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Biomedical subjects

R Aly

Publications and source records attributed to R Aly.

At least 55 records · Page 3Linked to original sources

Simplified experimental human dermatophytosis model.

The authors have improved and simplified previous methods for producing localized mycotic skin infections in an attempt to compare topical antifungal agents for their bioequivalency. Healthy human volunteers who had negative results for commercial, purified Trichophyton antigen (Trichophytin) were inoculated with Trichophyton mentagrophytes on two sites on each forearm in a randomized study designed to compare the antifungal activities of two ciclopirox olamine formulations. The lesions, easily induced by the authors' method, were localized and did not spread under the occlusive dressings. Infections established at the four sites on 26 subjects were treated twice daily for 14 days with the two active drug formulations and their vehicles. There were no significant differences in culture-documented cure rates or alleviation of clinical signs and symptoms between ciclopirox olamine lotion and cream. Each drug was significantly better than its vehicle. The authors' method seems to be effective and suitable for therapeutic studies.

Adult↗

Inhibition of microbial adherence by sphinganine.

Sphingosines (precursors and degeneration products of complex sphingolipids) are mediators in membrane second-messenger cascades and in a wide variety of functions in eukaryotic cells. Sphingosines are also lethal for gram-positive microorganisms. In addition to its direct effect, sphinganine is here reported to affect the adherence of Streptococcus mitis to buccal epithelial cells and of Staphylococcus aureus to nasal mucosal cells after incubation for 90 min at 37 degrees C. When the bacteria were pretreated with 8.1, 16.2, 32.5, or (for Strep. mitis) 65 microM sphinganine for 60 min at 37 degrees C, adherence counts were reduced for Staph. aureus by 27, 37, and 60% and for Strep. mitis by 19, 44, 54, and 73%, respectively (p < 0.001). In contrast, pretreatment of buccal cells with 81.2 microM lipid increased adherence by 14% (p < 0.01), but no change occurred at either 16.2 or 325 microM lipid. These results further demonstrate the double-edged ability of sphingosines to regulate cellular activities and their potential as multifunctional therapeutic agents for infectious diseases.

Bacterial Adhesion↗

Antimicrobial activity of stratum corneum lipids from normal and essential fatty acid-deficient mice.

Among the cutaneous effects of an essential fatty acid deficient (EFAD) diet are hyperdesquamation, increased transepidermal water loss (TEWL), and altered lipid profiles, characteristics also common to inflammatory dermatoses. Because fatty acids are antimicrobial, we examined the indigenous skin flora of normal and EFAD hairless mice, and compared the antimicrobial efficacy of lipids extracted from their stratum corneum. EFAD mice supported 100-fold more bacteria than normal mice, and were the only group from which Staphylococcus aureus were routinely isolated. Despite this greater carriage, in vitro experiments demonstrated that EFAD lipids are more lethal than normal lipids against Streptococcus pyogenes, S. aureus, S. epidermidis, Micrococcus sp., and a coryneform. Skin fungi were equally susceptible to both extracts. After thin layer chromatography, the most active fractions were found to be glycosphingolipids and phospholipids. EFAD extracts had 35% more free fatty acids and 75% more glycosphingolipids; normal extracts had more triglycerides and phospholipids. S. aureus strain 502A survived equally well on EFAD as on normal mice. Normal lipids applied on EFAD mice had no additional effect, but EFAD lipids on normal mice brought about a 35% reduction of the inoculated bacteria. If the mice were pretreated with alcohol, carriage of strain 502A was reduced by 71%. If instead the mice were previously washed with acetone to increase TEWL, a 97% reduction of the staphylococcus occurred. The application of normal flora to such acetone-washed mice decreased the efficacy to 76%. EFAD and normal lipids on human subjects were equally ineffective in eliminating strain 502A.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparative antibacterial efficacy of a 2-minute surgical scrub with chlorhexidine gluconate, povidone-iodine, and chloroxylenol sponge-brushes.

Chlorhexidine gluconate (Hibiclens), povidone-iodine (E-Z Scrub 201), and chloroxylenol (ParaSoft) sponge-brushes were compared for antibacterial efficacy in 2-minute surgical scrubs. Thirty-nine volunteers completed a 7-day baseline period and a 5-day treatment period. Thirteen participants were assigned to a chlorhexidine group, 12 to a povidone-iodine group, and 14 to a chloroxylenol group. Subjects followed a standardized protocol, performing 11 scrubs during the treatment period. Bacterial counts were taken by the glove-juice procedure immediately after scrubbing and at 3 and 6 hours later on days 1, 2, and 5. The use of chlorhexidine achieved significantly (p less than 0.01) greater adjusted mean log10 bacterial count reductions than did povidone-iodine and chloroxylenol at all sampling times, with greater reductions as the study progressed.

Adult↗

Restriction of bacterial growth under commercial catheter dressings.

