Biomedical subjects

B Lindman

Publications and source records attributed to B Lindman.

At least 19 recordsLinked to original sources

PubMed2006

The effect of chain length on the melting temperature and size of dialkyldimethylammonium bromide vesicles.

Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to obtain the gel to liquid-crystalline phase transition temperature (Tm) and the apparent hydrodynamic radius (Rh) of spontaneously formed cationic vesicles of dialkyldimethylammonium bromide salts (CnH2n+1)2(CH3)2N+.Br-, with varying chain lengths. The preparation of cationic vesicles from aqueous solution of these surfactants, for n=12, 14, 16 and 18 (DDAB, DTDAB, DHDAB and DODAB, respectively), requires the knowledge of the surfactant gel to liquid-crystalline phase transition temperature, or melting temperature (Tm) since below this temperature these surfactants are poorly or not soluble in water. That series of cationic surfactants has been widely investigated as vesicle-forming surfactants, although C12 and C18, DDAB and DODAB are by far the most investigated from this series. The dependence of Tm of these surfactants on the number n of carbons in the surfactant tails is reported. The Tm obtained by DSC increases non-linearly with n, and the vesicle apparent radius Rh is about the same for DHDAB and DODAB, but much smaller for DDAB.

Alkylation↗

PubMed2005

Polyion adsorption onto catanionic surfaces. A Monte Carlo study.

The adsorption of a single and negatively charged polyion with varying flexibility onto a surface carrying both negative and positive charges representing a charged membrane surface has been investigated by using a simple model employing Monte Carlo simulations. The polyion was represented by a sequence of negatively charged hard spheres connected with harmonic bonds. The charged surface groups were also represented by charged hard spheres, and they were positioned on a hard surface slightly protruding into the solution. The surface charges were either frozen in a liquidlike structure or laterally mobile. With a large excess of positive surface charges, the classical picture of a strongly adsorbed polyion with an extended and flat configuration emerged. However, adsorption also appeared at a net neutral surface or at a weakly negatively charged surface, and at these conditions the adsorption was stronger with a flexible polyion as compared to a semiflexible one, two features not appearing in simpler models containing homogeneously charged surfaces. The presence of charged surface patches (frozen surface charges) and the ability of polarization of the surface charges (mobile surface charges) are the main reasons for the enhanced adsorption. The stronger adsorption with the flexible chain is caused by its greater ability to spatially correlate with the surface charges.

Adsorption↗

PubMed2005

Surface complexation of DNA with insoluble monolayers. Influence of divalent counterions.

DNA interacts with insoluble monolayers made of cationic amphiphiles as well as with monolayers of zwitterionic lipids in the presence of divalent ions. Binding to dioctadecyldimethylammonium bromide (DODAB) or distearoyl-sn-glycero-3-phosphocholine (DSPC) monolayers in the presence of calcium is accompanied by monolayer expansion. For the positively charged DODAB monolayer, this causes a decrease of surface potential, while an increase is observed for the DSPC monolayers. Binding to dipalmitoyl-sn-glycero-3-phosphocholine preserves most of the liquid expanded-liquid condensed coexistence region. The liquid condensed domains adopt an elongated morphology in the presence of DNA, especially in the presence of calcium. The interaction of DNA with phospholipid monolayers is ion specific: the presence of calcium leads to a stronger interaction than magnesium and barium. These results were confirmed by bulk complexation studies.

Animals↗

PubMed2003

Relationship between the physical shape and the efficiency of oligomeric chitosan as a gene delivery system in vitro and in vivo.

