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At least 919 records · Page 51Linked to original sources
PubMed2004

Neuroprotective effects of a novel poly(ADP-ribose) polymerase-1 inhibitor, 2-[3-[4-(4-chlorophenyl)-1-piperazinyl] propyl]-4(3H)-quinazolinone (FR255595), in an in vitro model of cell death and in mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.

The massive activation of poly(ADP-ribose) polymerase-1 (PARP-1) by DNA-damaging stimuli, such as exposure to reactive oxygen species (ROS), can lead to cell injury via severe, irreversible depletion of the NAD and ATP pool, and PARP-1 inhibitors have been expected to rescue neurons from degeneration in a number of disease models. We have recently identified 2-[3-[4-(4-chlorophenyl)-1-piperazinyl] propyl]-4(3H)-quinazolinone (FR255595) as a novel and potent PARP-1 inhibitor through structure-based drug design and high-throughput screening. This compound potently inhibited PARP activity with an IC(50) value of 11 nM and was orally active and highly brain penetrable. Here, we show that prevention of PARP activation by FR255595 protects against both ROS-induced cells injury in vitro and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced nigrostriatal dopaminergic damage in an in vivo Parkinson's disease (PD) model. In cell death models in vitro, exposure of hydrogen peroxide induced cell death with PARP overactivation in PC12 cells and SH-SY5Y cells, and pre- and post-treatment with FR255595 (10(-9)-10(-5) M) significantly reduced PARP activation and cell death. In mouse MPTP model, MPTP (20 mg/kg i.p.) intoxication lead to PARP activation and cell damage in the nigrostriatal dopaminergic pathway, which was significantly ameliorated by oral administration of FR255595 (10-32 mg/kg), both in the substantia nigra and in the striatum via marked reduction of PARP activation, even with delayed treatment. These findings clearly indicate that the novel PARP-1 inhibitor FR255595 exerts neuroprotective effect through its potent PARP-1 inhibitory actions in PD model, suggesting that the drug could be an attractive candidate for several neurodegenerative disorders, including PD.

Animals↗
PubMed1997

Serum-free keloid fibroblast cell culture: an in vitro model for the study of aberrant wound healing.

The purpose of this study was to develop an in vitro serum-free keloid fibroblast model. Keloid formation remains a problem for every surgeon. Prior evaluations of fibroblast characteristics in vitro, especially those of growth factor measurement, have been confounded by the presence of serum-containing tissue culture media. The serum itself contains growth factors, yet has been a "necessary evil" to sustain cell growth. The design of this study is laboratory-based and uses keloid fibroblasts obtained from five patients undergoing facial (ear lobule) keloid removal in a university-affiliated clinic. Keloid fibroblasts were established in primary cell culture and then propagated in a serum-free environment. The main outcome measures included sustained keloid fibroblast growth and viability, which was comparable to serum-based models. The keloid fibroblast cell cultures exhibited logarithmic growth, sustained a high cellular viability, maintained a monolayer, and displayed contact inhibition. Demonstrating model consistency, there was no statistically significant difference between the mean cell counts of the five keloid fibroblast cell lines at each experimental time point. The in vitro growth of keloid fibroblasts in a serum-free model has not been done previous to this study. The results of this study indicate that the proliferative characteristics described are comparable to those of serum-based models. The described model will facilitate the evaluation of potential wound healing modulators, and cellular effects and collagen modifications of laser resurfacing techniques, and may serve as a harvest source for contaminant-free fibroblast autoimplants. Perhaps its greatest utility will be in the evaluation of endogenous and exogenous growth factors.

Cell Division↗
PubMed1994

Human placental mast cells as an in vitro model system in aspects of neuro-immunotoxicity testing.

1. In both the developing and adult nervous systems, nerve growth factor (NGF) influences neuronal survival, differentiation and recovery following insult. 2. The effect of NGF upon human placental mast cells (HPMC) was investigated, since it is known that rodent mast cells express a functional receptor for NGF and secrete histamine upon challenge with this neurotrophic factor. Furthermore, human placental tissue contains a significant amount of NGF and expresses a NGF receptor. 3. HPMC were shown to secrete histamine in a concentration dependent manner in response to NGF (0.001-10.0 micrograms ml-1) in the presence of the lipid cofactor phosphatidylserine (10.0 micrograms ml-1). 4. NGF induced histamine release from isolated HPMC with an EC50 of 0.1 microgram ml-1 NGF and maximal secretion of total cellular histamine of 22.3 +/- 3.4% at 3.0 micrograms ml-1. 5. The response was shown to be a secretory process, dependent upon the presence of exogenous calcium ions and to be pH- and temperature-sensitive. 6. HPMC are suggested to be a suitable primary cell model for use in aspects of in vitro toxicity testing, in terms of assessing the neuro-immunotoxic potential of neurotrophic therapeutics. In addition, mechanistic studies concerning those xenobiotics which may exert their neurotoxic effect via interaction with neurotrophic factors and, or their receptors, may be studied in this human cell model.

