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Sample records for acute dermal ld50

  1. The acute lethal dose 50 (LD50) of caffeine in albino rats.

    PubMed

    Adamson, Richard H

    2016-10-01

    An acute LD50 is a statistically derived amount of a substance that can be expected to cause death in 50% of the animals when given by a specified route as a single dose and the animals observed for a specified time period. Although conducting routine acute toxicity testing in rodents has been criticized, it can serve useful functions and also have practical implications. Material safety data sheets (MSDS) will reflect the acute toxicity of a substance and may require workers to wear protective gear, if appropriate, based on the LD50. There is no information in the scientific published literature which calculates a mean LD50 and standard deviation for caffeine administered orally to rats, using studies performed under good laboratory practice (GLP) or equivalent. This report does that and should be useful to manufacturers, packagers, transporters and regulators of this material. Using data from studies that are reproducible and reliable, the most accurate estimate of the acute LD50 of caffeine administered orally in male albino rats is hereby reported to be 367/mg/kg.

  2. Use of the adaptive classifier for determination of LD50 in the acute radiation disease.

    PubMed

    Vodicka, I; Hanus, J; Hradil, J

    1989-01-01

    In experiments on female Wistar rats a new method for the determination of LD50 is demonstrated and compared with the classical probit method using the same experimental animals. The method is applicable for the computation of LD50 and analogical quantities in man, too. The method is based on the application of an adaptive logical circuit (ADALINE) trained for the dichotomous prognostic classification of irradiated individuals quod vitam according to a set of clinical and laboratory indicators registered on the third day after irradiation. After the training procedure has been finished, the classifier makes possible an individual prognosis of survival or death. The analogue output signal according to which the classification is performed changes continually from negative to positive values and exhibits S-shaped relation to the radiation dose. Its zero value corresponds to the position of LD50 on the abscissa. For the construction of the searched function, i.e. for the optimum approximation of experimentally obtained values of the output signal, the method of the changeable polyhedron was applied belonging to the optimalization numerical methods used in the regulation technics. The computed value of LD50 was 7.80 Gy in rats very closely corresponding with the value 7.61 Gy determined by means of the classical probit method.

  3. Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL)

    PubMed Central

    Abal, Paula; Louzao, M. Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luis M.

    2017-01-01

    Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard. PMID:28245573

  4. Acute Oral Toxicity of Tetrodotoxin in Mice: Determination of Lethal Dose 50 (LD50) and No Observed Adverse Effect Level (NOAEL).

    PubMed

    Abal, Paula; Louzao, M Carmen; Antelo, Alvaro; Alvarez, Mercedes; Cagide, Eva; Vilariño, Natalia; Vieytes, Mercedes R; Botana, Luis M

    2017-02-24

    Tetrodotoxin (TTX) is starting to appear in molluscs from the European waters and is a hazard to seafood consumers. This toxin blocks sodium channels resulting in neuromuscular paralysis and even death. As a part of the risk assessment process leading to a safe seafood level for TTX, oral toxicity data are required. In this study, a 4-level Up and Down Procedure was designed in order to determine for the first time the oral lethal dose 50 (LD50) and the No Observed Adverse Effect Level (NOAEL) in mice by using an accurate well-characterized TTX standard.

  5. Assessment of the predictive capacity of the 3T3 Neutral Red Uptake cytotoxicity test method to identify substances not classified for acute oral toxicity (LD50>2000 mg/kg): results of an ECVAM validation study.

    PubMed

    Prieto, Pilar; Cole, Thomas; Curren, Rodger; Gibson, Rosemary M; Liebsch, Manfred; Raabe, Hans; Tuomainen, Anita M; Whelan, Maurice; Kinsner-Ovaskainen, Agnieszka

    2013-04-01

    Assessing chemicals for acute oral toxicity is a standard information requirement of regulatory testing. However, animal testing is now prohibited in the cosmetics sector in Europe, and strongly discouraged for industrial chemicals. Building on the results of a previous international validation study, a follow up study was organised to assess if the 3T3 Neutral Red Uptake cytotoxicity assay could identify substances not requiring classification as acute oral toxicants under the EU regulations. Fifty-six coded industrial chemicals were tested in three laboratories, each using one of the following protocols: the previously validated protocol, an abbreviated version of the protocol and the protocol adapted for an automation platform. Predictions were very similar among the three laboratories. The assay exhibited high sensitivity (92-96%) but relatively low specificity (40-44%). Three chemicals were under predicted. Assuming that most industrial chemicals are not likely to be acutely toxic, this test method could prove a valuable component of an integrated testing strategy, a read-across argument, or weight-of-evidence approach to identify non toxic chemicals (LD50>2000 mg/kg). However, it is likely to under predict chemicals acting via specific mechanisms of action not captured by the 3T3 test system, or which first require biotransformation in vivo.

  6. Comparative study of the assay of Artemia salina L. and the estimate of the medium lethal dose (LD50 value) in mice, to determine oral acute toxicity of plant extracts.

    PubMed

    Logarto Parra, A; Silva Yhebra, R; Guerra Sardiñas, I; Iglesias Buela, L

    2001-09-01

    Artemia salina L. (Artemiidae), the brine shrimp larva, is an invertebrate used in the alternative test to determine toxicity of chemical and natural products. In this study the Medium Lethal Concentrations (LC50 value) of 20 plant extracts, Aloe vera (L.) Burm. F. (Aloeaceae), Artemisia absinthium L. (Asteraceae); Citrus aurantium L. (Rutaceae); Cymbopogon citratus (DC. Ex Nees) Stapf (Poaceae); Datura stramonium L. (Solanaceae); Justicia pectoralis Jacq. (Acanthaceae); Musa x paradisiaca L. (Musaceae); Ocimum basilicum L.; O. gratissimum L.; O. tenuiflorum L. (Lamiaceae); Pimenta dioica (L.) Merr. (Myrtaceae); Piper auritum Kunth (Piperaceae); Plantago major L. (Plantaginaceae); Plectranthus amboinicus (Lour.) Spreng. (Lamiaceae); Ruta graveolens L. (Rutaceae); Senna alata (L.) Roxb. (Fabaceae); Stachytarpheta jamaicensis (L.) Vahl (Verbenaceae); and Thuja occidentalis L. (Cupressaceae), were determined using Artemia salina L. (Artemiidae), with the objective of relating the results to the LD50 values reported in mice (tested at three concentrations: 10, 100, and 1000 microg/mL, for each extract). We found good correlation between the in vivo and the in vitro tests (r = 0.85 p < 0.05), and this method is a useful tool for predicting oral acute toxicity in plant extracts.

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

    PubMed Central

    Prado-Ochoa, María Guadalupe; Gutiérrez-Amezquita, Ricardo Alfonso; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    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. PMID:24883331

  8. Assessment of acute oral and dermal toxicity of 2 ethyl-carbamates with activity against Rhipicephalus microplus in rats.

    PubMed

    Prado-Ochoa, María Guadalupe; Gutiérrez-Amezquita, Ricardo Alfonso; Abrego-Reyes, Víctor Hugo; Velázquez-Sánchez, Ana María; Muñoz-Guzmán, Marco Antonio; Ramírez-Noguera, Patricia; Angeles, Enrique; Alba-Hurtado, Fernando

    2014-01-01

    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.

  9. Acute Oral Toxicity (LD(50)) of CHF1 in Rats.

    DTIC Science & Technology

    1982-04-01

    dimethylsiloxane polymer) Chemical Abstract Service Registry No.: None Molecular structure: linear polydimethylsiloxa,,. Molecular weight: about 25,000 g/moles pH...discomfort may result if rubbed into the eye). 3. Chemical Name: isopropanol Chemical Abstract Service Registry No.: 67-63-0 Molecular structure: CH 3CHOHCH 3...isopropyl alcohol. The formulation is a suspension that must be agitated to maintain continuity. 1. Chemical Name: N,N-diethyl-n-toluamide Chemical

  10. An investigation on LD50 and subacute hepatic toxicity of Nigella sativa seed extracts in mice.

    PubMed

    Vahdati-Mashhadian, N; Rakhshandeh, H; Omidi, A

    2005-07-01

    Nigella sativa seeds (blackseed) have been used in traditional medicine for the treatment of a variety of diseases including diarrhea and asthma, and have been shown to have various useful pharmacological effects. In this study, acute and subacute toxicity of the aqueous, methanol and chloroform extracts of the seeds have been investigated. To determine their LD50, the aqueous, methanol and chloroform extracts were administered orally, in 4 different doses, 6, 9, 14 and 21 g/kg. Mortality rate and weight changes have also been measured in all groups for 3 and 7 days, respectively. No mortality has been observed in all groups and with all doses. Methanol extracts in all doses and chloroform extract in the dose of 21 g/kg significantly decreased animals weight. Hepatic toxicity of the extracts was also investigated in the dose of 6 g/kg/day orally for 14 consecutive days by measuring ALP, SGOT and SGPT activity in blood and hepatic histological study. Degenerative changes in hepatic cells have been observed only with aqueous extract of the seeds. In conclusion, Nigella sativa extracts are relatively nontoxic in the acute toxicity test, but the possibility of hepatic damage with its aqueous extract should be considered.

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

    PubMed

    Korani, M; Rezayat, S M; Gilani, K; Arbabi Bidgoli, S; Adeli, S

    2011-01-01

    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 tissue abnormalities than the subjects of acute tests. It seems that colloidal nanosilver has the potential to provide target organ toxicities in a dose- and time-dependent manner.

  12. LD50 and repellent effects of essential oils from Argentinian wild plant species on Varroa destructor.

    PubMed

    Ruffinengo, Sergio; Eguaras, Martin; Floris, Ignazio; Faverin, Claudia; Bailac, Pedro; Ponzi, Marta

    2005-06-01

    The repellent and acaricidal effects of some essential oils from the most typical wild plant species of northern Patagonia, Argentina, on Varroa destructor Anderson & Trueman were evaluated using a complete exposure test. Honey bees, Apis mellifera L., and mites (five specimens of each per dish) were introduced in petri dishes having different oil concentrations (from 0.1 to 25 micro per cage). Survival of bees and mites was registered after 24, 48, and 72 h. An attraction/repellence test was performed using a wax tube impregnated with essential oil and another tube containing wax only. The lowest LD50 values for mites were registered for Acantholippia seriphioides (A. Gray) Mold. (1.27 microl per cage) and Schinus molle L. (2.65 microl per cage) after 24 h, and for Wedelia glauca (Ortega) O. Hoffm. ex Hicken (0.59 microl per cage) and A. seriphioides (1.09 microl per cage) after 72 h of treatment. The oil with the highest selectivity ratio (A. mellifera LD50/V. destructor LD50) was the one extracted from S. molle (>16). Oils of Lippia junelliana (Mold.) Troncoso, Minthostachys mollis (HBK) Grieseb., and Lippia turbinata Grieseb. mixed with wax had repellent properties. None of the oils tested had attractive effects on Varroa mites.

  13. Emerging toxicity of 5,6-methylenedioxy-2-aminoindane (MDAI): Pharmacokinetics, behaviour, thermoregulation and LD50 in rats.

    PubMed

    Páleníček, Tomáš; Lhotková, Eva; Žídková, Monika; Balíková, Marie; Kuchař, Martin; Himl, Michal; Mikšátková, Petra; Čegan, Martin; Valeš, Karel; Tylš, Filip; Horsley, Rachel R

    2016-08-01

    MDAI (5,6-Methylenedioxy-2-aminoindane) has a reputation as a non-neurotoxic ecstasy replacement amongst recreational users, however the drug has been implicated in some severe and lethal intoxications. Due to this, and the fact that the drug is almost unexplored scientifically we investigated a broad range of effects of acute MDAI administration: pharmacokinetics (in sera, brain, liver and lung); behaviour (open field; prepulse inhibition, PPI); acute effects on thermoregulation (in group-/individually-housed rats); and systemic toxicity (median lethal dose, LD50) in Wistar rats. Pharmacokinetics of MDAI was rapid, maximum median concentration in serum and brain was attained 30min and almost returned to zero 6h after subcutaneous (sc.) administration of 10mg/kg MDAI; brain/serum ratio was ~4. MDAI particularly accumulated in lung tissue. In the open field, MDAI (5, 10, 20 and 40mg/kg sc.) increased exploratory activity, induced signs of behavioural serotonin syndrome and reduced locomotor habituation, although by 60min some effects had diminished. All doses of MDAI significantly disrupted PPI and the effect was present during the onset of its action as well as 60min after treatment. Unexpectedly, 40mg/kg MDAI killed 90% of animals in the first behavioural test, hence LD50 tests were conducted which yielded 28.33mg/kg sc. and 35mg/kg intravenous but was not established up to 40mg/kg after gastric administration. Disseminated intravascular coagulopathy (DIC) with brain oedema was concluded as a direct cause of death in sc. treated animals. Finally, MDAI (10, 20mg/kg sc.) caused hyperthermia and perspiration in group-housed rats. In conclusion, the drug had fast pharmacokinetics and accumulated in lipohilic tissues. Behavioural findings were consistent with mild, transient stimulation with anxiolysis and disruption of sensorimotor processing. Together with hyperthermia, the drug had a similar profile to related entactogens, especially 3

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

    USGS Publications Warehouse

    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.

  15. Oral LD50 toxicity modeling and prediction of per- and polyfluorinated chemicals on rat and mouse.

    PubMed

    Bhhatarai, Barun; Gramatica, Paola

    2011-05-01

    Quantitative structure-activity relationship (QSAR) analyses were performed using the LD(50) oral toxicity data of per- and polyfluorinated chemicals (PFCs) on rodents: rat and mouse. PFCs are studied under the EU project CADASTER which uses the available experimental data for prediction and prioritization of toxic chemicals for risk assessment by using the in silico tools. The methodology presented here applies chemometrical analysis on the existing experimental data and predicts the toxicity of new compounds. QSAR analyses were performed on the available 58 mouse and 50 rat LD(50) oral data using multiple linear regression (MLR) based on theoretical molecular descriptors selected by genetic algorithm (GA). Training and prediction sets were prepared a priori from available experimental datasets in terms of structure and response. These sets were used to derive statistically robust and predictive (both internally and externally) models. The structural applicability domain (AD) of the models were verified on 376 per- and polyfluorinated chemicals including those in REACH preregistration list. The rat and mouse endpoints were predicted by each model for the studied compounds, and finally 30 compounds, all perfluorinated, were prioritized as most important for experimental toxicity analysis under the project. In addition, cumulative study on compounds within the AD of all four models, including two earlier published models on LC(50) rodent analysis was studied and the cumulative toxicity trend was observed using principal component analysis (PCA). The similarities and the differences observed in terms of descriptors and chemical/mechanistic meaning encoded by descriptors to prioritize the most toxic compounds are highlighted.

  16. Acute Oral Toxicity (LD50) of 4-Nitrophenyl Monochloromethyl (Phenyl) Phosphinate (TA009) in Male Rats

    DTIC Science & Technology

    1984-10-01

    phosphinates hydrolyze readily in aqueous solutions, a vehicle which would minimize the rate of hydrolysis was required. A mixture of Tween 80 (Fisher...monochloroiethyl (phenyl) phosphinat_. formulated with Tween 80 , EtOH, and citrate buffer (LAIR SOP-OP-STX-45, Preparation of Compounds Unstable in Water...phosphinate. 16.0 ml Tween 80 8.0 ml (100 %) ethanol, 56.0 ml citrate buffer (50 mM) at a pH of 3.2. The vehicle was the same as above without phosphinate. pH

  17. Acute Oral Toxicity (LD50) of 4-Nitrophenyl Monochloromethyl (Phenyl) Phosphinate (TA009) in Female Rats

    DTIC Science & Technology

    1984-10-01

    chosen was a mixture of Tween 80 (Fisher Scientific Company, Fairlawn, NJ) ethanol and citrate buffer (pH 2.9). Additional information on the vehicle...phosphinate formulated with Tween 80 , EtOH, and citrate buffer (LAIR SOP-OP-STX-45, Preparation of Compounds Unstable in Water for SLRL Assay). A 2.0...percent phosphinate solution was prepared with 1.5 g 4- nitrophenyl monochloromethyl (phenyl) phosphinate. 15.0 ml Tween 80 7.5 ml (100 %) ethanol

  18. Acute Dermal Toxicity of Guanidine Hydrochloride in Rabbits

    DTIC Science & Technology

    1989-12-01

    with electric clippers (Oster®b Model A5, Size 40 blade, Sunbeam Corp, Milwaukee, WI) 24 hours before applying the test compound. The animals were...1984 2. Animals were close-clipped and examined 24 hours before dosing Justification: The laboratory rabbit is a proven mammalian model for dermal...died were necropsied within 16 hours after death. The remaining animls were killed by exsanguination while under pentobarbital anesthesia after a 14

  19. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CONTROL ACT (CONTINUED) IDENTIFICATION OF SPECIFIC CHEMICAL SUBSTANCE AND MIXTURE TESTING REQUIREMENTS... mixtures. In order to minimize the need for animal testing, the Agency encourages the review of existing acute toxicity information on mixtures that are substantially similar to the mixture under...

  20. Acute Dermal Toxicity of CHF1, CHR2 and Saline in Rabbits.

    DTIC Science & Technology

    1982-09-01

    yellowish-white foci in the liv*-r that are typical (f lecions caused by Eimeria stiedae , a coccidia that infects in-rahentic bile ducts of rabbits . Thene...AD-A12i 944 ACUTE DERI1ALTTOXICITY OF CHFi CHR2 AND SALINE IN / RABBITS (U) LETTERMAN ARMY INST OF RESEARCH PRESIDIO OF SAN FRANCISCO CA M A HANES ET...NdATIONiAL 3SPIA OF SITiOAM - 963 -A - INSTITUTE REPORT NO. 130 S ACUTE DERMAL TOXICITY OF CHF 1, CHR 2 AND SALINE IN RABBITS MARTHA A. HANES, DVM, CPT VC JOHN

  1. Extensive review of fish embryo acute toxicities for the prediction of GHS acute systemic toxicity categories.

    PubMed

    Scholz, Stefan; Ortmann, Julia; Klüver, Nils; Léonard, Marc

    2014-08-01

    Distribution and marketing of chemicals require appropriate labelling of health, physical and environmental hazards according to the United Nations global harmonisation system (GHS). Labelling for (human) acute toxicity categories is based on experimental findings usually obtained by oral, dermal or inhalative exposure of rodents. There is a strong societal demand for replacing animal experiments conducted for safety assessment of chemicals. Fish embryos are considered as alternative to animal testing and are proposed as predictive model both for environmental and human health effects. Therefore, we tested whether LC50s of the fish embryo acute toxicity test would allow effectively predicting of acute mammalian toxicity categories. A database of published fish embryo LC50 containing 641 compounds was established. For these compounds corresponding rat oral LD50 were identified resulting in 364 compounds for which both fish embryo LC50 and rat LD50 was available. Only a weak correlation of fish embryo LC50 and rat oral LD50 was obtained. Fish embryos were also not able to effectively predict GHS oral acute toxicity categories. We concluded that due to fundamental exposure protocol differences (single oral dose versus water-borne exposure) a reverse dosimetry approach is needed to explore the predictive capacity of fish embryos.

  2. Role of interleukin-1 and tumour necrosis factor in leukocyte recruitment to acute dermal inflammation

    PubMed Central

    Lopes, Nancy; Issekutz, Thomas B.

    1992-01-01

    The cytokines IL-1 and TNF-α are involved in inflammation and their production is stimulated by various agents, especially endotoxin (LPS). Here, using the human IL-1 receptor antagonist (IL-1RA) and a new monoclonal antibody (mAb 7F11) to rabbit TNF, the role of endogenous IL-l and TNF production in acute (3h) leukocyte (PMNL) recruitment to dermal inflammation in rabbits has been studied. IL-1RA inhibited by 27% the PMNL accumulation in reactions induced by killed Escherichia coli (p < 0.05) but not by LPS. The monoclonal antibody to TNF inhibited by 27% and 38% (p < 0.002) the PMNL accumulation in LPS and E. coli reactions respectively, but a combination of the mAb with IL-1RA was not more effective. Treatment of human umbilical vein endothelium with LPS for 3 h activated endothelium to induce PMNL transendothelial migration in vitro, which was not inhibited by IL-1RA, antibody to TNF-α, IL-1 or to IL-8. In conclusion, TNF and IL-1 may partially mediate acute PMNL infiltration in vivo to LPS and Gram negative bacteria, but there is a major IL-1/TNF independent mechanism, at least in dermal inflammation, which may be due to direct LPS activation of the microvasculature or perhaps the generation of cytokines other than IL-1 and TNF. PMID:18475483

  3. Alum adjuvanted rabies DNA vaccine confers 80% protection against lethal 50 LD50 rabies challenge virus standard strain.

    PubMed

    Garg, Rajni; Kaur, Manpreet; Saxena, Ankur; Prasad, Rajendra; Bhatnagar, Rakesh

    2017-03-03

    Rabies is a serious concern world-wide. Despite availability of rabies vaccines for long; their efficacy, safety, availability and cost effectiveness has been a tremendous issue. This calls for improvement of rabies vaccination strategies. DNA vaccination has immense potential in this regard. The DNA vaccine pgp.LAMP-1 conferred 60% protection to BALB/c mice against 20 LD50 rabies challenge virus standard (CVS) strain challenge. Upon supplementation with Emulsigen-D, the vaccine formulation conferred complete protection against lethal challenge. To assess the feasibility of this vaccine formulation for human use, it was tested along with other FDA approved adjuvants, namely, Alum, Immuvac, Montanide ISA720 VG. Enhanced immune response correlated with high IgG antibody titer, Th2 biased response with a high level of rabies virus neutralizing antibodies (RVNAs) and IgG1/IgG2a ratio >1, observed upon alum supplementation of the rabies DNA vaccine. The total IgG antibody titer was 2IU/ml and total RVNA titer was observed to be 4IU/ml which is eight times higher than the minimum protective titer recommended by WHO. Furthermore, it conferred 80% protection against challenge with 50 LD50 of the rabies CVS strain, conducted in compliance with the potency test for rabies recommended by the National Institutes of Health (NIH), USA. Previously, we have established pre-clinical safety of this vaccine as per the guidelines of Schedule Y, FDA as well as The European Agency for evaluation of Medicinal Products. The vaccine showed no observable toxicity at the site of injection as well as at systemic level in Wistar rats when administered with 10X recommended dose. Therefore, supplementation of rabies DNA vaccine, pgp.LAMP-1 with alum would lead to development of a non-toxic, efficacious, stable and affordable vaccine that can be used to combat high numbers of fatal rabies infections tormenting developing countries.

  4. Biosafety of an entomopathogenic fungus Isaria fumosorosea in an acute dermal test in rabbits.

    PubMed

    Brunner-Mendoza, Carolina; Navarro-Barranco, Hortensia; León-Mancilla, Benjamín; Pérez-Torres, Armando; Toriello, Conchita

    2017-03-01

    Isaria fumosorosea (formerly Paecilomyces fumosoroseus) is an entomopathogenic fungus that has been proposed as a low risk environmental alternative to the use of chemical insecticides to control agricultural pests and disease vectors. Although there are some mycoinsecticides already being marketed in many countries, not all their biosafety protocols have been published. The acute dermal toxicity test in an animal model is one in a series of biosafety protocols that must be developed, in order to provide information on health hazards, while taking into consideration the periods that the workers are in direct contact with the microbial agent when applied for the control of pests. For this test, we used I. fumosorosea monospore culture EH-506/3, isolated in Mexico from the Bemisia tabaci whitefly, applying a dose of 2 g/kg of animal body weight, on the shaved skin of 16 New Zealand rabbits, with an exposure time of 24 h. Clinical observations were conducted to evaluate the presence of erythema, edema and other alterations in the skin, as well as the behavior and health of the animals, for a period of 14 days. None of the rabbits showed clinical signs of any disease and their body weight corresponded to the expected weight for a healthy rabbit. The test showed no inflammatory reactions in the skin, supporting the safety of a single dose of this fungus in dermal exposure. Therefore, these data support the safety of I. fumosorosea EH-506/3 when applied to the skin.

  5. Monomethylarsonous acid (MMA(III)) and arsenite: LD(50) in hamsters and in vitro inhibition of pyruvate dehydrogenase.

    PubMed

    Petrick, J S; Jagadish, B; Mash, E A; Aposhian, H V

    2001-06-01

    Monomethylarsonous acid (MMA(III)), a metabolite of inorganic arsenic, has received very little attention from investigators of arsenic metabolism in humans. MMA(III), like sodium arsenite, contains arsenic in the +3 oxidation state. Although we have previously demonstrated that it is more toxic than arsenite in cultured Chang human hepatocytes, there are no data showing in vivo toxicity of MMA(III). When MMA(III) or sodium arsenite was administered intraperitoneally to hamsters, the LD(50)s were 29.3 and 112.0 micromol/kg of body wt, respectively. In addition, inhibition of hamster kidney or purified porcine heart pyruvate dehydrogenase (PDH) activity by MMA(III) or arsenite was determined. To inhibit hamster kidney PDH activity by 50%, the concentrations (mean +/- SE) of MMA(III) as methylarsine oxide, MMA(III) as diiodomethylarsine, and arsenite were 59.9 +/- 6.5, 62.0 +/- 1.8, and 115.7 +/- 2.3 microM, respectively. To inhibit activity of purified porcine heart PDH activity by 50%, the concentrations (mean +/- SE) of MMA(III) as methylarsine oxide and arsenite were 17.6 +/- 4.1 and 106.1 +/- 19.8 microM, respectively. These data demonstrate that MMA(III) is more toxic than inorganic arsenite, both in vivo and in vitro, and call into question the hypothesis that methylation of inorganic arsenic is a detoxication process.

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

    PubMed

    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.

  7. Measuring the potency labelling of onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin (®)) in an LD50 assay.

    PubMed

    Dressler, Dirk; Mander, Gerd; Fink, Klaus

    2012-01-01

    The biological potency of botulinum toxin (BT) drugs is determined by a standardised LD50 assay. However, the potency labelling varies vary amongst different BT drugs. One reason for this may be differences in the LD50 assays applied. When five unexpired batches of onabotulinumtoxinA (Botox(®)) and incobotulinumtoxinA (Xeomin(®)) are compared in the Xeomin(®) batch release assay, the potency variability of both BT drugs fell within the range allowed by the European Pharmacopoiea. Statistical analyses failed to detect differences in the potency labelling of both products. Although the existence of a conversion ratio has been questioned recently, our experimental data are in line with previous clinical experience showing that Botox(®) and Xeomin(®) can be compared using a 1:1 conversion ratio. Identical potency labelling allows easy exchange of both BT drugs in a therapeutic setting, and direct comparison of efficacy, adverse effects and costs.

  8. Fatality due to acute fluoride poisoning following dermal contact with hydrofluoric acid in a palynology laboratory.

    PubMed

    Muriale, L; Lee, E; Genovese, J; Trend, S

    1996-12-01

    A fatal accident involving concentrated hydrofluoric acid in a palynological laboratory is described. Similar deaths due to dermal exposure to concentrated hydrofluoric acid have been reported in the literature. It is evident that rigorous control measures including proper personal protective equipment and first aid are of utmost importance in the prevention of death and injury when handling hydrofluoric acid. Possible factors that may have contributed to the accident are reviewed.

  9. Evaluation of the Acute Toxicity, Irritation, Sensitization, and Subchronic Dermal Toxicity of Antimony Thioantimonate Lubricant

    DTIC Science & Technology

    1986-03-01

    ATA ....................... 17 12 Female Rabbit Hematology and Clinical Chemistry Values After 90-Day Dermal Exposure to ATA Material...the study, blood was drawn from the rabbits via cardiac puncture for hematologic and clinical chemistry preexposure determinations (Table 1). Blood was...brain weights of rabbits treated with the ATA. Hematology and clinical chemistry examinations conducted on male rabbits at 4 and 13 weeks of exposure and

  10. Acute and environmental toxicity studies with hexazinone

    SciTech Connect

    Kennedy, G.L. Jr.

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.

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

    PubMed

    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.

  12. Acute Intramuscular Toxicity (LD50) of 1,1’-Methylenebis (4- (Hydroxyimino) Methyl) Pyridinium Dibromide, (MMB-4) in Male Mice

    DTIC Science & Technology

    1983-04-01

    METHODS Test Substance Chemical name: 1,1 ’-Methylenebis[4-[(hydroxyimino) methyl] pyridinium] dibromide, (01MB-4) (TAO03) Chemical Abstract Service...name: 1,1 ’-Methylenebis[4-[(hydroxyimino)methyl] pyridiniumldibromide, (CMIB-1 𔃾 Chemical Abstract Service Registry Number: None Molecular formula

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

    PubMed Central

    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

  14. Acute and environmental toxicity studies with hexazinone.

    PubMed

    Kennedy, G L

    1984-08-01

    The acute toxicity of hexazinone, a herbicide intended for general noncropland areas and selected crop uses (alfalfa and sugarcane), has been evaluated to establish proper handling guidelines and to measure its potential impact on the environment. The material is slightly to moderately toxic when given as a single oral dose; its LD50 in male rats is 1690 mg/kg, in male guinea pigs 860 mg/kg, and in male dogs greater than 3400 mg/kg although in the dog emesis prevented accurate quantitation. When the material is administered intraperitoneally, the LD50 in rats is 530 mg/kg. Repeated doses (five oral doses per week for 2 weeks) of 300 mg/kg to rats produced slight weight loss in one of two replicate experiments. In both studies, no gross or histologic alterations were apparent. Hexazinone is a moderate to severe eye irritant in the rabbit and produced only mild erythema in rabbit skin at 5278 mg/kg, a dose which did not produce lethality or other clinical signs. Subchronic dermal exposures (10 consecutive doses) to rabbits produced increases in serum alkaline phosphatase and glutamic-pyruvic transaminase at the highest levels tested (680 and 770 mg/kg in two separate experiments) with no effects seen at 150 mg/kg. There were no alterations in livers from treated rabbits examined by light microscopy. No dermal sensitization was produced when concentrations of up to 50% were tested in guinea pigs. One-hour inhalation exposure of up to 7.48 mg/liter did not produce mortality in rats.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Acute Dermal Toxicity Potential of (E)-1,2,3,4-Tetrahydro-6-Methyl-1-(2-Methyl-1-Oxo-2-Butenyl) Quinoline (CHR 5) in Rabbits.

    DTIC Science & Technology

    1983-06-01

    typical of bacterial infection and the liver lesions were compatible with those caused by Eimeria stiedae , a protozoan parasite that frequently infects...quinoline (CHR 5) IN RABBITS LAWRENCE MULLEN, BS, SP4 MARTHA A. HANES, DVM, CPT VC and PAUL MELLICK, DVM, PhD, LTC VC TOXICOLOGY GROUP, DIVISION OF...I = ඛ 08 22 058 4. Acute Dermal Toxicity Potential of (E)-1,2,3,4-Tetrahydro-6-Methyl- 1-(2-Methyl-l-Oxo-2-Butenyl) Quinoline (CHR5) in Rabbits

  16. RNA-Seq Transcriptomic Responses of Full-Thickness Dermal Excision Wounds to Pseudomonas aeruginosa Acute and Biofilm Infection

    PubMed Central

    Chen, Tsute; Qian, Li-Wu; Fourcaudot, Andrea B.; Yamane, Kazuyoshi; Chen, Ping; Abercrombie, Johnathan J.; You, Tao; Leung, Kai P.

    2016-01-01

    Pseudomonas aeruginosa infections of wounds in clinical settings are major complications whose outcomes are influenced by host responses that are not completely understood. Herein we evaluated transcriptomic changes of wounds as they counter P. aeruginosa infection—first active infection, and then chronic biofilm infection. We used the dermal full-thickness, rabbit ear excisional wound model. We studied the wound response: towards acute infection at 2, 6, and 24 hrs after inoculating 106 bacteria into day-3 wounds; and, towards more chronic biofilm infection of wounds similarly infected for 24 hrs but then treated with topical antibiotic to coerce biofilm growth and evaluated at day 5 and 9 post-infection. The wounds were analyzed for bacterial counts, expression of P. aeruginosa virulence and biofilm-synthesis genes, biofilm morphology, infiltrating immune cells, re-epithelialization, and genome-wide gene expression (RNA-Seq transcriptome). This analysis revealed that 2 hrs after bacterial inoculation into day-3 wounds, the down-regulated genes (infected vs. non-infected) of the wound edge were nearly all non-coding RNAs (ncRNAs), comprised of snoRNA, miRNA, and RNU6 pseudogenes, and their down-regulation preceded a general down-regulation of skin-enriched coding gene expression. As the active infection intensified, ncRNAs remained overrepresented among down-regulated genes; however, at 6 and 24 hrs they changed to a different set, which overlapped between these times, and excluded RNU6 pseudogenes but included snRNA components of the major and minor spliceosomes. Additionally, the raw counts of multiple types of differentially-expressed ncRNAs increased on post-wounding day 3 in control wounds, but infection suppressed this increase. After 5 and 9 days, these ncRNA counts in control wounds decreased, whereas they increased in the infected, healing-impaired wounds. These data suggest a sequential and coordinated change in the levels of transcripts of multiple

  17. Acute toxicity of four anticholinesterase insecticides to American kestrels, eastern screech-owls and northern bobwhites

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Sparling, D.W.

    1991-01-01

    American kestrels (Falco sparverius), eastern screech-owls (Otus asio), and northern bobwhites (Colinus virginianus) were given single acute oral doses of four widely diverse anticholinesterase pesticides: EPN, fenthion, carbofuran, and monocrotophos. LD50s, based on birds that died within 5 d of dosage, were computed for each chemical in each species. Sex differences in the sensitivity of northern bobwhites in reproductive condition were examined. American kestrels were highly sensitive to all chemicals tested (LD50s 0.6--4.0 mg/kg). Eastern screech-owls were highly tolerant to EPN (LD50 274 mg/kg) but sensitive to the remaining chemicals (LD50s 1.5-3.9 mg/kg). Northern bobwhites were highly sensitive to monocrotophos (LD50 0.8 mg/kg) and less sensitive to the remaining chemicals (LD50s 4.6--31 mg/kg). Female bobwhites (LD50 3.1 mg/kg) were more sensitive to fenthion than males (LD50 7.0 mg/kg). Mean percent depression of brain cho[inesterase (ChE) of birds that died on the day of dosing exceeded 65% for all chemicals in all species. The response of one species to a given pesticide should not be used to predict the sensitivity of other species to the same pesticide. The need for research on several topics is discussed

  18. Acute toxicity of pesticides in adult and weanling rats.

    PubMed

    Gaines, T B; Linder, R E

    1986-08-01

    LD50 values were determined for 57 pesticides administered by the oral or dermal route to adult male and female Sherman rats. Thirty-six of the chemicals were also tested by the oral route in one sex of weanlings. Nine pesticides tested by the oral route (bufencarb, cacodylic acid, dialifor, deltamethrin, dicamba, diquat, quintozene, phoxim, pyrazon) and four tested by the dermal route (bufencarb, chlordimeform, dichlofenthion, leptophos) were more toxic to females than to males whereas famphur and 2,4,5-T (oral route) were less toxic to females. Eighteen of the test chemicals were more toxic to the adult than to the weanling and four compounds (leptophos, methidathion, pyrazon, and sulfoxide) were more toxic to the weanling. In additional studies the variability of the LD50 value over a 1-year period was examined for two typical insecticides. Six consecutive bimonthly oral LD50 determinations for parathion and DDT in adults of both sexes indicated that the LD50 values were little affected by the time of year that the tests were done.

  19. An evaluation of acute toxicity of colloidal silver nanoparticles.

    PubMed

    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.

  20. Evaluation of neurotoxicity of repeated dermal application of chlorpyrifos on hippocampus of adult mice.

    PubMed

    Mitra, Nilesh K; Siong, How Hee; Nadarajah, Vishna D

    2008-01-01

    Dermal absorption of chlorpyrifos, an organophosphate insecticide is important because of its use in agriculture and control of household pests. The objectives of this study are to investigate firstly, the biochemical changes in the blood and secondly, histomorphometric changes in the hippocampus of adult mice following dermal application of chlorpyrifos in sub-toxic doses. Male Swiss albino mice (60 days) were segregated into one control and two treated groups (n=10). Chlorpyrifos, diluted with xylene, was applied in doses of 1/2 of LD(50) (E1) and 1/5 of LD(50) (E2) over the tail of mice of the two treated groups, 6 hours daily for 3 weeks. AChE levels in the serum and brain were estimated using a spectrophotometric method (Amplex Red reagent). Coronal serial sections were stained with 0.2 % thionin in acetate buffer and pyramidal neurons of Cornu Ammonis of hippocampus were counted at 400x magnification using Image Pro Express software. At the end of 3 weeks, body weights were reduced significantly in E1 group. Serum AChE concentrations were reduced by 97 % in E1 and 74 % in E2 groups compared to controls. The neurons of CA 3 and CA 1 in the hippocampus showed evidences of morphological damage in both treated groups. Furthermore, the neuronal count was significantly reduced in CA 3 layer of hippocampus in E1 group.

  1. CDP-choline: acute toxicity study.

    PubMed

    Grau, T; Romero, A; Sacristán, A; Ortiz, J A

    1983-01-01

    The acute toxicity of a single dose of cytidine diphosphate choline (CDP-choline, citicoline, Somazina) by different administration routes in mice and rats has been studied. LD50 values were determined according to the cumulative method by Reed-Muench for mortality rate, and Pizzi's method for calculation of standard error.

  2. Consensus Modeling of Oral Rat Acute Toxicity

    EPA Science Inventory

    An acute toxicity dataset (oral rat LD50) with about 7400 compounds was compiled from the ChemIDplus database. This dataset was divided into a modeling set and a prediction set. The compounds in the prediction set were selected so that they were present in the modeling set used...

  3. Acute Dermal Irritation Study and Salmonella-Escherichia coli/Microsome Plate Incorporation Assay of Hydroprocessed Esters and Fatty Acids (HEFA) Bio-Based Jet Fuels

    DTIC Science & Technology

    2013-01-01

    Nutrition International, LLC (St. Louis MO), Certified High Fiber Rabbit LabDiet® 5325, is a certified feed with appropriate analyses performed by the...of the Safety of Chemicals in Foods, Drugs and Cosmetics – Dermal Toxicity. Association of Food and Drug Officials of the United States, Topeka, KS

  4. Acute toxicity of seeds of the sapodilla (Achras sapota L.).

    PubMed

    Singh, P D; Simon, W R; West, M E

    1984-01-01

    An aqueous extract of the sapodilla seed (Achras sapota L.) was acutely toxic to mice and rats (i.p. LD50 = 190 and 250 mg/kg, respectively) with symptoms of dyspnoea, apnoea and convulsions. Soxhlet extraction and chromatographic separation of the seed constituents yielded a brown amorphous solid containing saponin. This was heat-stable and toxic by the i.p. route (LD50 = 30-50 mg/kg) but non-toxic by the oral route in mice and rats. It is proposed that the toxicity of the sapodilla seed is due mainly to the saponin content.

  5. Non-animal Replacements for Acute Toxicity Testing.

    PubMed

    Barker-Treasure, Carol; Coll, Kevin; Belot, Nathalie; Longmore, Chris; Bygrave, Karl; Avey, Suzanne; Clothier, Richard

    2015-07-01

    Current approaches to predicting adverse effects in humans from acute toxic exposure to cosmetic ingredients still heavily necessitate the use of animals under EU legislation, particularly in the context of the REACH system, when cosmetic ingredients are also destined for use in other industries. These include the LD50 test, the Up-and-Down Procedure and the Fixed Dose Procedure, which are regarded as having notable scientific deficiencies and low transferability to humans. By expanding on previous in vitro tests, such as the animal cell-based 3T3 Neutral Red Uptake (NRU) assay, this project aims to develop a truly animal-free predictive test for the acute toxicity of cosmetic ingredients in humans, by using human-derived cells and a prediction model that does not rely on animal data. The project, funded by Innovate UK, will incorporate the NRU assay with human dermal fibroblasts in animal product-free culture, to generate an in vitro protocol that can be validated as an accepted replacement for the currently available in vivo tests. To date, the project has successfully completed an assessment of the robustness and reproducibility of the method, by using sodium lauryl sulphate (SLS) as a positive control, and displaying analogous results to those of the original studies with mouse 3T3 cells. Currently, the testing of five known ingredients from key groups (a surfactant, a preservative, a fragrance, a colour and an emulsifier) is under way. The testing consists of initial range-finding runs followed by three valid runs of a main experiment with the appropriate concentration ranges, to generate IC50 values. Expanded blind trials of 20 ingredients will follow. Early results indicate that this human cell-based test holds the potential to replace aspects of in vivo animal acute toxicity testing, particularly with reference to cosmetic ingredients.

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

    PubMed Central

    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. PMID:28255340

  7. Acute sarin exposure causes differential regulation of choline acetyltransferase, acetylcholinesterase, and acetylcholine receptors in the central nervous system of the rat.

    PubMed

    Khan, W A; Dechkovskaia, A M; Herrick, E A; Jones, K H; Abou-Donia, M B

    2000-09-01

    Acute neurotoxic effects of sarin (O:-isopropylmethylphosphonoflouridate) in male Sprague-Dawley rats were studied. The animals were treated with intramuscular (im) injections of either 1 x LD(50) (100 microg/kg), and sacrificed at 0. 5, 1, 3, 6, 15, or 20 h after treatment, or with im injections of either 0.01, 0.1, 0.5, or 1 x LD(50) and sacrificed 15 h after treatment. Plasma butyrylcholinesterase (BChE) and brain regional acetylcholinesterase (AChE) were inhibited (45-55%) by 30 min after the LD(50) dose. BChE in the plasma and AChE in cortex, brainstem, midbrain, and cerebellum remained inhibited for up to 20 h following a single LD(50) treatment. No inhibition in plasma BChE activity was observed 20 h after treatment with doses lower than the LD(50) dose. Midbrain and brainstem seem to be most responsive to sarin treatment at lower doses, as these regions exhibited inhibition (approximately 49% and 10%, respectively) in AChE activity following 0.1 x LD(50) treatment, after 20 h. Choline acetyltransferase (ChAT) activity was increased in cortex, brainstem, and midbrain 6 h after LD(50) treatment, and the elevated enzyme activity persisted up to 20 h after treatment. Cortex ChAT activity was significantly increased following a 0.1 x LD(50) dose, whereas brainstem and midbrain did not show any effect at lower doses. Treatment with an LD(50) dose caused a biphasic response in cortical nicotinic acetylcholine receptor (nAChR) and muscarinic acetylcholine receptor (m2-mAChR) ligand binding, using [(3)H]cytisine and [(3)H]AFDX-384 as ligands for nAChR and mAChR, respectively. Decreases at 1 and 3 h and consistent increases at 6, 15, and 20 h in nAChR and m2-mAChR were observed following a single LD(50) dose. The increase in nAChR ligand binding densities was much more pronounced than in mAChR. These results suggest that a single exposure of sarin, ranging from 0.1 to 1 x LD(50), modulates the cholinergic pathways differently and thereby causes dysregulation in

  8. Dermal exposure assessment.

    PubMed

    Schneider, T; Cherrie, J W; Vermeulen, R; Kromhout, H

    2000-10-01

    Assessing dermal exposure is a complex task. Even the most commonly used methods face fundamental problems and there are large gaps in the documentation and validation of sampling methods. Still larger uncertainties exist regarding strategies for measurement. We propose a strategy based on a conceptual model and which draws on the considerable insight gained for airborne contaminants, including EN 689 for assessing exposure by inhalation. The vast amount of air sampling data has provided good insight into the statistical properties of short-term and long-term exposure levels, which is essential for designing cost-effective exposure studies. For surface and skin contaminants an understanding of the distribution types and parameter values is only beginning to emerge. Transport rates away from the skin contaminant layer determine the 'memory' of a dermal sample and measurement principles are proposed depending on these rates. It is argued that uptake is the ultimate dermal exposure metric for risk assessment and should be the basis for devising dermal occupational exposure limits.

  9. 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

    DTIC Science & Technology

    2014-02-01

    to hydrocarbon (DSHC), is very different from the other fuels. Produced from fermentation of sugar by engineered microorganisms , this fuel is more...Wright-Patterson AFB, OH 45433-5707 Phone : (937) 904-9569 Email: David.Mattie@wpafb.af.mil 2.2 WIL Study Director: Jonathan M. Hurley, BS Staff...Toxicologist and Head of Acute Toxicology Phone : (419) 289-8700 Fax: (419) 289-3650 E-mail: jon.hurley@wilresearch.com 19 Distribution A

  10. Mammalian Toxicity of Munition Compounds. Phase 1. Acute Oral Toxicity Primary Skin and Eye Irritation, Dermal Sensitization, and Disposition and Metabolism

    DTIC Science & Technology

    1975-07-22

    and 6 days for 1,3-DNG and 1-MNG. WP caused depression, anorexia, and death in several days with enlarged yellow nutmeg livers. ^ 2,5-DNT was...several days. Animals that died were found to have large yellow nutmeg livers. Primary skin irritation and eye irritation tests were negative with a...amount of radioactivity is consistent with white phosphorus poisoning since enlarged nutmeg liver was observed in the acute oral toxicity study. The

  11. WEB-BASED INTERSPECIES CORRELATION ESTIMATION (WEB-ICE) FOR ACUTE TOXICITY: USER MANUAL V2

    EPA Science Inventory

    Predictive toxicological models are integral to environmental risk Assessment where data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ...

  12. Defining dermal adipose tissue.

    PubMed

    Driskell, Ryan R; Jahoda, Colin A B; Chuong, Cheng-Ming; Watt, Fiona M; Horsley, Valerie

    2014-09-01

    Here, we explore the evolution and development of skin-associated adipose tissue with the goal of establishing nomenclature for this tissue. Underlying the reticular dermis, a thick layer of adipocytes exists that encases mature hair follicles in rodents and humans. The association of lipid-filled cells with the skin is found in many invertebrate and vertebrate species. Historically, this layer of adipocytes has been termed subcutaneous adipose, hypodermis and subcutis. Recent data have revealed a common precursor for dermal fibroblasts and intradermal adipocytes during development. Furthermore, the development of adipocytes in the skin is independent from that of subcutaneous adipose tissue development. Finally, the role of adipocytes has been shown to be relevant for epidermal homoeostasis during hair follicle regeneration and wound healing. Thus, we propose a refined nomenclature for the cells and adipose tissue underlying the reticular dermis as intradermal adipocytes and dermal white adipose tissue, respectively.

  13. Flexible Dermal Armor in Nature

    NASA Astrophysics Data System (ADS)

    Yang, Wen; Chen, Irene H.; Mckittrick, Joanna; Meyers, Marc A.

    2012-04-01

    Many animals possess dermal armor, which acts primarily as protection against predators. We illustrate this through examples from both our research and the literature: alligator, fish (alligator gar, arapaima, and Senegal bichir), armadillo, leatherback turtle, and a lizard, the Gila monster. The dermal armor in these animals is flexible and has a hierarchical structure with collagen fibers joining mineralized units (scales, tiles, or plates). This combination significantly increases the strength and flexibility in comparison with a simple monolithic mineral composite or rigid dermal armor. This dermal armor is being studied for future bioinspired armor applications providing increased mobility.

  14. [Acute toxicity and bioavailability of nano red elemental selenium].

    PubMed

    Gao, X; Zhang, J; Zhang, L

    2000-01-30

    The reaction ratio of nano red elemental selenium (nanose) with GSH in vitro was one-tenth of that of sodium selenite. Mice were fed with nanose and sodium selenite separately at 50 micrograms/kg BW for 30 days. Both selenium forms could significantly increased Se concentration of blood, liver and activity of blood GSH-Px. Acute toxicity experiment of mice implied that the acute toxicity of nanose was nearly one-seventh of that of sodium selenite. The LD50 for nanose se was 112.98 mg kg BW, and the LD50 for sodium selenite was Se 15.72 mg/kg BW. The acute toxicity of nanose was low for mice.

  15. Genetics Home Reference: focal dermal hypoplasia

    MedlinePlus

    ... 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 ...

  16. [Acute radiation injury].

    PubMed

    Saito, Tsutomu

    2012-03-01

    Cell death due to DNA damage by ionizing radiation causes acute radiation injury of tissues and organs. Frequency and severity of the injuries increase according to dose increase, when the dose becomes more than threshold dose. The threshold dose of acute human radiation death is 1 Gy and LD50 of human is 4 Gy. Human dies due to the cerebrovascular syndrome, the gastrointestinal syndrome or the hematopoetic syndrome, when he received more than 20 Gy, 10-20 Gy or 3-8 Gy to his total body, respectively. Any tissue or organ, including embryo and fetus, does not show the acute injury, when it received less than 100 mSv. Acute injuries are usually reversible, and late injuries are sometimes irreversible.

  17. 40 CFR 157.22 - When required.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... appropriate test species, the product meets any of the following toxicity criteria: (1) The pesticide has an acute oral LD50 of 1.5 g/kg or less; (2) The pesticide has an acute dermal LD50 of 2000 mg/kg or less; (3) The pesticide has an acute inhalation LC50 of 2 mg/liter or less; (4) The pesticide is...

  18. Web-based Interspecies Correlation Estimation (Web-ICE) for Acute Toxicity: User Manual Version 3.1

    EPA Science Inventory

    Predictive toxicological models are integral to ecological risk assessment because data for most species are limited. Web-based Interspecies Correlation Estimation (Web-ICE) models are least square regressions that predict acute toxicity (LC50/LD50) of a chemical to a species, ge...

  19. Estimation of acute oral toxicity in rat using local lazy learning

    PubMed Central

    2014-01-01

    Background Acute toxicity means the ability of a substance to cause adverse effects within a short period following dosing or exposure, which is usually the first step in the toxicological investigations of unknown substances. The median lethal dose, LD50, is frequently used as a general indicator of a substance’s acute toxicity, and there is a high demand on developing non-animal-based prediction of LD50. Unfortunately, it is difficult to accurately predict compound LD50 using a single QSAR model, because the acute toxicity may involve complex mechanisms and multiple biochemical processes. Results In this study, we reported the use of local lazy learning (LLL) methods, which could capture subtle local structure-toxicity relationships around each query compound, to develop LD50 prediction models: (a) local lazy regression (LLR): a linear regression model built using k neighbors; (b) SA: the arithmetical mean of the activities of k nearest neighbors; (c) SR: the weighted mean of the activities of k nearest neighbors; (d) GP: the projection point of the compound on the line defined by its two nearest neighbors. We defined the applicability domain (AD) to decide to what an extent and under what circumstances the prediction is reliable. In the end, we developed a consensus model based on the predicted values of individual LLL models, yielding correlation coefficients R2 of 0.712 on a test set containing 2,896 compounds. Conclusion Encouraged by the promising results, we expect that our consensus LLL model of LD50 would become a useful tool for predicting acute toxicity. All models developed in this study are available via http://www.dddc.ac.cn/admetus. PMID:24959207

  20. Carbofuran occupational dermal toxicity, exposure and risk assessment†

    PubMed Central

    Gammon, Derek W; Liu, Zhiwei; Becker, John M

    2012-01-01

    BACKGROUND Carbofuran is a carbamate insecticide that inhibits AChE. Although toxic by ingestion in mammals, it has low dermal toxicity, with relatively few confirmed worker illnesses. This risk assessment describes its time of onset, time to peak effect and time to recovery in rats using brain AChE inhibition in acute and 21 day dermal studies; in vitro rat/human relative dermal absorption for granular (5G) and liquid (4F) formulations; occupational exposure estimates using the Pesticide Handlers' Exposure Database and Agricultural Handlers' Exposure Database (PHED/AHED). RESULTS The point of departure for acute risk calculation (BMDL10) was 6.7 mg kg−1 day−1 for brain AChE inhibition after 6 h exposure. In a 21 day study, the BMDL10 was 6.8 mg kg−1 day−1, indicating reversibility. At 75 mg kg−1 day−1, time of onset was ≤30 min and time to peak effect was 6–12 h. Rat skin had ca tenfold greater dermal absorption of carbofuran (Furadan® 5G or 4F) than human skin. Exposure estimates for 5G in rice and 4F in ten crops had adequate margins of exposure (>100). CONCLUSION Rat dermal carbofuran toxicity was assessed in terms of dose and time-related inhibition of AChE. Comparative dermal absorption in rats was greater than in humans. Worker exposure estimates indicated acceptable risk for granular and liquid formulations of carbofuran. Copyright © 2011 Society of Chemical Industry PMID:21834090

  1. Acute Oral and Intraperitoneal Toxicity Study of WR242511 and WR269410 in Rats

    DTIC Science & Technology

    1993-07-14

    survivors were also necropsied. The acute oral LD50 of WR242511 tartrate in male rats, administered in 1% Methylcellulose/O.4% Tween 80 by gavage, was...administered orally. The acute oral LDS0 of WR269410 in male rats, administered in 1% Methylcellulose/O.4% Tween 80 by gavage, was approximately four-fold...formulations in 0.1% Methylcellulose/O.4% Tween 80 at high enough concentrations to produce lethality, WR269410 was administered intraperitoneally as a

  2. Almost Unilateral Focal Dermal Hypoplasia

    PubMed Central

    Lee, Solam; Choe, Sung Jay

    2017-01-01

    Focal dermal hypoplasia, caused by mutations in PORCN, is an X-linked ectodermal dysplasia, also known as Goltz syndrome. Only seven cases of unilateral or almost unilateral focal dermal hypoplasia have been reported in the English literature and there have been no previously reported cases in the Republic of Korea. A 19-year-old female presented with scalp defects, skin lesions on the right leg and the right trunk, and syndactyly of the right fourth and fifth toes. Cutaneous examination revealed multiple atrophic plaques and a brown and yellow mass with fat herniation and telangiectasia that was mostly located on the lower right leg. She had syndactyly on the right foot and the scalp lesion appeared to be an atrophic, membranous, fibrotic alopecic scar. A biopsy of the calf revealed upper dermal extension of fat cells, dermal atrophy, and loss of dermal collagen. A diagnosis of almost unilateral focal dermal hypoplasia was made on the basis of physical and histologic findings. Henceforth, the patient was referred to a plastic surgeon and an orthopedics department to repair her syndactyly. PMID:28223754

  3. Acute oral toxicities of wildland fire control chemicals to birds

    USGS Publications Warehouse

    Vyas, N.B.; Spann, J.W.; Hill, E.F.

    2009-01-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24 h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R?) and two Class A fire suppressant foams (Silv-Ex? and Phos-Chek WD881?) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881? and Silv-Ex? were above the predetermined 2000 mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R?, Phos-Chek D-75F?, and Fire-Trol LCG-R? because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  4. Acute oral toxicities of wildland fire control chemicals to birds.

    PubMed

    Vyas, Nimish B; Spann, James W; Hill, Elwood F

    2009-03-01

    Wildland fire control chemicals are released into the environment by aerial and ground applications to manage rangeland, grassland, and forest fires. Acute oral 24h median lethal dosages (LD50) for three fire retardants (Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R) and two Class A fire suppressant foams (Silv-Ex and Phos-Chek WD881) were estimated for northern bobwhites, Colinus virginianus, American kestrels, Falco sparverius, and red-winged blackbirds, Agelaius phoeniceus. The LD50s of all chemicals for the bobwhites and red-winged blackbirds and for kestrels dosed with Phos-Chek WD881 and Silv-Ex were above the predetermined 2000mg chemical/kg body mass regulatory limit criteria for acute oral toxicity. The LD50s were not quantifiable for kestrels dosed with Fire-Trol GTS-R, Phos-Chek D-75F, and Fire-Trol LCG-R because of the number of birds which regurgitated the dosage. These chemicals appear to be of comparatively low order of acute oral toxicity to the avian species tested.

  5. Acute oral toxicity of the herbicide BUREX EKO in pheasants.

    PubMed

    Legáth, J; Mlynarcíková, H; Svický, E; Lenhardt, L; Kacmár, P; Benová, K; Kovác, G

    1996-12-01

    The aim of this study was to determine the acute LD50, clinical symptoms and pathological changes of acute BUREX EKO intoxication in pheasants according to OECD No 205. Medium lethal dose (LD50) of BUREX EKO in pheasant is 3.84 ml/kg body weight with the upper level of reliability 4.50 ml and lower level of reliability 3.27 ml/kg body weight. As far as the calculation to the effective substance is concerned it is 1077 mg of chloridazone per kg body weight with the interval of reliability from 919 to 1263 mg/kg body weight. Calculated the effective substance of chloridazone (3.84 ml is LD50 of BUREX EKO which contains 1077 mg of chloridazone) BUREX EKO can be classified as the moderately toxic substance to pheasants. There were following clinical symptoms of the BUREX EKO intoxication in pheasants: apathy, drowsiness, incapability to move, ruffled feathers, slight diarrhoea, strenuous respiration, tonico-clonical cramps before death, decease with the head expressively bent rearwards. There was a relatively fast beginning of rigor mortis in dead pheasants. Pathologico-anatomical dissection of the pheasants obtained under conditions of acute intoxication did not reveal any changes on the organs of both experimental and control pheasants which would be immediately connected with the effect of the administered substance. Hyperaemia was recorded by histologico-pathological investigation of the liver and kidneys. No changes on the brain and intestine wall were recorded.

  6. EVALUATING COMMERCIALLY AVAILABLE DERMAL ...

    EPA Pesticide Factsheets

    As the Human Exposure Program focuses on the exposure of children to pesticides, there are concerns about the effect, or perceived effect, of components of the sampling procedure on the health and well-being of the infant and the ability to collect pesticide residues. One concern involves the materials in wipes used to collect pesticide residues or other contact materials on the skin. In recent studies (e.g., National Human Exposure Assessment Survey; NHEXAS), isopropyl alcohol has been used as a solvent in conjunction with a cloth wipe to obtain samples from the hands of adults and children. Although isopropyl alcohol is generally considered innocuous, the use of commercially available products could eliminate concerns about exposure to alcohol. A few studies have evaluated the potential of commercially available baby wipes to collect personal exposure samples for metals research, but not for the area of pesticide research (Millson et al., 1994; Campbell et al., 1993; Lichtenwalner et al., 1993). Therefore, there is a need to evaluate the potential for using commercially available baby wipes for collecting pesticide samples from skin and other surfaces. Another concern involves establishing a convenient and safe method for assessing overall dermal exposure for children, especially for those in crawling stage. One route that the U .S. Environmental Protection Agency (EPA) would like to investigate is the use of cotton body suits (infant sleepers) as an indicator

  7. Chick embryo chorioallantoic membrane (CAM): an alternative predictive model in acute toxicological studies for anti-cancer drugs

    PubMed Central

    KUE, Chin Siang; TAN, Kae Yi; LAM, May Lynn; LEE, Hong Boon

    2015-01-01

    The chick embryo chorioallantoic membrane (CAM) is a preclinical model widely used for vascular and anti-vascular effects of therapeutic agents in vivo. In this study, we examine the suitability of CAM as a predictive model for acute toxicology studies of drugs by comparing it to conventional mouse and rat models for 10 FDA-approved anticancer drugs (paclitaxel, carmustine, camptothecin, cyclophosphamide, vincristine, cisplatin, aloin, mitomycin C, actinomycin-D, melphalan). Suitable formulations for intravenous administration were determined before the average of median lethal dose (LD50) and median survival dose (SD50) in the CAM were measured and calculated for these drugs. The resultant ideal LD50 values were correlated to those reported in the literature using Pearson’s correlation test for both intravenous and intraperitoneal routes of injection in rodents. Our results showed moderate correlations (r2=0.42 − 0.68, P<0.005–0.05) between the ideal LD50 values obtained using the CAM model with LD50 values from mice and rats models for both intravenous and intraperitoneal administrations, suggesting that the chick embryo may be a suitable alternative model for acute drug toxicity screening before embarking on full toxicological investigations in rodents in development of anticancer drugs. PMID:25736707

  8. Acute Dermal Irritation Study In New Zealand White Rabbits: Four Alcohol-to-Jet (ATJ) Synthetic Paraffinic Kerosene (SPK) Alternative Jet Fuels Compared With Petroleum-Derived JP-8

    DTIC Science & Technology

    2014-09-19

    fuel exposures resulted in very slight to slight remaining erythema and/or edema through study day 14. Normal handling of these ATJ SPK fuels by...findings during the study consisted of very slight to moderate erythema, as well as very slight to moderate edema . All fuel exposures resulted in very...slight to slight remaining erythema and/or edema through study day 14. A score of moderately irritating, as evaluated by the Primary Dermal Irritation

  9. Use of butterflies as nontarget insect test species and the acute toxicity and hazard of mosquito control insecticides.

