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1.
J Neurosci ; 39(19): 3713-3727, 2019 05 08.
Article in English | MEDLINE | ID: mdl-30846614

ABSTRACT

The demands on a sensory system depend not only on the statistics of its inputs but also on the task. In olfactory navigation, for example, the task is to find the plume source; allocation of sensory resources may therefore be driven by aspects of the plume that are informative about source location, rather than concentration per se. Here we explore the implications of this idea for encoding odor concentration. To formalize the notion that sensory resources are limited, we considered coding strategies that partitioned the odor concentration range into a set of discriminable intervals. We developed a dynamic programming algorithm that, given the distribution of odor concentrations at several locations, determines the partitioning that conveys the most information about location. We applied this analysis to planar laser-induced fluorescence measurements of spatiotemporal odor fields with realistic advection speeds (5-20 cm/s), with or without a nearby boundary or obstacle. Across all environments, the optimal coding strategy allocated more resources (i.e., more and finer discriminable intervals) to the upper end of the concentration range than would be expected from histogram equalization, the optimal strategy if the goal were to reconstruct the plume, rather than to navigate. Finally, we show that ligand binding, as captured by the Hill equation, transforms odorant concentration into response levels in a way that approximates information maximization for navigation. This behavior occurs when the Hill dissociation constant is near the mean odor concentration, an adaptive set-point that has been observed in the olfactory system of flies.SIGNIFICANCE STATEMENT The first step of olfactory processing is receptor binding, and the resulting relationship between odorant concentration and the bound receptor fraction is a saturating one. While this Hill nonlinearity can be viewed as a distortion that is imposed by the biophysics of receptor binding, here we show that it also plays an important information-processing role in olfactory navigation. Specifically, by combining a novel dynamic-programming algorithm with physical measurements of turbulent plumes, we determine the optimal strategy for encoding odor concentration when the goal is to determine location. This strategy is distinct from histogram equalization, the strategy that maximizes information about plume concentration, and is closely approximated by the Hill nonlinearity when the binding constant is near the ambient mean.


Subject(s)
Algorithms , Nonlinear Dynamics , Odorants , Smell/physiology , Spatial Navigation/physiology , Acetone/administration & dosage , Animals , Smell/drug effects , Spatial Navigation/drug effects
2.
Biol Pharm Bull ; 39(5): 794-8, 2016.
Article in English | MEDLINE | ID: mdl-27150149

ABSTRACT

Benzylacetone has appetite-enhancing and locomotor-reducing effects. The effective doses for these two outcomes overlap, and the weight gain of mice exposed to benzylacetone is caused by both appetite-enhancement and a reduction in locomotor activity. The appetite-enhancing effects of trans-cinnamaldehyde and benzylacetone have been reported previously. In this study, these appetite-enhancing effects were seen in mice after short-term, high-dose exposure.


Subject(s)
Acetone/analogs & derivatives , Acrolein/analogs & derivatives , Appetite Stimulants/administration & dosage , Appetite/drug effects , Acetone/administration & dosage , Acetone/pharmacology , Acrolein/administration & dosage , Acrolein/pharmacology , Administration, Inhalation , Animals , Appetite Stimulants/pharmacology , Body Weight/drug effects , Dose-Response Relationship, Drug , Male , Mice , Motor Activity/drug effects
3.
Toxicol Appl Pharmacol ; 281(1): 109-17, 2014 11 15.
Article in English | MEDLINE | ID: mdl-25283951

ABSTRACT

The overall goal of this research was to further develop and improve an existing skin diffusion model by experimentally confirming the predicted absorption rates of topically-applied volatile organic compounds (VOCs) based on their physicochemical properties, the skin surface temperature, and the wind velocity. In vitro human skin permeation of two hydrophilic solvents (acetone and ethanol) and two lipophilic solvents (benzene and 1,2-dichloroethane) was studied in Franz cells placed in a fume hood. Four doses of each (14)C-radiolabed compound were tested - 5, 10, 20, and 40ĀµLcm(-2), corresponding to specific doses ranging in mass from 5.0 to 63mgcm(-2). The maximum percentage of radiolabel absorbed into the receptor solutions for all test conditions was 0.3%. Although the absolute absorption of each solvent increased with dose, percentage absorption decreased. This decrease was consistent with the concept of a stratum corneum deposition region, which traps small amounts of solvent in the upper skin layers, decreasing the evaporation rate. The diffusion model satisfactorily described the cumulative absorption of ethanol; however, values for the other VOCs were underpredicted in a manner related to their ability to disrupt or solubilize skin lipids. In order to more closely describe the permeation data, significant increases in the stratum corneum/water partition coefficients, Ksc, and modest changes to the diffusion coefficients, Dsc, were required. The analysis provided strong evidence for both skin swelling and barrier disruption by VOCs, even by the minute amounts absorbed under these in vitro test conditions.