Calcium↗
PubMedDate not supplied

Penetration studies of vitamin E acetate applied from cosmetic formulations to the stratum corneum of an in vitro model using quantification by tape stripping, UV spectroscopy, and HPLC.

The skin activation and penetration capability of vitamin E acetate as an ingredient in a basic o/w cream (lamellar type), in liposomes (Rovisome) and microparticles (Roviparts), was investigated under in vitro conditions (BUS model) by the adhesive stripping method. The aim of the study was to compare the analytical results obtained by UV spectroscopy (transmission) and the conventional HPLC method. For the quantitative spectrometric assay, a classical least-squares evaluation of the spectra between 265 and 350 nm, based on the constituent spectra, was used. UV spectroscopy is an economic analytical method for evaluating a large population of samples of the horny layer taken by the adhesive tape stripping method, which is an established tool for depth profiling of substances within the stratum corneum. With regard to the irritation test, no cytotoxicity was recorded for all formulations tested. However, the Roviparts and Rovisome cream formulations induced a considerable activation of the epidermal cells that may contribute to the penetration efficiency of Rovisome-formulated vitamin E acetate. The Rovisome-formulated cream delivered a maximum amount of vitamin E acetate into the horny layer compared to the other formulations tested. The difference can be explained by an alteration of the plasticity of the horny layer inducing a strong reservoir capacity and an activation of upper epidermal cells. Moreover, the opening of the potential pathway for a follicular penetration may be part of the increased reservoir capacity.

Animals↗
PubMed2004

African trypanosome interactions with an in vitro model of the human blood-brain barrier.

The neurological manifestations of sleeping sickness in man are attributed to the penetration of the blood-brain barrier (BBB) and invasion of the central nervous system by Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. However, how African trypanosomes cross the BBB remains an unresolved issue. We have examined the traversal of African trypanosomes across the human BBB using an in vitro BBB model system constructed of human brain microvascular endothelial cells (BMECs) grown on Costar Transwell inserts. Human-infective T. b. gambiense strain IL 1852 was found to cross human BMECs far more readily than the animal-infective Trypanosoma brucei brucei strains 427 and TREU 927. Tsetse fly-infective procyclic trypomastigotes did not cross the human BMECs either alone or when coincubated with bloodstreamform T. b. gambiense. After overnight incubation, the integrity of the human BMEC monolayer measured by transendothelial electrical resistance was maintained on the inserts relative to the controls when the endothelial cells were incubated with T. b. brucei. However, decreases in electrical resistance were observed when the BMEC-coated inserts were incubated with T. b. gambiense. Light and electron microscopy studies revealed that T. b. gambiense initially bind at or near intercellular junctions before crossing the BBB paracellularly. This is the first demonstration of paracellular traversal of African trypanosomes across the BBB. Further studies are required to determine the mechanism of BBB traversal by these parasites at the cellular and molecular level.

Animals↗
PubMed2005

Activation of neutrophil granulocytes in an in vitro model of a cardiopulmonary bypass.

Activated neutrophils play a central role in the pathogenesis of postoperative organ dysfunction after surgery with cardiopulmonary bypass. The researchers used an in vitro roller pump model to investigate the relative importance of the biomaterial, platelets, plasma proteins including activated complement, and flow mode on neutrophil activation as shown by the adhesion, degranulation, and increased the surface expression of CD11b. Neutrophil adhesion to the biomaterial increased with platelet addition, but not with plasma. Biomaterial contact activated neutrophils in a serum-free buffer, but was significantly increased by activated complement. Platelets increased neutrophil degranulation in a serum-free buffer but tended to reduce it in plasma. CD11b expression increased in both media. Complement activation was higher with neutrophils alone than with neutrophils and platelets combined. The roller pump reduced neutrophil adhesion and increased degranulation compared to passive rotation. Neutrophil interaction with platelets and complement were more important for activation than biomaterial contact and use of the roller pump. Improvement of biocompatibility is dependent on modifying complement activation and platelet interaction with neutrophils.

