Intrahepatic cholestasis due to Treponema pallidum in an immunocompetent patient / Colestasis intrahepática por Treponema pallidum en paciente inmunocompetente

Hepatitis due to Treponema pallidum is a rare entity and its diagnosis represents a clinical challenge. Treponema pallidum should be considered as a presumptive etiology in all patients with acute liver disease, when other frequent causes have been ruled out. We present the case of a young, immunocompetent patient with elevated values in his liver tests, a cholestatic pattern, and maculopapular lesions on his palms and soles. Given his clinical picture, diagnostic tests, and response to the antimicrobial therapy, a diagnosis of cholestasis due to secondary syphilis has been established. It is important to include secondary syphilis within the possible causes of acute liver disease.

La hepatitis por Treponema pallidum es una entidad poco frecuente y su diagnóstico representa un reto clínico. Treponema pallidum debe considerarse como etiología presuntiva en todo paciente con enfermedad hepática aguda, en el cual se hayan descartado otras causas más frecuentes. Se presenta el caso de un paciente joven,  inmunocompetente, quien presentó elevación de los valores de las pruebas hepáticas con patrón colestásico y lesiones maculopapulares en palmas y plantas. Dado su cuadro clínico, las pruebas diagnósticas y la respuesta a la terapia antimicrobiana instaurada, se estableció el diagnóstico de colestasis por una sífilis secundario sifilítiao. Es importante incluir la sífilis secundaria entre las posibles causas de enfermedad hepática aguda.

Colestasis intrahepática por Treponema pallidum en paciente inmunocompetente / Intrahepatic cholestasis due to Treponema pallidum in an immunocompetent patient

La hepatitis por Treponema pallidum es una entidad poco frecuente y su diagnóstico representa un reto clínico. Treponema pallidum debe considerarse como etiología presuntiva en todo paciente con enfermedad hepática aguda, en el cual se hayan descartado otras causas más frecuentes. Se presenta el caso de un paciente joven, inmunocompetente, quien presentó elevación de los valores de las pruebas hepáticas con patrón colestásico y lesiones maculopapulares en palmas y plantas. Dado su cuadro clínico, las pruebas diagnósticas y la respuesta a la terapia antimicrobiana instaurada, se estableció el diagnóstico de colestasis por una sífilis secundario sifilítiao. Es importante incluir la sífilis secundaria entre las posibles causas de enfermedad hepática aguda.

Hepatitis due to Treponema pallidum is a rare entity and its diagnosis represents a clinical challenge. Treponema pallidum should be considered as a presumptive etiology in all patients with acute liver disease, when other frequent causes have been ruled out. We present the case of a young, immunocompetent patient with elevated values in his liver tests, a cholestatic pattern, and maculopapular lesions on his palms and soles. Given his clinical picture, diagnostic tests, and response to the antimicrobial therapy, a diagnosis of cholestasis due to secondary syphilis has been established. It is important to include secondary syphilis within the possible causes of acute liver disease.

Polyphilicity-An Extension of the Concept of Amphiphilicity in Polymers.

Recent developments in synthetic pathways as simple reversible-deactivation radical polymerization (RDRP) techniques and quantitative post-polymerization reactions, most notoriously 'click' reactions, leading to segmented copolymers, have broadened the molecular architectures accessible to polymer chemists as a matter of routine. Segments can be blocks, grafted chains, branchings, telechelic end-groups, covalently attached nanoparticles, nanodomains in networks, even sequences of random copolymers, and so on. In this review, we describe the variety of the segmented synthetic copolymers landscape from the point of view of their chemical affinity, or synonymous philicity, in bulk or with their surroundings, such as solvents, permeant gases, and solid surfaces. We focus on recent contributions, current trends, and perspectives regarding polyphilic copolymers, which have, in addition to hydrophilic and lipophilic segments, other philicities, for example, towards solvents, fluorophilic entities, ions, silicones, metals, nanoparticles, and liquid crystalline moieties.

Self-organization of poly(ethylene oxide) on the surface of aqueous salt solutions.

It is demonstrated that stable Langmuir films of poly(ethylene oxide) (PEO) can be formed up to surface pressures of 30 mN m(-1) when potassium carbonate K2CO3 is added to the aqueous subphase. Generally, PEO homopolymer cannot stay on the water surface at a surface pressure ≥10 mN m(-1) due to its high water solubility. To prepare stable monolayer films, PEO can be modified with hydrophobic moieties. However, by exploiting the salting out effect by adding certain salts (K2CO3 or MgSO4) into the aqueous subphase, not only very stable films but also unusual self-organization can be achieved by the PEO homopolymer on the surface of the aqueous solution. Thus, a series of OH-terminated PEOs is found to form a stable monolayer at K2CO3 concentrations of 2 M and above in the aqueous subphase, and the stability of the film increases with an increase in K2CO3 concentration. Hysteresis experiments are also carried out. During the phase transition induced by progressive compression, self-organization into well-defined domains with sizes in the micrometer range are observed, and with further compression and holding of the film for 30 min and above the microdomains transform into a crystalline morphology as visualized by Brewster angle microscopy.