BACKGROUND: Chitosans of high molecular weights have emerged as efficient nonviral gene delivery systems, but the properties and efficiency of well-defined low molecular weight chitosans (<5 kDa) have not been studied. We therefore characterized DNA complexes of such low molecular weight chitosans and related their physical shape and stability to their efficiency as gene delivery systems in vitro and in vivo. METHODS: Individual complexes between six different chitosan oligomers (6-, 8-, 10-, 12-, 14- and 24-mers) and fluorescence-labeled T4 DNA were visualized and classified into six physical shapes using video-enhanced fluorescence microscopy. The effects of chitosan chain length, charge ratio (+/-) and solvent properties (pH and ionic strength) on the stability and structure of the complexes were studied. Gene expression in vitro and in vivo were studied using a luciferase reporter gene. RESULTS: Free DNA appeared as extended coils. Chitosan complexes had a variety of physical shapes depending on the experimental conditions. In general, the fraction of complexes that had nonaggregated, globular structures increased with increasing chain length of the chitosan oligomer, increasing charge ratio and reduction of pH (from 6.5 to 3.5). A further increase in charge ratio for globular complexes or a further reduction in pH (to 2.5) increased the fraction of aggregates, indicating a window where pharmaceutically desirable globules are obtained. Gene transfection efficiencies in vitro and in vivo were related to the physical shape and stability of the complexes. Only the 24-mer formed stable complexes that gave a high level of gene expression comparable to that of high molecular weight ultrapure chitosan (UPC) in vitro and in vivo. CONCLUSIONS: Chitosan oligomers form complexes with DNA in a structure-dependent manner. We conclude that the 24-mer, which has more desirable physical properties than UPC, is more attractive as a gene delivery system than the conventional high molecular weight chitosans.

Adjuvants, Pharmaceutic↗

PubMed2002

DNA-lipid systems. A physical chemistry study.

It is well known that the interaction of polyelectrolytes with oppositely charged surfactants leads to an associative phase separation; however, the phase behavior of DNA and oppositely charged surfactants is more strongly associative than observed in other systems. A precipitate is formed with very low amounts of surfactant and DNA. DNA compaction is a general phenomenon in the presence of multivalent ions and positively charged surfaces; because of the high charge density there are strong attractive ion correlation effects. Techniques like phase diagram determinations, fluorescence microscopy, and ellipsometry were used to study these systems. The interaction between DNA and catanionic mixtures (i.e., mixtures of cationic and anionic surfactants) was also investigated. We observed that DNA compacts and adsorbs onto the surface of positively charged vesicles, and that the addition of an anionic surfactant can release DNA back into solution from a compact globular complex between DNA and the cationic surfactant. Finally, DNA interactions with polycations, chitosans with different chain lengths, were studied by fluorescence microscopy, in vivo transfection assays and cryogenic transmission electron microscopy. The general conclusion is that a chitosan effective in promoting compaction is also efficient in transfection.

Cations↗

PubMed2001

Modification of the lyotropic liquid crystalline microstructure of amphiphilic block copolymers in the presence of cosolvents.

This article reviews the results of recent investigations on the macroscopic (phase behavior) and microscopic (microstructure) aspects of the role of cosolvents on the self-assembly of amphiphilic copolymers. A comprehensive account of the systematic studies performed in ternary isothermal systems consisting of a representative poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymer (Pluronic P105, EO37PO58EO37), water and a polar cosolvent (such as glycerol, propylene glycol or ethanol) is presented. The effect of cosolvents on the copolymer phase behavior is quantified in terms of the highest cosolvent/water ratio able to maintain the liquid crystalline structures. The effect of cosolvents on the microstructure of the lyotropic liquid crystals is quantified in terms of the degree of relative swelling per cosolvent content per copolymer content, a parameter that characterizes the given cosolvent and copolymer. The set of correlations on the cosolvent effects on the phase behavior or microstructure to the cosolvent physicochemical characteristics (such as octanol/water partition coefficient or solubility parameter) have led to the development of a hypothesis that accounts for the cosolvent effects on the self-assembly of PEO-PPO-PEO block copolymers and can be used to predict them. The rich structural diversity and the potential for a precise an convenient modification of the lyotropic liquid crystalline microstructure of the PEO-PPO-PEO block copolymers is discussed in comparison to the phase behavior of the low-molecular nonionic surfactants.

Journal Article↗

PubMed2001

Sodium polyacrylate potentiates the anti-adhesion effect of a cellulose-derived polymer.