    PubMed

    Hoang, Tham C; Pryor, Rachel L; Rand, Gary M; Frakes, Robert A

    2011-04-01

    Honeybees are the standard insect test species used for toxicity testing of pesticides on nontarget insects for the U.S. Environmental Protection Agency (U.S. EPA) under the Federal Insecticide Fungicide and Rodenticide Act (FIFRA). Butterflies are another important insect order and a valued ecological resource in pollination. The current study conducted acute toxicity tests with naled, permethrin, and dichlorvos on fifth larval instar (caterpillars) and adults of different native Florida, USA, butterfly species to determine median lethal doses (24-h LD50), because limited acute toxicity data are available with this major insect group. Thorax- and wing-only applications of each insecticide were conducted. Based on LD50s, thorax and wing application exposures were acutely toxic to both caterpillars and adults. Permethrin was the most acutely toxic insecticide after thorax exposure to fifth instars and adult butterflies. However, no generalization on acute toxicity (sensitivity) of the insecticides could be concluded based on exposures to fifth instars versus adult butterflies or on thorax versus wing exposures of adult butterflies. A comparison of LD50s of the butterflies from this study (caterpillars and adults) with honeybee LD50s for the adult mosquito insecticides on a µg/organism or µg/g basis indicates that several butterfly species are more sensitive to these insecticides than are honeybees. A comparison of species sensitivity distributions for all three insecticides shows that permethrin had the lowest 10th percentile. Using a hazard quotient approach indicates that both permethrin and naled applications in the field may present potential acute hazards to butterflies, whereas no acute hazard of dichlorvos is apparent in butterflies. Butterflies should be considered as potential test organisms when nontarget insect testing of pesticides is suggested under FIFRA.

  10. Dermal uptake of petroleum substances.

    PubMed

    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.

  11. Acute oral toxicity of sodium cyanide in birds

    USGS Publications Warehouse

    Wiemeyer, Stanley N.; Hill, E.F.; Carpenter, J.W.; Krynitsky, A.J.

    1986-01-01

    Sensitivities of six avian species, black vulture (Coragyps atratus), American kestrel (Falco sparverius), Japanese quail (Coturnix japonica), domestic chicken (Gallus domesticus), eastern screech-owl (Otus asio), and European starling (Sturnus vulgaris), to acute poisoning by sodium cyanide (NaCN) were compared by single dose LD50's. Three species, domestic chickens, black vultures, and turkey vultures (Cathartes aura), were dosed with NaCN to determine cyanide residues in those that died and also in survivors, in addition to postmortem fate. Three flesh-eating species (black vulture, American kestrel, and eastern screech-owl; LD50's 4.0-8.6 mg/kg) were more sensitive to NaCN than three species (Japanese quail, domestic chicken, and European starling; LD50's 9.4-21 mg/kg) that fed predominantly on plant material. Elevated concentrations of cyanide were found in the blood of birds that died of cyanide poisoning; however, concentrations in birds that died overlapped those in survivors. Blood was superior to liver as the tissue of choice for detecting cyanide exposure. No gross pathological changes related to dosing were observed at necropsy.

  12. Prediction & Assessment of Dermal Exposure

    DTIC Science & Technology

    2007-11-02

    cutaneous exposure requires the transdermal penetration of the chemical. The unique permeation barrier properties of skin ensure that the kinetics of...following dermal exposure, therefore, requires that the rate of skin penetration in man be predictable. The specific aims of the project were: (1) to...derive, from a compre- hensive database of the percutaneous absorption/ penetration literature predictive ("structure-activity") algorithms to calculate a

  13. Acute and sub-acute toxicological assessment of the aqueous seed extract of Persea americana mill (Lauraceae) in rats.

    PubMed

    Ozolua, Raymond I; Anaka, Ogochukwu N; Okpo, Stephen O; Idogun, Sylvester E

    2009-07-03

    The aqueous seed extract of Persea americana Mill (Lauraceae) is used by herbalists in Nigeria for the management of hypertension. As part of our on-going scientific evaluation of the extract, we designed the present study to assess its acute and sub-acute toxicity profiles in rats. Experiments were conducted to determine the oral median lethal dose (LD(50)) and other gross toxicological manifestations on acute basis. In the sub-acute experiments, the animals were administered 2.5 g/kg (p.o) per day of the extract for 28 consecutive days. Animal weight and fluid intake were recorded during the 28 days period. Terminally, kidneys, hearts, blood/sera were obtained for weight, haematological and biochemical markers of toxicity. Results show that the LD(50) could not be determined after a maximum dose of 10 g/kg. Sub-acute treatment with the extract neither affected whole body weight nor organ-to-body weight ratios but significantly increased the fluid intake (P < 0.0001). Haematological parameters and the levels of ALT, AST, albumin and creatinine were not significantly altered. However, the concentration of total proteins was significantly increased in the treated group. In conclusion, the aqueous seed extract of P. americana is safe on sub-acute basis but extremely high doses may not be advisable.

  14. Health Effects Research on Munition Contaminated Dimethyl Sulfoxide Recrystallization Process Solvent. Phase I Studies.

    DTIC Science & Technology

    1985-07-01

    hepatotoxicity and possibly nephrotoxicity , although the latter mi8 ht be a secondary effect of DMSO- induced hemolysis. At present there is no clinical evidence...process stream samples and toxicological studies (oral LD50 in rats and mice, primary ocular and dermal irritation in rabbits, acute dermal toxicity...Assay (plate incorporation triplicate) - a mutagenic potential assay (b) Oral LD5 in rats and mice (c) Primary ocular and dermal irritation in rabbits (d

  15. Acute toxicity of diazinon is similar for eight stocks of bobwhite

    USGS Publications Warehouse

    Hill, E.F.; Camardese, M.B.; Heinz, G.H.; Spann, J.W.; DeBevec, A.B.

    1984-01-01

    Nine-week-old bobwhite (Colinus virginianus) from eight different game farms were tested for their sensitivity to an acute oral exposure of technical-grade diazinon (phosphorothioic acid O, O-diethyl-O-[6-methyl- 2-(1 -methylethy 1)-4-pyrimidinyl]ester). Extraneous variables associated with interlaboratory differences in husbandry were eliminated by incubating eggs and rearing chicks to test age for all stocks simultaneously in the same facilities at the Patuxent Wildlife Research Center. Under this single set of conditions, the responses of the eight stocks of bobwhite to diazinon were statistically inseparable, with LD50 values varying from 13 mg/kg (95% confidence interval, 8-21 mg/kg) to 17 mg/kg (95% confidence interval, 11-25 mg/kg). The pooled LD50 for the eight stocks was 14.7 mg/kg (95% confidence interval,13.1-16.5 mg/kg).

  16. ISSUES IN DERMAL EXPOSURE OF INFANTS

    EPA Science Inventory

    Infants' dermal exposures to environmental contaminants are expected to be different and, in many cases, much higher than adults. Because of the potential importance of the dermal exposure route, there is currently a significant amount of work being conducted to reduce the uncer...

  17. Acute exposure to sarin increases blood brain barrier permeability and induces neuropathological changes in the rat brain: dose-response relationships.

    PubMed

    Abdel-Rahman, A; Shetty, A K; Abou-Donia, M B

    2002-01-01

    results indicate that, the early brain damage after acute exposure to sarin is clearly dose-dependent, and that exposure to 1 x LD(50) sarin induces detrimental changes in many regions of the adult rat brain as early as 24 hours after the exposure. The early neuropathological changes observed after a single dose of 1 x LD(50) sarin could lead to a profound long-term neurodegenerative changes in many regions of the brain, and resulting behavioral abnormalities.

  18. Species Typing in Dermal Leishmaniasis

    PubMed Central

    Dujardin, Jean-Claude

    2015-01-01

    SUMMARY Leishmania is an infectious protozoan parasite related to African and American trypanosomes. All Leishmania species that are pathogenic to humans can cause dermal disease. When one is confronted with cutaneous leishmaniasis, identification of the causative species is relevant in both clinical and epidemiological studies, case management, and control. This review gives an overview of the currently existing and most used assays for species discrimination, with a critical appraisal of the limitations of each technique. The consensus taxonomy for the genus is outlined, including debatable species designations. Finally, a numerical literature analysis is presented that describes which methods are most used in various countries and regions in the world, and for which purposes. PMID:25672782

  19. Antioxidant Nanoplatforms for Dermal Delivery: Melatonin.

    PubMed

    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.

  20. Acute toxicity of gymnodimine to mice.

    PubMed

    Munday, Rex; Towers, Neale R; Mackenzie, Lincoln; Beuzenberg, Veronica; Holland, Patrick T; Miles, Christopher O

    2004-08-01

    The acute toxicity of the phycotoxin gymnodimine to female Swiss mice by intraperitoneal injection and by oral administration has been determined. Gymnodimine was highly toxic by injection, the LD50 being only 96 microg/kg. Animals either died within 10 min of injection or made a full recovery with no perceptible long-term effects. Gymnodimine was also toxic after oral administration by gavage (LD50 755 microg/kg), but was much less toxic when administered with food. No signs of toxicity were seen in mice voluntarily ingesting food containing gymnodimine at a level sufficient to give a dose of approximately 7500 microg/kg. Pre-treatment with physostigmine or neostigmine protected against injected gymnodimine, suggesting that the latter exerts its toxic effects via blockade of nicotinic receptors at the neuromuscular junction. The low toxicity of gymnodimine when ingested with food suggests that this compound is of low risk to humans, a conclusion that is consonant with anecdotal evidence for the absence of harmful effects in individuals consuming shellfish contaminated with gymnodimine.

  1. 49 CFR 173.132 - Class 6, Division 6.1-Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... it falls within any one of the following categories when tested on laboratory animals (whenever possible, animal test data that has been reported in the chemical literature should be used): (i) Oral... substance per mass of test animal (mg/kg). (2) LD50 for acute dermal toxicity means that dose of...

  2. 49 CFR 173.132 - Class 6, Division 6.1-Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... it falls within any one of the following categories when tested on laboratory animals (whenever possible, animal test data that has been reported in the chemical literature should be used): (i) Oral... substance per mass of test animal (mg/kg). (2) LD50 for acute dermal toxicity means that dose of...

  3. Toxicity of Pesticides. Agrichemical Fact Sheet 2.

    ERIC Educational Resources Information Center

    Hock, Winand K.

    This fact sheet gives the acute oral and dermal toxicity (LD 50) of over 250 pesticides in lab animals. The chemicals are categorized as fungicides, herbicides, insecticides, or miscellaneous compounds. One or more trade names are given for each pesticide. In addition, a brief explanation of toxicity determination is given. (BB)

  4. Oral and dermal pharmacokinetics of triclopyr in human volunteers.

    PubMed

    Carmichael, N G; Nolan, R J; Perkins, J M; Davies, R; Warrington, S J

    1989-11-01

    Blood levels and urinary excretion of triclopyr, the active ingredient in Garlon herbicides, were followed in six volunteers given single oral doses of 0.1 and 0.5 mg/kg body weight. Five of these volunteers later received dermal applications of Garlon 4 herbicide formulation equivalent to 3.7 mg triclopyr/kg body weight applied to the forearm. Following oral administration blood levels peaked at 2-3 h and declined to undetectable levels within 48 h; more than 80% of the dose was found as unchanged triclopyr in the urine. A two-compartment pharmacokinetic model was used to describe the time-course of triclopyr clearance; half-lives for the rapid initial and slower terminal phases were 1.3 h and 5.1 h respectively, and were independent of dose. Due to the slow half-life for dermal absorption (t1/2 = 16.8 h) the rapid initial elimination phase was obscured and the pharmacokinetics could be simplified by a one-compartment model. An average of 1.37% of the applied dose was recovered in the urine; when corrected for recovery after oral administration this was equivalent to an absorption of 1.65%. Triclopyr is slowly absorbed through skin and is rapidly eliminated. It has very low potential to accumulate in man or to be absorbed through the skin in acutely toxic amounts.

  5. Coverage of Deep Cutaneous Wounds Using Dermal Template in Combination with Negative-pressure Therapy and Subsequent Skin Graft

    PubMed Central

    Chang, Alexandre A.; Lobato, Rodolfo C.; Nakamoto, Hugo A.; Tuma, Paulo; Ferreira, Marcus C.

    2014-01-01

    Background: We consider the use of dermal matrix associated with a skin graft to cover deep wounds in the extremities when tendon and bone are exposed. The objective of this article was to evaluate the efficacy of covering acute deep wounds through the use of a dermal regeneration template (Integra) associated with vacuum therapy and subsequent skin grafting. Methods: Twenty patients were evaluated prospectively. All of them had acute (up to 3 weeks) deep wounds in the limbs. We consider a deep wound to be that with exposure of bone, tendon, or joint. Results: The average area of integration of the dermal regeneration template was 86.5%. There was complete integration of the skin graft over the dermal matrix in 14 patients (70%), partial integration in 5 patients (25%), and total loss in 1 case (5%). The wound has completely closed in 95% of patients. Conclusions: The use of Integra dermal template associated with negative-pressure therapy and skin grafting showed an adequate rate of resolution of deep wounds with low morbidity. PMID:25289363

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

    PubMed

    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.

  7. Acute toxicity testing in cultures of mouse neuroblastoma cells.

    PubMed

    Walum, E; Peterson, A

    1983-01-01

    Cultured mouse neuroblastoma cells (C1300) may be used as models for nerve cells since they have a number of properties in common with their normal counterparts in vivo. In order to test the possibility of using C1300 cells as alternative to experimental animals when testing for acute toxicity, cells (clone 41A3) were exposed to a number of common chemicals (CH3HgCl, CdCl2,HgCl2 ppDDT, n-butanol, benzene, dioxan, n-propanol, aceton and t-butanol). The toxic effect was quantified by measuring the degree of cell detachment in the cultures. The concentrations of chemicals that caused 25% of the total cell number to detach (TD25) were used for comparison with LD50 values. In spite of the very simplified situation in culture, where the toxicity of a substance is little or not at all influenced by factors like penetration, storage, metabolism and excretion a good correlation (corr. coeff. 0,98) was obtained between TD25 values and LD50 values. Good correlations between in vitro and in vivo tests have also been reported by others. One possible explanation to these findings could be simplified in vivo toxicokinetics of these substances when tested in high doses for general effects like animal death. If so, simple in vitro tests may be used for predicting acute toxicity of certain groups of substances.

  8. Estimating terrestrial amphibian pesticide body burden through dermal exposure

    EPA Science Inventory

    Dermal exposure presents a potentially significant but understudied route for pesticide uptake in terrestrial amphibians. Our study measured dermal uptake of pesticides of varying hydrophobicity (logKow) in frogs. Amphibians were indirectly exposed to one of five pesticide active...

  9. Effects of continuous wave and fractionated diode laser on human fibroblast cancer and dermal normal cells by zinc phthalocyanine in photodynamic therapy: A comparative study.

    PubMed

    Navaeipour, Farzaneh; Afsharan, Hadi; Tajalli, Habib; Mollabashi, Mahmood; Ranjbari, Farideh; Montaseri, Azadeh; Rashidi, Mohammad-Reza

    2016-08-01

    In this experimental study, cancer and normal cells behavior during an in vitro photodynamic therapy (PDT) under exposure of continuous wave (CW) and fractionated mode of laser with different irradiation power and time intervals was compared and investigated. At the first, human fibroblast cancer cell line (SW 872) and human dermal normal (HFFF2) cell line were incubated with different concentrations of zinc phthalocyanine (ZnPc), as a PDT drug. The cells, then, were irradiated with a 675nm diode laser and the cell viability was evaluated using MTT assay. Under optimized conditions, the viability of the cancer cells was eventually reduced to 3.23% and 13.17%, and that of normal cells was decreased to 20.83% and 36.23% using CW and fractionated diode lasers, respectively. In general, the ratio of ZnPc LD50 values for the normal cells to the cancer cells with CW laser was much higher than that of the fractionated laser. Subsequently, cancer cells in comparison with normal ones were found to be more sensitive toward the photodynamic damage induced by ZnPc. In addition, treatment with CW laser was found to be more effective against the cancer cells with a lower toxicity to the normal cells compared with the fractionated diode laser.

  10. LINKING DERMAL MODELING AND LOADING DATA TO PREDICT LONG-TERM DOSES FROM INTERMITTENT DERMAL CONTACT

    EPA Science Inventory

    In this paper we assess dermal exposure and dose resulting from intermittent contact with residue-contaminated surfaces. These estimates require an understanding of (1) the quantitative relationship between exposure and absorbed dose; (2) the impact of intermittent exposure on ...

  11. 40 CFR 798.2250 - Dermal toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... clinical abnormalities, gross lesions, identified target organs, body weight changes, effect on mortality... (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2250 Dermal toxicity. (a) Purpose. In...-observed-effect level and toxic effects associated with continuous or repeated exposure to a test...

  12. 40 CFR 798.2250 - Dermal toxicity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... clinical abnormalities, gross lesions, identified target organs, body weight changes, effect on mortality... (CONTINUED) HEALTH EFFECTS TESTING GUIDELINES Subchronic Exposure § 798.2250 Dermal toxicity. (a) Purpose. In...-observed-effect level and toxic effects associated with continuous or repeated exposure to a test...

  13. A Dermal Piercing Complicated by Mycobacterium fortuitum.

    PubMed

    Patel, Trisha; Scroggins-Markle, Leslie; Kelly, Brent

    2013-01-01

    Background. Dermal piercings have recently become a fashion symbol. Common complications include hypertrophic scarring, rejection, local infection, contact allergy, and traumatic tearing. We report a rare case of Mycobacterium fortuitum following a dermal piercing and discuss its medical implications and treatments. Case. A previously healthy 19-year-old woman presented complaining of erythema and edema at the site of a dermal piercing on the right fourth dorsal finger. She was treated with a 10-day course of trimethoprim-sulfamethoxazole and one course of cephalexin by her primary care physician with incomplete resolution. The patient stated that she had been swimming at a local water park daily. A punch biopsy around the dermal stud was performed, and cultures with sensitivities revealed Mycobacterium fortuitum. The patient was treated with clarithromycin and ciprofloxacin for two months receiving full resolution. Discussion. Mycobacterium fortuitum is an infrequent human pathogen. This organism is a Runyon group IV, rapidly growing nontuberculous mycobacteria, often found in water,soil, and dust. Treatment options vary due to the size of the lesion. Small lesions are typically excised, while larger lesions require treatment for 2-6 months with antibiotics. We recommend a high level of suspicion for atypical mycobacterial infections in a piercing resistant to other therapies.

  14. Dermal exudate macrophages. Induction in dermal chambers and response to lymphokines.

    PubMed Central

    Goihman-Yahr, M; Ulrich, M; Noya-León, A; Rojas, A; Convit, J

    1975-01-01

    Chambers were implanted in the dorsum of guinea-pigs at the dermal-subcutaneous junction. Exudates were induced and harvested. Macrophages obtained were able to migrate in vitro. If procured from sensitized donors, macrophage migration was inhibited by the corresponding antigen. Dermal exudate macrophages are therefore subject to the effect of lymphokines. The chamber model may be useful for in vivo studies of cell to cell and cell-parasite interactions. PMID:1212821

  15. A critical role of acute bronchoconstriction in the mortality associated with high-dose sarin inhalation: effects of epinephrine and oxygen therapies.

    PubMed

    Gundavarapu, Sravanthi; Zhuang, Jianguo; Barrett, Edward G; Xu, Fadi; Russell, Robert G; Sopori, Mohan L

    2014-01-15

    Sarin is an organophosphate nerve agent that is among the most lethal chemical toxins known to mankind. Because of its vaporization properties and ease and low cost of production, sarin is the nerve agent with a strong potential for use by terrorists and rouge nations. The primary route of sarin exposure is through inhalation and, depending on the dose, sarin leads to acute respiratory failure and death. The mechanism(s) of sarin-induced respiratory failure is poorly understood. Sarin irreversibly inhibits acetylcholine esterase, leading to excessive synaptic levels of acetylcholine and, we have previously shown that sarin causes marked ventilatory changes including weakened response to hypoxia. We now show that LD50 sarin inhalation causes severe bronchoconstriction in rats, leading to airway resistance, increased hypoxia-induced factor-1α, and severe lung epithelium injury. Transferring animals into 60% oxygen chambers after sarin exposure improved the survival from about 50% to 75% at 24h; however, many animals died within hours after removal from the oxygen chambers. On the other hand, if LD50 sarin-exposed animals were administered the bronchodilator epinephrine, >90% of the animals survived. Moreover, while both epinephrine and oxygen treatments moderated cardiorespiratory parameters, the proinflammatory cytokine surge, and elevated expression of hypoxia-induced factor-1α, only epinephrine consistently reduced the sarin-induced bronchoconstriction. These data suggest that severe bronchoconstriction is a critical factor in the mortality induced by LD50 sarin inhalation, and epinephrine may limit the ventilatory, inflammatory, and lethal effects of sarin.

  16. Toxicity of white phosphorus to waterfowl: acute exposure in mallards

    USGS Publications Warehouse

    Sparling, D.W.; Gustafson, M.; Klein, P.; Karouna-Renier, N.

    1997-01-01

    As part of an effort to understand extensive, white phosphorus (P4)-induced waterfowl mortality at Eagle River Flats, Fort Richardson, Alaska, we conducted a number of acute toxicity tests using penned mallards (Anas platyrhynchos) in 1993 and 1994. The 24-hr median lethal dose (LD50) for P4 dissolved in oil was 6.46 mg/kg in adult males and 6.96 mg/kg in adult females. Although the median lethal doses were not statistically different, the female dose-response curve had a statistically shallower slope than that of males. The LD50 for the ecologically more relevant pelletized form of P4 in adult males was 4.05 mg/kg. In mallards, one mechanism of P4 toxicity caused rapid (3 to 10 hr) mortality and had signs consistent with anoxia. A second, slower acting mechanism resulted in hepatic and renal pathology including extensive fat deposition in the liver and cellular necrosis. White phosphorus accumulated in adipose tissues, but only for a few days.

  17. Relative oral efficacy and acute toxicity of hydroxypyridin-4-one iron chelators in mice

    SciTech Connect

    Porter, J.B.; Morgan, J.; Hoyes, K.P.; Burke, L.C.; Huehns, E.R.; Hider, R.C. )

    1990-12-01

    The relationship between the oral efficacy and the acute toxicity of hydroxypyridin-4-one iron chelators has been investigated to clarify structure-function relationships of these compounds in vivo and to identify compounds with the maximum therapeutic safety margin. By comparing 59Fe excretion following oral or intraperitoneal administration of increasing doses of each chelator to iron-overloaded mice, the most effective compounds have been identified. These have partition coefficients (Kpart) above 0.3 in the iron-free form with a trend of increasing oral efficacy with increasing Kpart values (r = .6). However, this is achieved at a cost of increasing acute toxicity, as shown by a linear correlation between 59Fe excretion increase per unit dose and 1/LD50 (r = .83). A sharp increase in the LD50 values is observed for compounds with Kpart values above 1.0, suggesting that such compounds are unlikely to possess a sufficient therapeutic safety margin. Below a Kpart of 1.0, acute toxicity is relatively independent of lipid solubility. All the compounds are less toxic by the oral route than by the intraperitoneal route, although iron excretion is not significantly different by these two routes. At least five compounds (CP51, CP94, CP93, CP96, and CP21) are more effective orally than the same dose of intraperitoneal desferrioxamine (DFO) (P less than or equal to .02) or orally administered L1(CP20) (P less than or equal to .02).

  18. The prolonged gastrointestinal syndrome in rhesus macaques: the relationship between gastrointestinal, hematopoietic, and delayed multi-organ sequelae following acute, potentially lethal, partial-body irradiation.

    PubMed

    MacVittie, Thomas J; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M

    2012-10-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min(-1) to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  19. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... source material used in developing this TSCA test guideline is the Office of Prevention, Pesticides, and... known should be determined before the test. Acceptable alternative vehicles include gum arabic,...

  20. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... source material used in developing this TSCA test guideline is the Office of Prevention, Pesticides, and... known should be determined before the test. Acceptable alternative vehicles include gum arabic,...

  1. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... source material used in developing this TSCA test guideline is the Office of Prevention, Pesticides, and... known should be determined before the test. Acceptable alternative vehicles include gum arabic,...

  2. 40 CFR 799.9120 - TSCA acute dermal toxicity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... source material used in developing this TSCA test guideline is the Office of Prevention, Pesticides, and... known should be determined before the test. Acceptable alternative vehicles include gum arabic,...

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

    DTIC Science & Technology

    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

  4. Solvent-refined-coal (SRC) process: health programs. Final report of subcontract No. 12, industrial hygiene, clinical and toxicological programs. Interim report No. 75, August 1, 1980-March 31, 1982. [Oral, dermal, eye and inhalation (distillate only) administration

    SciTech Connect

    Not Available

    1982-05-01

    This final report summarizes the acute toxicity studies conducted on SRC-II materials as part of the toxicological program under the Solvent-Refined-Coal (SRC) Process Contract for the period August 1, 1980 through March 31, 1982. Three materials were studied in this part of the program: coal slurry, stripper tower bottoms, and middle distillate. The materials were evaluated for: toxicity when administered orally in a single dose to rats; toxicity when administered dermally in a single dose to the intact and abraded skin of rabbits; the eye irritation potential when instilled into the rabbit eye; and, the sensitization potential when applied to the intact skin of the guinea pig. In addition, the middle distillate was also evaluated for aspiration hazard and toxicity when administered once into the oral cavity of rats, and the acute inhalation toxicity of a vapor/aerosol mixture when administered to rats by whole body inhalation exposure for four hours. All studies were performed according to approved detailed protocols, FDA Good Laboratory Practice Regulations, and quality assurance audits. Based on the results of these studies, it has been concluded that the coal slurry is not acutely toxic by either the oral or dermal route, must be classified as a mild eye irritant, and may on occasion cause slight dermal sensitization. The stripper tower bottoms is not acutely toxic by either the oral or dermal route, is not an eye irritant, and may on occasion cause slight dermal sensitization. Middle distillate appears to show moderate toxicity by the acute oral route but no acute dermal toxicity, must be classified as a mild eye irritant and may on occasion cause slight dermal sensitization. Middle distillate was also deemed to be an aspiration hazard as would be expected and showed moderate toxicity by the acute inhalation route.

  5. Preparation and acute toxicology of nano-magnetic ferrofluid.

    PubMed

    Xia, Zefeng; Wang, Guobin; Tao, Kaixiong; Li, Jianxing; Tian, Yuan

    2005-01-01

    The nano-magnetic ferrofluid was prepared by chemical coprecipitation and its acute toxicology was investigated. The effective diameter (Eff. Diam. ) of the magnetic particles was about 19.9 nm, and the concentration of the ferrofluid was 17. 54 mg/ml. The acute toxic reaction and the main viscera pathological morphology of mice were evaluated after oral, intravenous and intraperitoneal administration of the nano-magnetic ferrofluid of different doses respectively. Half lethal dose (LD50) > 2104. 8 mg/kg,maximum non-effect dose (ED0) = 320. 10mg/kg with oral; LDs,> 438. 50 mg/kg, EDo = 160. 05 mg/kg with intravenous route; and LDso >1578. 6 mg/kg, ED0 = 320. 10 mg/kg with intraperitoneal administration. Degeneration and necrosis of viscera were not found. So the nano-magnetic ferrofluid, of which toxicity is very low, may be used as a drug carrier.

  6. DERMAL ADIPOCYTES: FROM IRRELEVANCE TO METABOLIC TARGETS?

    PubMed Central

    Kruglikov, Ilja L.; Scherer, Philipp E.

    2015-01-01

    Dermal white adipose tissue (dWAT) has found little appreciation in the past as a distinct entity from the better recognized subcutaneous white adipose tissue (sWAT). However, recent work has established dWAT as an important contributor to a multitude of processes, including immune response, wound healing and scarring, hair follicle growth and thermoregulation. Unique metabolic contributions are attributed to dWAT as well, at least in part due to thermic insulation properties and its response to cold exposure. Dermal adipocytes can also undergo adipocyte-myofibroblast transition (AMT), a process that is suspected to play an important role in a number of pathophysiological processes within the skin. Here, we discuss emerging concepts regarding dWAT physiology and its significance to a variety of cellular processes. PMID:26643658

  7. Dermal mass aspirate from a Persian cat.

    PubMed

    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.

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

    PubMed

    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.

  9. Assessment of dermal safety of Scutellaria baicalensis aqueous extract topical application on skin hypersensitivity.

    PubMed

    Kim, Tae-Won; Song, In-Bae; Lee, Hong-Ki; Kim, Myoung-Seok; Ham, Seoung-Ho; Cho, Jung-Hee; Lim, Jong-Hwan; Yun, Hyo-In

    2013-07-01

    Scutellaria baicalensis has been used as a traditional herbal medicine for bronchitis, hepatitis, and allergic diseases. The root of Scutellaria baicalensis contains active flavonoid components, including baicalin, baicalein, wogonoside, and wogonin, which have pharmaceutical properties. In the present study, the antiallergic properties of a standardized aqueous extract of S. baicalensis were evaluated, and the skin toxicity of its dermal application was also determined. The in vivo and in vitro assays were performed by using the β-hexosaminidase assay in rat basophilic leukemia cells (RBL-2H3) and cutaneous skin reaction in BALB/c mice, respectively. In addition, the acute dermal irritation/corrosion test was carried out in New Zealand white rabbits, and the skin sensitization test was conducted by Buhler's method in Hartley guinea pigs to estimate the safety of the standardized aqueous extract of S. baicalensis for topical application. β-Hexosaminidase release in RBL-2H3 was markedly decreased following treatment with the standardized aqueous extract of S. baicalensis. It also ameliorated antigen-induced ear swelling compared with the control group in BALB/c mice. In the toxicological studies, it did not induce any dermal irritation/corrosion in rabbits or skin sensitization in guinea pigs. Although still limited, these results concerning the toxicological effects of S. baicalensis could be an initial step toward the topical application of S. baicalensis extracts on hypersensitive skin.

  10. Towards global QSAR model building for acute toxicity: Munro database case study.

    PubMed

    Chavan, Swapnil; Nicholls, Ian A; Karlsson, Björn C G; Rosengren, Annika M; Ballabio, Davide; Consonni, Viviana; Todeschini, Roberto

    2014-10-09

    A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN) classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER) equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.

  11. Tungsten speciation and toxicity: acute toxicity of mono- and poly-tungstates to fish.

    PubMed

    Strigul, Nikolay; Koutsospyros, Agamemnon; Christodoulatos, Christos

    2010-02-01

    Tungsten is a widely used transition metal for which very limited information on environmental and toxicological effects is available. Of particular interest is the lack of information linking tungsten speciation and environmental effects. Tungsten anions may polymerize (depending upon concentration, pH, and aquatic geochemistry) in aquatic and soil systems. However, to this date, of all soluble tungstate species only monotungstates have been scrutinized to a fair extent in toxicological studies. The objective of this work is a comparative assessment of the acute toxicity of monotungstates (sodium tungstate, Na(2)WO(4)) and polytungstates (sodium metatungstate, 3Na(2)WO(4).9WO(3)) to Poecilia reticulate. The experiments have been performed according to the OEDC protocols 203 and 204. LD50 values for 1-14 days show that sodium metatungstate is significantly more toxic to fish than sodium tungstate. Based on LD50 (0.86-3.88gL(-1) or 4.67-21.1x10(-3)molNa(2)WO(4)L(-1)), sodium tungstate may be classified as a chemical of low toxicity to fish. Sodium metatungstate caused similar fish mortality to sodium tungstate when it was introduced in 55-80 times lower concentrations (in terms of molL(-1)) than sodium tungstate. LD50 values for sodium metatungstate range from 0.13 to 0.85gWL(-1) or 5.69 to 38.71x10(-5)mol 3Na(2)WO(4).9WO(3)L(-1). Based on these values sodium metatungstate can be classified as a moderate toxic agent to fish.

  12. Hip Capsular Reconstruction Using Dermal Allograft.

    PubMed

    Chahla, Jorge; Dean, Chase S; Soares, Eduardo; Mook, William R; Philippon, Marc J

    2016-04-01

    Because hip arthroscopic procedures are increasing in number, complications related to the operation itself are starting to emerge. Whereas the capsule has been recognized as an important static stabilizer for the hip, it has not been until recently that surgeons have realized the importance of its preservation and restoration. Disruption of the capsule during arthroscopic procedures is a potential contributor to postoperative iatrogenic hip instability. In cases of a symptomatic deficient capsule, a capsular reconstruction is mandatory because instability may lead to detrimental chondral and labral changes. The purpose of this report was to describe our technique for arthroscopic hip capsular reconstruction using dermal allograft.

  13. Evaluation of lymphangiogenesis in acellular dermal matrix

    PubMed Central

    Cherubino, Mario; Pellegatta, Igor; Tamborini, Federico; Cerati, Michele; Sessa, Fausto; Valdatta, Luigi

    2014-01-01

    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, lymphatic endothelial

  14. Mesenchymal stem cells induce dermal fibroblast responses to injury

    SciTech Connect

    Smith, Andria N.; Willis, Elise; Chan, Vincent T.; Muffley, Lara A.; Isik, F. Frank; Gibran, Nicole S.; Hocking, Anne M.

    2010-01-01

    Although bone marrow-derived mesenchymal stem cells have been shown to promote repair when applied to cutaneous wounds, the mechanism for this response remains to be determined. The aim of this study was to determine the effects of paracrine signaling from mesenchymal stem cells on dermal fibroblast responses to injury including proliferation, migration and expression of genes important in wound repair. Dermal fibroblasts were co-cultured with bone marrow-derived mesenchymal stem cells grown in inserts, which allowed for paracrine interactions without direct cell contact. In this co-culture model, bone marrow-derived mesenchymal stem cells regulate dermal fibroblast proliferation, migration and gene expression. When co-cultured with mesenchymal stem cells, dermal fibroblasts show increased proliferation and accelerated migration in a scratch assay. A chemotaxis assay also demonstrated that dermal fibroblasts migrate towards bone marrow-derived mesenchymal stem cells. A PCR array was used to analyze the effect of mesenchymal stem cells on dermal fibroblast gene expression. In response to mesenchymal stem cells, dermal fibroblasts up-regulate integrin alpha 7 expression and down-regulate expression of ICAM1, VCAM1 and MMP11. These observations suggest that mesenchymal stem cells may provide an important early signal for dermal fibroblast responses to cutaneous injury.

  15. CARD14 expression in dermal endothelial cells in psoriasis.

    PubMed

    Harden, Jamie L; Lewis, Steven M; Pierson, Katherine C; Suárez-Fariñas, Mayte; Lentini, Tim; Ortenzio, Francesca S; Zaba, Lisa C; Goldbach-Mansky, Raphaela; Bowcock, Anne M; Lowes, Michelle A

    2014-01-01

    Mutations in the caspase recruitment domain, family member 14 (CARD14) gene have recently been described in psoriasis patients, and explain the psoriasis susceptibility locus 2 (PSORS2). CARD14 is a scaffolding protein that regulates NF-κB activation, and psoriasis-associated CARD14 mutations lead to enhanced NF-κB signaling. CARD14 is expressed mainly in epidermal keratinocytes, but also in unidentified dermal cells. In this manuscript, the identity of the dermal cell types expressing CARD14, as well the potential functional consequence of overactive CARD14 in these dermal cell types, was determined. Using two-color immunofluorescence, dermal CARD14 did not co-localize with T-cells, dendritic cells, or macrophages. However, dermal CARD14 did highly co-localize with CD31(+) endothelial cells (ECs). CARD14 was also expressed non-dermal endothelial cells, such as aortic endothelial cells, which may indicate a role of CARD14(+)ECs in the systemic inflammation and cardiovascular comorbidities associated with psoriasis. Additionally, phosphorylated NF-κB was found in psoriatic CARD14(+) CD31(+) ECs, demonstrating this pathway is active in dermal ECs in psoriasis. Transfection of dermal ECs with psoriasis-associated CARD14 mutations resulted in increased expression of several chemokines, including CXCL10, IL-8, and CCL2. These results provide preliminary evidence that CARD14 expression in ECs may contribute to psoriasis through increased expression of chemokines and facilitating recruitment of immune cells into skin.

  16. IN VITRO DERMAL ABSORPTION OF FLAME RETARDANT CHEMICALS

    EPA Science Inventory

    ABSTRACT
    The use of flame retardant chemicals in furniture fabric could pose a potential health risk to consumers from dermal absorption of these compounds. The objective of this study was to examine the in vitro dermal absorption of two flame retardant chemicals, [14C]-d...

  17. Spectrum of PORCN mutations in Focal Dermal Hypoplasia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

    PubMed

    MacVittie, Thomas J; Farese, Ann M; Jackson, William

    2015-11-01

    Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total

  19. Fluzone® intra-dermal (Intanza®/Istivac® Intra-dermal): An updated overview.

    PubMed

    Bragazzi, Nicola Luigi; Orsi, Andrea; Ansaldi, Filippo; Gasparini, Roberto; Icardi, Giancarlo

    2016-10-02

    Influenza is a highly contagious respiratory acute viral disease which imposes a very heavy burden both in terms of epidemiology and costs, in the developed countries as well as in the developing ones. It represents a serious public health concern and vaccination constitutes an important tool to reduce or at least mitigate its burden. Despite the existence of a broad armamentarium against influenza and despite all the efforts and recommendations of international organisms to broaden immunization, influenza vaccination coverage is still far from being optimal. This, taken together with logistic and technical difficulties that can result into vaccine shortage, makes intra-dermal (ID) vaccines, such as Fluzone® ID and Intanza®, particularly attractive. ID vaccines are comparable and, in some cases, superior to intra-muscular/sub-cutaneous vaccines in terms of immunogenicity, safety, reactogenicity, tolerability and cross-protection profiles, as well as in terms of patient preference, acceptance and vaccine selection. Further advances, such as Fluzone® ID with alternative B strains and Quadrivalent Fluzone® ID or the possibility of self-administering the vaccines, make influenza ID vaccines even more valuable.

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

    PubMed

    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.

  1. Acute toxicity of pinnatoxins E, F and G to mice.

    PubMed

    Munday, Rex; Selwood, Andrew I; Rhodes, Lesley

    2012-11-01

    The acute toxicities to mice of pinnatoxins E, F and G, members of the cyclic imine group of phycotoxins, by intraperitoneal injection and/or oral administration, have been determined. These substances were all very toxic by intraperitoneal injection, with LD(50) values between 12.7 and 57 μg/kg. Pinnatoxin E was much less toxic by oral administration than by intraperitoneal injection, but this was not the case for pinnatoxin F. The median lethal doses of the latter substance by gavage and by voluntary intake were only 2 and 4 times higher than that by injection. The high oral toxicity of pinnatoxin F raises concerns as to the possibility of adverse effects of this substance in shellfish consumers, although it should be noted that no toxic effects in humans have been recorded with pinnatoxins or with any other compound of the cyclic imine group.

  2. DREAM: a method for semi-quantitative dermal exposure assessment.

    PubMed

    Van-Wendel-de-Joode, Berna; Brouwer, Derk H; Vermeulen, Roel; Van Hemmen, Joop J; Heederik, Dick; Kromhout, Hans

    2003-01-01

    This paper describes a new method (DREAM) for structured, semi-quantitative dermal exposure assessment for chemical or biological agents that can be used in occupational hygiene or epidemiology. It is anticipated that DREAM could serve as an initial assessment of dermal exposure, amongst others, resulting in a ranking of tasks and subsequently jobs. DREAM consists of an inventory and evaluation part. Two examples of dermal exposure of workers of a car-construction company show that DREAM characterizes tasks and gives insight into exposure mechanisms, forming a basis for systematic exposure reduction. DREAM supplies estimates for exposure levels on the outside clothing layer as well as on skin, and provides insight into the distribution of dermal exposure over the body. Together with the ranking of tasks and people, this provides information for measurement strategies and helps to determine who, where and what to measure. In addition to dermal exposure assessment, the systematic description of dermal exposure pathways helps to prioritize and determine most adequate measurement strategies and methods. DREAM could be a promising approach for structured, semi-quantitative, dermal exposure assessment.

  3. Human acellular dermal matrix grafts for rhinoplasty.

    PubMed

    Sherris, David A; Oriel, Brad S

    2011-09-01

    Rhinoplasty often relies on graft material for structural support in the form of cartilage, bone grafts, or fascia. In addition, pliable grafts are often helpful for contouring and can function as a barrier. Unfortunately, grafts carry the disadvantage of requiring an additional donor site, with associated complications. Human acellular dermal matrix (ADM) biological implants offer an exciting alternative for structural support and nonstructural implantation in rhinoplasty procedures. To examine the efficacy of ADM placement in rhinoplasty and septoplasty, the authors report the results from a series of 51 patients. In this series, there were no cases of infection, skin discoloration, seroma formation, septal perforation, significant resorption, extrusion, or other complications related to ADM placement. Therefore, the authors believe that ADM offers a safe and effective alternative to traditional grafting methods for functional and aesthetic rhinoplasty.

  4. Dermal and Ophthalmic Findings in Pseudohypoaldosteronism

    PubMed Central

    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

  5. The influence of vapor pressure of chemicals on dermal penetration.

    PubMed

    Gilpin, Sarah

    2014-01-01

    Dermal exposure is an important route of entry for chemicals in occupational and consumer settings. Key to this exposure is the penetration of the skin's barrier, and key to this penetration is a chemical's vapor pressure. Until now, vapor pressure and its effects on the skin have yet to be widely studied. This review aims to provide some historical background on early work on dermal penetration for volatile materials, which has helped form later research into the effects of vapor pressure on chemical risk assessment for dermal exposures. This review should be the start of an investigation into more in-depth coverage of vapor pressure and current prediction models.

  6. Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

    SciTech Connect

    Fonsart, Julien ||; Menet, Marie-Claude |; Decleves, Xavier ||; Galons, Herve |; Crete, Dominique; Debray, Marcel; Scherrmann, Jean-Michel ||; Noble, Florence ||

    2008-07-01

    The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism of MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg{sup -1} sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences.

  7. Characterization of the dinophysistoxin-2 acute oral toxicity in mice to define the Toxicity Equivalency Factor.

    PubMed

    Abal, Paula; Louzao, M Carmen; Cifuentes, José Manuel; Vilariño, Natalia; Rodriguez, Ines; Alfonso, Amparo; Vieytes, Mercedes R; Botana, Luis M

    2017-04-01

    Ingestion of shellfish with dinophysistoxin-2 (DTX2) can lead to diarrheic shellfish poisoning (DSP). The official control method of DSP toxins in seafood is the liquid chromatography-mass spectrometry analysis (LC-MS). However in order to calculate the total toxicity of shellfish, the concentration of each compound must be multiplied by individual Toxicity Equivalency Factor (TEF). Considering that TEFs caused some controversy and the scarce information about DTX2 toxicity, the aim of this study was to characterize the oral toxicity of DTX2 in mice. A 4-Level Up and Down Procedure allowed the characterization of DTX2 effects and the estimation of DTX2 oral TEF based on determination of the lethal dose 50 (LD50). DTX2 passed the gastrointestinal barrier and was detected in urine and feces. Acute toxicity symptoms include diarrhea and motionless, however anatomopathology study and ultrastructural images restricted the toxin effects to the gastrointestinal tract. Nevertheless enterocytes microvilli and tight junctions were not altered, disconnecting DTX2 diarrheic effects from paracellular epithelial permeability. This is the first report of DTX2 oral LD50 (2262 μg/kg BW) indicating that its TEF is about 0.4. This result suggests reevaluation of the present TEFs for the DSP toxins to better determine the actual risk to seafood consumers.

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

    NASA Astrophysics Data System (ADS)

    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, <μ>, however the average local dermal reflectivity <ρ>, decreased significantly following 1, 3, and 6 days of IMQ treatment (p < 0.001) in comparison to vehicle-treated control mice. In contrast, epidermal and dermal thickness changes were only significant when comparing controls and 6-day IMQ treated mice. This suggests that dermal alterations, attributed to 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.

  9. The acute toxicity of the death camas (Zigadenus species) alkaloid zygacine in mice, including the effect of methyllycaconitine coadministration on zygacine toxicity.

    PubMed

    Welch, K D; Panter, K E; Gardner, D R; Stegelmeier, B L; Green, B T; Pfister, J A; Cook, D

    2011-05-01

    Death camas (Zigadenus spp.) is a common poisonous plant on foothill rangelands in western North America. The steroidal alkaloid zygacine is believed to be the primary toxic component in death camas. Poisonings on rangelands generally occur in the spring when death camas is abundant, whereas other more desirable forage species are limited in availability. In most cases where livestock are poisoned by plants in a range setting, there is more than one potential poisonous plant in that area. One common poisonous plant that is often found growing simultaneously in the same area as death camas is low larkspur (Delphinium nuttallianum). Consequently, the objectives of this study were to conduct acute toxicity studies in mice and to determine if coadministration of low larkspur will exacerbate the toxicity of death camas. We first characterized the acute toxicity of zygacine in mice. The LD(50) of zygacine administered intravenously (i.v.) and orally was 2.0 ± 0.2 and 132 ± 21 mg/kg, respectively. The rate of elimination of zygacine from whole blood was determined to be 0.06 ± 0.01/min, which corresponds to an elimination half-life of 13.0 ± 2.7 min. The i.v. LD(50) of total alkaloid extracts from a Utah and a Nevada collection were 2.8 ± 0.8 and 2.2 ± 0.3 mg/kg, respectively. The i.v. LD(50) of methyllycaconitine (MLA), a major toxic alkaloid in low larkspur, was 4.6 ± 0.5 mg/kg, whereas the i.v. LD(50) of a 1:1 mixture of MLA and zygacine was 2.9 ± 0.7 mg/kg. The clinical signs in mice treated with this mixture were very similar to those of mice treated with zygacine alone, including the time of onset and death. These results suggest that there is an additive effect of coadministering these 2 alkaloids i.v. in mice. The results from this study increase knowledge and understanding regarding the acute toxicity of death camas. As combined intoxications are most likely common, this information will be useful in further developing management recommendations for

  10. Efficacy and safety of catnip (Nepeta cataria) as a novel filth fly repellent.

    PubMed

    Zhu, J J; Zeng, X-P; Berkebile, D; DU, H-J; Tong, Y; Qian, K

    2009-09-01

    Catnip (Nepeta cataria) is known for its pseudo-narcotic effects on cats. Recently, it has been reported as an effective mosquito repellent against several Aedes and Culex species, both topically and spatially. Our laboratory bioassays showed that catnip essential oil (at a dosage of 20 mg) resulted in average repellency rates of 96% against stable flies, Stomoxys calcitrans (L.) and 79% against houseflies, Musca domestica (L.), respectively. This finding suggested that the application of repellent could be used as part of filth fly management. Further evaluations of catnip oil toxicity were conducted to provide a broad-spectrum safety profile of catnip oil use as a potential biting and nuisance insect repellent in urban settings. Acute oral, dermal, inhalation, primary dermal and eye irritation toxicity tests were performed. The acute oral LD(50) of catnip oil was found to be 3160 mg/kg body weight (BW) and 2710 mg/kg BW in female and male rats, respectively. The acute dermal LD50 was > 5000 mg/kg BW. The acute inhalation LD50 was observed to be > 10,000 mg/m3. Primary skin irritation tested on New Zealand white rabbits showed that catnip oil is a moderate irritant. Catnip oil was classified as practically non-irritating to the eye. In comparison with other U.S. Environmental Protection Agency-approved mosquito repellents (DEET, picaridin and p-menthane-3,8-diol), catnip oil can be considered as a relatively safe repellent, which may cause minor skin irritation.

  11. Toxicological evaluation of neem (Azadirachta indica) oil: acute and subacute toxicity.

    PubMed

    Deng, Yun-xia; Cao, Mei; Shi, Dong-xia; Yin, Zhong-qiong; Jia, Ren-yong; Xu, Jiao; Wang, Chuan; Lv, Cheng; Liang, Xiao-xia; He, Chang-liang; Yang, Zhi-rong; Zhao, Jian

    2013-03-01

    Neem (Azadirachta indica), popularly known as traditional medicine is a native plant in India. Neem oil is a vegetable oil derived from seeds or fruits of the neem tree through pressing or solvent extraction, and largely used in popular medicine to have antifungal, antibacterial, antimalarial, antiparasitic, anti-inflammatory, as well as immunemodulatory properties in different animal species. In the present study, acute and 28-day subacute toxicity tests were carried out. In the acute toxicity test, the LD50 values of neem oil were found to be 31.95g/kg. The subacute treatment with neem oil failed to change body weight gain, food and water consumption. Serum biochemistry analysis showed no significant differences in any of the parameters examined under the dose of 1600mg/kg/day. Histopathological exams showed that the target organs of neem oil were testicle, liver and kidneys up to the dose of 1600mg/kg/day.

  12. Ability of transplanted cultured epithelium to respond to dermal papillae.

    PubMed

    Xing, L; Kobayashi, K

    2001-10-01

    Cultured epithelium has been used successfully in the treatment of extensive burns. Regenerated epidermis, however, lacks such as hair follicles and sweat glands that are common in mammalian skin. We attempted to determine whether cultured epithelium could be induced to form hair follicles by dermal papillae, which are most important for the morphogenesis and growth of hair follicles. We cultivated adult rat sole keratinocytes, obtained the cultured epithelium, and prepared recombinants consisting of cultured epithelium and fresh dermal papillae with or without the sole dermis. These recombinants were then transplanted underneath the dermis of the dorsal skin of syngeneic rats or athymic mice. Histologic examination revealed that the transplanted cultured epithelium formed the follicular structures with sebaceous gland-like structure following induction of the dermal papillae, especially when supported by the dermis. We concluded that transplanted cultured epithelium of adult rat sole keratinocytes can respond to growth signals from adult dermal papillae.

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

    PubMed

    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.

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

    SciTech Connect

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

    2007-07-01

    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, putting down new roofs, and operating the kettle at ground level. During multiple consecutive work shifts, 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 and by the presence of an old coal tar pitch roof. For each of the three analytes, the adjusted mean dermal exposures associated with tear-off were approximately four times higher than exposures associated with operating the kettle. Exposure to coal tar pitch was associated with a 6-fold increase in PAC exposure, an 8-fold increase in pyrene exposure and a 35-fold increase in BAP exposure. The presence of coal tar pitch was the primary determinant of dermal exposure, particularly for exposure to BAP. However, the task-based differences that were observed while controlling for pitch suggest that exposure to asphalt also contributes to dermal exposures.

  15. Early dermabrasion of deep dermal burns with sandpaper. Case reports.

    PubMed

    Floccard, B; Tixier, F; Chatot-Henry, D; Lacotte, B; Mehdaoui, H; Drault, J N

    1998-12-01

    Deep dermal burns are initially difficult to evaluate, and they sometimes heal spontaneously. We present our experience of dermabrasion with sandpaper in four patients. It is a useful alternative to early excision of the scar. Skin grafts are not always required and the aesthetic results are excellent. Dermabrasion should be considered routinely for all deep dermal burns and particularly for facial burns and those caused by scalds.

  16. Dermal schwannoma (neurilemmoma): a peculiar foreign body reaction?

    PubMed

    Kneitz, Hermann; Weyandt, Gerhard; Meissner, Christoph; Gebhart, Edith; Bröcker, Eva B

    2010-06-01

    Schwannoma is usually a subcutaneous benign neoplasm that derives from nerve sheath. Pain and neurologic symptoms are uncommon, and exclusively dermal tumors are very rare. Solitary schwannoma has a traumatic origin in some cases, and rarely occur as a part of neurofibromatosis or schwannomatosis. An association of deeply located schwannoma with foreign material has been reported in very few cases. To our knowledge, we present the first case of a painful dermal schwannoma in association to foreign material.

  17. Dermal mast cell responses in Paragonimus westermani-infected mice.

    PubMed

    Shin, M H

    1997-12-01

    This study was carried out to determine whether dermal mast cell responses to Paragonimus westermani in an abnormal host, the mouse, were dependent on the site of metacercarial inoculation. In mice during subcutaneous infection, the number of dermal mast cells were increased significantly (p < 0.05) at the first week (38.3/mm2) and then persisted at a high level until the sixth week (45.2/mm2) of infection compared with PBS-injected (control) mice (range: 19.4-25.1/mm2). In mice during oral infection, the number of dermal mast cells were increased significantly (p < 0.05) at two weeks (33.5/mm2) after infection and remained at these levels thereafter compared with non-infected (control) mice (range: 17.4-22.3/mm2). In mice both during subcutaneous and oral infection, the recruited dermal mast cells showed extensive degranulation at the second week (68.4% and 60.7%, respectively), reached a peak at the third week (81.4%, and 92.1%, respectively) and then declined slightly thereafter. By contrast, in both control mice, about 10% of dermal mast cells were degranulated. In conclusion, this study suggests that dermal mast cell responses to P. westermani in mice are dependent on cutaneous sensitization by larval excretory-secretory antigens, irrespective of infection route.

  18. Comparison of International Guidelines of Dermal Absorption Tests Used in Pesticides Exposure Assessment for Operators

    PubMed Central

    So, Jaehwan; Ahn, Junyoung; Lee, Tae-Hee; Park, Kyung-Hun; Paik, Min-Kyoung; Jeong, Mihye; Cho, Myung-Haing

    2014-01-01

    The number of farmers who have suffered from non-fatal acute pesticide poisoning has been reported to vary from 5.7% to 86.7% in South Korea since 1975. Absorption through the skin is the main route of exposure to pesticides for farmers who operate with them. Several in vitro tests using the skins of humans or animal and in vivo tests using laboratory animals are introduced for the assessment of human dermal absorption level of pesticides. The objective of this study is to evaluate and compare international guidelines and strategies of dermal absorption assessments and to propose unique approaches for applications into pesticide registration process in our situation. Until present in our situation, pesticide exposure level to operator is determined just using default value of 10 as for skin absorption ratio because of data shortage. Dermal absorption tests are requested to get exposure level of pesticides and to ultimately know the safety of pesticides for operators through the comparison with the value of AOEL. When the exposure level is higher than AOEL, the pesticide cannot be approved. We reviewed the skin absorption test guidelines recommended by OECD, EFSA and EPA. The EPA recommends assessment of skin absorption of pesticides for humans through the TPA which includes all the results of in vitro human and animal and animal in vivo skin absorption studies. OECD and EFSA, employ a tiered approach, which the requirement of further study depends on the results of the former stage study. OECD guidelines accept the analysis of pesticide level absorbed through skin without radioisotope when the recovery using the non-labeled method is within 80~120%. Various factors are reviewed in this study, including the origin of skin (gender, animal species and sites of skin), thickness, temperature and, etc., which can influence the integrity of results. PMID:25584144

  19. ABCB5 identifies immunoregulatory dermal cells

    PubMed Central

    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

  20. Vesicular carriers for dermal drug delivery.

    PubMed

    Sinico, Chiara; Fadda, Anna Maria

    2009-08-01

    The skin can offer several advantages as a route of drug administration although its barrier nature makes it difficult for most drugs to penetrate into and permeate through it. During the past decades there has been a lot of interest in lipid vesicles as a tool to improve drug topical delivery. Vesicular systems such as liposomes, niosomes, ethosomes and elastic, deformable vesicles provide an alternative for improved skin drug delivery. The function of vesicles as topical delivery systems is controversial with variable effects being reported in relation to the type of vesicles and their composition. In fact, vesicles can act as drug carriers controlling active release; they can provide a localized depot in the skin for dermally active compounds and enhance transdermal drug delivery. A wide variety of lipids and surfactants can be used to prepare vesicles, which are commonly composed of phospholipids (liposomes) or non-ionic surfactants (niosomes). Vesicle composition and preparation method influence their physicochemical properties (size, charge, lamellarity, thermodynamic state, deformability) and therefore their efficacy as drug delivery systems. A review of vesicle value in localizing drugs within the skin at the site of action will be provided with emphasis on their potential mechanism of action.

  1. Human dermal fibroblasts in psychiatry research.

    PubMed

    Kálmán, S; Garbett, K A; Janka, Z; Mirnics, K

    2016-04-21

    In order to decipher the disease etiology, progression and treatment of multifactorial human brain diseases we utilize a host of different experimental models. Recently, patient-derived human dermal fibroblast (HDF) cultures have re-emerged as promising in vitro functional system for examining various cellular, molecular, metabolic and (patho)physiological states and traits of psychiatric disorders. HDF studies serve as a powerful complement to postmortem and animal studies, and often appear to be informative about the altered homeostasis in neural tissue. Studies of HDFs from patients with schizophrenia (SZ), depression, bipolar disorder (BD), autism, attention deficit and hyperactivity disorder and other psychiatric disorders have significantly advanced our understanding of these devastating diseases. These reports unequivocally prove that signal transduction, redox homeostasis, circadian rhythms and gene*environment (G*E) interactions are all amenable for assessment by the HDF model. Furthermore, the reported findings suggest that this underutilized patient biomaterial, combined with modern molecular biology techniques, may have both diagnostic and prognostic value, including prediction of response to therapeutic agents.

  2. Dermal absorption of inorganic germanium in rats.

    PubMed

    Yokoi, Katsuhiko; Kawaai, Takae; Konomi, Aki; Uchida, Yuka

    2008-11-01

    So-called germanium 'health' products including dietary supplements, cosmetics, accessories, and warm bath service containing germanium compounds and metalloid are popular in Japan. Subchronic and chronic oral exposure of germanium dioxide (GeO(2)), popular chemical form of inorganic germanium causes severe germanium toxicosis including death and kidney dysfunction in humans and experimental animals. Intestinal absorption of neutralized GeO(2) or germanate is almost complete in humans and animals. However, it is not known whether germanium is cutaneously absorbed. We tested dermal absorption of neutralized GeO(2) or germanate using male F344/N rats. Three groups of rats were treated with a 3-h topical application of hydrophilic ointment containing graded level of neutralized GeO(2) (pH 7.4): 0, 0.21 and 0.42 mg GeO(2)/g. Germanium concentration in blood and tissues sampled from rats after topical application of inorganic germanium was measured by inductively coupled plasma-mass spectrometry. Animals topically applied 0.42 mg GeO(2)/g ointment had significantly higher germanium concentrations in plasma, liver, and kidney than those of rats that received no topical germanium. The results indicate that skin is permeable to inorganic germanium ion or germanate and recurrent exposure of germanium compounds may pose a potential health hazard.

  3. Emotional intelligence and electro-dermal activity.

    PubMed

    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 < .001) and age (Beta = -.24, -.31; p < .03) associated with EDA delta (stimulus response-baseline) scores, while the 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.

  4. Acellular dermal graft reinforcement at the hiatus.

    PubMed

    Freedman, Bruce

    2012-11-01

    The ideal technique to repair large hiatal and diaphragmatic defects remains controversial. Due to high recurrence rates with primary repair alone, attempts at crural reinforcement with various products has been investigated. Initial evaluation of synthetic mesh at the hiatus in retrospective studies led to the conclusion that there were too many serious complications with these products. The next step was to see how biologic grafts fared in this location. Beginning with porcine intestine submucosa in a laminated array and progressing through human and porcine acellular dermal matrices, multiple, retrospective studies looked at the efficacy and safety of these products. Unfortunately, most of these studies evaluated a small sample size with a relatively short follow-up period. The one study followed out to 5 years failed to show any benefit using the biologic (porcine intestinal submucosa) compared with the primary repair alone. Additional, prospective, randomized studies with ample numbers carried out for years will be necessary to see which biologic graft is not only safe but also successful in preventing recurrent herniations.

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

    PubMed

    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.