Subject(s)
Acetone/metabolism , Benzene/metabolism , Ethanol/metabolism , Ethylene Dichlorides/metabolism , Skin Absorption/physiology , Acetone/administration & dosage , Benzene/administration & dosage , Diffusion Chambers, Culture , Dose-Response Relationship, Drug , Ethanol/administration & dosage , Ethylene Dichlorides/administration & dosage , Forecasting , Humans , Skin Absorption/drug effects
4.
ScientificWorldJournal ; 2013: 956206, 2013.
Article in English | MEDLINE | ID: mdl-23576913

ABSTRACT

Interesting antimicrobial data from the stem bark of Sclerocarya birrea, which support its use in traditional medicine for the treatment of many diseases, have been delineated. The current study was aimed to further study some pharmacological and toxicological properties of the plant to scientifically justify its use. Anticancer activity of water and acetone extracts of S. birrea was evaluated on three different cell lines, HT-29, HeLa, and MCF-7 using the cell titre blue viability assay in 96-well plates. Apoptosis was evaluated using the acridine orange and propidium iodide staining method, while morphological structure of treated cells was examined using SEM. The acetone extract exhibited remarkable antiproliferative activities on MCF-7 cell lines at dose- and time-dependent manners (24 h and 48 h of incubation). The extract also exerted apoptotic programmed cell death in MCF-7 cells with significant effect on the DNA. Morphological examination also displayed apoptotic characteristics in the treated cells, including clumping, condensation, and culminating to budding of the cells to produce membrane-bound fragmentation, as well as formation of apoptotic bodies. The acetone extract of S. birrea possesses antiproliferative and apoptotic potential against MCF-7-treated cells and could be further exploited as a potential lead in anticancer therapy.


Subject(s)
Acetone/administration & dosage , Anacardiaceae/chemistry , Apoptosis/drug effects , Cell Proliferation/drug effects , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Plant Extracts/administration & dosage , Acetone/chemistry , Feasibility Studies , HT29 Cells , HeLa Cells , Humans , MCF-7 Cells , Neoplasms, Experimental/physiopathology , Treatment Outcome
5.
Med J Malaysia ; 67(2): 212-3, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22822647

ABSTRACT

Superglue in the ear as a foreign body is an uncommon presentation. We report the case of a lady who accidentally instilled superglue directly onto her tympanic membrane and presented five days later. We successfully removed the glue with acetone and managed to preserve the integrity of the tympanic membrane.


Subject(s)
Acetone/administration & dosage , Cyanoacrylates , Ear Canal , Foreign Bodies/therapy , Solvents/administration & dosage , Adult , Female , Humans
6.
Aviakosm Ekolog Med ; 46(2): 21-8, 2012.
Article in Russian | MEDLINE | ID: mdl-22953536

ABSTRACT

The paper presents the results of an investigation with mice subjected to isolated and successive exposure to a blend of chemical agents (acetone, ethanol, acetaldehyde) at MPC levels defined for piloted space vehicles followed by fractionated gamma-irradiation by daily 1 cGy (30 cGy total). The selected chemicals are the primary contributors to total air contamination and present in the prioritized list of compounds to be monitored to ensure air quality on piloted space vehicles. Radiation levels were determined with allowance for mice radiosensitivity to simulate the actual absorbed dose accumulated by crewmembers of orbital mission of up to a year in duration (10 cGy). Based on the findings in the hematopoietic system and erythrocyte biochemistry, energy exchange and redox parameters, pre-irradiation exposure to chemical agents within the MPC limits accentuated radiosensitivity gravely and, therefore, made mouse organism less tolerant to radiation. It was shown that adaptation of the hematopoietic system calls forth activation and significant straining of regulatory mechanisms equally in opposing to a single factor or combination of chemical and radiation exposure. The marked tension of these mechanisms persisted till day 30 of recovery.