Analysis of Variance↗
PubMed2005

Effects of fermentation products of pro- and prebiotics on trans-epithelial electrical resistance in an in vitro model of the colon.

Evidence from in vivo and in vitro studies suggests that the consumption of pro- and prebiotics may inhibit colon carcinogenesis; however, the mechanisms involved have, thus far, proved elusive. There are some indications from animal studies that the effects are being exerted during the promotion stage of carcinogenesis. One feature of the promotion stage of colorectal cancer is the disruption of tight junctions, leading to a loss of integrity across the intestinal barrier. We have used the Caco-2 human adenocarcinoma cell line as a model for the intestinal epithelia. Trans-epithelial electrical resistance measurements indicate Caco-2 monolayer integrity, and we recorded changes to this integrity following exposure to the fermentation products of selected probiotics and prebiotics, in the form of nondigestible oligosaccharides (NDOs). Our results indicate that NDOs themselves exert varying, but generally minor, effects upon the strength of the tight junctions, whereas the fermentation products of probiotics and NDOs tend to raise tight junction integrity above that of the controls. This effect was bacterial species and oligosaccharide specific. Bifidobacterium Bb 12 was particularly effective, as were the fermentation products of Raftiline and Raftilose. We further investigated the ability of Raftilose fermentations to protect against the negative effects of deoxycholic acid (DCA) upon tight junction integrity. We found protection to be species dependent and dependent upon the presence of the fermentation products in the media at the same time as or after exposure to the DCA. Results suggest that the Raftilose fermentation products may prevent disruption of the intestinal epithelial barrier function during damage by tumor promoters.

Anticarcinogenic Agents↗
PubMedDate not supplied

Demonstration of dual parallel jet interaction in an in vitro model of multivalvular disease by use of optical visualization and color Doppler flow mapping.

Parallel jets, such as those occurring in the heart in multivalvular diseases like combined mitral stenosis and aortic insufficiency, have created difficulty when color Doppler flow mapping or continuous wave Doppler has been used to localize or to measure the jets because they appear to merge. Dual jet interaction was reproduced in an in vitro transparent model by driving two parallel adjacent jets, one lower velocity, higher mass, through a 19 mm2 orifice, and the other higher peak velocity, smaller mass through two orifices, 0.27 mm2 and 1.5 mm2, by use of a solution of India ink and cornstarch to optically visualize the jet interaction and image the interaction by color Doppler. Consistent deviation of the lower velocity jet towards the higher velocity jet was observed, and the large jet angled more strongly towards the small jet for the 1.5 mm2 small jet orifice than for the 0.27 mm2 orifice for constant large and small jet velocities. There was a better linear correlation of the amount of large jet angulation to the ratio of both jets' Reynolds numbers than to the ratio of both flow rates. The jets interacted as close as 1.3 cm from their point of origin, and the region after the jets merged was a highly turbulent mixing zone where neither jet could be separately imaged or visualized. These observations suggest that relative velocity plays a primary role in determining jet interaction which is a recruitment phenomena but that other hydrodynamic parameters, such as flow rate and Reynolds numbers, determine the degree to which the jets deviate.

Aortic Valve Insufficiency↗
PubMed2006

Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's disease.

Huntington's disease (HD) is an autosomal dominant, inherited and fatal neurodegenerative disorder for which there is, at present, no effective treatment or cure. Striatal medium spiny neurons (MSN) are the most sensitive in HD. Dysregulation of glutamate/calcium signaling pathway emerges as a possible cause of striatal MSN neurodegeneration in HD. Here we evaluated five clinically relevant glutamate pathway inhibitors using previously developed in vitro HD model. We found that folic acid, gabapentin and lamotrigine did not protect HD neurons from glutamate-induced cell death, but memantine and riluzole were protective. Our results provide further support to potential use of memantine and riluzole for treatment of HD.

Amines↗
PubMed2004

Improvement of lipophilicity and membrane transport of cefuroxime using in vitro models.