  6. Methamphetamine residue dermal transfer efficiencies from household surfaces.

    PubMed

    Van Dyke, Mike; Martyny, John W; Serrano, Kate A

    2014-01-01

    Methamphetamine contamination from illegal production operations poses a potential health concern for emergency responders, child protective services, law enforcement, and children living in contaminated structures. The objective of this study was to evaluate dermal transfer efficiencies of methamphetamine from contaminated household surfaces. These transfer efficiencies are lacking for methamphetamine, and would be beneficial for use in exposure models. Surfaces were contaminated using a simulated smoking method in a stainless steel chamber. Household surfaces were carpet, painted drywall, and linoleum. Dermal transfer efficiencies were obtained using cotton gloves for two hand conditions, dry or saliva moistened (wet). In addition, three contact scenarios were evaluated for both hand conditions: one, two, or three contacts with contaminated surfaces. Dermal transfer efficiencies were calculated for both hand conditions and used as inputs in a Stochastic Human Exposure and Dose Simulation model (SHEDS-Multimedia, Office of Research and Development, United States Environmental Protection Agency, Research Triangle Park, N.C.). Results of this study showed that average dermal transfer efficiencies of methamphetamine ranged from 11% for dry hands to 26% for wet hands. There was a significantly higher wet transfer as compared to dry transfer for all surfaces. For wet hands, dermal transfer depended on surface type with higher transfer from carpet and linoleum as compared to drywall. Based on our estimates of dermal transfer efficiency, a surface contamination clearance level of 1.5 μg/100 cm(2) may not ensure absorbed doses remain below the level associated with adverse health effects in all cases. Additional dermal transfer studies should be performed using skin surrogates that may better predict actual skin transfer.

  7. A case of diffuse alveolar hemorrhage associated with hyaluronic acid dermal fillers

    PubMed Central

    Basora, Jose F.; Fernandez, Ricardo; Gonzalez, Modesto; Adorno, Jose

    2014-01-01

    Patient: Male, 25 Final Diagnosis: Diffuse alveolar hemorrhage Symptoms: Cough dry • short of breath Medication: — Clinical Procedure: — Specialty: — Objective: Unusual clinical course Background: Hyaluronic acid is a substance that is naturally present in the human body, especially in joints and eyes. Hyaluronic acid injectable gels have been available for the general market since 2003 as cosmetic dermal fillers and skin boosters. Diffuse alveolar hemorrhage is an acute event that threatens the life of the patient and can lead to pulmonary fibrosis. Alveolar hemorrhage associated with hyaluronic acid dermal fillers is an entity that to the best of our knowledge has never been described in the medical literature. Case Report: We describe a patient who presented with dyspnea and cough after a subcutaneous injection of hyaluronic acid, with radiographic abnormalities including ground glass opacities and consolidation. The patient underwent flexible bronchoscopy and was diagnosed with diffuse alveolar hemorrhage. Conclusions: This case emphasizes that this life threatening condition may occur with the use of this medication and physicians must be aware of this disorder, as early recognition and management can reduce morbidity. PMID:24826208

  8. Dermal injection of immunocytes induces psoriasis.

    PubMed

    Wrone-Smith, T; Nickoloff, B J

    1996-10-15

    Establishing direct and causal relationships among the confederacy of activated cell types present in psoriasis has been hampered by lack of an animal model. Within psoriatic plaques there are hyperplastic keratinocytes, infiltrating immunocytes, and activated endothelial cells. The purpose of this study was to determine if psoriasis is primarily a disorder of keratinocytes or the immune system. Using a newly developed experimental system in which full-thickness human skin is orthotopically transferred onto severe combined immunodeficient mice, autologous immunocytes were injected into dermis, and the resultant phenotype characterized by clinical, histologic, and immunophenotypic analyses. Engraftment of samples included both uninvolved/ symptomless (PN) skin removed from patients with psoriasis elsewhere, or from healthy individuals with no skin disease (NN skin). In 10 different experiments involving 6 different psoriasis patients, every PN skin was converted to a full-fledged psoriatic plaque skin by injection of autologous blood-derived immunocytes. In all but one psoriatic patient, the immunocytes required preactivation with IL-2 and superantigens to convert PN skin into psoriatic plaque skin. In every case, resultant plaques were characterized by visible presence of flaking and thickened skin, loss of the granular cell layer, prominent elongation of rete pegs with a dermal angiogenic tissue reaction, and infiltration within the epidermis by T cells. Lesional skin displayed 20 different antigenic determinants of the psoriatic phenotype. None of the four NN skin samples injected with autologous immunocytes converted to psoriatic plaques. We conclude that psoriasis is caused primarily by the ability of pathogenetic blood-derived immunocytes to induce secondary activation and disordered growth of endogenous cutaneous cells including keratinocytes and vascular endothelium.

  9. Dermal injection of immunocytes induces psoriasis.

    PubMed Central

    Wrone-Smith, T; Nickoloff, B J

    1996-01-01

    Establishing direct and causal relationships among the confederacy of activated cell types present in psoriasis has been hampered by lack of an animal model. Within psoriatic plaques there are hyperplastic keratinocytes, infiltrating immunocytes, and activated endothelial cells. The purpose of this study was to determine if psoriasis is primarily a disorder of keratinocytes or the immune system. Using a newly developed experimental system in which full-thickness human skin is orthotopically transferred onto severe combined immunodeficient mice, autologous immunocytes were injected into dermis, and the resultant phenotype characterized by clinical, histologic, and immunophenotypic analyses. Engraftment of samples included both uninvolved/ symptomless (PN) skin removed from patients with psoriasis elsewhere, or from healthy individuals with no skin disease (NN skin). In 10 different experiments involving 6 different psoriasis patients, every PN skin was converted to a full-fledged psoriatic plaque skin by injection of autologous blood-derived immunocytes. In all but one psoriatic patient, the immunocytes required preactivation with IL-2 and superantigens to convert PN skin into psoriatic plaque skin. In every case, resultant plaques were characterized by visible presence of flaking and thickened skin, loss of the granular cell layer, prominent elongation of rete pegs with a dermal angiogenic tissue reaction, and infiltration within the epidermis by T cells. Lesional skin displayed 20 different antigenic determinants of the psoriatic phenotype. None of the four NN skin samples injected with autologous immunocytes converted to psoriatic plaques. We conclude that psoriasis is caused primarily by the ability of pathogenetic blood-derived immunocytes to induce secondary activation and disordered growth of endogenous cutaneous cells including keratinocytes and vascular endothelium. PMID:8878440

  10. Characterization of Ovine Dermal Papilla Cell Aggregation

    PubMed Central

    Sari, Agnes Rosarina Prita; Rufaut, Nicholas Wolfgang; Jones, Leslie Norman; Sinclair, Rodney Daniel

    2016-01-01

    Context: The dermal papilla (DP) is a condensation of mesenchymal cells at the proximal end of the hair follicle, which determines hair shaft size and regulates matrix cell proliferation and differentiation. DP cells have the ability to regenerate new hair follicles. These cells tend to aggregate both in vitro and in vivo. This tendency is associated with the ability of papilla cells to induce hair growth. However, human papilla cells lose their hair-inducing activity in later passage number. Ovine DP cells are different from human DP cells since they do not lose their aggregative behavior or hair-inducing activity in culture. Nonetheless, our understanding of ovine DP cells is still limited. Aim: The aim of this study was to observe the expression of established DP markers in ovine cells and their association with aggregation. Subjects and Methods: Ovine DP cells from three different sheep were compared. Histochemistry, immunoflourescence, and polymerase chain reaction experiments were done to analyze the DP markers. Results: We found that ovine DP aggregates expressed all the 16 markers evaluated, including alkaline phosphatase and versican. Expression of the versican V0 and V3 isoforms, neural cell adhesion molecule, and corin was increased significantly with aggregation, while hey-1 expression was significantly decreased. Conclusions: Overall, the stable expression of numerous markers suggests that aggregating ovine DP cells have a similar phenotype to papillae in vivo. The stability of their molecular phenotype is consistent with their robust aggregative behavior and retained follicle-inducing activity after prolonged culture. Their phenotypic stability in culture contrasts with DP cells from other species, and suggests that a better understanding of ovine DP cells might provide opportunities to improve the hair-inducing activity and therapeutic potential of human cells. PMID:27625564

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

    SciTech Connect

    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.

  12. Evaluation of calcium magnesium acetate and road salt for contact hypersensitivity potential and dermal irritancy in humans.

    PubMed

    Cushman, J R; Duff, V A; Buteau, G H; Aust, L B; Caldwell, N; Lazer, W

    1991-04-01

    Calcium magnesium acetate (CMA) and road salt are both de-icing agents to which workers may be dermally exposed. A commercial formulation of CMA (Chevron Ice-B-Gon Deicer) and road salt were tested in a human repeat insult patch test to evaluate the contact hypersensitivity potential of these materials and to evaluate irritation following single or multiple applications. 72 of the initial 82 panelists completed the study. CMA and road salt (each at 10% and 30% w/w in distilled water; 0.3 ml) were administered under occlusive patches on the forearm for 14 h 3 x per week for 3 weeks. The panelists were challenged 2 weeks later; 2 panelists who had mild reactions were subsequently rechallenged 6 weeks later. Neither CMA nor road salt produced contact hypersensitivity in any panelists. Following the first application, moderate acute irritation was observed only at 1 skin site exposed to 30% road salt. Repeated exposure to CMA or road salt produced mild to moderate irritation. The highest incidence of moderate irritation was observed with 30% road salt. Thus, neither material is expected to cause significant dermal effects in exposed workers. CMA is expected to cause dermal irritation equivalent to or less than that caused by road salt.

  13. A study on mRNA expressions of fibronectin in dermal and cerebral wound healing for wound age estimation.

    PubMed

    Takamiya, Masataka; Kumagai, Reiko; Nakayashiki, Nori; Aoki, Yasuhiro

    2006-07-01

    We investigated mRNA expressions of fibronectin for wound age estimation during dermal and cerebral wound healing. Fibronectin mRNA expressions in the injured skin peaked at 8h post-injury. The expressions were detected in endothelial cells before and after injury, whereas they were detectable in the epidermal cells at 1-240 h, in fibroblasts at 1-72 h, in neutrophils and macrophages at 8-72 h, respectively. However, the expressions in epidermal cells became relatively weak in the subacute phase. Fibronectin mRNA expressions of the injured cerebrum increased after the intervention and peaked at 48 h, whereas there was a slight decrease during 24h post-injury. Although fibronectin mRNA was seen exclusively in the endothelial cells of the intact cerebrum, it was also detected in astrocytes during wound healing. From these findings, it was considered that fibronectin played an important role in dermal and cerebral wound healing. Expression of fibronectin mRNA was considered to indicate the acute phase of dermal wound healing, and the subacute phase of cerebral wound healing.

  14. The inhibitory effect of Zingiber corallinum Hance essential oil on drug-resistant bacteria and evaluation of its acute toxicity

    PubMed Central

    Yang, Ce; Zhou, Lin-Lin; Wang, Hai-Yan; Huang, Su-Na; Liu, Qing; Hu, Shi-Lin; Li, Ting-Rong; Chen, Yan-Bing; Jiang, Jian-Xin

    2011-01-01

    Summary Background The excessive and irregular use of antibiotics could result in the generation and diffusion of drug-resistant bacteria. The aim of this study was to investigate the inhibitory effect of Zingiber corallinum Hance essential oil (ZCHO) on drug-resistant bacteria, especially on drug-resistant Acinetobacter baumannii. Material/Methods Susceptibility testing was used to evaluate the effect of ZCHO on growth inhibition of drug-resistant bacteria by paper disk method. Mice orally administered with ZCHO were used to observe acute toxicity and to determine median lethal dose (LD50) of ZCHO. Broth dilution method was used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of ZCHO on drug-resistant Acinetobacter baumannii. Results ZCHO exhibited an obvious inhibitory effect not only on gram-negative drug-resistant bacteria including Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Acinetobacter baumannii, but also on gram-positive drug-resistant bacteria including Staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus. The ZCHO containing 79% terpinen-4-ol revealed better bacteriostatic effect than ZCHO with 34% terpinen-4-ol. The LD50 of ZCHO was 1790.427 mg/kg. The MIC and MBC of ZCHO on drug-resistant Acinetobacter baumannii were 1457.81 mg/L. Conclusions ZCHO has obvious bacteriostasis and bactericidal effects, especially against drug-resistant Acinetobacter baumannii. Therefore, ZCHO is a promising natural bioactive component with antibacterial effect and satisfactory safety due to its low toxicity. PMID:21525802

  15. Alteration of Skin Properties with Autologous Dermal Fibroblasts

    PubMed Central

    Thangapazham, Rajesh L.; Darling, Thomas N.; Meyerle, Jon

    2014-01-01

    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. PMID:24828202

  16. Alteration of skin properties with autologous dermal fibroblasts.

    PubMed

    Thangapazham, Rajesh L; Darling, Thomas N; Meyerle, Jon

    2014-05-13

    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.

  17. Efficient Generation of Chemically Induced Mesenchymal Stem Cells from Human Dermal Fibroblasts

    PubMed Central

    Lai, Pei-Lun; Lin, Hsuan; Chen, Shang-Fu; Yang, Shang-Chih; Hung, Kuo-Hsuan; Chang, Ching-Fang; Chang, Hsiang-Yi; Lu, Frank Leigh; Lee, Yi-Hsuan; Liu, Yu-Chuan; Huang, Hsiao-Chun; Lu, Jean

    2017-01-01

    Human mesenchymal stromal/stem cells (MSCs) are multipotent and currently undergoing hundreds of clinical trials for disease treatments. To date, no studies have generated induced MSCs from skin fibroblasts with chemicals or growth factors. Here, we established the first chemical method to convert primary human dermal fibroblasts into multipotent, induced MSC-like cells (iMSCs). The conversion method uses a defined cocktail of small molecules and growth factors, and it can achieve efficient conversion with an average rate of 38% in 6 days. The iMSCs have much higher clonogenicity than fibroblasts, and they can be maintained and expanded in regular MSC medium for at least 8 passages and further differentiated into osteoblasts, adipocytes, and chondrocytes. Moreover, the iMSCs can suppress LPS-mediated acute lung injury as effectively as bone marrow-derived mesenchymal stem cells. This finding may greatly benefit stem cell biology, cell therapy, and regenerative medicine. PMID:28303927

  18. Porcine dermal lesions produced by 1.3um laser pulses

    NASA Astrophysics Data System (ADS)

    Johnson, Thomas E.; Winston, Golda C. H.; Burton, Margaret B.; Greene, Willie L.

    2003-07-01

    An increasing number of industries, to include military, medicinal, and technological arenas, are using 1.3 micron laser systems for which current skin and eye guidelines are identical. No skin threshold, ED50 or exposure data are available. The mechanisms of laser-tissue interaction with skin at 1.3 microns are unknown. Together, these facts necessitate increased research to prevent future laser accidents and injuries. This study examines the method of interaction of 1.3 microns laser light with tissue in the Yorkshire pig. Our research addresses laser-tissue interaction through delivery using a Nd:YAG with an intracavity filter producing 1.3 micron light at 0.5 millisecond exposure time and in the range of 137 to 475 J/cm2. Laser exposure to Yorkshire pigs was evaluated for dermal lesion development. Lesions were appraised for acute, one-hour and 24-hour post exposure presentation.

  19. Sub-chronic Dermal Toxicity of Silver Nanoparticles in Guinea Pig: Special Emphasis to Heart, Bone and Kidney Toxicities.

    PubMed

    Korani, Mitra; Rezayat, Seyed Mahdi; Arbabi Bidgoli, Sepideh

    2013-01-01

    Silver nanoparticles (Ag NPs) have been widely used as new potent antimicrobial agents in cosmetic and hygienic products. Present study compares the tissue levels of Ag NPs in different organs of Guiana Pigs quantitatively after dermal application and analysis the morphological changes and pathological abnormalities on the basis of the Ag NPs tissue levels. Before toxicological assessments,the size of colloidal nanosilver was recorded by X-Ray Diffraction and Transmission Electron Microscope tests and the sizes of samples were recorded in sizes less than 100 nm. For toxicological evaluation, male guinea pigs were exposed to three concentrations of Ag NPs (100, 1000 and 10000 ppm) according to acute pretests for further assessments in subchronic model in a period of 13 weeks . A close correlation between dermal exposure and tissue levels of Ag NPs was found (p < 0.05) and tissue uptakes happened in dose dependent manner with the following ranking: ki dney>muscle>bone>skin>liver>heart >spleen. In histopathological studies, severe proximal convoluted tubule degeneration and distal convoluted tubule were seen in the kidneys of the middle and high-dose animals. Separated lines and marrow space narrow were determined as two major signs of bone toxicities which observed in three different dose levels of Ag NPs. Increased dermal dose of Ag NPs caused cardiocyte deformity, congestion and inflammation. The three different Ag NPs concentration gave comparable results for several endpoints measured in heart, bone and kidney, but differed in tissue concentrations and the extent of histopathological changes. It seems that Ag ions could be detected in different organs after dermal exposure ,which has the potential to provide target organ toxicities in a time and dose dependent manner.

  20. [Occipital dermal sinus associated to a cerebellar abscess. Case].

    PubMed

    Costa, J M; de Reina, L; Guillén, A; Claramunt, E

    2004-10-01

    Congenital dermal sinuses are tubular tracts which communicate the skin with deeper structures. It is a manifestation of defective separation of the ectoderm and neuroderm. The incidence is 1/2500-3000 births alive. Almost 10 % of congenital dermal sinuses are localized in the occipitocervical region. They are usually asymptomatic, unless an infectious process is concurrent (meningitis, abscess). We are presenting the case of a 12 months girl with unnoticed cutaneous stigmata in the occipital region, who was admitted with a meningeal syndrome and secondary neurological impairment. She had a cerebellar abscess and was treated with decompression by puncture of the abscess and antibiotics. When infection was resolved, congenital dermal sinus was excised. Process solves without morbidity. We reviewed the clinical and therapeutic features in cases reported previously in the literature.

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

    PubMed

    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.

  2. Neck Contracture Release With Matriderm Collagen/Elastin Dermal Matrix

    PubMed Central

    Greenwood, John E.; Mackie, Ian P.

    2011-01-01

    Aims: To demonstrate success with immediate split-skin graft application over Matriderm dermal matrix in a difficult neck contracture release. Methods: An aggressive neck contracture release, accompanied by complete platysmectomy, was followed by application of Matriderm, split-skin graft, Mepitel, and vacuum-assisted closure (VAC) dressing. Results: At VAC removal (day 7), graft take was almost complete over the dermal matrix and with minor “touch-up” were complete by day 9 postrepair. Results at 4 months show graft contraction and a marked diminution of the release obtained. The results, however, are still good and the patient is very happy. Conclusion: Immediate grafting over a dermal matrix appears to provide a good solution, with a gentle surgical learning curve, in this difficult postburn scenario. Postrelease contraction is, however, as inevitable as with other techniques. PMID:21451729

  3. Complications of acellular dermal matrices in breast surgery.

    PubMed

    Israeli, Ron

    2012-11-01

    Acellular dermal matrices have been used in breast surgery for a decade. They are widely used in implant-based breast reconstruction to provide coverage of the inferolateral aspects of the prosthesis. Numerous benefits have been reported with this approach including improved fold control, better support and control of the implant pocket with concomitant reduced risk of malposition, and improved lower pole expansion. Seroma, infection, mastectomy skin necrosis, and expander/implant loss are the most commonly reported complications with this approach, and the incidences vary widely among studies. Patient selection and adherence to established intraoperative technique principles related to acellular dermal matrix use are both critical to minimizing the risk of complications. Acellular dermal matrices are also being used in aesthetic breast surgery, revision breast surgery, and nipple reconstruction, but clinical experience is limited. This article reviews the complications associated with the use of matrices in breast surgery from the published literature.

  4. Biological effects of glycolic acid on dermal matrix metabolism mediated by dermal fibroblasts and epidermal keratinocytes.

    PubMed

    Okano, Yuri; Abe, Yumiko; Masaki, Hitoshi; Santhanam, Uma; Ichihashi, Masamitsu; Funasaka, Yoko

    2003-01-01

    Glycolic acid (GA), one of the alpha-hydroxy acids, is widely used as an agent for chemical peeling. Although there are several reports about the clinical effects of GA in the literature, its biological mechanism remains mostly unclear, and there are only a few reports about its effects on skin rejuvenation mediated by keratinocytes. The aim of this study was to investigate the effect of GA on the dermal matrix metabolism of keratinocytes and fibroblasts using in vitro and ex vivo systems. Our study shows that GA not only directly accelerates collagen synthesis by fibroblasts, but it also modulates matrix degradation and collagen synthesis through keratinocyte-released cytokines. We confirm that IL-1alpha is one of the primary mediators for matrix degradation released from keratinocytes after GA treatment. These results suggest that GA contributes to the recovery of photodamaged skin through various actions, depending on the skin cell type.

  5. Dermal absorption of mucopolysaccharide polysulfate (heparinoid) in human and minipig.

    PubMed

    Kumokawa, Tadao; Hirata, Kazumasa; Sato, Keiichi; Kano, Satoshi

    2011-01-01

    Dermal absorption of mucopolysaccharide polysulfate (MPS, the active ingredient of Hirudoid") in human and minipig was investigated by using 14C-labeled MPS. Three types of human and minipig skin samples were used: intact, dried and tape-stripped. At 24 h after application of 14C-MPS to intact human skin on a Franz cell in vitro, the radioactivity was detected in 0.98, 1.34, and 0.08% of the applied dose in stratum corneum, epidermal-dermal skin, and receptor fluid, respectively. In dried human skin, the amount of radioactivity detected was similar to that in intact human skin. By contrast, in tape-stripped human skin, higher radioactivity was detected in epidermal-dermal skin and receptor fluid (2.85 and 0.33% of the applied dose, respectively) than in intact or dried skin. Minipig skin showed 1.5 to 4.5 times greater dermal absorption of 14C-MPS, as compared with human skin. In an in vivo study with minipig, radioactivity was detected at the dosing skin site after dermal administration of 14C-MPS. The stability of 14C-MPS in human skin after dermal application was evaluated by agarose gel electrophoresis and ion-exchange chromatography. It was suggested that 14C-MPS absorbed into human skin would be stable because the chromatogram behaviors of the radioactivity on the two types of method were not shifted. Microautoradiography of human and minipig skins after 14C-MPS dosing showed that radioactivity was widely distributed in the epidermis in the area near hair follicles. The present results clearly demonstrate that MPS is stable and that a small fraction of it is percutaneously absorbed by human and minipig skin.

  6. Volume correction in the aging hand: role of dermal fillers

    PubMed Central

    Rivkin, Alexander Z

    2016-01-01

    The hands, just like the face, are highly visible parts of the body. They age at a similar rate and demonstrate comparable changes with time, sun damage, and smoking. Loss of volume in the hands exposes underlying tendons, veins, and bony prominences. Rejuvenation of the hands with dermal fillers is a procedure with high patient satisfaction and relatively low risk for complications. This study will review relevant anatomy, injection technique, clinical safety, and efficacy of dermal filler volumization of the aging hand. PMID:27621659

  7. Malathion dermal permeability in relation to dermal load: Assessment by physiologically based pharmacokinetic modeling of in vivo human data.

    PubMed

    Bogen, Kenneth T; Singhal, Ankur

    2017-02-01

    Estimates of dermal permeability (Kp), obtained by fitting an updated human PBPK model for malathion to previously reported data on excreted urinary metabolites after 29 volunteers were dermally exposed to measured values of [(14)C]malathion dermal load (L), were used to examine the empirical relationship between Kp and L. The PBPK model was adapted from previously reported human biokinetic and PBPK models for malathion, fit to previously reported urinary excretion data after oral [(14)C]malathion intake by volunteers, and then augmented to incorporate a standard Kp approach to modeling dermal-uptake kinetics. Good to excellent PBPK-model fits were obtained to all of 29 sets of cumulative urinary metabolite-excretion data (ave. [±1 SD] R(2) = 0.953 [±0.064]). Contrary to the assumption that Kp and L are independent typically applied for dermally administered liquids or solutions, the 29 PBPK-based estimates of Kp obtained for malathion exhibit a strong positive association with the 2/3rds power of L (log-log Pearson correlation = 0.925, p = ∼0). Possible explanations of this observation involving physico-chemical characteristics and/or in vivo cutaneous effects of malathion are discussed. The PBPK model presented, and our observation that Kp estimates obtained by fitting this model to human experimental urinary-excretion data correlate well with L(2/3), allow more realistic assessments of absorbed and metabolized dose during or after a variety of scenarios involving actual or potential dermal or multi-route malathion exposures, including for pesticide workers or farmers who apply malathion to crops.

  8. Determination of acute oral toxicity of flumethrin in honey bees.

    PubMed

    Oruc, H H; Hranitz, J M; Sorucu, A; Duell, M; Cakmak, I; Aydin, L; Orman, A

    2012-12-01

    Flumethrin is one of many pesticides used for the control and treatment of varroatosis in honey bees and for the control of mosquitoes and ticks in the environment. For the control of varroatosis, flumethrin is applied to hives formulated as a plastic strip for several weeks. During this time, honey bees are treated topically with flumethrin, and hive products may accumulate the pesticide. Honey bees may indirectly ingest flumethrin through hygienic behaviors during the application period and receive low doses of flumethrin through comb wax remodeling after the application period. The goal of our study was to determine the acute oral toxicity of flumethrin and observe the acute effects on motor coordination in honey bees (Apis mellifera anatoliaca). Six doses (between 0.125 and 4.000 microg per bee) in a geometric series were studied. The acute oral LD50 of flumethrin was determined to be 0.527 and 0.178 microg per bee (n = 210, 95% CI) for 24 and 48 h, respectively. Orally administered flumethrin is highly toxic to honey bees. Oral flumethrin disrupted the motor coordination of honey bees. Honey bees that ingested flumethrin exhibited convulsions in the antennae, legs, and wings at low doses. At higher doses, partial and total paralysis in the antennae, legs, wings, proboscises, bodies, and twitches in the antennae and legs were observed.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27428951

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

    PubMed

    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.

  11. THE PROLONGED GASTROINTESTINAL SYNDROME IN RHESUS MACAQUES: THE RELATIONSHIP BETWEEN GASTROINTESTINAL, HEMATOPOIETIC, AND DELAYED MULTI-ORGAN SEQUELAE FOLLOWING ACUTE, POTENTIALLY LETHAL, PARTIAL-BODY IRRADIATION

    PubMed Central

    MacVittie, Thomas J.; Bennett, Alexander; Booth, Catherine; Garofalo, Michael; Tudor, Gregory; Ward, Amanda; Shea-Donohue, Terez; Gelfond, Daniel; McFarland, Emylee; Jackson, William; Lu, Wei; Farese, Ann M.

    2014-01-01

    The dose response relationship for the acute gastrointestinal syndrome following total-body irradiation prevents analysis of the full recovery and damage to the gastrointestinal system, since all animals succumb to the subsequent 100% lethal hematopoietic syndrome. A partial-body irradiation model with 5% bone marrow sparing was established to investigate the prolonged effects of high-dose radiation on the gastrointestinal system, as well as the concomitant hematopoietic syndrome and other multi-organ injury including the lung. Herein, cellular and clinical parameters link acute and delayed coincident sequelae to radiation dose and time course post-exposure. Male rhesus Macaca mulatta were exposed to partial-body irradiation with 5% bone marrow (tibiae, ankles, feet) sparing using 6 MV linear accelerator photons at a dose rate of 0.80 Gy min−1 to midline tissue (thorax) doses in the exposure range of 9.0 to 12.5 Gy. Following irradiation, all animals were monitored for multiple organ-specific parameters for 180 d. Animals were administered medical management including administration of intravenous fluids, antiemetics, prophylactic antibiotics, blood transfusions, antidiarrheals, supplemental nutrition, and analgesics. The primary endpoint was survival at 15, 60, or 180 d post-exposure. Secondary endpoints included evaluation of dehydration, diarrhea, hematologic parameters, respiratory distress, histology of small and large intestine, lung radiographs, and mean survival time of decedents. Dose- and time-dependent mortality defined several organ-specific sequelae, with LD50/15 of 11.95 Gy, LD50/60 of 11.01 Gy, and LD50/180 of 9.73 Gy for respective acute gastrointestinal, combined hematopoietic and gastrointestinal, and multi-organ delayed injury to include the lung. This model allows analysis of concomitant multi-organ sequelae, thus providing a link between acute and delayed radiation effects. Specific and multi-organ medical countermeasures can be assessed for

  12. DISPOSITION OF BROMODICHLOROMETHANE IN HUMANS FOLLOWING ORAL AND DERMAL EXPOSURE

    EPA Science Inventory

    DISPOSITION OF BROMODICHLOROMETHANE IN HUMANS FOLLOWING ORAL AND DERMAL EXPOSURE. TL Leavens1, MW Case1, RA Pegram1, BC Blount2, DM DeMarini1, MC Madden1, and JL Valentine3. 1NHEERL, USEPA, RTP, NC, USA; 2CDC, Atlanta, GA, USA; 3RTI, RTP, NC, USA.
    The disinfection byproduct ...

  13. IN VIVO DERMAL ABSORPTION OF PYRETHROID PESTICIDES IN THE RAT

    EPA Science Inventory

    The potential for exposure to pyrethroid pesticides has risen recently because of their increased agricultural and residential use. The objective of this study was to examine the in vivo dermal absorption of bifenthrin, deltamethrin and cis-permethrin in the rat. Hair on...

  14. 40 CFR 795.228 - Oral/dermal pharmacokinetics.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... radioactivity following oral or dermal administration and total excretion following intravenous administration... repeated dosing study, shall be terminated at 7 days or after at least 90 percent of the radioactivity has... skin surface. Both the covering and the washing shall be assayed to recover residual radioactivity....

  15. 40 CFR 795.228 - Oral/dermal pharmacokinetics.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... radioactivity following oral or dermal administration and total excretion following intravenous administration... repeated dosing study, shall be terminated at 7 days or after at least 90 percent of the radioactivity has... skin surface. Both the covering and the washing shall be assayed to recover residual radioactivity....

  16. 40 CFR 795.228 - Oral/dermal pharmacokinetics.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... radioactivity following oral or dermal administration and total excretion following intravenous administration... repeated dosing study, shall be terminated at 7 days or after at least 90 percent of the radioactivity has... skin surface. Both the covering and the washing shall be assayed to recover residual radioactivity....

  17. Visual phototransduction components in cephalopod chromatophores suggest dermal photoreception.

    PubMed

    Kingston, Alexandra C N; Kuzirian, Alan M; Hanlon, Roger T; Cronin, Thomas W

    2015-05-15

    Cephalopod mollusks are renowned for their colorful and dynamic body patterns, produced by an assemblage of skin components that interact with light. These may include iridophores, leucophores, chromatophores and (in some species) photophores. Here, we present molecular evidence suggesting that cephalopod chromatophores - small dermal pigmentary organs that reflect various colors of light - are photosensitive. RT-PCR revealed the presence of transcripts encoding rhodopsin and retinochrome within the retinas and skin of the squid Doryteuthis pealeii, and the cuttlefish Sepia officinalis and Sepia latimanus. In D. pealeii, Gqα and squid TRP channel transcripts were present in the retina and in all dermal samples. Rhodopsin, retinochrome and Gqα transcripts were also found in RNA extracts from dissociated chromatophores isolated from D. pealeii dermal tissues. Immunohistochemical staining labeled rhodopsin, retinochrome and Gqα proteins in several chromatophore components, including pigment cell membranes, radial muscle fibers, and sheath cells. This is the first evidence that cephalopod dermal tissues, and specifically chromatophores, may possess the requisite combination of molecules required to respond to light.

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

    EPA Science Inventory

    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...

  19. DERMAL EXPOSURE ASSESSMENT: A SUMMARY OF EPA APPROACHES

    EPA Science Inventory

    This final report presents a concise description and evaluation of the approaches used in the Agency for dermal exposure assessment including a discussion about harmonization and research needs in this area. The report is intended to be used by EPA program offices in their effort...

  20. PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES

    EPA Science Inventory

    PULMONARY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO SELECTED DIISOCYANATES

    M.J.K. Selgrade, E.H. Boykin, N.H. Coates, D.L. Doerfler, S.H. Gavett
    Experimental Toxicology Div., National Health and Environmental Research Laboratory, Office of Research and Developmen...

  1. CONTROLLED, SHORT-TERM DERMAL AND INHALATION EXPOSURE TO CHLOROFORM

    EPA Science Inventory

    Studies were conducted to determine the uptake by humans of chloroform as a result of controlled short-term dermal and inhalation exposures. The approach used continuous real-time breath analysis to determine exhaled-breath profiles and evaluate chloroform kinetics in the huma...

  2. Dermal Contributions to Human Interfollicular Epidermal Architecture and Self-Renewal

    PubMed Central

    Lawlor, Kynan T.; Kaur, Pritinder

    2015-01-01

    The human interfollicular epidermis is renewed throughout life by populations of proliferating basal keratinocytes. Though interfollicular keratinocyte stem cells have been identified, it is not known how self-renewal in this compartment is spatially organized. At the epidermal-dermal junction, keratinocytes sit atop a heterogeneous mix of dermal cells that may regulate keratinocyte self-renewal by influencing local tissue architecture and signalling microenvironments. Focusing on the rete ridges and complementary dermal papillae in human skin, we review the identity and organisation of abundant dermal cells types and present evidence for interactions between the dermal microenvironment and the interfollicular keratinocytes. PMID:26602926

  3. Calcium pantothenate modulates gene expression in proliferating human dermal fibroblasts.

    PubMed

    Wiederholt, Tonio; Heise, Ruth; Skazik, Claudia; Marquardt, Yvonne; Joussen, Sylvia; Erdmann, Kati; Schröder, Henning; Merk, Hans F; Baron, Jens Malte

    2009-11-01

    Topical application of pantothenate is widely used in clinical practice for wound healing. Previous studies identified a positive effect of pantothenate on migration and proliferation of cultured fibroblasts. However, these studies were mainly descriptive with no molecular data supporting a possible model of its action. In this study, we first established conditions for an in vitro model of pantothenate wound healing and then analysed the molecular effects of pantothenate. To test the functional effect of pantothenate on dermal fibroblasts, cells were cultured and in vitro proliferation tests were performed using a standardized scratch test procedure. For all three donors analysed, a strong stimulatory effect of pantothenate at a concentration of 20 microg/ml on the proliferation of cultivated dermal fibroblasts was observed. To study the molecular mechanisms resulting in the proliferative effect of pantothenate, gene expression was analysed in dermal fibroblasts cultivated with 20 microg/ml of pantothenate compared with untreated cells using the GeneChip Human Exon 1.0 ST Array. A number of significantly regulated genes were identified including genes coding for interleukin (IL)-6, IL-8, Id1, HMOX-1, HspB7, CYP1B1 and MARCH-II. Regulation of these genes was subsequently verified by quantitative real-time polymerase chain reaction analysis. Induction of HMOX-1 expression by pantothenol and pantothenic acid in dermal cells was confirmed on the protein level using immunoblots. Functional studies revealed the enhanced suppression of free radical formation in skin fibroblasts cultured with panthenol. In conclusion, these studies provided new insight in the molecular mechanisms linked to the stimulatory effect of pantothenate and panthenol on the proliferation of dermal fibroblasts.

  4. Muse Cells Derived from Dermal Tissues Can Differentiate into Melanocytes.

    PubMed

    Tian, Ting; Zhang, Ru-Zhi; Yang, Yu-Hua; Liu, Qi; Li, Di; Pan, Xiao-Ru

    2017-02-07

    The objective of the authors has been to obtain multilineage-differentiating stress-enduring cells (Muse cells) from primary cultures of dermal fibroblasts, identify their pluripotency, and detect their ability to differentiate into melanocytes. The distribution of SSEA-3-positive cells in human scalp skin was assessed by immunohistochemistry, and the distribution of Oct4, Sox2, Nanog, and SSEA-3-positive cells was determined by immunofluorescence staining. The expression levels of Sox2, Oct4, hKlf4, and Nanog mRNAs and proteins in Muse cells were determined by reverse transcription polymerase chain reaction (RT-PCR) analyses and Western blots, respectively. These Muse cells differentiated into melanocytes in differentiation medium. The SSEA-3-positive cells were scattered in the basement membrane zone and the dermis, with comparatively more in the sebaceous glands, vascular and sweat glands, as well as the outer root sheath of hair follicles, the dermal papillae, and the hair bulbs. Muse cells, which have the ability to self-renew, were obtained from scalp dermal fibroblasts by flow cytometry sorting with an anti-SSEA-3 antibody. The results of RT-PCR, Western blot, and immunofluorescence staining showed that the expression levels of Oct4, Nanog, Sox2, and Klf4 mRNAs and proteins in Muse cells were significantly different from their parental dermal fibroblasts. Muse cells differentiated into melanocytes when cultured in melanocyte differentiation medium, and the Muse cell-derived melanocytes expressed the melanocyte-specific marker HMB45. Muse cells could be obtained by flow cytometry from primary cultures of scalp dermal fibroblasts, which possessed the ability of pluripotency and self-renewal, and could differentiate into melanocytes in vitro.

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

    PubMed

    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.

  6. Evaluation of acute and sub-acute toxicity of Pinus eldarica bark extract in Wistar rats

    PubMed Central

    Ghadirkhomi, Akram; Safaeian, Leila; Zolfaghari, Behzad; Agha Ghazvini, Mohammad Reza; Rezaei, Parisa

    2016-01-01

    Objective: Pinus eldarica (P. eldarica) is one of the most common pines in Iran which has various bioactive constituents and different uses in traditional medicine. Since there is no documented evidence for P. eldarica safety, the acute and sub-acute oral toxicities of hydroalcoholic extract of P. eldarica bark were investigated in male and female Wistar rats in this study. Materials and Methods: In the acute study, a single dose of extract (2000 mg/kg) was orally administered and animals were monitored for 7 days. In the sub-acute study, repeated doses (125, 250 and 500 mg/kg/day) of the extract were administered for 28 days and biochemical, hematological and histopathological parameters were evaluated. Results: Our results showed no sign of toxicity and no mortality after single or repeated administration of P. eldarica. The median lethal dose (LD50) of P. eldarica was determined to be higher than 2000 mg/kg. The mean body weight and most of the biochemical and hematological parameters showed normal levels. There were only significant decreases in serum triglyceride levels at the doses of 250 and 500 mg/kg of the extract in male rats (p<0.05 and p<0.01, respectively) and in monocyte counts at the highest dose of the extract in both male and female rats (p<0.05). Mild inflammation was also found in histological examination of kidney and liver tissues at the highest dose of extract. Conclusion: Oral administration of the hydroalcoholic extract of P. eldarica bark may be considered as relatively non-toxic particularly at the doses of 125 and 250 mg/kg. PMID:27761426

  7. Acute oral toxicity of 3-MCPD mono- and di-palmitic esters in Swiss mice and their cytotoxicity in NRK-52E rat kidney cells.

    PubMed

    Liu, Man; Gao, Bo-Yan; Qin, Fang; Wu, Ping-Ping; Shi, Hai-Ming; Luo, Wei; Ma, Ai-Niu; Jiang, Yuan-Rong; Xu, Xue-Bing; Yu, Liang-Li Lucy

    2012-10-01

    The acute oral toxicity of 1-palmitoyl-3-chloropropanediol (3-MCPD 1-monopalmitate) and 1,2-bis-palmitoyl-3-chloropropanediol (3-MCPD dipalmitate) in Swiss mice were examined, along with their cytotoxicity in NRK-52E rat kidney cells. LD50 (median lethal dose) value of 3-MCPD 1-monopalmitate was determined 2676.81 mg/kg body weight (BW). The results showed that 3-MCPD 1-monopalmitate dose-dependently decreased the mean body weight, and caused significant increase of serum urea nitrogen and creatinine in dead mice compared to the control and survived mice. Major histopathological changes in mice fed 3-MCPD 1-monopalmitate were renal tubular necrosis, protein casts and spermatids decrease in the seminiferous tubules. According to the limit test for 3-MCPD dipalmitate, LD50 value of 3-MCPD dipalmitate was presumed to be greater than 5000 mg/kg BW. Obvious changes were not observed on mean body weight, absolute and relative organ weight or serum urea nitrogen and creatinine levels in mice fed 3-MCPD dipalmitate. However, renal tubular necrosis, protein casts and spermatids decrease were also observed in the dead mice. In addition, MTT and LDH assay results only showed the cytotoxicity of 3-MCPD 1-monopalmitate in NRK-52E rat kidney cells in a dose-dependent manner. Together, the results indicated a greater toxicity of 3-MCPD 1-monopalmitate compared to 3-MCPD dipalmitate.

  8. Acute oral toxicity and liver oxidant/antioxidant stress of halogenated benzene, phenol, and diphenyl ether in mice: a comparative and mechanism exploration.

    PubMed

    Shi, Jiaqi; Feng, Mingbao; Zhang, Xuesheng; Wei, Zhongbo; Wang, Zunyao

    2013-09-01

    The lethal doses (LD50s) of fluorinated, chlorinated, brominated, and iodinated benzene, phenol, and diphenyl ether in mice were ascertained respectively under the consistent condition. The acute toxicity of four benzenes orders in fluorobenzene (FB) < iodobenzene < chlorobenzene≈bromobenzene, that of four phenols orders in 4-iodophenol≈4-bromophenol < 4-chlorophenol (4-MCP) < 4-fluorophenol (4-MFP), and that of four diphenyl ethers orders in 4,4'-iododiphenyl ether < 4,4'-difluorodiphenyl ether < 4,4'-dichlorodiphenyl ether≈4,4'-dibromodiphenyl ether. General behavior adverse effects were observed, and poisoned mouse were dissected to observe visceral lesions. FB, 4-MCP, and 4-MFP produced toxic faster than other halogenated benzenes and phenols, as they had lower octanol-water partition coefficients. Pathological changes in liver and liver/kidney weight changes were also observed. Hepatic superoxide dismutase, catalase activities, and malondialdehyde level were tested after a 28-day exposure, which reflects a toxicity order basically consistent with that reflected by the LD50s. By theoretical calculation and building models, the toxicity of benzene, phenol, and diphenyl ether were influenced by different structural properties.

  9. Acute, reproductive toxicity and two-generation teratology studies of a standardized quassinoid-rich extract of Eurycoma longifolia Jack in Sprague-Dawley rats.

    PubMed

    Low, Bin-Seng; Das, Prashanta Kumar; Chan, Kit-Lam

    2014-07-01

    The roots of Eurycoma longifolia Jack are popularly sought as herbal medicinal supplements to improve libido and general health amongst the local ethnic population. The major quassinoids of E. longifolia improved spermatogenesis and fertility but toxicity studies have not been well documented. The reproductive toxicity, two generation of foetus teratology and the up-and-down acute toxicity were investigated in Sprague-Dawley rats orally treated with quassinoid-rich E. longifolia extract (TAF273). The results showed that the median lethal dose (LD50 ) of TAF273 for female and male rats was 1293 and >2000 mg/kg, respectively. Fertility index and litter size of the TAF273 treated were significantly increased when compared with those of the non-treated animals. The TAF273-treated dams decreased in percentage of pre-implantation loss, post-implantation loss and late resorption. No toxic symptoms were observed on the TAF273-treated pregnant female rats and their foetuses were normal. The no-observed adverse effect level (NOAEL) obtained from reproductive toxicity and teratology studies of TAF273 in rats was 100 mg/kg body weight/day, being more than 10-fold lower than the LD50 value. Thus, any human dose derived from converting the rat doses of 100 mg/kg and below may be considered as safe for further clinical studies.

  10. [Antidotal effects of sulfhydryl compounds on acute poisonings by sodium ammonium dimethyl-2-(propane-1,3-dithiosulfate) monohydrate, nereistoxin and cartap].

    PubMed

    Cao, B J; Chen, Z K; Chi, Z Q

    1990-03-01

    Sodium dimercaptopropanesulphonate (DMPS) and sodium dimercaptosuccinate (DMS) were discovered to be effective antidotes for acute poisoning of insecticides SCD [sodium ammonium dimethyl-2-(propane-1,3-dithiosulfate) monohydrate], nereistoxin (4-N,N-dimethylamino-1,2-dithiolane) and cartap (dihydronereistoxin dicarbamate). In mice, DMPS (250 mg/kg) or DMS (1000 mg/kg) ip 20 min before SCD increased LD50 of ig SCD from 97 to 374 or 251 mg/kg, respectively. The prophylactic effect of DMPS was better than that of DMS. Administration of DMPS prior to cartap increased LD50 of ig cartap from 130 to 375 mg/kg. The therapeutic effect of DMPS was also demonstrated in SCD-poisoned conscious rabbits. DMPS 62.5 mg/kg or DMS 500 mg/kg iv completely antagonized the neuromuscular blockade and respiratory depression caused by SCD, nereistoxin and cartap in anesthetized rabbits. The antagonism of SCD-induced neuromuscular blockade by cysteine (400 mg/kg, iv) was less effective and of shorter duration than that by DMPS and DMS. Dimercaprol 50 mg/kg im showed little effect on SCD-induced paralysis. The antagonistic actions of sulfhydryl compounds on neuromuscular blockade induced by these insecticides probably belong to chemical antagonism.

  11. Histology of “placoderm” dermal skeletons: Implications for the nature of the ancestral gnathostome

    PubMed Central

    Giles, Sam; Rücklin, Martin

    2013-01-01

    Abstract The vertebrate dermal skeleton has long been interpreted to have evolved from a primitive condition exemplified by chondrichthyans. However, chondrichthyans and osteichthyans evolved from an ancestral gnathostome stem‐lineage in which the dermal skeleton was more extensively developed. To elucidate the histology and skeletal structure of the gnathostome crown‐ancestor we conducted a histological survey of the diversity of the dermal skeleton among the placoderms, a diverse clade or grade of early jawed vertebrates. The dermal skeleton of all placoderms is composed largely of a cancellar architecture of cellular dermal bone, surmounted by dermal tubercles in the most ancestral clades, including antiarchs. Acanthothoracids retain an ancestral condition for the dermal skeleton, and we record its secondary reduction in antiarchs. We also find that mechanisms for remodeling bone and facilitating different growth rates between adjoining plates are widespread throughout the placoderms. J. Morphol., 2013. © 2013 Wiley Periodicals, Inc. PMID:23378262

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

    SciTech Connect

    Tashiro, Kanae; Shishido, Mayumi; Fujimoto, Keiko; Hirota, Yuko; Yo, Kazuyuki; Gomi, Takamasa; Tanaka, Yoshitaka

    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.

  13. [EFFECT OF 4-METHYLPYRAZOLE ON IMMUNE RESPONSE, FUNCTION OF Th1 AND Th2 LYMPHOCYTES, AND CYTOKINE CONCENTRATION IN RAT BLOOD AFTER ACUTE METHANOL POISONING].

    PubMed

    Zabrodskii, P F; Maslyakov, V V; Gromov, M S

    2016-01-01

    It was established in experiments on noninbred albino rats that the acute intoxication with methanol (1.0 LD50) decreased cellular and humoral immune responses, Th2-lymphocyte activity (to a greater extent as compared to the function of Th1 cells), reduced the blood concentration of immunoregulatory (IFN-g, IL-2, IL-4) and proinflammatory (TNF, IL-1b, IL-6) cytokines on the average by 36.5% (p < 0.05), and did not affect the content of anti-inflammatory cytokines (IL-10, IL-13). Methanol antidote 4-methylpyrazole (non-competitive inhibitor of alcohol dehydrogenase) administered upon acute intoxication with methanol at a dose of 1.0 DL50 partially reduces the intoxication-induced suppression of humoral and cellular immune response, activity of T-helper cells, and production of IL-4 and restores blood levels of TNF, IL-1b, IFN-γ, IL-4, IL-2, IL-6 to the control values.

  14. Acute and Chronic Toxicity of an Aqueous Fraction of the Stem Bark of Stryphnodendron adstringens (Barbatimão) in Rodents

    PubMed Central

    Costa, Marco Antonio; Palazzo de Mello, João Carlos; Kaneshima, Edílson Nobuyoshi; Ueda-Nakamura, Tânia; Dias Filho, Benedito Prado; Audi, Elisabeth Aparecida

    2013-01-01

    Stryphnodendron adstringens has a high tannin content and is used as an antiseptic and antimicrobial and in the treatment of leucorrhea, gonorrhea, wound healing, and gastritis. The present study evaluated the toxic effects of the heptamer prodelphinidin (F2) from the stem bark of S. adstringens in rodents. In the acute toxicity test, the mice that received oral doses exhibited reversible effects, with an LD50 of 3.015 mg · kg−1. In the chronic toxicity test at 90 days, Wistar rats were treated with different doses of F2 (10, 100, and 200 mg · kg−1). In the biochemical, hematological, and histopathological examinations and open-field test, the different dose groups did not exhibit significant differences compared with controls. The present results indicate that F2 from the stem bark of S. adstringens caused no toxicity with acute and chronic oral treatment in rodents at the doses administered. PMID:23970938

  15. Acute contact toxicity test of insecticides (Cipermetrina 25, Lorsban 48E, Thionex 35) on honeybees in the southwestern zone of Uruguay.

    PubMed

    Carrasco-Letelier, Leonidas; Mendoza-Spina, Yamandú; Branchiccela, María Belén

    2012-07-01

    Glyphosate-resistant soybean cultivation is expanding rapidly in Uruguay, with its land area having increased by 95 times during the past 10 years. Because of the region's Neotropical conditions, insecticide use is required to ensure adequate soybean productivity. However, in areas shared by soybean crops and beekeepers - such as the southwestern zone of Uruguay (SWZU) - the use of insecticides can increase the risks of honeybee death and honey contamination. Uruguayan commercial and legal guidelines set out practices and field doses designed to prevent acute intoxication with insecticides. However, honeybees in the SWZU are predominantly a polyhybrid subspecies different from that used to set international reference values, and hence they may have a different acute toxicity response, thus rendering such precautions ineffective. The aim of this work was to assess the acute toxicity response of polyhybrid honeybees in the SWZU to cypermethrin (commercial formulation: Cipermetrina 25 Agrin®), chlorpyrifos (commercial formulation: Lorsban 48E®), and endosulfan (commercial formulation: Thionex 35®). Acute toxicity bioassays were conducted to determine the median lethal dose (LD(50)) of each insecticide for the honeybees. The results indicate that, compared with EU reference values, SWZU honeybees have a higher toxicological sensitivity to chlorpyrifos and endosulfan, and a lower toxicological sensitivity to cypermethrin, based on the commercial formulations tested. However, when these results were adjusted according to their field dose equivalents, only chlorpyrifos emerged as a potential problem for beekeeping, as the maximum recommended field dose of Lorsban 48E® for soybean crops in Uruguay is 23 times the corresponding LD(50) for honeybees in the SWZU.

  16. Data on acute toxicity of the progestin STS 557.

    PubMed

    Hillesheim, H G; Hoffmann, H

    1983-02-01

    In mice and rabbits of both sexes the acute toxicity of STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) was determined after its oral or parenteral (i.p., s.c.) administration. In rabbits increasing lethality was observed following STS 557 suspended in tylose solution at the dose range of 1.0 to 3.0 g/kg p.o. or i.p. The approximate LD50-values were 1.0 to 1.5 g/kg for the i.p. route and 1.0 to 2.0 g/kg for the oral route. Levonorgestrel injected i.p. did not cause any lethality up to the dose of 3.0 g/kg. After oral or s.c. administration to mice, doses of 4.0 g/kg STS 557 were well tolerated. A dose-related toxicity occurred only after i.p. doses between 0.5 and 1.0 g/kg (STS 557), and between 2.0 and 4.0 g/kg (levonorgestrel), respectively. Using an oily vehicle for the oral route in mice, the lethal threshold dose for STS 557 was lowered to about 2.0 g/kg. In conclusion, a low oral acute toxicity was determined for STS 557 corresponding to that of other progestagens like levonorgestrel or norethisterone.

  17. Evaluation of acute toxicity potential of water hyacinth leaves.

    PubMed

    Wu, Wenbiao; Guo, Xiaoguang; Huang, Mingliang

    2014-06-01

    Although higher protein yield per hectare of water hyacinth than that of soy, high protein content of its leaves and good essential amino acid pattern have been proven, its dietary toxicity for human or animal consumption has not yet been evaluated. Therefore, the acute toxicity of water hyacinth leaves has been evaluated by an animal feeding test. The concentrations of common toxic metals including cadmium, lead, platinum, palladium, tin, mercury, barium, silver, stibium and aluminum in the water hyacinth leaf powder (WHLP) used for the animal feeding test were within their maximum limits in food additives as reported by the World Health Organization. The median lethal dose (LD50) of WHLP was more than 16 g kg(-1) body weight. In the study, after feeding for 7 and 28 days, the body weight of all the mice increased. The results of hematological analysis, clinical biochemical analysis, histopathological evaluation, general dissection or investigations of internal organs, appearance and behavior observations did not indicate any adverse effects from the diet containing WHLP. It is therefore concluded that water hyacinth leaves are not acutely toxic.

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

    PubMed

    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.

  19. Walleye Dermal Sarcoma Virus: Molecular Biology and Oncogenesis

    PubMed Central

    Rovnak, Joel; Quackenbush, Sandra L.

    2010-01-01

    Retroviruses have been detected in most vertebrate species and are etiologic agents of a variety of neoplastic diseases. The study of retroviruses has been instrumental in uncovering the molecular mechanisms responsible for oncogenesis. Retroviruses have been isolated from three neoplastic diseases in fish, two of which affect the dermis and regress naturally coincident with spawning. This feature provides a unique model to study mechanisms of tumor development and regression. Three complex retroviruses, isolated from walleye (Sander vitreus) with dermal sarcoma and epidermal hyperplasia, are the members of the newest retroviral genus, Epsilonretrovirus. Three accessory proteins, encoded by walleye dermal sarcoma virus (WDSV), function in the regulation of host and viral gene expression and cell cycle, alter cell-signaling pathways to promote cell proliferation and block apoptosis, and, finally, induce apoptosis through dissipation of the mitochondrial membrane potential. PMID:21994717

  20. Evaluating dermal myelinated nerve fibers in skin biopsy

    PubMed Central

    Myers, M. Iliza; Peltier, Amanda C.; Li, Jun

    2012-01-01

    Although there has been extensive research on small, unmyelinated fibers in the skin, little research has investigated dermal myelinated fibers in comparison. Glabrous, non-hairy skin contains mechanoreceptors that afford a vantage point for observation of myelinated fibers that have previously been seen only with invasively obtained nerve biopsies. This review discusses current morphometric and molecular expression data of normative and pathogenic glabrous skin obtained by various processing and analysis methods for cutaneous myelinated fibers. Recent publications have shed light on the role of glabrous skin biopsy in identifying signs of peripheral neuropathy and as a potential biomarker of distal myelin and mechanoreceptor integrity. The clinical relevance of a better understanding of the role of dermal myelinated nerve terminations in peripheral neuropathy will be addressed in light of recent publications in the growing field of skin biopsy. PMID:23192899

  1. Creeping attachment: autogenous graft vs dermal matrix allograft.

    PubMed

    Haeri, A; Parsell, D

    2000-09-01

    For many years, free autogenous grafts have been used as a method of gaining keratinized tissue around teeth with mucogingival problems. Creeping attachment using autogenous graft material has been actively studied. In addition, biocompatible, acellular connective-tissue material has recently been used as an alternative to free gingival grafts to increase the zone of keratinization. This report presents a patient with bilateral mucogingival defects in the canine and premolar areas. The patient received an autogenous graft on one side and a dermal matrix allograft on the contralateral side. Creeping attachments were measured and compared at 3 months and 12 months after surgery. After 12 months of healing, an average of 1.23 mm of creeping attachment was measured on the free gingival graft side and 0.96 mm of creeping attachment was measured with the dermal matrix allograft.

  2. Lipid nanoparticles (SLN, NLC) in cosmetic and pharmaceutical dermal products.

    PubMed

    Pardeike, Jana; Hommoss, Aiman; Müller, Rainer H

    2009-01-21

    Solid lipid nanoparticles (SLN) are distinguishable from nanostructured lipid carriers (NLC) by the composition of the solid particle matrix. Both are an alternative carrier system to liposomes and emulsions. This review paper focuses on lipid nanoparticles for dermal application. Production of lipid nanoparticles and final products containing lipid nanoparticles is feasible by well-established production methods. SLN and NLC exhibit many features for dermal application of cosmetics and pharmaceutics, i.e. controlled release of actives, drug targeting, occlusion and associated with it penetration enhancement and increase of skin hydration. Due to the production of lipid nanoparticles from physiological and/or biodegradable lipids, this carrier system exhibits an excellent tolerability. The lipid nanoparticles are a "nanosafe" carrier. Furthermore, an overview of the cosmetic products currently on the market is given and the improvement of the benefit/risk ratio of the topical therapy is shown.

  3. Acute toxicity, twenty-eight days repeated dose toxicity and genotoxicity of vanadyl trehalose in kunming mice.

    PubMed

    Jiang, Pingzhe; Ni, Zaizhong; Wang, Bin; Ma, Baicheng; Duan, Huikun; Li, Xiaodan; Ma, Xiaofeng; Wei, Qian; Ji, Xiangzhen; Liu, Qiqi; Xing, Shuguang; Li, Minggang

    2017-04-01

    A new trend has been developed using vanadium and organic ligands to form novel compounds in order to improve the beneficial actions and reduce the toxicity of vanadium compounds. In present study, vanadyl trehalose was explored the oral acute toxicity, 28 days repeated dose toxicity and genotoxicity in Kunming mice. The Median Lethal Dose (LD50) of vanadyl trehalose was revealed to be 1000 mg/kg body weight in fasted Kunming mice. Stomach and intestine were demonstrated to be the main target organs of vanadyl trehalose through 28 days repeated dose toxicity study. And vanadyl trehalose also showed particular genotoxicity through mouse bone marrow micronucleus and mouse sperm malformation assay. In brief, vanadyl trehalose presented certain, but finite toxicity, which may provide experimental basis for the clinical application.

  4. Hair follicle signaling networks: a dermal papilla-centric approach.

    PubMed

    Ramos, Raul; Guerrero-Juarez, Christian F; Plikus, Maksim V

    2013-10-01

    Functional testing of dermal papilla (DP) signaling inputs into hair follicle (HF) morphogenesis and regeneration is becoming possible with the advent of new Cre lines. Targeted deletion of the signature genes in early DP precursors has revealed significant signaling redundancy during HF morphogenesis. Furthermore, the DP lineage commitment program can be exploited for generating highly inductive DP cells to be used in HF bioengineering assays.

  5. Dermal tunneling: a proposed treatment for depressed scars.

    PubMed

    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.

  6. Focal dermal hypoplasia: a case report and literature review.

    PubMed

    Murakami, Christiana; de Oliveira Lira Ortega, Adriana; Guimarães, Antônio Sérgio; Gonçalves-Bittar, Daniela; Bönecker, Marcelo; Ciamponi, Ana Lídia

    2011-08-01

    Focal dermal hypoplasia (FDH), also known as Goltz-Gorlin syndrome, is an autosomal dominant disease affecting tissues derived from the ectoderm and mesoderm. Knowledge and early diagnosis of the craniofacial alterations commonly found in patients with FDH provide oral health care professionals with effective preventive and therapeutic tools. This article aims to review the craniofacial characteristics present in FDH and the main systemic manifestations that have implications for dental management, while presenting a new case of the syndrome with novel oral findings.

  7. Esophageal squamous papillomas with focal dermal hypoplasia and eosinophilic esophagitis

    PubMed Central

    Pasman, Eric A; Heifert, Theresa A; Nylund, Cade M

    2017-01-01

    Focal dermal hypoplasia (FDH) is a rare disorder of the mesodermal and ectodermal tissues. Here we present an eight-year-old female known to have FDH who presents with poor weight gain and dysphagia. She was diagnosed with multiple esophageal papillomas and eosinophilic esophagitis. She was successfully treated with argon plasma coagulation and ingested fluticasone propionate, which has not been described previously in a child.

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

    DTIC Science & Technology

    2008-10-13

    release; distribution unlimited. 13. SUPPLEMENTARY NOTES 14. ABSTRACT The initial focus of this work was to test the hypothesis that dermal application...regulates the production of PGE2 (Pei et al., 1998) we tested the hypothesis that JP-8-induced PAF activates cytokine production and initiates immune...suppression. To test this hypothesis we pre-treated mice with a series of PAF receptor antagonists and then applied JP-8. The PAF receptor antagonists

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

    PubMed

    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.

  10. Dermal insecticide residues from birds inhabiting an orchard

    USGS Publications Warehouse

    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.

