Simultaneous Exposure to Intracellular and Extracellular Photosensitizers for the Treatment of Staphylococcus aureus Infections.

Staphylococcus aureus is a serious threat to public health due to the rise of antibiotic resistance in this organism, which can prolong or exacerbate skin and soft tissue infections (SSTIs). Methicillin-resistant S. aureus is a Gram-positive bacterium and a leading cause of SSTIs.

Cellular entry and nuclear targeting by a highly anionic molecular umbrella.

A fluorescently labeled, persulfated molecular umbrella ( 1) has been synthesized from cholic acid, lysine, spermine, and Coumarin 343 and found capable of entering live HeLa cells. The distributions of 1 throughout the cytoplasm and the nucleus were diffuse and punctate, respectively. This finding, together with its ability to cross liposomal membranes by passive diffusion, suggests that passive diffusion plays a significant role in the ability of 1 to enter cells.

Detecting cross talk between two halves of a phospholipid bilayer.

One of the most challenging questions that relates to the structure and function of biological membranes is whether the two halves of the bilayer "talk" to each other. In this letter, we show how the perturbation of the lateral organization of one leaflet of a fluid phospholipid bilayer by an external agent also alters the lateral organization of the adjoining leaflet. In addition, we show that the energy involved in such "cross talk" corresponds to ca.

Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections.

Molecular umbrella compounds may function as novel topical microbicides to prevent human immunodeficiency virus (HIV) and herpes simplex virus (HSV) infections. In a preliminary structure-activity investigation, one umbrella compound, designated Spm8CHAS, was identified which inhibited both HIV and HSV infections with no cellular toxicity. The objectives of the current studies were to define its spectrum of antiviral activity, characterize its mechanism of action, and explore the possibility of combining Spm8CHAS with HIV-specific reverse transcriptase inhibitors.

Cholesterol-phospholipid association in fluid bilayers: a thermodynamic analysis from nearest-neighbor recognition measurements.

The mixing behavior of exchangeable, disulfide-based mimics of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol has been examined as a function of temperature in host membranes made from DPPC and cholesterol in the liquid-disordered phase (ld), in the liquid-ordered phase (lo), and in the liquid-disordered/liquid-ordered coexistence region (ld/lo). In the ld region, lipid mixing was found to be temperature insensitive, reflecting close to ideal behavior. In contrast, a significant temperature dependence was observed in the lo phase from 45 to 60 degrees C, when 35 or 40 mol % sterol was present.

Ethanol-induced reorganization of the liquid-ordered phase: enhancement of cholesterol-phospholipid association.

This paper records what is believed to be the first evidence for the reorganization of the liquid-ordered phase by ethanol. Specifically, ethanol has been found to significantly enhance sterol-phospholipid association in liquid-ordered bilayers derived from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) plus cholesterol and also 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) plus cholesterol. The evidence for such reorganization comes from a series of nearest-neighbor recognition (NNR) experiments that have been carried out, where low concentrations of equilibrating lipid dimers (i.

Molecular umbrella-assisted transport of an oligonucleotide across cholesterol-rich phospholipid bilayers.

A series of molecular umbrella conjugates, derived from cholic acid, deoxycholic acid, spermidine, lysine, and 5-mercapto-2-nitrobenzoic acid, have been synthesized and found capable of transporting an attached 16-mer oligonucleotide (S-dT16) across liposomal membranes made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyldglycerol (POPG), and cholesterol [POPC/POPG/cholesterol (65/5/30; mol/mol/mol, v/v/v)] at 37 degrees C. Those molecular umbrellas containing four choloyl (or deoxycholoyl) groups resulted in significantly faster rates of transport as compared to those containing only two such moieties. A model that accounts for these membrane transport processes is proposed.

Transbilayer complementarity of phospholipids. Proof of principle.

