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1.
Langmuir ; 36(42): 12435-12450, 2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-33058724

RESUMO

Natural or synthetic polycations are used as biocides or as drug/gene carriers. Understanding the interactions between these macromolecules and cell membranes at the molecular level is therefore of great importance for the design of effective polymer biocides or biocompatible polycation-based delivery systems. Until now, details of the processes at the interface between polycations and biological systems have not been fully recognized. In this study, we consider the effect of strong polycations with quaternary ammonium groups on the properties of anionic lipid membranes that we use as a model system for protein-free cell membranes. For this purpose, we employed experimental measurements and atomic-scale molecular dynamics (MD) simulations. MD simulations reveal that the polycations are strongly hydrated in the aqueous phase and do not lose the water shell after adsorption at the bilayer surface. As a result of strong hydration, the polymer chains reside at the phospholipid headgroup and do not penetrate to the acyl chain region. The polycation adsorption involves the formation of anionic lipid-rich domains, and the density of anionic lipids in these domains depends on the length of the polycation chain. We observed the accumulation of anionic lipids only in the leaflet interacting with the polymer, which leads to the formation of compositionally asymmetric domains. Asymmetric adsorption of the polycation on only one leaflet of the anionic membrane strongly affects the membrane properties in the polycation-membrane contact areas: (i) anionic lipid accumulates in the region near the adsorbed polymer, (ii) acyl chain ordering and lipid packing are reduced, which results in a decrease in the thickness of the bilayer, and (iii) polycation-anionic membrane interactions are strongly influenced by the presence and concentration of salt. Our results provide an atomic-scale description of the interactions of polycations with anionic lipid bilayers and are fully supported by the experimental data. The outcomes are important for understanding the correlation of the structure of polycations with their activity on biomembranes.

2.
Langmuir ; 32(19): 5004-18, 2016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27115556

RESUMO

Interactions between polyethylenimines (PEIs) and phospholipid membranes are of fundamental importance for various biophysical applications of these polymers such as gene delivery. Despite investigations into the nature of these interactions, their molecular basis remains poorly understood. In this article, we combined experimental methods and atomistic molecular dynamics (MD) simulations to obtain comprehensive insight into the effect of linear and branched PEIs on zwitterionic and anionic bilayers used as simple models of mammalian cellular membranes. Our results show that PEIs adsorb only partially on the surface of zwitterionic membranes by forming hydrogen bonds to the lipid headgroups, whereas a large part of the polymer chains dangles freely in the aqueous phase. In contrast, PEIs readily adhere to and insert into the anionic membrane. The attraction of the polymer chains to the membrane is due to electrostatic interactions as well as hydrogen bonding between the amine groups of PEI and the phosphate groups of lipids. These interactions were found to induce a substantial reorganization of the bilayer in the polymer vicinity due to the reorientation of lipid molecules. The lipid headgroups were pulled toward the center of the membrane, which can facilitate transmembrane translocations of anionic lipids. Furthermore, the PEI-lipid interactions affect the stability of liposomal dispersions, but we did not see any evidence of disruption of the vesicular structures into small fragments at polymer concentrations typically used in gene therapy. Our results provide a detailed molecular-level description of the lipid organization in the membrane in the presence of polycations that can be useful in understanding their mechanisms of in vitro and in vivo cytotoxicity.


Assuntos
Membrana Celular/química , Lipídeos de Membrana/química , Polietilenoimina/química , Ligação de Hidrogênio , Conformação Molecular , Simulação de Dinâmica Molecular , Água/química
3.
Chem Phys Lipids ; 263: 105417, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950675