Available methods for postoperative adhesion prevention are insufficient. A previous study demonstrated that LM-200, a bioadhesive cellulose derivative was effective in reducing adhesions. Increasing the viscosity of a polymer solution enhances the tissue separating properties. Theoretically, a combination of sodium polyacrylate (PA) and LM-200 would give more viscous solutions than LM-200 alone, and thus be more efficacious. Therefore the efficacy of various combinations of LM-200 and PA was investigated. A lesion was created in the peritoneum of mice. The solutions to be tested, or saline, were given intraperitoneally. One week post-operatively, adhesion formation was quantified and expressed as a percentage of the original lesion covered with adhesions. PA (0.01 and 0.03 wt%) given separately did not differ in adhesion reducing effect from LM-200 (p = 0.3710 and 0.3481) but PA (0.1 wt%) resulted in significantly less adhesion formation (p = 0.0004). The effect of LM-200 increased significantly when adding PA (0.01 wt%) (p = 0.0007) or PA (0.03 wt%) (p < 0.0001). When adding PA (0.1 wt%) the effect was even more pronounced (p < 0.0001). The combination of a bioadhesive cellulose derivative and the polymer PA, was effective in reducing postoperative adhesion formation and a dose-dependent increase in efficacy was obtained compared to using the two components separately.

Abdomen↗

PubMed2001

Prevention of adhesions by surfactants and cellulose derivatives in mice.

OBJECTIVE: To evaluate the efficacy of hydrophobically modified ethyl (hydroxyethyl) cellulose (cellulose), sodium hyaluronate (hyaluronate) and phosphatidylglycerol, in the reduction of adhesion formation. DESIGN: Controlled study. SETTING: Experimental academic unit, Sweden. MATERIAL: NMRI mice. Solutions: (1) cellulose, (2) hyaluronate, (3) phosphatidylglycerol, (4) phosphatidylglycerol and cellulose, and (5) phosphatidylglycerol, cellulose and hyaluronate. INTERVENTIONS: A standard lesion was created in the parietal peritoneum in mice. One of the viscous solutions to be tested, or saline, was given intraperitoneally. MAIN OUTCOME MEASURES: Amount of adhesions found one week postoperatively. RESULTS: Cellulose; phosphatidylglycerol and cellulose; and phosphatidylglycerol, cellulose and hyaluronate all significantly reduced the amount of adhesions (p=0.0002, p=0.002, p < 0.0001), as did the hyaluronate alone (p < 0.05). Phosphatidylglycerol alone did not reduce the amount of adhesions. Combining cellulose with phosphatidylglycerol, or with hyaluronate, did not improve efficacy. CONCLUSION: Cellulose and hyaluronate were effective in reducing the formation of adhesions. Combining cellulose with hyaluronate or phosphatidylglycerol or both did not improve efficacy.

Animals↗

PubMed2000

Clinical significance of defective dendritic cell differentiation in cancer.

Defective dendritic cell (DC) function has been described previously in cancer patients and tumor-bearing mice. It can be an important factor in the escape of tumors from immune system control. However, the mechanism and clinical significance of this phenomenon remain unclear. Here, 93 patients with breast, head and neck, and lung cancer were investigated. The function of peripheral blood and tumor draining lymph node DCs was equally impaired in cancer patients, consistent with a systemic rather than a local effect of tumor on DCs. The number of DCs was dramatically reduced in the peripheral blood of cancer patients. This decrease was associated with the accumulation of cells lacking markers of mature hematopoietic cells. The presence of these immature cells was closely associated with the stage and duration of the disease. Surgical removal of tumor resulted in partial reversal of the observed effects. The presence of immature cells in the peripheral blood of cancer patients was closely associated with an increased plasma level of vascular endothelial growth factor but not interleukin 6, granulocyte macrophage colony-stimulating factor, macrophage colony-stimulating factor, interleukin 10, or transforming growth factor-beta and was decreased in lung cancer patients receiving therapy with antivascular endothelial growth factor antibodies. These data indicate that defective DC function in cancer patients is the result of decreased numbers of competent DCs and the accumulation of immature cells. This effect may have significant clinical implications.

Adult↗

PubMed1999

DNA conformational dynamics in the presence of catanionic mixtures.

DNA conformational behavior in the presence of non-stoichiometric mixtures of two oppositely charged surfactants, cetyltrimethylammonium bromide and sodium octyl sulfate, was directly visualized in an aqueous solution with the use of a fluorescence microscopy technique. It was found that in the presence of cationic-rich catanionic mixtures, DNA molecules exhibit a conformational transition from elongated coil to compact globule states. Moreover, if the catanionic mixtures form positively charged vesicles, DNA is adsorbed onto the surface of the vesicles in a collapsed globular form. When anionic-rich catanionic mixtures are present in the solution, no change in the DNA conformational behavior was detected. Cryogenic transmission electron microscopy, as well as measurements of translational diffusion coefficients of individual DNA chains, supported our optical microscopy observations.

