 to 1301.01 Da.Assays for 1,1-diphenyl-2-picrylhydrazyl(DPPH)radical scavenging activity indicate that oat peptide-rich extract has a direct and concentration-dependent antioxidant activity.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide(MTT)colorimetric assay and the TdT-mediated digoxigenin-dUTP nick-end labeling(TUNEL)assay for apoptosis showed that administration of H2O2 in human dermal fibroblasts caused cell damage and apoptosis.Pre-incubation of human dermal fibroblasts with the Oatp for 24 h markedly inhibited human dermal fibroblast injury induced by H2O2,but application oat peptides with H2O2 at same time did not.Pre-treatment of human dermal fibroblasts with Oatp significantly reversed the H2O2-induced decrease of superoxide dismutase(SOD)and the inhibition of malondialdehyde(MDA).The results demonstrate that oat peptides possess antioxidant activity and are effective against H2O2-induced human dermal fibroblast injury by the enhanced activity of SOD and decrease in MDA level.Our results suggest that oat bran will have the potential to be further explored as an antioxidant functional food in the prevention of aging-related skin injury.

  18. REDUCED WOUND CONTRACTION AND SCAR FORMATION IN PUNCH BIOPSY WOUNDS - NATIVE COLLAGEN DERMAL SUBSTITUTES - A CLINICAL-STUDY

    NARCIS (Netherlands)

    DEVRIES, HJC; ZEEGELAAR, JE; MIDDELKOOP, E; GIJSBERS, G; VANMARLE, J; WILDEVUUR, CHR; WESTERHOF, W

    In full-thickness skin wounds dermal regeneration usually fails, resulting in scar formation and wound contraction. We studied dermal regeneration by implantation of collagenous matrices in a human punch biopsy wound model. Matrices were made of native bovine collagen I fibres, and either hyaluronic

  19. Dermatokinetics of didecyldimethylammonium chloride and the influence of some commercial biocidal formulations on its dermal absorption in vitro

    NARCIS (Netherlands)

    Buist, H.E.; Heer, C. de; Burgsteden, J.A. van; Sandt, J.J.M. van de

    2007-01-01

    The in vitro dermal absorption kinetics of didecyldimethylammonium chloride (DDAC) was studied after single and multiple exposure. In addition, the influence of biocidal formulations on the absorption of DDAC was investigated. Following dermal exposure to DDAC in aqueous solution, less than 0.5% of

  20. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections.

    Science.gov (United States)

    Draughn, G Logan; Allen, C Leigh; Routh, Patricia A; Stone, Maria R; Kirker, Kelly R; Boegli, Laura; Schuchman, Ryan M; Linder, Keith E; Baynes, Ronald E; James, Garth; Melander, Christian; Pollard, Angela; Cavanagh, John

    2017-01-01

    2-Aminoimidazole (2-AI)-based compounds have been shown to efficiently disrupt biofilm formation, disperse existing biofilms, and resensitize numerous multidrug-resistant bacteria to antibiotics. Using Pseudomonas aeruginosa and Staphylococcus aureus, we provide initial pharmacological studies regarding the application of a 2-AI as a topical adjuvant for persistent dermal infections. In vitro assays indicated that the 2-AI H10 is nonbactericidal, resensitizes bacteria to antibiotics, does not harm the integument, and promotes wound healing. Furthermore, in vivo application of H10 on swine skin caused no gross abnormalities or immune reactions. Taken together, these results indicate that H10 represents a promising lead dermal adjuvant compound.

  1. Autologous smashed dermal graft with epidermal re-closure: Modified technique for acne scars

    Directory of Open Access Journals (Sweden)

    Umashankar Nagaraju

    2016-01-01

    Full Text Available Conventional technique of dermal grafting for acne scars where the source of filler material used is the patient′s own dermis requires longer surgical time, recovery period and can result in unsightly scars at the donor area. Hence, it is not suitable for treating a larger number of scars. Furthermore, these dermal grafts are firm and cannot be contoured to fit all types of acne scars. Occurrence of epidermal cyst and secondary infection is another complication if epidermis is not completely removed. Enzymatic techniques need trypsinisation which is expensive and requires laboratory facilities.