RESUMO

Chondroitin sulfates (CSs) are important components of the extracellular matrix and side chains of membrane proteoglycans. These polysaccharides are, therefore, likely to interact with plasma membranes and play a significant role in modulating cellular functions. So far, the details of the processes occurring at the interface between the extracellular matrix and cellular membranes are not fully understood. In this study, we used experimental methods and atomic-scale molecular dynamics (MD) simulations to reveal the molecular picture of the interactions between CS and phosphocholine (PC) membranes, used as a simplified model of cell membranes. MD simulations reveal that the polysaccharide associates to the PC bilayer as a result of electrostatic interactions between the positively charged quaternary ammonium groups of choline and the negatively charged sulfate groups of CS. Compared to an aqueous medium, the adsorbed polysaccharide chains adopt more elongated conformations, which facilitates the electrostatic interactions with the membrane, and have a high degree of freedom to change their conformations and to adhere to and detach from the membrane surface. Penetrating slightly between the polar groups of the bilayer, they form a loosely anchored layer, but do not intrude into the hydrophobic region of the PC bilayer. The CS adsorption spread the PC headgroups apart, which is manifested by an increase in the value of the area pre lipid. The expansion of the lipid polar groups weakens the dispersion interactions between the lipid acyl chains. As a result, the lipid membrane in the membrane-polysaccharide contact areas becomes more fluid. Our outcomes may help to understand in detail the interaction of chondroitin sulfate with zwitterionic membranes at the molecular level, which is of biological interest since many biological processes depend on lipid-CS interactions.

4.
Langmuir ; 28(1): 676-88, 2012 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-22085465

RESUMO

The interactions between synthetic polycations and phospholipid bilayers play an important role in some biophysical applications such as gene delivery or antibacterial usage. Despite extensive investigation into the nature of these interactions, their physical and molecular bases remain poorly understood. In this Article, we present the results of our studies on the impact of a hydrophobically modified strong polycation on the properties of a zwitterionic bilayer used as a model of the mammalian cellular membrane. The study was carried out using a set of complementary experimental methods and molecular dynamic (MD) simulations. A new polycation, poly(allyl-N,N-dimethyl-N-hexylammonium chloride) (polymer 3), was synthesized, and its interactions with liposomes composed of 2-oleoyl-1-palmitoyl-sn-glycero-3-phosphocholine (POPC) were examined using dynamic light scattering (DLS), zeta potential measurements, and cryo-transmission electron microscopy (cryo-TEM). Our results have shown that polymer 3 can efficiently associate with and insert into the POPC membrane. However, it does not change its lamellar structure, as was demonstrated by cryo-TEM. The influence of polymer 3 on the membrane functionality was studied by leakage experiments applying a fluorescence dye (calcein) encapsulated in the phospholipid vesicles. The MD simulations of model systems reveal that polymer 3 promotes formation of hydrophilic pores in the membrane, thus increasing considerably its permeability.


Assuntos
Lipídeos/química , Poliaminas/química , Espectroscopia de Ressonância Magnética , Simulação de Dinâmica Molecular , Polieletrólitos , Espectrofotometria Infravermelho
5.
Animals (Basel) ; 13(1)2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36611766

RESUMO

The aim of this study was to examine the influence of the level (1, 3, and 5 mg I/kg) and source of iodine (KI, Ca(IO3)2, and KIO3) on thyroid hormone and immunoglobulin concentrations in the blood serum of laying hens alongside a histological picture of the thyroid. In the first, birds were fed grain-soybean meal mixtures, and in the second, two kinds of diets based on corn-soybean or corn-soybean-rapeseed meal were applied. In the experiments, we determined the levels of the blood serum thyroid hormones fT3 and fT4, as well as the morphological structure of the thyroid gland. In the second experiment, the concentration of immunoglobulins in blood serum was assayed. In both experiments, no influence of iodine source on thyroid hormone concentration was observed. However, increasing the iodine level in the full mixture and adding rapeseed meal in both experiments caused an increase in fT3 concentration. Increasing I-addition in both experiments led to a decrease in thyroid gland follicle diameter. Rapeseed meal inclusion (at a level of 10%) to the complete hen mixture led to an increase in thyroid gland follicle diameter. Applying KIO3 as an iodine source in both experiments caused a decrease in the thyroid gland height of follicle epithelial cells. Immunoglobulin concentrations in the serum were not affected by experimental factors. The results suggest that the methodologies of studies on the bioavailability of minerals and the corresponding analytical methods require unification. The lack of such standardization makes it impossible to engage in a satisfactory discussion of the results and exchange experiences.

