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PubMed1999

High-resolution, submicron particle size distribution analysis using gravitational-sweep sedimentation.

Sedimentation velocity is a powerful tool for the analysis of complex solutions of macromolecules. However, sample turbidity imposes an upper limit to the size of molecular complexes currently amenable to such analysis. Furthermore, the breadth of the particle size distribution, combined with possible variations in the density of different particles, makes it difficult to analyze extremely complex mixtures. These same problems are faced in the polymer industry, where dispersions of latices, pigments, lacquers, and emulsions must be characterized. There is a rich history of methods developed for the polymer industry finding use in the biochemical sciences. Two such methods are presented. These use analytical ultracentrifugation to determine the density and size distributions for submicron-sized particles. Both methods rely on Stokes' equations to estimate particle size and density, whereas turbidity, corrected using Mie's theory, provides the concentration measurement. The first method uses the sedimentation time in dispersion media of different densities to evaluate the particle density and size distribution. This method works provided the sample is chemically homogeneous. The second method splices together data gathered at different sample concentrations, thus permitting the high-resolution determination of the size distribution of particle diameters ranging from 10 to 3000 nm. By increasing the rotor speed exponentially from 0 to 40,000 rpm over a 1-h period, size distributions may be measured for extremely broadly distributed dispersions. Presented here is a short history of particle size distribution analysis using the ultracentrifuge, along with a description of the newest experimental methods. Several applications of the methods are provided that demonstrate the breadth of its utility, including extensions to samples containing nonspherical and chromophoric particles.

Deuterium Oxide↗
PubMed1988

Trace analysis of airborne 1,6-hexamethylenediisocyanate and the related aminoisocyanate and diamine by glass capillary gas chromatography.

A capillary gas chromatographic method was developed for the analysis of complex air mixtures of 1,6-hexamethylenediisocyanate, 1,6-hexamethyleneaminoisocyanate and 1,6-hexamethylenediamine. The method is based on derivatization in the sampling step of the reactive isocyanate groups to corresponding urethane groups by the alkaline ethanolic solvent and a subsequent derivatization of remaining amino groups to amide groups with heptafluorobutyric acid anhydride. The overall procedure, including sampling, gave a linear response at air concentrations of 3-300 micrograms/m3 for 1,6-hexamethylenediisocyanate with a precision of ca. 4% at 15 micrograms/m3 and a detection limit of ca. 0.2 microgram/m3 using nitrogen selective detection. In a field measurement of air concentrations in welding work on lacquered metal parts at a motor-car workshop, concentrations of 1,6-hexamethylenediisocyanate above 600 micrograms/m3 were found. Also 1,6-hexamethyleneaminoisocyanate and 1,6-hexamethylenediamine were found at concentrations of the order of 15% of the 1,6-hexamethylenediisocyanate concentration.

Air Pollutants↗
PubMed1992

Urinary calculi associated with solvent abuse.

We describe 3 cases of urinary calculi that developed during the course of long-term solvent abuse. The patients regularly sniffed a lacquer thinner (major component toluene) or a cement (xylene and cyclohexane) for 2 to 6 years before the development of urolithiasis. The occurrence of proteinuria and hematuria was closely related to solvent sniffing in 2 of the 3 patients. Regular, long-term solvent abuse must be included in the causes of urolithiasis, particularly in juveniles and young adults.

Adult↗
PubMed2001

Evaluation of developmental toxicity in rats exposed to the environmental estrogen bisphenol A during pregnancy.