  11. Efficient In Vitro Electropermeabilization of Reconstructed Human Dermal Tissue.

    PubMed

    Madi, Moinecha; Rols, Marie-Pierre; Gibot, Laure

    2015-10-01

    DNA electrotransfer is a successful technic for gene delivery. However, its use in clinical applications is limited since little is known about the mechanisms governing DNA electrotransfer in the complex environment occurring in a tissue. The objectives of this work were to investigate the role of the extracellular matrix (ECM) in that process. Tumor ECM composition was shown to modulate in vivo gene electrotransfer efficiency. In order to assess the effects of ECM composition and organization, as well as intercellular junctions and communication, in normal tissue response to electric pulses, we developed an innovative three-dimensional (3D) reconstructed human connective tissue model. 3D human dermal tissue was reconstructed in vitro by a tissue engineering approach and was representative of in vivo cell organization since cell-cell contacts were present as well as complex ECM. This human cell model presented multiple layers of primary dermal fibroblasts embedded in a native, collagen-rich ECM. This dermal tissue could become a useful tool to study skin DNA electrotransfer mechanisms. As proof of the concept, we show here that the cells within this standardized 3D tissue can be efficiently electropermeabilized by milliseconds electric pulses. We believe that a better comprehension of gene electrotransfer in such a model tissue would help improve electrogene therapy approaches such as the systemic delivery of therapeutic proteins and DNA vaccination.

  12. Potential Health Effects Associated with Dermal Exposure to Occupational Chemicals

    PubMed Central

    Anderson, Stacey E; Meade, B Jean

    2014-01-01

    There are a large number of workers in the United States, spanning a variety of occupational industries and sectors, who are potentially exposed to chemicals that can be absorbed through the skin. Occupational skin exposures can result in numerous diseases that can adversely affect an individual’s health and capacity to perform at work. In general, there are three types of chemical–skin interactions of concern: direct skin effects, immune-mediated skin effects, and systemic effects. While hundreds of chemicals (metals, epoxy and acrylic resins, rubber additives, and chemical intermediates) present in virtually every industry have been identified to cause direct and immune-mediated effects such as contact dermatitis or urticaria, less is known about the number and types of chemicals contributing to systemic effects. In an attempt to raise awareness, skin notation assignments communicate the potential for dermal absorption; however, there is a need for standardization among agencies to communicate an accurate description of occupational hazards. Studies have suggested that exposure to complex mixtures, excessive hand washing, use of hand sanitizers, high frequency of wet work, and environmental or other factors may enhance penetration and stimulate other biological responses altering the outcomes of dermal chemical exposure. Understanding the hazards of dermal exposure is essential for the proper implementation of protective measures to ensure worker safety and health. PMID:25574139

  13. Dermal cells distribution on laser-structured ormosils.

    PubMed

    Sima, L E; Buruiana, E C; Buruiana, T; Matei, A; Epurescu, G; Zamfirescu, M; Moldovan, A; Petrescu, S M; Dinescu, M

    2013-02-01

    Several dermal substitutes for skin grafting are now commercially available, although their performance still needs improvement. Most artificial dermises have a lower take rate than autologous grafts and require more time for sufficient vascular ingrowth to overlay the skin graft. Herein we characterize new two-dimensional scaffolds for tissue-engineering applications, which were fabricated by two-photon polymerization (2PP) of ormosils hybrid materials. For the 2PP experiments, a Ti:sapphire laser was used to induce the photopolymerization. In this study we showed that the polymeric structures with controlled architectures produced via 2PP could be used as scaffolds for the in vitro culture and proliferation of human dermal fibroblasts. Fluorescence microscopy revealed that the fibroblasts' orientation was guided by the scaffold geometry, consisting of ormosils lines or grids. This 'dermal equivalent' was investigated for its ability to accommodate epidermal cells. To evaluate this interaction, two experimental approaches were hence used: (a) fibroblast-melanocyte co-cultures; and (b) fibroblast-keratinocyte organotypic cultures. During their growth on ormosil scaffolds, productive interaction of fibroblasts with both epidermal cell types was found. Moreover, this pseudo-dermis was shown to support the growth of keratinocytes for up to 8 days after their seeding.

  14. Estimating terrestrial amphibian pesticide body burden through dermal exposure.

    PubMed

    Van Meter, Robin J; Glinski, Donna A; Hong, Tao; Cyterski, Mike; Henderson, W Matthew; Purucker, S Thomas

    2014-10-01

    Dermal exposure presents a potentially significant but understudied route for pesticide uptake in terrestrial amphibians. Our study measured dermal uptake of pesticides of varying hydrophobicity (logKow) in frogs. Amphibians were indirectly exposed to one of five pesticide active ingredients through contact with contaminated soil: imidacloprid (logKow = 0.57), atrazine (logKow = 2.5), triadimefon (logKow = 3.0), fipronil (logKow = 4.11) or pendimethalin (logKow = 5.18). All amphibians had measurable body burdens at the end of the exposure in concentrations ranging from 0.019 to 14.562 μg/g across the pesticides tested. Atrazine produced the greatest body burdens and bioconcentration factors, but fipronil was more permeable to amphibian skin when application rate was considered. Soil partition coefficient and water solubility were much better predictors of pesticide body burden, bioconcentration factor, and skin permeability than logKow. Dermal uptake data can be used to improve risk estimates of pesticide exposure among amphibians as non-target organisms.

  15. Genetic Predisposition for Dermal Problems in Hexavalent Chromium Exposed Population

    PubMed Central

    Sharma, Priti; Bihari, Vipin; Agarwal, Sudhir K.; Goel, Sudhir K.

    2012-01-01

    We studied the effect of genetic susceptibility on hexavalent chromium induced dermal adversities. The health status of population was examined from the areas of Kanpur (India) having the elevated hexavalent chromium levels in groundwater. Blood samples were collected for DNA isolation to conduct polymorphic determination of genes, namely: NQO1 (C609T), hOGG1 (C1245G), GSTT1, and GSTM1 (deletion). Symptomatic exposed subjects (n = 38) were compared with asymptomatic exposed subjects (n = 108) along with asymptomatic controls (n = 148) from a non contaminated reference community. Exposed symptomatic group consisted of 36.8% subjects who were GSTM1 null genotyped as compared to asymptomatic where only 19.4% subjects were null. The exposed subjects with GSTM1 null genotype were more susceptible to dermal adversities in comparison with wild genotyped subjects (OR = 2.42; 95% CI = 1.071–5.451). Age, smoking, gender or duration of residence were not found to have any confounding effect towards this association. Association with other genes was not statistically significant, nonetheless, possible contribution by these genes cannot be ruled out. In conclusion, variation in the polymorphic status of GSTM1 gene may influence dermal outcomes among residents from Cr(VI) contaminated areas. Further studies are therefore, needed to examine these observations among different population groups. PMID:22919465

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

    PubMed

    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.

  17. Child dermal sediment loads following play in a tide flat.

    PubMed

    Shoaf, Marley B; Shirai, Jeffry H; Kedan, Golan; Schaum, John; Kissel, John C

    2005-09-01

    Dermal contact with sediment is sometimes identified as a pathway of concern in risk assessments. Dermal exposure to sediment is poorly characterized and exposure assessors may rely on default soil adherence values. The purpose of this study was to obtain sediment adherence data for a genuine exposure scenario, child play in a tide flat. This study reports direct measurements of sediment loadings on five body parts (face, forearms, hands, lower legs and feet) after play in a tide flat. Each of nine subjects participated in two timed sessions and pre- and post-activity sediment loading data were collected. Geometric mean (geometric standard deviation) dermal loadings (mg/cm(2)) on the face, forearm, hands, lower legs and feet for the combined sessions were 0.04 (2.9), 0.17 (3.1), 0.49 (8.2), 0.70 (3.6) and 21 (1.9), respectively. Participants' parents completed questionnaires regarding their child's typical activity patterns during tide flat play, exposure frequency and duration, clothing choices, bathing practices and clothes laundering. Data presented in this paper supplement very limited prior adherence data for sediment contact scenarios. Results will be useful to risk assessors considering exposure scenarios involving child activities at a coastal shoreline or tide flat.

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

    PubMed

    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.

  19. A Hydrogel Derived From Decellularized Dermal Extracellular Matrix

    PubMed Central

    Wolf, Matthew T.; Daly, Kerry A.; Brennan-Pierce, Ellen P.; Johnson, Scott A.; Carruthers, Christopher; D’Amore, Antonio; Nagarkar, Shailesh P.; Velankar, Sachin S.; Badylak, Stephen F.

    2012-01-01

    The ECM of mammalian tissues has been used as a scaffold to facilitate the repair and reconstruction of numerous tissues. Such scaffolds are prepared in many forms including sheets, powders, and hydrogels. ECM hydrogels provide advantages such as injectability, the ability to fill an irregularly shaped space, and the inherent bioactivity of native matrix. However, material properties of ECM hydrogels and the effect of these properties upon cell behavior are neither well understood nor controlled. The objective of this study was to prepare and determine the structure, mechanics, and the cell response in vitro and in vivo of ECM hydrogels prepared from decellularized porcine dermis and urinary bladder tissues. Dermal ECM hydrogels were characterized by a more dense fiber architecture and greater mechanical integrity than urinary bladder ECM hydrogels, and showed a dose dependent increase in mechanical properties with ECM concentration. In vitro, dermal ECM hydrogels supported greater C2C12 myoblast fusion, and less fibroblast infiltration and less fibroblast mediated hydrogel contraction than urinary bladder ECM hydrogels. Both hydrogels were rapidly infiltrated by host cells, primarily macrophages, when implanted in a rat abdominal wall defect. Both ECM hydrogels degraded by 35 days in vivo, but UBM hydrogels degraded more quickly, and with greater amounts of myogenesis than dermal ECM. These results show that ECM hydrogel properties can be varied and partially controlled by the scaffold tissue source, and that these properties can markedly affect cell behavior. PMID:22789723

  20. Health Impacts from Acute Radiation Exposure

    SciTech Connect

    Strom, Daniel J.

    2003-09-30

    Absorbed doses above1-2 Gy (100-200 rads) received over a period of a day or less lead to one or another of the acute radiation syndromes. These are the hematopoietic syndrome, the gastrointestinal (GI) syndrome, the cerebrovascular (CV) syndrome, the pulmonary syndrome, or the cutaneous syndrome. The dose that will kill about 50% of the exposed people within 60 days with minimal medical care, LD50-60, is around 4.5 Gy (450 rads) of low-LET radiation measured free in air. The GI syndrome may not be fatal with supportive medical care and growth factors below about 10 Gy (1000 rads), but above this is likely to be fatal. Pulmonary and cutaneous syndromes may or may not be fatal, depending on many factors. The CV syndrome is invariably fatal. Lower acute doses, or protracted doses delivered over days or weeks, may lead to many other health outcomes than death. These include loss of pregnancy, cataract, impaired fertility or temporary or permanent sterility, hair loss, skin ulceration, local tissue necrosis, developmental abnormalities including mental and growth retardation in persons irradiated as children or fetuses, radiation dermatitis, and other symptoms listed in Table 2 on page 12. Children of parents irradiated prior to conception may experience heritable ill-health, that is, genetic changes from their parents. These effects are less strongly expressed than previously thought. Populations irradiated to high doses at high dose rates have increased risk of cancer incidence and mortality, taken as about 10-20% incidence and perhaps 5-10% mortality per sievert of effective dose of any radiation or per gray of whole-body absorbed dose low-LET radiation. Cancer risks for non-uniform irradiation will be less.

  1. The neonicotinoid pesticide, imidacloprid, affects Bombus impatiens (bumblebee) sonication behavior when consumed at doses below the LD50.

    PubMed

    Switzer, Callin M; Combes, Stacey A

    2016-08-01

    We investigated changes in sonication (or buzz-pollination) behavior of Bombus impatiens bumblebees, after consumption of the neonicotinoid pesticide, imidacloprid. We measured sonication frequency, sonication length, and flight (wing beat) frequency of marked bees collecting pollen from Solanum lycopsersicum (tomato), and then randomly assigned bees to consume 0, 0.0515, 0.515, or 5.15 ng of imidacloprid. We recorded the number of bees in each treatment group that resumed sonication behavior after consuming imidacloprid, and re-measured sonication and flight behavior for these bees. We did not find evidence that consuming 0.0515 ng imidacloprid affected the sonication length, sonication frequency, or flight frequency for bees that sonicated after consuming imidacloprid; we were unable to test changes in these variables for bees that consumed 0.515 or 5.15 ng because we did not observe enough of these bees sonicating after treatment. We performed Cox proportional hazard regression to determine whether consuming imidacloprid affected the probability of engaging in further sonication behavior on S. lycopersicum and found that bumblebees who consumed 0.515 or 5.15 ng of imidacloprid were significantly less likely to sonicate after treatment than bees who consumed no imidacloprid. At the end of the experiment, we classified bees as dead or alive; our data suggest a trend of increasing mortality with higher doses of imidacloprid. Our results show that even modest doses of imidacloprid can significantly affect the likelihood of bumblebees engaging in sonication, a behavior critical for the pollination of a variety of crops and other plants.

  2. Comparison of brain mitochondrial cytochrome c oxidase activity with cyanide LD(50) yields insight into the efficacy of prophylactics.

    PubMed

    Marziaz, Mandy L; Frazier, Kathryn; Guidry, Paul B; Ruiz, Robyn A; Petrikovics, Ilona; Haines, Donovan C

    2013-01-01

    Cyanide inhibits cytochrome c oxidase, the terminal oxidase of the mitochondrial respiratory pathway, therefore inhibiting the cell oxygen utilization and resulting in the condition of histotoxic anoxia. The enzyme rhodanese detoxifies cyanide by utilizing sulfur donors to convert cyanide to thiocyanate, and new and improved sulfur donors are actively sought as researchers seek to improve cyanide prophylactics. We have determined brain cytochrome c oxidase activity as a marker for cyanide exposure for mice pre-treated with various cyanide poisoning prophylactics, including sulfur donors thiosulfate (TS) and thiotaurine (TT3). Brain mitochondria were isolated by differential centrifugation, the outer mitochondrial membrane was disrupted by a maltoside detergent, and the decrease in absorbance at 550 nm as horse heart ferrocytochrome c (generated by the dithiothreitol reduction of ferricytochrome c) was oxidized was monitored. Overall, the TS control prophylactic treatment provided significant protection of the cytochrome c oxidase activity. The TT3-treated mice showed reduced cytochrome c oxidase activity even in the absence of cyanide. In both treatment series, addition of exogenous Rh did not significantly enhance the prevention of cytochrome c oxidase inhibition, but the addition of sodium nitrite did. These findings can lead to a better understanding of the protection mechanism by various cyanide antidotal systems.

  3. Mitigation of the hematopoietic and gastrointestinal acute radiation syndrome by octadecenyl thiophosphate, a small molecule mimic of lysophosphatidic acid.

    PubMed

    Deng, Wenlin; Kimura, Yasuhiro; Gududuru, Veeresh; Wu, Wenjie; Balogh, Andrea; Szabo, Erzsebet; Thompson, Karin Emmons; Yates, C Ryan; Balazs, Louisa; Johnson, Leonard R; Miller, Duane D; Strobos, Jur; McCool, W Shannon; Tigyi, Gabor J

    2015-04-01

    We have previously demonstrated that the small molecule octadecenyl thiophosphate (OTP), a synthetic mimic of the growth factor-like mediator lysophosphatidic acid (LPA), showed radioprotective activity in a mouse model of total-body irradiation (TBI) when given orally or intraperitoneally 30 min before exposure to 9 Gy γ radiation. In the current study, we evaluated the effects of OTP, delivered subcutaneously, for radioprotection or radiomitigation from -24 h before to up to +72 h postirradiation using a mouse TBI model with therapeutic doses at around 1 mg/kg. OTP was injected at 10 mg/kg without observable toxic side effects in mice, providing a comfortable safety margin. Treatment of C57BL/6 mice with a single dose of OTP over the time period from -12 h before to +26 h after a lethal dose of TBI reduced mortality by 50%. When administered at +48 h to +72 h postirradiation (LD50/30 to LD100/30), OTP reduced mortality by ≥34%. OTP administered at +24 h postirradiation significantly elevated peripheral white blood cell and platelet counts, increased crypt survival in the jejunum, enhanced intestinal glucose absorption and reduced endotoxin seepage into the blood. In the 6.4-8.6 Gy TBI range using LD50/10 as the end point, OTP yielded a dose modification factor of 1.2. The current data indicate that OTP is a potent radioprotector and radiomitigator ameliorating the mortality and tissue injury of acute hematopoietic as well as acute gastrointestinal radiation syndrome.

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

    PubMed

    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.

  5. Dermal toxicity evaluation of neutralized Chemical Agent Identification Sets (CAIS) with an overview of the dermal toxicity of vesicant agents and their degradation products. Final report, January-September 1995

    SciTech Connect

    Olajos, E.J.; Cameron, K.P.; Way, R.A.; Manthei, J.H.; Heitkamp, D.H.

    1996-10-01

    Acute dermal toxicity (limit test) and skin irritation studies were conducted in New Zealand white rabbits to ascertain the systemic toxicity and skin-injury potential of chemically-neutralized Chemical Agent Identification Sets (CAIS). Studies also included the assessment of oxidant/solvent systems and solvent induced toxicity. The toxicity limit test consisted of a 24-hr occluded exposure to 1.0 ml/kg of `test article.` Dermal irritation studies were based on a 4-hr occluded exposure to 0.5 ml of `test article.` Chemical neutralization of CAIS resulted in complex product solutions (wastestreams) containing ppm levels of agent and an array of degradation products. Findings from the skin irritation testing of wastestreams and oxidant/solvent systems indicate that wastestream-induced skin effects (edema and erythema) were equivalent to or less in severity than the skin effects produced by exposure to oxidant/solvent systems. Systemic effects were not observed in 4/5 wastestream-exposed groups; however, 2/5 wastestream-treated groups exhibited systemic effects. Lethality was noted in only 1/5 wastestream-treated groups. Limit test data indicate that agents (HD, HN, or L) were destroyed by reaction with oxidant to less toxic materials.

  6. Antinociceptive, antiinflammatory and acute toxicity effects of Salvia leriifolia Benth seed extract in mice and rats.

    PubMed

    Hosseinzadeh, Hossein; Haddadkhodaparast, Mohammad H; Arash, Ali R

    2003-04-01

    The antinociceptive and antiinflammatory effects as well as the acute toxicity of Salvia leriifolia aqueous seed extract were studied in mice and rats. Antinociceptive activity was assessed using the hot-plate and tail flick tests. The effect on acute inflammation was studied using vascular permeability increased by acetic acid and xylene-induced ear oedema in mice. The activity against chronic inflammation was assessed using the cotton pellet test in rats. The LD(50) of the extract was found to be 19.5 g/kg (i.p.) in mice. The aqueous seed extract showed significant and dose-dependent (1.25-10 g/kg) antinociceptive activity over 7 h, and was inhibited by naloxone pretreatment. Significant and dose-dependent (2.5-10 g/kg) activity was observed against acute inflammation induced by acetic acid and in the xylene ear oedema test. In the chronic inflammation test the extract (2.5-5 g/kg) showed significant and dose-dependent antiinflammatory activity. The aqueous seed extract of S. leriifolia may therefore have supraspinal antinociceptive effects which may be mediated by opioid receptors, and showed considerable effects against acute and chronic inflammation.

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

    PubMed Central

    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

  8. The value of selected in vitro and in silico methods to predict acute oral toxicity in a regulatory context: results from the European Project ACuteTox.

    PubMed

    Prieto, P; Kinsner-Ovaskainen, A; Stanzel, S; Albella, B; Artursson, P; Campillo, N; Cecchelli, R; Cerrato, L; Díaz, L; Di Consiglio, E; Guerra, A; Gombau, L; Herrera, G; Honegger, P; Landry, C; O'Connor, J E; Páez, J A; Quintas, G; Svensson, R; Turco, L; Zurich, M G; Zurbano, M J; Kopp-Schneider, A

    2013-06-01

    ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6 months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD50>2000 mg/kg b.w.).

  9. Relevant In Vitro Predictors of Human Acellular Dermal Matrix-Associated Inflammation and Capsule Formation in a Nonhuman Primate Subcutaneous Tissue Expander Model.

    PubMed

    Sandor, Maryellen; Leamy, Patrick; Assan, Pearl; Hoonjan, Amardeep; Huang, Li-Ting; Edwards, Marianne; Zuo, Wenqi; Li, Hui; Xu, Hui

    2017-01-01

    Objective: Benchtop methods were evaluated for preclinical inflammation/capsule formation correlation following implantation of human acellular dermal matrices. Methods: Dermal matrices were compared with native dermis for structure (histology, scanning electron microscopy), collagen solubility (hydroxyproline), enzymatic susceptibility (collagenase), and thermal stability (differential scanning calorimetry). Results were compared with implantation outcomes in a primate tissue expander model. Results: Native dermis, electron beam-sterilized, and freeze-dried human acellular dermal matrices had equivalent morphology, acid-soluble collagen (60.5% ± 6.3%, 65.3% ± 3.2%, and 63.3% ± 2.4%, respectively), and collagenase resistance. Implant results showed minimal inflammation/matrix degradation, lack of capsule formation, insignificant elastic modulus change (57.65 ± 20.24 MPa out-of-package/44.84 ± 23.87 MPa in vivo), and low antibody induction (2- to 8-fold increase) for electron beam-sterilized matrix. Similar results for freeze-dried dermal matrix were previously observed. γ-Irradiated, γ-irradiated/freeze-dried, and ethanol-stored dermal matrices were statistically different from native dermis for acid-soluble collagen (82.4% ± 5.8%, 72.2% ± 6.2%, and 76.8% ± 5.0%, respectively) and collagenase digestion rate, indicating matrix damage. γ-Irradiated matrix-implanted animals demonstrated elevated inflammatory response, foreign body giant cells, capsule formation at the tissue expander junction, and robust matrix metalloproteinase-1 staining with significant elastic modulus decrease (37.43 ± 7.52 MPa out-of-package/19.58 ± 1.16 MPa in vivo). Antibody increase (32- to 128-fold) was observed 6 to 10 weeks following γ-irradiated matrix implantation. Ethanol-stored dermal matrix elicited an acute antibody response (4- to 128-fold increase, 2-4 weeks) and macrophage-concentrated synovial-like hyperplasia at the tissue expander junction, moderate matrix

  10. Relevant In Vitro Predictors of Human Acellular Dermal Matrix-Associated Inflammation and Capsule Formation in a Nonhuman Primate Subcutaneous Tissue Expander Model

    PubMed Central

    Leamy, Patrick; Assan, Pearl; Hoonjan, Amardeep; Huang, Li-Ting; Edwards, Marianne; Zuo, Wenqi; Li, Hui; Xu, Hui

    2017-01-01

    Objective: Benchtop methods were evaluated for preclinical inflammation/capsule formation correlation following implantation of human acellular dermal matrices. Methods: Dermal matrices were compared with native dermis for structure (histology, scanning electron microscopy), collagen solubility (hydroxyproline), enzymatic susceptibility (collagenase), and thermal stability (differential scanning calorimetry). Results were compared with implantation outcomes in a primate tissue expander model. Results: Native dermis, electron beam–sterilized, and freeze-dried human acellular dermal matrices had equivalent morphology, acid-soluble collagen (60.5% ± 6.3%, 65.3% ± 3.2%, and 63.3% ± 2.4%, respectively), and collagenase resistance. Implant results showed minimal inflammation/matrix degradation, lack of capsule formation, insignificant elastic modulus change (57.65 ± 20.24 MPa out-of-package/44.84 ± 23.87 MPa in vivo), and low antibody induction (2- to 8-fold increase) for electron beam–sterilized matrix. Similar results for freeze-dried dermal matrix were previously observed. γ-Irradiated, γ-irradiated/freeze-dried, and ethanol-stored dermal matrices were statistically different from native dermis for acid-soluble collagen (82.4% ± 5.8%, 72.2% ± 6.2%, and 76.8% ± 5.0%, respectively) and collagenase digestion rate, indicating matrix damage. γ-Irradiated matrix-implanted animals demonstrated elevated inflammatory response, foreign body giant cells, capsule formation at the tissue expander junction, and robust matrix metalloproteinase-1 staining with significant elastic modulus decrease (37.43 ± 7.52 MPa out-of-package/19.58 ± 1.16 MPa in vivo). Antibody increase (32- to 128-fold) was observed 6 to 10 weeks following γ-irradiated matrix implantation. Ethanol-stored dermal matrix elicited an acute antibody response (4- to 128-fold increase, 2-4 weeks) and macrophage-concentrated synovial-like hyperplasia at the tissue expander junction, moderate matrix

  11. Isolation of intact sub-dermal secretory cavities from Eucalyptus

    PubMed Central

    2010-01-01

    Background The biosynthesis of plant natural products in sub-dermal secretory cavities is poorly understood at the molecular level, largely due to the difficulty of physically isolating these structures for study. Our aim was to develop a protocol for isolating live and intact sub-dermal secretory cavities, and to do this, we used leaves from three species of Eucalyptus with cavities that are relatively large and rich in essential oils. Results Leaves were digested using a variety of commercially available enzymes. A pectinase from Aspergillus niger was found to allow isolation of intact cavities after a relatively short incubation (12 h), with no visible artifacts from digestion and no loss of cellular integrity or cavity contents. Several measurements indicated the potential of the isolated cavities for further functional studies. First, the cavities were found to consume oxygen at a rate that is comparable to that estimated from leaf respiratory rates. Second, mRNA was extracted from cavities, and it was used to amplify a cDNA fragment with high similarity to that of a monoterpene synthase. Third, the contents of the cavity lumen were extracted, showing an unexpectedly low abundance of volatile essential oils and a sizeable amount of non-volatile material, which is contrary to the widely accepted role of secretory cavities as predominantly essential oil repositories. Conclusions The protocol described herein is likely to be adaptable to a range of Eucalyptus species with sub-dermal secretory cavities, and should find wide application in studies of the developmental and functional biology of these structures, and the biosynthesis of the plant natural products they contain. PMID:20807444

  12. Stress responses of human dermal fibroblasts exposed to zinc pyrithione.

    PubMed

    Rudolf, Emil; Cervinka, Miroslav

    2011-07-28

    Zinc pyrithione is used as a topical agent in a range of medicinal and cosmetic applications. Despite its extensive use and reported beneficial effects in treatment of various dermal problems, its potential toxicity towards skin cells remains relatively underexplored. In this work we investigated effects of nM zinc pyrithione on cell stress response pathways of primary human skin fibroblasts during 24h of exposure. We demonstrate that zinc pyrithione-induced cytotoxity in dermal fibroblasts is dose-dependent and it associates with increased intracellular zinc concentrations and activated stress response pathways including p53 and stress kinase p38. Higher zinc pyrithione concentrations (500nM and above) stimulate oxidative stress and moderate DNA damage which occur in the presence of activated p38 kinase. Cells further upregulate the expression of p53 which increases its transcriptional activity while mitogenic signaling exemplified by mTOR (mammalian target of rapamycin) expression is suppressed and these steps lead to mitochondrial, caspase-dependent apoptosis. Conversely, lower zinc concentrations (125nM) fail to induce oxidative stress and significant DNA damage; however, treated cells still activate p38 and upregulate the expression and transcriptional activity of p53 and its target gene p21 as well as the expression of p16 in the presence of active mTOR pathway and a changed DNA methylation pattern. The end result is premature senescence phenotype. Specific pharmacological inhibitors as well as gene knockdown technology prove that an interaction between p38, p53 and mTOR might be responsible for these observed endpoints. Taken together, exposure of dermal fibroblasts to varying concentrations of zinc pyrithione may result in either cell death-apoptosis or cellular premature senescence which attests to the ability of this compound to affect this type of cells in an in vitro model system.

  13. Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures

    PubMed Central

    Yoshino, Atsushi; Polouliakh, Natalia; Meguro, Akira; Takeuchi, Masaki; Kawagoe, Tatsukata; Mizuki, Nobuhisa

    2016-01-01

    Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients. PMID:27621603

  14. Chum salmon egg extracts induce upregulation of collagen type I and exert antioxidative effects on human dermal fibroblast cultures.

    PubMed

    Yoshino, Atsushi; Polouliakh, Natalia; Meguro, Akira; Takeuchi, Masaki; Kawagoe, Tatsukata; Mizuki, Nobuhisa

    2016-01-01

    Components of fish roe possess antioxidant and antiaging activities, making them potentially very beneficial natural resources. Here, we investigated chum salmon eggs (CSEs) as a source of active ingredients, including vitamins, unsaturated fatty acids, and proteins. We incubated human dermal fibroblast cultures for 48 hours with high and low concentrations of CSE extracts and analyzed changes in gene expression. Cells treated with CSE extract showed concentration-dependent upregulation of collagen type I genes and of multiple antioxidative genes, including OXR1, TXNRD1, and PRDX family genes. We further conducted in silico phylogenetic footprinting analysis of promoter regions. These results suggested that transcription factors such as acute myeloid leukemia-1a and cyclic adenosine monophosphate response element-binding protein may be involved in the observed upregulation of antioxidative genes. Our results support the idea that CSEs are strong candidate sources of antioxidant materials and cosmeceutically effective ingredients.

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

    PubMed Central

    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

  16. Chronic dermal sinuses as a manifestation of histiocytosis X.

    PubMed Central

    Sacks, S H; Hall, I; Ragge, N; Pritchard, J

    1986-01-01

    Two young patients presented with generalised lymphadenopathy, otorrhoea, otitis, and rash. Over the next few years chronically discharging sinuses began to form over enlarged nodes and histological appearances were typical of histiocytosis X. In neither case were micro-organisms isolated from the lesions, and in both patients healing occurred with immunosuppressive agents. Chronic dermal sinus formation secondary to lymph node disease has never before been recorded as a manifestation of histiocytosis X. Histiocytosis X should therefore be considered in the differential diagnosis of "suppurative" lymphadenopathy so that appropriate treatment may be given without delay. Images Case 1 PMID:3084014

  17. Exposed tibial bone after burns: Flap reconstruction versus dermal substitute.

    PubMed

    Verbelen, Jozef; Hoeksema, Henk; Pirayesh, Ali; Van Landuyt, Koenraad; Monstrey, Stan

    2016-03-01

    A 44 years old male patient had suffered extensive 3rd degree burns on both legs, undergoing thorough surgical debridement, resulting in both tibias being exposed. Approximately 5 months after the incident he was referred to the Department of Plastic and Reconstructive Surgery of the University Hospital Gent, Belgium, to undergo flap reconstruction. Free flap surgery was performed twice on both lower legs but failed on all four occasions. In between flap surgery, a dermal substitute (Integra(®)) was applied, attempting to cover the exposed tibias with a layer of soft tissue, but also without success. In order to promote the development of granulation tissue over the exposed bone, small holes were drilled in both tibias with removal of the outer layer of the anterior cortex causing the bone to bleed and subsequently negative pressure wound therapy (NPWT) was applied. The limited granulation tissue resulting from this procedure was then covered with a dermal substitute (Glyaderm(®)), consisting of acellular human dermis with an average thickness of 0.25mm. This dermal substitute was combined with a NPWT-dressing, and then served as an extracellular matrix (ECM), guiding the distribution of granulation tissue over the remaining areas of exposed tibial bone. Four days after initial application of Glyaderm(®) combined with NPWT both tibias were almost completely covered with a thin coating of soft tissue. In order to increase the thickness of this soft tissue cover two additional layers of Glyaderm(®) were applied at intervals of approximately 1 week. One week after the last Glyaderm(®) application both wounds were autografted. The combination of an acellular dermal substitute (Glyaderm(®)) with negative pressure wound therapy and skin grafting proved to be an efficient technique to cover a wider area of exposed tibial bone in a patient who was not a candidate for free flap surgery. An overview is also provided of newer and simpler techniques for coverage of

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

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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.

  20. Evaluation of the Dermal Toxicity of LP1846.

    DTIC Science & Technology

    1989-09-01

    dinitro-l-chlorobenzene. ** Solvent = acetone in olive oil . Skin Patch Exposure Technique (closed Patch) The test sites were shaved with small-animal...0.007 0.44 4 0.01 and 0 .02b a LPG v/v% in distilled H20 Dinitrochlorobenzene w/v in 50% acetone/ olive oil (v/v) 29 Table 3 (continued) DERMAL...12 DNCB --- 0.007 0.4 6 Unsens. a LPG v/v% in distilled H O b DNCB w’v in 50% acetone olive oil (v/v) Primary Sensitization Results (Guinea Pigs) 30

  1. Contribution of dermal-derived mesenchymal cells during liver repair in two different experimental models

    PubMed Central

    Tan, Li; Dai, Tingyu; Liu, Dengqun; Chen, Zelin; Wu, Liao; Gao, Li; Wang, Yu; Shi, Chunmeng

    2016-01-01

    Progressive liver disease is a major health issue for which no effective treatment is available, leading to cirrhosis and orthotopic liver transplantation. However, the lack of availability of donor organs and other adverse factors including rejection limit its extensive clinical application. Cell-based therapy using mesenchymal stem/stromal cells (MSCs) may represent an attractive therapeutic option. Dermal-derived mesenchymal cells (DMCs) are attractive as one of the abundant sources from which to isolate mesenchymal cells for therapeutic applications and can be easily accessed with minimal harm to the donor. In this study, we used two different animal models to investigate potential therapeutic effect of DMCs transplantation in liver injury. We found that DMCs administration alleviated liver fibrosis and restored the liver function in fibrotic mice induced by CCl4. Furthermore, in an acute irradiation induced damage model, a unique population of DMCs could engraft into the liver tissue for a long period, exhibiting the phenotype of both mesenchymal cells and macrophage cells, and improve the survival of mice exposed to 8 Gy lethally total-body irradiation. These discoveries provide important evidence that DMCs therapy has a beneficial effect on liver injury, and provide new insight into liver injury therapy depending on the alternative cells. PMID:27126764

  2. In vitro investigations on the effect of dermal fibroblasts on keratinocyte responses to ultraviolet B radiation.

    PubMed

    Fernandez, Tara L; Van Lonkhuyzen, Derek R; Dawson, Rebecca A; Kimlin, Michael G; Upton, Zee

    2014-01-01

    Exposure to ultraviolet radiation is closely linked to the development of skin cancers in humans. The ultraviolet B (UVB) radiation wavelength (280-320 nm), in particular, causes DNA damage in epidermal keratinocytes, which are linked to the generation of signature premalignant mutations. Interactions between dermal fibroblasts and keratinocytes play a role in epidermal repair and regeneration after UVB-induced damage. To investigate these processes, established two and three-dimensional culture models were utilized to study the impact of fibroblast-keratinocyte crosstalk during the acute UVB response. Using a coculture system it was observed that fibroblasts enhanced keratinocyte survival and the repair of cyclobutane pyrimidine dimers (CPDs) after UVB radiation exposure. These findings were also mirrored in irradiated human skin coculture models employed in this study. Fibroblast coculture was shown to play a role in the expression and activation of members of the apoptotic cascade, including caspase-3 and Bad. Interestingly, the expression and phosphorylation of p53, a key player in the regulation of keratinocyte cell fate postirradiation, was also shown to be influenced by fibroblast-produced factors. This study highlights the importance of synergistic interactions between fibroblasts and keratinocytes in maintaining a functional epidermis while promoting repair and regeneration following UVB radiation-induced damage.

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

    PubMed

    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.

  4. Peroxide-based oxygen generating topical wound dressing for enhancing healing of dermal wounds.

    PubMed

    Chandra, Prafulla K; Ross, Christina L; Smith, Leona C; Jeong, Seon S; Kim, Jaehyun; Yoo, James J; Harrison, Benjamin S

    2015-01-01

    Oxygen generating biomaterials represent a new trend in regenerative medicine that aims to generate and supply oxygen at the site of requirement, to support tissue healing and regeneration. To enhance the healing of dermal wounds, we have developed a highly portable, in situ oxygen generating wound dressings that uses sodium percarbonate (SPO) and calcium peroxide (CPO) as chemical oxygen sources. The dressing continuously generated oxygen for more than 3 days, after which it was replaced. In the in vivo testing on porcine full-thickness porcine wound model, the SPO/CPO dressing showed enhanced wound healing during the 8 week study period. Quantitative measurements of wound healing related parameters, such as wound closure, reepithelialization, epidermal thickness and collagen content of dermis showed that supplying oxygen topically using the SPO/CPO dressing significantly accelerated the wound healing. An increase in neovascularization, as determined using Von Willebrand factor (vWF) and CD31 staining, was also observed in the presence of SPO/CPO dressing. This novel design for a wound dressing that contains oxygen generating biomaterials (SPO/CPO) for supplying topical oxygen, may find utility in treating various types of acute to chronic wounds.

  5. ISSUES IN UNDERSTANDING DERMAL EXPOSURES RESULTING FROM CONTACT WITH CONTAMINATED SURFACES, MEASURING SURFACE CONTAMINATION, AND CHARACTERIZING TRANSFERS

    EPA Science Inventory

    Although monitoring for surface contamination in work with radioactive materials and dermal monitoring of pesticide exposure to agricultural workers have been standard practice for 50 years, regular surface sampling and dermal monitoring methods have only been applied to indust...

  6. Liposome-containing Hibiscus sabdariffa calyx extract formulations with increased antioxidant activity, improved dermal penetration and reduced dermal toxicity.

    PubMed

    Pinsuwan, Sirirat; Amnuaikit, Thanaporn; Ungphaiboon, Suwipa; Itharat, Arunporn

    2010-12-01

    Hibiscus sabdariffa Linn, or Roselle, is a medicinal plant used extensively in traditional Thai medicine since ancient times. The extracts of Roselle calyces possess antioxidant activity and have potential for development as active ingredients in cosmetic products. However the limitations of using Roselle extracts in cosmetics are its low skin permeation and dermal irritation. Liposome technology is an obvious approach that might overcome these problems. Liposome formulations of standardized Roselle extracts were developed with various lipid components. The formulation showing the highest entrapment efficiency was selected for stability, skin permeation and dermal irritability studies. The liposome formulation with the highest entrapment efficiency (83%) and smalôlest particle size (332 mm) was formulated with phosphatidylcholine from soybean (SPC): Tween 80: deoxycholic acid (DA); 84:16:2.5 weight ratio, total lipid of 200 g/mL and 10% w/v Roselle extract in final liposomal preparation. This liposome formulation was found to be stable after storage at 4 degrees C, protected from light, for 2 months. The in vitro skin permeation studies, using freshly excised pig skin and modified Franz-diffusion cells, showed that the liposome formulation was able to considerably increased the rate of permeation of active compounds in Roselle extracts compared to the Roselle extract solution. The in vivo dermal irritability testing on rabbit skin showed that the liposome formulation dramatically decreased skin irritability compared to the unformulated extract. These results showed that the liposomes containing Roselle extracts had good stability, high entrapment efficacy, increased skin permeation and low skin irritation.

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

    PubMed

    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.

  8. In vitro dermal absorption of pyrethroid pesticides in human and rat skin

    EPA Science Inventory

    Dermal exposure to pyrethroid pesticides can occur during manufacture and application. This study examined the in vitro dermal absorption of pyrethroids using rat and human skin. Dermatomed skin from adult male Long Evans rats or human cadavers was mounted in flowthrough diffusi...

  9. IN VITRO DERMAL ABSORPTION OF PYRETHROID PESTICIDES IN RAT AND HUMAN SKIN

    EPA Science Inventory

    Pyrethriods are a class of neurotoxic pesticides and their use may lead to dermal exposure. This study examined the in vitro dermal absorption of pyrethroids in rat and human skin. Dorsal skin removed from adult male LD rats (hair clipped 24 h previously) was dermatomed and mou...

  10. DERMAL, ORAL, AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

    EPA Science Inventory

    Methyl tertiary butyl ether (MTBE), a gasoline additive, used to increase octane and reduce carbon monoxide emissions and ozone precursors has contaminated drinking water leading to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhalation ki...

  11. DERMAL, ORAL AND INHALATION PHARMACOKINETICS OF METHYL TERTIARY-BUTYL ETHER (MTBE) IN HUMAN VOLUNTEERS

    EPA Science Inventory


    Methyl tertiary butyl ether (MTBE), a gasoline additive used to increase octane and reduce carbon monoxide emissions and ozone precursors, has contaminated drinking water and can lead to exposure by oral, inhalation, and dermal routes. To determine its dermal, oral, and inhal...

  12. Acute toxicity and analgesic action of a combination of buclizine, codeine and paracetamol ('Migraleve') in tablet and suppository form in rats.

    PubMed

    Behrendt, W A; Cserepes, J

    1985-01-01

    Studies in rats were carried out to determine the acute toxicity and analgesic effect of a combination preparation ('Migraleve') containing codeine and paracetamol and the individual analgesics when given orally or by rectal administration. The results showed that the combination was no more toxic than paracetamol alone and, on the basis of the LD50:ED50 ratio, was less toxic by the oral than by the rectal route. In the rat-tail test, the combination induced a well-defined dose-dependent analgesic response which was greater after rectal administration. Codeine and paracetamol tested individually were effective only at relatively high dosage and, like the combination, their analgesic effects were greater after rectal administration and more clearly dose-dependent than after oral administration. Comparison of the area under the time-effect curves for the combination and the individual components confirmed the synergism between codeine and paracetamol.

  13. Acute toxicity of diphacinone in Northern bobwhite: Effects on survival and blood clotting

    USGS Publications Warehouse

    Rattner, Barnett A.; Horak, Katherine E.; Warner, Sarah E.; Johnston, John J.

    2010-01-01

    The anticoagulant rodenticide diphacinone was slightly toxic (acute oral LD50 2014 mg/kg) to Northern bobwhite (Colinus virginianus) in a 14-day acute toxicity trial. Precise and sensitive assays of blood clotting (prothrombin time, Russell?s Viper venom time, and thrombin clotting time) were adapted for use in quail, and this combination of assays is recommended to measure the effects of anticoagulant rodenticides. A single oral sublethal dose of diphacinone (434 mg/kg body weight) prolonged clotting time at 48 h post-dose compared to controls. At 783 mg/kg (approximate LD02), clotting time was prolonged at both 24 and 48 h post-dose. Prolongation of in vitro clotting time reflects impaired coagulation complex activity, and was detected before overt signs of toxicity were apparent at the greatest dosages (2868 and 3666 mg/kg) in the acute toxicity trial. These clotting time assays and toxicity data will assist in the development of a pharmacodynamic model to predict toxicity, and also facilitate rodenticide hazard and risk assessments in avian species.

  14. Acute and subchronic toxicity of naturally weathered Exxon Valdez crude oil in mallards and ferrets

    SciTech Connect

    Stubblefield, W.A.; Hancock, G.A.; Ford, W.H.; Ringer, R.K.

    1995-11-01

    The toxic properties of naturally weathered Exxon Valdez crude oil (WEVC) were assessed in a battery of acute and subchronic toxicity tests using mallards, Anas platyrhynchos, and European ferrets, Mustela putorius. Adult mallard acute oral toxicity study results indicated no mortalities or signs o toxicity, i.e., no-observed-adverse-effect level (NOAEL) and median lethal dose (LD50) > 5,000 mg/kg. Acute oral feeding and food avoidance tests with ducklings also indicated no toxicity (NOAEL and LC50 > 50,000 mg/kg diet) with no evidence of food avoidance (FAC50 > 20,000 mg/kg diet). No mortalities or toxic signs were noted in a 14-d feeding study with adult birds at dietary concentrations up to 100,000 mg WEVC/kg diet. Among clinical and physiological end points evaluated, the only significant difference noted was an increase in liver: body weight ratios in the 100,000-mg WEVC/kg diet dose group. No differences in clinical chemistry or hematological parameters were noted, and there were no consistent differences in histological evaluations of organ tissues. Daily oral doses of up to 5,000 mg/kg of WEVC over 5 d resulted in minimal effects on ferrets. Increased serum albumin concentrations were observed in the 5,000-mg/kg dose group females and decreased spleen weights were noted in females of all WEVC treatment groups. No other significant observations were noted.

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

    PubMed

    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.

  16. Effect of Arctium lappa (burdock) extract on canine dermal fibroblasts.

    PubMed

    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.

  17. Estimating Dermal Transfer of Copper Particles from the ...

    EPA Pesticide Factsheets

    Lumber pressure-treated with micronized copper was examined for the release of copper and copper micro/nanoparticles using a surface wipe method to simulate dermal transfer. In 2003, the wood industry began replacing CCA treated lumber products for residential use with copper based formulations. Micronized copper (nano to micron sized particles) has become the preferred treatment formulation. There is a lack of information on the release of copper, the fate of the particles during dermal contact, and the copper exposure level to children from hand-to-mouth transfer. For the current study, three treated lumber products, two micronized copper and one ionic copper, were purchased from commercial retailers. The boards were left to weather outdoors for approximately 1 year. Over the year time period, hand wipe samples were collected periodically to determine copper transfer from the wood surfaces. The two micronized formulations and the ionic formulation released similar levels of total copper. The amount of copper released was high initially, but decreased to a constant level (~1.5 mg m-2) after the first month of outdoor exposure. Copper particles were identified on the sampling cloths during the first two months of the experiment, after which the levels of copper were insufficient to collect interpretable data. After 1 month, the particles exhibited minimal changes in shape and size. At the end of 2-months, significant deterioration of the particles was

  18. CRH stimulates POMC activity and corticosterone production in dermal fibroblasts.

    PubMed

    Slominski, Andrzej; Zbytek, Blazej; Semak, Igor; Sweatman, Trevor; Wortsman, Jacobo

    2005-05-01

    It has been previously documented that human skin cells including epidermal keratinocytes and dermal fibroblasts produce and process proopiomelanocortin (POMC), corticotropin releasing hormone (CRH), and express functional CRH receptors type-1 (CRH-R1). The skin also has corticosteroidogenic activity, suggesting a functional connection between these elements. In the current study, we found that human dermal fibroblasts (but not normal epidermal keratinocytes) respond to CRH with stimulation of cAMP, with POMC gene and protein expression, and ACTH production and release. Furthermore, CRH and ACTH stimulate production of corticosterone in fibroblasts, with ACTH being more potent. Although cortisol-immunoreactivity accumulation/production in fibroblasts has been detected by ELISA, it appears to be constitutive (not affected by CRH or ACTH). These effects are absent in keratinocytes. Therefore, we propose that fibroblasts but not keratinocytes display a functional CRH-POMC-corticosteroid axis organized similarly to the hypothalamus-pituitary-adrenal (HPA) axis. However, it diverges from the HPA organization in its distal step, where CRH and ACTH stimulate production of corticosterone, instead of cortisol.

  19. Soil Organic Matter Content Effects on Dermal Pesticide ...

    EPA Pesticide Factsheets

    Agricultural landscapes serve as active amphibian breeding grounds despite their seemingly poor habitat value. Activity of adults and dispersal of metamorphs to and from agricultural ponds occurs in most species from spring through late summer or early fall, a time that coincides with pesticide applications on farm fields and crops. In terrestrial landscapes, dermal contact with contaminated soil and plant matter may lead to bioconcentration as well as lethal and sublethal effects in amphibians.Although the physiological structure of the amphibian dermis may facilitate pesticide uptake, soil properties may ultimately dictate bioavailability of pesticides in terrestrial habitats. The organic matter fraction of soil readily binds to pesticides, potentially decreasing the availability of pesticides adhering to biological matter. Soil partition coefficient dermal uptake of five pesticide active ingredients on either high or low organic matter soils. We predicted that amphibian body burdens would be a function of soil carbon content or Koc. with greater bioconcentration in individuals exposed to pesticides on sa

  20. Visible spectroscopic imaging studies of normal and ischemic dermal tissue

    NASA Astrophysics Data System (ADS)

    Zuzak, Karel J.; Schaeberle, Michael D.; Lewis, E. Neil; Levin, Ira W.

    2000-05-01

    We describe a non-invasive, in vivo hyperspectral imaging method for visualizing the spatial distribution of dermal tissue oxygenation. Real-time images of the dermis are acquired both at multiple, contiguous wavelengths and at relatively narrow spectral bandwidths to generate a data cube consisting of one spectral and two spatial dimensions. For data collection, the sample area is illuminated by radiation, which is delivered by liquid light guides from a quartz tungsten halogen source. Reflected light from the sample is first passed through a liquid crystal tunable filter and then imaged onto a silicon charged coupled device detector. The subsequently digitized data are presented in terms of spectral images reflecting multivariate least squares analyses based upon linear combinations of oxy- and deoxyhemoglobin reference spectra. The generated gray scale images directly represent the varying spatial distributions of dermal tissue oxygenation. As an example, imaging data are obtained from normal tissue and induced ischemic tissue for which both the venous and arterial blood flow was artificially occluded.

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

    PubMed

    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.

  2. Patient factors influencing dermal filler complications: prevention, assessment, and treatment

    PubMed Central

    De Boulle, Koenraad; Heydenrych, Izolda

    2015-01-01

    While rare, complications do occur with the esthetic use of dermal fillers. Careful attention to patient factors and technique can do much to avoid these complications, and a well-informed practitioner can mitigate problems when they do occur. Since cosmetic surgery is usually an elective process, requested by the patient, clinical trials are complex to organize and run. For this reason, an international group of practicing physicians in the field of esthetics came together to share knowledge and to try and produce some informed guidance for their colleagues, considering the literature and also pooling their own extensive clinical experience. This manuscript aims to summarize the crucial aspects of patient selection, including absolute contraindications as well as situations that warrant caution, and also covers important considerations for the pre- and posttreatment periods as well as during the procedure itself. Guidance is given on both immediate and long-term management of adverse reactions. The majority of complications are related to accepting patients inappropriate for treatment or issues of sterility, placement, volume, and injection technique. It is clear that esthetic practitioners need an in-depth knowledge of all aspects of treatment with dermal fillers to achieve optimal outcomes for their patients. PMID:25926750

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

    PubMed

    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.

  4. Dermal irritation of petrolatum in rabbits but not in mice, rats or minipigs.

    PubMed

    Chandra, S A; Peterson, R A; Melich, D; Merrill, C M; Bailey, D; Mellon-Kusibab, K; Adler, R

    2014-08-01

    Petrolatum is widely used in cosmetics, topical pharmaceuticals and also as a vehicle in dermal toxicity studies. New Zealand white rabbits treated with white petrolatum (vehicle control) in a 2-week dermal irritation study exhibited moderate to severe erythema starting on Day 7 that subsided towards the end of the study. Histological examination of abraded and non-abraded petrolatum-treated skin obtained at termination (Day 15) revealed mild acanthosis, hyperkeratosis, dermal edema with mixed inflammatory cells in the dermis. Macroscopic and microscopic features noted in rabbits were consistent with dermal irritation to petrolatum. Wistar-Han rats, CD1 mice, C57/Bl/6J mice and Göttingen minipigs treated topically with white petrolatum did not exhibit clinical or histologic evidence of dermal irritation. Therapeutic agents developed for topical application are generally tested in rabbits during some point in development. Interpretation of skin irritation data from a single species can impact risk assessment for humans and on product labeling.

  5. Hanford Tank Ventilation System Condensates and Headspace Vapors: An Assessment of Potential Dermal Exposures

    SciTech Connect

    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. An assessment of dermal exposure to heavy fuel oil (HFO) in occupational settings.

    PubMed

    Christopher, Yvette; Van Tongeren, Martie; Urbanus, Jan; Cherrie, John W

    2011-04-01

    Heavy fuel oil (HFO) components are a group of heavy petroleum streams produced in oil refineries from crude oil. Due to its physicochemical properties, the dermal route is an important route of exposure. However, no information on dermal exposure levels for HFO has previously been published. A method for measuring dermal HFO levels was developed using wipe sampling and measuring phenanthrene and naphthalene as markers of HFO exposure. Measurement surveys were carried out in four different types of facilities: oil refineries, distribution terminals, energy providers, and an engine building and repair company. Dermal wipe samples were collected from different anatomical regions: neck, hands, and forearms. The frequency of tasks with potential for dermal HFO exposure was generally low at these facilities, with the exception of the distribution terminals and the engine building and repair site. The geometric mean (GM) dermal load on the hands was ∼0.1 μg cm(-2) for both left and right hand and 0.013 and 0.019 μg cm(-2) for the left and right forearm, respectively. With one exception, all results from the neck samples were below the limit of detection. The highest dermal loads for the hands and forearms were found in the engine building and repair facility (hands: GM = 1.6 μg cm(-2); forearms: GM = 0.41 μg cm(-2)). The tasks with the highest dermal loads were the maintenance (hands: GM = 1.7 μg cm(-2)) and cleaning tasks (hands: GM = 0.24 μg cm(-2)). Actual dermal loads were low when compared with workplace dermal exposure measurements reported by other researchers for similar scenarios with other substances. This may be explained by high compliance of gloves use by workers during HFO handling tasks and likely avoidance of contact with HFO due to its high viscosity and the requirement to keep HFO at elevated temperatures during storage, transport, and use.

  7. Noninvasive assessment of dermal carotenoids as a biomarker of fruit and vegetable intake123

    PubMed Central

    Cartmel, Brenda; Scarmo, Stephanie; Lin, Haiqun; Leffell, David J; Welch, Erin; Ermakov, Igor; Bhosale, Prakash; Bernstein, Paul S; Gellermann, Werner

    2010-01-01

    Background: Resonance Raman spectroscopy (RRS) has been suggested as a feasible method for noninvasive carotenoid measurement of human skin. However, before RRS measures of dermal carotenoids can be used as a biomarker, data on intra- and intersubject variability and validity are needed. Objective: The purpose of this study was to evaluate the reproducibility and validity of RRS measures of dermal total carotenoids and lycopene in humans. Design: In study 1, 74 men and women with diverse skin pigmentation were recruited. RRS measures of the palm, inner arm, and outer arm were obtained at baseline, 1 wk, 2 wk, 1 mo, 3 mo, and 6 mo (to maximize seasonal variation). The RRS device used visible light at 488 nm to estimate total carotenoids and at 514 nm to estimate lycopene. Reproducibility was assessed by intraclass correlation coefficients (ICCs). In study 2, we recruited 28 subjects and assessed dietary carotenoid intake, obtained blood for HPLC analyses, performed RRS measures of dermal carotenoid status, and performed dermal biopsies (3-mm punch biopsy) with dermal carotenoids assessed by HPLC. Results: ICCs for total carotenoids across time were 0.97 (palm), 0.95 (inner arm), and 0.93 (outer arm). Total dermal carotenoids assessed by RRS were significantly correlated with total dermal carotenoids assessed by HPLC of dermal biopsies (r = 0.66, P = 0.0001). Similarly, lycopene assessed by RRS was significantly correlated with lycopene assessed by HPLC of dermal biopsies (r = 0.74, P < 0.0001). Conclusion: RRS is a feasible and valid method for noninvasively assessing dermal carotenoids as a biomarker for studies of nutrition and health. PMID:20685953

  8. Research on acute toxicity and the behavioral effects of methanolic extract from psilocybin mushrooms and psilocin in mice.

    PubMed

    Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V; Halama, Marek; Wieczorek, Piotr P

    2015-03-27

    The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers.

  9. Research on Acute Toxicity and the Behavioral Effects of Methanolic Extract from Psilocybin Mushrooms and Psilocin in Mice

    PubMed Central

    Zhuk, Olga; Jasicka-Misiak, Izabela; Poliwoda, Anna; Kazakova, Anastasia; Godovan, Vladlena V.; Halama, Marek; Wieczorek, Piotr P.

    2015-01-01

    The pharmacological activities and acute toxicity of the psilocin (PC) and dried residues of the crude extracts of psychotropic mushrooms were investigated in mice. The hallucinogenic substances were effectively isolated, by using methanol, from the species of Psilocybe semilanceata and Pholiotina cyanopus, that were collected in the north-east region of Poland. The chemical analysis of these extracts, which was performed by liquid chromatography with mass spectrometry detection (LC-MS), indicated the presence of psilocin and other hallucinogenic substances, including indolealkylamines and their phosphorylated analogues. When the pure psilocin or fungal extracts were used, slight differences in determined LD50 values were observed. However, the application of PC evoked the highest level of toxicity (293.07 mg/kg) compared to the activity of extracts from Ph. cyanopus and P. semilanceata, where the level of LD50 was 316.87 mg/kg and 324.37 mg/kg, respectively. Furthermore, the behavioral test, which considered the head-twitching response (HTR), was used to assess the effects of the studied psychotropic factors on the serotonergic system. Both, the fungal extracts and psilocin evoked characteristic serotoninergic effects depending on the dose administered to mice, acting as an agonist/partial agonist on the serotonergic system. A dose of 200 mg/kg 5-hydroxytryptophan (5-HTP) induced spontaneous head-twitching in mice (100% effect), as a result of the formation of 5-hydroxytryptamine (5-HT) in the brain. Compared to the activity of 5-HTP, the intraperitoneal administration of 1mg/kg of psilocin or hallucinogenic extracts of studied mushrooms (Ph. cyanopus and P. semilanceata) reduced the number of head-twitch responses of about 46% and 30%, respectively. In contrast, the administration of PC exhibited a reduction of about 60% in HTR numbers. PMID:25826052

  10. Toxic Epidermal Necrolysis and Acute Kidney Injury due to Glyphosate Ingestion

    PubMed Central

    Indirakshi, J.; Sunnesh, A.; Aruna, M.; Reddy, M. Hari Krishna; Kumar, Anil C. V.; Chandra, V. Sarat; Sangeetha, B.; Katyarmal, D. T.; Ram, R.; Kumar, V. Siva

    2017-01-01

    The literature, particularly from India, is scarce on the renal effects of glyphosate poisoning. Glyphosate causes toxicity not only after its ingestion but also after dermal exposure by inhalation route and on eye exposure. We present a patient report of glyphosate consumption which resulted in toxic epidermal necrolysis – the first report after glyphosate consumption and acute kidney injury.

  11. Acute toxicity and mutagenicity of the copper complex of pyruvaldehyde-bis (N-4-methylthiosemicarbazone), Cu-PTSM.

    PubMed

    Kostyniak, P J; Nakeeb, S M; Schopp, E M; Maccubbin, A E; John, E K; Green, M A; Kung, H F

    1990-12-01

    Cu-PTSM is a potential imaging agent for the heart and brain when labeled with either 64Cu or 62Cu. Unlabeled Cu-PTSM was evaluated for its acute toxicity and mutagenicity. Cu-PTSM had an i.v. LD50 of 26 mg kg-1 in the rat and 2 mg kg-1 in the rabbit. At necropsy, rats exhibited severely hemorrhagic lungs, histological findings of acute pulmonary congestion, hemorrhage and edema, and mild congestion in kidney, liver and brain. The rabbit displayed marked polymorphonuclear infiltration in alveoli, peribronchial and periarterial areas with marked macrophage hyperplasia, congestion and mild hemorrhage into alveolar spaces. No effects were found in kidney, liver, testes or brain. Administration of 2.16 micrograms kg-1 day-1 for 5 days per week for 2 weeks resulted in no changes in histopathology, hematology or clinical chemistry parameters. This daily dose is at least 300 times the diagnostic dose intended for use in man. Cu-PTSM was not mutagenic when tested in the absence of S9 supernatant, but elicited a weakly mutagenic response in the presence of S9. Since acute effects in the lung occur at doses approaching 300,000 times the diagnostic dose, it is highly unlikely that the clinical use of Cu-PTSM would result in any acute adverse effects.

  12. Phytochemical Screening and Acute Toxicity of Aqueous Extract of Leaves of Conocarpus erectus Linnaeus in Swiss Albino Mice.

    PubMed

    Nascimento, Dayane K D; Souza, Ivone A DE; Oliveira, Antônio F M DE; Barbosa, Mariana O; Santana, Marllon A N; Pereira, Daniel F; Lira, Eduardo C; Vieira, Jeymesson R C

    2016-09-01

    Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

  13. Cystitis - acute

    MedlinePlus

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  14. Irradiated PVAl membrane swelled with chitosan solution as dermal equivalent

    NASA Astrophysics Data System (ADS)

    Rodas, A. C. D.; Ohnuki, T.; Mathor, M. B.; Lugao, A. B.