6.
Carbohydr Polym ; 297: 119999, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36184131

RESUMO

Hydrophobically modified chondroitin sulfate (CS) is widely used in the preparation of nano-sized drug delivery systems. Herein, the behavior of amphiphilic CSs in aqueous media and the drug accumulation inside the formed micelle-like structures were studied using experimental methods and molecular dynamics simulations. In particular, we focused on the impact of the degree of substitution (DS) with hydrophobic groups and the presence of drug on the morphology of the nanostructures and their molecular organization. Our results show that with increasing DS, the morphology of the amphiphilic CS nanostructures changes from irregular, loosely packed nanogels to cylindrical micelles with a core-shell architecture. These structures can efficiently accumulate hydrophobic drugs. However, the drug molecules preferentially locate at the interface between the hydrophobic part and the hydrophilic corona formed by the CS chains. Our work provides detailed information that may be relevant to the development of amphiphilic polysaccharide-based drug delivery systems.


Assuntos
Sulfatos de Condroitina , Micelas , Sulfatos de Condroitina/química , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Nanogéis , Água
7.
ACS Omega ; 6(18): 12168-12178, 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34056370

RESUMO

Nanoparticles made of amphiphilic block copolymers are commonly used in the preparation of nano-sized drug delivery systems. Poly(styrene)-block -poly(acrylic acid) (PS-PAA) copolymers have been proposed for drug delivery purposes; however, the drug loading capacity and cytotoxicity of PS-PAA nanoparticles are still not fully recognized. Herein, we investigated the accumulation of a model hydrophobic drug, curcumin, and its spatial distribution inside the PS-PAA nanoparticles. Experimental methods and atomistic molecular dynamics simulations were used to understand the molecular structure of the PS core and how curcumin molecules interact and organize within the PS matrix. The hydrophobic core of the PS-PAA nanoparticles consists of adhering individually coiled polymeric chains and is compact enough to prevent post-incorporation of curcumin. However, the drug has a good affinity for the PS matrix and can be efficiently enclosed in the PS-PAA nanoparticles at the formation stage. At low concentrations, curcumin is evenly distributed in the PS core, while its aggregates were observed above ca. 2 wt %. The nanoparticles were found to have relatively low cytotoxicity to human skin fibroblasts, and the presence of curcumin further increased their biocompatibility. Our work provides a detailed description of the interactions between a hydrophobic drug and PS-PAA nanoparticles and information on the biocompatibility of these anionic nanostructures which may be relevant to the development of amphiphilic copolymer-based drug delivery systems.

8.
Langmuir ; 26(19): 15076-9, 2010 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-20804190

RESUMO

Dioctadecyldimethylammonium bromide (DODAB) is a double-chained quaternary ammonium surfactant that assembles in water into bilayer structures. This letter reports the molecular dynamics (MD) computer simulations of the DODAB bilayer at 25 °C. The simulations show that the surfactant membrane arranges spontaneously into the rippled phase (P(ß)(')) at that temperature. The ordering within the chain fragment closest to the hydrophilic head (carbon atoms 1-5) is relatively low. It grows significantly for the carbon atoms located in the center of the membrane (atoms 6-17). The C6-C17 chain fragments are well aligned and tilted by ca. 15° with respect to the bilayer normal.

9.
Antioxidants (Basel) ; 9(11)2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171823

RESUMO

The objective of the study was to test the effect of diets supplemented with ß-alanine, L-histidine, and carnosine on the histidine dipeptide content and the antioxidative status of chicken breast muscles and blood. One-day-old Hubbard Flex male chickens were assigned to five treatments: control diet (C) and control diet supplemented with 0.18% L-histidine (ExpH), 0.3% ß-alanine (ExpA), a mix of L-histidine\ß-alanine (ExpH+A), and 0.27% carnosine (ExpCar). After 28 days, chicken breast muscles and blood samples were analyzed for the antioxidant enzyme activity (catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD)), carnosine and anserine content, amino acid profile, and anti-radical activity (ABTS, DPPH, ferric reducing antioxidant power (FRAP)). The results of the study showed that carnosine supplementation effectively increased body weight and breast muscle share in chicken carcasses. Carnosine and L-histidine supplementation with or without ß-alanine increased carnosine content in chicken breast muscles up to 20% (p = 0.003), but the boost seems to be too low to affect the potential antioxidant capacity and amino acid content. The ß-alanine-enriched diet lowered dipeptide concentration in chicken blood serum (p = 0.002) and activated catalase in chicken breast muscles in relation to the control group (p = 0.003). It can be concluded that histidine or dipeptide supplementation of chicken diets differently affected the total antioxidant potential: in breast muscles, it increased dipeptide content, while in blood cell sediment (rich in erythrocytes), increased SOD and GPx activities were observed.