Subject(s)
Acetaldehyde/toxicity , Acetone/toxicity , Erythrocytes/drug effects , Ethanol/toxicity , Gamma Rays/adverse effects , Acetaldehyde/administration & dosage , Acetone/administration & dosage , Air Pollutants/toxicity , Animals , Environmental Monitoring/methods , Erythrocytes/radiation effects , Ethanol/administration & dosage , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Oxidation-Reduction , Space Flight , Time Factors
7.
Skin Res Technol ; 17(1): 51-5, 2011 Feb.
Article in English | MEDLINE | ID: mdl-20923460

ABSTRACT

BACKGROUND/PURPOSE: Skin hydration is essential for skin health. Moisturized skin is generally regarded as healthy and healthy looking. It is thus speculated that there may be appearance benefits of skin moisturization. This means that there are corresponding changes in the optical properties when skin is moisturized. METHODS: The appearance of the skin is the result of light reflection, scattering and absorption at various skin layers of the stratum corneum, epidermis, dermis and beyond. The appearance benefits of skin moisturization are likely primarily due to the changes in the optical properties of the stratum corneum. We hypothesize that the major optical effect of skin moisturization is the decrease of light scattering at the skin surface, i.e., the stratum corneum. This decrease of surface scattering corresponds to an increase of light penetration into the deeper layers of the skin. An experiment was conducted to measure the corresponding change in skin spectral reflectance, the skin scattering coefficient and skin translucency with a change in skin hydration. In the experiment, skin hydration was decreased with the topical application of acetone and alcohol and increased with the topical application of known moisturizers and occlusives such as PJ. RESULT AND CONCLUSION: It was found that both the skin spectral reflectance and the skin scattering coefficient increased when the skin was dehydrated and decreased when the skin was hydrated. Skin translucency increased as the skin became moisturized. The results agree with the hypothesis that there is less light scattering at the skin surface and more light penetration into the deeper skin layers when the skin is moisturized. As a result, the skin appears darker, more pinkish and more translucent.


Subject(s)
Beauty , Emollients/administration & dosage , Models, Biological , Optics and Photonics , Skin/drug effects , Acetone/administration & dosage , Alcohols/administration & dosage , Computer Simulation , Dehydration/chemically induced , Dehydration/pathology , Emollients/pharmacokinetics , Humans , Scattering, Radiation , Skin/metabolism , Skin Absorption/drug effects , Skin Care/methods , Water/metabolism
8.
Neurourol Urodyn ; 29(3): 501-5, 2010 Mar.
Article in English | MEDLINE | ID: mdl-19618450

ABSTRACT

AIMS: Nociceptive behavior and its relationship with bladder dysfunction were investigated in two cystitis models, which were induced by intraperitoneal (i.p.) injection of cyclophosphamide (CYP) or intravesical instillation of acetone, using freely moving, non-catheterized conscious rats. METHODS: Female Sprague-Dawley rats were used. Cystitis was induced by i.p. injection of CYP (100 and 200 mg/kg) or intravesical instillation of acetone (10%, 30%, and 50%) via a polyethylene catheter temporarily inserted into the bladder through the urethra. Then the incidence of nociceptive behavior (immobility with decreased breathing rates) was scored. Voided urine was collected simultaneously and continuously to measure bladder capacity. The plasma extravasation in the bladder was quantified by an Evans blue (EB) dye leakage technique. RESULTS: CYP (100 mg/kg, i.p.) induced nociceptive behavior without affecting bladder capacity or EB concentration in the bladder. A higher dose of CYP (200 mg/kg, i.p.) decreased bladder capacity and increased EB levels as well as nociceptive behavior. In contrast, intravesical instillation of acetone (30%) decreased bladder capacity and increased EB levels, but evoked nociceptive behavior less frequently compared with CYP-treated animals. In capsaicin-pretreated rats, nociceptive behavior induced by CYP or acetone was reduced; however, the overall effects of CYP or acetone on bladder capacity and bladder EB levels were unaffected. CONCLUSIONS: These results suggest that there is a difference in the induction process of nociceptive behavior and small bladder capacity after two different types of bladder irritation, and that C-fiber sensitization is more directly involved in pain sensation than reduced bladder capacity.


Subject(s)
Cystitis/physiopathology , Disease Models, Animal , Nociceptors/physiology , Urination , Acetone/administration & dosage , Administration, Intravesical , Animals , Cyclophosphamide/administration & dosage , Cystitis/chemically induced , Female , Injections, Intraperitoneal , Rats , Rats, Sprague-Dawley
9.
J Pharm Biomed Anal ; 172: 94-102, 2019 Aug 05.
Article in English | MEDLINE | ID: mdl-31029804

ABSTRACT

The molecular organization of stratum corneum (SC) lipids is important for maintaining the barrier properties of the skin. The majority of intercellular lipids are in a solid state at normal humidity (RH) and ambient temperature; however, several studies indicate that a small fraction exist in a fluid state. In a previous work, a preferential solubilization of fluid skin lipids by acetone (Ac) was envisaged. A different change in the skin permeability related to the different lipid structures of the extracted lipids was suggested. To increase the knowledge of the specific role of different lipids on skin structure, a selective lipid modification is proposed. This study assess the effect of Ac on skin barrier lipids in-depth. Synchrotron based Fourier-transform infrared microspectroscopy (FTIR), which is used to study SC lipid organization, revealed a more ordered lipid organization after Ac treatment. In vitro experiments using Franz cells, which were selected to follow the SC barrier function capability, demonstrated that Ac-treated skin retained caffeine and ibuprofen on the SC with very low permeation of both compounds into the deeper skin layers. In vitro transepidermal water loss (TEWL) measurements revealed the ability of Ac to induce a less water permeated skin. Although an important lipid fraction has been removed, Ac skin treatment brings to a skin where the remaining lipids promote an improved barrier function. These results could lead to a better understanding of the role of different lipid components in skin structure.