Bisphenol A (BPA) is an essential component of epoxy resins used in the lacquer lining of metal food cans, as a component of polycarbonates, and in dental sealants. The present study was conducted in an attempt to evaluate the adverse effects of the environmental estrogen BPA on initiation and maintenance of pregnancy and embryofetal development after maternal exposure during the entire period of pregnancy in Sprague-Dawley rats. The test chemical was administered by gavage to mated females from days 1 to 20 of gestation (sperm in varginal lavage = day 0) at dose levels of 0, 100, 300, and 1000 mg/kg. All females were subjected to caesarean section on day 21 of gestation and their fetuses were examined for external, visceral and skeletal abnormalities. In the 1000 mg/kg group, significant toxic effects including abnormal clinical signs, decreased maternal body weight and body weight gain, and reduced food consumption were observed in pregnant rats. An increase in pregnancy failure was also found in the successfully mated females. In addition, increased number of embryonal deaths, increased postimplantation loss, reduced litter size and fetal body weight, and decreased number of fetal ossification centers of several skeletal districts were seen. On the contrary, no significant changes induced by BPA were detected in the number of corpora lutea and implantation sites and by fetal morphological examinations. In the 300 mg/kg group, suppressed maternal body weight and body weight gain, decreased food intake and reduced body weight of male fetuses were seen. There were no adverse signs of either maternal toxicity or developmental toxicity in the 100 mg/kg group. It was concluded that BPA administration during the entire period of pregnancy in rats produced pregnancy failure, pre- and postimplantation loss, fetal developmental delay and severe maternal toxicity, but no embryo-fetal dysmorphogenesis at an oral exposure level of 1000 mg/kg.

Air Pollutants↗
PubMed2003

Quantitative structure-activity relationships for estrogen receptor binding affinity of phenolic chemicals.

The estrogen receptor (ER) binding affinities of 25 compounds including 15 industrial phenolic chemicals, two phytoestrogens, three natural steroids and one man-made steroid were detected by a binding competition assay. The 17 industrial phenolic chemicals were selected as objective compounds because they are possibly released from epoxy and polyester-styrene resins used in lacquer coatings of concrete tank and lining of steel pipe in water supply system. A quantitative structure-activity relationship (QSAR) for structurally diverse phenols, nine alkylphenols with only one alkyl group, four hydroxyl biphenyls, bisphenol A and four natural and man-made estrogens was established by applying a quantum chemical modeling method. Logarithm of octanol-water coefficient (logPow), molecular volume (V(m)), and energies of the highest occupied molecular orbital ( epsilon (HOMO)) and lowest unoccupied molecular orbital ( epsilon (LUMO)) were selected as hydrophobic, steric (V(m)), and electronic chemical descriptors, respectively. Chemicals capable of ER binding had large V(m) and high epsilon (HOMO), while the effects of logPow and epsilon (LUMO) on the binding affinity could not be identified. The QSAR made successful predictions for the three phytoestrogens. Also, the successful prediction of ER-binding affinity for biochanin A, another phytoestrogen, two indicators of pH (phenolphthalin and phenolphthalein) and one alkylphenolic chemical with three alkyl groups (4-methyl-2,6-di-butyl-phenol), by amending the V(m) in the above-mentioned QSAR according to the electron-density distribution (or HOMO density) is an additional step in the elucidation of chemical steric and electronic parameters for predicting the binding affinities of phenolic compounds.

Estrogens, Non-Steroidal↗
PubMed2003

Clear lens extraction for the correction of high myopia.

OBJECTIVE: To evaluate the postoperative outcomes and intraoperative and postoperative complications of clear lens extraction (CLE) with posterior chamber intraocular lens (IOL) implantation in highly myopic eyes. DESIGN: Retrospective case series. PARTICIPANTS: One hundred seven patients (190 eyes) who had undergone CLE with posterior chamber IOL implantation and who had been observed for at least 3 years after surgery. METHODS: Medical records of patients who had undergone CLE with posterior chamber IOL implantation to treat high myopia (axial length >26.00 mm) over 7 years (January 1990 to December 1996) were reviewed. Visual acuity and refractive error were assessed before and after surgery, and perioperative, intraoperative, and postoperative complications were recorded. MAIN OUTCOME MEASURES: Axial length, preoperative and final best spectacle-corrected visual acuity (BSCVA), preoperative and postoperative spherical equivalent (SE), argon laser treatments, surgical complications, neodymium:yttrium-aluminum-garnet (Nd:YAG) laser capsulotomy, retinal detachment (RD), time from surgery or Nd:YAG capsulotomy to RD, subfoveal choroidal neovascularization (CNV), and follow-up period. RESULTS: The mean postoperative follow-up period was 4.78 years (range, 3.10-8.03 years). Final BSCVA was better than preoperative BSCVA in 159 eyes (83.68%), equal in 24 eyes (12.63%), and worse in 7 eyes (3.68%). Postoperative BSCVA was 20/40 or better in 136 eyes (71.60%) vs. 52 eyes (27.36%) before surgery (P<0.001). The mean final postoperative SE was -1.22 diopters. The risk of Nd:YAG laser capsulotomy was 77.89%. The incidence of RD was 2.10%; retinal reattachment was achieved in all cases, and none of these eyes had worse final BSCVA than before surgery. Subfoveal CNV developed in 4 eyes (2.10%) of 3 patients; all of these eyes presented with a macular lacquer crack. CONCLUSIONS: Clear lens extraction with posterior chamber IOL implantation has good outcomes with acceptable predictability and improvement in best-corrected visual acuity. During follow-up, patients tended to remain stable, and the risk of retinal detachment was low. We attribute our favorable results to careful patient selection and follow-up.

