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PubMed1989

Nocardia asteroides keratitis associated with extended-wear soft contact lenses.

Chronic unilateral keratitis developed in a 34-year-old woman who wore extended-wear contact lenses. A clinical response was not obtained until Nocardia asteroides was correctly identified as the causal agent. The response to 30% sulfacetamide was dramatic. We review the clinical presentation of Nocardia keratitis and recommendations for management. Use of corticosteroids should be avoided in Nocardia keratitis. This opportunistic organism should be considered in patients who wear contact lenses in whom infectious keratitis develops.

Adult↗
PubMed1978

Route of absorption of drug and ointment after application to the eye.

Chloramphenicol, tetracycline hydrochloride, sodium sulfacetamide, and fluorescein sodium prepared in both aqueous solutions and ointments were placed in the conjunctival sac of humans. Each drug soon was tasted in the back of the mouth with no difference being noticed with the use of aqueous solution or ointment. Tetracycline and fluorescein studies showed that systemic absorption were similar regardless of whether solution or ointment were used. Furthermore, it was found that the ointment passed through the lacrimal drainage system and into the nose and throat. The ocular contact time of ointment with the eye is greater than that of water, and ointment is much more slowly absorbed via the lacrimal drainage system. Both the drugs and the ointment base applied topically to the eye travel through the nasolacrimal system as the way of elimination when given in the small volumes that are held by the conjunctival sac.

Absorption↗
PubMedDate not supplied

[The role of Chlamydia trachomatis in the etiology of conjunctivitis].

PURPOSE: To turn attention to the etiological importance of chlamydia in chronic conjunctivitis. METHODS: From December 1993 to November 1994 the authors examined 95 patients with chronic conjunctivitis for the presence of Chlamydia trachomatis antigens in conjunctival epithelial cells using direct immunofluorescent antibody tests. RESULTS: The test was positive in 23 patients and most of them responded positively to general tetracycline treatment combined with locally used Sulfacetamide or Floxal. CONCLUSION: Chlamydia trachomatis are common causes of conjunctivitis in adults.

Administration, Topical↗
PubMed1977

Trachoma in Punjab: a study of the prevalence and of mass treatment.

During the years 1971-1974 the prevalence of trachoma in the state of Punjab/Northwest-India was investigated among 11,172 persons of all age-groups. The overall prevalence came to 71,07%. Active and progressive stages (WHO stages I and II) were most common among children and adolescents, whereas complicated cases (WHO stage IV) were found predominantly beyond 45 years of age. Regressive cases (WHO stage III) were equally distributed throughout all ages. To our opinion bacterial conjunctivitis is an important factor preceding the infection with the TRIC-agent. Bacterial conjunctivitis is favoured by adverse climatic conditions (duststorms). A masstreatment using local sulfacetamide was started among 4500 children with trachoma, 1966 children could be seen after 6 months. The incidence of trachoma had dropped to 30%. For mass-treatment in a developing country topical application of antibiotics or sulfas seems advisable. Still more important is health-education, which at the moment is lacking everywhere.

Adolescent↗
PubMed2000

New treatments and therapeutic strategies for acne.

Successful management of acne requires careful patient evaluation followed by consideration of several patient and medication factors when selecting a particular therapeutic regimen. Within the last few years, several new agents for the treatment of acne have become available that afford greater flexibility in the treatment of this prevalent dermatologic disorder. These include adapalene, tazarotene, 2 new topical tretinoin formulations, azelaic acid, a new sodium sulfacetamide formulation, and an oral contraceptive recently approved by the Food and Drug Administration for the treatment of acne. After a brief overview of the pathophysiology of acne and existing therapies, this review evaluates the new antiacne agents and how they can be integrated into a successful treatment strategy that takes into account acne severity and predominant lesion type as well as age, skin type, lifestyle, motivation, and the presence of coexisting conditions.

Acne Vulgaris↗
PubMed1983

Effect of topical antibiotic solutions on corneal epithelial wound healing.

The eight topical antibiotic solutions that we use most frequently were tested for their effect on corneal epithelial wound healing in the rabbit. Five percent cefazolin sodium and a mixture of neomycin sulfate, polymyxin B sulfate, and gramicidin (Neosporin) had the least effect on epithelial healing rates and quality of healing, 10% sulfacetamide sodium and an artificial tear had intermediate effects, and gentamicin sulfate, tobramycin, and chloramphenicol were the most toxic. No substantial differences were found between gentamicin and the newer aminoglycoside, tobramycin, and the "fortified" preparations of these two drugs did not seem to be more toxic than the 0.3% solutions. Therefore, topical antibiotic solutions vary in their effects on the corneal epithelium, and not all antibiotics should be considered innocuous when used in the treatment of epithelial defects.