Enantiopure chiral poly(glycerol methacrylate) self-assembled monolayers knock down protein adsorption and cell adhesion.

Chirality plays a fundamental role not only in biological systems, but also in synthetic materials intended for bio-applications. Self-assembled monolayers (SAMs) are prepared on gold surfaces through a "grafting to" method from racemic or enantiopure chiral poly(glycerol methacrylate)s (PGMA(rac), PGMA(R), and PGMA(S)), having a thiol endgroup. Such SAMs constitute a chemically and structurally well-defined model substrate for studying protein adsorption and cell adhesion as a function of the polymer chirality. Surface plasmon resonance measurements reveal that PGMA SAMs greatly reduce the adsorption of bovine serum albumin (BSA) compared to bare gold surfaces. Interestingly, enantiopure SAMs based on PGMA(R) or PGMA(S) show a significantly larger reduction in BSA adsorption than PGMA(rac)-covered surfaces. Studies with the monocytic cell line THP-1 show a similar relationship between enantiopurity of PGMA SAMs and the extent of cell adhesion. Ellipsometry and Raman spectroscopy measurements indicate that SAMs formed by PGMA(rac) have a higher grafting density compared to SAMs of PGMA(R) and PGMA(S). This seems to be due to the ability of PGMA(rac) to form more intermolecular hydrogen bonds among polymer chains compared to the enantiopure PGMAs. Circular dichroism spectroscopy provide evidence that enantiopure polymers adopt a chiral ordered conformation, most likely helical, in aqueous solutions. It is concluded that a higher water content of SAMs formed by enantiopure PGMA(S) and PGMA(R) SAMs arises from the macromolecular chiral conformation adopted by their enantiopure PGMA chains, and it is the decisive reason for the reduced BSA adsorption and cell adhesion as compared to PGMA(rac) SAMs.

Block copolymers in giant unilamellar vesicles with proteins or with phospholipids.

Biocompatible, highly water-soluble, nonionic, amphiphilic block copolymers having different hydrophobic blocks and architectures, but similar molecular size and chemical nature of the hydrophilic blocks, were investigated to check for their ability to form hybrid giant unilamellar vesicles with proteins, and for their interactions with giant unilamellar phospholipid vesicles (GUV). PGM14-b-PPO34-b-PGM14 (PGM-PPO-PGM) consists of a poly(propylene oxide) middle block and outer poly(glycerol monomethacrylate) blocks. Ch-PEG32-b-IPG18 (Ch-PEG-IPG) and Ch-PEG30-b-hbPG17 (Ch-PEG-hbPG) have a linear poly(ethylene glycol) block, linked to a cholesterol end group and to a linear (IPG) or hyperbranched (hbPG) polyglycerol block. Fluorescently-labelled polymers were synthesised to image and analyse the self-assembling and interaction processes using confocal laser scanning microscopy (CLSM). By implementing a novel strategy for polymersomes formation the copolymers were found to spontaneously form giant unilamellar vesicles with proteins in aqueous solution. Furthermore, the investigation of the interaction of the block copolymers with different phospholipid GUVs provided detailed information about the structure-behaviour relationship. Additionally, it was found that these neutral copolymers are able to cross artificial and natural phospholipid membranes.

Formation of 2D spherulites in Langmuir films of amphiphilic T-shaped liquid crystals.

Langmuir films of facial T-shaped amphiphilic liquid crystals were studied at the air-water interface. The liquid crystals were composed of three incompatible segments: a central rigid rodlike p-terphenyl (TP) group, two flexible hydrophobic n-alkyl terminal chains of identical length linked through ether bonds, and one hydrophilic lateral chain of three ethylene oxide units with a carboxyl end group. In order to determine the influence of the alkyl chain length on the characteristics of condensed films three TPs having n-alkyl chains with eight (TP8/3), ten (TP10/3) or 16 (TP16/3) carbon atoms were investigated. Surface pressure - mean molecular area isotherms revealed clear differences. TP8/3 and TP10/3 exhibit an extended plateau region where a phase transition from monolayer to multilayer takes place. On the other hand, the TP16/3 isotherm showed a distinct maximum ('spike') corresponding to a surprising surface crystallization process which is reported for the first time for a Langmuir film of a liquid crystal. Brewster angle microscopy clearly confirmed these differences: TP8/3 and TP10/3 formed circular domains with liquid crystalline order, while TP16/3 formed well-defined two-dimensional polycrystalline spherulites which are fractured after further compression. The film thickness determined by X-ray reflectivity measurements correlated with a multilayer formation for TP10/3. The morphology of Langmuir-Blodgett (LB) films transferred onto silicon wafers and studied by atomic force microscopy also confirmed the striking different behavior (multilayer formation vs. 2D crystallization) of the TPs under investigation.