Adult↗
PubMed1984

Natural history of choroidal neovascularization in degenerative myopia.

We studied 354 eyes with myopic chorioretinal degeneration by means of standard clinical evaluation and fluorescein angiography. The eyes were classified on the basis of the degree of chorioretinal degeneration found in the posterior pole. Lacquer cracks (breaks in Bruch's membrane) were noted in 82% of the 149 eyes with choroidal neovascular membranes (CNM) and in 96% of the 58 eyes with isolated subretinal hemorrhages. These hemorrhages were reabsorbed without adverse visual sequelae in 32 eyes that were followed; in 14 of these eyes that were followed closely, the average time of reabsorption was 6.4 weeks. Seventy eyes with CNM were followed for an average of 40.9 months. In 96% of these eyes the CNM remained stable or regressed, leaving an atrophic, nonexudative scar. This study indicates that CNM in degenerative myopia is usually self-limited.

Adolescent↗
PubMed1999

Visual acuity outcomes of patients 50 years of age and older with high myopia and untreated choroidal neovascularization.

OBJECTIVE: To evaluate visual outcomes of untreated submacular choroidal neovascularization (CNV) in patients 50 years of age and older with high myopia. DESIGN: Retrospective observational case series. PARTICIPANTS: Twenty-two eyes in 22 patients were studied. All were 50 years of age and older with myopia of 6.0 diopters (D) or greater or an axial length of 25.5 mm or greater. Patients had untreated CNV documented by clinical examination and fluorescein angiography at two medical centers between 1986 and 1997. INTERVENTION: Demographic and clinical data were abstracted from patients' medical records. MAIN OUTCOME MEASURE: Visual acuity at 1 year after CNV diagnosis. RESULTS: The study included 22 eyes of 22 patients (mean age, 63.1 years; mean refraction, -11.0 D). Baseline visual acuity (VA) in the study eye was 20/40 or greater in 2 (9%) patients, 20/50 to 20/150 in 9 (41%) patients, and 20/200 or less in 11 (50%) patients. Drusen were present in seven (32%) eyes, and lacquer cracks were noted in ten (45%) eyes. Mean refractive error was -7.0 D for patients with drusen and -12.5 D for patients without drusen. Choroidal neovascularization was less than 0.25 disc diameters (DD) in 11 (50%) eyes, 0.25 to 0.5 DD in 5 (23%) eyes, and greater than 0.5 DD in 6 (27%) eyes. Visual acuity in the study eye 1 year after CNV diagnosis was 20/40 or greater in 3 (14%) patients, 20/50 to 20/150 in 3 (14%) patients, and 20/200 or less in 16 (73%) eyes. The presence of drusen was significantly associated with older age and a lower degree of myopia but was not associated with size of the CNV or visual acuity outcome. CONCLUSION: When compared to patients younger than 50 years of age with high myopia and CNV reported in previous publications, the patients in the current series generally have poorer visual outcomes.

Aged↗
PubMed2000

Spectroscopic and electrochemical properties of the Met86Gln mutant of Achromobacter cycloclastes pseudoazurin.