    2005-07-01

    Synthetic membranes as dermal equivalent can be applied at in vitro studies for developing new transdermal drugs or cosmetics. These membranes could be composed to mimic the dermis and seed cultivated keratinocytes as epidermal layer on it. The endothelial cells ingrowth to promote neovascularization and fibroblasts ingrowth to promote the substitution of this scaffold by natural components of the dermis. As, they can mimic the scaffold function of dermis; the membranes with biological interaction could be used for in vivo studies as dermal equivalent. For this application, poly(vinyl alcohol) (PVAl) membranes crosslinked by gamma radiation were swelled with chitosan solution. PVAl do not interact with the organism when implanted and is intended to mimic the mechanical characteristics of the dermal scaffold. The chitosan as a biocompatible biosynthetic polysaccharide were incorporated into PVAl membranes to improve the organism response. Degradation of chitosan by the organism occurs preferably by hydrolysis or enzymatic action, for example, by lysozyme. For this purpose the swelling kinetic of PVAl membranes with chitosan solution were performed and it was verified their degradation in vitro. The results showed that the swelling equilibrium of the PVAl membranes with chitosan membranes was reached in 120 h with average swelling of 1730%. After swelling, PVAl and chitosan/PVAl membranes were dried and immersed in phosphate buffer solution pH 5.7 and pH 7.4, with and without lysozyme, as those pH values are the specific physiologic pH for external skin and the general physiological pH for the organism, respectively. It was verified that the pure PVAl membrane did not showed change in their mass during 14 days. PVAl membranes swelled with chitosan solution showed mass decrease from 1 to 14 days inside these solutions. The highest mass decrease was verified at pH 5.7 in phosphate buffer solution without lysozyme. The smallest mass decrease was verified at pH 7.4 in

  15. Acute toxicity of gasoline and some additives.

    PubMed Central

    Reese, E; Kimbrough, R D

    1993-01-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. PMID:8020435

  16. Acute toxicity of gasoline and some additives

    SciTech Connect

    Reese, E.; Kimbrough, R.D.

    1993-12-01

    The acute toxicity of gasoline; its components benzene, toluene, and xylene; and the additives ethanol, methanol, and methyl tertiary butyl ether are reviewed. All of these chemicals are only moderately to mildly toxic at acute doses. Because of their volatility, these compounds are not extensively absorbed dermally unless the exposed skin is occluded. Absorption through the lungs and the gastrointestinal tract is quite efficient. After ingestion, the principal danger for a number of these chemicals, particularly gasoline, is aspiration pneumonia, which occurs mainly in children. It is currently not clear whether aspiration pneumonia would still be a problem if gasoline were diluted with ethanol or methanol. During the normal use of gasoline or mixtures of gasoline and the other solvents as a fuel, exposures would be much lower than the doses that have resulted in poisoning. No acute toxic health effects would occur during the normal course of using automotive fuels. 128 refs., 7 tabs.

  17. Dermal uptake of phthalates from clothing: Comparison of model to human participant results.

    PubMed

    Morrison, G C; Weschler, C J; Bekö, G

    2016-11-11

    In this research, we extend a model of transdermal uptake of phthalates to include a layer of clothing. When compared with experimental results, this model better estimates dermal uptake of diethylphthalate and di-n-butylphthalate (DnBP) than a previous model. The model predictions are consistent with the observation that previously exposed clothing can increase dermal uptake over that observed in bare-skin participants for the same exposure air concentrations. The model predicts that dermal uptake from clothing of DnBP is a substantial fraction of total uptake from all sources of exposure. For compounds that have high dermal permeability coefficients, dermal uptake is increased for (i) thinner clothing, (ii) a narrower gap between clothing and skin, and (iii) longer time intervals between laundering and wearing. Enhanced dermal uptake is most pronounced for compounds with clothing-air partition coefficients between 10(4) and 10(7) . In the absence of direct measurements of cotton cloth-air partition coefficients, dermal exposure may be predicted using equilibrium data for compounds in equilibrium with cellulose and water, in combination with computational methods of predicting partition coefficients.

  18. Dermal and ocular exposure systems for the development of models of sulfur mustard-induced injury.

    PubMed

    Weber, Waylon M; Kracko, Dean A; Lehman, Mericka R; Cox, Christopher E; Cheng, Yung-Sung; Grotendorst, Gary R; McDonald, Jacob D

    2011-09-01

    Sulfur mustard (SM) is a chemical threat agent for which the effects have no current treatment. Due to the ease of synthesis and dispersal of this material, the need to develop therapeutics is evident. The present article details the techniques used to develop SM laboratory exposure systems for the development of animal models of ocular and dermal injury. These models are critical to enable evaluation of SM injury and therapeutics against that injury. Iterative trials were conducted to optimize dermal and ocular injury models in guinea pigs and rabbits respectively. The goal was a homogeneous and diffuse ocular and dermal injury that compares to the human injury. Dermal exposures were conducted by either a flow-past or static vapor cup system. Ocular exposures were conducted by a static exposure system. Ocular and dermal exposures were conducted with vaporized SM. Vapor concentrations increased with time in the dermal and ocular exposure systems but were stable with varying amounts of applied SM. A dermal deposition estimation study was also conducted. Deposited volumes increased with exposure time.

  19. Comparison of dermal and inhalation routes of entry for organic chemicals

    NASA Technical Reports Server (NTRS)

    Jepson, Gary W.; Mcdougal, James N.; Clewell, Harvey J., III

    1992-01-01

    The quantitative comparison of the chemical concentration inside the body as the result of a dermal exposure versus an inhalation exposure is useful for assessing human health risks and deciding on an appropriate protective posture. In order to describe the relationship between dermal and inhalation routes of exposure, a variety of organic chemicals were evaluated. The types of chemicals chosen for the study were halogenated hydrocarbons, aromatic compounds, non-polar hydrocarbons and inhalation anesthetics. Both dermal and inhalation exposures were conducted in rats and the chemicals were in the form of vapors. Prior to the dermal exposure, rat fur was closely clipped and during the exposure rats were provided fresh breathing air through latex masks. Blood samples were taken during 4-hour exposures and analyzed for the chemical of interest. A physiologically based pharmacokinetic model was used to predict permeability constants (cm/hr) consistent with the observed blood concentrations of the chemical. The ratio of dermal exposure to inhalation exposure required to achieve the same internal dose of chemical was calculated for each test chemical. The calculated ratio in humans ranged from 18 for styrene to 1180 for isoflurane. This methodology can be used to estimate the dermal exposure required to reach the internal dose achieved by a specific inhalation exposure. Such extrapolation is important since allowable exposure standards are often set for inhalation exposures, but occupational exposures may be dermal.

  20. Estrogen Depletion Results in Nanoscale Morphology Changes in Dermal Collagen

    PubMed Central

    Fang, Ming; Liroff, Kaitlin G.; Turner, A. Simon; Les, Clifford M.; Orr, Bradford G.; Holl, Mark M. Banaszak

    2012-01-01

    Tissue cryo-sectioning combined with Atomic Force Microscopy (AFM) imaging reveals that the nanoscale morphology of dermis collagen fibrils, quantified using the metric of D-periodic spacing, changes under the condition of estrogen depletion. Specifically, a new subpopulation of fibrils with D-spacings in the region between 56 and 59 nm is present two years following ovariectomy in ovine dermal samples. In addition, the overall width of the distribution, both values above and below the mean, has increased. The change in width due to an increase in lower values of D-spacings was previously reported for ovine bone; however, this report demonstrates that the effect is also present in non-mineralized collagen fibrils. A non-parametric Kolmogrov-Smirnov test of the cumulative density function indicates a statistical difference in the sham and OVX D-spacing distributions (p < 0.01). PMID:22437310

  1. [Evaluation of liberation of caffeine from dermal semisolids drugs].

    PubMed

    Kodadová, Alexandra; Vitková, Zuzana; Herdová, Petra

    2013-10-01

    The paper deals with formulation of caffeine into dermal semisolid dosage forms - hydrogels. Caffeine was chosen as a model drug because its properties can be successfully used just in hydrogels. Protective and tranquilization effects can be used in the preparations for sunbathing, and its lipolytic and regenerative effect can be used for the treatment of androgenic alopecia or cellular bioprotection. The aim of the study was to investigate the influence of different concentrations of chitosan and caffeine on the liberation of gels. Besides, stability of the prepared samples was evaluated by means of the evaluation of their rheological parameters. Based on the obtained results, there was determined the optimal drug concentration - caffeine 0.2% (w/w) and also the gel forming substance - chitosan 2.3% (w/w).

  2. Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

    PubMed

    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.

  3. Bioactives from probiotics for dermal health: functions and benefits.

    PubMed

    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.

  4. Lycopene from tomatoes: vesicular nanocarrier formulations for dermal delivery.

    PubMed

    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.

  5. Microporous Dermal-Like Electrospun Scaffolds Promote Accelerated Skin Regeneration

    PubMed Central

    Bonvallet, Paul P.; Culpepper, Bonnie K.; Bain, Jennifer L.; Schultz, Matthew J.; Thomas, Steven J.

    2014-01-01

    The goal of this study was to synthesize skin substitutes that blend native extracellular matrix (ECM) molecules with synthetic polymers which have favorable mechanical properties. To this end, scaffolds were electrospun from collagen I (col) and poly(ɛ-caprolactone) (PCL), and then pores were introduced mechanically to promote fibroblast infiltration, and subsequent filling of the pores with ECM. A 70:30 col/PCL ratio was determined to provide optimal support for dermal fibroblast growth, and a pore diameter, 160 μm, was identified that enabled fibroblasts to infiltrate and fill pores with native matrix molecules, including fibronectin and collagen I. Mechanical testing of 70:30 col/PCL scaffolds with 160 μm pores revealed a tensile strength of 1.4 MPa, and the scaffolds also exhibited a low rate of contraction (<19%). Upon implantation, scaffolds should support epidermal regeneration; we, therefore, evaluated keratinocyte growth on fibroblast-embedded scaffolds with matrix-filled pores. Keratinocytes formed a stratified layer on the surface of fibroblast-remodeled scaffolds, and staining for cytokeratin 10 revealed terminally differentiated keratinocytes at the apical surface. When implanted, 70:30 col/PCL scaffolds degraded within 3–4 weeks, an optimal time frame for degradation in vivo. Finally, 70:30 col/PCL scaffolds with or without 160 μm pores were implanted into full-thickness critical-sized skin defects. Relative to nonporous scaffolds or sham wounds, scaffolds with 160 μm pores induced accelerated wound closure, and stimulated regeneration of healthy dermal tissue, evidenced by a more normal-appearing matrix architecture, blood vessel in-growth, and hair follicle development. Collectively, these results suggest that microporous electrospun scaffolds are effective substrates for skin regeneration. PMID:24568584

  6. Microporous dermal-like electrospun scaffolds promote accelerated skin regeneration.

    PubMed

    Bonvallet, Paul P; Culpepper, Bonnie K; Bain, Jennifer L; Schultz, Matthew J; Thomas, Steven J; Bellis, Susan L

    2014-09-01

    The goal of this study was to synthesize skin substitutes that blend native extracellular matrix (ECM) molecules with synthetic polymers which have favorable mechanical properties. To this end, scaffolds were electrospun from collagen I (col) and poly(ɛ-caprolactone) (PCL), and then pores were introduced mechanically to promote fibroblast infiltration, and subsequent filling of the pores with ECM. A 70:30 col/PCL ratio was determined to provide optimal support for dermal fibroblast growth, and a pore diameter, 160 μm, was identified that enabled fibroblasts to infiltrate and fill pores with native matrix molecules, including fibronectin and collagen I. Mechanical testing of 70:30 col/PCL scaffolds with 160 μm pores revealed a tensile strength of 1.4 MPa, and the scaffolds also exhibited a low rate of contraction (<19%). Upon implantation, scaffolds should support epidermal regeneration; we, therefore, evaluated keratinocyte growth on fibroblast-embedded scaffolds with matrix-filled pores. Keratinocytes formed a stratified layer on the surface of fibroblast-remodeled scaffolds, and staining for cytokeratin 10 revealed terminally differentiated keratinocytes at the apical surface. When implanted, 70:30 col/PCL scaffolds degraded within 3-4 weeks, an optimal time frame for degradation in vivo. Finally, 70:30 col/PCL scaffolds with or without 160 μm pores were implanted into full-thickness critical-sized skin defects. Relative to nonporous scaffolds or sham wounds, scaffolds with 160 μm pores induced accelerated wound closure, and stimulated regeneration of healthy dermal tissue, evidenced by a more normal-appearing matrix architecture, blood vessel in-growth, and hair follicle development. Collectively, these results suggest that microporous electrospun scaffolds are effective substrates for skin regeneration.

  7. Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

    PubMed Central

    Tracy, Lauren E.; Minasian, Raquel A.; Caterson, E.J.

    2016-01-01

    Significance: Fibroblasts play a critical role in normal wound healing. Various extracellular matrix (ECM) components, including collagens, fibrin, fibronectin, proteoglycans, glycosaminoglycans, and matricellular proteins, can be considered potent protagonists of fibroblast survival, migration, and metabolism. Recent Advances: Advances in tissue culture, tissue engineering, and ex vivo models have made the examination and precise measurements of ECM components in wound healing possible. Likewise, the development of specific transgenic animal models has created the opportunity to characterize the role of various ECM molecules in healing wounds. In addition, the recent characterization of new ECM molecules, including matricellular proteins, dermatopontin, and FACIT collagens (Fibril-Associated Collagens with Interrupted Triple helices), further demonstrates our cursory knowledge of the ECM in coordinated wound healing. Critical Issues: The manipulation and augmentation of ECM components in the healing wound is emerging in patient care, as demonstrated by the use of acellular dermal matrices, tissue scaffolds, and wound dressings or topical products bearing ECM proteins such as collagen, hyaluronan (HA), or elastin. Once thought of as neutral structural proteins, these molecules are now known to directly influence many aspects of cellular wound healing. Future Directions: The role that ECM molecules, such as CCN2, osteopontin, and secreted protein, acidic and rich in cysteine, play in signaling homing of fibroblast progenitor cells to sites of injury invites future research as we continue investigating the heterotopic origin of certain populations of fibroblasts in a healing wound. Likewise, research into differently sized fragments of the same polymeric ECM molecule is warranted as we learn that fragments of molecules such as HA and tenascin-C can have opposing effects on dermal fibroblasts. PMID:26989578

  8. Skin telocytes versus fibroblasts: two distinct dermal cell populations

    PubMed Central

    Kang, Yuli; Zhu, Zaihua; Zheng, Yonghua; Wan, Weiguo; Manole, Catalin G; Zhang, Qiangqiang

    2015-01-01

    It is already accepted that telocytes (TCs) represent a new type of interstitial cells in human dermis. In normal skin, TCs have particular spatial relations with different dermal structures such as blood vessels, hair follicles, arrector pili muscles or segments of sebaceous and/or eccrine sweat glands. The distribution and the density of TCs is affected in various skin pathological conditions. Previous studies mentioned the particular (ultra)structure of TCs and also their immunophenotype, miR imprint or proteome, genome or secretome features. As fibroblast is the most common intersitital cell (also in human dermis), a dedicated comparison between human skin TCs and fibroblasts (Fbs) was required to be performed. In this study, using different techniques, we document several points of difference between human dermis TCs and Fbs. By transmission electron microscopy (TEM) and scanning electron microscopy (SEM), we demonstrated TCs with their hallmark cellular prolongations – telopodes. Thus, we showed their ultrastructural distinctiveness from Fbs. By RayBio Human Cytokine Antibody Array V analyses performed on the supernatant from separately cultured TCs and Fbs, we detected the cytokine profile of both cell types, individually. Two of 79 detected cytokines – epithelial-derived neutrophil-activating peptide 78 and granulocyte chemotactic protein-2 – were 1.5 times higher in the supernatant of TCs (comparing with Fbs). On the other hand, 37 cytokines were at least 1.5 higher in Fbs supernatant (comparing with TCs), and among them six cytokines – interleukin 5, monocyte chemotactic protein-3 (MCP-3), MCP-4, macrophage inflammatory protein-3, angiogenin, thrombopoietin – being 9.5 times higher (results also confirmed by ELISA testing). In summary, using different techniques, we showed that human dermal TCs and Fbs are different in terms of ultrastructure and cytokine profile. PMID:26414534

  9. Effect of water temperature on dermal exposure to chloroform.

    PubMed

    Gordon, S M; Wallace, L A; Callahan, P J; Kenny, D V; Brinkman, M C

    1998-06-01

    We have developed and applied a new measurement methodology to investigate dermal absorption of chloroform while bathing. Ten subjects bathed in chlorinated water while breathing pure air through a face mask. Their exhaled breath was delivered to a glow discharge source/ion trap mass spectrometer for continuous real-time measurement of chloroform in the breath. This new method provides abundant data compared to previous discrete time-integrated breath sampling methods. The method is particularly well suited to studying dermal exposure because the full face mask eliminates exposure to contaminated air. Seven of the 10 subjects bathed in water at two or three different temperatures between 30 degrees C and 40 degrees C. Subjects at the highest temperatures exhaled about 30 times more chloroform than the same subjects at the lowest temperatures. This probably results from a decline in blood flow to the skin at the lower temperatures as the body seeks to conserve heat forcing the chloroform to diffuse over a much greater path length before encountering the blood. These results suggest that pharmacokinetic models need to employ temperature-dependent parameters. Two existing models predict quite different times of about 12 min and 29 min for chloroform flux through the stratum corneum to reach equilibrium. At 40 degrees C, the time for the flux to reach a near steady-state value is 6-9 min. Although uptake and decay processes involve several body compartments, the complicating effect of the stratum corneum lag time made it difficult to fit multiexponential curves to the data; however, a single-compartment model gave a satisfactory fit.

  10. Disposition of benzophenone-3 after dermal administration in male rats.

    PubMed

    Okereke, C S; Abdel-Rhaman, M S; Friedman, M A

    1994-08-01

    Benzophenone-3 (2-hydroxy-4-methoxybenzophenone, BZ-3) is a UV absorber that is used extensively in medicine, cosmetics and industry as a sunscreen and color fastener. Exposure to the chemical is through the dermal and oral route. Bioavailability of the chemical absorbed through the skin is different from that seen through the oral route. The disposition of BZ-3 was investigated after dermal administration of 100 mg/kg body weight (body wt.) in Sprague-Dawley rats. Blood samples were collected at various intervals and the parent compound and its metabolites were analyzed by HPLC. Absorption was rapid as the parent compound and its metabolites were detected in plasma 5 min post-administration. The half-life (t1/2) of absorption was 3.45 h corresponding to an absorption rate constant of 0.2 h-1. Peak plasma concentration of 35 +/- 4.5 micrograms/ml (mean +/- standard error of the mean, S.E.) was attained at 2.5 h post-administration. Disappearance from the plasma was biphasic with different half-lives (1.3 for alpha phase and 15.05 h. for beta phase), the area under the plasma concentration versus time curve was 211.1 +/- 38.2 micrograms/ml/h (mean +/- S.E). There was also extensive binding of BZ-3 and its metabolites to plasma proteins. Three metabolites were identified in plasma, 2,4-dihydroxybenzophenone (DHB) and 2,2'-dihydroxy-4-methoxybenzophenone (DHMB) were the major metabolites detected in the plasma, while 2,3,4-trihydroxybenzophenone (THB) was detected in trace amounts. Tissue distribution studies revealed that THB was the major metabolite followed by DHB (both free and conjugated) in all tissues examined. The liver contained the highest amount followed by the kidney, spleen and testes, respectively.

  11. Biomonitoring as a tool in the human health risk characterization of dermal exposure.

    PubMed

    Boogaard, P J

    2008-04-01

    Dermal exposure is an important factor in risk characterization. In occupational settings it becomes relatively more important because of the continuous reduction in inhalation exposure. In the public health arena, dermal exposure may also form a significant contribution to the total exposure. Dermal exposure, however, is difficult to assess directly because it is determined by a host of factors, which are difficult to quantify. As a consequence, dermal exposure is often estimated by application of models for external exposure. In combination with modeled or measured data for percutaneous penetration, these provide an estimate for the internal exposure that is directly related to the systemic effects. The advantages and drawbacks of EASE (Estimation and Assessment of Substance Exposure) and RISKOFDERM (Risk Assessment of Occupational Dermal Exposure), two models for external exposure that are mentioned in the Technical Guidance Document for the European Union risk assessments performed under the Existing Substances Regulation (EEC/793/93), are discussed. Although new chemicals regulation (REACh, 1907/2006/EC) is now in place in the European Union, the principles applied under the previous legislation do not change and the same models will continue to be used. The results obtained with these models for styrene, 2-butoxyethanol, and 1-methoxy-2-propanol in specific exposure scenarios are compared with an alternative method that uses biomonitoring data to assess dermal exposure. Actual external exposure measurements combined with measured or modeled percutaneous penetration data give acceptable results in risk assessment of dermal exposure, but modeled data of external dermal exposure should only be used if no other data are available. However, if available, biomonitoring should be considered the method of choice to assess (dermal) exposure.

  12. [Health protection for rural workers: the need to standardize techniques for quantifying dermal exposure to pesticides].

    PubMed

    Selmi, Giuliana da Fontoura Rodrigues; Trapé, Angelo Zanaga

    2014-05-01

    Quantification of dermal exposure to pesticides in rural workers, used in risk assessment, can be performed with different techniques such as patches or whole body evaluation. However, the wide variety of methods can jeopardize the process by producing disparate results, depending on the principles in sample collection. A critical review was thus performed on the main techniques for quantifying dermal exposure, calling attention to this issue and the need to establish a single methodology for quantification of dermal exposure in rural workers. Such harmonization of different techniques should help achieve safer and healthier working conditions. Techniques that can provide reliable exposure data are an essential first step towards avoiding harm to workers' health.

  13. Safety and toxicological evaluation of Aflapin: a novel Boswellia-derived anti-inflammatory product.

    PubMed

    Krishnaraju, A V; Sundararaju, D; Vamsikrishna, U; Suryachandra, R; Machiraju, G; Sengupta, K; Trimurtulu, G

    2010-11-01

    Boswellia serrata gum resin has been used for treatment of various ailments in different cultures for thousands of years. Aflapin(®) is a novel synergistic composition derived from B. serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. To assess the safety of Aflapin, a battery of acute and sub-acute toxicity studies were conducted in various animal models according to the OECD test guidelines. The acute oral LD50 of Aflapin was greater than 5000 mg/kg in female Sprague Dawley (SD) rats. Acute dermal LD50 of Aflapin was greater than 2000 mg/kg in SD rats. A primary dermal irritation study conducted using New Zealand White rabbits indicated that Aflapin is non-irritating to skin. Aflapin caused minimal ocular irritation in a primary eye irritation test conducted on New Zealand Albino rabbits. A repeat dose 28-day sub-acute oral toxicity study in SD rats demonstrated no significant signs of toxicity. Various evaluations including hematology, clinical chemistry, gross necropsy, and histopathology did not show any significant adverse changes. The NOAEL of Aflapin was found to be greater than 2500 mg/kg body weight. These studies demonstrate broad spectrum safety of Aflapin in animal models.

  14. The acute gastrointestinal subsyndrome of the acute radiation syndrome: a rhesus macaque model.

    PubMed

    MacVittie, Thomas J; Farese, Ann M; Bennett, Alexander; Gelfond, Daniel; Shea-Donohue, Terez; Tudor, Gregory; Booth, Catherine; McFarland, Emylee; Jackson, William

    2012-10-01

    The development of medical countermeasures against the acute gastrointestinal subsyndrome of the acute radiation syndrome in humans requires well characterized and validated animal models. These models must adhere to the criteria of the U.S. Food and Drug Administration's Animal Rule and consider the natural history and clinical context of the human radiation response and treatment in the nuclear terrorist scenario. The models must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity, including concurrent damage in other organs, such as the bone marrow, that may contribute to the overall mortality and morbidity. There are no such models of the gastrointestinal syndrome in response to total-body irradiation in the nonhuman primate. Herein, these parameters are defined for the rhesus macaque exposed to potentially lethal doses of radiation and administered medical management. Rhesus macaques (n = 69) were exposed bilaterally to 6 MV linear accelerator-derived photon total body irradiation to midline tissue (thorax) doses ranging from 10.0 to 14.0 Gy at 0.80 Gy min(-1). Following irradiation, all animals were administered supportive care consisting of fluids, anti-emetics, anti-diarrheal medication, antibiotics, blood transfusions, analgesics, and nutrition. The primary endpoint was survival at 15 d post-irradiation. Secondary endpoints included indices of dehydration, diarrhea, weight loss, hematological parameters, cellular histology of the small and large intestine, and mean survival time of decedents. Mortality within the 15-d in vivo study defined the acute gastrointestinal syndrome and provided an LD30/15 of 10.76 Gy, LD50/15 of 11.33 Gy, and an LD70/15 of 11.90 Gy. Intestinal crypt and villus loss were dose- and time-dependent with an apparent nadir 7 d post-irradiation and recovery noted thereafter. Severe myelosuppression and thrombocytopenia were noted in all animals, requiring the administration of

  15. Blaschko Linear Enamel Defects – A Marker for Focal Dermal Hypoplasia: Case Report of Focal Dermal Hypoplasia

    PubMed Central

    Gysin, Stefan; Itin, Peter

    2015-01-01

    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. PMID:26078738

  16. Wound Bed Preparation With a Dermal Substitute (Hyalomatrix® PA) Facilitates Re-epithelialization and Healing: Results of a Multicenter, Prospective, Observational Study on Complex Chronic Ulcers (The FAST Study).

    PubMed

    Caravaggi, Carlo; Grigoletto, Francesco; Scuderi, Nicolò

    2011-08-01

    The FAST study evaluated the performance and safety of Hyalomatrix® PA (a dermal substitute) in the treatment of chronic wounds of different etiology. This was a multicenter, prospective, observational study involving 70 Italian centers and 262 elderly patients. Patients were observed from the start of treatment with a dermal substitute (Hyalomatrix® PA [HPA]) until healthy dermal tissue suitable for a thin autograft was visible or until the growth of new epithelium from the wound edge was reported. Tracking the wound edge advancement was used to assess the dermal substitute's performance. The main endpoint was the reduction in threshold area (≥ 10%) of the ulcer. Treated ulcers were characterized as follows: 46% vascular, 25% diabetic foot, 12% traumatic wounds, 2% pressure ulcers and 15% other. Re-epithelization (≥ 10%) was achieved in 83% of ulcers in a median time of 16 days. Twenty-six percent (26%) of wounds achieved 75% re-epithelization within the 60-day follow-up period using only HPA treatment. A follow-up showed that 84% of ulcers achieved complete re-epithelialization by secondary intention. These findings indicate that HPA is a safe and effective dermal substitute. The results show that the re-epithelization process following HPA treatment is independent upon etiology, area, and depth of the ulcer, and treatment is more effective on acute ulcer formation.

  17. Contact between dermal papilla cells and dermal sheath cells enhances the ability of DPCs to induce hair growth.

    PubMed

    Yamao, Mikaru; Inamatsu, Mutsumi; Ogawa, Yuko; Toki, Hiroshi; Okada, Taro; Toyoshima, Koh-ei; Yoshizato, Katsutoshi

    2010-12-01

    We previously showed that cultured rat dermal papilla cells (DPCs) retain their hair-inducing capacity on afollicular epidermal cell (EPCs). Here, we examined the hair growth-inducing capacity of differently subcultured DPCs by transplanting them, along with rat EPCs, onto the backs of nude mice (graft chamber assay). DPCs at passage (p) 6 (DPCs(p6) or, more generally, low-passage DPCs) induced hair formation. However, DPCs(p>30) (high-passage DPCs) had no such activity and induced only subepidermal hair follicles (HFs) that were not encapsulated by the dermal sheath (DS). Thus, we examined the effect of DS cells (DSCs(p=1)) on the ability of DPCs(p=60) to induce hair growth by testing a mixture of these two cell types (cotransplant) in the graft chamber assay, in which DSCs(p=1) and DPCs(p=60) were labeled with enhanced green fluorescent protein (EGFP) and 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI), respectively. These cotransplants generated hairs as actively as did DPCs(p=6) transplants. Their HFs were encapsulated with EGFP(+)-DS and had DPs consisting largely of EGFP(+)-DPCs (47%) and DiI(+)-DPCs (43%), indicating a major contribution of DSC(p=1)-derived DPCs to HF induction. In addition, the results of in vitro coculture of DPCs(p=60) and DSCs(p=1) suggest that high-passage DPCs stimulate the expression of certain trichogenic genes in DSCs.

  18. Acute Dermal Irritation Study of JP-8 and S-8 in New Zealand White Rabbits

    DTIC Science & Technology

    2011-01-01

    Severe erythema ( beet or crimson red) to slight eschar formation (injuries in depth) Value Edema Formation 0 No edema 1 Very slight edema (barely...severe erythema (definite red in color and area well defined) 4 Severe erythema ( beet or crimson red) to slight eschar formation (injuries in depth

  19. Acute Toxicity of Amorphous Silica Nanoparticles in Intravenously Exposed ICR Mice

    PubMed Central

    Wang, Wen; Jin, Minghua; Du, Zhongjun; Li, Yanbo; Duan, Junchao; Yu, Yongbo; Sun, Zhiwei

    2013-01-01

    This study aimed to evaluate the acute toxicity of intravenously administrated amorphous silica nanoparticles (SNPs) in mice. The lethal dose, 50 (LD50), of intravenously administrated SNPs was calculated in mice using Dixon's up-and-down method (262.45±33.78 mg/kg). The acute toxicity was evaluated at 14 d after intravenous injection of SNPs at 29.5, 103.5 and 177.5 mg/kg in mice. A silicon content analysis using ICP-OES found that SNPs mainly distributed in the resident macrophages of the liver (10.24%ID/g), spleen (34.78%ID/g) and lung (1.96%ID/g). TEM imaging showed only a small amount in the hepatocytes of the liver and in the capillary endothelial cells of the lung and kidney. The levels of serum LDH, AST and ALT were all elevated in the SNP treated groups. A histological examination showed lymphocytic infiltration, granuloma formation, and hydropic degeneration in liver hepatocytes; megakaryocyte hyperplasia in the spleen; and pneumonemia and pulmonary interstitial thickening in the lung of the SNP treated groups. A CD68 immunohistochemistry stain indicated SNPs induced macrophage proliferation in the liver and spleen. The results suggest injuries induced by the SNPs in the liver, spleen and lungs. Mononuclear phagocytic cells played an important role in the injury process. PMID:23593469

  20. Respiratory failure induced by acute organophosphate poisoning in rats: effects of vagotomy.

    PubMed

    Gaspari, Romolo J; Paydarfar, David

    2009-03-01

    Acute organophosphate (OP) poisoning causes respiratory failure through two mechanisms: central apnea and pulmonary dysfunction. The vagus nerve is involved in both the central control of respiratory rhythm as well as the control of pulmonary vasculature, airways and secretions. We used a rat model of acute OP poisoning with and without a surgical vagotomy to explore the role of the vagus in OP-induced respiratory failure. Dichlorvos (2,2-dichlorovinyl dimethyl phosphate) injection (100mg/kg subcutaneously, 3 x LD50) resulted in progressive hypoventilation and apnea in all animals, irrespective of whether or not the vagi were intact. However, vagotomized animals exhibited a more rapidly progressive decline in ventilation and oxygenation. Artificial mechanical ventilation initiated at onset of apnea resulted in improvement in oxygenation and arterial pressure in poisoned animals with no difference between vagus intact or vagotomized animals. Our observations suggest that vagal mechanisms have a beneficial effect during the poisoning process. We speculate that vagally mediated feedback signals from the lung to the brainstem serve as a modest protective mechanism against central respiratory depressive effects of the poison and that bulbar-generated efferent vagal signals do not cause sufficient pulmonary dysfunction to impair pulmonary gas exchange.

  1. Safety assessment of vitacoxib: Acute and 90-day sub-chronic oral toxicity studies.

    PubMed

    Wang, Jianzhong; Sun, Feifei; Tang, Shusheng; Zhang, Suxia; Lv, Pengyue; Li, Jing; Cao, Xingyuan

    2017-02-24

    Vitacoxib, is a newly developed coxibs NSAID (selective inhibitors of cyclooxygenase-2). To date, no experimental data have been published concerning its safety for use as an additive in the human diet. In the present study, we assessed the acute and sub-chronic toxicity of vitacoxib administered by gavage. The acute toxicity tests in Sprague Dawley (SD) rats and ICR mice demonstrated that vitacoxib at a dose of 5000 mg/kg BW failed to alter any of the parameters studied. In the 90-day sub-chronic toxicity test, vitacoxib was administered to SD rats at the doses of 0 (control), 5, 10, 20, 30, and 60 mg/kg BW. The results demonstrated that there were no significant differences for most indexes of sub-chronic toxicity throughout the experiment at the dose of 5-20 mg/kg BW, indicating no apparent dose-dependent. However, there were significant histopathology changes in the liver and kidney, and alterations in some biochemical parameters in the 60 mg/kg BW group. Based on these findings, the gavage LD50 was determined to be > 5000 mg/kg in SD rats and ICR mice, and the 90-day gavage no-observed-adverse-effect level (NOAEL) of vitacoxib was considered to be 20 mg/kg BW under the present study conditions.

  2. Acute and subacute toxicity assessment of lutein in lutein-deficient mice.

    PubMed

    Nidhi, Bhatiwada; Baskaran, Vallikannan

    2013-10-01

    Dietary lutein consumption is lower than the actual recommended allowances to prevent macular degeneration; thus dietary lutein supplements have been recommended. This study aimed to investigate potential adverse effect of lutein from Tagetes erecta in lutein-deficient (LD) male mice. Preliminary acute toxicity study revealed that the LD50 exceeded the highest dose of 10000 mg/kg BW. In a subacute study, male mice were gavaged with 0, 100, 1000 mg/kg BW/day for a period of 4 wk. Plasma lutein levels increased dose dependently (P < 0.01) after acute and subacute feeding of lutein in LD mice. Compared to the control (peanut oil without lutein) group, no treatment-related toxicologically significant effects of lutein were prominent in clinical observation, ophthalmic examinations, body, and organ weights. Further, no toxicologically significant findings were eminent in hematological, histopathological, and other clinical chemistry parameters. In the oral subacute toxicity study, the no-observed-adverse-effect level (NOAEL) for lutein in LD mice was determined as 1000 mg/kg/day, the highest dose tested.

  3. Photoprotective effect and acute oral systemic toxicity evaluation of the novel heterocyclic compound LQFM048.

    PubMed

    Vinhal, Daniela C; de Ávila, Renato Ivan; Vieira, Marcelo S; Luzin, Rangel M; Quintino, Michelle P; Nunes, Liliane M; Ribeiro, Antonio Carlos Chaves; de Camargo, Henrique Santiago; Pinto, Angelo C; Dos Santos Júnior, Helvécio M; Chiari, Bruna G; Isaac, Vera; Valadares, Marize C; Martins, Tatiana Duque; Lião, Luciano M; de S Gil, Eric; Menegatti, Ricardo

    2016-08-01

    The new heterocyclic derivative LQFM048 (3) (2,4,6-tris ((E)-ethyl 2-cyano-3-(4-hydroxy-3-methoxyphenyl)acrylate)-1,3,5-triazine) was originally designed through the molecular hybridization strategy from Uvinul® T 150 (1) and (E)-ethyl 2-cyano-3-(4hydroxy-3-methoxyphenyl)acrylate (2) sunscreens, using green chemistry approach. This compound was obtained in global yields (80%) and showed an interesting redox potential. In addition, it is thermally stable up to temperatures around 250°C. It was observed that LQFM048 (3) showed a low degradation after 150min of sunlight exposure at 39°C, whereas the extreme radiation conditions induced a considerable photodegradation of the LQFM048 (3), especially when irradiated by VIS and VIS+UVA. During the determination of sun protection factor, LQFM048 (3) showed interesting results, specially as in association with other photoprotective compounds and commercial sunscreen. Additionally, the compound (3) did not promote cytotoxicity for 3T3 fibroblasts. Moreover, it was not able to trigger acute oral systemic toxicity in mice, being classified as a compound with low acute toxicity hazard (2.000mg/kg>LD50<5.000mg/kg). Therefore, this compound synthesized using green chemistry approach is promising showing potential to development of a new sunscreen product with advantage of presenting redox potential, indicating antioxidant properties.

  4. Acute toxicity effects of Prunus avium fruit extract and selection of optimum dose against radiation exposure.

    PubMed

    Sisodia, Rashmi; Sharma, K; Singh, Smita

    2009-01-01

    The objective of the study was to evaluate the acute toxicity of different doses of the methanolic extract of the fruit pulp of Prunus avium (family Rosaceae), which is used ethno-medicinally for the treatment of various diseases, and to find out the optimal dose of Prunus avium extract against 10 Gy gamma-radiation exposure. To test acute toxicity in mice, different doses of PAE (Prunus avium fruit extract) were given orally for 15 consecutive days, after which the animals were observed for another 15 days; the LD50/15 of the methanolic extract was calculated to be 4.947 gm/kg body weight (b.wt). In optimum dose selection against radiation exposure, oral administration of 450 mg/kg b.wt/d of PAE for 15 consecutive days before exposure to 10 Gy of gamma-radiation was found to afford maximum protection in terms of body weight and survivability of the mice in comparison to other doses.

  5. Hypoglycemic activity and acute oral toxicity of chromium methionine complexes in mice.

    PubMed

    Tang, Hai-yan; Xiao, Qing-gui; Xu, Hong-bin; Zhang, Yi

    2015-01-01

    The hypoglycemic activity of chromium methionine (CrMet) in alloxan-induced diabetic (AID) mice was investigated and compared with those of chromium trichloride hexahydrate (CrCl3·6H2O) and chromium nicotinate (CrNic) through a 15-day feeding experiment. The acute oral toxicity of CrMet was also investigated in ICR (Institute for Cancer Research) mice by a single oral gavage. The anti-diabetic activity of CrMet was explored in detail from the aspects of body weight (BW), blood glucose, triglyceride, total cholesterol, liver glycogen levels, aspartate transaminase (AST) and alanine transaminase (ALT) levels. The obtained results showed that CrMet had beneficial effects on glucose and lipid metabolism, and might possess hepatoprotective efficacy for diabetes. Daily treatment with 500 and 1000μg Cr/kg BW of CrMet in AID mice for 15 days indicated that this low-molecular-weight organic chromium complex had better bioavailability and more beneficial effects on diabetics than CrCl3·6H2O. CrMet also had advantage over CrNic in the control of AST and ALT activities. Acute toxicity studies revealed that CrMet had low toxicity potential and relatively high safety margins in mice with the LD50 value higher than 10.0g/kg BW. These findings suggest that CrMet might be of potential value in the therapy and protection of diabetes.

  6. Dermal bone in early tetrapods: a palaeophysiological hypothesis of adaptation for terrestrial acidosis.

    PubMed

    Janis, Christine M; Devlin, Kelly; Warren, Daniel E; Witzmann, Florian

    2012-08-07

    The dermal bone sculpture of early, basal tetrapods of the Permo-Carboniferous is unlike the bone surface of any living vertebrate, and its function has long been obscure. Drawing from physiological studies of extant tetrapods, where dermal bone or other calcified tissues aid in regulating acid-base balance relating to hypercapnia (excess blood carbon dioxide) and/or lactate acidosis, we propose a similar function for these sculptured dermal bones in early tetrapods. Unlike the condition in modern reptiles, which experience hypercapnia when submerged in water, these animals would have experienced hypercapnia on land, owing to likely inefficient means of eliminating carbon dioxide. The different patterns of dermal bone sculpture in these tetrapods largely correlates with levels of terrestriality: sculpture is reduced or lost in stem amniotes that likely had the more efficient lung ventilation mode of costal aspiration, and in small-sized stem amphibians that would have been able to use the skin for gas exchange.

  7. LPS-Stimulated Human Skin-Derived Stem Cells Enhance Neo-Vascularization during Dermal Regeneration

    PubMed Central

    Rapoport, Daniel H.; Kruse, Charli; Schumann, Sandra; Stang, Felix H.; Siemers, Frank; Matthießen, Anna E.

    2015-01-01

    High numbers of adult stem cells are still required to improve the formation of new vessels in scaffolds to accelerate dermal regeneration. Recent data indicate a benefit for vascularization capacity by stimulating stem cells with lipopolysaccharide (LPS). In this study, stem cells derived from human skin (SDSC) were activated with LPS and seeded in a commercially available dermal substitute to examine vascularization in vivo. Besides, in vitro assays were performed to evaluate angiogenic factor release and tube formation ability. Results showed that LPS-activated SDSC significantly enhanced vascularization of the scaffolds, compared to unstimulated stem cells in vivo. Further, in vitro assays confirmed higher secretion rates of proangiogenic as well as proinflammatoric factors in the presence of LPS-activated SDSC. Our results suggest that combining activated stem cells and a dermal substitute is a promising option to enhance vascularization in scaffold-mediated dermal regeneration. PMID:26565617

  8. ESTIMATING CONTAMINANT DOSE FOR INTERMITTENT DERMAL CONTACT: MODEL DEVELOPMENT, TESTING, AND APPLICATION

    EPA Science Inventory

    Assessments of aggregate exposure to pesticides and other surface contamination in residential environments are often driven by assumptions about dermal contacts. Accurately predicting cumulative doses from realistic skin contact scenarios requires characterization of exposure sc...

  9. Advective and diffusive dermal processes for estimating terrestrial amphibian pesticide exposure

    EPA Science Inventory

    Background/Question/Methods Dermal exposure presents a potentially significant but understudied route for pesticide uptake in terrestrial amphibians. Historically, evaluation of pesticide risk to both amphibians and reptiles has been achieved by comparing ingestion and inhalat...

  10. BREATH MEASUREMENT AND MODELS TO ASSESS VOC DERMAL ABSORPTION IN WATER

    EPA Science Inventory

    Dermal exposure to volatile organic compounds (VOCs) in water results from environmental contamination of surface, ground-, and drinking waters. This exposure occurs both in occupational and residential settings. Compartmental models incorporating body burden measurements have ...

  11. USE OF THE MACROACTIVITY APPROACH TO ASSESS CHILDREN'S DERMAL EXPOSURE TO PESTICIDES IN RESIDENTIAL ENVIRONMENTS

    EPA Science Inventory

    In the macroactivity approach, dermal exposure is estimated using empirically-derived transfer coefficients (TC) to aggregate the mass transfer associated with a series of contacts with a contaminated medium. The macroactivity approach affords the possibility of developing scr...

  12. Dermal morphogenesis controls lateral line patterning during postembryonic development of teleost fish.

    PubMed

    Wada, Hironori; Ghysen, Alain; Satou, Chie; Higashijima, Shin-Ichi; Kawakami, Koichi; Hamaguchi, Satoshi; Sakaizumi, Mitsuru

    2010-04-15

    The lateral line system displays highly divergent patterns in adult teleost fish. The mechanisms underlying this variability are poorly understood. Here, we demonstrate that the lateral line mechanoreceptor, the neuromast, gives rise to a series of accessory neuromasts by a serial budding process during postembryonic development in zebrafish. We also show that accessory neuromast formation is highly correlated to the development of underlying dermal structures such as bones and scales. Abnormalities in opercular bone morphogenesis, in endothelin 1-knockdown embryos, are accompanied by stereotypic errors in neuromast budding and positioning, further demonstrating the tight correlation between the patterning of neuromasts and of the underlying dermal bones. In medaka, where scales form between peridermis and opercular bones, the lateral line displays a scale-specific pattern which is never observed in zebrafish. These results strongly suggest a control of postembryonic neuromast patterns by underlying dermal structures. This dermal control may explain some aspects of the evolution of lateral line patterns.

  13. FEASIBILITY OF USING THE MACROACTIVITY APPROACH TO ASSESS CHILDREN'S DERMAL EXPOSURE TO PESTICIDES

    EPA Science Inventory

    Results derived from an initial assessment of critical exposure pathways for children indicate that dermal contact may result in high residential exposures to pesticides. However, data on children's exposures and activities are insufficient to support quantitative assessments ...

  14. STUDY TO TEST THE FEASIBILITY OF USING THE MACROACTIVITY APPROACH TO ASSESS DERMAL EXPOSURE

    EPA Science Inventory

    In the macroactivity approach, dermal exposure is estimated using empirically-derived transfer coefficients to aggregate the mass transfer associated with a series of contacts with a contaminated medium. The macroactivity approach affords the possibility of developing screenin...

  15. Acute and subchronic toxicity as well as evaluation of safety pharmacology of eucalyptus oil-water emulsions

    PubMed Central

    Hu, Zhiqiang; Feng, Ruizhang; Xiang, Fa; Song, Xu; Yin, Zhongqiong; Zhang, Chao; Zhao, Xinghong; Jia, Renyong; Chen, Zhenzhen; Li, Li; Yin, Lizi; Liang, Xiaoxia; He, Changliang; Shu, Gang; Lv, Cheng; Zhao, Ling; Ye, Gang; Shi, Fei

    2014-01-01

    Essential oil has performed a variety of indirect services used as insect/pest repellent. The present study investigated the acute and subchronic toxicity of eucalyptus oil emulsion in water (EOE). In addition, we conduct safety pharmacology evaluation of EOE to supplement the toxicity tests and provide a basis for a comprehensive understanding of the toxicity of EOE. Acute administration of EOE was done as single dose from 2772 mg to 5742 mg of EOE per kg/bodyweight (b.wt.) and subchronic toxicity study for thirty days was done by daily oral administration of EOE at doses of 396, 792 and 1188 mg/kg b.wt. In SPF SD rats. The acute toxicity study showed the LD50 of EOE was 3811.5 mg/kg. The subchronic toxicity study suggested the high-dose and middle-dose EOE slowed down the growth of male rats. The clinical pathology showed the high-dose and middle-dose EOE could cause damage to liver and kidney. The safety pharmacology indicated that EOE had no side effects on rats. These results suggest that EOE is a safe veterinary medicine for external use. PMID:25663980

  16. Antifungal activity of recombinant human macrophage colony-stimulating factor in models of acute and chronic candidiasis in the rat.

    PubMed

    Vitt, C R; Fidler, J M; Ando, D; Zimmerman, R J; Aukerman, S L

    1994-02-01

    Models of acute and chronic candidiasis were developed in Fischer 344 rats to evaluate the therapeutic efficacy of recombinant human macrophage colony-stimulating factor (rhM-CSF) alone and in combination with the antifungal agent fluconazole. In the acute model, rats were challenged by intravenous injection with 2 x 10(6) Candida albicans, approximately 4 times the LD50. Daily subcutaneous (sc) bolus injections of rhM-CSF for 10 days plus a single sc bolus dose of 0.3 mg/kg of fluconazole improved the median survival time from 5 days (32% survival) with fluconazole alone to > 30 days (88% survival) in the rhM-CSF- and fluconazole-treated rats. In the chronic model, daily sc bolus injections of rhM-CSF for 10 days plus a single sc bolus dose of 1.0 mg/kg of fluconazole decreased the median titer of C. albicans cultured from the kidneys by 10-fold at 15 and 30 days after infection. These studies showed that rhM-CSF treatment improved the therapeutic outcome in both the acute and chronic rat model of candidiasis when used with fluconazole, a standard fungistatic agent.

  17. Dermal melanin concentration of yellow perch Perca flavescens in relation to water transparency.

    PubMed

    Rheault, G; Langevin, M; Cabana, G; Glémet, H

    2015-11-01

    A positive relationship was observed between Secchi disc depth and dermal melanin concentration in yellow perch Perca flavescens sampled from 11 humic lakes located on the Canadian Shield in southern Quebec (Canada). Secchi disc depth explained 23% of the variations of dermal melanin concentration. Secchi disc depth and thus water transparency appear to have a positive influence on melanin production in the dermis of P. flavescens.

  18. Laser-induced transepidermal elimination of dermal content by fractional photothermolysis

    NASA Astrophysics Data System (ADS)

    Hantash, Basil M.; Bedi, Vikramaditya P.; Sudireddy, Vasanthi; Struck, Steven K.; Herron, G. Scott; Chan, Kin Foong

    2006-07-01

    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 µm or 140 µm 1/e2 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

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

    PubMed

    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

  20. Sexual dimorphisms in the dermal denticles of the lesser-spotted catshark, Scyliorhinus canicula (Linnaeus, 1758).

    PubMed

    Crooks, Neil; Babey, Lucy; Haddon, William J; Love, Adrian C; Waring, Colin P

    2013-01-01

    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.

  1. FIZZ1-induced myofibroblast transdifferentiation from adipocytes and its potential role in dermal fibrosis and lipoatrophy.

    PubMed

    Martins, Vanessa; Gonzalez De Los Santos, Francina; Wu, Zhe; Capelozzi, Vera; Phan, Sem H; Liu, Tianju

    2015-10-01

    Subcutaneous lipoatrophy characteristically accompanies dermal fibrosis with de novo emergence of myofibroblasts such as in systemic sclerosis or scleroderma. Recently dermal adipocytes were shown to have the capacity to differentiate to myofibroblasts in an animal model. Transforming growth factor β can induce this phenomenon in vitro; however its in vivo significance is unclear. Because found in inflammatory zone 1 (FIZZ1) is an inducer of myofibroblast differentiation but an inhibitor of adipocyte differentiation, we investigated its potential role in adipocyte transdifferentiation to myofibroblast in dermal fibrosis. FIZZ1 caused significant and rapid suppression of the expression of fatty acid binding protein 4 and peroxisome proliferator-activated receptor-γ in adipocytes, consistent with dedifferentiation with loss of lipid and Oil Red O staining. The suppression was accompanied subsequently with stimulation of α-smooth muscle actin and type I collagen expression, indicative of myofibroblast differentiation. In vivo FIZZ1 expression was significantly elevated in the murine bleomycin-induced dermal fibrosis model, which was associated with significant reduction in adipocyte marker gene expression and subcutaneous lipoatrophy. Finally, FIZZ1 knockout mice exhibited significantly reduced bleomycin-induced dermal fibrosis with greater preservation of the subcutaneous fat than wild-type mice. These findings suggested that the FIZZ1 induction of adipocyte transdifferentiation to myofibroblast might be a key pathogenic mechanism for the accumulation of myofibroblasts in dermal fibrosis.

  2. Characterization of dermal plates from armored catfish Pterygoplichthys pardalis reveals sandwich-like nanocomposite structure.

    PubMed

    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.

  3. Restorative effect of hair follicular dermal cells on injured human hair follicles in a mouse model.

    PubMed

    Yamao, Mikaru; Inamatsu, Mutsumi; Okada, Taro; Ogawa, Yuko; Ishida, Yuji; Tateno, Chise; Yoshizato, Katsutoshi

    2015-03-01

    No model is available for examining whether in vivo-damaged human hair follicles (hu-HFs) are rescued by transplanting cultured hu-HF dermal cells (dermal papilla and dermal sheath cells). Such a model might be valuable for examining whether in vivo-damaged hu-HFs such as miniaturized hu-HFs in androgenic alopecia are improvable by auto-transplanting hu-HF dermal cells. In this study, we first developed mice with humanized skin composed of hu-keratinocytes and hu-dermal fibroblasts. Then, a 'humanized scalp model mouse' was generated by transplanting hu-scalp HFs into the humanized skin. To demonstrate the usability of the model, the lower halves of the hu-HFs in the model were amputated in situ, and cultured hu-HF dermal cells were injected around the amputated area. The results demonstrated that the transplanted cells contributed to the restoration of the damaged HFs. This model could be used to explore clinically effective technologies for hair restoration therapy by autologous cell transplantation.

  4. Successful treatment of complex traumatic and surgical wounds with a foetal bovine dermal matrix.

    PubMed

    Hayn, Ernesto

    2014-12-01

    A foetal bovine dermal repair scaffold (PriMatrix, TEI Biosciences) was used to treat complex surgical or traumatic wounds where the clinical need was to avoid skin flaps and to build new tissue in the wound that could be reepithelialised from the wound margins or closed with a subsequent application of a split-thickness skin graft (STSG). Forty-three consecutive cases were reviewed having an average size of 79·3 cm(2) , 50% of which had exposed tendon and/or bone. In a subset of wounds (44·7%), the implantation of the foetal dermal collagen scaffold was also augmented with negative pressure wound therapy (NPWT). Complete wound healing was documented in over 80% of the wounds treated, whether the wound was treated with the foetal bovine dermal scaffold alone (95·2%) or when supplemented with NPWT (82·4%). The scaffold successfully incorporated into wounds with exposed tendon and/or bone to build vascularised, dermal-like tissue. The new tissue in the wound supported STSGs however, in the majority of the cases (88·3%); wound closure was achieved through reepithelialisation of the incorporated dermal scaffold by endogenous wound keratinocytes. The foetal bovine dermal repair scaffold was found to offer an effective alternative treatment strategy for definitive closure of challenging traumatic or surgical wounds on patients who were not suitable candidates for tissue flaps.

  5. The application of dermal papillary rings in dermatology by in vivo confocal laser scanning microscopy

    NASA Astrophysics Data System (ADS)

    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)

    PubMed Central

    Crooks, Neil; Babey, Lucy; Haddon, William J.; Love, Adrian C.; Waring, Colin P.

    2013-01-01

    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. PMID:24116179

  7. Evaluation of electrospun PCL/gelatin nanofibrous scaffold for wound healing and layered dermal reconstitution.

    PubMed

    Chong, E J; Phan, T T; Lim, I J; Zhang, Y Z; Bay, B H; Ramakrishna, S; Lim, C T

    2007-05-01

    The current design requirement for a tissue engineering skin substitute is that of a biodegradable scaffold through which fibroblasts can migrate and populate. This artificial "dermal layer" needs to adhere to and integrate with the wound, which is not always successful for the current artificial dermal analogues available. The high cost of these artificial dermal analogues also makes their application prohibitive both to surgeons and patients. We propose a cost-effective composite consisting of a nanofibrous scaffold directly electrospun onto a polyurethane dressing (Tegaderm, 3M Medical) - which we call the Tegaderm-nanofiber (TG-NF) construct - for dermal wound healing. Cell culture is performed on both sides of the nanofibrous scaffold and tested for fibroblast adhesion and proliferation. It is hoped that these studies will result in a fibroblast-populated three-dimensional dermal analogue that is feasible for layered applications to build up thickness of dermis prior to re-epithelialization. Results obtained in this study suggest that both the TG-NF construct and dual-sided fibroblast-populated nanofiber construct achieved significant cell adhesion, growth and proliferation. This is a successful first step for the nanofiber construct in establishing itself as a suitable three-dimensional scaffold for autogenous fibroblast populations, and providing great potential in the treatment of dermal wounds through layered application.

  8. Enhanced anti-diabetic activity of a combination of chromium(III) malate complex and propolis and its acute oral toxicity evaluation.

    PubMed

    Wu, Xiang-Yang; Li, Fang; Zhao, Ting; Mao, Guang-Hua; Li, Jing; Qu, Hong-Yuan; Ren, Yue-Na; Yang, Liu-Qing

    2012-07-01

    In order to obtain the additional benefit of anti-diabetic activity and protective effects of liver injury for diabetes, the anti-diabetic effect and acute oral toxicity of a combination of chromium(III) malate complex (Cr(2)(LMA)(3)) and propolis were assessed. The anti-diabetic activity of the combination of the Cr(2)LMA(3) and propolis was compared with Cr(2)(LMA)(3) and propolis alone in alloxan-induced diabetic mice by daily oral gavage for a period of 2 weeks. Acute oral toxicity of the combination of the Cr(2)LMA(3) and propolis was tested using ICR mice at the dose of 1.0-5.0 g/kg body mass by a single oral gavage and observed for a period of 2 weeks. The results of the anti-diabetic activity of the combination from the aspects of blood glucose level, liver glycogen level, and the activities of aspartate transaminase, alanine transaminase, and alkaline phosphatase indicated that the increased anti-diabetic activity and the protective efficacy of liver injury for diabetes were observed. In acute toxicity study, LD(50) (median lethal dose) value for the combination was greater than 5.0 g/kg body mass. The combination of Cr(2)LMA(3) and propolis might represent the nutritional supplement with potential therapeutic value to control blood glucose and exhibit protective efficacy of liver injury for diabetes and non-toxicity in acute toxicity.

  9. HYALURONIC ACID IN DERMAL REJUVENATION: AN IN VITRO STUDY.

    PubMed

    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. Optical coherence tomography: imaging architect for dermal microdialysis in psoriasis

    NASA Astrophysics Data System (ADS)

    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.

  11. Nanoparticles and their interactions with the dermal barrier

    PubMed Central

    Stracke, Frank; Hansen, Steffi; Schaefer, Ulrich F

    2009-01-01

    The dermal application of drugs is promising due to the ease of application. In this context nano-scale carrier systems were already evaluated in several studies with respect to the skin interaction and the impact on drug penetration. At the same time the upcoming production of engineered nano-scale materials requires a thorough safety evaluation. Drug delivery as well as risk assessment depends crucially on the ability of such carriers to overcome the skin barrier and reach deeper tissue layers. Therefore, the interaction of nanoparticles with skin and especially skin models is an intriguing field. However, the data obtained do not show a clear image on the effect of nano-carriers. Especially the penetration of such particles is an open and controversially discussed topic. The literature reports different results mainly on pig or murine skin showing strong penetration (pig and mouse) or the opposite. Looking only at the sizes of the particles also no conclusive picture can be obtained. Nevertheless, size is regarded to play an important role for skin penetration. Furthermore, the state of the skin influences penetration (hydration) and the mechanical stress is of outmost importance. PMID:20592791

  12. Potential dermal wound healing agent in Blechnum orientale Linn

    PubMed Central

    2011-01-01

    Background Blechnum orientale Linn. (Blechnaceae) is used ethnomedicinally to treat wounds, boils, blisters or abscesses and sores, stomach pain and urinary bladder complaints. The aim of the study was to validate the ethnotherapeutic claim and to evaluate the effects of B. orientale water extract on wound healing activity. Methods Water extract of B. orientale was used. Excision wound healing activity was examined on Sprague-Dawley rats, dressed with 1% and 2% of the water extract. Control groups were dressed with the base cream (vehicle group, negative control) and 10% povidone-iodine (positive control) respectively. Healing was assessed based on contraction of wound size, mean epithelisation time, hydroxyproline content and histopathological examinations. Statistical analyses were performed using one way ANOVA followed by Tukey HSD test. Results Wound healing study revealed significant reduction in wound size and mean epithelisation time, and higher collagen synthesis in the 2% extract-treated group compared to the vehicle group. These findings were supported by histolopathological examinations of healed wound sections which showed greater tissue regeneration, more fibroblasts and angiogenesis in the 2% extract-treated group. Conclusions The ethnotherapeutic use of this fern is validated. The water extract of B. orientale is a potential candidate for the treatment of dermal wounds. Synergistic effects of both strong antioxidant and antibacterial activities in the extract are deduced to have accelerated the wound repair at the proliferative phase of the healing process. PMID:21835039

  13. Developmental timing of perchlorate exposure alters threespine stickleback dermal bone

    PubMed Central

    Furin, Christoff G.; von Hippel, Frank A.; Postlethwait, John; Buck, C. Loren; Cresko, William A.; O’Hara, Todd M.

    2015-01-01

    Adequate levels of thyroid hormone are critical during development and metamorphosis, and for maintaining metabolic homeostasis. Perchlorate, a common contaminant of water sources, inhibits thyroid function in vertebrates. We utilized threespine stickleback (Gasterosteus aculeatus) to determine if timing of perchlorate exposure during development impacts adult dermal skeletal phenotypes. Fish were exposed to water contaminated with perchlorate (30 mg/L or 100 mg/L) beginning at 0, 3, 7, 14, 21, 42, 154 or 305 days post fertilization until sexual maturity at one year of age. A reciprocal treatment moved stickleback from contaminated to clean water on the same schedule providing for different stages of initial exposure and different treatment durations. Perchlorate exposure caused concentration-dependent significant differences in growth for some bony traits. Continuous exposure initiated within the first 21 days post fertilization had the greatest effects on skeletal traits. Exposure to perchlorate at this early stage can result in small traits or abnormal skeletal morphology of adult fish which could affect predator avoidance and survival. PMID:25753171

  14. Oral phenotype and variation in focal dermal hypoplasia.

    PubMed

    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.

  15. Evaluation of dermal symptoms in hypothyroidism and hyperthyroidism.

    PubMed

    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.