The effect on the normal cutaneous flora after iodine and alcohol disinfection of the skin of three commercially available moisture-permeable polyurethane dressings was compared with that of a gauze-and-tape dressing. Dressings also were evaluated clinically for membrane adhesion and skin erythema, pruritus, hyperpigmentation, vesiculitis, and tenderness. Each of 50 healthy volunteers and 49 long-term inpatients, 25 of whom were receiving antibiotic therapy, received simultaneously on their volar forearm patches of Op-Site, Tegaderm, Uniflex, and gauze dressings. Controls consisted of one exposed skin site and one covered with moisture-retaining vinylidene film (Saran Wrap). Although after 3 days of adhesion, commercial dressings prevented indigenous flora from returning to normal population densities, no significant quantitative differences were found between them and the gauze-and-tape dressing. Generally, all clinical dressings maintained normal flora at one tenth the population of the uncovered site; the Saran Wrap control supported 100-fold more bacteria than the exposed site. No differences were discovered in the levels of gram-negative bacteria, or among patient groups and between patients and healthy subjects, except for the lower incidence of erythema and itching among patients compared with healthy subjects.

Adult↗

In vitro and in vivo antistaphylococcal activity of human stratum corneum lipids.

Despite the assumption that sebum-derived fatty acids are responsible for cutaneous antimicrobial defense, no studies have assessed the contribution of epidermis-derived lipids. Herein, we tested the antistaphylococcal effects of human stratum corneum lipids, enriched in endogenous, keratinocyte-derived species obtained by lipid extraction and thin-layer chromatography, for antimicrobial activity in both in vitro and in vivo systems. Whereas the most potent species in vitro were the free fatty acids, polar lipids and glycosphingolipids also demonstrated antistaphylococcal activity in vitro, while other neutral lipids displayed virtually none, results that were confirmed with authentic standards in vitro. In a pilot study on delipidized forearm test sites in human volunteers, naturally occurring free fatty acids, polar lipids, and glycosphingolipids exhibited significantly more antistaphylococcal activity than other stratum corneum lipids or vehicle controls. Finally, biopsy specimens of incubated skin sites demonstrated penetration of staphylococci through lipid-enriched intercellular domains. These results provide the first evidence that endogenous, epidermis-derived skin lipids may contribute to cutaneous antimicrobial resistance.

Fatty Acids, Nonesterified↗

Microbial adherence to vulvar epithelial cells.

Under uniform experimental conditions, different degrees of selective attachment of Staphylococcus aureus and Candida albicans to epithelial cells of the labium majus, the labium minus, and the vagina were compared and contrasted with those found in studies with cells of the buccal and nasal mucosa and forearm skin by a novel analysis of adherence density. For both micro-organisms, the larger, rougher cells of the labium majus gave the highest adherence scores matched only by the interaction of S. aureus with fully keratinised nasal epithelial cells. Increasing acidity to pH 3.5 enhanced microbial adherence to vaginal cells. Menstruation also influenced attachment; highest densities were reached between the third and fourth weeks of the cycle. Autogenous ribitol teichoic acid was found to block the attachment of S. aureus to labium majus and labium minus cells by 76% and 81% respectively, and to vaginal cells by 66%. Adherence is considered to be an important attribute of vulvar ecology and may be a determinant of infectious disease.

Adhesiveness↗

Adherence of Pityrosporum orbiculare to human stratum corneum cells.

This investigation demonstrates the capacity of Pityrosporum orbiculare to adhere to human stratum corneum cells in vitro; this may be an important initial step in its colonization of stratum corneum. Adherence was significantly higher when incubation for 120 min (mean 9.4 adherent yeasts) was compared to 60 min (mean 3.5 adherent yeasts, P less than 0.001), but not to 90 min (mean 8.6 adherent yeasts, P greater than 0.05). Adherence was higher at an incubation temperature of 37 degrees C (mean 10.0 adherent yeasts) as compared with 25 degrees C (mean 4.0, P less than 0.001), but not at 32 degrees C (mean 8.0, P greater than 0.1). There was no significant difference in adherence related to the anatomic area (forearm, back, and chest) from which the stratum corneum cells have been collected. No difference was seen in adherence between different Pityrosporum strains, but it increased significantly with inoculum size of P. orbiculare, being optimal at 10(7) cells ml-1. The adherence of P. orbiculare and Staphylococcus epidermidis to stratum corneum cells was not influenced by incubation of the organisms together or alone. This model opens possibilities to study the influence of: stratum corneum cells from diseased skin compared with controls; antibodies; and types of surface receptors and antimycotics on P. orbiculare adherence to stratum corneum cells.

Humans↗

Skin occlusion: effect on Pityrosporum orbiculare, skin PCO2, pH, transepidermal water loss, and water content.