The mutant replacing the Met86 ligand of Achromobacter cycloclastes pseudoazurin (Ac-pAz) with Gln has been prepared and spectroscopically and electrochemically characterized. Ac-pAz has four ligands (2His, Cys, and Met) and donates one electron to its cognate Cu-containing nitrite reductase (Ac-NIR). The mutant ([Met86Gln]pAz) shows the electronic absorption and CD spectra considerably similar to those of zucchini mavicyanin (Mv) and lacquer and cucumber stellacyanins (St) having 2His, Cys, and Gln. The EPR signal of the mutant has an axial character, although those of Mv and St show rhombic signals. The findings indicate that the Cu site having Gln might be a distorted trigonal geometry. The half-wave potentials (E(1/2)) of [Met86Gln]pAz and the intermolecular electron-transfer rate constant (kET) from the mutant to Ac-NIR were determined by cyclic voltammetry at pH 7.0 and 25 degrees C. The E(1/2) is +134 mV (versus NHE) and the coordination of Gln instead of Met negatively shifts the E(1/2) of Ac-pAz (+260 mV (versus NHE)). The kET of [Met86Gln]pAz (1.2x10(6) M(-1) s(-1)) is larger than that of the recombinant Ac-pAz (7.5x10(5) M(-1) s(-1)).

Alcaligenes↗
PubMed2000

Onychomycosis caused by nondermatophytic molds: clinical features and response to treatment of 59 cases.

BACKGROUND: Nail invasion by nondermatophytic molds (NDM) is considered uncommon with prevalence rates ranging from 1.45% to 17. 6%. OBJECTIVE: We report the clinical features and response to treatment of onychomycosis caused by these molds. METHODS: From 1995 through 1998 we performed a mycologic study on 1548 patients affected by nail disorders, and we diagnosed 431 cases of onychomycosis including 59 cases of onychomycosis caused by molds. These include 17 patients with onychomycosis caused by Scopulariopsis brevicaulis, 26 patients with onychomycosis caused by Fusarium sp, 9 patients with onychomycosis caused by Acremonium sp, and 7 patients with onychomycosis caused by Aspergillus sp. RESULTS: Onychomycosis caused by S brevicaulis, Fusarium sp, and Aspergillus sp may often be suspected by clinical examination. In fact 38 of 50 patients with onychomycosis resulting from these molds were affected by proximal subungual onychomycosis associated with inflammation of the proximal nailfold. In our experience mold onychomycosis is not significantly associated with systemic diseases or immunodepression. NDM are difficult to eradicate; by using and combining different treatments (systemic itraconazole, systemic terbinafine, topical terbinafine after nail plate avulsion, and ciclopirox nail lacquer) we were able to cure only 69.2% of patients with S brevicaulis onychomycosis, 71.4% of patients with Acremonium onychomycosis, and 40% of patients with Fusarium onychomycosis. Aspergillus onychomycosis, on the other hand, responded very well to therapy and all our patients were cured after systemic or topical treatment. Eradication of the mold produced a complete cure of the nail abnormalities in all the patients who responded to treatment. CONCLUSION: Clinical examination usually suggests diagnosis of onychomycosis resulting from NDM. Topical treatment can be more successful than systemic therapy to cure onychomycosis caused by S brevicaulis, Fusarium sp, and Acremonium sp.

Administration, Topical↗
PubMed1994

Topical and surgical treatment of onychomycosis.

Dermatophytes, yeasts, and molds can be the causative organisms of fungal nail infections. Alternatives to the systemic management of onychomycosis include topical and surgical treatments. Traditionally, topical agents used as monotherapy for onychomycosis are only able to inhibit the growth of fungal nail infections; clinical and mycologic cures have recently been observed after treatment with some of the newer preparations. In contrast, surgical treatments almost always need to be used in conjunction with either topical or systemic antifungal therapy. An efficacious topical treatment alternative for onychomycosis involves applying antifungal agents concurrently or sequentially with the removal or debridement of the infected nail structures. Alternatively, the application of antifungal lacquer to fingernail and toenail fungal infections may also be an effective topical therapy for the treatment of less severe forms of onychomycosis.

