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Biomedical subjects

S Nacht

Publications and source records attributed to S Nacht.

At least 19 recordsLinked to original sources
PubMed1991

Controlled release of benzoyl peroxide from a porous microsphere polymeric system can reduce topical irritancy.

Skin absorption of benzoyl peroxide from a topical lotion containing freely dispersed drug was compared with that from the same lotion in which the drug was entrapped in a controlled-release styrene-divinylbenzene polymer system. In an in vitro diffusion system, statistically significant (p = 0.01) differences were found in the content of benzoyl peroxide in excised human skin and in percutaneous absorption. In vivo, significantly (p = 0.002) less benzoyl peroxide was absorbed through rhesus monkey skin from the polymeric system. This controlled release of benzoyl peroxide to skin can alter the dose relation that exists between efficacy and skin irritation. Corresponding studies showed reduced skin irritation in cumulative irritancy studies in rabbits and human beings, whereas in vivo human antimicrobial efficacy studies showed that application of the formulations containing entrapped benzoyl peroxide significantly reduced counts of Propionibacterium acnes (p less than 0.001) and aerobic bacteria (p less than 0.001) and the free fatty acid/triglyceride ratio in skin lipids. These findings support the hypothesis that, at least for this drug, controlled topical delivery can enhance safety without sacrificing efficacy.

Administration, Cutaneous↗
PubMed1983

Benzoyl peroxide: percutaneous penetration and metabolic disposition. II. Effect of concentration.

The effect of drug concentrations of 2.5%, 5%, and 10% upon the transepidermal penetration of 14C-benzoyl peroxide in a lotion vehicle was assessed in excised human skin and in vivo in the rhesus monkey. In vitro, penetration of benzoyl peroxide was concentration-dependent, both as to rate and to amount, as measured by the hourly recovery of the metabolite, benzoic acid, from the dermal side of the model. In vivo, the higher the concentration of benzoyl peroxide applied, the greater the amount absorbed, as indicated by the urinary excretion of 14C-benzoic acid. Metabolic disposition of benzoyl peroxide, in turn, was unaffected by drug concentration. In all instances, the benzoyl peroxide absorbed was excreted rapidly in urine as benzoic acid; no hippuric acid was detected at any time. We conclude that (1) use of the excised human skin model for this compound can provide useful data in studies of the effects of vehicle and concentration on topical drug delivery, (2) the transepidermal delivery of benzoyl peroxide, but not its metabolic disposition, is concentration-dependent, and (3) the renal clearance of the systemically absorbed drug is so rapid that it precludes passage through the liver--therefore, no systemic toxicity due to drug accumulation can be expected.

Administration, Topical↗
PubMed1983

Percutaneous absorption, blood levels, and urinary excretion of resorcinol applied topically in humans.

The absorption and metabolic disposition of 2% resorcinol applied topically in a hydroalcoholic vehicle was determined in three human subjects. The drug penetrated the skin at a rate of 0.37 micrograms/cm2/hour. After 2 weeks of bid application of 800 mg resorcinol to about 30% of body surface of each subject, an average of 1.64% of the dosage was being excreted in 24-hour urine specimens as the glucuronide or as the sulfate conjugate. There was no resorcinol in blood drawn at weeks 1, 2, 3, and 4, or nor were there any abnormalities in thyroid function or blood chemistries at weeks 2, 3, and 4. Resorcinol (2%) appears safe for topical use in humans.

Administration, Topical↗
PubMed1983

Comparative activity of benzoyl peroxide and hexachlorophene. In vivo studies against propionibacterium acnes in humans.

The bactericidal effects of benzoyl peroxide (5% lotion) and hexachlorophene (3% colloidal suspension) against Propionibacterium acnes were compared in nine healthy college students who had the microbiological and skin lipid characteristics typical of acne vulgaris, but no active lesions. Each of the two medications was applied twice daily, to opposite sides of the face, for four consecutive weeks. Hexachlorophene was effective against surface aerobes but only slightly active against P acnes. It marginally reduced free fatty acid concentrations in surface lipids and in follicular porphyrin fluorescence. Conversely, benzoyl peroxide virtually eliminated P acnes and aerobes and induced substantially decreased free fatty acid concentrations and follicular fluorescence. We conclude that benzoyl peroxide exerts its antimicrobial action in the follicles and inhibits P acnes, while the antimicrobial effectiveness of hexachlorophene is limited to the skin surface.

Acne Vulgaris↗
PubMed1982

Effect of lipids on the aggregation and permeability of human stratum corneum.

The role of stratum corneum (SC) constituents in SC barrier properties was assessed directly in vitro in a reaggregated system. Fragments of SC from the sole of the foot (hyperplastic tissue) and from the calf (normal tissue) were reduced, separately, to individual cells and these cells were depleted of lipids by solvent extraction. Lipids taken from the cells themselves or from SC from other areas of the body were then added to the cells. None of the fractions used allowed for reaggregation of plantar SC cells, or of trypsinized calf SC cells. In contrast, calf SC cells reaggregated equally well with all lipids and formed coherent SC sheets. At equal lipid:cell ratios, however, plantar lipid-calf cell SC sheets were about three time more permeable to water than calf lipid-calf cell SC sheets. The effectiveness of the barrier function of the SC sheets was directly proportional to the amount of added lipid. We conclude that in normal SC the extractable lipids are intimately involved in cellular adhesion/dyshesion and in barrier formation.