Subject(s)
Acetone/administration & dosage , Epidermis/metabolism , Solvents/administration & dosage , Water Loss, Insensible/drug effects , Administration, Cutaneous , Animals , Caffeine/administration & dosage , Caffeine/pharmacokinetics , Epidermis/drug effects , Ibuprofen/administration & dosage , Ibuprofen/pharmacokinetics , Lipid Metabolism/drug effects , Lipids/analysis , Lipids/chemistry , Models, Animal , Permeability/drug effects , Spectroscopy, Fourier Transform Infrared , Sus scrofa
10.
Pharmacol Biochem Behav ; 89(1): 101-5, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18096214

ABSTRACT

INTRODUCTION: Acetone is an ubiquitous ingredient in many household products (e.g., glue solvents, air fresheners, adhesives, nail polish, and paint) that is putatively abused; however, there is little empirical evidence to suggest that acetone alone has any abuse liability. Therefore, we systematically investigated the conditioned response to inhaled acetone in a place conditioning apparatus. METHOD: Three groups of male, Sprague-Dawley rats were exposed to acetone concentrations of 5000, 10,000 or 20,000 ppm for 1 h in a conditioned place preference apparatus alternating with air for 6 pairing sessions. A place preference test ensued in an acetone-free environment. To test the preference of acetone as a function of pairings sessions, the 10,000 ppm group received an additional 6 pairings and an additional group received 3 pairings. The control group received air in both compartments. Locomotor activity was recorded by infrared photocells during each pairing session. RESULTS: We noted a dose response relationship to acetone at levels 5000-20,000 ppm. However, there was no correlation of place preference as a function of pairing sessions at the 10,000 ppm level. Locomotor activity was markedly decreased in animals on acetone-paired days as compared to air-paired days. CONCLUSION: The acetone concentrations we tested for these experiments produced a markedly decreased locomotor activity profile that resemble CNS depressants. Furthermore, a dose response relationship was observed at these pharmacologically active concentrations, however, animals did not exhibit a positive place preference.


Subject(s)
Acetone/pharmacology , Conditioning, Operant/drug effects , Solvents/pharmacology , Acetone/administration & dosage , Administration, Inhalation , Animals , Area Under Curve , Dose-Response Relationship, Drug , Male , Motor Activity/drug effects , Rats , Rats, Sprague-Dawley , Solvents/administration & dosage
11.
J Commun Dis ; 40(4): 255-61, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19579717

ABSTRACT

Acetone extracts of leaves and seeds from the Tribulus terrestris (Zygophyllaceae) were tested against mature and immature different mosquito vectors under laboratory condition. The extract showed strong larvicidal, properties 100 per cent mortality in the 3rd-instar larvae was observed in the bioassays with An. culicifacies Giles species A, An. stephensi Liston, Culex quinquefasciatus Say and Aedes aegypti Linn, against 200 ppm of the leaf acetone extract and 100 ppm seed acetone extract. The LC50 values of leaf acetone extract estimated for 3rd-instars An. culicifacies species A, An. stephensi, Cx. quinquefasciatus and Ae. aegypti after 24 hour of exposure were 117, 124, 168 and 185 ppm respectively. The LC50 values of seed acetone extract estimated for 3rd-instars An. culicifacies species A, An. stephensi, Cx. quinquefasciatus and Ae. aegypti after 24 hour of exposure were 100, 72, 91 and 91 ppm respectively. It is confirmed from the LC50 values that the seed acetone extract of T. terrestris is more effective compared to leaf extracts. A significant (P<0.004) higher concentration of acetone extract leaf was required to kill equal number of larvae i.e. against acetone extract of seed. The seed acetone extract showed strong repellent activity against adults mosquitoes. Per cent protection obtained against Anopheles culicifacies species A 100% repellency in 1 h, 6 h; Anopheles stephensi 100% repellency in 0 h, 4 h, 6 h; and Culex quinquefasciatus 100% repellency in 0 h, 2 h, 4 h, at 10% concentration respectively. Against Deet- 2.5% An. culicifacies Giles species A has shown 100% repellency in 1 h, 2 h, 6 h, An. stephensi Liston 99% repellency in 4 h, and Culex quinquefasciatus Say has shown 100% repellency in 1 h, 2 h.