Administration, Topical↗
PubMed1977

Multiple sulfa compounds: high-pressure liquid chromatographic assay and mobile phase correlation.

A mixture of sulfacetamide, sulfathiazole, and sulfabenzamide was used to develop a rapid high-pressure liquid chromatographic assay. In addition, this study provided a means to develop concepts relating solvent molar polarization parameters and retention times. A linear correlation between molar polarization and retention time was observed and will permit reasonably rapid predictions about the dependent variable.

Chromatography, High Pressure Liquid↗
PubMed1981

Viscoelastic stress/strain behavior of pharmaceutical tablets: analysis during unloading and postcompression periods.

The processes of nonequilibrium generation and decay of axial and radial stresses within tablet compacts were analyzed in terms of three-dimensional linear viscoelastic theory. A rotary tablet press was instrumented to measure punch and die wall stresses during the compression and postcompression periods. Following compression, tablets were permitted to remain at the compression site within the die, and the die wall stress was followed. Microcrystalline cellulose, spray-processed lactose, and sulfacetamide are known to have different compression characteristics and were found to differ significantly in their viscoelastic parameters. Compacts assumed their final viscoelastic state prior to the time of punch separation. Theory permits separation of material behavior into dilation and distortion components. Dilation, thought to be dependent on voids, was elastic in all cases. Distortion effects could be described well by a Kelvin solid model. Results indicate that viscoelastic properties are functions of compression conditions and may be useful in adjusting compression conditions to avoid problems such as capping.

Chemistry, Pharmaceutical↗
PubMed1994

Effects of four penetration enhancers on corneal permeability of drugs in vitro.

The usefulness of penetration enhancers in promoting drug permeation across the cornea was investigated for drugs varying from hydrophilic to lipophilic. Four purported penetration enhancers [Azone (laurocapram), hexamethylenelauramide, hexamethyleneoctanamide, and decylmethylsulfoxide] were employed. Corneal permeability coefficients of drugs that were either hydrophilic (acetazolamide, cimetidine, guanethidine, and sulfacetamide), moderately lipophilic (bunolol and prednisolone), or lipophilic (flurbiprofen and its amide analogue) were measured in the absence or in the presence of various Azone concentrations. The effects of penetration enhancers on the corneal penetration of cimetidine were also compared. The corneal penetration of hydrophilic compounds was enhanced by at least 20-fold at 0.1% Azone. For prednisolone and bunolol, the maximal enhancement was at 0.025-0.1% Azone and was marginal (two- to 5-fold), whereas Azone inhibited rather than enhanced the corneal penetration of the lipophilic flurbiprofen and its amide analogue. All four enhancers behaved similarly in enhancing corneal penetration of cimetidine and corneal hydration after incubation in vitro. Possible mechanisms of penetration enhancers on corneal drug penetration were discussed. Penetration enhancers may have clinical benefits in improving ocular drug delivery of hydrophilic compounds, however, their utility may depend on the toxicological profiles.

Animals↗
PubMed1993

A comparison between the effect of topical and systemic carbonic anhydrase inhibitors on aqueous humor secretion.