10.
Int J Pharm ; 591: 120031, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33130219

RESUMO

Micro- and nanostructures prepared from biodegradable homopolymers and amphiphilic block copolymers (AmBCs) have found application as drug-delivery systems (DDSs). The ability to accumulate a drug is a very important parameter characterizing a given DDS. This work focuses on the impact of DDS size, the packing of polymer chains in the DDS, and drug - polymer matrix compatibility on the hydrophobic drug - loading capacity (DLC) of nano/microcarriers prepared from a biodegradable polymer or its copolymer. Using experimental measurements in combination with atomistic molecular dynamics simulations, an analysis of curcumin encapsulation in microspheres (MSs) from polylactide (PLA) homopolymer and nanoparticles (NPs) from PLA-block-poly(2-methacryloyloxyethylphosphorylcholine) AmBC was performed. The results show that curcumin has good affinity for the PLA matrix due to its hydrophobic nature. However, the DLC value is limited by the fact that curcumin only accumulates in the peripheral part of these structures. Such uneven drug distribution in the PLA matrix results from the non-homogeneous density of MSs (non-uniform packing of the polymer chains in the coil). The results also indicate that the MSs can retain a greater amount of hydrophobic drug compared to the NPs, which is associated with the formation of drug aggregates inside the PLA microparticles.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Portadores de Fármacos , Tamanho da Partícula , Poliésteres , Polietilenoglicóis
11.
ACS Biomater Sci Eng ; 5(2): 780-794, 2019 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33405839

RESUMO

Polycations are an attractive class of macromolecules with promising applications as drug/gene carriers and biocides. The chemical structure and concentration of a polycation determine its interaction with cellular membranes and, hence, are crucial parameters for designing efficient nontoxic polycations. However, the interaction of polycations with biomembranes at the molecular level and the corresponding free-energy landscape is not well understood. In this work, we investigate the molecular mechanism of interaction between a strong polycation substituted with alkyl moieties and zwitterionic membranes via long-time-scale all-atom molecular dynamics simulations and free-energy calculations combined with Langmuir monolayer, atomic force microscopy, and calcein-release experimental measurements. We found that the membrane activity of the polycation and its ability to induce pores in the membranes can be attributed to the polycation-induced changes in the bilayer organization, such as reduced membrane thickness, increased disorder of the acyl chains, reduced packing, and electrostatic field gradients between membrane leaflets. These changes facilitate the penetration of water into the membrane and the formation of aqueous defects/pores. The calculated free-energy profiles indicate that the polycation lowers the nucleation barrier for pore opening and the free energy for pore formation in a concentration-dependent manner. Above the critical coverage of the membrane, the polycation nucleates spontaneous pores in zwitterionic membranes. Our work demonstrates the potential of combining enhanced sampling methods in MD simulations with experiments for a quantitative description of various events in the polycation-membrane interaction cycle, such as strong adsorption on the membrane due to hydrophobic and electrostatic interactions, and pore formation.

12.
J Phys Chem B ; 122(28): 7080-7090, 2018 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-29927603

RESUMO

Nanoparticles made of amphiphilic block copolymers comprising biodegradable core-forming blocks are very attractive for the preparation of drug-delivery systems with sustained release. Their therapeutic applications are, however, hindered by low values of the drug-loading content (DLC). The compatibility between the drug and the core-forming block of the copolymer is considered the most important factor affecting the DLC value. However, the molecular picture of the hydrophobic drug-copolymer interaction is still not fully recognized. Herein, we examined this complex issue using a range of experimental techniques in combination with atomistic molecular dynamics simulations. We performed an analysis of the interaction between itraconazole, a model hydrophobic drug, and a poly(ethylene glycol)-poly(lactide- co-glycolide) (PEG-PLGA) copolymer, a biodegradable copolymer commonly used for the preparation of drug-delivery systems. Our results clearly show that the limited capacity of the PEG-PLGA nanoparticles for the accumulation of hydrophobic drugs is due to the fact that the drug molecules are located only at the water-polymer interface, whereas the interior of the PLGA core remains empty. These findings can be useful in the rational design and development of amphiphilic copolymer-based drug-delivery systems.