  16. The effect of thrombocytopenia on dermal wound healing.

    PubMed

    Szpaderska, Anna M; Egozi, Eric I; Gamelli, Richard L; DiPietro, Luisa A

    2003-06-01

    The immediate appearance of platelets in wounds and the ability of platelets to release growth factors suggest that platelets are an important trigger of the tissue repair process. To examine the effect of systemic thrombocytopenia on both the inflammatory and proliferative aspects of wound healing, adult mice were rendered thrombocytopenic by intraperitoneal administration of a rabbit antimouse platelet serum. Full-thickness excisional dermal wounds were prepared and analyzed for inflammatory cell content, growth factor production, reepithelialization, collagen synthesis, and angiogenesis at multiple time points after injury. Compared to control mice, thrombocytopenic mice exhibited significantly altered wound inflammation. Wounds of thrombocytopenic mice contained significantly more macrophages and T cells, yet exhibited neutrophil content similar to wounds from control mice. Surprisingly, thrombocytopenic mice exhibited no delay in the reparative aspects of wound healing. The rate of wound reepithelialization, collagen synthesis, and angiogenesis was nearly identical for thrombocytopenic and control mice. Analysis of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor beta1, keratinocyte growth factor, and epidermal growth factor revealed no difference in the levels of these growth factors in the wounds of control and thrombocytopenic mice. Taken together, the results suggest that the presence of platelets may influence wound inflammation, but that platelets do not significantly affect the proliferative aspects of repair, including wound closure, angiogenesis, and collagen synthesis.

  17. Sunscreens promote repair of ultraviolet radiation-induced dermal damage.

    PubMed

    Kligman, L H; Akin, F J; Kligman, A M

    1983-08-01

    Chronic UV irradiation profoundly damages the dermis of human and animal skin. These alterations were thought to be irreversible. Recently, we showed that substantial repair occurred in hairless mice after stopping UV exposure. A band of new connective tissue was laid down subepidermally. The present study focussed on whether repair would occur if animals were protected by sunscreens after dermal damage was induced and irradiation was continued. Albino hairless mice were exposed to Westinghouse FS20 sunlamps thrice weekly for 30 weeks. The daily dose of UV (UVB + UVA) was 0.17 J/cm2. Sunscreens of sun protection factors (SPF) 6 and 15 were applied after 10 and 20 weeks of irradiation. Biopsies were taken at 10, 20, 30, and 45 weeks of the experiment. With both sunscreens, especially SPF-15, previously damaged dermis was repaired during continued irradiation. Repair occurred in situ and, in severely damaged skin, in the novel form of subepidermal reconstruction zones of new connective tissue with parallel collagen bundles and a network of fine elastic fibers.

  18. Dkk2/Frzb in the dermal papillae regulates feather regeneration.

    PubMed

    Chu, Qiqi; Cai, Linyan; Fu, Yu; Chen, Xi; Yan, Zhipeng; Lin, Xiang; Zhou, Guixuan; Han, Hao; Widelitz, Randall B; Chuong, Cheng-ming; Wu, Wei; Yue, Zhicao

    2014-03-15

    Avian feathers have robust growth and regeneration capability. To evaluate the contribution of signaling molecules and pathways in these processes, we profiled gene expression in the feather follicle using an absolute quantification approach. We identified hundreds of genes that mark specific components of the feather follicle: the dermal papillae (DP) which controls feather regeneration and axis formation, the pulp mesenchyme (Pp) which is derived from DP cells and nourishes the feather follicle, and the ramogenic zone epithelium (Erz) where a feather starts to branch. The feather DP is enriched in BMP/TGF-β signaling molecules and inhibitors for Wnt signaling including Dkk2/Frzb. Wnt ligands are mainly expressed in the feather epithelium and pulp. We find that while Wnt signaling is required for the maintenance of DP marker gene expression and feather regeneration, excessive Wnt signaling delays regeneration and reduces pulp formation. Manipulating Dkk2/Frzb expression by lentiviral-mediated overexpression, shRNA-knockdown, or by antibody neutralization resulted in dual feather axes formation. Our results suggest that the Wnt signaling in the proximal feather follicle is fine-tuned to accommodate feather regeneration and axis formation.

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

    PubMed Central

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

    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 and two evaluators analyzed the same images using digital morphometric techniques (RGB split colors (I) and color deconvolution (II)). Automated type I collagen density estimation in the papillary dermis (two techniques) were correlated with visual evaluations (Spearman's rho coefficients of 0.48 and 0.62 (p<0.01)). With regard to the inter-observer repeatability, the four evaluators who used visual classification had an intraclass correlation coefficient (for absolute agreement) of 0.53, while the other two evaluators who used digital analysis (algorithm II) had an intraclass correlation coefficient of 0.97. PMID:26560217

  20. Dermal wound healing is subject to redox control

    PubMed Central

    Roy, Sashwati; Khanna, Savita; Nallu, Kishore; Hunt, Thomas K.; Sen, Chandan K.

    2006-01-01

    Previously we have reported in vitro evidence suggesting that that H2O2 may support wound healing by inducing VEGF expression in human keratinocytes (JBC 277: 33284–90). Here, we test the significance of H2O2 in regulating wound healing in vivo. Using the Hunt-Schilling cylinder approach we present first evidence that the wound site contains micromolar concentration of H2O2. At the wound site, low concentrations of H2O2 supported the healing process especially in p47phox and MCP-1 deficient mice where endogenous H2O2 generation is impaired. Higher doses of H2O2 adversely influenced healing. At low concentrations, H2O2 facilitated wound angiogenesis in vivo. H2O2 induced FAK phosphorylation both in wound-edge tissue in vivo as well as in human dermal microvascular endothelial cells (HMEC). H2O2 induced site-specific (Tyr-925 & Tyr-861) phosphorylation of FAK. Other sites, including the Tyr-397 autophosphorylation site, were insensitive to H2O2. Adenoviral gene delivery of catalase impaired wound angiogenesis and closure. Catalase over-expression slowed tissue remodeling as evident by a more incomplete narrowing of the hyperproliferative epithelium region and incomplete eschar formation. Taken together, this work presents the first in vivo evidence indicating that strategies to influence the redox environment of the wound site may have a bearing on healing outcomes. PMID:16126008

  1. Acute Bronchitis

    MedlinePlus

    ... can also cause acute bronchitis. To diagnose acute bronchitis, your health care provider will ask about your symptoms and listen to your breathing. You may also have other tests. Treatments include rest, fluids, and aspirin (for adults) or ...

  2. The spindle-shaped cells in cutaneous Kaposi's sarcoma. Histologic simulators include factor XIIIa dermal dendrocytes.

    PubMed Central

    Nickoloff, B. J.; Griffiths, C. E.

    1989-01-01

    Kaposi's sarcoma is a neoplasm that develops as multifocal lesions, often involving the skin, characterized by a complex histologic picture including numerous vascular spaces, perivascular and interstitial spindle-shaped cells, and extravasated erythrocytes, lymphocytes, and plasma cells. Using an antibody against factor XIIIa, which identifies dermal dendrocytes, numerous factor XIIIa-positive dermal dendrocytes were detected among the spindle-shaped cells in 12 acquired immune deficiency syndrome (AIDS)-associated, and five non-AIDS-associated Kaposi's sarcoma lesions. The factor XIIIa-positive dermal dendrocytes were also increased in histologic simulators of Kaposi's sarcoma such as dermatofibroma, angiomatoid malignant fibrous histiocytoma, granuloma annulare, and early wound healing, but were absent in keloids. The increased number of dermal dendrocytes, which are often in an angiocentric configuration and which also express CD4, lymphocyte function associated antigen-1 (LFA-1), and Leu M3 in Kaposi's sarcoma, may be important to the angioproliferative response. The results suggested that the spindle-shaped cells that are present in a variety of cutaneous lesions are dermal dendrocytes and belong to the reticuloendothelial system, unlike other mesenchymal cell types such as the endothelial cell. Apparently a diverse array of stimuli, including human immunodeficiency virus type-1 (HIV-1) infection and trauma, can stimulate the accumulation of factor XIIIa expressing dermal dendrocytes in the skin. These cells can then participate in different stages of a variety of cutaneous alterations including Kaposi's sarcoma, dermatofibroma, granuloma annulare, and early wound healing. Thus, the factor XIIIa-positive dermal dendrocyte is a common cellular denominator among diverse clinical entities that share some histologic features. Images Figure 1 Figure 2 Figure 3 p797-a PMID:2573283

  3. Do androgens influence hair growth by altering the paracrine factors secreted by dermal papilla cells?

    PubMed

    Randall, V A; Hibberts, N A; Thornton, M J; Merrick, A E; Hamada, K; Kato, S; Jenner, T J; de Oliveira, I; Messenger, A G

    2001-01-01

    Androgens regulate many aspects of human hair growth in both sexes. After puberty they transform tiny vellus follicles in many areas, e.g. the face, to terminal ones producing long, thick, pigmented hairs. In genetically predisposed individuals, androgens also cause the reverse transformation of terminal scalp follicles into vellus ones, causing balding. In the current hypothesis for androgen action, androgens control most follicular cells indirectly acting via the mesenchyme-derived dermal papilla which regulates many aspects of follicular activity. In this model androgens binding to androgen receptors in dermal papilla cells alter their production of regulatory molecules which influence other follicular components; these molecules may be soluble paracrine factors and/or extracellular matrix proteins. This hypothesis is supported by immunohistochemical localisation of androgen receptors in dermal papilla cell nuclei and the demonstrations that androgen receptor content and testosterone metabolism patterns of cultured dermal papilla cells from various body sites reflect hair growth in androgen-insensitivity syndromes. The next question is whether androgens alter the paracrine factors secreted by dermal papilla cells. Cultured dermal papilla cells do release soluble, proteinaceous factors into their media which stimulate the growth of keratinocytes and other dermal papilla cells. This mitogenic potential can cross species from humans to rodents. Importantly, testosterone in vitro stimulates the mitogenic potential of beard cells, but in contrast inhibits production by balding scalp cells reflecting their in vivo androgenic responses. Since androgens in vitro do alter the secretion of paracrine factors the current focus lies in identifying specific factors produced, e.g. IGF-I and stem cell factor (SCF), using ELISA and RT-PCR, and comparing their expression in cells from follicles with varying responses to androgens in vivo or under androgen stimulation in vitro

  4. Triiodothyronine (T3) inhibits hyaluronate synthesis in a human dermal equivalent by downregulation of HAS2.

    PubMed

    Pouyani, Tara; Sadaka, Basma H; Papp, Suzanne; Schaffer, Lana

    2013-03-01

    Triiodothyronine (T3) is a thyroid hormone that can have varying effects on skin. In order to assess the effects of T3 on the human dermis, we prepared dermal equivalents using neonatal dermal cells via the process of self-assembly in the presence of differing concentrations of T3. These dermal equivalents were prepared in the absence of serum and a three dimensional matrix allowing for the direct assessment of different concentrations of T3 on dermal extracellular matrix formation. Three different concentrations of T3 were chosen, 20 pM, which is part of the base medium, 0.2 nM T3 and 2 nM T3. We find that self-assembled dermal equivalents formed under these conditions show a progressive "thinning" with increasing T3 concentrations. While we observed no change in total collagen content, inhibition of hyaluronate (HA) synthesis was observed in the 0.2- and 2-nM T3 constructs as compared to the 20-pM construct. Other glycosaminoglycan synthesis was not affected by increasing T3 concentrations. In order to identify the gene(s) responsible for inhibition of HA synthesis in the 2-nM T3 dermal equivalent, we conducted a differential gene array analysis. The results of these experiments demonstrate the differential expression of 40 genes, of these, 34 were upregulated and 6 genes were downregulated. The results from these experiments suggest that downregulation of HAS2 may be responsible for inhibition of hyaluronate synthesis in the self-assembled 2-nM T3 human dermal matrix.

  5. The fate of dienochlor administered orally and dermally to rats.

    PubMed

    Quistad, G B; Mulholland, K M; Skinner, W S

    1986-09-15

    Within four days of receiving a single oral dose (1 mg/kg) of [U-ring-14C]dienochlor [bis(pentachloro-2,4-cyclopentadien-1-yl)] female rats excreted 2 and 88% of the applied 14C in urine and feces, respectively. Metabolites could not be identified and the preponderance of the fecal radioactivity consisted of unextractable 14C-labeled residues. Within 1 day virtually all of the dienochlor had been degraded by rats, with only traces of parent dienochlor in excreta and tissues. After four days only 2% of the applied dose remained in tissues (mainly kidney, liver, and gastrointestinal tract). Pharmacokinetic studies with blood plasma and bile showed dienochlor (and/or its metabolites) to be poorly absorbed. Rats were exposed dermally for 24 hr to [14C]dienochlor formulated as Pentac WP miticide both as an aqueous suspension and as an undiluted wettable powder. Half of the dose adhered to the skin and the other half was found in gauze patches used to protect the treated skin. After a 24-hr exposure over 60% of the radiolabel that adhered to skin was removed by washing with an aqueous soap solution and 86% of this rinsing solution was unmetabolized dienochlor. The dienochlor and its metabolites were transported inefficiently from the application site; only 1% of the applied dose was detected in urine plus feces and less than or equal to 0.2% in tissues. With application rates that simulate field exposure by humans, the actual residue of dienochlor and metabolites in skin (i.e., not removable by washing) is about thirteen times higher following exposure to dienochlor as undiluted wettable powder than as an aqueous suspension.

  6. Parameter optimization toward optimal microneedle-based dermal vaccination.

    PubMed

    van der Maaden, Koen; Varypataki, Eleni Maria; Yu, Huixin; Romeijn, Stefan; Jiskoot, Wim; Bouwstra, Joke

    2014-11-20

    Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles. Microneedles are used to deliver a drug into the skin in a minimally-invasive and potentially pain free manner. Besides, the skin is a potent immune organ that is highly suitable for vaccination. However, there are several factors that influence the penetration ability of the skin by microneedles and the immune responses upon microneedle-based immunization. In this study we assessed several different microneedle arrays for their ability to penetrate ex vivo human skin by using trypan blue and (fluorescently or radioactively labeled) ovalbumin. Next, these different microneedles and several factors, including the dose of ovalbumin, the effect of using an impact-insertion applicator, skin location of microneedle application, and the area of microneedle application, were tested in vivo in mice. The penetration ability and the dose of ovalbumin that is delivered into the skin were shown to be dependent on the use of an applicator and on the microneedle geometry and size of the array. Besides microneedle penetration, the above described factors influenced the immune responses upon microneedle-based vaccination in vivo. It was shown that the ovalbumin-specific antibody responses upon microneedle-based vaccination could be increased up to 12-fold when an impact-insertion applicator was used, up to 8-fold when microneedles were applied over a larger surface area, and up to 36-fold dependent on the location of microneedle application. Therefore, these influencing factors should be considered to optimize microneedle-based dermal immunization technologies.

  7. Dermatologic findings of focal dermal hypoplasia (Goltz syndrome).

    PubMed

    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.

  8. Comparison of measured dermal dust exposures with predicted exposures given by the EASE expert system.

    PubMed

    Hughson, Graeme W; Cherrie, John W

    2005-03-01

    Estimation and Assessment of Substance Exposure (EASE) is a rule-based computer expert system used by regulatory authorities within the European Union to assist in assessing exposure for both new and existing substances. It can provide estimates of both inhalation exposure levels and dermal exposure levels to the hands and forearms. This article describes the results of a study in which measurements of workplace dermal zinc exposures were collected for an industry-wide risk assessment and also compared with the levels predicted by EASE. Measurements were obtained from subjects in seven different workplaces that were producing or working with zinc metal or zinc compounds. The work activities were grouped a priori into one of three categories used by EASE for dermal exposure assessment: 'non-dispersive use with intermittent direct handling', 'wide dispersive use with intermittent direct handling' and 'wide dispersive use with extensive direct handling'. The predicted exposure ranges for these categories are 0.1-1, 1-5 and 5-15 mg cm(-2) day(-1). Although the average measured exposure levels for each of the categories increased in line with the predictions from EASE, the model overestimated dermal exposure to the hands by a factor of approximately 50 when the mid-point of the EASE range was compared with the measured mean exposure. Furthermore, a significant additional exposure was found on other parts of the workers' bodies for which EASE does not provide any estimates. Interpretation of the dermal exposure data was complicated by the use of protective gloves, which might have limited the amount of zinc dust adhering to the workers' skin. However, observation of the work activities suggested that the pattern of glove use was such that they would not provide a consistent level of protection. This study provided an opportunity to collect a large amount of dermal zinc exposure data for risk assessment purposes and also enabled a dermal sampling method to be developed

  9. Estimation of individual dermal and respiratory uptake of polycyclic aromatic hydrocarbons in 12 coke oven workers.

    PubMed Central

    VanRooij, J G; Bodelier-Bade, M M; Jongeneelen, F J

    1993-01-01

    Twelve workers from a coke plant in The Netherlands participated in an intensive skin monitoring programme combined with personal air sampling and biological monitoring during five consecutive eight hour workshifts. The purpose of the study was to make a quantitative assessment of both the dermal and respiratory intake of polycyclic aromatic hydrocarbons (PAHs). Pyrene was used as a marker compound for both dermal and respiratory exposure to PAHs. The biological measure for the internal exposure to PAHs was urinary 1-OH-pyrene concentration. Measurements on exposure pads at six skin sites showed that mean total skin contamination of the 12 workers ranged between 21 and 166 micrograms pyrene a day. The dermal uptake of pyrene ranged between 4 and 34 micrograms/day, which was about 20% of the pyrene contamination on skin. The mean concentration of total pyrene in the breathing zone air of the 12 coke oven workers ranged from 0.1 to 5.4 micrograms/m3. The mean respiratory uptake of pyrene varied between 0.5 and 32.2 micrograms/day. Based on the estimates of the dermal and respiratory pyrene uptake it is concluded that an average 75% (range 28%-95%, n = 12) of the total absorbed amount of pyrene enters the body through the skin. Because of the difference in the pyrene:benzo(a)pyrene ratio between the air samples and the skin contamination samples, the dermal uptake of benzo(a)pyrene was also estimated. This was about 51% of the total absorbed amount (range 8%-92%, n = 12). The total excreted amount of urinary 1-OH-pyrene as a result of exposure to PAHs during the five consecutive workshifts varied between 36 and 239 nmol. A multiple regression model of the mass balance between pyrene dose (both dermal and respiratory) and 1-OH-pyrene excretion confirmed the relevance of the dermal exposure route. The variation in urinary 1-OH-pyrene excretion was determined more by the dermal pyrene dose than by the respiratory dose. The model showed an estimate of the percentage of

  10. Characterization and assessment of dermal and inhalable nickel exposures in nickel production and primary user industries.

    PubMed

    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

  11. Role of clothing in both accelerating and impeding dermal absorption of airborne SVOCs.

    PubMed

    Morrison, Glenn C; Weschler, Charles J; Bekö, Gabriel; Koch, Holger M; Salthammer, Tunga; Schripp, Tobias; Toftum, Jørn; Clausen, Geo

    2016-01-01

    To assess the influence of clothing on dermal uptake of semi-volatile organic compounds (SVOCs), we measured uptake of selected airborne phthalates for an individual wearing clean clothes or air-exposed clothes and compared these results with dermal uptake for bare-skinned individuals under otherwise identical experimental conditions. Using a breathing hood to isolate dermal from inhalation uptake, we measured urinary metabolites of diethylphthalate (DEP) and di-n-butylphthalate (DnBP) from an individual exposed to known concentrations of these compounds for 6 h in an experimental chamber. The individual wore either clean (fresh) cotton clothes or cotton clothes that had been exposed to the same chamber air concentrations for 9 days. For a 6-h exposure, the net amounts of DEP and DnBP absorbed when wearing fresh clothes were, respectively, 0.017 and 0.007 μg/kg/(μg/m(3)); for exposed clothes the results were 0.178 and 0.261 μg/kg/(μg/m(3)), respectively (values normalized by air concentration and body mass). When compared against the average results for bare-skinned participants, clean clothes were protective, whereas exposed clothes increased dermal uptake for DEP and DnBP by factors of 3.3 and 6.5, 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.

  12. Management of gingival recession with acellular dermal matrix graft: A clinical study

    PubMed Central

    Balaji, V. R.; Ramakrishnan, T.; Manikandan, D.; Lambodharan, R.; Karthikeyan, B.; Niazi, Thanvir Mohammed; Ulaganathan, G.

    2016-01-01

    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. PMID:27829749

  13. A three-dimensional atlas of human dermal leukocytes, lymphatics, and blood vessels.

    PubMed

    Wang, Xiao-Nong; McGovern, Naomi; Gunawan, Merry; Richardson, Connor; Windebank, Martin; Siah, Tee-Wei; Lim, Hwee-Ying; Fink, Katja; Li, Jackson L Yao; Ng, Lai G; Ginhoux, Florent; Angeli, Veronique; Collin, Matthew; Haniffa, Muzlifah

    2014-04-01

    Dendritic cells (DCs), macrophages (Mφ), and T cells are major components of the skin immune system, but their interstitial spatial organization is poorly characterized. Using four-channel whole-mount immunofluorescence staining of the human dermis, we demonstrated the three-dimensional distribution of CD31(+) blood capillaries, LYVE-1(+) lymphatics, discrete populations of CD11c(+) myeloid DCs, FXIIIa(+) Mφ, and lymphocytes. We showed phenotypic and morphological differences in situ between DCs and Mφ. DCs formed the first dermal cellular layer (0-20 μm beneath the dermoepidermal junction), Mφ were located deeper (40-60 μm), and CD3(+) lymphocytes were observed throughout (0-60 μm). Below this level, DCs, T cells, and the majority of Mφ formed stable perivascular sheaths. Whole-mount imaging revealed the true extent of dermal leukocytes previously underestimated from cross-section views. The total area of apical dermis (0-30 μm) contained approximately 10-fold more myeloid DCs than the entire blood volume of an average individual. Surprisingly, <1% of dermal DCs occupied lymphatics in freshly isolated skin. Dermal DCs rapidly accumulated within lymphatics, but Mφ remained fixed in skin explants cultured ex vivo. The leukocyte architecture observed in normal skin was distorted in inflammation and disease. These studies illustrate the micro-anatomy of dermal leukocytes and provide further insights into their functional organization.

  14. A review of adipocyte lineage cells and dermal papilla cells in hair follicle regeneration

    PubMed Central

    Zhang, Peipei; Kling, Russell E; Ravuri, Sudheer K; Kokai, Lauren E; Rubin, J Peter; Chai, Jia-ke

    2014-01-01

    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. PMID:25383178

  15. Dermal fillers in aesthetics: an overview of adverse events and treatment approaches

    PubMed Central

    Funt, David; Pavicic, Tatjana

    2013-01-01

    Background The ever-expanding range of dermal filler products for aesthetic soft tissue augmentation is of benefit for patients and physicians, but as indications and the number of procedures performed increase, the number of complications will likely also increase. Objective To describe potential adverse events associated with dermal fillers and to provide structured and clear guidance on their treatment and avoidance. Methods Reports of dermal filler complications in the medical literature were reviewed and, based on the publications retrieved and the authors’ extensive experience, recommendations for avoiding and managing complications are provided. Results Different dermal fillers have widely varying properties, associated risks, and injection requirements. All dermal fillers have the potential to cause complications. Most are related to volume and technique, though some are associated with the material itself. The majority of adverse reactions are mild and transient, such as bruising and trauma-related edema. Serious adverse events are rare, and most are avoidable with proper planning and technique. Conclusion For optimum outcomes, aesthetic physicians should have a detailed understanding of facial anatomy; the individual characteristics of available fillers; their indications, contraindications, benefits, and drawbacks; and ways to prevent and avoid potential complications. PMID:24363560

  16. Plasma and dermal pharmacokinetics of terpinen-4-ol in rats following intravenous administration.

    PubMed

    Chooluck, K; Singh, R P; Sathirakul, K; Derendorf, H

    2013-02-01

    Terpinen-4-ol, a naturally occurring monoterpene, has been shown to possess antibacterial, antioxidant and anti-inflammatory activities. Furthermore, recent reports have demonstrated that terpinen-4-ol could be developed as new therapies against melanoma either in systemic administration or targeted drug delivery. The purpose of this study was to investigate the pharmacokinetics of terpinen-4-ol in rat plasma and dermal tissue following intravenous (i.v.) bolus injection of terpinen-4-ol at a dose of 2 mg/kg. Unbound concentrations of terpinen-4-ol in dermis were continuously determined by dermal microdialysis. Simultaneously, a conventional blood sampling was performed. The concentrations of terpinen-4-ol in plasma and microdialysates were determined by validated gas chromatography-mass spectrometry. Following i.v. bolus administration, terpinen-4-ol rapidly distributed into the dermis and reached relatively low levels with an average maximum concentration (Cmax) of 0.10 +/- 0.06 microg/ml in comparison with a plasma Cmax of 6.30 +/- 1.90 microg/ml. The free terpinen-4-ol concentrations in dermal tissue were lower than the corresponding total and free plasma concentrations for the entire length of study, indicating that plasma levels do not provide information of actual terpinen-4-ol concentrations in the skin. This study demonstrates that dermal microdialysis is an effective and minimally invasive tool to evaluate the dermal pharmacokinetics of terpinen-4-ol following systemic administration.

  17. Acute and subchronic toxicological evaluation of the semipurified extract of seeds of guaraná (Paullinia cupana) in rodents.

    PubMed

    Antonelli-Ushirobira, T M; Kaneshima, E N; Gabriel, M; Audi, E A; Marques, L C; Mello, J C P

    2010-07-01

    We evaluated the toxicity of a semipurified extract (EPA fraction, containing caffeine and several flavan-3-ols and proanthocyanidins) of seeds of the native Amazon plant Paullinia cupana (guaraná) in rodents. Acute toxicity was tested in male Swiss mice, which received different doses orally (OR) and intraperitoneally (ip); control groups received water. These tests produced acute mortality, with LD(50) of 1.825 g/kg (OR) and 0.827 g/kg (ip), and a significant weight decrease in lungs of mice receiving a dose of 0.1g/kg. In the repeated-dose toxicity test, the EPA was administered OR daily to male and female Wistar rats at doses of 30, 150, and 300 mg/kg/day/90 days. Their behavior, mortality, weight changes, laboratory tests, and the weights and histopathology of organs were evaluated. No rats died during the tests. Males dosed at 150 or 300 mg/kg gained weight more slowly and lost kidney weight (absolute and relative weights, compared to the control group). Hematological and biochemical tests showed few changes, differing somewhat between males and females; the histopathological evaluation indicated no significant changes. These results indicate that the EPA fraction of guaraná caused no toxicity in rats at the smallest dose evaluated (30 mg/kg). No other species was evaluated.

  18. Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

    PubMed

    Ito, Tomohiro; Ono, Tomoko; Sato, Atsuya; Goto, Kazunori; Miura, Takehito; Wakame, Koji; Nishioka, Hiroshi; Maeda, Takahiro

    2014-03-01

    The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement.

  19. A Quantitative Structure Activity Relationship for acute oral toxicity of pesticides on rats: Validation, domain of application and prediction.

    PubMed

    Hamadache, Mabrouk; Benkortbi, Othmane; Hanini, Salah; Amrane, Abdeltif; Khaouane, Latifa; Si Moussa, Cherif

    2016-02-13

    Quantitative Structure Activity Relationship (QSAR) models are expected to play an important role in the risk assessment of chemicals on humans and the environment. In this study, we developed a validated QSAR model to predict acute oral toxicity of 329 pesticides to rats because a few QSAR models have been devoted to predict the Lethal Dose 50 (LD50) of pesticides on rats. This QSAR model is based on 17 molecular descriptors, and is robust, externally predictive and characterized by a good applicability domain. The best results were obtained with a 17/9/1 Artificial Neural Network model trained with the Quasi Newton back propagation (BFGS) algorithm. The prediction accuracy for the external validation set was estimated by the Q(2)ext and the root mean square error (RMS) which are equal to 0.948 and 0.201, respectively. 98.6% of external validation set is correctly predicted and the present model proved to be superior to models previously published. Accordingly, the model developed in this study provides excellent predictions and can be used to predict the acute oral toxicity of pesticides, particularly for those that have not been tested as well as new pesticides.

  20. Toxicity assessment of perfluorooctane sulfonate using acute and subchronic male C57BL/6J mouse models.

    PubMed

    Xing, Jiali; Wang, Gang; Zhao, Jichun; Wang, Eryin; Yin, Boxing; Fang, Dongsheng; Zhao, Jianxin; Zhang, Hao; Chen, Yong Q; Chen, Wei

    2016-03-01

    Perfluorooctane sulfonate (PFOS) is a principal representative and the final degradation product of several commercially produced perfluorinated compounds. However, PFOS has a high bioaccumulation potential and therefore can exert toxicity on aquatic organisms, animals, and cells. Considering the widespread concern this phenomenon has attracted, we examined the acute and subchronic toxic effects of varying doses of PFOS on adult male C57BL/6 mice. The acute oral LD50 value of PFOS in male C57BL/6J mice was 0.579 g/kg body weight (BW). Exposure to the subchronic oral toxicity of PFOS at 2.5, 5, and 10 mg PFOS/kg BW/day for 30 days disrupted the homeostasis of antioxidative systems, induced hepatocellular apoptosis (as revealed by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay), triggered liver injury (as evidenced by the increased serum levels of aspartate aminotransferase, alanine amino transferase, alkaline phosphatase, and gamma-glutamyl transpeptidase and by the altered histology), and ultimately increased the liver size and relative weight of the mice. PFOS treatment caused liver damage but only slightly affected the kidneys and spleen of the mice. This study provided insights into the toxicological effects of PFOS.

  1. Acute and sub-chronic toxicological evaluation of hydro-methanolic extract of Coriandrum sativum L. seeds

    PubMed Central

    Patel, Dipak; Desai, Swati; Devkar, Ranjitsinh; Ramachandran, A.V.

    2012-01-01

    Coriandrum sativum L. (CS) seeds are known to possess therapeutic potentials against a variety of physiological disorders. This study assesses acute and sub-chronic toxicity profile of hydro-methanolic extract of CS seeds using OECD guidelines. In acute toxicity study, mice were once orally administered 1000, 3000 and 5000 mg/kg body weight of CS extract. There were no any behavioral alterations or mortality recorded in CS treated groups. The LD50 value was more than 5000 mg/kg body weight. In the sub-chronic oral toxicity study, the animals were orally administered with CS extract (1000, 2000 and 3000mg/kg body weight) daily for 28 days whereas; vehicle control group received 0.5 % carboxy methyl cellulose. There was significant reduction in food intake, body weight gain and plasma lipid profiles of CS2 and CS3 (2000 and 3000 mg/kg body weight respectively) groups as compared to the control group. However, there were no alterations in haematological profile, relative organ weights, histology and plasma markers of damage of vital organs (heart, liver and kidney). The overall finding of this study indicates that CS extract is non-toxic up to 3000 mg/kg body weight and can be considered as safe for consumption. PMID:27847445

  2. Acute and Subchronic Oral Toxicity Evaluation of Aqueous Root Extract of Dicoma anomala Sond. in Wistar Rats

    PubMed Central

    Balogun, Fatai Oladunni; Tom Ashafa, Anofi Omotayo

    2016-01-01

    The present study evaluated the safety of aqueous root extract of Dicoma anomala (AQRED) through acute and subchronic toxicity studies. Single oral dose of AQRED at the concentration of 0, 5, 300, and 2000 mg/kg as well as 125, 250, and 500 mg/kg/day was administered to rats for 14-day acute and 90-day subchronic oral toxicity studies. The results revealed no mortalities or observed clinical signs of toxicity in all the rats during both investigation periods. In subchronic toxicity testing, administration of AQRED also did not cause any changes in body weight as well as food and water consumption patterns. The haematological parameters and blood chemistry revealed no significant difference (p > 0.05) between the treatment and the control except in platelet count, alkaline phosphatase, and sodium levels where there was a significant increase (p < 0.05), although there was also a significant reduction (p < 0.05) in alanine transaminase, aspartate transaminase, and creatinine when compared to control. However, these changes were not reflecting the results from histology. Conclusively, the obtained results suggested that the LD50 of AQRED is in excess of 2000 mg/kg and its oral administration for 90 days revealed that it is unlikely to be toxic, hence, safe. PMID:27200099

  3. Efficacy of Pistacia khinjuk Fruits on Viability of Hydatid Cyst Protoscoleces and Its Acute Toxicity in Mice Model

    PubMed Central

    MAHMOUDVAND, Hossein; MIRBADIE, Seyed Reza; GHASEMI KIA, Mehdi; BADPARVA, Ebrahim; SHAMSADINI LORI, Saeedeh; FASIHI HARANDI, Majid

    2016-01-01

    Background: This investigation aimed to evaluate the in vitro scolicidal effects of Pistacia khinjuk methanolic extract against protoscoleces of hydatid cysts and its acute toxicity in mice NMRI model. Methods: Protoscoleces were aseptically extracted from sheep livers having hydatid cysts. Various concentrations of the essential oil (12.5–100 mg/mL) were used for 10 to 60 min. Viability of protoscoleces was confirmed using eosin exclusion test (0.1% eosin staining). Twenty-four male NMRI mice were used to assess the acute toxicity of P. khinjuk. Results: P. khinjuk extract at the concentrations of 100 mg/mL after 10 min of exposure killed 100% of protoscoleces. Similarly, the mean of mortality rate of protoscoleces after 20 min of exposure to the concentration of 50 mg/mL was 100%. The LD50 of the intraperitoneal injection of the P. khinjuk methanolic extract was 2.8 g/kg and the maximum non-fatal dose was 1.7 g/kg. Conclusion: The findings demonstrated effective scolicidal effects of P. khinjuk extract with no considerable toxicity that might be a natural source for the producing of new scolicidal agent. PMID:28127345

  4. Acute and subacute oral toxicity assessment of the oil extracted from Attalea phalerata Mart ex Spreng. pulp fruit in rats.

    PubMed

    Freitas de Lima, Fernando; Traesel, Giseli Karenina; Menegati, Sara Emilia Lima Tolouei; Santos, Ariany Carvalho Dos; Souza, Roosevelt Isaias Carvalho; de Oliveira, Vinícius Soares; Sanjinez-Argandoña, Eliana Janet; Cardoso, Claudia Andrea Lima; Oesterreich, Silvia Aparecida; Vieira, Maria do Carmo

    2017-01-01

    Attalea phalerata Mart. ex Spreng., popularly known as "bacuri", is a native plant from the brazilian Cerrado and used in folk medicine as a pulmonary decongestant, an anti-inflammatory for joints and antipyretic. There is an expectation about the use in chronic disease of the Attalea phalerata oil since its composition is high in carotenoids and beneficial fatty acids. The aim of the study was to evaluate the toxicological profile of the oil extracted from Attalea phalerata Mart. ex Spreng. pulp (APO). Acute and subacute toxicity studies were performed in male and female Wistar rats according to the OECD - Guidelines 425 and 407. For the acute toxicity, one single dose of the APO (2000mg/kg) was administered by gavage to five female rats. In the subacute toxicity, four different doses (125, 250, 500 and 1000mg/kg) of the APO were administered to male and female rats for 28 consecutive days. No deaths or behavioral changes were observed during both experiments as well as no changes in organ weights, hematological, histopathological parameters. The biochemical parameters showed changes in phosphatase alkaline and albumin levels, however these values are within the normal range for the species. A significant reduction in cholesterol and triglycerides was also observed in some of the animals treated with the APO. Therefore, the LD50 is higher than 2000mg/kg and the APO oil can be considered safe at the doses tested in rats. However, further assessments are required in order to proceed to clinical studies in humans.

  5. Acute and sub-chronic toxicological evaluation of hydro-methanolic extract of Coriandrum sativum L. seeds.

    PubMed

    Patel, Dipak; Desai, Swati; Devkar, Ranjitsinh; Ramachandran, A V

    2012-01-01

    Coriandrum sativum L. (CS) seeds are known to possess therapeutic potentials against a variety of physiological disorders. This study assesses acute and sub-chronic toxicity profile of hydro-methanolic extract of CS seeds using OECD guidelines. In acute toxicity study, mice were once orally administered 1000, 3000 and 5000 mg/kg body weight of CS extract. There were no any behavioral alterations or mortality recorded in CS treated groups. The LD50 value was more than 5000 mg/kg body weight. In the sub-chronic oral toxicity study, the animals were orally administered with CS extract (1000, 2000 and 3000mg/kg body weight) daily for 28 days whereas; vehicle control group received 0.5 % carboxy methyl cellulose. There was significant reduction in food intake, body weight gain and plasma lipid profiles of CS2 and CS3 (2000 and 3000 mg/kg body weight respectively) groups as compared to the control group. However, there were no alterations in haematological profile, relative organ weights, histology and plasma markers of damage of vital organs (heart, liver and kidney). The overall finding of this study indicates that CS extract is non-toxic up to 3000 mg/kg body weight and can be considered as safe for consumption.

  6. Field evaluation of repellency of a polyherbal essential oil against blackflies and its dermal toxicity using rat model.

    PubMed

    Sunil, D; Bipul, R; Pronobesh, C; Das, N G; Hazarika, S; Bhola, R K; Vijay, V; Lokendra, S

    2012-09-01

    In the present study we have evaluated the repellent activity of mixture of Curcuma longa, Zanthoxylum limonella and Pogostemon heyneanus essential oils in 1:1:2 ratio at 5%, 10% and 20% concentration against blackflies in northeastern India. Initially the essential oil mixture tested here has been found effective against Aedes albopictus mosquitoes. The average protection recorded in 20% concentration (170.56 ± 4.0; 95% CI = 162.09-179.02) was higher as compared to other two concentrations (F = 90.2; p<0.0001; df = 53). Percentage repellency and repellency index was found to be higher in 20% concentration (p ≤ 0.017). No appreciable clinical and behavioral signs were observed in the acute dermal toxicity using rat model. No changes were observed in biochemical profiles of treatment group animals. Similarly, no prominent lesions were observed in vital organs of treatment in both the sexes. The study concludes that tested repellent is safe for use and has multi-insects repellent property.

  7. Molecular modifications of dermal and epidermal biomarkers following UVA exposures on reconstructed full-thickness human skin.

    PubMed

    Meloni, Marisa; Farina, Anne; de Servi, Barbara

    2010-04-01

    Ultraviolet A (UVA) radiation adversely affects skin health and appearance via multiple molecular pathways. Biologically relevant UVA damage are classified as short-term effects (e.g. formation of reactive oxygen species [ROS], inflammation, photo-oxidation, DNA damage, immunosuppression, photoallergy and cell-mediated contact hypersensitivity) or long-term effects (elastosis, photoageing and photocarcinogenesis). Single and chronic experimental exposure to UVA are limited in humans by ethical concerns, and furthermore it is impossible to quantify long-term endpoints such as photoageing over the life-span of a human volunteer. The aim of the present study was to investigate the biological relevance of the Phenion FT skin model for use in photobiological studies. Biological responses to acute and repeated UVA exposures were investigated by monitoring the kinetics of gene expression during the post-irradiation period. By using a dynamic approach, we were able to define early and stable markers of UVA-induced effects that could be predictive of UVA damage in vivo. The transcriptomic approach applied to 3D human tissues appears to be an encouraging method for gaining a deeper understanding of the UVA effects on skin and for studying the dermal response with non-invasive techniques.

  8. Dermal absorption of fumigant gases during HAZMAT incident exposure scenarios-Methyl bromide, sulfuryl fluoride, and chloropicrin.

    PubMed

    Gaskin, Sharyn; Heath, Linda; Pisaniello, Dino; Edwards, John W; Logan, Michael; Baxter, Christina

    2017-01-01

    Accidental or intentional releases of toxic gases or vapors are the most common occurrence in hazardous material (HAZMAT) incidents that result in human injuries. The most serious hazard from exposure to gases or vapors is via the respiratory system. Dermal uptake, as a secondary route, is still a concern, most acutely for the unprotected public. There is a limited evidence base describing skin absorption of toxic gases and vapors in HAZMAT exposure scenarios, which are relatively brief compared with traditional test periods for skin absorption studies. We describe research designed to provide experimental data to support decision-making by first responders regarding skin decontamination in HAZMAT-focused exposure scenarios involving toxic gases. We present findings for three common fumigants, methyl bromide, sulfuryl fluoride, and chloropicrin assessed using an Organization for Economic Co-operation and Development in vitro toxicology protocol utilizing human skin and gas/vapor exposures. Results indicate that for atmospheric concentrations that would be lethal via inhalation (LCLo), intact skin provides an excellent barrier to exposures up to 30 min, with little influence of common clothing fabric and high temperature and humidity conditions. The findings may challenge the current HAZMAT dogma requiring mass personal decontamination by strip and shower for short-term exposures to sulfuryl fluoride and chloropicrin gas/vapor.

  9. Cardiac and renal nitrosative-oxidative stress after acute poisoning by a nerve agent Tabun.

    PubMed

    Dimov, Dimo; Hadjiolova, Radka; Kanev, Kamen; Tomova, Radka; Michova, Anna; Todorov, Todor; Murdjev, Rumen; Boneva, Temenujka; Dimova, Ivanka

    2015-01-01

    We hypothesized that Tabun poisoning, as well as other organophosphorous treatment, cause specific organs' oxidative changes that have not previously been substantiated investigated. In this regard, a marker for nitrosative-oxidative stress in the main haemodynamic organs (heart and kidney) could reveal the existence of such changes. In this study, for the first time we studied the nitrosative/oxidative stress in heart and kidney after acute Tabun (Ethyl N,N- Dimethylphosphoramidocyanidate) poisoning measuring by immunohistochemistry the expression of 3-nitrotyrosine--a marker for nitrosative-oxidative stress. We investigated nitrotyrozine expression in three different groups of animals (with at least 3 animals in each group): the first group was treated with 0.5 LD50 Tabun and organs were collected after 24 h; the second group received vehicle for the same period; in the third group a highly specific re-activator was applied immediately after Tabun application. Heart and kidney were collected after 24 h. The levels of nitrotyrozine production significantly increased (more than 3 times) in cardiomyocytes after Tabun. The application of re-activator slightly reduced these levels not reaching the basal heart levels. Nitrotyrozine expression in kidney increased more than 2 times after Tabun and application of re-activator did not change it significantly. In conclusion, our study evidently demonstrated that Tabun trigger oxidative-nitrosative stress in heart and kidney and these cellular effects should be protected by an additional anti-oxidant therapy, since acetylcholinesterase re-activator is not efficient in this manner.

  10. Safety evaluation of Se-methylselenocysteine as nutritional selenium supplement: acute toxicity, genotoxicity and subchronic toxicity.

    PubMed

    Yang, Hui; Jia, Xudong

    2014-12-01

    The significant toxicity of selenium emphasizes the need to assess the health risk of various selenocompounds as nutritional supplements. Se-methylselenocysteine (SeMC) was recently reported to be more bioactive but the toxicological effects have not been sufficiently characterized. This study aimed to evaluate the safety of SeMC and provide the Acceptable Daily Intake (ADI) for its use in human diet. Our results demonstrated that SeMC, with the Median Lethal Dose (LD50) of 12.6 and 9.26mg/kg BW in female and male mice, was of high potent of health hazard under acute oral exposure, but a battery of tests including Ames test, micronucleus assay and mouse sperm malformation assay suggested that SeMC was not genotoxic. The repeated dose study indicated little systemic toxicity of SeMC at supernutritional levels (0.5, 0.7, 0.9mg/kg BW/day) after 90-day oral exposure. Importantly, the 95% lower confidence value of Benchmark Dose (BMDL) was estimated as 0.34mg/kg BW/day according to the elevated relative liver weight. The ADI for human was established at 3.4μg/kg BW/day. The results suggested greater safety of SeMC as a nutritional selenium supplement, but health risk needs to be further evaluated when SeMC is applied beyond this level to achieve cancer chemoprevention.

  11. Acute and Subchronic Toxicity Study of Euphorbia hirta L. Methanol Extract in Rats

    PubMed Central

    Yuet Ping, Kwan; Darah, Ibrahim; Chen, Yeng; Sreeramanan, Subramaniam

    2013-01-01

    Despite Euphorbia hirta L. ethnomedicinal benefits, very few studies have described the potential toxicity. The aim of the present study was to evaluate the in vivo toxicity of methanolic extracts of E. hirta. The acute and subchronic oral toxicity of E. hirta was evaluated in Sprague Dawley rats. The extract at a single dose of 5000 mg/kg did not produce treatment related signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the LD 50 of this plant was estimated to be more than 5000 mg/kg. In the repeated dose 90-day oral toxicity study, the administration of 50 mg/kg, 250 mg/kg, and 1000 mg/kg/day of E. hirta extract per body weight revealed no significant difference (P > 0.05) in food and water consumptions, body weight change, haematological and biochemical parameters, relative organ weights, and gross findings compared to the control group. Macropathology and histopathology examinations of all organs including the liver did not reveal morphological alteration. Analyses of these results with the information of signs, behaviour, and health monitoring could lead to the conclusion that the long-term oral administration of E. hirta extract for 90 days does not cause sub-chronic toxicity. PMID:24386634

  12. Antidiarrheal activity and acute oral toxicity of Mentha longifolia L. essential oil

    PubMed Central

    Jalilzadeh-Amin, Ghader; Maham, Massoud

    2015-01-01

    Objectives: Mentha longifolia L. (Lamiaceae) is an annual herb that is used in the Iranian traditional medicine for treating stomach and intestinal disorders. The purpose of this study was to determine the protective effect of M. longifolia on experimental diarrhea in a rat model. Materials and Methods: The antidiarrheal activity of essential oil of M. longifolia (20-80 mg/kg) was investigated against castor oil-induced diarrhea in rats using loperamide as the standard reference drug. In acute toxicity evaluation, rats were orally administrated with single dose of EOML at doses ranging from 10 to 1000 mg/kg. Results: EOML caused a significant (p<0.05) and dose-dependent decrease of gastrointestinal transit, nevertheless, it could not block the inhibitory effect of atropine (0.1 mg/kg). EOML at oral doses of 20 and 80 mg/kg protected the animals against castor oil-induced diarrhea significantly (p<0.05). EOML decreased the intestinal fluid accumulation as indicated by the significantly (p<0.05 to p<0.001) decrease compared to control. The oral LD50 of EOML was found to be 470 mg/kg in rat. Conclusion: Since the inhibition of intestinal hyperactivity and hypersecretory are the bases of the treatment of diarrhea, results obtained in the present study suggest that EOML is endowed with antidiarrheal activity. EOML is moderately toxic for oral medication. PMID:25949954

  13. Citrus peel extract attenuates acute cyanide poisoning-induced seizures and oxidative stress in rats.

    PubMed

    Abdel Moneim, Ahmed E

    2014-01-01

    The primary aimed of this study was to investigate the potential protective effects of methanolic extract of citrus peel (MECP) on acute cyanide (KCN) poisoning-induced seizures and oxidative stress in rats. The intraperitoneal LD50 value of KCN (6.3 mg/Kg bwt), based on 24 hrs mortality, was significantly increased by 9, 52 or 113% by oral administration of MECP (500 mg/Kg bwt) pre-administered for 1, 2 and 3 days, respectively, in rats in a time-dependent manner. Intraperitoneal injection of the sublethal dose of KCN (3 mg/Kg bwt) into rats increased, 24 hrs later, lipid peroxidation (LPO), nitric oxide (NO), glutamate levels and acetylcholinesterase (AChE) activity in hippocampus, striatum and cerebral cortex. KCN also decreased brain glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities in these animals. Pre-treatment of rats with MECP inhibited KCN-induced increases in LPO, NO, and glutamate levels and AChE activity as well as decreases in brain GSH level and SOD and CAT activities. In addition, KCN significantly decreased norepinephrine, dopamine and serotonin levels in different brain regions which were resolved by MECP. From the present results, it can be concluded that the neuroprotective effects of MECP against KCN-induced seizures and oxidative stress may be due to the inhibition of oxidative stress overproduction and maintenance of antioxidant defense mechanisms.

  14. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    PubMed Central

    Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

    2014-01-01

    Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

  15. Acute oral toxicity and bacterial translocation studies on potentially probiotic strains of lactic acid bacteria.

    PubMed

    Zhou, J S; Shu, Q; Rutherfurd, K J; Prasad, J; Gopal, P K; Gill, H S

    2000-01-01

    Three potentially probiotic lactic acid bacteria (LAB) strains, Lactobacillus rhamnosus HN001 (DR20(TM)), Lb. acidophilus HN017 and Bifidobacterium lactis HN019 (DR10()), have recently been identified and characterized. The present study was designed to evaluate the acute oral toxicity of these strains to mice, and also to investigate bacterial translocation and gut mucosal pathology in BALB/c mice fed HN019, HN001 or HN017 for 8 consecutive days at a high dose of 10(11)cfu/mouse/day. Results showed that these probiotic strains had no adverse effect on general health status, feed intake, body weight gain and intestinal mucosal morphology (villus height, crypt depth, epithelial cell height and mucosal thickness). No viable bacteria were recovered from blood and tissue samples (mesenteric lymph nodes, liver and spleen) of mice, and no treatment-associated illness or death was observed. According to these results, the oral LD(50) of HN019, HN001 and HN017 is more than 50g/kg/day for mice, and their acceptable daily intake (ADI) value is 35g dry bacteria per day for a 70-kg person. This suggests that the probiotic strains HN019, HN001 and HN017 are non-pathogenic and likely to be safe for human consumption.

  16. Acute toxicity and mutagenic activity of Mexican plants used in traditional medicine.

    PubMed

    Déciga-Campos, Myrna; Rivero-Cruz, Isabel; Arriaga-Alba, Myriam; Castañeda-Corral, Gabriela; Angeles-López, Guadalupe E; Navarrete, Andrés; Mata, Rachel

    2007-03-21

    The present work was undertaken to determine safety parameters of selected Mexican medicinal plants chosen on the basis of their frequency of medicinal use and commercial importance. The medicinal herbs included Amphipteryngium adstringens, Hintonia standleyana, Hintonia latiflora, Piper sanctum, Haemathoxylon brasiletto, Iostephane heterophylla, Valeriana procera, Arracacia tolucensis, Brickellia veronicaefolia, Scaphyglottis livida, Exostema caribaeum, Hippocratea excelsa, Ligusticum porteri, Poliomintha longiflora and Gnaphalium sp. In the acute toxicity studies in mice performed according to the Lorke procedure, Exostema caribaeum, Hippocratea excelsa, Ligusticum porteri and Poliomintha longiflora were the most toxic with LD(50) values between 1085 and 2mg/kg. The Ames test revealed that Gnaphalium sp. and Valeriana procera extracts induced mutations of S. typhimurium TA98 with or without the S9 microsomal fraction, and TA100 in the presence of the enzymatic fraction, respectively. The tincture of Valeriana procera, however, was non-mutagenic. Finally, in the Artemia salina lethality test Brickellia veronicaefolia, Arracacia tolucensis, Poliomintha longiflora and Piper sanctum caused significant mortality of the crustacean larvae with LC(50) in the range of 37-227 microg/mL.

  17. Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging

    PubMed Central

    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

  18. Insights into reptile dermal contaminant exposure: Reptile skin permeability to pesticides.

    PubMed

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

    2016-07-01

    There is growing interest in improving ecological risk assessment exposure estimation, specifically by incorporating dermal exposure. At the same time, there is a growing interest in amphibians and reptiles as receptors in ecological risk assessment, despite generally receiving less research than more traditional receptors. Previous research has suggested that dermal exposure may be more important than previously considered for reptiles. We measured reptile skin permeability to four pesticides (thiamethoxam, malathion, tebuthiuron, trifluralin) using ventral skin samples. All four pesticides penetrated the skin but generally had low permeability. There was no apparent relationship between physicochemical properties and permeability coefficients. Malathion had a significantly greater permeability rate at all time points compared to the other pesticides. Tebuthiuron had a greater permeability than thiamethoxam. Reptiles and mammals appear to have similar skin permeability suggesting that dermal exposure estimates for mammals may be representative of reptiles.

  19. Phenotypic modulations of human umbilical vein endothelial cells and human dermal fibroblasts using two angiogenic assays.

    PubMed

    Bikfalvi, A; Cramer, E M; Tenza, D; Tobelem, G

    1991-01-01

    Different angiogenic assays in vitro have helped to define various events underlying angiogenesis. In this report we have compared the phenotypic modifications of human umbilical vein endothelial cells (HUVE cells) and human dermal fibroblasts using Matrigel and collagen gels. Both HUVE cells and human dermal fibroblasts form a network of anastomosing cords that apparently resemble blood capillaries when grown on Matrigel. The whole network was formed by several cellular aggregates joined to each other by cellular cords. Lumen formation was not observed in this angiogenic system. In opposite, considerable differences between HUVE cells and human dermal fibroblasts were observed in the three-dimensional angiogenic assay on collagen gels described by Montesano et al [14]. These results indicate that data obtained with angiogenic systems using Matrigel must be interpreted with caution and that the assay described by Montesano et al [14], is more reliable to describe angiogenesis.

  20. Thorns and dermal denticles of skates Atlantoraja cyclophora and A. castelnaui: Microscopic features and functional implications.

    PubMed

    Rangel, Bianca de Sousa; Wosnick, Natascha; Magdanelo Leandro, Rafael; Amorim, Alberto Ferreira de; Kfoury Junior, José Roberto; Rici, Rose Eli Grassi

    2016-12-01

    Some batoid species are covered with dermal denticles (or placoid scales) that occasionally develop into thorns. In sexually mature males, sharp teeth and alar thorns found on the apex of the lateral disc are used to hold the female during copulation. This study set out to analyze microscopic features of modified dermal denticles and thorns and to investigate sexual dimorphism in Atlantoraja cyclophora and A. castelnaui species. Skin samples collected from areas covered with thorns were fixed in 10% formaldehyde, processed and analyzed using scanning electron microscopy. Alar thorn morphology varied within species, while caudal thorn, rostral and caudal dermal denticle morphology varied within and between species. These structures play an important role in the protection and reproduction of the species studied and constitute important taxonomic information, given they are often the only elements preserved in archaeological sites and fossil records.

  1. Alopecia in Rhesus macaques correlates with immunophenotypic alterations in dermal inflammatory infiltrates consistent with hypersensitivity etiology

    PubMed Central

    Kramer, Joshua; Fahey, Michele; Santos, Rosemary; Carville, Angela; Wachtman, Lynn; Mansfield, Keith

    2010-01-01

    Background Although alopecia is a commonly recognized problem affecting many captive Rhesus macaque colonies, there is no consensus as to the underlying etiology or appropriate course of management. Methods and Results We performed skin biopsies on a group of Rhesus macaques and demonstrate that alopecia is associated with superficial dermal perivascular mononuclear cell infiltrates and skin pathology consistent with chronic hypersensitivity dermatitis. Immunohistochemistry demonstrated that the inflammation is primarily composed of CD4+ cells admixed with histiocytes and mast cells. Inflammation is correlated with degree of alopecia. Further analysis in different groups of macaques revealed that animals born outdoors or infected with lung mites had reduced dermal inflammatory cell infiltrates and a lower incidence of alopecia. Conclusions These findings support a hypothesis that an altered housing status resulting in decreased pathogen burden in Rhesus macaque colonies may contribute to dermal immunophenotypic alterations and subsequent development of dermatitis with resultant alopecia. PMID:20102458

  2. Characterization and evolution of dermal filaments from patients with Morgellons disease

    PubMed Central

    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. PMID:23326202

  3. Characterization and evolution of dermal filaments from patients with Morgellons disease.

    PubMed

    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.

  4. Cell therapy for full-thickness wounds: are fetal dermal cells a potential source?

    PubMed

    Akershoek, J J; Vlig, M; Talhout, W; Boekema, B K H L; Richters, C D; Beelen, R H J; Brouwer, K M; Middelkoop, E; Ulrich, M M W

    2016-04-01

    The application of autologous dermal fibroblasts has been shown to improve burn wound healing. However, a major hurdle is the availability of sufficient healthy skin as a cell source. We investigated fetal dermal cells as an alternative source for cell-based therapy for skin regeneration. Human (hFF), porcine fetal (pFF) or autologous dermal fibroblasts (AF) were seeded in a collagen-elastin substitute (Novomaix, NVM), which was applied in combination with an autologous split thickness skin graft (STSG) to evaluate the effects of these cells on wound healing in a porcine excisional wound model. Transplantation of wounds with NVM+hFF showed an increased influx of inflammatory cells (e.g., neutrophils, macrophages, CD4(+) and CD8(+) lymphocytes) compared to STSG, acellular NVM (Acell-NVM) and NVM+AF at post-surgery days 7 and/or 14. Wounds treated with NVM+pFF presented only an increase in CD8(+) lymphocyte influx. Furthermore, reduced alpha-smooth muscle actin (αSMA) expression in wound areas and reduced contraction of the wounds was observed with NVM+AF compared to Acell-NVM. Xenogeneic transplantation of NVM+hFF increased αSMA expression in wounds compared to NVM+AF. An improved scar quality was observed for wounds treated with NVM+AF compared to Acell-NVM, NVM+hFF and NVM+pFF at day 56. In conclusion, application of autologous fibroblasts improved the overall outcome of wound healing in comparison to fetal dermal cells and Acell-NVM, whereas application of fetal dermal fibroblasts in NVM did not improve wound healing of full-thickness wounds in a porcine model. Although human fetal dermal cells demonstrated an increased immune response, this did not seem to affect scar quality.

  5. Histology of the heterostracan dermal skeleton: Insight into the origin of the vertebrate mineralised skeleton

    PubMed Central

    Marquart, Chloe L.

    2015-01-01

    ABSTRACT 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

  6. Protective effect of oat bran extracts on human dermal fibroblast injury induced by hydrogen peroxide.

    PubMed

    Feng, Bing; Ma, Lai-ji; Yao, Jin-jing; Fang, Yun; Mei, Yan-ai; Wei, Shao-min

    2013-02-01

    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 (H(2)O(2)). 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 H(2)O(2) 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 H(2)O(2), but application oat peptides with H(2)O(2) at same time did not. Pre-treatment of human dermal fibroblasts with Oatp significantly reversed the H(2)O(2)-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 H(2)O(2)-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.

  7. Histology of the heterostracan dermal skeleton: Insight into the origin of the vertebrate mineralised skeleton.

    PubMed

    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

  8. Comparing anti-hyperglycemic activity and acute oral toxicity of three different trivalent chromium complexes in mice.

    PubMed

    Li, Fang; Wu, Xiangyang; Zou, Yanmin; Zhao, Ting; Zhang, Min; Feng, Weiwei; Yang, Liuqing

    2012-05-01

    Three different ligands (rutin, folate and stachyose) of chromium(III) complexes were compared to examine whether they have similar effect on anti-hyperglycemic activity as well as the acute toxicity status. Anti-hyperglycemic activities of chromium rutin complex (CrRC), chromium folate complex (CrFC) and chromium stachyose complex (CrSC) were examined in alloxan-induced diabetic mice with daily oral gavage for a period of 2 weeks at the dose of 0.5-3.0 mg Cr/kg. Acute toxicities of CrRC and CrFC were tested using ICR mice at the dose of 1.0-5.0 g/kg with a single oral gavage and observed for a period of 2 weeks. Biological activities results indicated that only CrRC and CrFC could decrease blood glucose level, reduce the activities of aspartate transaminase, alanine transaminase, alkaline phosphatase, and increase liver glycogen level. In acute toxicity study, LD(50) values for both CrRC and CrFC were above 5.0 g/kg. The minimum lethal dose for CrFC was above 5.0 g/kg, while that for CrRC was 1.0 g/kg. Anti-diabetic activity of those chromium complexes was not similar and their acute toxicities were also different. CrFC represent an optimal chromium supplement among those chromium complexes with potential therapeutic value to control blood glucose in diabetes and non-toxicity in acute toxicity.