Most beta-lactam antibiotics cannot be absorbed orally and, therefore, must be administered intravenously (i.v.) or intramuscularly (i.m.). Because of the obvious drawbacks of drug delivery by injection, the development of alternatives with enhanced oral bioavailability is receiving much attention in pharmaceutical research. Cefuroxime exhibiting significant advantages in the parental treatment of common infections, was used as model drug in the present study. The effect of the cationic absorption enhancers (four quaternary ammonium salts) on the lipophilicity of cefuroxime was investigated by means of the n-octanol/water system. The results on partitioning coefficients in the n-octanol/buffer system were confirmed using an in vitro transport model with artificial (dodecanol collodium membrane) and biological membranes (Charles-River guinea pig).

Animals↗
PubMedDate not supplied

In vitro models to study hepatotoxicity.

Drug discovery and development consists of a series of processes starting with the demonstration of pharmacological effects in experimental cell and animal models and ending with drug safety and efficacy studies in patients. A main limitation is often the unacceptable level of toxicity with the liver as the primary target organ. Therefore, approaches to study hepatic toxicity in the early phase of drug discovery represent an important step towards rational drug development. A variety of in vitro liver models have been developed in the past years. Next to their use in drug development, they can also be applied to study environmental toxins and their hepatotoxicity. The 3 main approaches are ex vivo isolated and perfused organ models, precision-cut liver slices and cell culture models. Although the advantage of whole organ perfusions is based on the assessment of physiologic parameters such as bile production and morphologic parameters such as tissue histology, cell culture models can be efficiently used to assess cellular metabolism, cytotoxicity and genotoxicity. The advantage of precision-cut liver slices is based on the juxtaposition of cellular assays and tissue morphology. None of these models can be compared as they all focus on different fields of hepatoxicology. For the future, the ideal setup for testing the hepatic toxicity of a new compound could of primary studies in cell or slice cultures to assess cellular effects and secondary studies using ex vivo perfused organs to examine gross organ function parameters and histology.

Cell Culture Techniques↗
PubMed1988

HT-29 cells are an in vitro model for the generation of cell polarity in epithelia during embryonic differentiation.

A monoclonal antibody that recognizes a membrane glycoprotein specific for the apical membrane of human colonic epithelial cells has been used to follow the differentiation and polarization of a cell line, HT-29, derived from a human colon adenocarcinoma. When these cells formed a polarized epithelium, the antigen was concentrated at the apical plasma membrane. It was also found intracellularly in vesicles and vacuoles. When HT-29 cells were undifferentiated and unpolarized, the antigen was not expressed significantly at the plasma membrane but was found concentrated in the membranes of intracellular vacuoles. Cells not yet organized into an epithelium may thus synthesize a membrane protein specific for their future apical membranes and store it intracellularly until the polarization process takes place. Intermediary stages of differentiation were occasionally recognized. They are characterized by a small number of cells surrounding an intercellular lumen. These lumina displayed apical membrane features (the presence of the apical antigen, of some microvilli, and of junctional complexes), although the cells were not fully differentiated. The differentiation process in HT-29 cells is apparently similar to that observed during embryonic development of the intestine. Therefore, HT-29 cells represent a useful model system to study epithelial differentiation in vitro.

Adenocarcinoma↗
PubMed2004

An accelerated in vitro model for adhesive testing.

PURPOSE: To develop a pilot in vitro accelerated laboratory testing protocol for assessing marginal sealing capability of dental adhesives. METHODS: Occlusal cavities were prepared in 20 human molar teeth and restored with Spectrum TPH resin composite. Prime & Bond NT and Prompt L-Pop served as the adhesive for eight teeth each. An experimental self-etching adhesive system was used on the remaining four teeth. Each specimen was subjected in sequential fashion to the following challenges: 400,000 wear cycles in a Leinfelder simulator; 5000 thermocycles between water baths maintained at 5 degrees C and 55 degrees C with a dwell time of 40 seconds in each; and a repetition of the 400,000 wear cycles. Polyvinyl siloxane impressions were made at baseline and after each challenge. Microleakage was assessed following silver nitrate staining and marginal degradation was evaluated using light microscopy and the stone casts made from the impressions taken during the project. RESULTS: Microleakage analysis yielded the following median leakage values: Prime & Bond NT - 0; Prompt L-Pop - 1; and experimental self-etching adhesive - 3. The Wilcoxon sign rank test demonstrated significant differences between all three adhesives (P < or = 0.05). Evaluation of the stone casts demonstrated that marginal gaps were more prevalent after the second wear challenge.

