Biomedical subjects

K M Abu-Salah

Publications and source records attributed to K M Abu-Salah.

8 recordsLinked to original sources

PubMed1996

Inhibition of erythrocyte membrane ATPases with antisickling and anaesthetic substances and ionophoric antibiotics.

A study has been carried out into the effects of clinically important antisickling and anaesthetic substances and ionophoric antibiotics on the activities of (Na+, K+)- and (Ca+2, Mg2+)-ATPases of the human erythrocyte membrane. In general, these drugs, with the exception of nystatin, inhibit both types of enzymic activities but with varying degrees of efficacy. (Ca2+, Mg2+)-ATPases was more sensitive to the lipophilic anaesthetics and (Na+,K+)-ATPase to the ionophoric antibiotic, amphotericin B. These results are explained in the light of the partition coefficients of these drugs in erythrocyte membranes, their effects on the fluidity of the erythrocytes membranes, the changes they induce in the permeability properties of erythrocytes and the subsequent effect of procaine on sickling of erythrocytes, and their potential interaction with specific membrane components.

Adenosine Triphosphatases↗

PubMed1996

Amphotericin B: an update.

Amphotericin B is the most important clinically and best defined chemically of the macrolide heptaene antibiotics. A fermentation product of the soil actinomycetes Streptomyces nodosus, amphotericin B binds selectively to ergosterol in the cell membrane of susceptible fungi, inducing changes in permeability that can produce lethal cell injury. Available since 1960, amphotericin B remains the treatment of choice for most serious systemic fungal infections. This review highlights some important aspects of the physicochemical properties of amphotericin B and their utilisation in its quantitative determination in biological fluids. Its mechanism of action is re-appraised in the light of recent results with regard to its effects on the physical and functional properties of synthetic and natural membranes. Attempts to reduce its toxic effects to host cells and to improve its therapeutic index are evaluated. In addition, the therapeutic values of amphotericin B, apart from its antibiotic activity, are discussed.

Amphotericin B↗

PubMed1992

Lipid composition and fluidity of the erythrocyte membrane in copper-deficient rats.

The influence of dietary copper on lipid composition, phospholipid fatty acid and protein profiles and fluidity of the erythrocyte membranes of rats is reported. In general Cu deficiency in rats induced some changes in the phospholipid-fatty acid profile of erythrocyte membranes when compared with Cu-adequate animals. Stearic (18:0) and docosadienoic (22:2n-3) acids contents, for example, were significantly increased (P < 0.001) while oleic (18:1n-9) and linolenic (18:3n-3) acid contents were significantly depressed (P < 0.001) as a result of Cu deficiency. Moreover the cholesterol:phospholipids molar ratio and the cholesterol (mol):membrane proteins (mg) ratio in Cu-deficient rats were, to different degrees, significantly lower than in animals fed on Cu-adequate diets. In addition, diets deficient in Cu led to a reduction in erythrocyte membrane fluidity (P < 0.001) as assessed by the intramolecular excimer fluorescence of 1,3-di(1-pyrenyl) propane. However, no significant alteration in the phospholipid:protein ratio was observed as a result of differences in dietary treatment. The pattern of erythrocyte membrane proteins obtained with sodium dodecyl sulphate-polyacrylamide gel electrophoresis did not seem to be influenced by Cu-deficient diets.

Animals↗

PubMed1992

Alteration of the permeability of the human erythrocyte membrane to cations by liposome-incorporated amphotericin B.

Some effects of liposome-incorporated amphotericin B on the permeability of the human erythrocyte membrane to potassium and sodium ions is reported. The influence of cholesterol and amphotericin B in causing a shift towards smaller and larger liposomes, respectively, is also described. Phosphatidylcholine liposomes containing amphotericin B in a molar ratio of 7.4 +/- 0.1 (mean +/- SD) antibiotic to 1000 phospholipid reduced the initial rates of K+ and Na+ transport across the erythrocyte membrane to 40 +/- 2.6% and 0%, respectively, of their rates in the presence of comparable concentrations of free amphotericin B. Amphotericin B incorporated into liposomes (8.2 +/- 0.15 mumol antibiotic per 1000 mumol total lipid) composed of cholesterol and phosphatidylcholine (in a molar ratio of 3:7) reduced the initial rate of K+ transport to 19 +/- 0.8% of its value measured in the presence of a comparable concentration of free antibiotic. These results suggest that liposomes containing specified amounts of amphotericin B, especially liposomes also containing cholesterol in addition to phosphatidylcholine, could be used as a method of controlling K+ transport across the erythrocyte and possibly other types of cellular membranes, thereby limiting antibiotic toxicity to some mammalian tissues.

