Biomedical subjects

M Suwalsky

Publications and source records attributed to M Suwalsky.

50 records · Page 3Linked to original sources

PubMedDate not supplied

X-ray studies on phospholipid bilayers. X. Interactions with chlortetracycline hydrochloride.

This study deals with the structural perturbations that the antibiotic chlortetracycline hydrochloride (CTC) can produce on phospholipid bilayers. Two multibilayer systems, one built-up of dimyristoylphosphatidylethanolamine (DMPE) and the other of dimyristoylphosphatidylcholine (DMPC) were allowed to interact with different concentrations of CTC in the absence and presence of water. The study was carried out by X-ray diffraction methods and all experiments were done below the phospholipid main transition temperatures. The results showed that CTC produced significant perturbations on DMPC even in the absence of water, whereas they were much milder in DMPE.

Chlortetracycline↗

PubMedDate not supplied

X-ray studies on phospholipid bilayers. XI. Interactions with chloramphenicol.

Chloramphenicol is a widely used antibiotic with low levels of toxicity. However, scanning electron microscopy revealed morphological changes in human erythrocytes when they interacted in vitro with therapeutical concentrations of chloramphenicol. To explain this shape change, a study concerned with the possible interactions of this antibiotic with bilayers built-up of phospholipids located in either side of the red cell membrane was performed by X-ray diffraction. Results indicated that chloramphenicol was unable to perturb in any significant extent the structure of the phospholipids under study. The only noticeable effects were phase transitions produced to dimyristoylphosphatidylethanolamine bilayers.

Chloramphenicol↗

PubMedDate not supplied

X-ray studies on phospholipid bilayers. XII. Interactions of pentachlorophenol with myelin.

Pentachlorophenol (PCP) is a widely used pesticide, particularly for the preservation of wood. Given its high toxicity and resistance to degradation it has become a dangerous environmental pollulant. Due to its high lipophilicity, PCP is able to partition into the lipid bilayer of cell membranes disrupting several vital functions. The present research was concerned with the effects that the chronic administration of PCP could produce in vivo to the sciatic nerve of rats. X-ray diffraction patterns obtained from freshly dissected and dried sciatic nerves of PCP treated rats did not show significant differences in their reflections with respect to those present in the patterns from untreated animals. However, morphological studies performed by optical and electron microscopy showed degenerative changes in about 10% of the A and B type of nerve fibers.

Animals↗

PubMedDate not supplied

X-ray studies on phospholipid bilayers. XIV. Interactions with the antiarrhythmic asocainol.

Asocainol (ASOC) belongs to class I of the antiarrhythmic drugs, i.e., those that exert their action at the level of the sodium channels of the myocardial cell membrane. It has been suggested that their molecular mechanism of action might be through nonspecific interactions with phospholipids that surround the channel proteins. In order to test this hypothesis, ASOC was made to interact with two multibilayer systems, one built-up of dimyristoylphosphatidylcholine (DMPC) and the other of dimyristoylphosphatidylethanolamine (DMPE). These are the type of lipids that are respectively found in the outer and inner monolayers of human erythrocytes. The experiments were carried out in a hydrophobic as well as in a hydrophilic medium below the phospholipid main transition temperatures. The perturbing effect of ASOC upon the bilayer structures was determined by X-ray diffraction. It was found that ASOC was able to fluidize DMPC in both media but not to DMPE.

Anti-Arrhythmia Agents↗

PubMedDate not supplied

X-ray studies on phospholipid bilayers. XIII. Interactions with gentamicin.

This study deals with the structural perturbations that the aminoglycoside antibiotic gentamicin (GENT) can produce to phospholipid bilayers. Two multi-bilayer systems, one built-up of dimyristoylphosphatidylcholine (DMPC) and the other of dimyristoylphosphatidylethanolamine (DMPE) were allowed to interact with GENT. The experiments were performed in both a hydrophobic and a hydrophilic medium below the phospholipid main transition temperatures. X-ray diffraction techniques were used to determine the extent of the perturbation induced by GENT. The maximum effect was attained when GENT interacted with DMPC in the hydrophobic medium. On the other hand, GENT in aqueous solutions was unable to perturb in any significant extent the structure of the phospholipids under study.

Carbohydrate Conformation↗

PubMedDate not supplied

Interaction of the antiarrhythmic drug procainamide with phospholipid bilayers.

