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1.
Part Fibre Toxicol ; 12: 18, 2015 Jun 27.
Article in English | MEDLINE | ID: mdl-26116549

ABSTRACT

BACKGROUND: The lung epithelial tissue barrier represents the main portal for entry of inhaled nanoparticles (NPs) into the systemic circulation. Thus great efforts are currently being made to determine adverse health effects associated with inhalation of NPs. However, to date very little is known about factors that determine the pulmonary translocation of NPs and their subsequent distribution to secondary organs. METHODS: A novel two-step approach to assess the biokinetics of inhaled NPs is presented. In a first step, alveolar epithelial cellular monolayers (CMLs) at the air-liquid interface (ALI) were exposed to aerosolized NPs to determine their translocation kinetics across the epithelial tissue barrier. Then, in a second step, the distribution to secondary organs was predicted with a physiologically based pharmacokinetic (PBPK) model. Monodisperse, spherical, well-characterized, negatively charged gold nanoparticles (AuNP) were used as model NPs. Furthermore, to obtain a comprehensive picture of the translocation kinetics in different species, human (A549) and mouse (MLE-12) alveolar epithelial CMLs were exposed to ionic gold and to various doses (i.e., 25, 50, 100, 150, 200 ng/cm(2)) and sizes (i.e., 2, 7, 18, 46, 80 nm) of AuNP, and incubated post-exposure for different time periods (i.e., 0, 2, 8, 24, 48, 72 h). RESULTS: The translocation kinetics of the AuNP across A549 and MLE-12 CMLs was similar. The translocated fraction was (1) inversely proportional to the particle size, and (2) independent of the applied dose (up to 100 ng/cm(2)). Furthermore, supplementing the A549 CML with two immune cells, i.e., macrophages and dendritic cells, did not significantly change the amount of translocated AuNP. Comparison of the measured translocation kinetics and modeled biodistribution with in vivo data from literature showed that the combination of in vitro and in silico methods can accurately predict the in vivo biokinetics of inhaled/instilled AuNP. CONCLUSION: Our approach to combine in vitro and in silico methods for assessing the pulmonary translocation and biodistribution of NPs has the potential to replace short-term animal studies which aim to assess the pulmonary absorption and biodistribution of NPs, and to serve as a screening tool to identify NPs of special concern.


Subject(s)
Computer Simulation , Epithelial Cells/metabolism , Gold Compounds/pharmacokinetics , Metal Nanoparticles , Models, Biological , Respiratory Mucosa/metabolism , Administration, Inhalation , Aerosols , Animals , Biological Transport , Cell Line, Tumor , Gold Compounds/administration & dosage , Gold Compounds/blood , Humans , Mice , Particle Size , Tissue Distribution
2.
Contact Dermatitis ; 62(4): 193-200, 2010 Apr.
Article in English | MEDLINE | ID: mdl-20433442

ABSTRACT

The high frequency of contact allergy to gold in patients with dermatitis was established after exhaustive skin testing, determining the right test agent, the best concentration, and repeated test readings. Metallic gold in contact with skin is slowly ionized, permitting absorption and haptenisation. Contact allergy to gold is statistically correlated to the presence of dental gold. But in many case reports it has also been attributed to wearing gold jewellery, albeit not statistically demonstrated. Epicutaneous testing with gold salts increases the blood gold level, and by intramuscular injection systemic contact dermatitis is provoked in an allergic individual. In coronary heart disease, gold-coated intravascular stents have been shown to be correlated to contact allergy and even to an increased risk of restenosis. Gold is far from inert.


Subject(s)
Dermatitis, Allergic Contact/etiology , Gold/adverse effects , Dental Prosthesis , Dermatitis, Allergic Contact/blood , Dermatitis, Allergic Contact/immunology , Gold/blood , Gold/immunology , Gold Compounds/adverse effects , Gold Compounds/blood , Gold Compounds/immunology , Humans , Jewelry , Patch Tests , Skin Absorption , Stents
3.
Acta Crystallogr C ; 66(Pt 1): m4-8, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20048413

