Intrinsic BMP Antagonist Gremlin-1 as a Novel Circulating Marker in Pulmonary Arterial Hypertension.

Gremlin-1, an intrinsic antagonist of bone morphogenetic protein (BMP) signaling, has been implicated in the pathophysiology of pulmonary arterial hypertension (PAH). However, it is unknown whether gremlin-1 can be detected in the circulation of PAH patients and whether it is associated with patients' functional status and outcome. With a mean level of 242 ± 24 ng/ml, gremlin-1 levels of 31 PAH patients were significantly elevated compared to 151 ± 18 ng/ml in 15 age- and gender-matched healthy subject (p = 0.016). In PAH patients, increasing gremlin-1 levels correlated with N-terminal prohormone of brain natriuretic peptide levels (r = 0.608, p < 0.001) and inversely with the 6-minute walking distance (r = -0.412, p = 0.029). Furthermore, gremlin-1 significantly stratified survival in PAH patients (p = 0.015). Gremlin-1 may represent a new biomarker for PAH which can be linked directly to the underlying pathomechanism. Elevated levels of gremlin-1 are associated with patients' functional status and survival, thus gremlin-1 neutralization could represent a potential therapeutic strategy to increase BMPR2 signaling.

Diflunisal salts of bupivacaine, lidocaine and morphine. Use of the common ion effect for prolonging the release of bupivacaine from mixed salt suspensions in an in vitro dialysis model.

The present work describes the characterization of diflunisal salts of the analgesic agents bupivacaine, lidocaine, and morphine including their solubility behaviour and release characteristics from solutions and selected salt suspensions in vitro using the rotating dialysis cell model. The solubility of the 1:1 salts at pH 7.4 differed by a factor of 9 with the bupivacaine and lidocaine salts representing the poorest and most soluble salt (0.73 and 6.6mM, respectively). Common ion effects were observed for the diflunisal salts of bupivacaine and morphine when various concentrations of the lidocaine-diflunisal salt were present in aqueous buffer (pH 7.4). The most pronounced salting-out effect was observed for the poorest soluble salt. From Setschenow type plots apparent salting-out constants of 265 M(-1) (bupivacaine) and 54.7 M(-1) (morphine) were calculated. After instillation of mixed salt suspensions comprising the diflunisal salts of bupivacaine and lidocaine into the donor cell of the release model, lidocaine appeared rapidly in the acceptor phase. After clearance of lidocaine from the donor cell, equal and constant fluxes of bupivacaine and diflunisal were observed. The residence times of bupivacaine within the donor compartment was prolonged with increasing lidocaine-diflunisal salt load in the mixed suspensions whereas the slopes of the linear part of the bupivacaine release profiles were affected to a minor extent only. The obtained data indicate that local multimodal analgesia, characterized by rapid onset and extended duration of action, can be achieved upon injection of mixed suspensions of salts differing with respect to aqueous solubility comprising a common ion into a small body compartment (such as the joint cavity).

Novel Carbon Nanotube/Cellulose Composite Fibers As Multifunctional Materials.

Electroconductive fibers composed of cellulose and carbon nanotubes (CNTs) were spun using aqueous alkaline/urea solution. The microstructure and physical properties of the resulting fibers were investigated by scanning electron microscopy, Raman microscopy, wide-angle X-ray diffraction, tensile tests, and electrical resistance measurements. We found that these flexible composite fibers have sufficient mechanical properties and good electrical conductivity, with volume resistivities in the range of about 230-1 Ohm cm for 2-8 wt % CNT loading. The multifunctional sensing behavior of these fibers to tensile strain, temperature, environmental humidity, and liquid water was investigated comprehensively. The results show that these novel CNT/cellulose composite fibers have impressive multifunctional sensing abilities and are promising to be used as wearable electronics and for the design of various smart materials.