Animals↗
PubMed1982

Pharmacokinetics of resorcinol in the rat.

Pharmacokinetic data on resorcinol were obtained from studies in the rat. The drug, administered subcutaneously in an aqueous solution, rapidly cleared plasma vir urine and did not accumulate in tissues. In the urine, the major metabolite of resorcinol was the glucuronide. Repeated dosing for 30 days with maximum tolerated daily doses of 100 mg/kg did not alter pharmacokinetic parameters, nor did it cause overt toxic signs or adverse reactions. The animals' body weight, blood values, levels of serum T3 and T4' and the gross and microscopic appearance of the thyroid gland and spinal cord remained within normal limits throughout the study.

Animals↗
PubMed1981

The composition of the skin surface lipids of the gerbil.

The skin surface lipids of the gerbil were found to consist sterol esters (10%), wax diesters (36.3%), triacylglycerol (26.1%), free fatty alcohols (8.8%), free fatty acids (5.4%), cholesterol (8.4%) and polar lipids (5%). The wax diesters, identified as Type II, were made up of saturated 1,2-diols with odd carbon number, esterified with two molecules of unsubstituted fatty acids with even carbon number. Both the triacylglycerols and the free fatty acid fractions had saturated and unsaturated components. The free and esterified sterols were all cholesterol. The sterol esters contained saturated monoenoic and dienoic fatty acids, with both straight- and branched-chain components. The fatty alcohols were all straight-chain in structure, mostly of even carbon number. Comparison of these results with those previously reported for other species, indicates that the gerbil skin surface lipids are unique in that they contain diacyl alkane diols and fatty alcohols, both of which consist exclusively of saturated components.

Animals↗
PubMed1981

Benzoyl peroxide: percutaneous penetration and metabolic disposition.

The transepidermal penetration and metabolic disposition of 14C-benzoyl peroxide were assessed in vitro (excised human skin) and in vivo (rhesus monkey). In vitro, the benzoyl peroxide penetrated into the skin, through the stratum corneum or the follicular openings, or both, and was recovered on the dermal side as benzoic acid. In vivo, benzoic acid was recovered from urine in amounts equivalent to 45% and 98% of the radiolabel following, respectively, topical and intramuscular administration of small amounts of 14C-benzoyl peroxide. We conclude that benzoyl peroxide penetrates as such into the skin layers and is converted therein to benzoic acid, which, in turn is absorbed into the systemic circulation. Renal clearance of the metabolite is sufficiently rapid as to preclude its hepatic conjugation with glycine, since following topical administration to rhesus monkeys, no hippuric acid was found in the urine, as could have been expected had a significant amount of benzoic acid passed through the liver.

Administration, Topical↗
PubMed1978

A method for measuring desquamation and its use for assessing the effects of some common exfoliants.

Desquamation has been measured in the past by a counting chamber technique after corneocytes are removed from the skin surface and disaggregated in a dilute surfactant solution. However, we have found that complete corneocyte disaggregation is not always possible when these aggregates are recovered from sites where patent peeling is induced. Corneocyte counting in such instances is difficult or impossible. We have devised a method of measuring desquamation wherein the desquamating cells are determined as the total alkali-soluble protein after they are removed from the skin surface with an inert, self-hardening gel. Highly reproducible desquamation rates are obtained, characteristic of the individual subject. Using some common exfoliants, we show that pharmacologic response, observed as an increase in desquamation rate, is also an individual characteristic.

Adult↗
PubMed1978

A reexamination of the potential comedogenicity of sulfur.

The present study was designed to reexamine the question of the potential comedogenicity of topical sulfur. Studies were done by two different investigators in two separate institutions with groups of 12 and 40 subjects, respectively. Biopsy specimens were obtained from the occluded test sites before and after a six-week period of treatment. Each subject received a patch test of 5% sulfur in either an octoxynol 9 (Triton X-100) or a carbomer 934P (Carbopol 934P) vehicle and one of two controls consisting of the Triton X-100 vehicle or a dry patch test. We conclude that no trend or correlation was noted between the presence or absence of sulfur in the formulation and the appearance of comedones. The Triton X-100 vehicle itself appeared to be comedogenic under the experimental conditions.

Acne Vulgaris↗
PubMed1977

Viscoelastic properties of intact human skin: instrumentation, hydration effects, and the contribution of the stratum corneum.

Past attempts to relate mechanical properties of the stratum corneum to its state of hydration or disease condition have been hampered by the lack of adequate in vivo methodology. With the technique described herein, viscoelastic properties of the skin surface can be measured in vivo or on excised skin in vitro. This method is sensitive enough to detect changes in the properties of the stratum corneum induced by topically applied agents or by mechanical disruption of it. The viscoelastic data suggest that the outermost layers of the stratum corneum may become dry in vivo despite their proximity to the underlying wet tissue, and that the instrument is sensitive enough to measure the changes that occur. It also appears that the in vivo behavior of the stratum corneum is similar to that of isolated stratum corneum membranes which become brittle when they are dried and supple when they are hydrated.