We have assessed the onset and duration of decreased intraocular pressure and aqueous humor flow contrasting systemic and topical administration of carbonic anhydrase inhibitors. The relationship between physiological effects and fractional activity of carbonic anhydrase isoenzymes in the eye was also investigated. Experiments were performed in normotensive New Zealand white rabbits. Intraocular pressure was determined manometrically or tonometrically and aqueous humor flow by sulfacetamide clearance. We studied methazolamide (25 mg kg-1), ethoxzolamide (4 mg kg-1), and MK-927 (2% in 0.5% hydroxyethylcellulose, topical, pH 4.8). There is an immediate reduction in intraocular pressure (1.2 and 1.8 mmHg by 2 min) and aqueous flow (33% and 40% by 5 min) following intravenous dosing with either methazolamide or ethoxzolamide. This correlates with rapid appearance of drug in the anterior uvea and very low fractional activity of ocular carbonic anhydrase isoenzymes II (cytosolic) and IV (membrane bound). Peak intraocular pressure reduction averaged 4.2 +/- 0.68 mmHg and 4.5 +/- 0.8 mmHg for methazolamide and ethoxzolamide at 60 and 45 min, respectively. Peak flow reduction was 38% for methazolamide and 40% for ethoxzolamide, at 5 min. Aqueous flow and intraocular pressure returned to baseline at 7 and 4 hr following methazolamide and ethoxzolamide, respectively. This corresponds to decay of drug from ocular tissues and significant increases in fractional activity of carbonic anhydrase isoenzymes. Topical MK-927 resulted in a 1.2 mmHg decrease in pressure by 5 min. This correlated with the early appearance of drug in the anterior uvea prior to its appearance in aqueous humor and very low fractional activity of carbonic anhydrase isoenzymes. Intraocular pressure decreased 3.6 +/- 0.35 mmHg at 1 hr and returned to baseline by 6 hr. Aqueous flow was reduced 12% by 5 min and 35% at 1 hr. The appearance of MK-927 in the anterior uvea prior to detection in aqueous suggests a significant non-corneal route of absorption following topical administration. Topical MK-927 results in a more gradual reduction in intraocular pressure and flow, although peak effects are not statistically different from systemic carbonic anhydrase inhibitors. The time of pressure return to baseline is also comparable to systemic carbonic anhydrase inhibitors. Because the relations between carbonic anhydrase II and carbonic anhydrase IV in the ciliary process are not yet clear and since the drugs have different affinities for the isozymes, the precise degree of fractional inhibition necessary for pharmacological effect is not certain, but based on drug concentration in the anterior uvea, may take 98% inhibition for full intraocular pressure reduction.

Administration, Topical↗
PubMed1988

Aneuploidy detection with a short-term hexaploid wheat assay.

A new type of assay for the identification of agents causing aneuploidy is described. This assay takes advantage of allohexaploid wheat in which monosomic and nullisomic cell lineages can be genetically detected. The wheat strain used (Neatby's virescens) was homozygous for a pair of recessive alleles (v1) which in homozygous condition interfere with normal pigmentation of the leaves at low temperature whereas at higher temperature nearly normal green color formation is permitted. In a single dose this allele cannot suppress the formation of green color even at low temperature, i.e., it is hemizygous ineffective. This locus is in the short arm of chromosome 3B near the centromere. As a consequence of non-disjunction of this chromosome twin sectors may be detected, in which the monosomic cell lineages appear green whereas the trisomic sectors display with color on a cream-colored background at low temperature. This genetic system can also be used for the detection of deletions or duplications involving the short arm of chromosome 3B, and to some extent the A- and the D-genome homeologues. We have determined the pattern of differentiation of the shoot apex and on that basis we can separate the independent genetic events from reappearance of the sectors of common origin in the successive leaves. Such an understanding of development of the leaf sectors permits a quantitative estimation of the genetic response of the plants to mutagenic factors. We have found that X-rays, gamma-rays, p-fluorophenylalanine, 3-aminotriazole, caffeine, vinblastin sulfate, benzo[a]pyrene and auramine significantly increased aneuploidy, and diethylstilbestrol, sulfacetamide, safrole and dichlorvos caused some increase of sectoring. Cytological data on root tips of irradiated seeds support the interpretation of the mechanism of sector formation in the leaves. The test is simple, fast, inexpensive, and it does not require elaborate facilities or highly trained technicians. The trials were well reproducible during a period of 3 years in 2 laboratories. Therefore we consider the new assay a useful complement to other tests of chemicals or physical agents that may cause non-disjunction and other chromosomal aberrations in human populations.

Aneuploidy↗
PubMed2004

Quantitative analysis of twelve sulfonamides in honey after acidic hydrolysis by high-performance liquid chromatography with post-column derivatization and fluorescence detection.