Amphotericin B↗

PubMed1991

Perturbation of the fluidity of the erythrocyte membrane with ionophoric antibiotics and lipophilic anaesthetics.

The fluidity of the rat erythrocyte membrane was evaluated by measurement of excimer fluorescence of an intra-molecular forming fluorophore, 1,3-di(1-pyrenyl)propane. The polyene ionophoric antibiotics, amphotericin B and nystatin, were found to fluidize the erythrocyte membrane, as assessed by the increase in the excimer/monomer fluorescence intensity ratio, by 42 and 13%, respectively, compared with control samples. In contrast, of the peptide ionophoric antibiotics, valinomycin demonstrated about twice the effect which gramicidin A had on depressing the fluidity of the erythrocyte membrane. On the other hand, the general lipophilic anaesthetics, propanidid and althesin, led to an increase, by 70 and 32%, respectively, while the local anaesthetic, procaine, led to a decrease by 20%, in the fluidity of the erythrocyte membrane. These results were explained in the light of the partition coefficients determined for these drugs in decane and native membranes, their affinities for specific membrane components and the changes which they induce in the permeability properties of erythrocyte and other biological membranes.

Anesthetics↗

PubMed1988

Influence of amphotericin B on the transport of phosphate, sulphate and potassium ions across the human erythrocyte membrane.

Some effects of the clinically important fungicidal antibiotic amphotericin B on the transport of phosphate, sulphate and potassium ions across the membrane of the human erythrocyte were investigated. In general, amphotericin B inhibited the transport of the anions to about the same degree and stimulated the transport of the cation. At low concentrations, the inhibition of both phosphate and sulphate ion transport was concentration-dependent. A plateau was reached at 47 and 52% transport for phosphate and sulphate, respectively, beyond which no further inhibition was obtained. In contrast, the initial rate of potassium ion release from erythrocytes was stimulated. This effect was also concentration-dependent. The observed stimulatory effect on cation efflux was attributed to penetration of the antibiotic into the membrane of the erythrocyte, leading to the formation of specific channels. The inhibition of transport of anions, however, was attributed to alteration in the fluidity of the lipid bilayer consequent to channel formation.

Amphotericin B↗

PubMed1985

Comparison of water exposed area of cholera toxin when free in solution and bound to liposomes containing the ganglioside GM1.

Membrane impermeable diazocoupling reagents were used for studying the water exposure of subunits (alpha, beta, gamma) of cholera toxin (CT) when bound to liposomes containing the ganglioside GM1 (Lip-GM1). The interaction between CT with Lip-GM1 shielded the binding region in particular, since a maximum of one amino acid residue on each beta subunit was modifiable. When CT was labeled free in solution five residues of each beta subunit can be coupled, but it produced loss of binding ability. New area of beta subunit was exposed to reagents after having removed alpha subunit. This labeling may serve as a tool to assess the topology of CT upon binding with Lip-GM1.

Chemical Phenomena↗

PubMed1977

Labelling of egg phosphatidylcholine vesicles and myelin membrane with a photoreactive lipophilic reagent.

The preparation and isolation of [3H]phenyl azide, a photosensitive non-polar probe, is reported. The reagent partitions into the lipid bilayer of egg phosphatidylcholine vesicles and bovine myelin membranes. On photoactivation to generate the nitrene grouping, as much as 90% of the covalently attached label is associated with the fatty acyl residues of the constituent phospholipid molecules. The remainder is found in the polar head groups. The cholesterol component of myelin membranes is also heavily labelled. These results suggest that such reagents may be used to probe the hydrophobic regions of natural membranes.

Animals↗