A series of nearest-neighbor recognition (NNR) experiments have been carried out, which provide a rigorous test of the existence of transbilayer complementarity of phospholipids, that is, the ability of phospholipids to select complementary phospholipids from an adjoining monolayer as nearest neighbors. The application of this test to membranes derived from exchangeable phospholipids bearing myristoyl groups (A), stearoyl groups (B), and one stearoyl and one n-dodecyl group (C) in the presence of analogous nonexchangeable templates made from A', B' and C' provides compelling evidence for such complementarity in the physiologically relevant fluid phase.

A chemical sensor for the liquid-ordered phase.

The mixing properties of exchangeable phospholipids, derived from 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, with an exchangeable form of cholesterol have been used to monitor the transition from the liquid-disordered to the liquid-ordered phase in cholesterol-containing bilayers, made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-3-phosphocholine, respectively.

Transbilayer complementarity of phospholipids in cholesterol-rich membranes.

Lipid-lipid interactions across cholesterol-rich phospholipid bilayers were investigated by measuring nearest-neighbor preferences of exchangeable phospholipids derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), in the presence of nonexchangeable dimers (i.e., templates) made from DMPE or DSPE.

Persulfated molecular umbrellas as anti-HIV and anti-HSV agents.

A series of persulfated molecular umbrellas have been synthesized from putrescine, spermidine, spermine, lysine, and cholic acid (1a, 2a, 3a, 4a, and 5a) and their anti-HIV and anti-HSV activities determined. Despite it size, the most active of these conjugates (5a) was able to cross phospholipid bilayers made from 1-palmitoyl-2-oleyol-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG). The unique combination of anti-viral activity, an ability to cross hydrophobic barriers, a lack of cytotoxicity, and a simple three-step synthesis from biogenic starting material suggests that 5a and related conjugates may be exploitable as a novel class of anti-viral agents for systemic and topical applications.

A quantitative assessment of the influence of permanent kinks on the mixing behavior of phospholipids in cholesterol-rich bilayers.

The mixing behavior of a phospholipid containing a cis-cyclopropyl moiety (1) with one that contains two myristoyl groups (3a) has been investigated in fluid bilayers via the nearest-neighbor recognition (NNR) method. In the absence of cholesterol, these lipids mix ideally. In the presence of cholesterol, they show a modest preference for homo-phospholipid association.

Probing the hydration of lipid bilayers using a solvent isotope effect on phospholipid mixing.

Nearest-neighbor recognition experiments, which have been carried out using exchangeable dimers derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine,and 1-palmitoyl-2-oleoyl-sn-glycerophosphoethanolamine, indicate that replacement of H2O by D2O can significantly influence phospholipid mixing, but only in bilayers that are saturated and devoid of cholesterol. These findings, together with those of previous electron spin resonance spin-labeling studies,indicate that mammalian membranes, which are rich in cholesterol and unsaturated phospholipids, are ideal hydrophobic barriers.

Detection of unusual lipid mixing in cholesterol-rich phospholipid bilayers: the long and the short of it.

Nearest-neighbor recognition studies have revealed that favored sterol-phospholipid associations can be reversed in a fluid bilayer that contains relatively long (high melting) and short (low melting) phospholipids, when the sterol content is sufficiently high; that is, like-lipids now become favored nearest-neighbors. A possible origin of this effect is briefly discussed.

Transbilayer complementarity of phospholipids. A look beyond the fluid mosaic model.

Lipid-lipid interactions across a phospholipid bilayer were probed by measuring the nearest-neighbor preferences of exchangeable phospholipid monomers derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in the presence of nonexchangeable DMPE- or DSPE-based dimers. Each of these permanent dimers promoted homophospholipid association to the same extent, whereas the corresponding nonexchangeable monomers were without effect. These results support a model in which the longer phospholipids in one monolayer leaflet preferentially associate with shorter ones in the adjoining monolayer.

[Ruthenium(II)(bpy)(2)L](2+), where L are imidazo[f]-1,10-phenanthrolines: synthesis, photophysics and binding with DNA.