ABSTRACT

The structure of the hydrated gold(III) tetrachloride salt of L-ecgonine {hydronium tetrakis[(1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8-azoniabicyclo[3.2.1]octane-2-carboxylate pentakis[tetrachloridoaurate(III)] hexahydrate}, (C(9)H(16)NO(3))(4)(H(3)O)[AuCl(4)](5).6H(2)O, demonstrates an unprecedented stoichiometric relationship between the cations and anions in the unit cell. The previous tropane alkaloid structures, including the related hydrochloride salts, all have a cation-anion ratio of 1:1, as does the anhydrous salt described here, namely (1R,2R,3S,5S,8S)-3-hydroxy-8-methyl-8-azoniabicyclo[3.2.1]octane-2-carboxylate tetrachloridoaurate(III), (C(9)H(16)NO(3))[AuCl(4)]. The hydrated salt, however, consists of four monopositive N-protonated units of the alkaloid and five [AuCl(4)](-) counter-ions, plus seven solvent water molecules. The H atom required for change balance has been assigned to a water molecule. In addition, the hydrate has a novel arrangement, with all seven of the water molecules and all of the O atoms in the cations participating in an alternating arrangement of interleaved sheets of the anionic species. Both the hydrate and the anhydrous salt of the same toxicologically important marker for cocaine show that the cation and anion are in close proximity to each other, as was found in the gold(III) tetrachloride salt of L-cocaine.


Subject(s)
Cocaine/analogs & derivatives , Cocaine/chemistry , Gold Compounds/chemistry , Cocaine/blood , Crystallography, X-Ray , Forensic Toxicology/methods , Gold Compounds/blood , Humans , Molecular Structure , Salts , Water/chemistry
4.
Metallomics ; 1(5): 427-33, 2009 Sep.
Article in English | MEDLINE | ID: mdl-21305147

ABSTRACT

The increasing incidence of human immunodeficiency virus (HIV) infection and the associated acquired immune deficiency syndrome (AIDS) mortality rates as well as the sometimes severe side effects of highly active anti retroviral therapy (HAART) warrants the continuous search for new, less toxic drug candidates. The anti-HIV activity (inhibition of reverse transcriptase-RT and protease-PR in direct enzyme assays) of eleven gold(i) phosphine compounds are reported here. Uptake of the compounds by peripheral blood mononuclear cells (PBMCs) was demonstrated by inductively coupled plasma atomic emission spectroscopy (ICP-AES) while the effect of the compounds on cell viability was assessed using flow cytometry with annexin V and propidium iodide (PI). Of the 11 gold compounds tested, 7 significantly (p < 0.05) inhibited RT activity at concentrations of 25 and 250 µM while 3 compounds significantly inhibited its activity at 6.25 µM. In the anti-protease assay, 4 of the compounds significantly inhibited the enzyme (p < 0.05) at 100 µM. All of the compounds were taken up by PBMCs (demonstrated by ICP-AES) and were non toxic to these cells at clinically tolerable concentrations. The potential of these novel gold(i) phosphine compounds as anti-HIV agents is therefore promising and worthy of further investigation.


Subject(s)
Gold Compounds/pharmacology , HIV Protease Inhibitors/pharmacology , HIV Reverse Transcriptase/antagonists & inhibitors , HIV-1/enzymology , Phosphines/pharmacology , Reverse Transcriptase Inhibitors/pharmacology , Cell Survival/drug effects , Flow Cytometry , Gold Compounds/blood , HIV Protease/metabolism , HIV Protease Inhibitors/blood , Leukocytes, Mononuclear/metabolism , Phosphines/blood , Reverse Transcriptase Inhibitors/blood , Spectrophotometry, Atomic
5.
Indian J Exp Biol ; 39(9): 892-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11831371

ABSTRACT

Gold containing Ayurvedic preparation, Swarna Vasant Malti, was given to 20 male persons in a dose of 100 mg twice a day for 40 days under supervision of Ayurvedic physicians. The total cumulative intake of 160 mg of gold at the rate of 4 mg per day in this form did not have any toxic effect on human body as evidenced by clinical examination, unaltered body weight, absence of urinary pathology and by 30 sensitive biochemical and enzymatic tests. The gold from this Ayurvedic preparation was found in plasma and erythrocytes, excreted partly in urine and was present in semen. Gold binding to albumin and hemoglobin slightly increased their electrophoretic mobility towards anode. This gold preparation seemed to increase sperm motility and prostatic activity.


Subject(s)
Gold Compounds/pharmacology , Medicine, Ayurvedic , Blood Chemical Analysis , Gold Compounds/blood , Gold Compounds/urine , Heart Function Tests , Humans , Kidney Function Tests , Liver Function Tests , Male , Middle Aged , Pancreatic Function Tests , Safety , Spectrophotometry, Infrared
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