Biomechanical Phenomena↗
PubMed1976

The in vitro permeability of skin and buccal mucosa to selected drugs and tritiated water.

The permeability of whole human skin, human dermis, whole pig skin, and canine buccal mucosa have been determined for four chemically different solutes: tritiated water, amphetamine, estradiol, and ouabain. Several new in vitro techniques for isolation, preservation, and permeability determination of these membranous tissues are described. Water permeabilities of human epidermis and dermis using these techniques agree well with published results. Human and porcine skins are very similar with respect to water permeability, while buccal mucosa is similar to dermis in its permeability characteristics to the four representative test agents. The permeability of hydrated whole skin is determined by the permeability of the epidermis, and the dermis and buccal mucosa behave as if they are water barriers exhibiting a permeability of about 30% of the diffusion through pure water, a difference that can be ascribed to the porosity and/or tortuosity of the tissue matrix.

Amphetamines↗
PubMed1972

The role of iron in the pathogenesis of porphyria cutanea tarda. An in vitro model.

Porphyria cutanea tarda (PCT) is characterized biochemically by excessive hepatic synthesis and urinary excretion of uroporphyrin I. Clinical evidence has implicated iron in the pathogenesis of PCT. The synthesis of the normally occurring isomer of uroporphyrin, namely uroporphyrin III, from porphobilinogen (PBG) requires two enzymes; uroporphyrinogen I synthetase and uroporphyrinogen III cosynthetase (COSYN). In the absence of COSYN only uroporphyrinogen I is formed. These experiments were designed to study the effect of iron on porphyrin biosynthesis in porcine and human crude liver extracts and to measure COSYN activity in the presence of iron.Mitochondria-free crude liver extracts were prepared in 0.25 m sucrose at pH 7.4 by centrifugation at 37,000 g. Preparations were incubated with either 0.2 mm amino-levulinic acid (ALA) or 0.1 mm PBG. The addition of ferrous ion (either from ferritin iron [4 mug/ml] and cysteine [6.7 mm] or ferrous ammonium sulfate [0.3 mm Fe] and cysteine) significantly increased the rate of uroporphyrin synthesis from either ALA or PBG. The predominant porphyrin synthesized in the presence of ferrous ion was uroporphyrin I whereas coproporphyrin III predominated in its absence. Orthophenanthroline blocked these effects of ferrous ion.To investigate the effect of ferrous ion on COSYN, crude liver extracts were incubated with ferrous ammonium sulfate (0.3 mm Fe) and cysteine (6.7 mm) and the COSYN activity of the incubates was assayed directly. In both porcine and human extracts ferrous ion caused marked inhibition of COSYN activity. Orthophenanthroline blocked the inhibitory effect.Inactivation of COSYN by heating resulted in marked enhancement of porphyrin synthesis from PBG. The sole product was uroporphyrin I.Thus, inactivation of COSYN results in accelerated synthesis of uroporphyrin I. This effect of ferrous ion provides a possible biochemical explanation for the excess production and excretion of uroporphyrin I in patients with PCT and the reversal of this defect by phlebotomy.

Ammonia-Lyases↗
PubMed1970

The role of ceruloplasmin in iron metabolism.

The importance of ceruloplasmin in iron metabolism was studied in swine made hypoceruloplasminemic by copper deprivation. When the plasma ceruloplasmin level fell below 1% of normal, cell-to-plasma iron flow became sufficiently impaired to cause hypoferremia, even though total body iron stores were normal. When ceruloplasmin was administered to such animals, plasma iron increased immediately and continued to rise at a rate proportional to the logarithm of the ceruloplasmin dose. The administration of inorganic copper induced increases in plasma iron only after ceruloplasmin appeared in the circulation. Thus, ceruloplasmin appeared to be essential to the normal movement of iron from cells to plasma. Studies designed to define the mechanism of action of ceruloplasmin were based on the in vitro observation that ceruloplasmin behaves as an enzyme (ferroxidase) that catalyzes oxidation of ferrous iron. Retention of injected ferrous iron in the plasma of ceruloplasmin-deficient swine was significantly less than that of ferric iron, reflecting impaired transferrin iron binding. Rat ceruloplasmin, which has little ferroxidase activity, was much less effective than porcine or human ceruloplasmin in inducing increases in plasma iron. These observations suggest that ceruloplasmin acts by virtue of its ferroxidase activity. Eight patients with Wilson's disease were evaluated in order to investigate iron metabolism in a disorder characterized by reduced ceruloplasmin levels. Evidence of iron deficiency was found in six of these, and in five of the six, plasma ceruloplasmin was less than 5% of normal. In comparison, the two patients without evidence of iron deficiency had ceruloplasmin levels of 11 and 18% of normal. It is suggested that iron deficiency tends to occur in those patients with Wilson's disease who have the severest degrees of hypoceruloplasminemia, possibly because of defective transfer of iron from intestinal mucosal cells to plasma.

Animals↗