Several hypotheses link the molecular mechanism of action of the antiarrhythmic drugs (AAD) that belong to class I to non-specific interactions with phospholipids sited in the neighborhood of sodium channels in the membrane of the myocardium. Procainamide (PROC), one of the least lipophilic drugs of this group, was induced to interact with bilayers of dimyristoylphosphatidylcholine (DMPC) and dimirystoylphosphatidylethanolamine (DMPE), liposomes of DMPC and human erythrocytes. The perturbing effects of PROC upon these systems were respectively determined by X-ray diffraction, fluorescence spectroscopy and scanning electron microscopy. It was found that PROC exerted very little effect upon DMPC and DMPE even at such a high concentration as 10 mM. However, at therapeutical plasma concentrations, PROC induced shape changes in vitro to red cells.

Dimyristoylphosphatidylcholine↗

PubMedDate not supplied

Molecular interactions of quinidine with phospholipid bilayers.

Quinidine (QUIN) is one of the most important and efficient antiarrhythmic drugs (AAD). It belongs to class I, which are the drugs that exert their action at the level of the sodium channels in the membrane of the myocard. Several hypotheses support the idea that the molecular mechanism of action of the AAD is via nonspecific interactions with phospholipids sited in the neighborhood of the channels. In order to probe the validity of these hypotheses, QUIN was made to interact with the phospholipids dimyristoylphosphadidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). These interactions were performed in a hydrophobic and a hydrophilic medium under a wide range of molar ratios. The resulting products were analyzed by X-ray diffraction. QUIN solutions were also made to interact with DMPC liposomes, which were studied by fluorescent spectroscopy. Finally, human erythrocytes which were incubated with QUIN solutions were observed by scanning electron microscopy. The results of these experiments proved that QUIN indeed interacted with phospholipid bilayers.

Anti-Arrhythmia Agents↗

PubMedDate not supplied

Interaction of penicillin G with the human erythrocyte membrane and models.

Penicillin G (PEN) is a widely used antibiotic whose mechanism of action is related to the interference with the synthesis of bacteria cell wall. In order to evaluate its perturbing effect upon human cell membranes PEN was made to interact with human erythrocytes, isolated resealed human erythrocyte membranes and molecular models. The latter were multibilayers of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) as well as DMPC large unilamellar vesicles. These studies were performed by scanning electron microscopy, fluorescence spectroscopy and X-ray diffraction methods. The observed results coincide in that PEN did not exert any significant effect upon the structures of the red cell membrane neither on its molecular models. This is in agreement with its reported lack of major toxicity and hematological reactions.

Dimyristoylphosphatidylcholine↗

PubMedDate not supplied

Interaction of the organochlorine pesticide dieldrin with phospholipid bilayers.

Dieldrin is an organochlorine insecticide highly toxic for human beings. Although its exact mechanism of action is not well known, there is evidence that it acts at the cell membrane level. In fact, the lipophilicity of the pesticide as well as that of the phospholipid bilayer present in biological membranes makes the latter a most likely target for the interaction of dieldrin with living organisms. In order to evaluate its perturbing effect upon cell membranes the pesticide was made to interact with human erythrocytes and molecular models. These studies were performed by scanning electron microscopy on erythrocytes, fluorescence spectroscopy on dimyristoylphosphatidylcholine (DMPC) large unilamellar vesicles and X-ray diffraction on multilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). It was observed that dieldrin particularly interacted with DMPC liposomes and multilayers perturbing its molecular arrangements. However, no effect was noticed on erythrocytes, which might be due to its high cholesterol content.

Cell Membrane↗

PubMedDate not supplied

Interaction of the anticancer drug tamoxifen with the human erythrocyte membrane and molecular models.

Tamoxifen is a non steroidal antiestrogen drug extensively used in the prevention and treatment of hormone-dependent breast cancer. To evaluate its perturbing effect upon cell membranes it was made to interact with human erythrocytes and molecular models. These consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and of dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipids classes located in the outer and inner leaflets of the erythrocyte membrane, respectively. Experiments by fluorescence spectroscopy showed that tamoxifen interacted with DMPC vesicles fluidizing both its polar head and acyl chain regions. These results were confirmed by X-ray diffraction which indicated that tamoxifen perturbed the same regions of the lipid. However, it did not cause any significant structural perturbation to DMPE bilayers. The examination by electron microscopy of human erythrocytes incubated with tamoxifen revealed that they changed their normal discoid shape to stomatocytes. According to the bilayer couple hypothesis, this result means that the drug is inserted in the inner leaflet of the erythrocyte membrane. Given the fact that tamoxifen did not interact with DMPE, it is concluded that it interacted with a protein located in the cytoplasmic moiety of the erythrocyte membrane.