Subject(s)
Acetone/administration & dosage , Culicidae/drug effects , Insect Vectors/drug effects , Malaria/prevention & control , Plant Extracts/administration & dosage , Tribulus/chemistry , Acetone/chemistry , Animals , Dose-Response Relationship, Drug , Humans , Insect Repellents/administration & dosage , Insecticides/administration & dosage , Larva/drug effects , Mosquito Control/methods , Plant Leaves/chemistry , Seeds/chemistry
12.
Curr Drug Deliv ; 15(7): 987-997, 2018.
Article in English | MEDLINE | ID: mdl-29268685

ABSTRACT

BACKGROUND: Biodegradable nanoparticles with diameters between 100 nm and 500 nm are of great interest in the contexts of targeted delivery. OBJECTIVE: The present work provides a review concerning the effect of binary organic solvents together with emulsifier on particle size as well as the influence of particle size on the in vitro drug release and uptake behavior. METHODS: The polymeric lipid nanoparticles (PLNs) with different particle sizes were prepared by using binary solvent dispersion method. Various formulation parameters such as binary organic solvent composition and emulsifier types were evaluated on the basis of their effects on particle size and size distribution. PLNs had a strong dependency on the surface tension, intrinsic viscosity and volatilization rate of binary organic solvents and the hydrophilicity/hydrophobicity of emulsifiers. Acetone-methanol system together with pluronic F68 as emulsifier was proved to obtain the smallest particle size. Then the PLNs with different particle sizes were used to investigate how particle size at nanoscale affects interacted with tumor cells. RESULTS: As particle size got smaller, cellular uptake increased in tumor cells and PLNs with particle size of ~120 nm had the highest cellular uptake and fastest release rate. The paclitaxel (PTX)-loaded PLNs showed a size-dependent inhibition of tumor cell growth, which was commonly influenced by cellular uptake and PTX release. CONCLUSION: The PLNs would provide a useful means to further elucidate roles of particle size on delivery system of hydrophobic drugs.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Lactic Acid/administration & dosage , Nanoparticles/administration & dosage , Paclitaxel/administration & dosage , Polyglycolic Acid/administration & dosage , Acetone/administration & dosage , Acetone/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Cell Survival/drug effects , Drug Liberation , Emulsifying Agents/administration & dosage , Emulsifying Agents/chemistry , Humans , Lactic Acid/chemistry , Lipids/administration & dosage , Lipids/chemistry , MCF-7 Cells , Methanol/administration & dosage , Methanol/chemistry , Microscopy, Electron, Transmission , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Paclitaxel/chemistry , Particle Size , Poloxamer/administration & dosage , Poloxamer/chemistry , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Solvents/administration & dosage , Solvents/chemistry
13.
Toxicology ; 234(1-2): 59-72, 2007 May 05.
Article in English | MEDLINE | ID: mdl-17382449

ABSTRACT

Chlordecone (CD) and mirex (M) differ by a single carbonyl group in CD in place of two chlorines in M. Although both compounds are lipophilic, their tissue distributions differ markedly: CD concentrations are highest in liver; M concentrations are highest in fat. We used tissue time course data in rats from our laboratory for CD and M and literature data from monkeys to develop PBPK models to study differences in liver and fat partitioning. The PK model for M had partitioning in tissue without specific hepatic binding. The CD model had partitioning similar to M, and also included liver binding: the maximal binding (B(max)) and binding affinity constant (Kd) required to describe the rat data were 370 nmol/g liver and 100 nM, respectively. To see if other ketones with electron withdrawing constituents at the alpha carbon were also preferentially distributed to liver, we developed a PBPK description for tissue distribution of hexafluoroacetone (HFA). Compared to acetone, HFA is known to be preferentially sequestered in liver and more slowly excreted unchanged from the body. Acetone is more equally distributed to tissues. HFA distribution was evaluated with a PBPK model that included hepatic binding. B(max) and Kd were 1.58 micromol/g liver and 301 microM. In summary, liver sequestration of CD and HFA most likely represents relatively high-affinity but reversible binding of activated carbonyls in these compounds (activated by the presence of electron withdrawing substituents on the alpha-carbons) with glutathione and glutathione transferases, that are present at much higher concentrations in liver than in other tissues. Strong, but reversible hemithioketal formation with active sulfhydryls may also be associated with the toxic responses to CD and HFA.