Three Ru(II) complexes of type as [Ru(II)(bpy)(2)L](2+) were synthesized, where L are l,10-phenanthroline derivatives of imidazole (1), having at position 2 alpha-naphthyl (2), 3-methoxy-4-hydroxy-phenyl (3). All complexes show intense MLCT transition both in acetonitrile and in water and also exhibit strong emission at room temperature, which is efficiently quenched by oxygen as well as, to some extent, by water. The binding of complexes 1-3 to calf thymus DNA was investigated by using electronic absorption, steady-state luminescence, luminescence quenching, excited-state lifetime and circular dichroism spectra.

[Diagnostic effect of bronchoalveolar lavage in early lung injury caused by enterogenic infection in rat].

Objective: To study the diagnostic effect of bronchoalveolar lavage in early lung injury by observing changes in inflammatory mediators in early lung injury caused by enterogenic infection.

Methods: Eighty-four Sprague-Dawley rats were randomly divided into infection group and sham-operation group. Cecal ligation and perforation was utilized to produce abdominal infection in rats.

Quantifying the effects of deuterium substitution on phospholipid mixing in bilayer membranes. A nearest-neighbor recognition investigation.

Nearest-neighbor recognition measurements have established that the effects of deuterium substitution on phospholipid mixing are exceedingly small. Thus, the mixing behavior of an exchangeable phospholipid bearing two stearoyl chains with a homologue containing two myristoyl chains in gel-fluid bilayers, fluid bilayers, cholesterol-rich fluid bilayers, and gel-fluid bilayers that have been enriched with cholesterol correspond to a difference in the free energy of mixing that is less than 2.2 cal/mol of hydrogen in all cases.

Fully detachable molecular umbrellas as peptide delivery agents.

A persulfated molecular umbrella, derived from cholic acid and spermidine, has been covalently attached to H-Tyr-D-Ala-Gly-Phe-D-Leu-OH (DADLE) by use of an o-dithiobenzyl carbamate linkage. Treatment of the resulting conjugate (1) with glutathione in solution resulted in the liberation of the free form of the peptide. Addition of 1 to glutathione-entrapped liposomes, prepared from 1-palmitoyl-2-oleyol-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG), and cholesterol [POPC/POPG/cholesterol, 72/4/24 (mol/mol/mol)], resulted in the delivery of DADLE into their aqueous interior.

Kinetic evidence for the existence and mechanism of formation of a barrel stave structure from pore-forming dendrimers.

A dendritic approach to the construction of a homologous series of pore-forming amphiphiles has been developed, based on the use of spermidine, spermine, lysine, and cholic acid. A kinetic analysis of Na+ transport across bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine by three dendritic amphiphiles has provided the strongest evidence to date for a barrel stave structure.

An unusual photosensitizer: dyad of eosin-tris(2,2'-bipyridine)Ru(II).

[structure: see text] A dyad of eosin and tris(2,2'-bipyridine)Ru(II) was prepared, and its photophysical properties were investigated. The photosensitization of eosin is greatly enhanced by introduction of tris(2,2'-bipyridine)Ru(II), which is verified via photooxygenation of anthracene derivatives. The electron-transfer mechanism of photosensitization is also discussed.

[Analysis of platelets in the monitoring of systemic inflammatory response syndrome of critically ill patients].

Objective: To study the clinical significance of the variance of platelets in systemic inflammatory response syndrome(SIRS) of critical illness.

Methods: Two hundred and thirteen critically ill patients in ICU, who suffered from SIRS, sepsis and multiple organ dysfunction syndrome (MODS), were enrolled in this study and divided into two groups, survivor group (n=151) and non-survivor group (n=62). Platelet, white blood cell counts and acute physiology and chronic health evaluation II (APACHE II) score were performed immediately after hospitalization, 3 days, 7 days, and 10 days later.