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Biomedical subjects

W Abraham

Publications and source records attributed to W Abraham.

At least 37 records · Page 2Linked to original sources
PubMed1990

Interaction between corneocytes and stratum corneum lipid liposomes in vitro.

Small unilamellar vesicles were made from a mixture of epidermal ceramides (45%), cholesterol (35%), free fatty acids (15%) and cholesteryl sulfate (5%). Isolated corneocytes prepared from pig epidermis were added to the liposomes and the interaction between corneocytes and liposomes was studied by (1) thin-section electron microscopy and (2) monitoring the release of aqueous contents of the vesicles by following the fluorescence intensity of carboxyfluorescein entrapped in the vesicles. The vesicles adsorbed readily onto the corneocytes and slowly transformed into lamellar sheets. Enhanced fluorescence intensity indicated a corneocyte-induced membrane fusion process that resulted in the release of aqueous contents of the vesicles. The results suggest a cohesive role for the corneocyte cell envelope, which consists of a monomolecular layer of lipids covalently bound to the outside of a cross-linked protein envelope. This may be one of the major factors in the reassembly of extruded membranous disks into lamellar sheets which occurs during the final stages of epidermal differentiation.

Animals↗
PubMed1989

Pharmacological profile of MDL 26,024GO: a novel antiasthmatic agent.

MDL 26,024GO was shown to be an orally absorbed mediator release inhibitor in the rat PCA and PPA tests. In addition, the compound was shown to both elicit and inhibit elicitation of the Bezold-Jarisch reflex in the dog. MDL 26,024GO also significantly reduced Ascaris-induced changes in pulmonary mechanics in cynomolgus monkeys. The compound inhibited both early and late phase antigen induced-changes in Ascaris-sensitive sheep, as well as the increased airway hyperreactivity which normally follows antigen challenge. These results suggest the compound may have therapeutic potential in the treatment of asthma.

Animals↗
PubMed1989

Preparation of model membranes for skin permeability studies using stratum corneum lipids.

Liposomes were prepared from stratum corneum lipids consisting of epidermal ceramides (55% by weight), cholesterol (25%), free fatty acids (15%), and cholesteryl sulfate (5%). Multiple lamellae were formed by air-drying the liposomal suspensions on hydrophilic filter disks, and water permeabilities through these filter-supported lamellae were measured using a diffusion cell. Ultrastructure of the lipid lamellae was characterized by scanning and thin-section electron microscopy. Water flux data and ultrastructure of the model membranes are discussed in relation to stratum corneum, the horny layer of the epidermis that constitutes the epidermal barrier.

Animals↗
PubMed1988

Effect of epidermal acylglucosylceramides and acylceramides on the morphology of liposomes prepared from stratum corneum lipids.

Epidermal acylglucosylceramides (AGC) and acylceramides (AC) cause aggregation and stacking of stratum corneum lipid liposomes formed from a lipid mixture containing epidermal ceramides (40%), cholesterol (25%), palmitic acid (25%), and cholesteryl sulfate (10%). This demonstrates the ability of these sphingolipids to hold adjacent bilayers in close apposition and their roles in the assembly of lamellar structures in the epidermis. However, AGC and AC in their hydrogenated form also caused aggregation and stacking of the stratum corneum lipid liposomes. This throws into doubt the proposed structural specificity of linoleate in the function of AGC and AC as molecular rivets in the assembly of the epidermal lamellar granules and the stratum corneum intercellular lamellae, respectively.

Animals↗
PubMed1988

The role of calcium antagonists in bronchial reactivity.