A quantitative HPLC-fluorescence method for the simultaneous determination of 12 sulfonamides (sulfaguanidine, sulfanilamide, sulfacetamide, sulfadiazine, sulfathiazole, sulfapyridine, sulfamerazine, sulfamether, sulfamethazine, sulfamethoxypyridazine, sulfachloropyridazine and sulfadoxine) in honey was developed and validated. Sample pretreatment included acidic hydrolysis, followed by liquid-liquid extraction and solid-phase extraction on a strong cation exchanger. LC separation was performed in 45 min, with a total analysis time of 60 min. Identification and quantitation were based on retention time and fluorescence intensity, respectively. Peak area ratios of the target analytes and the internal standard were fit to a linear least-squares regression curve with a weighting factor of 1/x. Limits of detection and quantitation (LOQ) had values of 1 or 2 and 2 or 5 ng/g, respectively. Linearity was obtained with an average coefficient of determination (R2) higher than 0.997, over a dynamic range from the LOQ value up to 100ng/g. The method demonstrated good intra- and interbatch precision and accuracy. No interferences with the peaks of interest were observed throughout the chromatographic run. Sample pretreatment provided efficient cleanup, while post-column derivatization with fluorescamine proved to be a reproducible derivatization technique enabling a sensitive and rugged quantitative determination of sulfonamides.

Chromatography, High Pressure Liquid↗
PubMed2006

Determination of sulfonamide antibiotics in wastewater: a comparison of solid phase microextraction and solid phase extraction methods.

In recent years, pharmaceutical and personal care products (PPCPs) have been detected in diverse environments (including groundwater, river water, and municipal wastewater). In order to evaluate their environmental impact, PPCPs must first be accurately determined. In this study, we focused on developing methods to accurately determine 10 sulfonamide antibiotics: sulfaguanidine, sulfacetamide, sulfadiazine, sulfathiazine, sulfapyridine, sulfamerazine, sulfamethazine, sulfamethoxazole, sulfadimethoxine, and sulfasalazine. While sulfonamides can easily be determined in pure water, wastewater influent and effluent collected from sewage treatment plants in Burlington and Toronto (Ontario) were found to generate confounding matrix effects. In an effort to overcome these matrix effects, we developed a solid phase microextraction (SPME) method to determine sulfonamides. Of the five different fiber assemblies investigated, the carbowax/divinylbenzene (CW/DVB) fiber produced the optimal response to sulfonamides. The SPME method was further optimized for sorption time (20min), solution salinity (10%, w/v, KCl), pH (4.5), and static desorption time (30min). When compared to solid phase extraction (SPE) using MCX cartridges, we observed that despite having higher MDLs and poorer sensitivity, SPME possessed the advantage of speed and reduced solvent usage. Most importantly, in contrast to SPE, when we applied the SPME method to fortified wastewater samples, we were generally able to accurately determine (i.e., recover) those sulfonamides that were present. Therefore, we conclude that SPME is a viable method for overcoming matrix effects in environmental samples.

Anti-Bacterial Agents↗
PubMed2004

Analysis in Escherichia coli of Plasmodium falciparum dihydropteroate synthase (DHPS) alleles implicated in resistance to sulfadoxine.

Mutations in Plasmodium falciparum dihydropteroate synthase have been linked to resistance to the antimalarial drug, sulfadoxine, which competes with the dihydropteroate synthase substrate, p-aminobenzoate. In an effort to evaluate the role of these mutations in a simple model system, we have expressed six relevant alleles of the P. falciparum dihydropteroate synthase gene in Escherichia coli. When each construct was produced in a dihydropteroate synthase disrupted E. coli strain that required thymidine, the thymidine requirement was lost, indicating heterologous complementation had occurred. In the presence of sulfadoxine, the growth of the strain with the wild-type dihydropteroate synthase allele was inhibited while those containing each of the five mutant alleles grew, indicating that these mutations can confer sulfadoxine resistance in E. coli. When tested against twelve additional 'sulfa' drugs a variety of responses were obtained. All strains were resistant to sulfadiazine, but the wild-type allele conferred sensitivity to all other sulfa drugs. Three alleles conferred resistance to dapsone, a drug that is to be targetted for a new regime of malaria treatment in Africa. All mutant alleles remained sensitive to sulfachloropyridazine and sulfacetamide. These results suggest new drugs that could be tried for effective malaria treatment.

Alleles↗
PubMed2004

Molecular characterization of bifunctional hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase from Plasmodium falciparum.