  2. Increased dermal mast cell prevalence and susceptibility to development of basal cell carcinoma in humans

    DEFF Research Database (Denmark)

    Grimbaldeston, Michele A; Skov, Lone; Finlay-Jones, John J

    2002-01-01

    Exposure to ultraviolet B (UVB) radiation (280-320 nm) is the primary etiologic factor associated with the development of basal cell carcinoma (BCC). The outgrowth of these keratinocyte-derived skin lesions is enhanced by the ability of UVB to impair an immune response that would otherwise...... by sun exposure. Two sections (4 microm) per biopsy were immunohistochemically stained for detection of histamine-containing dermal mast cells. Computer-generated image analysis evaluated dermal mast cell prevalence in both sections by quantifying the total number of mast cells according to the total...

  3. Rat hair follicle dermal papillae have an extracellular matrix containing basement membrane components

    DEFF Research Database (Denmark)

    Couchman, J R

    1986-01-01

    Dermal papillae are small mesenchymally derived zones at the bases of hair follicles which have an important role in hair morphogenesis in the embryo and control of the hair growth cycle in postnatal mammals. The cells of the papilla are enmeshed in a dense extracellular matrix which undergoes...... extensive changes in concert with the hair cycle. Here it is shown that this matrix in anagen pelage follicles of postnatal rats contains an abundance of basement membrane components rather than dermal components such as interstitial collagens. In particular, type IV collagen, laminin, and basement membrane...

  4. Coverage of Megaprosthesis with Human Acellular Dermal Matrix after Ewing's Sarcoma Resection: A Case Report

    Directory of Open Access Journals (Sweden)

    Robert M. Whitfield

    2011-01-01

    Full Text Available A 23-year-old female with Ewing's Sarcoma underwent tibial resection and skeletal reconstruction using proximal tibial allograft prosthetic reconstruction with distal femur endoprosthetic reconstruction and rotating hinge. Human acellular dermal matrix, (Alloderm, LifeCell, Branchburg, NJ, USA, was used to wrap the skeletal reconstruction. Soft tissue reconstruction was completed with a rotational gastrocnemius muscle flap and skin graft. Despite prolonged immobilization, the patient quickly regained full range of motion of her skeletal reconstruction. Synthetic mesh, tapes and tubes are used to perform capsule reconstruction of megaprosthesis. This paper describes the role of human acellular dermal matrix in capsule reconstruction around a megaprosthesis.

  5. Coverage of Megaprosthesis with Human Acellular Dermal Matrix after Ewing's Sarcoma Resection: A Case Report.

    Science.gov (United States)

    Whitfield, Robert M; Rinard, Jeremy; King, David

    2011-01-01

    A 23-year-old female with Ewing's Sarcoma underwent tibial resection and skeletal reconstruction using proximal tibial allograft prosthetic reconstruction with distal femur endoprosthetic reconstruction and rotating hinge. Human acellular dermal matrix, (Alloderm, LifeCell, Branchburg, NJ, USA), was used to wrap the skeletal reconstruction. Soft tissue reconstruction was completed with a rotational gastrocnemius muscle flap and skin graft. Despite prolonged immobilization, the patient quickly regained full range of motion of her skeletal reconstruction. Synthetic mesh, tapes and tubes are used to perform capsule reconstruction of megaprosthesis. This paper describes the role of human acellular dermal matrix in capsule reconstruction around a megaprosthesis.

  6. Human dermal safety studies with eflornithine HCl 13.9% cream (Vaniqa), a novel treatment for excessive facial hair.

    Science.gov (United States)

    Hickman, J G; Huber, F; Palmisano, M

    2001-01-01

    Eflornithine HCl 13.9% cream (Vaniqa) is a novel treatment for the management of unwanted facial hair in women. This paper reports the results of four modified open-label, within-subject vehicle-controlled studies evaluating the dermal safety of this topical treatment. In a repeated insult patch test (230 subjects), erythema with oedema occurred in 38.9% of subjects treated with eflornithine HCl 13.9% cream and 4.8% of subjects treated with vehicle cream. Challenge applications at previously untested sites following the three-week induction period produced noticeable erythema or greater on only four sites treated with eflornithine HCl 13.9% cream and one vehicle-treated site. The erythema at these sites subsided substantially within 24 hours. In a three-week cumulative irritation study (30 subjects), the mean irritation score for sites treated with eflornithine HCl 13.9% cream was 1.33, compared with 0.76 at vehicle-treated sites and 3.09 at positive-control (sodium lauryl sulphate-treated) sites (p < 0.001 between all three groups). In a phototoxicity study (25 subjects), irradiated sites showed either no reaction (40% of both sites treated with eflornithine HCl 13.9% cream and vehicle-treated sites), or mild erythema subsiding in all cases but one within 24 hours. No reaction was seen at non-irradiated sites. In a photocontact allergy study (30 subjects), challenge with eflornithine HCl 13.9% cream or its vehicle alone produced either no reaction or mild erythema subsiding within 24 hours at both irradiated and non-irradiated sites. No serious adverse events were reported during the studies, and the only adverse events considered related to treatment were pruritus (three subjects) and dry skin at test site (one subject). These results demonstrate that eflornithine HCl 13.9% cream does not have contact sensitising, photocontact allergic or phototoxic properties. It can cause irritation under exaggerated conditions of use. Eflornithine HCl 13.9% cream, therefore