Acid Etching, Dental↗
PubMed2000

Screening of anti-hypoxia/reoxygenation agents by an in vitro model. Part 1: Natural inhibitors for protein tyrosine kinase activated by hypoxia/reoxygenation in cultured human umbilical vein endothelial cells.

Protein tyrosine kinase (PTK) signaling pathways play important roles in ischemia/reperfusion (I/R) or hypoxia/reoxygenation (H/R) injuries. Inhibition of PTK activation can protect against I/R- or H/R-induced damages. As one part of our work for seeking bioactive compounds from natural sources against I/R or H/R, in the present study we examined the effects of 54 compounds purified from various traditional Chinese herbs on H/R-induced PTK activation by means of an in vitro H/R model in cultured human umbilical vein endothelial cells (HUVEC). The results demonstrated that an increase in PTK activation was induced after 2 h of reoxygenation. Compounds 2 (macrostemososide A), 3 (laxogenin-3-O-beta-D-xylopyranosyl-(1-->4)-alpha-L-arabinopyra nosyl- (1-->6)-beta-D-glucopyranoside), 4 (chinenoside II), 7 (ginsenoside-Rd), 52 (icariin), 53 (icariside), and 54 (icaritin) showed relatively obvious inhibition on this H/R-induced PTK activation. Compounds 5 (beta-sitosterol) and 6 (daucosterine), especially 5, completely blocked such an increased activation of PTK induced by H/R. On the contrary, compound 29 (isocumarine) significantly promoted PTK activation further. Moreover, the effects of these compounds on PTK activation were dose-dependent.

Cell Hypoxia↗
PubMed1994

An in vitro model of ethanol-dependent liver cell injury.

Primary cultures of adult rat hepatocytes were incubated (6 to 96 hr) with 50 to 150 mmol/L ethanol, 0.5 mmol/L linoleate, 0.5 mmol/L palmitate, 0.5 mmol/L 4-methylpyrazole, 0 to 25 mumol/L vitamin E phosphate or selected combinations of these agents. Agent-dependent changes in liver cell viability (AST release and reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and function (phospholipid peroxidation, hydrolysis, biosynthesis and triacylglycerol biosynthesis) were determined. The influence of ethanol on liver cell function and viability was dose and incubation time dependent. Short periods (24 hr or less) of exposure to 100 mmol/L ethanol increased liver cell triacylglycerol biosynthesis and phospholipid hydrolysis, peroxidation and biosynthesis without altering cell viability. However, longer periods (72 hr or more) of exposure to 100 or 150 mmol/L ethanol resulted in significant reductions (30% to 50%) in cell viability, function and phosphatidylcholine biosynthesis and content. The ethanol-dependent decreases in cell function and viability were potentiated by linoleate and reduced by vitamin E phosphate, palmitate and 4-methylpyrazole. These results suggest that ethanol-induced liver cell injury in vitro is not a result of ethanol per se, but factors such as acetaldehyde or oxyradicals produced as a consequence of ethanol metabolism. Therefore the incubation of cultured hepatocytes with ethanol may be an appropriate model in vitro for determining the mechanisms by which ethanol intake disrupts liver cell function in vivo.

Animals↗
PubMed2001

Methamphetamine-induced rapid and reversible changes in dopamine transporter function: an in vitro model.

This laboratory has demonstrated that a single methamphetamine (METH) injection rapidly and reversibly decreases the activity of the dopamine transporter (DAT), as assessed ex vivo in synaptosomes prepared from treated rats. This decrease does not occur because of residual drug introduced by the original injection or nor is it associated with a change in binding of the DAT ligand WIN35428. The purpose of this study was to elucidate the mechanism or mechanisms of this METH effect by determining whether direct application of this stimulant to synaptosomes causes changes in DAT similar to those observed ex vivo. Similar to the ex vivo effect, incubation of striatal synaptosomes with METH decreased DAT activity, but not WIN35428 binding: the effect on activity was not eliminated by repeated washing of synaptosomes. Also, as observed ex vivo, incubation with 3,4-methylenedioxymethamphetamine, but not cocaine or methylphenidate, caused a METH-like reduction in DAT function. The rapid and reversible METH-induced diminution in DAT activity did not occur because of a change in membrane potential, as assessed in vitro and ex vivo by [(3)H]tetraphenylphosphonium accumulation. However, the METH-related decline in DAT function may be attributed to phosphorylation because NPC15437, a protein kinase C inhibitor, attenuated the METH-induced decline in DAT function. Similarities between previously reported effects ex vivo of a single METH injection on serotonin and norepinephrine transporter function and effects of direct METH application in vitro were also found. Together, these data demonstrate that the in vitro incubation model mimics the rapid and reversible effects observed after a single METH injection.