Formation of structured polygonal nanoparticles by phase-separated comb-like polymers.

A simple approach using comb-like polymers that undergo nanophase separation between the polyester backbone and the stearoyl side chains is proposed for the preparation of structured non-spherical nanoparticles from a nanoemulsion. Depending on the degree of esterification of the OH groups of poly(glycerol adipate) differently ordered nanostructures is obtained. A perfect lamellar arrangement is obtained for polymers with a high degree of esterification and leads to spherical nanoparticles with an internal onion-like structure. However, when the degree of esterification is only 20 mol%, polygonal nanoparticles with an internal pseudo-hexagonal structure are obtained. The differences in the nanoparticle shapes are related to the volume fraction of the paraffinic pool.

Spontaneous Formation of Giant Bioactive Protein-Block Copolymer Vesicles in Water.

A novel strategy for the formation, without the need for organic solvents, of stable giant proteopolymersomes from the highly water-soluble triblock copolymer poly(2,3-dihydroxypropyl methacrylate)-b-poly(propylene oxide)-b-poly(2,3-dihydroxypropyl methacrylate) and the protein assembly streptavidin (SAv)-biotin-bovine serum albumin is presented. The method yields bioactive polymersomes with sizes in the tens of micrometers range having an SAv-functionalized membrane, thus, offering binding sites for a broad range of biotin conjugates. The vesiculation mechanism and the distribution of polymer and proteins in the proteopolymersomes membrane are investigated by confocal laser scanning microscopy and supported by molecular dynamic simulations.

Noninvasive in vivo monitoring of the biofate of 195 kDa poly(vinyl alcohol) by multispectral fluorescence imaging.

A comprehensive knowledge of the in vivo fate of polymers is essential for their potential application in humans. In this study, the body distribution, accumulation, and elimination processes of intraperitoneally (ip) administered poly(vinyl alcohol) (PVA) in mice were investigated in detail. Two derivatives of PVA (195 kDa) having covalently bound fluorescent dye labels were synthesized and used to follow PVA in vivo by noninvasive multispectral fluorescence imaging over several months. Detailed ex vivo fluorescence imaging was performed additionally and combined with tissue accumulation studies using confocal microscopy. Filtration and confocal imaging at appropriate synthetic membranes, used as models for glomerular filtration, confirmed a considerable PVA permeation. This investigation yields new scientific findings about the fate of PVA in vivo. PVA accumulated in fat tissue at high levels, which suggests that PVA is suitable not only for abdominal surgeries but also for controlled release applications after ip or subcutaneous injection.

In-vivo studies on intraperitoneally administrated poly(vinyl alcohol).

The fate of poly(vinyl alcohol) (PVA, 195,000 g/mol) was studied in rabbits and nude mice after intraperitoneal (i.p.) administration. In-vivo fluorescence imaging using nude mice allowed for studies of tetramethylrhodamine labeled PVA distribution in the body and tracking the urinary excretion. The excreted PVA was studied in detail after collecting the urine of rabbits over a time period of 28 days. The PVA was separated from the urine by dialysis and analyzed by FTIR spectroscopy, (1)H-NMR spectroscopy, and size exclusion chromatography (SEC). Even after extensive dialysis, it was found that the excreted PVA showed a characteristic brownish color. The spectroscopic techniques revealed that this color was caused by the urine pigment (a metabolite of bilirubin) that could not be separated completely from the PVA. SEC showed unambiguously that the PVA with the very high molar mass had a glomerular permeability in the kidneys. Simultaneously, histological studies of the kidneys and the liver demonstrated that the tissues did not show any obvious damage.

Adsorbed and spread films of amphiphilic triblock copolymers based on poly(2,3-dihydroxypropyl methacrylate) and poly(propylene oxide) at the air-water interface.