  7. EAMJ Dec. Repeatability.indd

    African Journals Online (AJOL)

    2008-12-12

    Dec 12, 2008 ... Results:Kappa values for four-week repeatability for the wheeze and asthma questions were 0.61 ... for logistic, cultural and ethical reasons, to use ... individual with baseline forced expiratory volume in .... period is likely to also include the effects of true ... data, the writing of the manuscript or the decision.

  8. Acute and 28-day subchronic toxicity studies of mangiferin, a glucosylxanthone isolated from Mangifera indica L. stem bark.

    Directory of Open Access Journals (Sweden)

    Yalena Prado

    2015-02-01

    Full Text Available Context: Pharmacological properties of mangiferin have been reported, but few studies have investigated mangiferin toxicity. Aims: To study the acute and 28-day toxicity effects of mangiferin in rodents. Methods: Single doses of mangiferin were administered by oral or i.p. route or were applied dermally to Sprague-Dawley rats and Balb/C mice. Clinical symptoms of animals were observed during 14 days after treatment. Animals also received single oral doses daily for 28 consecutive days. Blood biochemistry, hematology and pathology findings were reported. Results: In the acute study, no toxic effects were observed after dermal exposure to mangiferin 2000 mg/kg but transient dyspnea, flank position and piloerection were observed after oral administration to this xanthone. I.p. administration induced similar toxicity signs, but at the highest dose (2000 mg/kg all mice, one female rat and one male rat died. Rats orally treated with mangiferin (250-1000 mg/kg for 28 days did not show any abnormal clinical signs or hematology alterations, when compared to control group animals. Histopathological alterations like vacuolar degeneration, necrosis and increment of apoptosis of the acinar cells were observed in the exocrine pancreas of rats at 1000 mg/kg. This suggesting that exocrine pancreas was the target organ for mangiferin’s toxicity. Conclusions: These studies indicated that acute and subchronic toxicities of mangiferin for oral exposure are low.

  9. Directionality switchable gain stabilized linear repeater

    Science.gov (United States)

    Ota, Takayuki; Ohmachi, Tadashi; Aida, Kazuo

    2004-10-01

    We propose a new approach to realize a bidirectional linear repeater suitable for future optical internet networks and fault location in repeater chain with OTDR. The proposed approach is the linear repeater of simple configuration whose directionality is rearranged dynamically by electrical control signal. The repeater is composed of a magneto-optical switch, a circulator, a dynamically gain stabilized unidirectional EDFA, and control circuits. The repeater directionality is rearranged as fast as 0.1ms by an electrical control pulse. It is experimentally confirmed that OTDR with the directionality switchable repeater is feasible for repeater chain. The detailed design and performance of the repeater are also discussed, including the multi-pass interference (MPI) which may arise in the proposed repeater, the effect of the MPI on SNR degradation of the repeater chain and the feed-forward EDFA gain control circuit.

  10. Comparative dermal carcinogenesis of shale and petroleum-derived distillates.

    Science.gov (United States)

    Clark, C R; Walter, M K; Ferguson, P W; Katchen, M

    1988-03-01

    Ten test materials derived from petroleum or hydrotreated shale oils were applied 3 times/week for up to 105 weeks to the shaved skin of 25 male and 25 female C3H/HeN mice per group. Mineral oil and benzo(a) pyrene (0.15%) were control materials. Clinical observations were recorded during the study. At death, histopathologic examination was conducted on skin, internal organs and any gross lesions. Exposures to some materials were ended midway in the study due to severe irritation. Chronic toxicity of all materials was limited to inflammatory and degenerative skin changes. Significant increases over control incidence of skin tumors (squamous cell carcinoma and fibrosarcoma) occurred with both petroleum and shale-derived naphtha (21%, 50%), Jet A (26%, 28%), JP-4 (26%, 50%), and crude oils (84%, 54%). Severely hydrotreated shale oil and petroleum and shale-derived diesel distillates were not considered tumorigenic. Results indicate that toxicity of comparable petroleum and shale-derived fractions was qualitatively similar and confirm earlier findings that hydrotreating reduces or eliminates carcinogenicity of raw shale oil.