3,4-Methylenedioxyamphetamine↗
PubMed2003

Ornithine decarboxylase activity in in vivo and in vitro models of cerebral ischemia.

Ornithine decarboxylase (ODC) is considered the rate-limiting enzyme in polyamine biosynthesis, and an increase in putrescine after central nervous system (CNS) injury appears to be involved in neuronal death. Cerebral ischemia and reperfusion trigger an active series of metabolic events, which eventually lead to neuronal death. In the present study, ODC activity was evaluated following transient focal cerebral ischemia and reperfusion in rat. The middle cerebral artery (MCA) was occluded for 2 h in male rats with an intraluminal suture technique. Animals were sacrificed between 3 and 48 h of reperfusion following MCA occlusion, and ODC activity was assayed in cortex and striatum. ODC activity was also estimated in an in vitro ischemia model using primary rat cortical neuron cultures, at 6-24 h reoxygenation following 1 h oxygen-glucose deprivation (OGD). In cortex, following ischemia, ODC activity was increased at 3 h (P < .05), reached peak levels by 6-9 h (P < .001) and returned to sham levels by 48 h reperfusion. In striatum the ODC activity followed a similar time course, but returned to basal levels by 24 h. This suggests that ODC activity is upregulated in rat CNS following transient focal ischemia and its time course of activation is region specific. In vitro, ODC activity showed a significant rise only at 24 h reoxygenation following ischemic insult. The release of lactate dehydrogenase (LDH), an indicator for cell damage, was also significantly elevated after OGD. 0.25 mM alpha-difluoromethylornithine (DFMO) inhibited ischemia-induced ODC activity, whereas a 10-mM dose of DFMO appears to provide some neuroprotection by suppressing both ODC activity and LDH release in neuronal cultures, suggesting the involvement of polyamines in the development of neuronal cell death.

Animals↗
PubMed1984

Development of an in vitro model for determining the fate of chemicals applied to skin.

An in vitro apparatus was developed to determine the evaporation and percutaneous penetration of radiolabeled chemicals applied to pig skin. The dermal side of the skin was mounted on a penetration cell. Appearance of radioactivity in the fluid flowing past the dermal side of the skin indicated percutaneous penetration. An evaporation manifold, with replaceable vapor traps, was mounted on the stratum corneum side of the skin. Using the model, the influence of a number of factors (storage conditions, flow rate and composition of fluid in the penetration cell, and temperature and humidity of air flowing through the evaporation manifold) on the disposition of chemicals on the skin was determined. The percutaneous penetration and evaporation of N,N-diethyl-m-toluamide were determined on skin samples immediately after excision and after a freezing period of 1 to 6 weeks at -80 degrees C. Progressively greater percutaneous penetration values were associated with samples which had the greater storage times. Thereafter, only fresh skin was used. When the penetration cell flow was increased from 5 to 10 ml/hr of Tyrodes solution, or when porcine serum was substituted for Tyrodes solution as the fluid flowing through the penetration cell, no significant difference was found in total percutaneous penetration of several control compounds. However, total percutaneous penetration of N,N-diethyl-m-toluamide more than doubled when the air temperature was increased from 20 to 32 degrees C, whereas total evaporation decreased. Increasing the humidity of air flowing through the evaporation manifold enhanced the percutaneous penetration of polar organic compounds but had little effect of the percutaneous penetration of highly lipid soluble organic compounds. Using the model under standardized conditions, the percutaneous penetration of 10 control compounds (N,N-diethyl-m-toluamide, benzoic acid, caffeine, three steroids, and four insecticides) were found to correlate with the corresponding published values for man (r = 0.77, p = 0.05). The skin disposition of the nerve agent analog (diisopropylfluorophosphate, DFP) and simulant (diethyl malonate) was determined using the model. When applied to the skin at a dose of 0.1 mg/cm2, DFP and diethyl malonate were lost from the skin surface mainly by evaporation. Skin penetration was limited due to loss by evaporation.

Animals↗