Anions↗

PubMed1998

Polymers that reduce intraperitoneal adhesion formation.

BACKGROUND: Viscous macromolecules and phospholipids have been shown to reduce postoperative adhesion formation. The ideal agent, or combination of agents, still remains to be identified. METHODS: The effect of hydrophobically modified ethyl (hydroxyethyl) cellulose (HM-EHEC) and polyquarternium-24 (LM-200), two cellulose-derived polymers, and of sphingomyelin, was examined in an animal model. Adhesions were induced in the parietal peritoneum in a standardized manner and quantity, and the morphology of adhesion formation was evaluated after 7 days. RESULTS: A significant reduction in adhesion formation was seen in animals receiving LM-200 (P=0.013) and HM-EHEC (P=0.012) as a short-term treatment compared with controls given saline, but not in animals receiving sphingomyelin (P=0.733). Additional effects were seen in the animals receiving LM-200 as a prolonged treatment (P< 0.001) compared with controls. There was no difference in the magnitude of the inflammatory response between the groups. CONCLUSION: These results suggest that hydrophobically modified polymers are efficient in reducing adhesions, without affecting the inflammatory response.

Animals↗

PubMed1996

Cytokine control of interstitial collagenase and collagenase-3 gene expression in human chondrocytes.

Human collagenase-3 expression, previously seen only in a breast tumor tissue, is here shown to be expressed in primary human chondrocytes derived from the joint tissue and in transformed human chondrocytes. Its mRNA is inducible by the inflammatory cytokines interleukin-1beta plus tumor necrosis factor-alpha, but not by phorbol 12-myristate 13-acetate and only slightly by the growth factors platelet-derived growth factor and epidermal growth factor. Human synovial fibroblasts, another prominent cell type in the joint tissue, do not produce collagenase-3 message. Expression of the murine collagenase, which is possibly the counterpart of human collagenase-3, is induced by interleukin-1beta plus tumor necrosis factor-alpha, and its full induction requires the presence of the transcription factor, c-FOS. This family of transcription factors also plays a role in induction of human collagenase-3, since it binds to the AP-1 site of this matrix metalloproteinase.

Animals↗

PubMed1996

On the importance of hydroxyl groups in the polar head-group of nonionic surfactants and membrane lipids.

In this review properties of natural membrane lipids and surfactants synthesized from natural substances, such as paraffin chain alcohols and carbohydrates, are compared with those of synthetic surfactants of the polyoxyethylene type. Special attention is paid to the characteristic solution properties of nonionic surfactants with hydroxyl groups as the hydrophilic moiety, including alkyl glyceryl ethers and alkyl glucosides and maltosides, which are compared with those with oxyethylene groups. The major properties of the hydrophilic moiety are lipophobicity and hydrophilicity. Lipophobicity is an important property of oil-soluble surfactants, in particular for the polyoxyethylene alkyl ether type of surfactants where a too high lipophobicity may result in solubility in water.

Carbohydrate Sequence↗

PubMed1990

Deuterium nuclear magnetic resonance studies on the interaction of glycophorin with 1,2-dimyristoylamido-1,2-deoxyphosphatidylcholine.

Membrane dynamics of dimyristoylphosphatidylcholine (DMPC) lipid bilayer which contains glycophorin with an artificial boundary lipid, 1,2-dimyristoylamido-1,2-deoxyphosphatidylcholine (DDPC), was investigated by 2H-NMR technique. For this purpose, both DMPC and DDPC were deuterated at the position of the 8th carbon atom of their acyl chains. Comparing, with DMPC bilayers, DDPC bilayers showed larger deuterium quadrupole splitting (delta nu rho) by approx. 2 kHz. This was explicable in terms of the stabilization of the membrane due to the formation of a strong hydrogen bonding in bilayers. Addition of glycophorin to the DMPC or DDPC single bilayers caused an increase in the delta nu rho value. The delta nu rho value of DMPC/DDPC mixed lipid bilayer was smaller than that of each single lipid bilayer DDPC in the DDPC/DMPC mixed bilayer was not phase-separated but homogeneously distributed. In glycophorin-reconstituted DMPC-d4/DDPC mixed bilayers, the delta nu rho of DMPC-d4 was almost identical to that of the simple DMPC-d4 bilayer. On the other hand, the delta nu rho of DDPC-d4 in the DMPC/DDPC-d4 mixed bilayer increased significantly upon the reconstitution of glycophorin. Judging from these data, we concluded that, in the DDPC/DMPC mixed bilayer which contains glycophorin, DMPC simply behaves as the matrix lipid, while DDPC surrounds glycophorin and certainly plays a role of the boundary lipid.