Calcium (Ca) ions play an important pathophysiologic role in allergic reactions. Thus, mediator release from mast cells, synthesis of some newly formed chemical mediators, airway smooth muscle contraction, and nerve-impulse conduction are all dependent on the availability and flux of Ca ions. It is likely, therefore, that Ca antagonists would modify allergic bronchoconstriction. In vitro, Ca antagonists have been demonstrated to inhibit mediator release (histamine, slow-reacting substance of anaphylaxis, and platelet-activating factor) from mast cells, passively sensitized human lung fragments, and leukocytes. Ca antagonists have also been found to inhibit synthesis of leukotrienes in rat lungs and cyclooxygenase products in sheep, possibly by inactivating phospholipase A2 and/or 5-lipoxygenase. In addition, nifedipine, verapamil, and gallopamil have demonstrated inhibition of airway smooth muscle contractions to histamine, carbachol, and antigen in various species. In vivo effects of Ca antagonists are variable, depending on the species, experimental design, the stimulus or the agonist, and the Ca antagonist used. Animal studies have demonstrated the inhibition of histamine, methacholine, citric acid, and prostaglandin F2 alpha-induced bronchoconstriction in guinea pigs and dogs by intravenous nifedipine. In contrast, verapamil inhibited antigen-induced bronchoconstriction in allergic sheep without any effect on histamine- and carbachol-induced responses. Ca antagonists (nifedipine and verapamil) have been of limited value in human subjects and generally have no significant bronchodilating activity. Both nifedipine and verapamil prevent the exercise-induced asthma and partly attenuate the histamine and methacholine-induced bronchoconstriction. Oral nifedipine is generally more effective than oral verapamil against acute antigen-induced bronchoconstriction; however, this efficacy may be limited by systemic side effects. Inhaled Ca antagonists may be more effective and free of systemic side effects, as demonstrated by greater efficacy of inhaled verapamil. A new Ca antagonist, gallopamil (a methoxy derivative of verapamil), is being investigated as an aerosol, and preliminary studies in animals and humans have found it fourfold to seventeenfold more potent than verapamil. In sheep, gallopamil has been found to attenuate histamine, carbachol, and platelet-activating factor-induced bronchoconstriction, as well as to inhibit early and late-phase allergic airway responses. Studies in human subjects have also demonstrated the inhibition of antigen-induced bronchoconstriction by inhaled gallopamil, with efficacy comparable or better than cromolyn sodium.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Fusion patterns of liposomes formed from stratum corneum lipids.

Stratum corneum lipid liposomes formed from epidermal ceramides (40%), cholesterol (25%), palmitic acid (25%), and cholesteryl sulfate (10%), when exposed to hypertonic medium, form flattened liposomes. Epidermal acylglucosyl-ceramides (AGCs) and acylceramides (ACs) cause aggregation and fusion of these flattened vesicles. This could serve as a model to study (a) the fusion of membranous disks in the intercellular space of the stratum corneum and (b) the roles of AGCs and ACs in the assembly of lamellar structures in the epidermis.

Animals↗
PubMed1988

Should the patella be resurfaced in total knee arthroplasty? Efficacy of patellar resurfacing.

To assess the long-term efficacy of patellar resurfacing, 100 knees were evaluated in 84 patients. The operations were performed between 1978 and 1982. The follow-up period ranged from 60 to 103 months. The diagnosis was degenerative joint disease (DJD) in 83%, rheumatoid arthritis in 12%, and miscellaneous in 5% of the knees. The implant (47 knees) and nonimplant (53 knees) groups were comparable with respect to age, body size, and length of follow-up period. The analysis revealed equivocal results. Considering all diagnostic categories combined, rest pain was marginally better in the resurfaced group (p = 0.04), but this difference resulted from an unequal distribution of subjects between mild and zero pain categories. Pain with walking, maximum walking distance, ability to climb stairs and rise from a chair, active arc of motion, extensor lag, and quadriceps strength were similar in the two groups. When the DJD group was considered separately, no significant difference emerged. There was little evidence to support a recommendation for routine patellar resurfacing in total knee arthroplasty.

Activities of Daily Living↗
PubMed1987

Skin lipids: an update.

The stratum corneum lipids, responsible for the epidermal water barrier, consist principally of ceramides, cholesterol, cholesteryl sulfate, and free fatty acids. These lipids are arranged in multiple intercellular lamellae that provide an efficient water barrier because of the crystalline array of the straight and predominantly saturated lipid chains. Interlamellar linkages provided by lipids based on 30-carbon omega-hydroxyacids may be responsible for holding together the intercellular lamellae as well as for assembly of the lamellar granules of the granular cells. The normally ordered exfoliation of corneocytes as they arrive at the surface seems to require hydrolysis of the cholesteryl sulfate to free cholesterol. The sebaceous glands secrete continuously, producing sebum that consists predominantly of triglycerides, wax esters, and squalene. High rates of sebum production per sebocyte result in low levels of linoleate in the sebaceous esters, subjecting the follicular epithelium to essential fatty acid deficiency and the characteristic hyperkeratosis that results in comedo formation. Suppression of sebum production by drugs elevates sebum linoleate concentration and relieves follicular hyperkeratosis. Thus, sebum continues to be a prime suspect in the crime of acne. Low levels of sebaceous gland activity are not correlated with the occurrence of dry skin.

Acne Vulgaris↗
PubMed1987

Stratum corneum lipid liposomes: calcium-induced transformation into lamellar sheets.