  9. Protective Effects of Triphala on Dermal Fibroblasts and Human Keratinocytes

    PubMed Central

    Varma, Sandeep R.; Sivaprakasam, Thiyagarajan O.; Mishra, Abheepsa; Kumar, L. M. Sharath; Prakash, N. S.; Prabhu, Sunil; Ramakrishnan, Shyam

    2016-01-01

    Human skin is body’s vital organ constantly exposed to abiotic oxidative stress. This can have deleterious effects on skin such as darkening, skin damage, and aging. Plant-derived products having skin-protective effects are well-known traditionally. Triphala, a formulation of three fruit products, is one of the most important rasayana drugs used in Ayurveda. Several skin care products based on Triphala are available that claim its protective effects on facial skin. However, the skin protective effects of Triphala extract (TE) and its mechanistic action on skin cells have not been elucidated in vitro. Gallic acid, ellagic acid, and chebulinic acid were deduced by LC-MS as the major constituents of TE. The identified key compounds were docked with skin-related proteins to predict their binding affinity. The IC50 values for TE on human dermal fibroblasts (HDF) and human keratinocytes (HaCaT) were 204.90 ± 7.6 and 239.13 ± 4.3 μg/mL respectively. The antioxidant capacity of TE was 481.33 ± 1.5 mM Trolox equivalents in HaCaT cells. Triphala extract inhibited hydrogen peroxide (H2O2) induced RBC haemolysis (IC50 64.95 μg/mL), nitric oxide production by 48.62 ± 2.2%, and showed high reducing power activity. TE also rescued HDF from H2O2-induced damage; inhibited H2O2 induced cellular senescence and protected HDF from DNA damage. TE increased collagen-I, involucrin and filaggrin synthesis by 70.72 ± 2.3%, 67.61 ± 2.1% and 51.91 ± 3.5% in HDF or HaCaT cells respectively. TE also exhibited anti-tyrosinase and melanin inhibition properties in a dose-dependent manner. TE increased the mRNA expression of collagen-I, elastin, superoxide dismutase (SOD-2), aquaporin-3 (AQP-3), filaggrin, involucrin, transglutaminase in HDF or HaCaT cells, and decreased the mRNA levels of tyrosinase in B16F10 cells. Thus, Triphala exhibits protective benefits on skin cells in vitro and can be used as a potential ingredient in skin care formulations. PMID:26731545

  10. Evaluation of in vitro vs. in vivo methods for assessment of dermal absorption of organic flame retardants: a review.

    PubMed

    Abdallah, Mohamed Abou-Elwafa; Pawar, Gopal; Harrad, Stuart

    2015-01-01

    There is a growing interest to study human dermal exposure to a large number of chemicals, whether in the indoor or outdoor environment. Such studies are essential to predict the systemic exposure to xenobiotic chemicals for risk assessment purposes and to comply with various regulatory guidelines. However, very little is currently known about human dermal exposure to persistent organic pollutants. While recent pharmacokinetic studies have highlighted the importance of dermal contact as a pathway of human exposure to brominated flame retardants, risk assessment studies had to apply assumed values for percutaneous penetration of various flame retardants (FRs) due to complete absence of specific experimental data on their human dermal bioavailability. Therefore, this article discusses the current state-of-knowledge on the significance of dermal contact as a pathway of human exposure to FRs. The available literature on in vivo and in vitro methods for assessment of dermal absorption of FRs in human and laboratory animals is critically reviewed. Finally, a novel approach for studying human dermal absorption of FRs using in vitro three-dimensional (3D) human skin equivalent models is presented and the challenges facing future dermal absorption studies on FRs are highlighted.

  11. Dermal carotenoids as measured by resonance Raman spectroscopy as a biomarker of response to a fruit/vegetable intervention study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dermal carotenoid status may have utility as a biomarker for vegetable and fruit consumption. Resonance Raman spectroscopy (RRS) is a valid, non-invasive method to assess dermal carotenoids as a biomarker of usual vegetable and fruit intake, but has not been evaluated in response to a whole-diet in...

  12. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections.

    PubMed

    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.

  13. Nanocrystalline titanium dioxide and magnesium oxide in vitro dermal absorption in human skin.

    PubMed

    van der Merwe, Deon; Tawde, Snehal; Pickrell, John A; Erickson, Larry E

    2009-01-01

    The dermal absorption potential of a nanocrystalline magnesium oxide (MgO) and titanium dioxide (TiO(2)) mixture in dermatomed human skin was assessed in vitro using Bronaugh-type flow-through diffusion cells. Nanocrystalline material was applied to the skin surface at a dose rate of 50 mg/cm(2) as a dry powder, as a water suspension, and as a water/surfactant (sodium lauryl sulfate) suspension, for 8 hours. Dermal absorption of nanocrystalline MgO and TiO(2) through human skin with intact, functional stratum corneum was not detectable under the conditions of this experiment.

  14. Evaluation of a 2-aminoimidazole variant as adjuvant treatment for dermal bacterial infections

    PubMed Central

    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. PMID:28138218

  15. [Standard prescriptions for the formulation of medicinal preparations in pharmacies. I. Suspensions for dermal administration].

    PubMed

    Subert, J; Kolár, J; Vasková, V

    2008-04-01

    The paper summarizes the present state of standard prescriptions for the formulation of suspensions for dermal administration in the Czech Republic and compares it with the NRF (Neues Rezeptur-Formularium in Deuscher Arzneimittel-Codex) standard prescriptions. The analysis of medical prescriptions for suspensions for dermal administration dispensed in the pharmacies of the Czech Republic has revealed that 18.8 % of the prescriptions were for 50% suspension of zinc(II) oxide in sunflower oil. This preparation should therefore become a candidate for standardization as a monograph in the national part of the Czech Pharmacopoeia.

  16. Simple analytical test and a formula to predict the potential for dermal carcinogenicity from petroleum oils

    SciTech Connect

    Haas, J.M.; Dimeler, G.R.; Basil, E.W.; Wilkins, G.W.; Nutter, J.S.

    1987-11-01

    A correlation for predicting dermal carcinogenicity of petroleum oils in laboratory animals has been developed using two simple analytical tests. The tests are the Food and Drug Administration test (FDA) commonly used to measure white oil purity, and a viscosity test. In the correlation, FDA is a measure of aromaticity, and viscosity is used to account for molecular weight. The FDA test alone appears to be comparable to other predictors now in use, but incorporating viscosity significantly increases the accuracy of predicting dermal carcinogenicity. A formula is proposed, using both the FDA test results and viscosity, that predicts the percentage of mice which will develop neoplastic skin tumors.

  17. Autologous Smashed Dermal Graft with Epidermal Re-closure: Modified Technique for Acne Scars

    PubMed Central

    Nagaraju, Umashankar; Chikkaiah, Mahesh K; Raju, Belliappa P; Agarwal, Priyanka

    2016-01-01

    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. PMID:28163459

  18. Mechanisms of Mycotoxin-induced Dermal Toxicity and Tumorigenesis Through Oxidative Stress-related Pathways

    PubMed Central

    Doi, Kunio; Uetsuka, Koji

    2014-01-01

    Among the many mycotoxins, T-2 toxin, citrinin (CTN), patulin (PAT), aflatoxin B1 (AFB1) and ochratoxin A (OTA) are known to have the potential to induce dermal toxicity and/or tumorigenesis in rodent models. T-2 toxin, CTN, PAT and OTA induce apoptosis in mouse or rat skin. PAT, AFB1 and OTA have tumor initiating properties, and OTA is also a tumor promoter in mouse skin. This paper reviews the molecular mechanisms of dermal toxicity and tumorigenesis induced in rodent models by these mycotoxins especially from the viewpoint of oxidative stress-mediated pathways. PMID:24791061

  19. Dermal Influence on Epidermal Resurfacing during the Repair of Split Thickness Wounds.

    DTIC Science & Technology

    1983-08-15

    RESOLUTION TEST CHART N~ATIONAL BU.REAU OF STANDAPOS -1465 AW 4/ % % R %. . - -. ’. - ., PHOTOGRAPH THIS SHEET i.&6MAi- 1jNrLL(AC~t o~j 6PIA6PJ4AL ~I~ 00...epidermal and dermal interrelationships during wound repair. Platelets contain a growth factor for dermal fibroblasts. We are testing the effects of...examine the effects on the epidermis of adding a factor that affects the dermis (factors from platelets). Two methods were used to test for a

  20. [Elaboration of biodegradable polymer substrate for cultivation of human dermal fibroblasts].

    PubMed

    Shved, Iu A; Kukhareva, L V; Zorin, I M; Solov'ev, A Iu; Blinova, M I; Bilibin, A Iu; Pinaev, G P

    2006-01-01

    The influence of polylactic acid (PLA) surface films on the pattern of cell behavior was studied. The human dermal fibroblasts were cultivated on PLA covered glasses. The hydrophobic nature of PLA films depends on the availability of polymer solvent in the film preparation. PLA films obtained from a more polar solvent--aceton--appeared to be more hydrophilic than those obtained from methylene chloride. More hydrophilic polymer films also appeared to be more preferable for cell cultivation, and human dermal fibroblasts demonstrated a better adhesion and proliferation on hydrophilic rather than on hydrophobic PLA films.

  1. Distinct Requirements for Cranial Ectoderm and Mesenchyme-Derived Wnts in Specification and Differentiation of Osteoblast and Dermal Progenitors

    PubMed Central

    Goodnough, L. Henry; DiNuoscio, Gregg J.; Ferguson, James W.; Williams, Trevor; Lang, Richard A.; Atit, Radhika P.

    2014-01-01

    The cranial bones and dermis differentiate from mesenchyme beneath the surface ectoderm. Fate selection in cranial mesenchyme requires the canonical Wnt effector molecule β-catenin, but the relative contribution of Wnt ligand sources in this process remains unknown. Here we show Wnt ligands are expressed in cranial surface ectoderm and underlying supraorbital mesenchyme during dermal and osteoblast fate selection. Using conditional genetics, we eliminate secretion of all Wnt ligands from cranial surface ectoderm or undifferentiated mesenchyme, to uncover distinct roles for ectoderm- and mesenchyme-derived Wnts. Ectoderm Wnt ligands induce osteoblast and dermal fibroblast progenitor specification while initiating expression of a subset of mesenchymal Wnts. Mesenchyme Wnt ligands are subsequently essential during differentiation of dermal and osteoblast progenitors. Finally, ectoderm-derived Wnt ligands provide an inductive cue to the cranial mesenchyme for the fate selection of dermal fibroblast and osteoblast lineages. Thus two sources of Wnt ligands perform distinct functions during osteoblast and dermal fibroblast formation. PMID:24586192

  2. A comparison of the potency of newly developed oximes (K347, K628) and currently available oximes (obidoxime, HI-6) to counteract acute neurotoxic effects of Tabun in rats.

    PubMed

    Kassa, Jirí; Karasová, Jana Zdarová; Tesarová, Sandra; Musílek, Kamil; Kuca, Kamil

    2010-01-01

    The ability of newly developed oximes (K347, K628) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with currently available oximes (obidoxime, HI-6) using a functional observational battery. The neuroprotective effects of the oximes studied (K347, K628, obidoxime, HI-6) combined with atropine on rats poisoned with tabun at a sublethal dose (220 microg/kg i.m.; 80% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by a functional observational battery and automatic measurement of motor activity at 24 hours following tabun challenge. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive 24 hours following tabun challenge. Both newly developed oximes (K347, K628) combined with atropine are able to decrease tabun-induced neurotoxicity in the case of sublethal poisonings but they do not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease the tabun-induced acute neurotoxicity is higher than that of the oxime HI-6 and it is slightly slower than the neuroprotective efficacy of obidoxime. As the neuroprotective potency of both newly developed oximes (K347, K628) is not as high as the potency of obidoxime, they are not a suitable replacement for obidoxime for the treatment of acute tabun poisonings.

  3. [Acute toxicity of bemithyl and bromithyl].

    PubMed

    Bugaeva, L I; Spasov, A A; Verovskiĭ, V E; Iezhitsa, I N

    2000-01-01

    The experiments on rats showed for bemithyl LD50 = 581.48 (350.17-965.57) mg/kg and for bromithyl LD50 = 1750.30 (1463.07-2093.92) mg/kg (males) and 1584.29 (1280.46-1960.22) mg/kg (females). The therapeutic ratios are 4-6 for both drugs, while the toxicity index is 10-15 for bemithyl and 20 <196> 22 for bromithyl. It was established that ergotropic effects prevail in the toxicity of bemithyl administered in the 20-80 mg/kg dose range, while trophotropic effects are dominating at doses above 100 mg/kg. Bromithyl exhibits a dose-dependent trophotropic effect in the entire dose range.

  4. Lymphatic Vascular Response to Acute Inflammation

    PubMed Central

    Lachance, Pier-Anne; Hazen, Amy; Sevick-Muraca, Eva M.

    2013-01-01

    During acute inflammation, functioning lymphatics are believed to reduce edema and to provide a transiting route for immune cells, but the extent at which the dermal lymphatic remodeling impacts lymphatic transport or the factors regulating these changes remains unclear. Herein we quantify the increase in lymphatic endothelial cells (LECs) and examine the expression of pro-angiogenenic and lymphangiogenic factors during acute cutaneous hypersensitivity (CHS). We found that LECs actively proliferate during CHS but that this proliferation does not affect the lymphatic vessel density. Instead, lymphatic remodeling is accompanied by lymphatic vessel leakiness and lower ejection of lymph fluid, which is observed only in the proximal lymphatic vessel draining the inflamed area. LECs and the immune cells release growth factors and cytokines during inflammation, which impact the lymphatic microenvironment and function. We identified that FGF-2, PLGF-2, HGF, EGF, and KC/CXCL17 are differentially expressed within tissues during acute CHS, but both VEGF-C and VEGF-D levels do not significantly change. Our results indicate that VEGF-C and VEGF-D are not the only players and other factors may be responsible for the LECs proliferation and altered lymphatic function in acute CHS. PMID:24086691

  5. Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts.

    PubMed

    Yoon, Jong Hyuk; Kim, Jaeyoon; Lee, Hyeongjoo; Kim, So Young; Jang, Hwan-Hee; Ryu, Sung Ho; Kim, Beom Joon; Lee, Taehoon G

    2012-11-23

    The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the β1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate peptide for the treatment of skin aging and wrinkles.

  6. A novel device to create consistent deep dermal burns in a porcine model.

    PubMed

    Menon, Seema; Chan, Queenie; Bertinetti, Monique; Harvey, John G; Hei, Erik R La; Holland, Andrew Ja

    2016-01-01

    We conducted this study to evaluate a novel device to create a consistent and reproducible deep partial thickness burn in a porcine model. A thermostatically controlled, heated aluminium disc device was fashioned by the Biomedical Department of our institution. Contact burns were made on the flank of two Great White pigs by applying the device heated to 92°C at intervals of 5, 10, 15 and 20 seconds to four separate test areas area of skin. Biopsies for histological analysis of burn depth were taken on day 0 at 10 minutes post burn and on day 8. Biopsies taken at day 0 revealed superficial to mid-dermal burns, with minimal dermal edema and necrosis. Those from day 8 showed mid to deep dermal edema and necrosis in all four test areas following a 20 second contact duration burn. The new contact burn device was able to create a consistent deep dermal burn after 20 seconds of contact. We anticipate that this new device could be used to investigate the development of hypertrophic scarring in a porcine model.

  7. CYTOKINE PROFILES DO NOT PREDICT ANTIBODY RESPONSES AND RESPIRATORY HYPERRESPONSIVENESS FOLLOWING DERMAL EXPOSURE TO ISOCYANATES

    EPA Science Inventory

    Rationale: Cytokine profiling of local lymph node responses following dermal exposure has been proposed as a test to identify chemicals that pose a risk of occupational asthma. The present study tested the hypothesis that relative differences in cytokine profiles for dini...

  8. Transdermal Delivery of Iron Using Soluble Microneedles: Dermal Kinetics and Safety.

    PubMed

    Modepalli, Naresh; Shivakumar, H Nanjappa; McCrudden, Maeliosa T C; Donnelly, Ryan F; Banga, Ajay; Murthy, S Narasimha

    2016-03-01

    Currently, the iron compounds are administered via oral and parenteral routes in patients of all ages, to treat iron deficiency. Despite continued efforts to supplement iron via these conventional routes, iron deficiency still remains the most prevalent nutritional disorder all over the world. Transdermal replenishment of iron is a novel, potential approach of iron replenishment. Ferric pyrophosphate (FPP) was found to be a suitable source of iron for transdermal replenishment. The safety of FPP was assessed in this project by challenging the dermal fibroblast cells with high concentration of FPP. The cell viability assay and reactive oxygen species assay were performed. The soluble microneedle array was developed, incorporated with FPP and the kinetics of free iron in the skin; extracellular fluid following dermal administration of microneedle array was investigated in hairless rats. From the cell based assays, FPP was selected as one of the potential iron sources for transdermal delivery. The microneedles were found to dissolve in the skin fluid within 3 hours of administration. The FPP concentration in the dermal extracellular fluid declined after complete dissolution of the microneedle array. Overall, the studies demonstrated the safety of FPP for dermal delivery and the feasibility of soluble microneedle approach for transdermal iron replenishment therapy.

  9. Phototoxic Risk Assessments on Benzophenone Derivatives: Photobiochemical Assessments and Dermal Cassette-Dosing Pharmacokinetic Study.

    PubMed

    Seto, Yoshiki; Ohtake, Hiroto; Kato, Masashi; Onoue, Satomi

    2015-08-01

    This study aimed to qualify photosafety screening on the basis of photochemical and pharmacokinetic (PK) data on dermally applied chemicals. Six benzophenone derivatives (BZPs) were selected as model compounds, and in vitro photochemical/phototoxic characterization and dermal cassette-dosing PK study were carried out. For comparison, an in vivo phototoxicity test was also conducted. All of the BZPs exhibited strong UVA/UVB absorption with molar extinction coefficients of over 2000 M(-1) × cm(-1), and benzophenone and ketoprofen exhibited significant reactive oxygen species (ROS) generation upon exposure to simulated sunlight (about 2.0 mW/cm(2)); however, ROS generation from sulisobenzone and dioxybenzone was negligible. To verify in vitro phototoxicity, a 3T3 neutral red uptake phototoxicity test was carried out, and benzophenone and ketoprofen were categorized to be phototoxic chemicals. The dermal PK parameters of ketoprofen were indicative of the highest dermal distribution of all BZPs tested. On the basis of its in vitro photochemical/phototoxic and PK data, ketoprofen was deduced to be highly phototoxic. The rank of predicted phototoxic risk of BZPs on the basis of the proposed screening strategy was almost in agreement with the results from the in vivo phototoxicity test. The combined use of photochemical and cassette-dosing PK data would provide reliable predictions of phototoxic risk for candidates with high productivity.

  10. Dermal fibroblasts contribute to multiple tissues in the accessory limb model.

    PubMed

    Hirata, Ayako; Gardiner, David M; Satoh, Akira

    2010-05-01

    The accessory limb model has become an alternative model for performing investigations of limb regeneration in an amputated limb. In the accessory limb model, a complete patterned limb can be induced as a result of an interaction between the wound epithelium, a nerve and dermal fibroblasts in the skin. Studies should therefore focus on examining these tissues. To date, however, a study of cellular contributions in the accessory limb model has not been reported. By using green fluorescent protein (GFP) transgenic axolotl tissues, we can trace cell fate at the tissue level. Therefore, in the present study, we transgrafted GFP skin onto the limb of a non-GFP host and induced an accessory limb to investigate cellular contributions. Previous studies of cell contribution to amputation-induced blastemas have demonstrated that dermal cells are the progenitors of many of the early blastema cells, and that these cells contribute to regeneration of the connective tissues, including cartilage. In the present study, we have determined that this same population of progenitor cells responds to signaling from the nerve and wound epithelium in the absence of limb amputation to form an ectopic blastema and regenerate the connective tissues of an ectopic limb. Blastema cells from dermal fibroblasts, however, did not differentiate into either muscle or neural cells, and we conclude that dermal fibroblasts are dedifferentiated along its developmental lineage.

  11. Cadherin 11 Involved in Basement Membrane Damage and Dermal Changes in Melasma.

    PubMed

    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. Comparison of Calcium and Barium Microcapsules as Scaffolds in the Development of Artificial Dermal Papillae

    PubMed Central

    Liu, Yang; Lin, Changmin; Zeng, Yang; Li, Haihong; Cai, Bozhi; Huang, Keng; Yuan, Yanping; Li, Yu

    2016-01-01

    This study aimed to develop and evaluate barium and calcium microcapsules as candidates for scaffolding in artificial dermal papilla. Dermal papilla cells (DPCs) were isolated and cultured by one-step collagenase treatment. The DPC-Ba and DPC-Ca microcapsules were prepared by using a specially designed, high-voltage, electric-field droplet generator. Selected microcapsules were assessed for long-term inductive properties with xenotransplantation into Sprague-Dawley rat ears. Both barium and calcium microcapsules maintained xenogenic dermal papilla cells in an immunoisolated environment and induced the formation of hair follicle structures. Calcium microcapsules showed better biocompatibility, permeability, and cell viability in comparison with barium microcapsules. Before 18 weeks, calcium microcapsules gathered together, with no substantial immune response. After 32 weeks, some microcapsules were near inflammatory cells and wrapped with fiber. A few large hair follicles were found. Control samples showed no marked changes at the implantation site. Barium microcapsules were superior to calcium microcapsules in structural and mechanical stability. The cells encapsulated in hydrogel barium microcapsules exhibited higher short-term viability. This study established a model to culture DPCs in 3D culture conditions. Barium microcapsules may be useful in short-term transplantation study. Calcium microcapsules may provide an effective scaffold for the development of artificial dermal papilla. PMID:27123456

  13. Characterization of acellular dermal matrices (ADMs) prepared by two different methods.

    PubMed

    Walter, R J; Matsuda, T; Reyes, H M; Walter, J M; Hanumadass, M

    1998-03-01

    The efficacy of acellular dermal matrix (ADM) in the treatment of full-thickness skin injuries as a dermal substitute depends on its low antigenicity, capacity for rapid vascularization, and stability as a dermal template. These properties will be determined largely by the final composition of the ADM. We have treated human skin with either Dispase followed by Triton X-100 detergent or NaCl followed by SDS detergent, cryosectioned the resulting ADMs, and then characterized them immunohistochemically. Staining for cell-associated antigens (HLA-ABC, HLA-DR, vimentin, desmin, talin), extracellular matrix components (chondroitin sulfate, fibronectin, laminin, vitronectin, hyaluronic acid), elastin, and collagen type VII was dramatically reduced or absent from ADMs prepared by both methods. However, significant amounts of elastin, keratan sulfate, laminin, and collagen types III and IV were still observed in both ADMs. Both methods of ADM preparation resulted in extensive extraction of both cellular and extracellular components of the skin but retention of the basic dermal architecture. In general, ADM prepared by the NaCl-SDS method retained larger amounts of each antigen than did that prepared by the Dispase-Triton method. This was most evident for laminin and type VII collagen but larger amounts of type IV collagen, fibronectin, desmin, elastin, and HLA-DR were also evident in the NaCl-SDS ADM.

  14. ESTIMATING CHILDREN'S DERMAL AND NON-DIETARY INGESTION EXPOSURE AND DOSE WITH EPA'S SHEDS MODEL

    EPA Science Inventory

    A physically-based stochastic model (SHEDS) has been developed to estimate pesticide exposure and dose to children via dermal residue contact and non-dietary ingestion. Time-location-activity data are sampled from national survey results to generate a population of simulated ch...

  15. Comparison of Calcium and Barium Microcapsules as Scaffolds in the Development of Artificial Dermal Papillae.

    PubMed

    Liu, Yang; Lin, Changmin; Zeng, Yang; Li, Haihong; Cai, Bozhi; Huang, Keng; Yuan, Yanping; Li, Yu

    2016-01-01

    This study aimed to develop and evaluate barium and calcium microcapsules as candidates for scaffolding in artificial dermal papilla. Dermal papilla cells (DPCs) were isolated and cultured by one-step collagenase treatment. The DPC-Ba and DPC-Ca microcapsules were prepared by using a specially designed, high-voltage, electric-field droplet generator. Selected microcapsules were assessed for long-term inductive properties with xenotransplantation into Sprague-Dawley rat ears. Both barium and calcium microcapsules maintained xenogenic dermal papilla cells in an immunoisolated environment and induced the formation of hair follicle structures. Calcium microcapsules showed better biocompatibility, permeability, and cell viability in comparison with barium microcapsules. Before 18 weeks, calcium microcapsules gathered together, with no substantial immune response. After 32 weeks, some microcapsules were near inflammatory cells and wrapped with fiber. A few large hair follicles were found. Control samples showed no marked changes at the implantation site. Barium microcapsules were superior to calcium microcapsules in structural and mechanical stability. The cells encapsulated in hydrogel barium microcapsules exhibited higher short-term viability. This study established a model to culture DPCs in 3D culture conditions. Barium microcapsules may be useful in short-term transplantation study. Calcium microcapsules may provide an effective scaffold for the development of artificial dermal papilla.

  16. Implantation of placenta-derived mesenchymal stem cells accelerates murine dermal wound closure through immunomodulation

    PubMed Central

    Wang, Haifeng; Chen, Lianyu; Liu, Yang; Luo, Bangzhen; Xie, Nanzi; Tan, Tao; Song, Lige; Erli, Pei; Luo, Ming

    2016-01-01

    Background: Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus. Although previous studies have established that inflammation, ischemia and neuropathy contribute to the development of DFU, it is still an unmet medical need due to lack knowledge of cellular and molecular mechanisms associated with DFU. In the present study, we tested our hypothesis that subcutaneous application of human placental mesenchymal stem cells (PMSCs) can accelerate diabetic dermal wound healing by modulating immunoresponse. Methods and Results: By using an in vivo excisional wound healing model in Goto-Kakizaki (GK) rats, we found that injection of PMSCs accelerates wound closure. Further studies revealed that application of PMSCs can regulate inflammation associated with wound healing by controlling secretion of pro- and anti-inflammatory factors, the beneficial effects can be partially blocked by application of antibodies against interleukin-10 (IL-10). Furthermore, in vitro experiments suggested that co-culture of PMSCs with human dermal fibroblasts can significantly inhibit activation of NF-ĸB induced by lipopolysaccharides (LPS), indicating the molecular mechanism of PMSCs mediated immunomodulation. Conclusion: Taken together, our study suggested that the immunomodulation of PMSCs play an important role on diabetic dermal wound healing process, thus PMSCs might represent an attractive choice for treatment of diabetes dermal wound and DFU. PMID:27904691

  17. Race Does Not Predict Melanocyte Heterogeneous Responses to Dermal Fibroblast-Derived Mediators

    PubMed Central

    Sirimahachaiyakul, Pornthep; Sood, Ravi F.; Muffley, Lara A.; Seaton, Max; Lin, Cheng-Ta; Qiao, Liang; Armaly, Jeffrey S.; Hocking, Anne M.; Gibran, Nicole S.

    2015-01-01

    Introduction 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. Methods and Materials 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. Results 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. Discussion 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. PMID:26418010

  18. Staphylococcus aureus induces hypoxia and cellular damage in porcine dermal explants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. ...

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

    PubMed Central

    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

  20. Soil organic matter content effects on dermal pesticide bioconcentration in American toads (Bufo americanus).

    EPA Science Inventory

    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...

  1. Outcome of Dermal Grafting in the Management of Atrophic Facial Scars

    PubMed Central

    Shilpa, Kanathur; Sacchidanand, S; Leelavathy, Budamakuntla; Shilpashree, Padmanabha; Divya, Gorur; Ranjitha, Rammurthy; Lakshmi, DV

    2016-01-01

    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. PMID:28163456

  2. Hair follicles' transit-amplifying cells govern concurrent dermal adipocyte production through Sonic Hedgehog.

    PubMed

    Zhang, Bing; Tsai, Pai-Chi; Gonzalez-Celeiro, Meryem; Chung, Oliver; Boumard, Benjamin; Perdigoto, Carolina N; Ezhkova, Elena; Hsu, Ya-Chieh

    2016-10-15

    Growth and regeneration of one tissue within an organ compels accommodative changes in the surrounding tissues. However, the molecular nature and operating logic governing these concurrent changes remain poorly defined. The dermal adipose layer expands concomitantly with hair follicle downgrowth, providing a paradigm for studying coordinated changes of surrounding lineages with a regenerating tissue. Here, we discover that hair follicle transit-amplifying cells (HF-TACs) play an essential role in orchestrating dermal adipogenesis through secreting Sonic Hedgehog (SHH). Depletion of Shh from HF-TACs abrogates both dermal adipogenesis and hair follicle growth. Using cell type-specific deletion of Smo, a gene required in SHH-receiving cells, we found that SHH does not act on hair follicles, adipocytes, endothelial cells, and hematopoietic cells for adipogenesis. Instead, SHH acts directly on adipocyte precursors, promoting their proliferation and their expression of a key adipogenic gene, peroxisome proliferator-activated receptor γ (Pparg), to induce dermal adipogenesis. Our study therefore uncovers a critical role for TACs in orchestrating the generation of both their own progeny and a neighboring lineage to achieve concomitant tissue production across lineages.

  3. Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Focal dermal hypoplasia is an X-linked dominant disorder characterized by patchy hypoplastic skin and digital, ocular, and dental malformations. We used array comparative genomic hybridization to identify a 219-kb deletion in Xp11.23 in two affected females. We sequenced genes in this region and fou...

  4. Cytotoxic evaluation of biomechanically improved crosslinked ovine collagen on human dermal fibroblasts.

    PubMed

    Awang, M A; Firdaus, M A B; Busra, M B; Chowdhury, S R; Fadilah, N R; Wan Hamirul, W K; Reusmaazran, M Y; Aminuddin, M Y; Ruszymah, B H I

    2014-01-01

    Earlier studies in our laboratory demonstrated that collagen extracted from ovine tendon is biocompatible towards human dermal fibroblast. To be able to use this collagen as a scaffold in skin tissue engineering, a mechanically stronger scaffold is required that can withstand manipulation before transplantation. This study was conducted to improve the mechanical strength of this collagen sponge using chemical crosslinkers, and evaluate their effect on physical, chemical and biocompatible properties. Collagen sponge was crosslinked with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and glutaraldehyde (GA). Tensile test, FTIR study and mercury porosimetry were used to evaluate mechanical properties, chemical property and porosity, respectively. MTT assay was performed to evaluate the cytotoxic effect of crosslinked collagen sponge on human dermal fibroblasts. The FTIR study confirmed the successful crosslinking of collagen sponge. Crosslinking with EDC and GA significantly increased the mechanical strength of collagen sponge, with GA being more superior. Crosslinking of collagen sponge significantly reduced the porosity and the effect was predominant in GA-crosslinked collagen sponge. The GA-crosslinked collagen showed significantly lower, 60% cell viability towards human dermal fibroblasts compared to that of EDC-crosslinked collagen, 80% and non-crosslinked collagen, 100%. Although the mechanical strength was better when using GA but the more toxic effect on dermal fibroblast makes EDC a more suitable crosslinker for future skin tissue engineering.

  5. Ocular findings in quarter horses with hereditary equine regional dermal asthenia

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to compare ocular structures of Quarter Horses homozygous for hereditary equine regional dermal asthenia (HERDA) with those of Quarter Horses not affected by HERDA (control horses) and to determine the frequency of new corneal ulcers for horses with and without HERDA ...

  6. Dermal pharmacokinetics of Terpinen-4-ol following topical administration of Zingiber cassumunar (plai) oil.

    PubMed

    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.

  7. DERMAL AND MOUTHING TRANSFERS OF SURFACE RESIDUES MEASURED USING FLUORESCENCE IMAGING

    EPA Science Inventory

    To reduce the uncertainty associated with current estimates of children's exposure to pesticides by dermal contact and non-dietary ingestion, residue transfer data are required. Prior to conducting exhaustive studies, a screening study to develop and test methods for measuring...

  8. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype.

    PubMed

    de la Puente, Pilar; Ludeña, Dolores; López, Marta; Ramos, Jennifer; Iglesias, Javier

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering.

  9. 40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... radiolabeled test substance to result in a level of commercial hexane in the blood that approximates the level... test substance intravenously (i.e., Group A), the concentration of test substance in blood and excreta... inhalation and dermal routes (i.e., Groups B through F), the concentration of test substance in blood...

  10. 40 CFR 795.232 - Inhalation and dermal pharmacokinetics of commercial hexane.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... radiolabeled test substance to result in a level of commercial hexane in the blood that approximates the level... test substance intravenously (i.e., Group A), the concentration of test substance in blood and excreta... inhalation and dermal routes (i.e., Groups B through F), the concentration of test substance in blood...

  11. Kinetics of 3-(4-methylbenzylidene)camphor in rats and humans after dermal application

    SciTech Connect

    Schauer, Ute M.D.; Voelkel, Wolfgang; Heusener, Alexander; Colnot, Thomas; Broschard, Thomas H.; Landenberg, Friedrich von; Dekant, Wolfgang . E-mail: dekant@toxi.uni-wuerzburg.de

    2006-10-15

    The toxicokinetics of 4-MBC after dermal administration were investigated in human subjects and in rats. Humans (3 male and 3 female subjects) were exposed to 4-MBC by topical application of a commercial sunscreen formulation containing 4% 4-MBC (w/w), covering 90% of the body surface and resulting in a mean dermal 4-MBC dose of 22 mg/kg bw. In rats, dermal 4-MBC doses of 400 and 2000 mg/kg bw were applied in a formulation using an occlusive patch for 24 h. Concentrations of 4-MBC and its metabolites were monitored over 96 h in plasma (rats and humans) and urine (humans). In human subjects, plasma levels of 4-MBC peaked at 200 pmol/ml in males and 100 pmol/ml in females 6 h after application and then decreased to reach the limit of detection after 24 h (females), respectively, 36 h (males). After dermal application of 4-MBC, peak plasma concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were 50-80 pmol/ml at 12 h and of 3-(4-carboxybenzylidene)camphor were 100-200 pmol/ml at 24 h. In male and female rats, peak plasma levels of 4-MBC were 200 (dose of 400 mg/kg bw) and 1 200 pmol/ml (dose of 2000 mg/kg bw). These levels remained constant for up to 24-48 h after dermal application. Peak plasma concentrations of 3-(4-carboxybenzylidene)-6-hydroxycamphor were 18,000 pmol/ml (males) and of 3-(4-carboxybenzylidene)camphor were 55,000 pmol/ml (females) between 48 and 72 h after application of the high dose of 4-MBC. In human subjects, only a small percentage of the dermally applied dose of 4-MBC was recovered in the form of metabolites in urine, partly as glucuronides. The obtained results suggest a more intensive biotransformation of 4-MBC in rats as compared to humans after dermal application and a poor absorption of 4-MBC through human skin.

  12. Acute Pancreatitis and Pregnancy

    MedlinePlus

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  13. Clinical Performance of a Dermal Filler Containing Natural Glycolic Acid and a Polylactic Acid Polymer

    PubMed Central

    Macchetto, Pedro Cervantes; Durán Páramo, Rosa Margarita

    2010-01-01

    Lipoatrophy is a condition that affects certain individuals, most commonly those who are infected with the human immunodeficiency virus.1–3 Injectable fillers are used for the treatment of these dermal contour deformities to smooth dermal depressions formed by the loss of volume. These dermal fillers (also known as soft tissue augmentation devices) can correct contour deformities caused by lipoatrophy in patients who are human immunodeficiency virus positive or negative. The product used in this study is a patented, second-generation, injectable, dermal collagen stimulator that combines glycolic acid and polylactic acid. The glycolic acid used is not a polymer, but rather an acid derived from sugar cane. Its chemical structure corresponds to that of an alpha-hydroxy acid. Glycolic acid is a well-characterized agent that is present in a number of cosmetic products. Polylactic acid is a synthetic, biocompatible, biodegradable, inert, synthetic polymer from the poly a-hydroxy-acid family that is believed to stimulate fibroblasts to produce more collagen, thus increasing facial volume. Together, polylactic acid and glycolic acid act in concert to 1) stimulate collagen production and 2) hydrate the outer layers of the skin. A multicenter, clinical investigation authorized by the Mexican Secretariat of Health was conducted between September 20, 2002, and September 19, 2004. This clinical study was conducted in male patients between 32 and 60 years of age with lipoatrophy as a result of highly active antiretroviral therapy for human immunodeficiency virus infection. The study objective was to measure the improvement of contour deformities after the injection of a dermal collagen stimulator containing glycolic acid and polylactic acid. In addition to safety, this dermal filler was assessed when used to correct volume deformities caused by lipoatrophy in subjects who are human immunodeficiency virus positive. Thirty male subjects participated and were treated as follows

  14. Effect of sub-acute oral cyanide administration in rats: protective efficacy of alpha-ketoglutarate and sodium thiosulfate.

    PubMed

    Tulsawani, R K; Debnath, M; Pant, S C; Kumar, Om; Prakash, A O; Vijayaraghavan, R; Bhattacharya, R

    2005-09-10

    Chronic toxicity of cyanide in humans and animals has been previously described. Alpha-ketoglutarate (alpha-KG) and sodium thiosulfate (STS) are known to confer remarkable protection against acute cyanide poisoning in rodents. Their efficacy against sub-acute or chronic cyanide exposure is not known. The objective of the present study was to assess the sub-acute toxicity of potassium cyanide (KCN) in female rats following oral administration of 7.0 mg/kg (0.5 LD50) for 14 d. The effect of alpha-KG (oral; 1.0 g/kg) and/or STS (intraperitoneal, 1.0 g/kg) on cyanide toxicity was also evaluated. Various hematological and biochemical indices were determined after 7 d of treatment and additional parameters like organ-body weight index (OBI) and histology of brain, heart, lung, liver, kidney and spleen were performed after 14 and 21 d (recovery group) of cyanide exposure. Sub-acute exposure of KCN did not produce any significant change in body weight of the animals, OBI, hematology and the levels of blood urea, creatinine, aspartate aminotransferase, triiodothyronine (T3) and tetraiodothyronine (T4). The levels of temporal glutathione disulfide (GSSG) and hepatic malondialdehyde (MDA), reduced glutathione (GSH) and GSSG were unaffected. However, in KCN treated animals elevated levels of blood glucose and reduced levels of alanine aminotransferase were observed. Activities of cytochrome c oxidase in the brain and rhodanese in the liver were diminished. Reduced levels of GSH and enhanced levels of MDA in brain were observed. Increased levels of blood thiocyanate were observed in all the treatments of KCN. Additionally, KCN also produced various histological changes in the brain, heart, liver and kidney. Although, treatment of alpha-KG and STS alone significantly blunted the toxicity of KCN, concomitant use of both interventions afforded to maximum protection. This study indicates a promising role of alpha-KG and STS for the treatment of prolonged cyanide exposures.

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

    PubMed

    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

  16. Fertilizer use and self-reported respiratory and dermal symptoms among tree planters.

    PubMed

    Gorman Ng, Melanie; Stjernberg, Ernst; Koehoorn, Mieke; Demers, Paul A; Winters, Meghan; Davies, Hugh W

    2013-01-01

    In British Columbia, some tree planting operations require workers to fertilize planted seedlings with polymer-coated nitrogen, phosphorus, and potassium (NPK) fertilizers. This study examined respiratory and dermal health associated with fertilizer exposure among tree planters. We interviewed 223 tree planters using an adapted version of the American Thoracic Society questionnaire supplemented with questions on dermal health. Subjects were grouped by categories of increasing duration of exposure, with workers who had not worked with fertilizer as a reference group. The relationship between exposure and reported work-related symptoms was analyzed using logistic regression, adjusting for age, cumulative tobacco cigarettes smoked, marijuana smoking status, sex, and exposure to abrasive spruce needles. An elevated odds ratio was seen for work-related cough, phlegm, nasal symptoms, nosebleed, and skin rash in the highest exposure group (>37 days of fertilizer use in the past 2 years) but was significant only for phlegm (odds ratio = 3.59, 95% confidence interval = 1.10-11.70). Trends of increasing odds ratios with increasing exposure were seen for cough, phlegm, nasal symptoms, and skin rash. The results suggest a weak association between respiratory and dermal irritation and work with fertilizer. Results highlight the need for further exposure monitoring within the tree planting industry, and larger studies to investigate the relationship between work with fertilizer and respiratory and dermal health symptoms. [Supplementary materials are available for this article. Go to the publisher's online edition of the Journal of Occupational and Environmental Hygiene for the following free supplemental resource: a PDF file containing a respiratory and dermal health questionnaire.].

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

    PubMed Central

    Ryu, Hwa Jung; Seo, Mu Yeb; Jung, Sung Kyu; Maeng, Eun Ho; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Taek-Jin; Jo, Ki-Yeon; Kim, Yu-Ri; Cho, Kyu-Bong; Kim, Meyoung-Kon; Lee, Beom Jun; Son, Sang Wook

    2014-01-01

    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 was dose-dependent irritation at the site of application, there were no abnormal findings related to ZnO NPs in other organs. Increased concentrations of ZnO in the liver, small intestine, large intestine, and feces were thought to result from oral ingestion of ZnO NPs via licking. Penetration of ZnO NPs through the skin seemed to be limited via the dermal route. This study demonstrates that there was no observed adverse effect of ZnO NPs up to 1,000 mg/kg body weight when they are applied dermally. PMID:25565832

  18. Human dermal absorption of chlorinated organophosphate flame retardants; implications for human exposure.

    PubMed

    Abou-Elwafa Abdallah, Mohamed; Pawar, Gopal; Harrad, Stuart

    2016-01-15

    Tris-2-chloroethyl phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCIPP) and tris-1,3-dichloropropyl phosphate (TDCIPP) are organophosphate flame retardants (PFRs) widely applied in a plethora of consumer products despite their carcinogenic potential. Human dermal absorption of these PFRs is investigated for the first time using human ex vivo skin and EPISKIN™ models. Results of human ex vivo skin experiments revealed 28%, 25% and 13% absorption of the applied dose (500 ng/cm(2), finite dose) of TCEP, TCIPP and TDCIPP, respectively after 24h exposure. The EPISKIN™ model showed enhanced permeability values (i.e. weaker barrier), that were respectively 16%, 11% and 9% for TCEP, TCIPP and TDCIPP compared to human ex vivo skin. However, this difference was not significant (P>0.05). Estimated permeability constants (Kp, cm/h) showed a significant negative correlation with log Kow for the studied contaminants. The effect of hand-washing on dermal absorption of PFRs was investigated. Washing reduced overall dermal absorption, albeit to varying degrees depending on the physicochemical properties of the target PFRs. Moreover, slight variations of the absorbed dose were observed upon changing the dosing solution from acetone to 20% Tween 80 in water, indicating the potential influence of the dose vehicle on the dermal absorption of PFRs. Finally, estimated dermal uptake of the studied PFRs via contact with indoor dust was higher in UK toddlers (median ΣPFRs=36 ng/kg bw day) than adults (median ΣPFRs=4 ng/kg bw day). More research is required to fully elucidate the toxicological implications of such exposure.

  19. Comparative Host Response of 2 Human Acellular Dermal Matrices in a Primate Implant Model

    PubMed Central

    Sandor, Maryellen; Singh, Devinder; Silverman, Ronald P.; Xu, Hui; De Deyne, Patrick G.

    2014-01-01

    Objective: We examined the differences in capsule formation between 2 commercially available human acellular dermal matrices in a nonhuman primate model. Methods: Primates were implanted dorsally with a subcutaneously placed tissue expander and randomized into 3 groups, receiving skin coverage only, coverage with non-irradiated freeze-dried human acellular dermal matrix, or coverage with gamma-irradiated human acellular dermal matrix. After 9 weeks, soft tissue around the tissue expander was excised and evaluated qualitatively and quantitatively to assess extent of inflammation (CD68 antibodies and interleukin-6 levels), degradation and fibrosis (matrix metalloproteinase-1 and procollagen-1 staining), and mechanical (tensile) strength. Results: Histological evaluation of tissue around the tissue expander indicated differences in host response, suggesting capsule presence in the gamma-irradiated matrix group but not the freeze-dried matrix group. The extent of local inflammation was much higher in the gamma-irradiated matrix group which demonstrated mean (standard deviation) localized interleukin-6 concentration of 67.3 (53.6) vs 16.3 (6.7) pg/mg protein in the non-irradiated matrix group. There was robust degradation and fibrotic response in the gamma-irradiated matrix group versus the freeze-dried matrix group. Mechanical testing indicated mean (standard deviation) ultimate tensile strength of 12.0 (7.1) N in the gamma-irradiated matrix group versus 99.3 (48.8) N in the freeze-dried matrix group. Conclusions: Enclosure of a tissue expander with human acellular dermal matrix untreated by gamma irradiation led to minimal inflammation and minimal evidence of fibrosis/capsule around the tissue expander compared with robust capsule formation around the tissue expander that was covered by a gamma-irradiated human acellular dermal matrix. PMID:24570768

  20. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    SciTech Connect

    Puente, Pilar de la

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  1. Patterns of dermal exposure to hazardous substances in European union workplaces.

    PubMed

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

    2004-04-01

    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 types) in five countries in Europe. In order to optimize data collection and to develop a representative picture of dermal exposure, scenarios (tasks made up of a series of activities) were grouped together into dermal exposure operation units (DEOs). The allocation of scenarios to relevant DEOs was achieved on the basis of similarities of exposure routes, tasks and professional judgement. Sampling and quantification procedures were based on the approaches recommended by the OECD protocol. The laboratories involved in the analysis of the samples participated in quality assurance programmes. This exercise resulted in 419 body measurements and 437 measurements on hands expressed in terms of formulation (product) in use. Exposures for a given scenario varied by several orders of magnitude. The extent and patterns of exposure were found to be dependent on various exposure determinants, including inter- and intra-scenario variations. Hands were found to be the most contaminated parts of the body. Exposure patterns for liquid and solid contaminants were different. On the basis of the analysis of the data presented here, the averaged results (median and 95th percentile) for a given DEO unit should not be used as a representative measure of dermal exposure for all scenarios within that DEO without taking the exposure determinants into account. However, the data could be used to develop an exposure matrix (indicative exposure distributions) for different types of scenario and workplace, using determinants of exposure and a Bayesian approach to integrating expert opinion.

  2. Dermal filler complications: a clinicopathologic study with a spectrum of histologic reaction patterns.

    PubMed

    El-Khalawany, Mohamed; Fawzy, Sameh; Saied, Asmaa; Al Said, Mohammed; Amer, Ahmed; Eassa, Bayoumi

    2015-02-01

    Although dermal fillers are generally accepted as safe and well-tolerable cosmetic tools, adverse reaction still forms a prognostic problem. The aim of this study was to demonstrate the clinicopathologic patterns of dermal filler complications in our center. A 5-year single-center study that included patients complained from filler complications and referred to the dermatopathology unit in Al-Azhar University for histologic assessment. The study included 38 female patients with an average age of 47 years. The mean onset of complications was 14.6 ± 5.27 months after injection. The injected material included hyaluronic acid (18.4%), silicone (52.6%), bovine collagen (15.8%) and polyacrylamide hydrogel (13.2%). Most lesions were located on the face (55.3%), less commonly on the hands (18.4%), buttocks (21%), and rarely on the vulva (5.3%). The clinical spectrum included indurated plaque (23.7%), nodular lesion (31.6%), inflammatory mass (15.8%), atrophic lesion (10.5%), skin discoloration (13.1%) and ulceration (5.3%). Histologically, granulomatous reaction was the major finding, either a foreign body granuloma (34.2%) or infectious granuloma (13.2%). Other histologic reactions included dermal pseudocysts with chronic inflammation (26.3%), dermal fibrosis (15.8%), and eosinophilic panniculitis (10.5%). Our results confirmed that dermal fillers could be manifested with variable clinical presentations and show different histologic reactions. Because of long-standing duration until complications occur, history taking is crucial and should be emphasized in every suspected patient. It is hoped that this article will increase awareness for recognition of these variable complications and help select the appropriate therapy.

  3. Staphylococcus aureus Induces Hypoxia and Cellular Damage in Porcine Dermal Explants

    PubMed Central

    Lone, Abdul G.; Atci, Erhan; Renslow, Ryan; Beyenal, Haluk; Noh, Susan; Fransson, Boel; Abu-Lail, Nehal; Park, Jeong-Jin; Gang, David R.

    2015-01-01

    We developed a porcine dermal explant model to determine the extent to which Staphylococcus aureus biofilm communities deplete oxygen, change pH, and produce damage in underlying tissue. Microelectrode measurements demonstrated that dissolved oxygen (DO) in biofilm-free dermal tissue was 4.45 ± 1.17 mg/liter, while DO levels for biofilm-infected tissue declined sharply from the surface, with no measurable oxygen detectable in the underlying dermal tissue. Magnetic resonance imaging demonstrated that biofilm-free dermal tissue had a significantly lower relative effective diffusion coefficient (0.26 ± 0.09 to 0.30 ± 0.12) than biofilm-infected dermal tissue (0.40 ± 0.12 to 0.48 ± 0.12; P < 0.0001). Thus, the difference in DO level was attributable to biofilm-induced oxygen demand rather than changes in oxygen diffusivity. Microelectrode measures showed that pH within biofilm-infected explants was more alkaline than in biofilm-free explants (8.0 ± 0.17 versus 7.5 ± 0.15, respectively; P < 0.002). Cellular and nuclear details were lost in the infected explants, consistent with cell death. Quantitative label-free shotgun proteomics demonstrated that both proapoptotic programmed cell death protein 5 and antiapoptotic macrophage migration inhibitory factor accumulated in the infected-explant spent medium, compared with uninfected-explant spent media (1,351-fold and 58-fold, respectively), consistent with the cooccurrence of apoptosis and necrosis in the explants. Biofilm-origin proteins reflected an extracellular matrix-adapted lifestyle of S. aureus. S. aureus biofilms deplete oxygen, increase pH, and induce cell death, all factors that contribute to impede wound healing. PMID:25847960

  4. TRPV4 ion channel is a novel regulator of dermal myofibroblast differentiation.

    PubMed

    Sharma, Shweta; Goswami, Rishov; Merth, Michael; Cohen, Jonathan; Lei, Kai Y; Zhang, David X; Rahaman, Shaik O

    2017-03-01

    Scleroderma is a multisystem fibroproliferative disease with no effective medical treatment. Myofibroblasts are critical to the fibrogenic tissue repair process in the skin and many internal organs. Emerging data support a role for both matrix stiffness, and transforming growth factor β1 (TGFβ1), in myofibroblast differentiation. Transient receptor potential vanilloid 4 (TRPV4) is a mechanosensitive ion channel activated by both mechanical and biochemical stimuli. The objective of this study was to determine the role of TRPV4 in TGFβ1- and matrix stiffness-induced differentiation of dermal fibroblasts. We found that TRPV4 channels are expressed and functional in both human (HDF) and mouse (MDF) dermal fibroblasts. TRPV4 activity (agonist-induced Ca(2+) influx) was induced by both matrix stiffness and TGFβ1 in dermal fibroblasts. TGFβ1 induced expression of TRPV4 proteins in a dose-dependent manner. Genetic ablation or pharmacologic antagonism of TRPV4 channel abrogated Ca(2+) influx and both TGFβ1-induced and matrix stiffness-induced myofibroblast differentiation as assessed by i) α-smooth muscle actin expression/incorporation into stress fibers, ii) generation of polymerized actin, and iii) expression of collagen-1. We found that TRPV4 inhibition abrogated TGFβ1-induced activation of AKT but not of Smad2/3, suggesting that the mechanism by which profibrotic TGFβ1 signaling in dermal fibroblasts is modified by TRPV4 may be through non-Smad pathways. Altogether, these data identify a novel reciprocal functional link between TRPV4 activation and TGFβ1 signals regulating dermal myofibroblast differentiation. These findings suggest that therapeutic inhibition of TRPV4 activity may provide a targeted approach to the treatment of scleroderma.

  5. Human Dermal Fibroblasts Demonstrate Positive Immunostaining for Neuron- and Glia- Specific Proteins

    PubMed Central

    Janmaat, C. J.; de Rooij, K. E; Locher, H; de Groot, S. C.; de Groot, J. C. M. J.; Frijns, J. H. M.; Huisman, M. A.

    2015-01-01

    In stem cell cultures from adult human tissue, undesirable contamination with fibroblasts is frequently present. The presence of fibroblasts obscures the actual number of stem cells and may result in extracellular matrix production after transplantation. Identification of fibroblasts is difficult because of the lack of specific fibroblast markers. In our laboratory, we isolate and expand neural-crest-derived stem cells from human hair follicle bulges and investigate their potential to differentiate into neural cells. To establish cellular identities, we perform immunohistochemistry with antibodies specific for glial and neuronal markers, and use fibroblasts as negative control. We frequently observe that human adult dermal fibroblasts also express some glial and neuronal markers. In this study, we have sought to determine whether our observations represent actual expression of these markers or result from cross-reactivity. Immunohistochemistry was performed on human adult dermal fibroblasts using acknowledged glial and neuronal antibodies followed by verification of the data using RT-qPCR. Human adult dermal fibroblasts showed expression of the glia-specific markers SOX9, glial fibrillary acidic protein and EGR2 (KROX20) as well as for the neuron-specific marker class III β-tubulin, both at the protein and mRNA level. Furthermore, human adult dermal fibroblasts showed false-positive immunostaining for S100β and GAP43 and to a lower extent for OCT6. Our results indicate that immunophenotyping as a tool to determine cellular identity is not as reliable as generally assumed, especially since human adult dermal fibroblasts may be mistaken for neural cells, indicating that the ultimate proof of glial or neuronal identity can only be provided by their functionality. PMID:26678612

  6. [Acute pancreatitis].

    PubMed

    Hecker, M; Mayer, K; Askevold, I; Collet, P; Weigand, M A; Krombach, G A; Padberg, W; Hecker, A

    2014-03-01

    Acute pancreatitis is a potentially fatal disease with individually differing expression of systemic involvement. For this reason early diagnosis with subsequent risk stratification is essential in the clinical management of this frequent gastroenterological disorder. Severe forms of acute pancreatitis occur in approximately 20 % of cases often requiring intensive care monitoring and interdisciplinary therapeutic approaches. In the acute phase adequate fluid replacement and sufficient analgesic therapy is of major therapeutic importance. Concerning the administration of antibiotics and the nutritional support of patients with acute pancreatitis a change in paradigms could be observed in recent years. Furthermore, endoscopic, radiological or surgical interventions can be necessary depending on the severity of the disease and potential complications.

  7. Bronchitis - acute

    MedlinePlus

    ... to breathe. Other symptoms of bronchitis are a cough and coughing up mucus. Acute means the symptoms ... diagnosed with chronic bronchitis, you must have a cough with mucus on most days for at least ...

  8. Acute Bronchitis

    MedlinePlus

    ... bronchitis? Acute bronchitis is inflammation of your bronchial tree. The bronchial tree consists of tubes that carry air into your ... weeks or months. This happens because the bronchial tree takes a while to heal. A lasting cough ...

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

    PubMed

    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 <1% of harmful compounds were misclassified as non-toxic. Since repeated dose toxicity studies can be performed in vivo until 2013, the proposed approach could have an immediate impact for the testing of cosmetic ingredients.

  10. Antinociceptive, anti-inflammatory effects and acute toxicity of aqueous and ethanolic extracts of Myrtus communis L. Aerial parts in mice.

    PubMed

    Hosseinzadeh, Hossein; Khoshdel, Mohammad; Ghorbani, Maryam

    2011-12-01

    Myrtus communis L. aerial parts have been used in traditional medicine for the treatment of inflammatory disease. In this study 350 mice were divided into three main groups: negative (saline), positive (morphine or diclofenac) controls, and test groups. The acute toxicity was assessed for 2 days. Antinociceptive activity was performed using hot plate and writhing tests. The anti-inflammatory effect was investigated using xylene-induced ear edema and a cotton pellet test. According to phytochemical screening, the extracts contained tannins, alkaloids, and flavonoids. The LD50 values of the aqueous and ethanolic extracts were 0.473 and 0.79 g/kg, respectively. In hot plate test, the aqueous and ethanolic extracts showed significant antinociceptive activity that was inhibited by naloxone. The extracts exhibited antinociceptive activity against acetic acid-induced writhing and also showed significant activity against acute inflammation which was dose dependent for aqueous extract. The ethanolic (0.05 g/kg) and aqueous extracts (0.005, 0.015, and 0.03 g/kg) demonstrated anti-inflammatory effects against chronic inflammation. The aqueous and ethanolic extracts of the aerial parts of M communis L. showed antinociceptive effects and these may be mediated by opioid receptors.

  11. Acute effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate, on cardiovascular parameters in anaesthetized, artificially ventilated rats.

    PubMed

    Watanabe, Yoshimasa; Itoh, Takeo; Shiraishi, Hiroaki; Maeno, Yoshitaka; Arima, Yosuke; Torikoshi, Aiko; Namera, Akira; Makita, Ryosuke; Yoshizumi, Masao; Nagao, Masataka

    2013-10-01

    The organophosphorus compound sarin irreversibly inhibits acetylcholinesterase. We examined the acute cardiovascular effects of a sarin-like organophosphorus agent, bis(isopropyl methyl)phosphonate (BIMP), in anaesthetized, artificially ventilated rats. Intravenous administration of BIMP (0.8mg/kg; the LD50 value) induced a long-lasting increase in blood pressure and tended to increase heart rate. In rats pretreated with the non-selective muscarinic-receptor antagonist atropine, BIMP significantly increased both heart rate and blood pressure. In atropine-treated rats, hexamethonium (antagonist of ganglionic nicotinic receptors) greatly attenuated the BIMP-induced increase in blood pressure without changing the BIMP-induced increase in heart rate. In rats treated with atropine plus hexamethonium, intravenous phentolamine (non-selective α-adrenergic receptor antagonist) plus propranolol (non-selective β-adrenergic receptor antagonist) completely blocked the BIMP-induced increases in blood pressure and heart rate. In atropine-treated rats, the reversible acetylcholinesterase inhibitor neostigmine (1mg/kg) induced a transient increase in blood pressure, but had no effect on heart rate. These results suggest that in anaesthetized rats, BIMP induces powerful stimulation of sympathetic as well as parasympathetic nerves and thereby modulates heart rate and blood pressure. They may also indicate that an action independent of acetylcholinesterase inhibition contributes to the acute cardiovascular responses induced by BIMP.

  12. Detection of Botulinum Neurotoxin Serotype B at Sub Mouse LD50 Levels by a Sandwich Immunoassay and its Application to Toxin Detection in Milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recombinant peptide fragments of the light chain, the transmembrane and receptor-binding domains of the heavy chain of BoNT/B were expressed in Escherichia coli as GST-fusion proteins and purified. These proteins were used to immunize BALB/c mice for the generation of monoclonal antibodies (mAbs). A...

  13. Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guinea-pig

    PubMed Central

    Kasali, Félicien Mushagalusa; Kadima, Justin Ntokamunda; Mpiana, Pius Tshimankinda; Ngbolua, Koto-te-Nyiwa; Tshibangu, Damien Sha-Tshibey

    2013-01-01

    Objective To verify the antidiabetic activity of leaf extracts from Physalis peruviana L. popularly used in the Eastern part of the Democratic Republic of the Congo and to point out the possible toxicity. Method Aqueous decoctions prepared from dried leaves powder were administrated to guinea pigs at the dose range of 100 mg/kg to 3.2 g/kg of body weight. The hypoglycemic activity was evaluated by glucose tolerance test, loading animals with glucose 4 g/kg and measuring blood glucose concentrations at various times. The effect was compared to the control and glibenclamide as antidiabetic reference drug. Acute toxicity was evaluated by recording mortality rate, changes on blood biomarkers and damage caused to vital organs. Results At a dose of 100 mg/kg, the aqueous extract induced a significant reduction of peak concentration at 30 min after glucose loading as compared with control or reference (P<0.05). At doses greater than 400 mg, some alterations on blood, kidney and liver markers were observed. Upper 800 mg/kg, mortality was observed with LD50 estimated at about 1 280 mg/kg. At the autopsy, vital organs were in haemorrhage and swelling state. Conclusion The crude aqueous extracts from the leaves of Physalis peruviana L. present hypoglycemic activity in animal model, but at high doses the plant may cause severe intoxication.

  14. Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack).

    PubMed

    Li, Ching-Hao; Liao, Jiunn-Wang; Liao, Po-Lin; Huang, Wei-Kuang; Tse, Ling-Shan; Lin, Cheng-Hui; Kang, Jaw-Jou; Cheng, Yu-Wen

    2013-01-01

    Tongkat Ali (Eurycoma longifolia) is an indigenous traditional herb in Southern Asia. Its powdered root has been processed to produce health supplements, but no detailed toxicology report is available. In this study, neither mutagenicity nor clastogenicity was noted, and acute oral LD50 was more than 6 g/kg b.w. After 4-week subacute and 13-week subchronic exposure paradigms (0, 0.6, 1.2, and 2 g/kg b.w./day), adverse effects attributable to test compound were not observed with respect to body weight, hematology, serum biochemistry, urinalysis, macropathology, or histopathology. However, the treatment significantly reduced prothrombin time, partial thromboplastin time, blood urea nitrogen, creatinine, aspartate aminotransferase, creatine phosphate kinase, lactate dehydrogenase, and cholesterol levels, especially in males (P < 0.05). These changes were judged as pharmacological effects, and they are beneficial to health. The calculated acceptable daily intake (ADI) was up to 1.2 g/adult/day. This information will be useful for product development and safety management.