Administration, Topical↗
PubMed2003

Comparative assessment of gastrointestinal irritant potency in man of tin(II) chloride and tin migrated from packaging.

Tin is present in low concentrations in most canned foods and beverages, the highest levels being found in products packaged in unlacquered or partially lacquered tinplate cans. A limited number of case-reports of acute gastrointestinal disorders after consumption of food containing 100-500 mg/kg tin have been reported, but these reports suffer many insufficiencies. Controlled clinical studies on acute effects of tin migrated from packaging suggest a threshold concentration for adverse effects (AEs) of >730 mg/kg. Two separate randomised, single-centre, double-blind, crossover studies, enabling comparison of the tolerability of tin added as tin(II) chloride at concentrations of <0.5, 161, 264 and 529 mg/kg in 250 ml tomato juice in 20 volunteers (Study 1) and tin migrated from packaging at concentrations of <0.5, 201 and 267 mg/kg in 250 ml tomato soup in 24 volunteers (Study 2) were carried out. Distribution studies were conducted to get insight in the acute AEs of low molecular weight (<1000 Da) tin species in the soluble fraction of food products. Results show that the chemical form of tin and not the elemental concentration per se determines the severity of AEs. A clear dose-response relationship was only observed when tin was added as tin(II) chloride in tomato juice. No clinically significant AEs were reported in Study 2 and comparison of the incidence of tin-related AEs showed no difference between the dose levels (including control). Tin species of low molecular weight in supernatant represented 31-32% of total tin in canned tomato soup versus 56-61% in juice freshly spiked with tin(II) chloride. Differences in the incidence of AEs following administration of tomato juice with 161 and 264 mg of tin per kg and tomato soup with 201 and 267 mg of tin per kg likely results from differences in the concentration of low molecular weight tin species and in the nature of tin complexes formed. The results of this work demonstrate that tin levels up to 267 mg/kg in canned food cause no AEs in healthy adults and support the currently proposed tin levels of 200 mg/kg and 250 mg/kg for canned beverages and canned foods, respectively, as safe levels for adults in the general population.

Adolescent↗
PubMed2003

Tin in canned food: a review and understanding of occurrence and effect.

Tinplate is light gauge, steel sheet or strip, coated on both sides with commercially pure tin and has been used for well over a hundred years as a robust form of food packaging. Altogether, about 25,000 million food cans are produced and filled in Europe per annum, about 20% of these having plain internal (unlacquered) tin-coated steel bodies. Worldwide, the total for food packaging is approximately 80,000 million cans. Tinplate is also extensively used for the production of beverage cans. Europe produces and fills over 15,000 million tinplate beverage cans per annum all of which are internally lacquered. The use of tinplate for food and beverage packaging, will result in some tin dissolving into the food content, particularly when plain uncoated internal surfaces are used. The Provisional Tolerable Weekly Intake for tin is 14 mg/kg body weight and recommended maximum permissible levels of tin in food are typically 250 mg/kg (200 mg/kg UK) for solid foods and 150 mg/kg for beverages. However, the question arises as to whether evidence exists that such elevated levels of tin in food in any way constitute a risk to human health. This review considers the factors affecting the dissolution of tin, the reported measurements/surveys of actual levels of tin in canned foods and the studies and reports of acute (short term) toxicity relating to the ingestion of elevated levels of tin in food products. Chronic studies are mentioned, but are not covered in detail, since the review is mainly concerned with possible effects from the ingestion of single high doses. From published data, there appears to be a small amount of evidence suggesting that consumption of food or beverages containing tin at concentrations at or below 200 ppm has caused adverse gastrointestinal effects in an unknown but possibly small proportion of those exposed. However, the evidence supporting this assertion is derived from reports of adverse effects which offer data that are limited, incomplete or of uncertain veracity. Clinical studies provide greater confidence regarding the effects of exposure concentration and dose, but few relevant studies have been made. Adverse gastrointestinal effects were observed in limited clinical studies at concentrations of 700 ppm or above, although no adverse gastrointestinal effects were also reported in two studies at higher concentrations. Overall, therefore, the published data do not present a particularly comprehensive profile on the toxic hazard to man of acute exposure to divalent inorganic tin. A food survey suggested that the contents of almost 4% of plain internal tinplate food cans contain over 150 mg/kg of tin and over 2.5 million such cans are consumed every year in the UK alone. Despite this, in the last 25 years, there have been no reports of acute effects attributable to tin contamination in the range 100-200 ppm. These facts strongly suggest that there is little evidence for an association between the consumption of food containing tin at concentrations up to 200 ppm and significant acute adverse gastrointestinal effects. Clearly though, only further clinical studies will generate unequivocal evidence that current legislative limits provide safe levels for adults in the general population.