Subject(s)
Acetone/analogs & derivatives , Chlordecone/pharmacokinetics , Fluorocarbons/pharmacokinetics , Liver/metabolism , Models, Biological , Acetone/administration & dosage , Acetone/chemistry , Acetone/pharmacokinetics , Administration, Oral , Algorithms , Animals , Chlordecone/administration & dosage , Chlordecone/chemistry , Drug Evaluation, Preclinical , Female , Fluorocarbons/administration & dosage , Fluorocarbons/chemistry , Hydrophobic and Hydrophilic Interactions , Injections, Intravenous , Insecticides/administration & dosage , Insecticides/chemistry , Insecticides/pharmacokinetics , Lipid Metabolism/drug effects , Macaca mulatta , Male , Mirex/administration & dosage , Mirex/chemistry , Mirex/pharmacokinetics , Molecular Conformation , Rats , Rats, Sprague-Dawley , Tissue Distribution
14.
Aviakosm Ekolog Med ; 40(3): 50-4, 2006.
Article in Russian | MEDLINE | ID: mdl-17193970

ABSTRACT

Chronic combined exposure to low concentrations of chemical substances (equal to the maximal admissible limits for space vehicles) is fraught with an increase in chromosomal aberrations in bone marrow cells as compared with the spontaneous chromosome aberration rate. In addition to the cytogenetic evidence, there were also statistical phase shifts in metabolic parameters of erythrocytes (enzymes involved in the basal metabolism and a number of metabolites), leukocyte count in peripheral blood, and the total quantity of karyocytes in the bone marrow. No significant changes were found in organs of the immune and reproductive systems.


Subject(s)
Acetone/adverse effects , Air Pollutants/adverse effects , Ammonia/adverse effects , Bone Marrow Cells/drug effects , Chromosome Aberrations/chemically induced , Environmental Exposure/adverse effects , Ethanol/adverse effects , Acetone/administration & dosage , Ammonia/administration & dosage , Animals , Bone Marrow Cells/pathology , Dose-Response Relationship, Drug , Drug Combinations , Environment, Controlled , Ethanol/administration & dosage , Follow-Up Studies , Male , Maximum Tolerated Dose , Mice , Mice, Inbred C57BL , Mice, Inbred CBA , Rats , Rats, Wistar , Spacecraft
15.
Nucl Med Biol ; 32(2): 201-8, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15721766

ABSTRACT

The phenomenon of inhalant abuse is a growing problem in the US and many countries around the world. Yet, relatively little is known about the pharmacokinetic properties of inhalants that underlie their abuse potential. While the synthesis of 11C-labeled toluene, acetone and butane has been proposed in the literature, none of these compounds has been developed as radiotracers for PET studies. In the present report we extend our previous studies with [11C]toluene to include [11C]acetone and [11C]butane with the goal of comparing the pharmacokinetic profiles of these three volatile abused substances. Both [11C]toluene and [11C]acetone were administered intravenously and [11C]butane was administered via inhalation to anesthesized baboons. Rapid and efficient uptake of radiolabeled toluene and acetone into the brain was followed by fast clearance in the case of toluene and slower kinetics in the case of acetone. [11C]Butane was detected in the blood and brain following inhalation, but the levels of radioactivity in both tissues dropped to half of the maximal values over the period of less than a minute. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled acetone and butane in nonhuman primates. These data provide insight into the pharmacokinetic features possibly associated with the abuse liability of toluene, acetone and butane.


Subject(s)
Acetone/pharmacokinetics , Brain/diagnostic imaging , Brain/metabolism , Butanes/pharmacokinetics , Substance Abuse Detection/methods , Acetone/administration & dosage , Acetone/chemical synthesis , Administration, Inhalation , Animals , Butanes/administration & dosage , Butanes/chemical synthesis , Carbon Radioisotopes/pharmacokinetics , Feasibility Studies , Injections, Intravenous , Isotope Labeling/methods , Metabolic Clearance Rate , Papio , Radionuclide Imaging , Radiopharmaceuticals/administration & dosage , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution
16.
J Leukoc Biol ; 68(4): 471-8, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11037967

ABSTRACT

Dermal cells expressing a macrophage C-type lectin (mMGL) were previously suggested to migrate to regional lymph nodes during the sensitization phase of delayed-type hypersensitivity (DTH). The migration seemed to be induced by the solvent used to dissolve the antigen, and the DTH response was significantly enhanced by the migration. In this study, immunohistochemical analysis of skin after epicutaneous application of one of such solvents, a mixture of acetone and dibutylphthalate (AD), revealed a transient decrease in the number of mMGL-positive cells in the dermis. A similar decrease in this cell population was also observed in an ex vivo assay with skin explants excised from AD-treated sites. Conditioned medium from organ culture of AD-treated skin induced a similar decrease of mMGL-positive cells in untreated dermis, indicating the involvement of soluble factors. mMGL-positive cells seemed to represent a unique subpopulation of F4/80-positive dermal cells.