  15. Acute and subchronic toxicity as well as evaluation of safety pharmacology of traditional Chinese medicine “Huhezi”

    PubMed Central

    Chen, Yaqin; Chen, Shufan; Song, Chenhui; Yin, Zhongqiong; Chen, Zhenzhen; Jia, Renyong; Liang, Xiaoxia; Li, Lixia; Zou, Yuanfeng; He, Changliang; Ye, Gang; Lv, Cheng

    2015-01-01

    The study was conducted to evaluate the toxicity and safety pharmacology of the traditional Chinese medicine, “Huhezi” granules. The results of acute toxicity test showed that the granules’ LD50 was more than 5000 mg/kg, which indicated that the “Huhezi” belonged to actually non-toxic drug. Subchronic toxicity study showed that non-toxic reaction were detected in high (1000 mg/kg), medium (500 mg/kg) and low dose (250 mg/kg) of “Huhezi” groups by measuring rat body weight, organ coefficient, blood physiological indexes and blood biochemical indexes. Pathological examination showed that no tissue lesions were observed in test organs except liver (mild granular degenerationand reversible vesicular degeneration), spleen (Langerhans cells infiltrating) and kidney (homogeneous red staining of renal tubule). Safety pharmacology study found that “Huhezi” had no effects on the central nervous system, respiratory system and cardiovascular system. These results suggested that the dose of “Huhezi” at or below 1000 mg/kg through oral administration is considered safe. PMID:26550447

  16. Acute and chronic toxicity studies on partially purified hypoglycemic preparation from water extract of bark ofFicus bengalensis.

    PubMed

    Gupta, S; Shukla, R; Prabhu, K M; Aggrawal, S; Rusia, U; Murthy, P S

    2002-01-01

    Acute and chronic toxicity studies were conducted to assess toxicity of a partially purified preparation from the water extract of the bark ofFicus bengalensis, which was demonstrated in our earlier studies to have significant hypoglycemic and hypocholesteroiemic effect on alloxan induced, mild and severe diabetes in rabbits. LD(50) of this preparation was found to be ∼1 gm/kg in rats when given orally. For chronic toxicity studies 3 doses of aqueous preparation were given to 3 groups of rats. First group received 5 times ED(50) (50 mg/kg), second group 10 times ED(50) (100 mg/kg) and the third group 15 times ED(50) (150 mg/kg) for 3 months. Fourth group which served as control was given water. After three months, blood was collected for studying biochemical and hematological parameters. Blood glucose, serum cholesterol, liver and kidney function tests, haemoglobin, total and differential leukocyte count were determined. Animals were sacrificed and histopathological examination of liver, heart and kidneys was carried out. Results of the study showed that partially purified preparation fromFicus bengalensis is not toxic by all the above mentioned parameters.

  17. Evaluation of Acute 13-Week Subchronic Toxicity and Genotoxicity of the Powdered Root of Tongkat Ali (Eurycoma longifolia Jack)

    PubMed Central

    Liao, Jiunn-Wang; Liao, Po-Lin; Huang, Wei-Kuang; Tse, Ling-Shan; Lin, Cheng-Hui; Kang, Jaw-Jou; Cheng, Yu-Wen

    2013-01-01

    Tongkat Ali (Eurycoma longifolia) is an indigenous traditional herb in Southern Asia. Its powdered root has been processed to produce health supplements, but no detailed toxicology report is available. In this study, neither mutagenicity nor clastogenicity was noted, and acute oral LD50 was more than 6 g/kg b.w. After 4-week subacute and 13-week subchronic exposure paradigms (0, 0.6, 1.2, and 2 g/kg b.w./day), adverse effects attributable to test compound were not observed with respect to body weight, hematology, serum biochemistry, urinalysis, macropathology, or histopathology. However, the treatment significantly reduced prothrombin time, partial thromboplastin time, blood urea nitrogen, creatinine, aspartate aminotransferase, creatine phosphate kinase, lactate dehydrogenase, and cholesterol levels, especially in males (P < 0.05). These changes were judged as pharmacological effects, and they are beneficial to health. The calculated acceptable daily intake (ADI) was up to 1.2 g/adult/day. This information will be useful for product development and safety management. PMID:24062779

  18. Comparison of the acute inhibitory effects of Tetrodotoxin (TTX) in rat and human neuronal networks for risk assessment purposes.

    PubMed

    Kasteel, Emma E J; Westerink, Remco H S

    2017-03-15

    Tetrodotoxin (TTX) is an extremely toxic marine neurotoxin. TTX inhibits voltage-gated sodium channels, resulting in a potentially lethal inhibition of neurotransmission. Despite numerous intoxications in Asia and Europe, limited (human) toxicological data are available for TTX. Additionally, the degree of interspecies differences for TTX is not well established, hampering the use of available (animal) data for human risk assessment and establishing regulatory limits for TTX concentrations in (shell)fish. We therefore used micro-electrode array (MEA) recordings as an integrated measure of neurotransmission to demonstrate that TTX inhibits neuronal electrical activity in both primary rat cortical cultures and human-induced pluripotent stem cell (hIPSC)-derived iCell(®) neurons in co-culture with hIPSC-derived iCell(®) astrocytes, with IC50 values of 7 and 10nM, respectively. From these data combined with LD50 values and IC50 concentrations of voltage-gated sodium channels derived from literature it can be concluded that interspecies differences are limited for TTX. Consequently, we used experimental animal data to derive a human acute reference dose of 1.33μg/kg body weight, which corresponds to maximum concentration of TTX in shellfish of 200μg/kg.

  19. Peoniflorin suppresses tumor necrosis factor-α induced chemokine production in human dermal microvascular endothelial cells by blocking nuclear factor-κB and ERK pathway.

    PubMed

    Chen, Tao; Guo, Zai-Pei; Jiao, Xiao-Yan; Jia, Rui-Zhen; Zhang, Yu-Hong; Li, Jing-Yi; Huang, Xu-Lei; Liu, Hong-Jie

    2011-07-01

    Peoniflorin (PF) extracted from the root of Paeonia lactiflora pall displays anti-inflammation and antioxidant properties in several animal models. Chemokines are vital for directing the movement of circulating leukocytes to the sites of inflammation and are involved in the pathogenesis of various inflammatory skin diseases. Herein, we investigated the effects and potential mechanisms of PF on tumor necrosis factor-α (TNF-α) induced chemokine production in human dermal microvascular endothelial cells. Human dermal microvascular endothelial cell line (HMEC-1) was treated by TNF-α with or without PF. PF markedly attenuated TNF-α-induced chemokines (including CCL2, CCL5, CCL20, CXCL8, CXCL16 and CX3CL1) mRNA expression in HMEC-1. PF also reduced the secretion of these chemokines in culture supernatants. In addition, endothelial activation in the presence of PF markedly blocked the chemotactic activities of TNF-α-stimulated HMEC-1 supernatant on promyelocytic leukemia cell line (HL-60) or the acute mature monocytic leukemia cell line (THP-1) cell migration. Furthermore, Western blot data revealed TNF-α upregulated phosphorylation of inhibitor of κB-α (IκBα) and phosphorylation of extracellular signal-regulated kinase (ERK)1/2, which was almost completely reversed by PF. Finally, PF inhibited nuclear factor-κB (NF-κB) nuclear translocation to the nucleus. Taken together, our data provide the first evidence that PF has an anti-inflammatory ability against TNF-α-induced chemokine production and leukocyte migration, which may be at least partly related to the inhibition of NF-κB and ERK pathway. PF may be a candidate medicine for the treatment of inflammatory skin diseases.

  20. A nonhuman primate model of the hematopoietic acute radiation syndrome plus medical management.

    PubMed

    Farese, Ann M; Cohen, Melanie V; Katz, Barry P; Smith, Cassandra P; Jackson, William; Cohen, Daniel M; MacVittie, Thomas J

    2012-10-01

    The development of medical countermeasures against the hematopoietic subsyndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to morbidity and mortality. Herein, the authors define these parameters for a nonhuman primate exposed to total body radiation and administered medical management. A blinded, randomized study (n = 48 rhesus macaques) determined the lethal dose-response relationship using bilateral 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90 Gy at 0.80 Gy min(-1). Following irradiation, animals were monitored for complete bloodcounts, body weight, temperature, diarrhea, and hydration status for 60 d. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics, and nutrition. The primary endpoint was survival at 60 d post-irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents, and tissue histology. The study defined an LD30/60 of 7.06 Gy, LD50/60 of 7.52 Gy, and an LD70/60 of 7.99 Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule.

  1. A Nonhuman Primate Model of the Hematopoietic Acute Radiation Syndrome Plus Medical Management

    PubMed Central

    Farese, A.M.; Cohen, M.V.; Katz, B. P.; Smith, C. P.; Jackson, W.; Cohen, D. M.; MacVittie, T.J.

    2012-01-01

    The development of medical countermeasures against the hematopoietic sub-syndrome of the acute radiation syndrome requires well characterized and validated animal models. The model must define the radiation dose- and time-dependent relationships for mortality and major signs of morbidity to include other organ damage that may contribute to the morbidity and mortality. Herein, we define these parameters for the nonhuman primate exposed to total-body radiation and administered medical management. A blinded, randomized study (n=48 rhesus macaques) determined the lethal dose response relationship using bilateral, 6 MV linear accelerator photon radiation to doses in the range of 7.20 to 8.90Gy at 0.80Gy minute−1. Following irradiation animals were monitored for complete blood counts, body weight, temperature, diarrhea, and hydration status for 60 days. Animals were administered medical management consisting of intravenous fluids, prophylactic antibiotics, blood transfusions, anti-diarrheals, analgesics and nutrition. The primary endpoint was survival at 60 days post irradiation; secondary endpoints included hematopoietic-related parameters, number of transfusions, incidence of documented infection, febrile neutropenia, severity of diarrhea, mean survival time of decedents and tissue histology. The study defined an LD30/60 of 7.06Gy, LD50/60 of 7.52Gy, and an LD70/60 of 7.99Gy with a relatively steep slope of 1.13 probits per linear dose. This study establishes a rhesus macaque model of the hematopoietic acute radiation syndrome and shows the marked effect of medical management on increased survival and overall mean survival time for decedents. Furthermore, following a nuclear terrorist event, medical management may be the only treatment administered at its optimal schedule. PMID:22929469

  2. Genotoxicity and acute and subchronic toxicity studies of a standardized methanolic extract of Ficus deltoidea leaves

    PubMed Central

    Farsi, Elham; Shafaei, Armaghan; Hor, Sook Yee; Khadeer Ahamed, Mohamed B.; Yam, Mun Fei; Asmawi, Mohd Z.; Ismail, Zhari

    2013-01-01

    OBJECTIVE: Ficus deltoidea leaves have been used in traditional medicine in Southeast Asia to treat diabetes, inflammation, diarrhea, and infections. The present study was conducted to assess the genotoxicity and acute and subchronic toxicity of a standardized methanol extract of F. deltoidea leaves. METHODS: Sprague Dawley rats were orally treated with five different single doses of the extract and screened for signs of toxicity for two weeks after administration. In the subchronic study, three different doses of the extract were administered for 28 days. Mortality, clinical signs, body weight changes, hematological and biochemical parameters, gross findings, organ weights, and histological parameters were monitored during the study. Genotoxicity was assessed using the Ames test with the TA98 and TA100 Salmonella typhimurium strains. Phytochemical standardization was performed using a colorimeter and high-performance liquid chromatography. Heavy metal detection was performed using an atomic absorption spectrometer. RESULTS: The acute toxicity study showed that the LD50 of the extract was greater than 5000 mg/kg. In the subchronic toxicity study, there were no significant adverse effects on food consumption, body weight, organ weights, mortality, clinical chemistry, hematology, gross pathology, or histopathology. However, a dose-dependent increase in the serum urea level was observed. The Ames test revealed that the extract did not have any potential to induce gene mutations in S. typhimurium, either in the presence or absence of S9 activation. Phytochemical analysis of the extract revealed high contents of phenolics, flavonoids, and tannins. High-performance liquid chromatography analysis revealed high levels of vitexin and isovitexin in the extract, and the levels of heavy metals were below the toxic levels. CONCLUSION: The no-observed adverse effect level of F. deltoidea in rats was determined to be 2500 mg/kg. PMID:23778480

  3. Acute oral toxicity of chemicals in terrestrial life stages of amphibians: Comparisons to birds and mammals.

    PubMed

    Crane, Mark; Finnegan, Meaghean; Weltje, Lennart; Kosmala-Grzechnik, Sylwia; Gross, Melanie; Wheeler, James R

    2016-10-01

    Amphibians are currently the most threatened and rapidly declining group of vertebrates and this has raised concerns about their potential sensitivity and exposure to plant protection products and other chemicals. Current environmental risk assessment procedures rely on surrogate species (e.g. fish and birds) to cover the risk to aquatic and terrestrial life stages of amphibians, respectively. Whilst a recent meta-analysis has shown that in most cases amphibian aquatic life stages are less sensitive to chemicals than fish, little research has been conducted on the comparative sensitivity of terrestrial amphibian life stages. Therefore, in this paper we address the questions "What is the relative sensitivity of terrestrial amphibian life stages to acute chemical oral exposure when compared with mammals and birds?" and "Are there correlations between oral toxicity data for amphibians and data for mammals or birds?" Identifying a relationship between these data may help to avoid additional vertebrate testing. Acute oral amphibian toxicity data collected from the scientific literature and ecotoxicological databases were compared with toxicity data for mammals and birds. Toxicity data for terrestrial amphibian life stages are generally sparse, as noted in previous reviews. Single-dose oral toxicity data for terrestrial amphibian life stages were available for 26 chemicals and these were positively correlated with LD50 values for mammals, while no correlation was found for birds. Further, the data suggest that oral toxicity to terrestrial amphibian life stages is similar to or lower than that for mammals and birds, with a few exceptions. Thus, mammals or birds are considered adequate toxicity surrogates for use in the assessment of the oral exposure route in amphibians. However, there is a need for further data on a wider range of chemicals to explore the wider applicability of the current analyses and recommendations.

  4. Acute and chronic toxicological studies of Ajuga iva in experimental animals.

    PubMed

    El Hilaly, Jaouad; Israili, Zafar H; Lyoussi, Badiâa

    2004-03-01

    Ajuga iva (L.) Schreber (AI), is widely used in the Moroccan pharmacopoeia as a panacea (cure-all), and specifically for gastrointestinal disorders and diabetes, and as an anthelmintic. No toxicological investigations have been carried out on this plant. We have previously observed that single oral doses (2-14 g/kg) of a lyophilised aqueous extract of AI (AI-extract) in mice or daily oral administration of 10 mg/kg of AI-extract in rats for 2 weeks did not result in any adverse effects. We have now evaluated AI-extract for its behavioural and pharmaco-toxicological effects after acute and chronic administration by the oral and intraperitoneal routes in rats and mice. No toxicity was observed in mice after single oral doses of as high as 14 g/kg of the AI-extract. However, single intraperitoneal injections of the AI-extract (1500-5500 mg/kg BW) produced a dose-dependent increase in adverse effects in the general behaviour and the mortality rate; the LD50 of acute intraperitoneal dose was 3.6 g/kg. In chronic toxicological studies in rats, the AI-extract (administered orally at daily doses of 100, 300 and 600 mg/kg for 3 months), did not cause any changes in haematological and biochemical parameters, with the exception of a transient rise in platelet counts and a short-term decrease in serum glucose levels. Histopathological examination of the brain, liver and the kidneys at the end of the study (3 months) showed normal architecture suggesting no morphological disturbances.

  5. Development of dermal denticles in skates (Chondrichthyes, Batoidea): patterning and cellular differentiation.

    PubMed

    Miyake, T; Vaglia, J L; Taylor, L H; Hall, B K

    1999-07-01

    Patterning, cellular differentiation, and developmental sequences of dermal denticles (denticles) are described for the skate Leucoraja erinacea. Development of denticles proceeds caudo-rostrally in the tail and trunk. Once three rows of denticles form in the tail and trunk, denticles begin to appear in the region of the pelvic girdle, medio-caudal to the eyes and on the pectoral fins. Although timing of cellular differentiation of denticles differs among different locations of the body, cellular development of a denticle is identical in all locations. Thickening of the epidermis as a denticle lamina marks initiation of development. A single lamina for each denticle forms, and a small group of mesenchymal cells aggregates underneath it. The lamina then invaginates caudo-rostrally to form the inner- and outer-denticle epithelia (IDE and ODE, respectively). Before nuclei of IDE cells are polarized, enameloid matrix appears between the basement membrane of the IDE and the apical surface of the pre-odontoblasts. Pre-dentin is then laid down along with collagenous materials. Von Kossa stain visualizes initial mineralization of dentin, but not enameloid. During the growth of a denticle, dense fibrous connective tissue of the dermis forms the deep dermal tissue over the dorsal musculature. Attachment fibers and tendons anchor denticles and dorsal musculature, respectively, on deep dermal tissue. Basal tissue of the denticles develops as the denticle crown grows. If the basal tissue is bone of attachment, then the cells along the basal tissue would be osteoblasts. However, these cells could not be distinguished from odontoblasts using immunolocalization of type I pro-collagen (Col I), alkaline phosphatase (APase), and neural cell adhesion molecule (N-CAM). Well-developed dentin, (not pre-dentin), the enameloid matrix (probably when it begins to mineralize), and deep dermal tissue are Verhoeff stain-positive, suggesting that these tissues contain elastin and/or elastin

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

    DTIC Science & Technology

    1996-10-01

    100 Aquatic Toxicity: LC 5. (rainbow trout): 43,800 yg/L (96 hr) LC5 0 (blue gill): 100,000 ug/L (96 hr) LC50 ( Daphnia magna ): 28,900 ug/L (48 hr...on Foods, Drugs , and Cosmetics", In: Dermal Toxicity, pp 49-52, Assoc. of Food and Drug Officers of the U.S., Topeka, KS (1965). Draize, J.H...ingredient of powder laundry bleaches. DCDMH contains about 66% "available chlorine". Other uses of DCDYIH are: (1) as an intermediate drug and

  7. Acute and sub-acute oral toxicity assessment of the methanolic extract from leaves of Hibiscus rosa-sinensis L. in mice

    PubMed Central

    Nath, Purobi; Yadav, Arun K.

    2015-01-01

    Background: The leaves of Hibiscus rosa-sinensis L. (Malvaceae) are used for the treatment of dysentery and diarrhea, to promote draining of abscesses and as analgesic agent in the traditional medicine of Cook Islands, Haiti, Japan and Mexico. Aim: The present study investigated the oral acute and subacute toxicity of methanol leaf extract of H. rosa-sinensis in mice. Materials and Methods: In the acute toxicity study, a single oral dose of 2000 mg/kg of extract was given to five mice at 48 h intervals. Animals were observed individually for any clinical signs of toxicity or mortality for 14 days. In the sub-acute toxicity study, mice were treated with 400 mg/kg and 800 mg/kg doses of the extract for 14 days. The hematological and biochemical parameters and histopathology of liver and kidneys of animals were studied at the end of the experiment. Results: For acute treatment, the extract did not reveal any signs of toxicity or mortality in any animal, during the 14 days observation period. The LD50 of extract was estimated to be greater than 2000 mg/kg. In the sub-acute toxicity study, administration of 400 mg/kg and 800 mg/kg doses of extract to mice for two weeks did not reveal any marked adverse effects on hematological, biochemical parameters and histopathology of liver and kidney in the 400 mg/kg group. However, hepato-renal toxicity as evidenced by elevated levels of alanine aminotransferase, aspartate aminotransferase, total and indirect bilirubin, urea and creatinine was seen in the animals that received 800 mg/kg dose of extract for 14 days. In addition, in the same group of animals, the histological assessments of liver and kidney also showed various adverse effects viz. dilated sinusoids, apoptotic nuclei and inflammatory infiltrate inside sinusoidal capillaries in the liver, and marked the disorganization of tubules and glomeruli, and enlarged interstitial spaces in the kidney. Conclusion: The results of this study suggest that for traditional medicinal

  8. A multicenter prospective trial evaluating fetal bovine dermal graft (Xenform® Matrix) for pelvic reconstructive surgery

    PubMed Central

    2010-01-01

    Background A prospective multicenter clinical study was performed to evaluate the safety and efficacy of a bovine dermal graft (Xenform® Matrix, Boston Scientific, Natick, MA, USA) during vaginal reconstructive surgery. Methods Forty-five women with ICS stage 2 or higher pelvic organ prolapse (POP) were enrolled at 4 centers. POP-Q, pelvic floor function (PFDI-20), sexual function (PISQ-12), and patient satisfaction tools were used to assess subjects at baseline, and at 2 and 6 weeks, and 3, 6 and 12 months post surgery. The significance of symptom score changes at 6 months and 1 year were determined by the t-test for paired data. Forty-three of the 45 patients completed the 12 month study. Results The majority of the subjects had cystocele (98%) and/or rectocele (84%) defects at study entry. At 12 months, 74% of the defects had improved to a stage 0 or 1. Mean PFDI-20 scores improved by 72% (p < 0.001) at 12 months, and PISQ-12 scores were maintained during the follow-up period indicating no decline in sexual function. Three subjects experienced one serious adverse event each; one of the adverse events (constipation) was deemed by the study physician to be unrelated to Xenform®. One subject had severe pyelonephritis resulting in dialysis. This subject had a previous history of pyelonephritis, sepsis and acute renal failure. The third subject had a reported recurrent cystocele of moderate severity, possibly related to the device. No graft related erosions or pain lasting more than 30 days were reported. No subjects withdrew due to an adverse event. Conclusion This study is the first to investigate the use of Xenform® Matrix in vaginal reconstructive surgery among patients with POP. Significant improvement was maintained at 12 months utilizing both objective and subjective assessment tools, confirming the safety and efficacy of this material in vaginal surgery. Trial Registration ClinicalTrials.gov NCT01244165 PMID:21144043

  9. DEVELOPMENT AND EVALUATION OF AN AGGREGATE SURFACE SAMPLING METHOD FOR USE IN ASSESSING DERMAL EXPOSURES OF YOUNG CHILDREN

    EPA Science Inventory

    In the macroactivity approach, dermal exposure is estimated using empirically-derived transfer coefficients to aggregate the mass transfer associated with a series of contacts with a contaminated medium. The macroactivity approach affords the possibility of developing screenin...

  10. Histopathological analysis of the progression pattern of subungual melanoma: late tendency of dermal invasion in the nail matrix area.

    PubMed

    Shin, Hyun-Tae; Jang, Kee-Taek; Mun, Goo-Hyun; Lee, Dong-Youn; Lee, Jason B

    2014-11-01

    Subungual melanoma is a rare subtype of melanoma that usually originates and spreads from the nail matrix. Because of its poor prognosis and short matrix-to-bone distance, amputation has been traditionally performed. Recently, conservative surgery has been attempted for early subungual melanoma, but the evidence supporting this practice is sparse. As little is known about the progression pattern of subungual melanoma, further advances on the subject may provide better guidance on the optimal surgical approach. Histopathology slides, clinical records, and photographs of 23 cases of subungual melanoma were reviewed. For all cases, each area of the nail unit-proximal nail fold, nail matrix, nail bed, and/or hyponychium-in longitudinal sections was available for histological examination. Growth pattern, dermal invasion, and thickness were assessed in each area of the nail unit. There were five cases of melanoma in situ. Eighteen cases showed dermal invasion in at least one area of the nail unit. There were no cases showing dermal invasion in the nail matrix area only. In four cases, dermal invasion involved areas of the nail unit other than the nail matrix. In 14 cases, dermal invasion involved the nail matrix area as well as other areas of the nail unit. Except for one case, the nail matrix area showed thinner dermal invasion compared with dermal invasion in other areas of the nail unit. In conclusion, dermal invasion of subungual melanoma in the nail matrix area tends to occur later than other areas of the nail unit. Longitudinal incisional biopsy is necessary to accurately evaluate melanoma invasion. The findings of this study suggest that conservative surgical treatment for early subungual melanoma may be justified as the nail matrix area, an area of thin dermis and close proximity to the underlying bone, appears to be more resistant to invasion.

  11. High Prevalence of Respiratory and Dermal Symptoms Among Ethiopian Flower Farm Workers.

    PubMed

    Hanssen, Vegard Mjelde; Nigatu, Amare Workiye; Zeleke, Zeyede Kebede; Moen, Bente Elisabeth; Bråtveit, Magne

    2015-01-01

    The flower industry is among the most important export industries in Ethiopia, employing more than 50,000 workers. The working conditions and health status among workers in Ethiopian flower industry are not documented. A questionnaire-based interview was conducted among 213 flower industry workers from 3 flower farms and 60 control workers from supermarkets from February to March 2012. A walk-through survey was also performed on the 3 flower farms. Interviewed flower farm workers have high prevalences of respiratory and dermal symptoms, which are rarely reported among controls. Female workers inside the greenhouses on the 3 flower farms have significantly more respiratory and dermal symptoms than workers outside the greenhouse, also when adjusting for age and education. Limited access to personal protection equipment (PPE) and unsafe pesticide routines are documented. This study indicates that working in these flower greenhouses might be associated with adverse health effects.

  12. In vitro cytotoxicity assays of solid lipid nanoparticles in epithelial and dermal cells

    NASA Astrophysics Data System (ADS)

    Ridolfi, D. M.; Marcato, P. D.; Machado, D.; Silva, R. A.; Justo, G. Z.; Durán, N.

    2011-07-01

    In recent years, the interest in nanostructured systems to drug delivery has increased because they offer several advantages over conventional dosage forms. Solid Lipid Nanoparticles (SLN) have been highlighted among these systems because they have advantages such as high physical stability, protection against drug degradation and ease of scale-up and manufacturing, without using organic solvent. The aim of this work was to evaluate the potential of SLN, by in vitro cytotoxicity assays, for dermal drug delivery. SLN of three different lipids were prepared by hot high pressure homogenization and the cytotoxicity was assessed by 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test in mouse 3T3 fibroblasts and human HaCaT keratinocytes. SLN showed no cytotoxic potential suggesting a great potential for dermal application.

  13. Dermal/transdermal delivery of small interfering RNA and antisense oligonucleotides- advances and hurdles.

    PubMed

    Ita, Kevin

    2017-03-01

    A diverse array of nucleic acids has been studied by several researchers for the management of several diseases. Among these compounds, small interfering RNA and antisense oligonucleotides have attracted considerable attention. Antisense oligonucleotides are synthetic single stranded strings of nucleic acids that bind to RNA and thereby alter or reduce expression of the target RNA while siRNAs, on the other hand, are double-stranded RNA molecules which can hybridize with a specific mRNA sequence and block the translation of numerous genes. One of the main obstacles in the dermal or transdermal delivery of these compounds is their low skin permeability. In this review, various techniques used to enhance the delivery of these molecules into or across the skin are described and in some cases, the correlation between enhanced dermal/transdermal delivery and therapeutic efficacy is highlighted.

  14. Isolation of fungi belonging to the genera Geotrichum and Trichosporum from human dermal lesions.

    PubMed

    Restrepo, A; De Uribe, L

    1976-08-30

    Isolates of Geotrichum and Trichosporum spp. obtained from patients with a variety of dermal lesions were studied. Among 2,202 cases examined, microorganisms of these genera were recovered from 100 (4,5%); there were 38 isolated of Geotrichum- and 62 of Trichosporum- spp. Most isolations were obtained from nails: 52 cases. The species most frequently found were T. beigelii (25 cases) and G. candidum (30 cases). In 50 of the patients, these fungi were isolated in pure culture, in an additional 40 Trichosporum spp. were found. Mixed cultures with C. albicans were observed in 28 patients, with other Candida spp. in 16 and with dermatophytes in 6. Among the patients whose isolations occurred in pure cultures, the number of colonies recovered was large in 20 cases, 1 with Geotrichum candidum - 19 with Trichosporum (16 T. beigelii, 3 T. capitatum). The relationship between the isolated yeast-like fungi and the dermal lesion was considered to be direct in these 20 patients.

  15. Treatment of photoaged skin with topical tretinoin increases epidermal-dermal anchoring fibrils

    SciTech Connect

    Woodley, D.T.; Briggaman, R.A. ); Zelickson, A.S. ); Hamilton, T.A.; Weiss, J.S.; Ellis, C.N.; Voorhees, J.J. )

    1990-06-13

    Topical 0.1% tretinoin or vehicle control was applied daily to the forearm skin of six caucasian adults for 4 months. Two-millimeter punch biopsy specimens were obtained from treatment sites at the beginning and end of the study period for electron microscopy. Anchoring fibrils within the epidermal-dermal junction of skin treatment sites were quantitated by blinded, standardized, computer-assisted morphometry. After 4 months of continual daily treatment, skin sites that received topical tretinoin showed double the anchoring fibril density compared with vehicle control sites. The possible mechanism by which topical tretinoin increases anchoring fibrils in skin include the drug's property of inhibiting collagenase, a dermal enzyme that degrades anchoring fibril collagen. The authors speculate that increased numbers of collagenous anchoring fibrils within the papillary dermis of human skin is one of the connective-tissue correlates of the clinical improvement observed in photoaged skin after treatment with topical tretinoin.

  16. Recovery after tetraplegia caused by dermal sinus infection: intramedullary abscess and tetraparesis.

    PubMed

    Houx, Laetitia; Brochard, Sylvain; Peudenier, Sylviane; Dam Hieu, Phong; Rémy-Néris, Olivier

    2011-03-01

    Congenital dermal sinuses result from abnormal neurulation, and are uncommon. A spinal intramedullary abscess secondary to an infected dermoid cyst is very rare, and the functional prognosis is usually quite poor. We report on a 16-month-old child with tetraplegia secondary to intramedullary abscesses because of a dermoid cyst infection associated with a dermal sinus. The abscesses were drained, and the dermoid cyst was removed. Antibiotics were administered for 6 weeks after neurosurgery. The child was followed at a pediatric rehabilitation department. After 1 year, he was able to walk quickly and had regained appropriate upper limb motor function for his age. However, bladder sphincter dyssynergia persisted, requiring intermittent catheterization. This case highlights the importance of early diagnosis for surgical intervention and prolonged antibiotic therapy. Long-term follow-up by a multidisciplinary team allowed for the effective management of related neurologic, orthopedic, and bladder disorders.

  17. Protective Effect of Strawberry Extract against Inflammatory Stress Induced in Human Dermal Fibroblasts.

    PubMed

    Gasparrini, Massimiliano; Forbes-Hernandez, Tamara Y; Giampieri, Francesca; Afrin, Sadia; Mezzetti, Bruno; Quiles, Josè L; Bompadre, Stefano; Battino, Maurizio

    2017-01-21

    A protracted pro-inflammatory state is a major contributing factor in the development, progression and complication of the most common chronic pathologies. Fruit and vegetables represent the main sources of dietary antioxidants and their consumption can be considered an efficient tool to counteract inflammatory states. In this context an evaluation of the protective effects of strawberry extracts on inflammatory stress induced by E. coli LPS on human dermal fibroblast cells was performed in terms of viability assays, ROS and nitrite production and biomarkers of oxidative damage of the main biological macromolecules. The results demonstrated that strawberry extracts exerted an anti-inflammatory effect on LPS-treated cells, through an increase in cell viability, and the reduction of ROS and nitrite levels, and lipid, protein and DNA damage. This work showed for the first time the potential health benefits of strawberry extract against inflammatory and oxidative stress in LPS-treated human dermal fibroblast cells.

  18. Use of Ir192 interstitial brachytherapy for an equine malignant dermal schwannoma.

    PubMed

    Saulez, M N; Voigt, A; Steyl, J C A; van Wilpe, E; Kotzen, J; Daniels, F

    2009-12-01

    A 10-year-old Hanoverian mare was evaluated for a right buccal swelling that recurred 3 months following surgical resection. Ultrasonographic examination showed a broadly pedunculated subcutaneous mass at the level of 106-109 and 406-409 cheek teeth associated with an erosive mucosal lesion on the inside of the cheek. Histological examination of a biopsy specimen revealed a well-demarcated, malignant, dermal schwannoma. Following subcutaneous placement of platinum coated Ir192 wires under general anaesthesia, low-dose radiation of 5 gray per day was delivered for 14 days. Short-term complications included loss of patency of the right nasolacrimal duct, erythema, dermatitis, leukotrichia and left-sided deviation of the muzzle. Ten months later, there has been no tumour recurrence. Findings suggest that the use of interstitial brachytherapy should be considered for a malignant, dermal schwannoma that has recurred or is not amenable to surgery.

  19. Skin Pigmentation and Pigmentary Disorders: Focus on Epidermal/Dermal Cross-Talk

    PubMed Central

    Bastonini, Emanuela; Kovacs, Daniela

    2016-01-01

    Variation in human skin and hair color is the most notable aspect of human variability and several studies in evolution, genetics and developmental biology contributed to explain the mechanisms underlying human skin pigmentation, which is responsible for differences in skin color across the world's populations. Despite skin pigmentation is primarily related to melanocytes functionality, the surrounding keratinocytes and extracellular matrix proteins and fibroblasts in the underlying dermal compartment actively contribute to cutaneous homeostasis. Many autocrine/paracrine secreted factors and cell adhesion mechanisms involving both epidermal and dermal constituents determine constitutive skin pigmentation and, whenever deregulated, the occurrence of pigmentary disorders. In particular, an increased expression of such mediators and their specific receptors frequently lead to hyperpigmentary conditions, such as in melasma and in solar lentigo, whereas a defect in their expression/release is related to hypopigmented disorders, as seen in vitiligo. All these interactions underline the relevant role of pigmentation on human evolution and biology. PMID:27274625

  20. Determination of ADME and bioavailability following intravenous, oral, and dermal routes of exposure.

    PubMed

    Saghir, Shakil A

    2009-08-01

    Humans are exposed to chemicals either voluntarily or involuntarily through several routes. Therapeutic drugs are introduced into the human system via a number of routes including, but not limited to, oral, inhalation, intravenous (i.v.), topical, and subcutaneous. For occupational and environmental chemicals, the major routes of human exposure are inhalation, dermal, and oral. To determine the extent of exposure to chemicals, the concentration of the active molecules is measured in a biological medium. Determination of absolute and/or relative bioavailability of occupational and environmental chemical exposure through different routes is critical in understanding the risk to the general population of a low-level exposure to these chemicals. This unit describes typical protocol designs to generate data for the calculation of absorption, distribution, metabolism, and elimination (ADME) and absolute and relative bioavailability of chemicals when exposed through i.v., oral, and dermal routes.

  1. Topical treatments for hydrofluoric acid dermal burns. Further assessment of efficacy using an experimental piq model.

    PubMed

    Dunn, B J; MacKinnon, M A; Knowlden, N F; Billmaier, D J; Derelanko, M J; Rusch, G M; Naas, D J; Dahlgren, R R

    1996-05-01

    Several topical treatments for hydrofluoric acid dermal burns (Zephiran, calcium acetate and magnesium hydroxide antacid soaks, and calcium gluconate gel) were assessed for efficacy in a pig model. Gross appearance and histopathology of treated and untreated burn sites were evaluated. For superficial burns, Zephiran was most effective; calcium acetate, magnesium hydroxide antacid, and calcium gluconate gel were less effective. For deep burns, gross observations showed that calcium acetate and Zephiran were most efficacious, whereas histopathology indicated comparable efficacy of Zephiran, calcium acetate, and calcium gluconate gel for all skin layers. Magnesium hydroxide antacid demonstrated efficacy only for the subdermis. The clinically beneficial effects of both Zephiran and calcium gluconate gel were affirmed. Although results suggest that calcium acetate and magnesium-containing antacids may be beneficial for human hydrofluoric acid dermal burns, these are not established clinical treatments.

  2. Polysaccharides isolated from Phellinus gilvus enhances dermal wound healing in streptozotocin-induced diabetic rats.

    PubMed

    Bae, Jae-Sung; Jang, Kwang-Ho; Jin, Hee-Kyung

    2005-06-01

    Dermal wound healing is a complex process that involved inflammation leading to re-epithelialization, granulation tissue, and tissue remodeling. Previous studies from our laboratory have shown that polysaccharides isolated from fungus, Phellinus gilvus (PG) have various anti-inflammatory activities. In present study, we have assessed the effect of polysaccharides from PG on the dermal wound healing of polysaccharides from PG in streptozotocin-induced diabetic rat model. Six of 6-mm circular wounds were created with biopsy punch on the 4th day after induction of diabetes. After 24 hours, each test substance was applied to the wound twice a day for next 5 days. Circular wounds treated with PG showed significantly reduced wound contraction and complete reepithelialization, as compared to wounds of non-treated (p<0.05). These results show that polysaccharides isolated from PG enhanced wound repair in diabetic impaired healing, and could be developed as a wound healing agent in such clinical settings.

  3. Focal Dermal Hypoplasia with Uterus Bicornis and Renal Ectopia: Case Report and Review of the Literature

    PubMed Central

    Lopez-Porras, Rocío F.; Arroyo, Carlos; Soto-Vega, Elena

    2011-01-01

    Focal dermal hypoplasia (FDH) is a rare inherited genodermatosis with an X-linked dominant trait. FDH is associated with skin defects and other abnormalities of bone, nails, hair, limbs, teeth and eyes. We present the case of a 26-year-old female in the 27th pregnancy week and a previous history of miscarriage. After careful physical examination and dermal biopsy, histopathology revealed that the patient was a carrier of FDH. This is the first report in the literature describing that FDH is associated with uterus bicornis and renal ectopia. Our association could be attributable to early embryonic abnormalities related with FDH because both the uterus bicornis and the renal ectopia originate around the 3th-6th week of embryonic development. We are unable to confirm that the miscarriages were caused by inherited FDH or that uterus bicornis was the cause. We conducted a literature review using the following terms: FDH, Goltz syndrome, uterus bicornis, and renal ectopia. PMID:21941481

  4. Ultra-small NLC for improved dermal delivery of coenyzme Q10.

    PubMed

    Schwarz, Julia C; Baisaeng, Nuttakorn; Hoppel, Magdalena; Löw, Monika; Keck, Cornelia M; Valenta, Claudia

    2013-04-15

    Coenzyme Q10 (CoQ10) acts as an antioxidant in the skin and is frequently contained in anti-aging products. In previous studies, it could be shown that nano-structured lipid carriers (NLC) with a size of about 230 nm are beneficial for the dermal delivery of CoQ10. They increased Q10 skin penetration when compared to equally sized nanoemulsion. In this study, ultra-small NLC were prepared with even smaller mean particles sizes of around 80 nm. The influence of this decrease of particle size was investigated in terms of skin permeation and penetration as well as physicochemical stability of the NLC. Improved dermal delivery of CoQ10 by ultra-small NLC could be achieved.

  5. Human volunteer study on the inhalational and dermal absorption of N-methyl-2-pyrrolidone (NMP) from the vapour phase.

    PubMed

    Bader, Michael; Wrbitzky, Renate; Blaszkewicz, Meinolf; Schäper, Michael; van Thriel, Christoph

    2008-01-01

    N-Methyl-2-pyrrolidone (NMP) is a versatile organic solvent frequently used for surface cleaning such as paint stripping or graffiti removal. Liquid NMP is rapidly absorbed through the skin but dermal vapour phase absorption might also play an important role for the uptake of the solvent. This particular aspect was investigated in an experimental study with 16 volunteers exposed to 80 mg/m(3) NMP for 8 h under either whole-body, i.e. inhalational plus dermal, or dermal-only conditions. Additionally, the influence of moderate physical workload on the uptake of NMP was studied. The urinary concentrations of NMP and its metabolites 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) were followed for 48 h and analysed by gas chromatography-mass spectrometry (GC-MS). Percutaneous uptake delayed the elimination peak times and the apparent biological half-lives of NMP and 5-HNMP. Under resting conditions, dermal-only exposure resulted in the elimination of 71 +/- 8 mg NMP equivalents as compared to 169 +/- 15 mg for whole-body exposure. Moderate workload yielded 79 +/- 8 mg NMP (dermal-only) and 238 +/- 18 mg (whole-body). Thus, dermal absorption from the vapour phase may contribute significantly to the total uptake of NMP, e.g. from workplace atmospheres. As the concentration of airborne NMP does not reflect the body dose, biomonitoring should be carried out for surveillance purposes.

  6. Occupational dermal exposure to nanoparticles and nano-enabled products: Part 2, exploration of exposure processes and methods of assessment.

    PubMed

    Brouwer, Derk H; Spaan, Suzanne; Roff, Martin; Sleeuwenhoek, Anne; Tuinman, Ilse; Goede, Henk; van Duuren-Stuurman, Birgit; Filon, Francesca Larese; Bello, Dhimiter; Cherrie, John W

    2016-08-01

    Over the past decade, the primary focus of nanotoxicology and nanoenvironmental health and safety efforts has been largely on inhalation exposure to engineered nanomaterials, at the production stage, and much less on considering risks along the life cycle of nano-enabled products. Dermal exposure to nanomaterials and its health impact has been studied to a much lesser extent, and mostly in the context of intentional exposure to nano-enabled products such as in nanomedicine, cosmetics and personal care products. How concerning is dermal exposure to such nanoparticles in the context of occupational exposures? When and how should we measure it? In the first of a series of two papers (Larese Filon et al., 2016), we focused our attention on identifying conditions or situations, i.e. a combination of nanoparticle physico-chemical properties, skin barrier integrity, and occupations with high prevalence of skin disease, which deserve further investigation. This second paper focuses on the broad question of dermal exposure assessment to nanoparticles and attempts to give an overview of the mechanisms of occupational dermal exposure to nanoparticles and nano-enabled products and explores feasibility and adequacy of various methods of quantifying dermal exposure to NOAA. We provide here a conceptual framework for screening, prioritization, and assessment of dermal exposure to NOAA in occupational settings, and integrate it into a proposed framework for risk assessment.

  7. Laminin peptide YIGSR induces collagen synthesis in Hs27 human dermal fibroblasts

    SciTech Connect

    Yoon, Jong Hyuk; Kim, Jaeyoon; Lee, Hyeongjoo; Kim, So Young; Jang, Hwan-Hee; Ryu, Sung Ho; Kim, Beom Joon; Lee, Taehoon G.

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer We identify a function of the YIGSR peptide to enhance collagen synthesis in Hs27. Black-Right-Pointing-Pointer YIGSR peptide enhanced collagen type 1 synthesis both of gene and protein levels. Black-Right-Pointing-Pointer There were no changes in cell proliferation and MMP-1 level in YIGSR treatment. Black-Right-Pointing-Pointer The YIGSR effect on collagen synthesis mediated activation of FAK, pyk2 and ERK. Black-Right-Pointing-Pointer The YIGSR-induced FAK and ERK activation was modulated by FAK and MEK inhibitors. -- Abstract: The dermal ECM is synthesized from fibroblasts and is primarily compromised of fibrillar collagen and elastic fibers, which support the mechanical strength and resiliency of skin, respectively. Laminin, a major glycoprotein located in the basement membrane, promotes cell adhesion, cell growth, differentiation, and migration. The laminin tyrosine-isoleucine-glycine-serine-arginine (YIGSR) peptide, corresponding to the 929-933 sequence of the {beta}1 chain, is known to be a functional motif with effects on the inhibition of tumor metastasis, the regulation of sensory axonal response and the inhibition of angiogenesis through high affinity to the 67 kDa laminin receptor. In this study, we identified a novel function of the YIGSR peptide to enhance collagen synthesis in human dermal fibroblasts. To elucidate this novel function regarding collagen synthesis, we treated human dermal fibroblasts with YIGSR peptide in both a time- and dose-dependent manner. According to subsequent experiments, we found that the YIGSR peptide strongly enhanced collagen type 1 synthesis without changing cell proliferation or cellular MMP-1 level. This YIGSR peptide-mediated collagen type 1 synthesis was modulated by FAK inhibitor and MEK inhibitor. This study clearly reveals that YIGSR peptide plays a novel function on the collagen type 1 synthesis of dermal fibroblasts and also suggests that YIGSR is a strong candidate

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

    PubMed

    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.

  9. Laminin α5 in the keratinocyte basement membrane is required for epidermal-dermal intercommunication.

    PubMed

    Wegner, Jeannine; Loser, Karin; Apsite, Gunita; Nischt, Roswitha; Eckes, Beate; Krieg, Thomas; Werner, Sabine; Sorokin, Lydia

    2016-12-01

    Laminin α5 is broadly expressed in the epidermal basement membrane (BM) of mature mice and its elimination at this site (Lama5(Ker5) mouse) results in hyperproliferation of basal keratinocytes and a delay in hair follicle development, which correlated with upregulation of the dermally-derived laminin α2 and laminin α4 chains in the epidermal BM and of tenascin-C subjacent to the BM. In vitro studies revealed laminin 511 to be strongly adhesive for primary keratinocytes and that loss of laminin α5 does not result in cell autonomous defects in proliferation. Flow cytometry reveals that the loss of laminin α5 resulted in increased numbers of CD45(+), CD4(+) and CD11b(+) immune cells in the skin, which temporo-spatial analyses revealed were detectable only subsequent to the loss of laminin α5 and the appearance of the hyperproliferative keratinocyte phenotype. These findings indicate that immune cell changes are the consequence and not the cause of keratinocyte hyperproliferation. Loss of laminin α5 in the epidermal BM was also associated with changes in the expression of several dermally-derived growth factors involved in keratinocyte proliferation and hair follicle development in adult but not new born Lama5(Ker5) skin, including KGF, EGF and KGF-2. In situ binding of FGF-receptor-2α (IIIb)-Fc chimera (FGFR2IIIb) to mouse skin sections revealed decoration of several BMs, including the epidermal BM, which was absent in Lama5(Ker5) skin. This indicates reduced levels of FGFR2IIIb ligands, which include KGF and KGF-2, in the epidermal BM of adult Lama5(Ker5) skin. Our data suggest an initial inhibitory effect of laminin α5 on basal keratinocyte proliferation and migration, which is exacerbated by subsequent changes in growth factor expression by epidermal and dermal cells, implicating laminin α5 in epidermal-dermal intercommunication.

  10. Ophthalmologic findings in an 18-month-old boy with focal dermal hypoplasia.

    PubMed

    Young, Marielle P; Sawyer, Briana L; Hartnett, M Elizabeth

    2014-04-01

    Focal dermal hypoplasia is a rare X-linked dominant disorder with in utero lethality in males. Affected patients have been reported to have several different mutations in the PORCN gene on chromosome Xp11.23. Dysplastic mesodermal and ectodermal tissue causes clinical findings in the skin, skeleton, teeth, central nervous system, and eyes of affected patients. We describe the ophthalmologic findings in an 18-month-old boy with mosaicism of a novel mutation in PORCN.

  11. Autochthonous disseminated dermal and visceral leishmaniasis in an AIDS patient, southern Thailand, caused by Leishmania siamensis.

    PubMed

    Bualert, Lertwut; Charungkiattikul, Wiwat; Thongsuksai, Paramee; Mungthin, Mathirut; Siripattanapipong, Suradej; Khositnithikul, Rommanee; Naaglor, Tawee; Ravel, Christophe; El Baidouri, Fouad; Leelayoova, Saovanee

    2012-05-01

    We report the first establishment of in vitro cultivation and genotypic characterization of Leishmania siamensis isolated from an autochthonous disseminated dermal and visceral leishmaniasis in a Thai acquired immunodeficiency syndrome (AIDS) patient. The molecular identification has shown that the parasite was identical to L. siamensis, a recently described Leishmania species reported in the southern provinces of Thailand. The phylogenetic analysis has confirmed L. siamensis as closely related to the zoonotic Leishmania species L. enrietti.

  12. Apigenin induces dermal collagen synthesis via smad2/3 signaling pathway.

    PubMed

    Zhang, Y; Wang, J; Cheng, X; Yi, B; Zhang, X; Li, Q

    2015-04-13

    Decrease in fibroblast-produced collagen has been proven to be the pivotal cause of skin aging, but there is no satisfactory drug which directly increases dermal thickness and collage density. Here we found that a flavonoid natural product, apigenin, could significantly increase collagen synthesis. NIH/3T3 and primary human dermal fibroblasts (HDFs) were incubated with various concentrations of apigenin, with dimethyl sulfoxide (DMSO) serving as the negative control. Real-time reverse-transcription polymerase chain reaction (PCR), Western Blot, and Toluidine blue staining demonstrated that apigenin stimulated type-I and type-III collagen synthesis of fibroblasts on the mRNA and protein levels. Meanwhile, apigenin did not induce expression of alpha smooth muscle actin (α-SMA) in vitro and in vivo, a fibrotic marker in living tissues. Then the production of collagen was confirmed by Masson's trichrome stain, Picrosirius red stain and immunohistochemistry in mouse models. We also clarified that this compound induced collagen synthesis by activating smad2/3 signaling pathway. Taken together, without obvious influence on fibroblasts' apoptosis and viability, apigenin could promote the type-I and type-III collagen synthesis of dermal fibroblasts in vitro and in vivo, thus suggesting that apigenin may serve as a potential agent for esthetic and reconstructive skin rejuvenation.

  13. The influence of water mixtures on the dermal absorption of glycol ethers

    SciTech Connect

    Traynor, Matthew J.; Wilkinson, Simon C.; Williams, Faith M. . E-mail: F.M.Williams@ncl.ac.uk

    2007-01-15

    Glycol ethers are solvents widely used alone and as mixtures in industrial and household products. Some glycol ethers have been shown to have a range of toxic effects in humans following absorption and metabolism to their aldehyde and acid metabolites. This study assessed the influence of water mixtures on the dermal absorption of butoxyethanol and ethoxyethanol in vitro through human skin. Butoxyethanol penetrated human skin up to sixfold more rapidly from aqueous solution (50%, 450 mg/ml) than from the neat solvent. Similarly penetration of ethoxyethanol was increased threefold in the presence of water (50%, 697 mg/ml). There was a corresponding increase in apparent permeability coefficient as the glycol ether concentration in water decreased. The maximum penetration rate of water also increased in the presence of both glycol ethers. Absorption through a synthetic membrane obeyed Fick's Law and absorption through rat skin showed a similar profile to human skin but with a lesser effect. The mechanisms for this phenomenon involves disruption of the stratum corneum lipid bilayer by desiccation by neat glycol ether micelles, hydration with water mixtures and the physicochemical properties of the glycol ether-water mixtures. Full elucidation of the profile of absorption of glycol ethers from mixtures is required for risk assessment of dermal exposure. This work supports the view that risk assessments for dermal contact scenarios should ideally be based on absorption data obtained for the relevant formulation or mixture and exposure scenario and that absorption derived from permeability coefficients may be inappropriate for water-miscible solvents.

  14. Nanocrystals of medium soluble actives--novel concept for improved dermal delivery and production strategy.

    PubMed

    Zhai, Xuezhen; Lademann, Jürgen; Keck, Cornelia M; Müller, Rainer H

    2014-08-15

    After use in oral pharmaceutical products, nanocrystals are meanwhile applied to improve the dermal penetration of cosmetic actives (e.g. rutin, hesperidin) and of drugs. By now, nanocrystals are only dermally applied made from poorly soluble actives. The novel concept is to formulate nanocrystals also from medium soluble actives, and to apply a dermal formulation containing additionally nanocrystals. The nanocrystals should act as fast dissolving depot, increase saturation solubility and especially accumulate in the hair follicles, to further increase skin penetration. Caffeine was used as model compound with relevance to market products, and a particular process was developed for the production of caffeine nanocrystals to overcome the supersaturation related effect of crystal growth and fiber formation - typical with medium soluble compounds. It is based on low energy milling (pearl milling) in combination with low dielectric constant dispersion media (water-ethanol or ethanol-propylene glycol mixtures) and optimal stabilizers. Most successful was Carbopol(®) 981 (e.g. 20% caffeine in ethanol-propylene glycol 3:7 with 2% Carbopol, w/w). Nanocrystals with varied sizes can now be produced in a controlled process e.g. 660 nm (optimal for hair follicle accumulation) to 250 nm (optimal for fast dissolution). The short term test proved stability over 2 months of the present formulation being sufficient to perform in vivo testing of the novel concept.

  15. Dermal Exposure Assessment to Pesticides in Farming Systems in Developing Countries: Comparison of Models

    PubMed Central

    Lesmes Fabian, Camilo; Binder, Claudia R.

    2015-01-01

    In the field of occupational hygiene, researchers have been working on developing appropriate methods to estimate human exposure to pesticides in order to assess the risk and therefore to take the due decisions to improve the pesticide management process and reduce the health risks. This paper evaluates dermal exposure models to find the most appropriate. Eight models (i.e., COSHH, DERM, DREAM, EASE, PHED, RISKOFDERM, STOFFENMANAGER and PFAM) were evaluated according to a multi-criteria analysis and from these results five models (i.e., DERM, DREAM, PHED, RISKOFDERM and PFAM) were selected for the assessment of dermal exposure in the case study of the potato farming system in the Andean highlands of Vereda La Hoya, Colombia. The results show that the models provide different dermal exposure estimations which are not comparable. However, because of the simplicity of the algorithm and the specificity of the determinants, the DERM, DREAM and PFAM models were found to be the most appropriate although their estimations might be more accurate if specific determinants are included for the case studies in developing countries. PMID:25938911

  16. Quantitative analysis of intrinsic skin aging in dermal papillae by in vivo harmonic generation microscopy

    PubMed Central

    Liao, Yi-Hua; Kuo, Wei-Cheng; Chou, Sin-Yo; Tsai, Cheng-Shiun; Lin, Guan-Liang; Tsai, Ming-Rung; Shih, Yuan-Ta; Lee, Gwo-Giun; Sun, Chi-Kuang

    2014-01-01

    Chronological skin aging is associated with flattening of the dermal-epidermal junction (DEJ), but to date no quantitative analysis focusing on the aging changes in the dermal papillae (DP) has been performed. The aim of the study is to determine the architectural changes and the collagen density related to chronological aging in the dermal papilla zone (DPZ) by in vivo harmonic generation microscopy (HGM) with a sub-femtoliter spatial resolution. We recruited 48 Asian subjects and obtained in vivo images on the sun-protected volar forearm. Six parameters were defined to quantify 3D morphological changes of the DPZ, which we analyzed both manually and computationally to study their correlation with age. The depth of DPZ, the average height of isolated DP, and the 3D interdigitation index decreased with age, while DP number density, DP volume, and the collagen density in DP remained constant over time. In vivo high-resolution HGM technology has uncovered chronological aging-related variations in DP, and sheds light on real-time quantitative skin fragility assessment and disease diagnostics based on collagen density and morphology. PMID:25401037

  17. Dermal exposure assessment to pesticides in farming systems in developing countries: comparison of models.

    PubMed

    Lesmes-Fabian, Camilo; Fabian, Camilo Lesmes; Binder, Claudia R

    2015-04-29

    In the field of occupational hygiene, researchers have been working on developing appropriate methods to estimate human exposure to pesticides in order to assess the risk and therefore to take the due decisions to improve the pesticide management process and reduce the health risks. This paper evaluates dermal exposure models to find the most appropriate. Eight models (i.e., COSHH, DERM, DREAM, EASE, PHED, RISKOFDERM, STOFFENMANAGER and PFAM) were evaluated according to a multi-criteria analysis and from these results five models (i.e., DERM, DREAM, PHED, RISKOFDERM and PFAM) were selected for the assessment of dermal exposure in the case study of the potato farming system in the Andean highlands of Vereda La Hoya, Colombia. The results show that the models provide different dermal exposure estimations which are not comparable. However, because of the simplicity of the algorithm and the specificity of the determinants, the DERM, DREAM and PFAM models were found to be the most appropriate although their estimations might be more accurate if specific determinants are included for the case studies in developing countries.

  18. DOXYCYCLINE HYDROGELS WITH REVERSIBLE DISULFIDE CROSSLINKS FOR DERMAL WOUND HEALING OF MUSTARD INJURIES

    PubMed Central

    Anumolu, SivaNaga S; Menjoge, Anupa R.; Deshmukh, Manjeet; Gerecke, Donald; Stein, Stanley; Laskin, Jeffrey; Sinko, Patrick J.

    2010-01-01

    Doxycycline hydrogels containing reversible disulfide crosslinks were investigated for a dermal wound healing application. Nitrogen mustard (NM) was used as a surrogate to mimic the vesicant effects of the chemical warfare agent sulfur mustard. An 8-arm-poly(ethylene glycol) (PEG) polymer containing multiple thiol (-SH) groups was crosslinked using hydrogen peroxide (H2O2 hydrogel) or 8-arm-S-thiopyridyl (S-TP hydrogel) to form a hydrogel in situ. Formulation additives (glycerin, PVP and PEG 600) were found to promote dermal hydrogel retention for up to 24 h. Hydrogels demonstrated high mechanical strength and a low degree of swelling (<1.5%). Doxycycline release from the hydrogels was biphasic and sustained for up to 10-days in vitro. Doxycycline (8.5 mg/cm3) permeability through NM-exposed skin was elevated as compared to non vesicant-treated controls at 24, 72 and 168 h post exposure with peak permeability at 72 h. The decrease in doxycycline permeability at 168 h correlates to epidermal reepithelialization and wound healing. Histology studies of skin showed that doxycycline-loaded (0.25% w/v) hydrogels provided improved wound healing response on NM-exposed skin as compared to untreated skin and skin treated with placebo hydrogels in a SKH-1 mouse model. In conclusion, PEG-based doxycycline hydrogels are promising for dermal wound healing application of mustard injuries. PMID:20950853

  19. Apigenin Induces Dermal Collagen Synthesis Via smad2/3 Signaling Pathway

    PubMed Central

    Zhang, Y.; Wang, J.; Cheng, X.; Yi, B.; Zhang, X.; Li, Q.

    2015-01-01

    Decrease in fibroblast-produced collagen has been proven to be the pivotal cause of skin aging, but there is no satisfactory drug which directly increases dermal thickness and collage density. Here we found that a flavonoid natural product, apigenin, could significantly increase collagen synthesis. NIH/3T3 and primary human dermal fibroblasts (HDFs) were incubated with various concentrations of apigenin, with dimethyl sulfoxide (DMSO) serving as the negative control. Real-time reverse-transcription polymerase chain reaction (PCR), Western Blot, and Toluidine blue staining demonstrated that apigenin stimulated type-I and type-III collagen synthesis of fibroblasts on the mRNA and protein levels. Meanwhile, apigenin did not induce expression of alpha smooth muscle actin (α-SMA) in vitro and in vivo, a fibrotic marker in living tissues. Then the production of collagen was confirmed by Masson’s trichrome stain, Picrosirius red stain and immunohistochemistry in mouse models. We also clarified that this compound induced collagen synthesis by activating smad2/3 signaling pathway. Taken together, without obvious influence on fibroblasts’ apoptosis and viability, apigenin could promote the type-I and type-III collagen synthesis of dermal fibroblasts in vitro and in vivo, thus suggesting that apigenin may serve as a potential agent for esthetic and reconstructive skin rejuvenation. PMID:26150153

  20. Melanocyte stimulating hormone peptides inhibit TNF-alpha signaling in human dermal fibroblast cells.

    PubMed

    Hill, R P; MacNeil, S; Haycock, J W

    2006-02-01

    Alpha-melanocyte stimulating hormone (alpha-MSH) has been identified as a potent anti-inflammatory in various tissues including the skin. It has previously been shown in skin cell keratinocytes and melanocytes/melanoma cells that MSH peptides inhibit TNF-alpha stimulated NF-kappaB activity and intercellular adhesion molecule-1 (ICAM-1) upregulation. However, the precise anti-inflammatory role of MSH peptides in dermal fibroblasts is unclear. Some studies report on pro-inflammatory responses, while others on anti-inflammatory responses. The present study confirms MC1R expression in cultured human dermal fibroblasts and reports that the MSH peptides alpha-MSH and KP(-D-)V inhibit TNF-alpha stimulated NF-kappaB activity and ICAM-1 upregulation, consistent with an anti-inflammatory role. However, involvement of IkappaB-alpha regulation by either peptide was not confirmed, supporting a mechanism independent of the NF-kappaB inhibitor. In conclusion, alpha-MSH and KP(-D-)V peptides have an anti-inflammatory action on dermal fibroblast signaling by inhibiting the pro-inflammatory activity of TNF-alpha in vitro.