The effect of 8 days skin occlusion on Pityrosporum orbiculare, bacteria, skin PCO2, pH, transepidermal water loss (TEWL), and water content (WC) was studied. P. orbiculare counts increased from a baseline of 2.1 X 10(2)/cm2 to 2.3 X 10(3)/cm2 after 3 days occlusion; bacterial counts increased from 2.9 X 10(3)/cm2 to 1.8 X 10(5)/cm2 after 8 days occlusion. pH increased during occlusion from 5.6 to a maximum at day 3 of 6.7; TEWL increased to a maximum of 11.74 g m-2 h- after 3 days occlusion compared with 4.39 g m-2 h-1 before. P. orbiculare counts, pH, and TEWL were lower at 8 days than at 3 days occlusion. WC and PCO2 remained high after 8 days; relative WC was then 60.6% compared with 52.5% before occlusion; PCO2 was 63.1 mm Hg compared with 53.1 mm Hg before occlusion. The increased levels of these factors may partially explain the higher risk of infection in occluded compared with non-occluded skin.

Adolescent↗

The Staphylococcus aureus receptor for fibronectin.

The Staphylococcus aureus binding site for human fibronectin was determined by unique biologic assays based upon the specific adherence of the bacterium to nasal epithelial cells. Fibronectin treatment of S. aureus caused a reduction in adherence tallies on high granular and fully keratinized cells compared to controls (p less than 0.05; p less than 0.001). Spinous and low granular cells showed no significant differences. The cell wall materials N-acetyl-D-glucosamine, N-acetyl muramic acid, and protein A were unable to inhibit the coupling of fibronectin to S. aureus. Only ribitol teichoic acid had this property. Furthermore, fibronectin could neutralize the adherence-blocking ability of teichoic acid, which affects keratinized cells. Thus, teichoic acid seems to be a receptor for fibronectin.

Binding Sites↗

Competitive adherence as a mechanism of bacterial interference.

To determine whether competition among bacteria for specific attachment sites on host cells can explain bacterial interference, Staphylococcus aureus strain 502A was tested in turn against two different nasal coryneforms, a strain of Pseudomonas aeruginosa, and a virulent strain of S. aureus, all in the presence of nasal mucosal cells. Particularly examined was the influence of sequence in which bacteria were presented to the nasal cells in comparison with initial mixtures and individual suspensions. Results paralleled those observed in clinical prophylaxis: the bacterium first to adhere to the epithelial cells was able, under uniform conditions, to interfere with the colonization of subsequently added bacteria. Secondary adherence was not eliminated but substantially reduced, and was probably related to steric blockage by the initial colonizer and its particular ability to dissociate from the host cell.

Adhesiveness↗

Quantitative variations in distribution of Pityrosporum orbiculare on clinically normal skin.

The lipophilic yeast Pityrosporum orbiculare has been cultured quantitatively, in 10 volunteers, from clinically normal skin on the chest, back, upper arm, lower leg, and dorsal aspect of the hand. The highest count was on the back (mean 333/cm2) and chest (mean 327/cm2). This was statistically significant higher than on the upper arm (mean 21/cm2), lower leg (mean 13/cm2), and dorsal aspect of the hand (mean 2/cm2). The variations in number of P. orbiculare parallels both regional variations in sebum excretion and the distribution of tinea versicolor lesions.

Adolescent↗

Growth and filament production of Pityrosporum orbiculare and P. ovale on human stratum corneum in vitro.

When Pityrosporum orbiculare and P. ovale were incubated with stratum corneum epithelial cells, suspended in phosphate-buffered saline for 90 min at 37 degrees C, short filaments were produced in 11-17.5% of the yeast cells. A successful culture of P. orbiculare and P. ovale on human stratum corneum in vitro is described. When the stratum corneum pieces were incubated for 5 days in an environment with 7% CO2, a picture resembling that seen microscopically in tinea versicolor was observed. Filaments were produced in 39-48% of P. orbiculare and P. ovale cells; the longest pseudohyphae, 40-60 microns, were produced by P. ovale. This culture method provides the possibility of studying the parasitic mycelium form of P. orbiculare and P. ovale in vitro. The influence of antimycotics, other drugs, and interaction with other microorganisms can be studied.

Cells, Cultured↗

Importance of the keratinized epithelial cell in bacterial adherence.

The effect of cellular pathology and keratinization of skin and nasal cells upon binding of Staphylococcus aureus were examined. Adherence with epithelial cells obtained from either the skin or nasal mucosa of patients with atopic dermatitis was greater than that observed with normal cells (p less than 0.001); the difference in adherence between psoriatic and normal cells was not statistically significant. Tested nasal cells were microscopically differentiated into 4 general types based on stage or layer of keratinization: spinous, low granular, high granular, and keratin. The degree of adherence was related to the progress of keratinization. Data indicated the existence of 2 types of receptors for S. aureus on nasal cells: One, present upon both granular and fully keratinized cells, is not blocked by teichoic acid and appears responsible for the higher bacterial counts on atopic cells; the second is found on keratinized cells only and is susceptible to teichoic acid.

Adhesiveness↗