Antineoplastic Agents, Hormonal↗

PubMedDate not supplied

The anticancer drug adriamycin interacts with the human erythrocyte membrane.

Adriamycin is an aminoglycosidic anthracycline antibiotic widely used in the treatment of cancer. Increasing reports point to the involvement of cell membranes in its mechanism of action. The interaction of adriamycin with human erythrocytes was investigated in order to determine the membrane binding sites and the resultant structural perturbation. Electron microscopy revealed that red cells incubated with the therapeutical concentration of the drug in human plasma changed their discoid shape to both stomatocytes and echinocytes. According to the bilayer couple hypothesis, this means that adriamycin was incorporated into either the inner or outer leaflets of the erythrocyte membrane. To explain this unusual result, the drug was incubated with molecular models. One of them consisted of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE) multilayers, representative of phospholipid classes located in the outer and inner leaflets of the erythrocyte membrane, respectively. X-ray diffraction showed that adriamycin interaction perturbed the polar head and acyl chain regions of both lipids. Fluorescence spectroscopy on another model, consisting of DMPC large unilamellar vesicles (LUV), confirmed the X-ray results in that adriamycin fluidized its hydrophobic moiety. It is concluded that adriamycin incorporates into both erythrocyte leaflets affecting its membrane structure.

Adult↗

PubMedDate not supplied

The anticancer drug cisplatin interacts with the human erythrocyte membrane.

Drugs which exert their effects by interacting with DNA cause structural and functional membrane alterations which may be essential for growth inhibition by these agents. This paper describes the interaction of cisplatin with the human erythrocyte membrane and models constituted by bilayers of dimyristoylphosphatidylethanolamine (DMPE) and diacylphosphatidylserine (DAPS), representative of phospholipid classes located in the inner monolayer of the erythrocyte membrane, and of dimyristoylphosphatidylcholine (DMPC), a class present in its outer monolayer. Cisplatin ability to perturb DMPE, DAPS and DMPC bilayer structures was determined by X-ray diffraction and fluorescence spectroscopy. Electron microscopy disclosed that human erythrocytes incubated with 35 microM cisplatin, which is its therapeutical concentration in serum, developed cup-shaped forms (stomatocytes). According to the bilayer couple hypothesis, this means that the drug is inserted into the inner monolayer of the erythrocyte membrane, a conclusion supported by the studies on model systems.

Adult↗

PubMedDate not supplied

Dibucaine-induced modification of sodium transport in toad skin and of model membrane structures.

The interaction of the local anesthetic dibucaine with the isolated toad skin and membrane models is described. The latter consisted of human erythrocytes, isolated unsealed human erythrocyte membranes (IUM), large unilamellar vesicles (LUV) of dimyristoylphosphatidylcholine (DMPC) and phospholipid multilayers built-up of DMPC and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. Results indicate a significant decrease in the potential difference (PD) and in the short-circuit current (Isc) after the application of dibucaine in toad skin, which may be interpreted as reflecting inhibition of the active transport of ions. This finding might be explained on the basis of the results obtained from fluorescence spectroscopy and X-ray diffraction studies on membrane models. In fact, dibucaine induced structural perturbations in IUM, DMPC LUV and phospholipid multilayers. Scanning electron microscopy revealed that dibucaine induced erythrocyte stomatocytosis. According to the bilayer couple hypothesis an echinocytic type of shape change would have been expected given the preferential interaction of dibucaine with DMPC. Although it is still premature to define the molecular mechanism of action of dibucaine, the experimental results confirm the important role played by the phospholipid bilayers in the association of the anesthetic with cell membranes.

Animals↗

PubMedDate not supplied

X-ray studies on phospholipid bilayers. I. Polymorphic forms of dimyristoyl lecithin.

A structural study of the synthetic phospholipid, L-alpha-dimyristoyl lecithin (DML), habs been made by X-ray fiber diffraction methods. Three different types of oriented specimens were prepared. They were X-ray photographed under the same conditions, including temperature and relative humidity. Three different types of diffraction patterns, corresponding to different conformations and/or packing arrangements, were found. They are characterized by their unit cell dimensions, space group, molecular conformations, and packing arrangements.

Dimyristoylphosphatidylcholine↗