The epidermal water barrier in mammalian stratum corneum is formed of broad lamellar sheets of lipids consisting principally of ceramides (40%), cholesterol (25%), cholesteryl sulfate (10%), and free fatty acids (25%). Such lipid mixtures have been shown to form lipid bilayers in the form of small, unilamellar liposomes when sonicated at 80 degrees C in water containing Tris buffer and 100 mM NaCl. In the present study it is shown that such liposomes are slowly transformed into large unilamellar liposomes and then into broad lamellar sheets after the addition of stoichiometric amounts of calcium chloride. The presence of free fatty acids was a necessary condition for this calcium-induced fusion. These observations may provide a useful analogy for the transformation of flattened liposomes into broad lamellar sheets that occurs during transition of epidermal granular cells into corneocytes.

Animals↗
PubMed1987

Essential fatty acids and epidermal integrity.

The intercellular spaces of the stratum corneum contain multilamellar lipid sheets derived from the extruded contents of lamellar granules. In the absence of linoleic acid, lamellar granules appear empty, and only fragmentary extracellular sheets are found. This defective differentiation is attributable to substitution of oleate for linoleate in O-acylsphingolipids. Normally, linoleate is ester-linked to 30- to 34-carbon omega-hydroxyacids, which, in turn, are amide-linked to sphingosine. Acylglucosylceramides, bearing a beta-D-glucosyl moiety on the sphingosine, may provide the driving force for lamellar granule assembly. The omega-hydroxyacyl chains are long enough to span a lipid bilayer, while the linoleate inserts into an adjacent bilayer. This interaction could promote assembly of lamellar granules. It has also been proposed that acylceramides may stabilize the extracellular sheets by a similar mechanism. In addition, the horny cell has been found to possess a covalently bound lipid envelope consisting principally of omega-hydroxyacylsphingosines derived from O-acylsphingolipids.

Animals↗
PubMed1987

Glucosylsterol and acylglucosylsterol of snake epidermis: structure determination.

The structures of two classes of glycolipids, acylglucosylsterol and glucosylsterol, from snake epidermis have been determined by chemical, spectroscopic, and gas-liquid chromatographic methods. The acylglucosylsterol consists of a glucose molecule attached to cholesterol and an ester-linked fatty acid on carbon 6 of the sugar. The major ester-linked fatty acids are palmitic, stearic, and oleic. The glucosylsterol consists of glucose attached to cholesterol. These unusual glycolipids may play a role in epidermal barrier function in snakes and it is concluded that these sterol glycosides may remain in the reptiles as a vestige of a more primitive barrier-forming mechanism.

Animals↗
PubMed1986

Skin surface lipids of the mink.

Skin surface lipids from mink (Mustela vison) were collected in acetone and analyzed by thin-layer chromatography and gas chromatography. The principal components were wax monoesters (92%), cholesteryl esters (5%), free fatty acids (1%), fatty alcohols (1%) and cholesterol (1%). The fatty acids and alcohols contained in these lipids were composed principally of homologous series of straight chained omega 7-unsaturated structures (C16-C24), accompanied by lesser proportions of homologous series of saturated (C14-C22) and omega 9-unsaturated (C18-C22) structures.

Animals↗
PubMed1986

Preparation of liposomes from stratum corneum lipids.

Mammalian stratum corneum contains multiple intercellular lipid bilayers that constitute the epidermal water barrier. Unlike all other biologic membranes, the epidermal lamellae do not contain phospholipids, as a result of which the ability of the stratum corneum lipid mixture to form bilayers has been questioned. In the present study, a lipid mixture containing only epidermal ceramides (40%), cholesterol (25%), palmitic acid (25%), and cholesteryl sulfate (10%), approximating the composition of stratum corneum lipids, formed stable, unilamellar liposomes when sonicated at 80 degrees C in buffer containing 100 mM NaCl, 5 mM Tris, and 1 mM EDTA at pH 7.5. The size and form of the liposomes were studied by both freeze fracture and negative staining electron microscopy. Lipid mixtures from which either the palmitic acid or the cholesteryl sulfate were omitted were still capable of forming similar liposomes, but a mixture of ceramides and cholesterol, or ceramides alone, were incapable of forming liposomes. The results indicate that lipid mixtures similar to those found in stratum corneum are capable of forming bilayers at physiologic pH.

Animals↗
PubMed1986

Lipids of chicken epidermis.