Assuntos
Portadores de Fármacos/química , Itraconazol/química , Nanopartículas/química , Poliésteres/química , Polietilenoglicóis/química , Difusão Dinâmica da Luz , Interações Hidrofóbicas e Hidrofílicas , Itraconazol/metabolismo , Simulação de Dinâmica Molecular , Água/química
13.
J Phys Chem B ; 121(30): 7318-7326, 2017 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-28678504

RESUMO

Interaction of polycations with lipid membranes is a very important issue in many biological and medical applications such as gene delivery or antibacterial usage. In this work, we address the influence of hydrophobic substitution of strong polycations containing quaternary ammonium groups on the polymer-zwitterionic membrane interactions. In particular, we focus on the polymer tendency to adsorb on or/and incorporate into the membrane. We used complementary experimental and computational methods to enhance our understanding of the mechanism of the polycation-membrane interactions. Polycation adsorption on liposomes was assessed using dynamic light scattering (DLS) and zeta potential measurements. The ability of the polymers to form hydrophilic pores in the membrane was evaluated using a calcein-release method. The polymer-membrane interaction at the molecular scale was explored by performing atomistic molecular dynamics (MD) simulations. Our results show that the length of the alkyl side groups plays an essential role in the polycation adhesion on the zwitterionic surface, while the degree of substitution affects the polycation ability to incorporate into the membrane. Both the experimental and computational results show that the membrane permeability can be dramatically affected by the amount of alkyl side groups attached to the polycation main chain.


Assuntos
Lipossomos/química , Poliaminas/química , Adsorção , Compostos de Amônio/química , Microscopia Crioeletrônica , Difusão Dinâmica da Luz , Interações Hidrofóbicas e Hidrofílicas , Lipossomos/metabolismo , Simulação de Dinâmica Molecular , Poliaminas/metabolismo , Polieletrólitos
14.
J Phys Chem B ; 109(42): 19664-75, 2005 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-16853543

RESUMO

The hydration of sulfonated polyimide membranes in their protonated form is probed by infrared spectrometry using a recently described method. The membranes considered are the homopolymer, made of identical sulfonated repeat units, and two block copolymers composed of these units plus similar ones with no sulfonic groups in two different proportions. The experiments consist of registering series of spectra of these membranes at various hygrometries of the surrounding atmosphere. The quantitative analysis of the evolution of these spectra allows one to measure precisely the water uptake and to define in terms of chemical reactions the various hydration mechanisms that are active at a definite value of the hygrometry. It shows how the dried homopolymer significantly differs from the two dried block copolymers: in the homopolymer, a good proportion of SO(3)H groups that represent 83% of sulfonate groups, cannot establish H-bonds on C=O groups that are in a relatively small number. As a consequence, all coexisting SO(3)(-) groups are H-bonded to single H(3)O(+) cations with no extra H(2)O molecules. In both dried block copolymers, each SO(3)H group (60% of the sulfonate groups) establishes H-bonds on C=O groups that are in a sufficiently great number. These H-bonds stabilize these SO(3)H groups, and coexisting SO(3)(-) groups are H-bonded to cations that are found in the form of H(5)O(2)(+) or H(7)O(3)(+) that contain several H(2)O molecules. When the hygrometry increases, these differences get less marked but can be precisely defined.

15.
J Phys Chem B ; 119(22): 6646-57, 2015 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-25965670

RESUMO

Sterically stabilized liposomes (SSLs) (PEGylated liposomes) are applied as effective drug delivery vehicles. Understanding the interactions between hydrophobic compounds and PEGylated membranes is therefore important to determine the effectiveness of PEGylated liposomes for delivery of drugs or other bioactive substances. In this study, we have combined fluorescence quenching analysis (FQA) experiments and all-atom molecular dynamics (MD) simulations to study the effect of membrane PEGylation on the location and orientation of 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin (p-THPP) that has been used in our study as a model hydrophobic compound. First, we consider the properties of p-THPP in the presence of different fluid phosphatidylcholine bilayers that we use as model systems for protein-free cell membranes. Next, we studied the interaction between PEGylated membranes and p-THPP. Our MD simulation results indicated that the arrangement of p-THPP within zwitterionic membranes is dependent on their free volume, and p-THPP solubilized in PEGylated liposomes is localized in two preferred positions: deep within the membrane (close to the center of the bilayer) and in the outer PEG corona (p-THPP molecules being wrapped with the polymer chains). Fluorescence quenching methods confirmed the results of atomistic MD simulations and showed two populations of p-THPP molecules as in MD simulations. Our results provide both an explanation for the experimental observation that PEGylation improves the drug-loading efficiency of membranes and also a more detailed molecular-level description of the interactions between porphyrins and lipid membranes.