  11. Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma.

    Science.gov (United States)

    Kim, Nan-Hyung; Choi, Soo-Hyun; Lee, Tae Ryong; Lee, Chang-Hoon; Lee, Ai-Young

    2016-06-15

    Basement membrane (BM) disruption and dermal changes (elastosis, collagenolysis, vascular ectasia) have been reported in melasma. Although ultraviolet (UV) irradiation can induce these changes, UV is not always necessary for melasma development. Cadherin 11 (CDH11), which is upregulated in some melasma patients, has previously been shown to stimulate melanogenesis. Because CDH11 action requires cell-cell adhesion between fibroblasts and melanocytes, BM disruption in vivo should facilitate this. The aim of this study was to examine whether CDH11 overexpression leads to BM disruption and dermal changes, independent of UV irradiation. Immunohistochemistry/immunofluorescence, real-time PCR, Western blotting, and zymography suggested that BM disruption/dermal changes and related factors were present in the hyperpigmented skin of CDH11-upregulated melasma patients and in CDH11-overexpressing fibroblasts/keratinocytes. The opposite was seen in CDH11-knockdown cells. UV irradiation of the cultured cells did not increase CDH11 expression. Collectively, these data demonstrate that CDH11 overexpression could induce BM disruption and dermal changes in melasma, regardless of UV exposure.

  12. BIOCOMPATIBILITY AND TISSUE REGENERATING CAPACITY OF CROSS-LINKED DERMAL SHEEP COLLAGEN

    NARCIS (Netherlands)

    VANWACHEM, PB; VANLUYN, MJA; DAMINK, LHHO; DIJKSTRA, PJ; FEIJEN, J; NIEUWENHUIS, P

    1994-01-01

    The biocompatibility and tissue regenerating capacity of four crosslinked dermal sheep collagens (DSC) was studied. In vitro, the four DSC versions were found to be noncytotoxic or very low in cytoxicity. After subcutaneous implantation in rats, hexamethylenediisocyanate-crosslinked DSC (HDSC) seldo

  13. TFE-PLASMA POLYMERIZED DERMAL SHEEP COLLAGEN FOR THE REPAIR OF ABDOMINAL-WALL DEFECTS

    NARCIS (Netherlands)

    VANDERLAAN, JS; LOPEZ, GP; VANWACHEM, PB; NIEUWENHUIS, P; RATNER, BD; BLEICHRODT, RP; SCHAKENRAAD, JM

    1991-01-01

    The aim of this study was to design and evaluate a degradable biomaterial for the repair of abdominal wall defects. Hexamethylenediisocyanate-tanned dermal sheep collagen (HDSC) was plasma-polymerized with tetrafluoroethylene (TFE) which resulted in a hydrophobic surface on the visceral side (TFE-HD

  14. Role of clothing in both accelerating and impeding dermal absorption of airborne SVOCs

    DEFF Research Database (Denmark)

    Morrison, Glenn C.; Weschler, Charles J.; Bekö, Gabriel

    2016-01-01

    .5, respectively. Even for non-occupational environments, wearing clothing that has adsorbed/absorbed indoor air pollutants can increase dermal uptake of SVOCs by substantial amounts relative to bare skin.Journal of Exposure Science and Environmental Epidemiology advance online publication, 10 June 2015; doi:10.1038...

  15. Water permeability parameters of dermal fibroblast employed in tissue engineering in subzero temperatures

    Institute of Scientific and Technical Information of China (English)