Chemical Phenomena↗

PubMed1990

Heparin and heparan sulfate delimit nephron formation in fetal metanephric kidneys.

Formation of nephrons from primitive mesenchyme in fetal kidneys is induced by ureteric buds. Nephron induction is closely coordinated with branching morphogenesis of the ureteric bud. Having previously shown that branching of the primitive ureter is associated with de novo synthesis of chondroitin sulfate proteoglycan and release of free heparan sulfate glycosaminoglycan chains, we asked whether glycosaminoglycans influence nephron development. Fetal mouse kidneys were incubated in organ cultures containing heparan sulfate, heparin, chondroitin sulfate, or hyaluronate. After 48 hr the number of nephrons at each developmental stage was enumerated by light microscopic analysis of serial tissue sections. Kidneys incubated in heparin or in heparan sulfate contained up to 10-fold fewer nephrons than did kidneys incubated in control conditions or in chondroitin sulfate or hyaluronic acid. Maturation of nephrons, however, was unaffected. Inhibition of nephron development was associated with binding of labeled heparin to primitive mesenchyme and altered tissue distribution of fibronectin. Branching morphogenesis was impaired in kidneys exposed to heparin but not to heparan sulfate or to de-N-sulfated, N-acetylated heparin. The capacity of glycosaminoglycans to inhibit nephron formation depended on sugar composition and O-sulfation but not GAG chain size or charge density. Thus, heparan sulfate may have the capacity to specifically control formation of nephrons in fetal metanephric kidneys in vitro.

Animals↗

PubMed1986

Vesicle formation in aqueous solutions of bile salt and monoacylglycerol.

We have investigated by means of quasielastic light scattering and freeze-fracture electron microscopy the aggregation behavior of aqueous solutions of taurocholate and monoolein. A spontaneous micelle-to-vesicle transition has been observed upon dilution of a mixed micellar solution. The size and stability of the micelles and vesicles present in these solutions has been studied as a function of the concentration and incubation time.

Freeze Fracturing↗

PubMed1985

Coexistence of simple and mixed bile salt-lecithin micelles: an NMR self-diffusion study.

The aggregation behavior of bile salt and lecithin in aqueous solutions at 20 degrees C was studied from bile salt, lecithin, and aggregate self-diffusion coefficients obtained by means of a Fourier-transform NMR pulsed-gradient spin-echo technique. The results strongly support the coexistence of simple bile salt micelles and mixed bile salt-lecithin micelles under physiologic conditions.

Bile Acids and Salts↗

PubMed1982

NMR studies on parvalbumin phylogeny and ionic interactions.

The inspection of several muscular parvalbumins from different species by two NMR methods (113Cd resonance and 1H relaxation measurements) allows two classes of parvalbumins to be distinguished according to their ion-binding properties. This result is in agreement with the phylogenetic classification of parvalbumins in two series, alpha and beta, which was established on the basis of the primary structures of these proteins. All parvalbumins are characterized by the presence of two primary cationic sites CD and EF, with structural features closely related to those already known on the basis of X-ray crystallographic studies of the beta parvalbumin pI 4.25 from carp muscle. However, parvalbumins of the beta series are characterized by a secondary cation (Ca2+, Mg2+ and other cations) binding site which is absent (or at least inaccessible) in parvalbumins of the alpha series. The major component from thornback ray (pI 4.45) behaves as an alpha parvalbumin as shown by the present NMR studies, although its primary structure suggests a closer similarity with the parvalbumins of the beta series.

Animals↗