Subject(s)
Carrier Proteins/metabolism , Dermatitis, Allergic Contact/pathology , Dermis/pathology , Lectins, C-Type , Lectins/metabolism , Macrophages/drug effects , Membrane Proteins , Acetone/administration & dosage , Acetone/pharmacology , Administration, Cutaneous , Animals , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/therapeutic use , Antigens, Differentiation/analysis , Asialoglycoproteins , Biological Factors/chemistry , Biological Factors/isolation & purification , Biological Factors/physiology , Carrier Proteins/antagonists & inhibitors , Carrier Proteins/immunology , Cell Movement/drug effects , Cell Size , Culture Media, Conditioned/pharmacology , Dermatitis, Allergic Contact/immunology , Dermatitis, Allergic Contact/therapy , Dermis/drug effects , Dermis/metabolism , Dibutyl Phthalate/administration & dosage , Dibutyl Phthalate/pharmacology , Female , Immunization, Passive , Interleukin-1/antagonists & inhibitors , Interleukin-1/immunology , Lectins/antagonists & inhibitors , Lectins/immunology , Macrophages/immunology , Macrophages/pathology , Mice , Mice, Inbred ICR , Molecular Weight , Organ Culture Techniques , Solvents/administration & dosage , Solvents/pharmacology , Specific Pathogen-Free Organisms
17.
Am J Med ; 83(5): 833-40, 1987 Nov.
Article in English | MEDLINE | ID: mdl-3118711

ABSTRACT

Defatting the skin with acetone or ether is widely used in the regimen for disinfection of insertion sites of central venous catheters in total parenteral nutrition. The fatty acids secreted by normal skin play an important role in regulation of the cutaneous microbial ecosystem, and it can be questioned whether application of a solvent might paradoxically promote colonization by pathogenic microorganisms. The clinical value of defatting catheter insertion sites was prospectively studied in a controlled, randomized trial: 100 subclavian catheters inserted for total parenteral nutrition were given identical site care except that with one half of the catheters, the site was defatted with acetone prior to catheter insertion and as part of the every-other-day site care regimen. Cutaneous colonization was found in only 130 (24.5 percent) of 531 site cultures in both groups, but was strongly predictive of concordant colonization of the catheter (relative risk, 22.1, p less than 0.001) and catheter-related septicemia (all four cases). No significant differences were observed between the two groups in cutaneous colonization of sites (22.7 percent and 27.0 percent), in colonization of catheters on removal (four catheters [8 percent] in each group) or in catheter-related septicemia (two catheters [4 percent] in each group). However, pain or inflammation of the insertion site was twice as frequent in the acetone group (80 percent versus 35 percent, p less than 0.001). Defatting with acetone as part of the regimen for cutaneous disinfection does not improve microbial removal or reduce the incidence of catheter-related infection, but increases cutaneous inflammation and patient discomfort.


Subject(s)
Acetone/administration & dosage , Bacterial Infections/prevention & control , Catheterization, Central Venous/adverse effects , Disinfection/methods , Parenteral Nutrition, Total , Skin/drug effects , Sterilization/methods , Adult , Clinical Trials as Topic , Female , Humans , Male , Prospective Studies , Random Allocation , Risk Factors , Sepsis/prevention & control , Skin/microbiology
18.
Toxicology ; 67(3): 249-65, 1991 May.
Article in English | MEDLINE | ID: mdl-2048129

ABSTRACT

Rats were exposed to 0, 0.1, 1, and 12 ppm of hexafluoroacetone (HFA) for 6 h/day, 5 days/week for 90 days. The exposed rats were killed after 30 or 90 days exposure, and 28 or 84 days post-exposure (PE). There were no exposure-related pathological lesions in the rats exposed to 0.1 or 1.0 HFA for 90 days. After 30 days exposure to 12 ppm HFA, rats showed lower body weight gain, testicular atrophy, and oligospermia or aspermia in the epididymal tubules. At 30 days exposure, the atrophic testes had marked depletion of round spermatids in spermatogenic stages I-VIII and elongated spermatids in spermatogenic stages IX-XIV, but mature spermatids appeared only slightly decreased. Numerous spermatocytes in meiotic division in spermatogenic stage XIV were necrotic. At 90 days exposure, the testes showed severe atrophy with almost all seminiferous tubules affected and both immature and mature spermatids had disappeared from the seminiferous tubules. The epididymal tubules were devoid of spermatozoa. After 28 days PE, regeneration of atrophic testes was evident but varied markedly among the exposed rats. The number of seminiferous tubules producing elongated and mature spermatids was significantly lower than that of normal testes. Many seminiferous tubules had not regained normal spermatogenesis and the epididymal tubules showed marked oligospermia. After 84 days PE, normal spermatogenesis was still only partially restored to the atrophic testes, with many of the regenerating tubules still devoid of normal spermatogenesis.