    WANG; Xin; CHENG; Qikang; GAO; Cai; YANG; Pengfei; HUA; Tse

    2005-01-01

    Fibroblast is a crucial kind of cell in the construction of the tissue engineered dermal equivalent. In order to optimize the cryopreservation protocols of the tissue- engineered dermis, the characteristics of dermal fibroblast in subzero temperatures are required, which include the water permeability of the cell membrane and the apparent activation energy. Using the differential scanning calorimeter (DSC), the volumetric shrinkage during freezing of human dermal fibroblast suspensions was obtained at the cooling rate of 5℃·min-1 in the presence of extracellular ice. To ensure the presence of extracellular ice, a small quantity of ice nucleation bacteria (INA bacteria), pseudomonas syringae was added in the samples. And based on the Karlsson's model, a nonlinear- least-squares curve fitting technique was implemented to calculate the cryogenic parameters. At the reference temperature TR (= 0℃), the water permeability of membrane Lpg = 0.578μm·min-1·atm-1 and the apparent activation energy ELP = 308.8 kJ·mol-1. These parameters were then used to simulate water transport of fibroblast during constant cooling at rates between 0.01―50℃·min-1. The simulation results were analyzed to predict the amount of water left in the cell after dehydration and the "optimal cooling rate" for fibroblast cryopreservation. For the dermal fibroblast with DMEM solution, a cooling rate of 4.6℃·min-1 was optimal.

  16. Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal explants

    Science.gov (United States)

    Methicillin-resistant Staphylococcus aureus (MRSA) can infect wounds and produce difficult-to- treat biofilms. To determine the extent that MRSA biofilms can deplete oxygen, change pH and damage host tissue, we developed a porcine dermal explant model on which we cultured GFP-labeled MRSA biofilms. ...

  17. Dermal Absorption of Nanomaterials Titanium Dioxide and Zinc Oxide Based Sunscreen

    DEFF Research Database (Denmark)

    Beer, Christiane; Dokkedahl, Karin Stenderup; Wang, Jing

    of nanomaterials in products on the Danish market and their consequences on consumers and the environment. Furthermore, the aim is to clarify possible risks that might be associated with nanomaterials for consumers and the environment. The current project ’Dermal Absorption of Nanomaterials Titanium Dioxide...

  18. In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

    NARCIS (Netherlands)

    Olde damink, L.H.H.; Olde Damink, L.H.H.; Dijkstra, Pieter J.; van Luyn, M.J.A.; van Wachem, P.B.; Nieuwenhuis, P.; Feijen, Jan

    1996-01-01

    Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) crosslinked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide hydrochloride and N-hydroxysuccinimide (E/N-DSC) towards enzymatic degradation. Contrary to

  19. In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

    NARCIS (Netherlands)

    Damink, LHHO; Dijkstra, PJ; vanLuyn, MJA; vanWachem, PB; Nieuwenhuis, P; Feijen, J

    Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) cross-inked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide (EIN-DSC) towards enzymatic degradation. Contrary to

  20. High prevalence of dermal parasites among coral reef fishes of Curaçao

    NARCIS (Netherlands)

    M.A. Bernal; S.R. Floeter; M.R. Gaither; G.O. Longo; R. Morais; C.E.L. Ferreira; M.J.A. Vermeij; L.A. Rocha

    2015-01-01

    During expeditions to Curaçao in August and October of 2013, a large number of fish infected with dermal parasites was observed. Infected individuals presented black spots and white blemishes on their skin and fins that were easily observed by divers, and which have been associated with infections b

  1. Assessment of dermal exposure during airless spray painting using a quantitative visualisation technique

    NARCIS (Netherlands)

    Brouwer, D.H.; Lansink, C.M.; Cherrie, J.W.; Hemmen, J.J. van

    2000-01-01

    The range of dermal exposure to non-volatile compounds during spray painting was studied in a semi-experimental study involving three enterprises and 12 painters. A fluorescent tracer was added to the paint and deposition of the tracer on clothing and uncovered parts of the skin was assessed using v

  2. In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

    NARCIS (Netherlands)

    Damink, LHHO; Dijkstra, PJ; vanLuyn, MJA; vanWachem, PB; Nieuwenhuis, P; Feijen, J

    1996-01-01

    Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) cross-inked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide hydrochloride and N-hydroxysuccinimide (EIN-DSC) towards enzymatic degradation. Contrary to non-cross-

  3. Changes in the mechanical properties of dermal sheep collagen during in vitro degradation

    NARCIS (Netherlands)

    Olde Damink, L.H.H.; Dijkstra, P.J.; Luyn, van M.J.A.; Wachem, van P.B.; Nieuwenhuis, P.; Feijen, J.