The lipids from chicken epidermis were analyzed by a combination of quantitative thin-layer and gas-liquid chromatography and by chemical and spectroscopic methods. The lipid groups present included wax diesters (34%), triglycerides (32%), sterols (11%), phospholipids (11%), nonphosphorus-containing sphingolipids (3%), beta-D-glucosylsterols (3%), 6-O-acyl-beta-D-glucosylsterols (2%), steryl esters (1%), cholesteryl sulfate (1%), and free fatty acids (1%). The major phospholipids were phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, and the sphingolipids included ceramides, glucosylceramides, O-acylceramides, and O-acylglucosylceramides. Glucosylsterols and acylglucosylsterols have not been found in mammalian skin, and may be relevant to the evolutionary history of the epidermal water barrier. The wax diesters contained mainly 16-, 18-, and 20-carbon saturated fatty acids esterified to 20- through 24-carbon threo and erythro 2,3-diols, while the chicken epidermal triglycerides contained some very long-chain (26-40 carbon) saturated fatty acids. These wax diesters and unusual triglycerides may be of significance in human health.

Animals↗
PubMed1985

Uropygiols: confirmation of structure by proton magnetic resonance.

Lipids were extracted from excised uropygial glands of domestic chickens and the wax diesters were isolated by preparative thin-layer chromatography (TLC). The diesters were hydrolyzed and the liberated diols were resolved by boric acid TLC into two fractions. These were investigated by proton magnetic resonance at 360 MHz of the free diols and of their acetonide derivatives. The results showed that the cis and trans acetonides, formed from the erythro and threo isomers of the diols, respectively, could be distinguished by the degree of magnetic nonequivalence of the two acetonide methyl groups in each molecule. On the presumption that the cis isomer should show the greater nonequivalence of the methyl groups, this configuration was assigned to the acetonides of these diols which had the lesser TLC mobility on boric acid/silica gel. This agrees with the assignment of configuration made by earlier workers on the basis of the relative TLC mobility of the diol isomers on boric acid/silica gel, but was contrary to a previous assignment based on gas-liquid chromatographic (GLC) retention times. We conclude that the erythro isomers of the diols are characterized by lower mobility on boric acid TLC, as well as on silica gel TLC, and form acetonides that have longer retention times on GLC, and greater nonequivalence of the acetonide methyl groups in the NMR spectrum, than do the acetonides of the threo isomers.

Animals↗
PubMed1985

Linoleate-rich acylglucosylceramides of pig epidermis: structure determination by proton magnetic resonance.

The structure of the linoleate-rich acylglycosylceramides isolated from pig epidermis has been reinvestigated. Gas-liquid chromatographic analysis of the alditol acetates produced from the sugar component indicated that 90% of the hexose is glucose while the remaining 10% is galactose. The predominance of the beta-D-glucosyl group was confirmed by 360 MHz proton magnetic resonance spectroscopy. The magnetic resonance method was also used to prove that the ester-linked linoleic acid is actually attached to the omega-hydroxyl group of the long chain hydroxyacid, not to the sugar as had been reported previously. A key spectral feature supporting this new structural assignment was a triplet at 3.82 ppm, which indicates methylene protons between another methylene and an ester linkage. After saponification, this signal moved to 3.33 ppm, a chemical shift expected for a methylene bearing a free hydroxyl group. Furthermore, all of the sugar ring protons could be accounted for both before and after acetylation. No evidence was found to suggest that an ester is attached to the sugar ring in the native material. It is concluded that the principal porcine epidermal acylglycosylceramide is 1-beta-D-glucosyl-N-(omega-O-linoleoyl)-triacontanoylsphingosine.

Animals↗
PubMed1984

Differences between inhaled and intravenous carbachol in detecting O3-induced airway effects.

The response of specific lung resistance (SRL) to inhalation of 5 and 10 mg/ml carbachol was compared with the response of SRL to intravenous infusion of 2 and 5 micrograms/kg carbachol before and after a 2-day exposure to 0.5 ppm ozone (O3) in eight conscious sheep. Airway reactivity was defined as the slope of the dose-response curve and airway sensitivity as the largest increase in SRL after carbachol challenge. O3 exposure did not alter mean airway reactivity or mean airway sensitivity as determined by inhalation challenge. In contrast, O3 exposure significantly increased mean airway reactivity by 34% (P less than 0.01) and mean airway sensitivity by 31% (P less than 0.01) as assessed by intravenous challenge. The failure of O3 exposure to enhance responsiveness to inhaled carbachol may have been related to decreased airway penetration of the aerosol, possibly due to mucus hypersecretion. However, O3 exposure may have had a direct effect on the airway smooth muscle, thereby explaining the increased response to infused carbachol.

Aerosols↗