A 2118-base pair gene encoding the bifunctional hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate syntheses of Plasmodium falciparum (pfPPPK-DHPS) was expressed under the control of the T5 promoter in a DHPS-deficient Escherichia coli strain. The enzyme was purified to near homogeneity using nickel affinity chromatography followed by gel filtration and migrates as an intense band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with apparent mass of approximately 83 kDa. Gel filtration suggested that the native pfPPPK-DHPS might exist as a tetramer of identical subunits. The enzyme was found to be Mg2+ - and ATP-dependent and had optimal temperature ranging from 37 to 45 degrees C with peak activity at pH 10. Sodium chloride and potassium chloride at 0.2 and 0.4 M, respectively, activated the activity of the enzyme but higher salt concentrations were inhibitory. Guanidine-HCl and urea inhibited the enzyme activity by 50% at 0.25 and 0.9 M, respectively. Kinetic properties of the recombinant pfPPPK-DHPS were investigated. Sulfathiazole and dapsone were potent inhibitors of pfPPPK-DHPS, whilst sulfadoxine, sulfanilamide, sulfacetamide and p-aminosalicylic acid were less inhibitory. Our construct provides an abundant source of recombinant pfPPPK-DHPS for crystallization and drug screening.

Adenosine Triphosphate↗
PubMed2003

3-Aminophenol as a novel coupling agent for the spectrophotometric determination of sulfonamide derivatives.

A rapid, simple and sensitive spectrophotometric method for the determination of some sulfa drugs is described. The method is based on the formation of orange yellow colored azo product by the diazotization of sulfonamides, viz., dapsone (DAP), sulfathiazole (SFT), sulfadiazine (SFD), sulfacetamide (SFA), sulfamethoxazole (SFMx), sulfamerazine (SFMr), sulfaguanidine (SFG) and sulfadimidine (SFDd) followed by a coupling reaction with 3-aminophenol in aqueous medium. Absorbance of the resulting orange yellow product is measured at 460 nm and is stable for 6 days at 27 degrees C. Beer's law is obeyed in the concentration range of 0.05-8.0 microg/ml at the wavelength of maximum absorption. The method is successfully employed for the determination of sulfonamides in various pharmaceutical preparations and common excipients used as additives in pharmaceuticals do not interfere in the proposed method. Plausible reaction mechanism is proposed for the formation of the azo product.

Aminophenols↗
PubMed1997

Arabidopsis dihydropteroate synthase: general properties and inhibition by reaction product and sulfonamides.

Dihydropteroate synthase (DHPS) (EC 2.5.1.15) was extracted from leaves of Arabidopsis thaliana and purified 21-fold by ion-exchange chromatography. This enzyme preparation was then characterized for several of its properties. Michaelis-Menten constants for the substrates, p-aminobenzoic acid and dihydropteridine diphosphate were estimated to be 2.5 and 91 microM, respectively. In an optimized assay, the reaction product, dihydropteroic acid, competitively inhibited the enzyme activity with a Ki of 81 microM. However, neither dihydropteroic acid nor tetrahydrofolate, products further downstream in the biosynthetic pathway inhibited enzymatic activity. This appears to be the first report of product inhibition of DHPS from a higher plant. The relative inhibitory properties of several sulfonamides, analogues of p-aminobenzoic acid, were also examined. The substitutions on the amide nitrogen of the sulfonamides influenced the degree of inhibition; thus I50 values for the inhibition of the DHPS activity by sulfanilamide, sulfacetamide and sulfadiazine were estimated to be 18.6, 9.6 and 4.2 microM, respectively. The competitive pattern of inhibition was shown in experiments with sulfadiazine.

Arabidopsis↗
PubMed2002

Iminodibenzyl as a novel coupling agent for the spectrophotometric determination of sulfonamide derivatives.

A rapid, selective and simple spectrophotometric method for the determination of sulfa-drugs is described. The method is based on the formation of violet colored azo product by the diazotization of sulfonamides, viz. sulfathiazole (SFT), sulfadiazine (SFD), sulfacetamide (SFA), sulfamethoxazole (SFMx), sulfamerazine (SFMr), sulfaguanidine (SFG) and sulfadimidine (SFDd) followed by a coupling reaction with iminodibenzyl in alcohol medium. Absorbance of the resulting violet azo product is measured at 570-580 nm and is stable for 24 h at 27 degrees C. Beer's law is obeyed in the concentration range of 0.05-6.0 microg ml(-1) at the wavelength of maximum absorption. The method is successfully employed for the determination of sulfonamides in various pharmaceutical preparations and common excipients used as additives in pharmaceuticals do not interfere in the proposed method. The method offers the advantages of simplicity, rapidity and sensitivity without the need for extraction or heating. A reaction mechanism is proposed for the formation of the violet azo product.

Anti-Infective Agents↗