    1995-01-01

    The changes in tensile strength, elongation at break, and high strain modulus of dermal sheep collagen (DSC) during in vitro degradation using bacterial collagenase were studied. The changes in mechanical properties were compared with the change in weight of the samples as a function of degradation

  4. CHANGES IN THE MECHANICAL-PROPERTIES OF DERMAL SHEEP COLLAGEN DURING IN-VITRO DEGRADATION

    NARCIS (Netherlands)

    DAMINK, LHHO; DIJKSTRA, PJ; VANLUYN, MJA; VANWACHEM, PB; NIEUWENHUIS, P; FEIJEN, J

    1995-01-01

    The changes in tensile strength, elongation at break, and high strain modulus of dermal sheep collagen (DSC) during in vitro degradation using bacterial collagenase were studied. The changes in mechanical properties were compared with the change in weight of the samples as a function of degradation

  5. In vitro degradation of dermal sheep collagen cross-linked using a water-soluble carbodiimide

    NARCIS (Netherlands)

    Olde Damink, L.H.H.; Dijkstra, P.J.; Luyn, van M.J.A.; Wachem, van P.B.; Nieuwenhuis, P.; Feijen, J.

    1996-01-01

    Bacterial collagenase was used to study the susceptibility of dermal sheep collagen (DSC) crosslinked with a mixture of the water-soluble carbodiimide 1-ethyl-3-(3-dimethyl aminopropyl)-carbodiimide hydrochloride and N-hydroxysuccinimide (E/N-DSC) towards enzymatic degradation. Contrary to non-cross

  6. Dermal pharmacokinetics of Terpinen-4-ol following topical administration of Zingiber cassumunar (plai) oil.

    Science.gov (United States)

    Chooluck, Kotchaphan; Singh, Rajendra P; Sathirakul, Korbtham; Derendorf, Hartmut

    2012-11-01

    The purpose of this study was to investigate dermal pharmacokinetics of terpinen-4-ol in rats following topical administration of plai oil derived from the rhizomes of Zingiber cassumunar Roxb. Unbound terpinen-4-ol concentrations in dermal tissue were measured by microdialysis. The dermal pharmacokinetic study of terpinen-4-ol was performed under non-occlusive conditions. The oil was topically applied at a dose of 2, 4, and 8 mg/cm2 plai oil corresponding to the amount of 1.0, 1.9, and 3.8 mg/cm2 terpinen-4-ol, respectively. Following topical application of the oil, terpinen-4-ol rapidly distributed into the dermis and demonstrated linear pharmacokinetics with no changes in the dose-normalized area under the concentration-time curves across the investigated dosage range. The mean percentages of free terpinen-4-ol distributed in the dermis per amount of administered were 0.39 ± 0.06 %, 0.41 ± 0.08 %, and 0.30 ± 0.03 % for 2, 4, and 8 mg/cm2 doses, respectively. The dermal pharmacokinetics of terpinen-4-ol could provide information for its further formulation development and therapy schedules. Georg Thieme Verlag KG Stuttgart · New York.

  7. Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators.

    Directory of Open Access Journals (Sweden)

    Pornthep Sirimahachaiyakul

    Full Text Available Abnormal pigmentation following cutaneous injury causes significant patient distress and represents a barrier to recovery. Wound depth and patient characteristics influence scar pigmentation. However, we know little about the pathophysiology leading to hyperpigmentation in healed shallow wounds and hypopigmentation in deep dermal wound scars. We sought to determine whether dermal fibroblast signaling influences melanocyte responses.Epidermal melanocytes from three Caucasians and three African-Americans were genotyped for single nucleotide polymorphisms (SNPs across the entire genome. Melanocyte genetic profiles were determined using principal component analysis. We assessed melanocyte phenotype and gene expression in response to dermal fibroblast-conditioned medium and determined potential mesenchymal mediators by proteome profiling the fibroblast-conditioned medium.Six melanocyte samples demonstrated significant variability in phenotype and gene expression at baseline and in response to fibroblast-conditioned medium. Genetic profiling for SNPs in receptors for 13 identified soluble fibroblast-secreted mediators demonstrated considerable heterogeneity, potentially explaining the variable melanocyte responses to fibroblast-conditioned medium.Our data suggest that melanocytes respond to dermal fibroblast-derived mediators independent of keratinocytes and raise the possibility that mesenchymal-epidermal interactions influence skin pigmentation during cutaneous scarring.

  8. High prevalence of dermal parasites among coral reef fishes of Curaçao

    NARCIS (Netherlands)

    Bernal, M.A.; Floeter, S.R.; Gaither, M.R.; Longo, G.O.; Morais, R.; Ferreira, C.E.L.; Vermeij, M.J.A.; Rocha, L.A.