The adsorption behavior of the novel type of water-soluble amphiphilic triblock copolymers PGMA-b-PPO-b-PGMA at the air-water interface is studied by tensiometry and monolayer techniques. In particular, (PGMA(14))(2)-PPO(34) is found to be strongly surface active (Pi(max) approximately 38.1 mN/m, cmc approximately 50 microM), in spite of having a relatively short hydrophobic PPO middle block. Time-dependent adsorption measurements exhibit two different types of adsorption kinetics depending on concentration. Monolayers deposited by spreading form pseudo-Langmuir films, in spite of (PGMA(14))(2)-PPO(34) high water solubility. The transition from a dilute to a semidilute regime during compression of the monolayer occurs at a mean molecular area around 4424 A(2)/molecule (Pi = 0.03 mN/m). Above Pi = 2.1 mN/m (1291 A(2)/molecule) PGMA segments begin to change from a flat two-dimensional conformation to loops and tails protruding into the subphase. The onset of the conformational change for PO segments takes place at a mean molecular area of approximately 625 A(2)/molecule (Pi = 15.5 mN/m). In the range Pi approximately 21.4-23.8 mN/m the PPO blocks adopt a three-dimensional conformation. A new methodology for the estimation of the amount of polymer absorbed at the interface (Gamma) as a function of the solution bulk concentration from tensiometry measurements in pseudo-Langmuir spread films is proposed. The obtained adsorption isotherm suggests the occurrence of a conformational change of the PPO block segments toward conformations having smaller molar areas for actual bulk concentrations above 6.0 x 10(-8) M. The surface tension versus polymer bulk concentration curve (gamma vs ln C) exhibits a sharp break at low concentrations, which is probably due to a conformational change within the adsorbed layer. A theoretical multiple conformation model reproduces satisfactorily the experimental dependency of surface pressure on polymer adsorption (Pi vs Gamma) at low and intermediate ranges of polymer concentrations in the solution bulk. A ratio of approximately eight between the average molecular areas at low coverage and at full coverage confirms that (PGMA(14))(2)-PPO(34) chains are highly flexible and able to adopt very different conformations during the transition of the adsorbed polymer film from a highly diluted to a nearly saturated state. There are some experimental indications that nonequilibrium effects might determine a bimodal conformational distribution within the adsorbed (PGMA(14))(2)-PPO(34) layer, which departs substantially from the equilibrium adsorption picture.

Infrared reflection absorption spectroscopy coupled with Brewster angle microscopy for studying interactions of amphiphilic triblock copolymers with phospholipid monolayers.

Novel water-soluble amphiphilic triblock copolymers poly(glycerol monomethacrylate)-b-poly(propylene oxide)-b-poly(glycerol monomethacrylate) (PGMA-b-PPO-b-PGMA) were synthesized because of their expected enhanced ability to interact with biological membranes compared to the well-known poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PEO-b-PPO-b-PEO) block copolymers. Their bulkier hydrophilic PGMA blocks might induce a disturbance in the packing of liquid-crystalline lipid bilayers in addition to the effect caused by the hydrophobic PPO block alone. To gain a better insight into the polymer-membrane interactions at the molecular level, the adsorption kinetics and concomitant interactions of (PGMA14)(2-)PPO(34) with model membranes of dipalmitoylphosphatidylcholine (DPPC) and dimyristoylphosphatidylcholine (DMPC) were monitored using infrared reflection absorption spectroscopy (IRRAS) coupled with Brewster angle microscopy (BAM) and surface pressure (pi) measurements. The maximum penetration surface pressure of ca. 39 mN/m suggests that (PGMA14)(2-)PPO(34) is able to insert into lipid monolayers even above the so-called monolayer-bilayer equivalent pressure of 30-35 mN/m. Copolymer adsorption to a liquid-expanded DPPC-d62 monolayer proceeds in a two-step mechanism: (i) initially only the more hydrophobic PPO middle block penetrates the lipid monolayer; (ii) following the liquid-expanded-liquid-condensed (LE-LC) phase transition, the bulky PGMA hydrophilic blocks are dragged into the headgroup region as the PPO block inserts further into the fatty acid region. The adsorption kinetics is considerably faster for DMPC-d54 monolayers due to their higher fluidity. Copolymer adsorption to an LC-DPPC-d62 monolayer leads to a change in the monolayer packing by forcing the lipid alkyl chains into a more vertical orientation, their tilt angle with respect to the surface normal being reduced from initially 30 degrees +/- 3 degrees to 18 degrees +/- 3 degrees. BAM images rule out macroscopic phase separation and show that coalescence of DPPC-d62 LC domains takes place at relatively low surface pressures of pi > or = 23 mN/m, suggesting that (PGMA14)(2-)PPO (34) partitions into both LE as well as LC domains.