Assuntos
Interações Hidrofóbicas e Hidrofílicas , Lipossomos/química , Polietilenoglicóis/química , Porfirinas/química , Conformação Molecular , Simulação de Dinâmica Molecular , Espectrometria de Fluorescência
16.
J Phys Chem B ; 118(1): 144-51, 2014 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-24350646

RESUMO

Poly(ethylene glycol) (PEG) is a polymer commonly used for functionalization of drug molecules to increase their bloodstream lifetime, hence efficacy. However, the interactions between the PEGylated drugs and biomembranes are not clearly understood. In this study, we employed atomic-scale molecular dynamics (MD) simulations to consider the behavior of two drug molecules functionalized with PEG (tetraphenylporphyrin used in cancer phototherapy and biochanin A belonging to the isoflavone family) in the presence of a lipid bilayer. The commonly held view is that functionalization of a drug molecule with a polymer acts as an entropic barrier, inhibiting the penetration of the drug molecule through a cell membrane. Our results indicate that in the bloodstream there is an additional source of electrostatic repulsive interactions between the PEGylated drugs and the lipid bilayer. Both the PEG chain and lipids can bind Na(+) ions, thus effectively becoming positively charged molecules. This leads to an extra repulsive effect resulting from the presence of salt in the bloodstream. Thus, our study sheds further light on the role of PEG in drug delivery.


Assuntos
Genisteína/química , Bicamadas Lipídicas/química , Polietilenoglicóis/química , Porfirinas/química , Simulação de Dinâmica Molecular , Estrutura Molecular
17.
J Phys Chem B ; 116(16): 4889-97, 2012 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-22482736

RESUMO

Natural or synthetic porphyrins are being used as photosensitizers in photodiagnosis (PD) and photodynamic therapy (PDT) of malignancies and some other diseases. Understanding the interactions between porphyrins and cell membranes is therefore important to rationalize the uptake of photosensitizers and their passive transport through cell membranes. In this study, we consider the properties of hematoporphyrin (Hp), a well-known photosensitizer for PD and PDT, in the presence of a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer that we use as a model system for protein-free cell membranes. For this purpose, we employed 200 ns atomic-scale molecular dynamics (MD) simulations for five systems containing the neutral (Hp(0)) or the dianionic form (Hp(2-)) of Hp and the POPC bilayer. MD simulations allowed one to estimate the position, orientation, and dynamics of Hp molecules inside the membrane. The dye molecules were found to reside in the phospholipid headgroup area close to the carbonyl groups of the POPC acyl chains. Their orientations were dependent on the protonation state of two propionic groups. Hp(2-) was found to have a lower affinity to enter the membrane than the neutral form. The dianions, being in the aqueous phase, formed stable dimers with a strictly determined geometry. Our results fully supported the experimental data and provide a more detailed molecular-level description of the interactions of photosensitizers with lipid membranes.


Assuntos
Hematoporfirinas/química , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Fosfatidilcolinas/química , Água/química
18.
Curr Drug Metab ; 12(7): 667-78, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21561431

RESUMO

L-Carnitine is an endogenous molecule involved in fatty acid metabolism, biosynthesized within the human body using amino acids: L-lysine and L-methionine, as substrates. L-Carnitine can also be found in many foods, but red meats, such as beef and lamb, are the best choices for adding carnitine into the diet. Good carnitine sources also include fish, poultry and milk. Essentially, L-carnitine transports the chains of fatty acids into the mitochondrial matrix, thus allowing the cells to break down fat and get energy from the stored fat reserves. Recent studies have started to shed light on the beneficial effects of L-carnitine when used in various clinical therapies. Because L-carnitine and its esters help reduce oxidative stress, they have been proposed as a treatment for many conditions, i.e. heart failure, angina and weight loss. For other conditions, such as fatigue or improving exercise performance, L-carnitine appears safe but does not seem to have a significant effect. The presented review of the literature suggests that continued studies are required before L-carnitine administration could be recommended as a routine procedure in the noted disorders. Further research is warranted in order to evaluate the biochemical, pharmacological, and physiological determinants of the response to carnitine supplementation, as well as to determine the potential benefits of carnitine supplements in selected categories of individuals who do not have fatty acid oxidation defects.