    2016-01-01

    During expeditions to Curaçao in August and October of 2013, a large number of fish infected with dermal parasites was observed. Infected individuals presented black spots and white blemishes on their skin and fins that were easily observed by divers, and which have been associated with infections b

  9. Crosslinking and modification of dermal sheep collagen using 1,4-butanediol diglycidyl ether

    NARCIS (Netherlands)

    Zeeman, R; Dijkstra, PJ; van Wachem, PB; van Luyn, MJA; Hendriks, M; Cahalan, PT; Feijen, J

    1999-01-01

    Crosslinking of dermal sheep collagen (DSC) was accomplished using 1,4-butanediol diglycidyl ether (BDDGE). At pH values > 8.0, epoxide groups of BDDGE will react with amine groups of collagen. The effects of BDDGE concentration, pH, time, and temperature were studied. Utilization of a 4-wt % BDDGE

  10. RELATIONS BETWEEN INVITRO CYTOTOXICITY AND CROSS-LINKED DERMAL SHEEP COLLAGENS

    NARCIS (Netherlands)

    VANLUYN, MJA; VANWACHEM, PB; DAMINK, LO; DIJKSTRA, PJ; FEIJEN, J; NIEUWENHUIS, P

    Collagen-based biomaterials have found various applications in the biomedical field. However, collagen-based biomaterials may induce cytotoxic effects. This study evaluated possible cytotoxic effects of (crosslinked) dermal sheep collagen (DSC) using a 7-d-methylcellulose cell culture with human

  11. Reliability of a semi-quantitative method for dermal exposure assessment (DREAM)

    NARCIS (Netherlands)

    Wendel de Joode, B. van; Hemmen, J.J. van; Meijster, T.; Major, V.; London, L.; Kromhout, H.

    2005-01-01

    Valid and reliable semi-quantitative dermal exposure assessment methods for epidemiological research and for occupational hygiene practice, applicable for different chemical agents, are practically nonexistent. The aim of this study was to assess the reliability of a recently developed semi-quantita

  12. Immunopathology of post kala-azar dermal leishmaniasis (PKDL): T-cell phenotypes and cytokine profile

    DEFF Research Database (Denmark)

    Ismail, A; El Hassan, A M; Kemp, K

    1999-01-01

    In Sudan, post kala-azar dermal leishmaniasis (PKDL) caused by Leishmania donovani develops in half of the patients treated for visceral leishmaniasis (kala-azar). In most patients lesions heal spontaneously, but in others symptoms are severe and persist for years. This study examined...

  13. Exposure to fungicides in fruit growing: Re-entry time as a predictor for dermal exposure

    NARCIS (Netherlands)

    Tielemans, E.; Louwerse, E.; Cock, J. de; Brouwer, D.; Zielhuis, G.; Heederik, D.

    1999-01-01

    As part of a European Concerted Action on Male Reproduction Capability an exposure assessment survey was conducted among seasonal workers in the fruit growing sector in the Netherlands. Dermal exposure to the fungicides captan and tolylfluanid was measured using cotton gloves (12 persons) and skin p

  14. Red blood cell lysate modulates the expression of extracellular matrix proteins in dermal fibroblasts.

    Science.gov (United States)

    Akbari, Amir; Li, Yunyuan; Kilani, Ruhangiz T; Ghahary, Aziz

    2012-11-01

    During the early stage of wound healing process, blood clots can be served as a temporary extracellular matrix (ECM) to let skin cell migration and proliferation. The red blood cells are generally thought as inert bystanders in the early and inflammatory phase of wound healing. Here, we provide evidence that red blood cells (RBC) also play an important role in modulation of key ECM components such as type-I collagen, α-smooth muscle actin, fibronectin, and matrix metalloproteinases (MMPs). In this study, we used western blot analysis and showed a significant increase in the level of MMP-1, 2, 3. Furthermore, we found that RBC lysate significantly down-regulates type-I collagen and α-smooth muscle actin while up-regulates fibronectin expression in dermal fibroblasts. To further explore the mechanism by which RBC lysate modulates MMP-1 expression, the effect of inhibitors for three MAPK signaling pathways on RBC inducing MMP-1 expression by dermal fibroblasts were tested. The result showed that the inhibitor of ERK1/2 could abrogate the stimulatory effect of RBC lysate on MMP-1 expression in dermal fibroblasts. Consistently, RBC treatment results in an increase of ERK1/2 phosphorylation in dermal fibroblast. In conclusion, these findings suggest that RBC lysate can modulate the expression of MMPs and key ECM components which are important in healing process.