Subject(s)
Acetone/analogs & derivatives , Fluorocarbons/toxicity , Testis/drug effects , Acetone/administration & dosage , Acetone/toxicity , Administration, Inhalation , Animals , Atrophy , Body Weight/drug effects , Epididymis/drug effects , Female , Fluorocarbons/administration & dosage , Male , Oligospermia/chemically induced , Organ Size/drug effects , Rats , Sertoli Cells/drug effects , Spermatids/drug effects , Spermatogenesis/drug effects
19.
Toxicol Lett ; 56(1-2): 187-96, 1991 Apr.
Article in English | MEDLINE | ID: mdl-2017777

ABSTRACT

Deposition of inspired acetone vapor in the surgically isolated upper respiratory tract (URT) of the anesthetized B6C3F1 mouse was measured under unidirectional constant velocity flow conditions for comparison with our previous studies on the rat, hamster and guinea-pig. Acetone metabolism in mouse nasal mucosal homogenates was examined in vitro. Acetone was metabolized by nasal homogenates via an NADPH-dependent pathway with a Vmax of 12 micrograms/min/whole nose and an apparent Km of 72 micrograms/ml. The enzyme responsible was not identified; however, metabolism was inhibited by pyrazole but not inhibited by metyrapone or incubation under nitrogen. URT deposition efficiency was measured at flow rates of 21, 33 or 70 ml/min and averaged 25, 20 and 14%, respectively; the efficiencies at each flow rate were significantly different (P less than 0.01). Deposition was measured at inspired concentrations ranging from 1,500-20,000 micrograms/liter. Deposition efficiencies were similar at all concentrations; the lack of saturation suggests this vapor was not metabolized when inspired. Kinetic analysis of the deposition data revealed that metabolism rates of inspired acetone were only a small fraction of that measured in vitro, suggesting that in vitro data could not be directly extrapolated to the in vivo setting. Deposition efficiency of acetone in the URT of the mouse was similar to that previously observed in the URT of the F344 rat, but was less efficient than that in the Sprague-Dawley rat and more efficient than that in the hamster or guinea-pig.


Subject(s)
Acetone/pharmacokinetics , Nasal Cavity/metabolism , Nasal Mucosa/metabolism , Acetone/administration & dosage , Acetone/blood , Acetone/metabolism , Administration, Inhalation , Animals , Dose-Response Relationship, Drug , Kinetics , Male , Mice , Mice, Inbred Strains , Nasal Cavity/physiology , Perfusion , Rats , Rats, Inbred F344 , Rats, Inbred Strains , Respiration/physiology
20.
Toxicol Lett ; 57(1): 47-54, 1991 Jun.
Article in English | MEDLINE | ID: mdl-2048161

ABSTRACT

Acetone potentiation of liver injury is greater when corn oil is given with acetone 18 h prior to a challenge with CCl4. This study aimed to further characterize the effects of the vehicle used to administer acetone on the severity of acetone-potentiated CCl4-induced liver injury. The more severe acetone-potentiated liver injury observed when corn oil was the vehicle does not seem to be due to greater liver acetone concentrations. When corn oil was used as the vehicle to administer acetone, liver and blood CCl4 concentrations were not significantly different from those where water was the vehicle. Therefore the relationship between blood or liver acetone concentration and plasma ALT activity for orally-administered acetone was modified by corn oil. Liver triglyceride concentration measured 18 h after a gavage of corn oil was significantly higher than that for the water-treated group. A direct effect of corn oil on liver, in particular a promotion of the propagation phase in the lipid peroxidation process induced by CCl4, is proposed to explain the increase in acetone-potentiated CCl4-induced liver injury.


Subject(s)
Acetone/pharmacology , Carbon Tetrachloride/toxicity , Liver/drug effects , Acetone/administration & dosage , Acetone/pharmacokinetics , Administration, Inhalation , Administration, Oral , Alanine Transaminase/metabolism , Animals , Corn Oil/administration & dosage , Corn Oil/pharmacology , Drug Synergism , Liver/metabolism , Liver/pathology , Male , Rats , Rats, Inbred Strains , Triglycerides/metabolism
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