Assuntos
Carnitina/metabolismo , Carnitina/farmacologia , Estresse Oxidativo/fisiologia , Animais , Carnitina/uso terapêutico , Suplementos Nutricionais , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/fisiologia , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/fisiologia , Estresse Oxidativo/efeitos dos fármacos
19.
J Phys Chem B ; 114(47): 15483-94, 2010 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-21058682

RESUMO

Interactions between small organic molecules and lipid or cell membranes are important because of their role in the distribution of biologically active substances inside the membrane and their permeation through the cell membranes. In the current paper, we have explored the effect of the attachment of long hydrocarbon tails on the behavior of small organic molecule inside the lipid membrane. Naphthalene with two decyloxy groups attached at the opposite sites of the ring (2,6-bis(decyloxy)naphthalene, 3) was synthesized and incorporated into phosphatidylcholine (PC) vesicles. Fluorescence methods as well as molecular dynamic (MD) simulations were used to estimate the position, orientation, and migration of compound 3 in PC bilayer. It was found that the naphthalene ring of compound 3 resides in the upper acyl chain region of the bilayer and the hydrocarbon tails are directed to the center of the bilayer. As was shown with cryotransmission electron microscopy (cryo-TEM), such lipidlike conformation enables compound 3 to be incorporated into liposomes at a very high content without their disintegration. Moreover, compound 3 can migrate from one leaflet to other. The mechanism of this process is, however, different from that characteristic of the flip-flop event of lipid molecules in the membrane. Finally, the possible application of compound 3 as a rotational molecular probe for monitoring fluidity of liposomal membrane in the acyl side chain region was checked by studies of the effect of cholesterol on the fluorescence anisotropy of 3.


Assuntos
Bicamadas Lipídicas/química , Naftalenos/química , Simulação de Dinâmica Molecular , Naftalenos/síntese química , Fosfatidilcolinas/química , Teoria Quântica , Espectrometria de Fluorescência
20.
Artigo em Inglês | MEDLINE | ID: mdl-11867291

RESUMO

The purpose of the present investigation is to compare the ability of chickens, ducks and geese to digest and utilise a diet containing a relatively large amount of barley (40%) rich in beta-glucan (18 g kg(-1)) and NSP (137 g kg(-1)) of which 35 g kg(-1) were soluble non-starch polysaccharides (NSP). The diets were offered to the birds (50 chickens, 40 ducks and 30 geese) in the period from hatching to 42 days of age. The digestibility of NSP was measured during the last week of the growth period using chromic oxide as an indigestible marker. Emphasis was on total NSP, soluble and insoluble NSP and their constituent sugar residues (rhamnose, fucose, arabinose, xylose, mannose, galactose, glucose and glucuronic acid). The degradation of NSP to short chain fatty acids (SCFA) was determined in the small intestine, caeca and large intestine. Although significant differences were found between species to the extent of degradation of individual soluble, insoluble and total NSP residues in the small intestine and caeca, the overall apparent digestibility of total NSP was similar (39-42%). On the basis of the digestibility of the NSP sugar residues and the formation of SCFA in the gut, the energy value of NSP was estimated on 2.8, 3.2 and 2.7 kJ g(-1) NSP ingested (P>0.05) in chickens, ducks and geese, respectively. On average, NSP contributed approximately 3.5% of metabolisable energy (ME) in the three poultry species.


Assuntos
Ração Animal , Hordeum , Polissacarídeos/farmacocinética , Aves Domésticas/metabolismo , Animais , Peso Corporal , Carboidratos/farmacocinética , Ceco/metabolismo , Galinhas , Digestão , Patos , Ingestão de Alimentos , Metabolismo Energético , Ácidos Graxos/metabolismo , Gansos , Concentração de Íons de Hidrogênio , Intestino Grosso/metabolismo , Intestino Delgado/metabolismo , Masculino , Aves Domésticas/crescimento & desenvolvimento , Amido/farmacocinética
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