Animals↗
PubMed1994

Modification of glass channel walls for separation of biological particles by gravitational field-flow fractionation.

In the gravitational field-flow fractionation of complex samples, various interaction and adsorption phenomena can occur in separation channels that influence fractionation and complicate the explanation of resulting fractograms. To overcome these problems, the glass surface was modified to create charge-free, non-adsorbing hydrophilic media for the mild treatment of hydrophilic biological particles. The modification was carried out in two steps: (1) by a simple lacquering of the glass surface with polystyrene diluted in toluene and (2) subsequent adsorption of a detergent layer on polystyrene. Essential suppression of ionic interactions between soluble low-molecular-mass compounds and the channel wall and decreased adsorption effects were demonstrated in separations of blood samples by gravitational field-flow fractionation.

Adsorption↗
PubMed2002

Drug delivery to the nail following topical application.

The absorption of drugs into the nail unit, following topical application to the nail plate, is highly desirable to treat nail disorders, such as onychomycosis (fungal infections of the nail). Nail permeability is however quite low and limits topical therapy to early/mild disease states. In this paper, the recent research into ungual drug delivery is reviewed. The nail unit and the two most common diseases affecting the nail--onychomycosis and nail psoriasis--are briefly described to set the scene and to give an overview of the nature and scope of the problem. The factors, which affect drug uptake and permeation through the nail plate such as solute molecular size, hydrophilicity/hydrophobicity, charge, and the nature of the vehicle, are then discussed, followed by ways of enhancing drug transport into and through the nail plate. Finally, drug-containing nail lacquers which, like cosmetic varnish, are brushed onto the nail plates to form a film, and from which drug is released and penetrates into the nail, are reviewed.

Administration, Topical↗
PubMed2003

The use of oral antifungal agents to treat onychomycosis.

Onychomycosis has been treated for years with oral antifungal agents, and more recently in the United States with a topical nail lacquer. Griseofulvin was the first significant oral agent available to manage onychomycosis. The introduction of the azoles (ketoconazole, itraconazole, and fluconazole) and the allylamine, terbinafine, led to improved cure rates and a broad spectrum of activity. Pharmacokinetic studies have shown that the newer oral agents penetrate the nail within approximately one to two weeks after the start of therapy and remain for several months after the end of treatment. This article reviews the oral antifungal agents used to treat onychomycosis.

Administration, Oral↗
PubMed2003

Treatment of nondermatophyte mold and Candida onychomycosis.

Mold onychomycosis often can be clinically suspected because of the presence of periungual inflammation. Treatment with systemic antifungals is very effective in onychomycosis caused by Aspergillus sp. Scopulariopsis brevicaulis and Fusarium sp. infection are difficult to eradicate and treatment with systemic antifungals should always be associated with topical treatment with nail lacquers. Candida onychomycosis is always a sign of immunodepression. Systemic treatment with itraconazole or fluconazole is usually effective, but relapses are very common.

Administration, Cutaneous↗
PubMed2002

Nail fungal infections and treatment.

Treating onychomycosis may be a tantalizing problem depending on the age of the patient, the condition's modifications, and the status of the peripheral circulation. The clinician will have to choose among three main possibilities: topical therapy with the new nail lacquers, new oral drugs, and removal of the nail plate. A combination of different modalities often provides the best option.

Bandages↗