  15. Factors influencing success of pelvic organ prolapse repair using porcine dermal implant Pelvicol.

    NARCIS (Netherlands)

    Boer, T.A. de; Gietelink, D.A.; Hendriks, J.C.M.; Vierhout, M.E.

    2010-01-01

    OBJECTIVE: To evaluate factors influencing pelvic organ prolapse (POP) recurrence after repair surgery with a porcine dermal collagen implant (Pelvicol). STUDY DESIGN: From December 2003 to August 2005, 78 patients with mainly stage 3 pelvic organ prolapse by the Pelvic Organ Prolapse Quantification

  16. Dermal Matrices and Bioengineered Skin Substitutes: A Critical Review of Current Options

    Directory of Open Access Journals (Sweden)

    Heidi Debels, MD

    2015-01-01

    Conclusions: Skin substitutes are a useful tool in plastic and reconstructive surgery practices as an alternative to skin grafts. In the choice of substitute, the general plastic surgery principle of replacing like tissue with like tissue seems to be still standing, and products most resembling the natural dermal extracellular matrix should be preferred.

  17. Outcome of dermal grafting in the management of atrophic facial scars

    Directory of Open Access Journals (Sweden)

    Kanathur Shilpa

    2016-01-01

    Full Text Available Background: Scars over the face are cosmetically and psychologically disturbing. Various techniques have been described and are being practiced in the management of these scars. Aims and Objectives: This study was undertaken to study the safety, effectiveness of using dermal grafts as fillers in the management of facial scars due to acne, chickenpox, trauma or any others. Materials and Methods: Fifteen patients with atrophic facial scars of varied aetiology and willing for surgery were considered for dermal graft technique. After pre-operative workup, subcision was done 2 weeks before planned surgery. Depending on the type of scar, grafts were inserted using pocket or road railing techniques. Scar improvement was assessed based on patient satisfaction. Results: Linear scars showed excellent improvement. Acne, varicella and traumatic scars also showed good improvement. However, two patients did not appreciate improvement due to marked surface irregularities as the scars were elevated. They were further subjected to LASER and chemical peel resurfacing. Conclusion: Dermal grafting can be used in the management of any round to oval facial scar which is soft, prominent and at least 4-5 mm across; linear scars at least 2-3 mm across and 3-4 cm in length. However, scars with prominent surface irregularities need further resurfacing techniques along with dermal grafting. Limitations: Limitations of the study include small sample size, and only subjective assessment of the scar has been taken into consideration to assess the outcome.

  18. Determinants of Dermal Exposure Relevant for Exposure Modelling in Regulatory Risk Assessment

    NARCIS (Netherlands)

    Marquart, J.; Brouwer, D.H.; Gijsbers, J.H.J.; Links, I.H.M.; Warren, N.; Hemmen, J.J. van

    2003-01-01

    Risk assessment of chemicals requires assessment of the exposure levels of workers. In the absence of adequate specific measured data, models are often used to estimate exposure levels. For dermal exposure only a few models exist, which are not validated externally. In the scope of a large European

  19. Experimental dermatological surgery: An animal model for developing skills with dermal fillers

    Directory of Open Access Journals (Sweden)

    Juliana Catucci Boza

    2011-01-01

    Full Text Available The importance of laboratory experiments in the formation of physicians is well recognized since they facilitate scientific development and enhance technical skills. Dermal filling procedures are performed for the correction of wrinkles, rhytids, scars, and lipodystrophy. Till date, experimental models for the training of dermal filling techniques have not been studied. To demonstrate an experimental laboratory model for the training of dermal filling techniques in an animal model. The heads of pigs were used for this purpose, together with Carbopol gel at different densities, which was used to simulate the fillers available in the market. Needles and specific cannulas were used to apply the fillers into the creases and other areas of the pig skin. The pig head appears to be a suitable model for this training. Carbopol gel is a good choice for simulating fillers. This model of laboratory experiment requires a minimum of infrastructure; it is a low-cost alternative and facilitates practical training in the application of dermal fillers.

  20. Soil organic matter content effects on dermal pesticide bioconcentration in American toads (Bufo americanus).

    Science.gov (United States)

    Pesticides have been implicated as a major factor in global amphibian declines and may pose great risk to terrestrial phase amphibians moving to and from breeding ponds on agricultural landscapes. Dermal uptake from soil is known to occur in amphibians, but predicting pesticide a...