Brain natriuretic peptide in pulmonary arterial hypertension: biomarker and potential therapeutic agent

B-type natriuretic peptide (BNP) is a member of the natriuretic peptide family, a group of widely distributed, but evolutionarily conserved, polypeptide mediators that exert myriad cardiovascular effects. BNP is a potent vasodilator with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. Circulating levels of BNP correlate with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH). Elevated plasma BNP levels are associated with increased mortality in patients with PAH and a fall in BNP levels after therapy is associated with improved survival. These findings have important clinical implications in that a noninvasive blood test may be used to identify PAH patients at high-risk of decompensation and to guide pulmonary vasodilator therapy. BNP also has several biologic effects that could be beneficial to patients with PAH. However, lack of a convenient method for achieving sustained increases in circulating BNP levels has impeded the development of BNP as a therapy for treating pulmonary hypertension. New technologies that allow transdermal or oral administration of the natriuretic peptides have the potential to greatly accelerate research into therapeutic use of BNP for cor pulmonale and pulmonary vascular diseases. This review will examine the basic science and clinical research that has led to our understanding of the role of BNP in cardiovascular physiology, its use as a biomarker of right ventricular function and its therapeutic potential for managing patients with pulmonary vascular disease

Ambrisentan for the treatment of pulmonary arterial hypertension

Ambrisentan is an endothelin receptor antagonist (ERA) that was recently approved for treatment of pulmonary arterial hypertension (PAH). Endothelin (ET) is a potent vasoconstrictor with mitogenic, hypertrophic and pro-inflammatory properties that is upregulated in pulmonary hypertensive diseases. The biologic effects of ET are mediated by 2 cell surface receptors termed ETA and ETB. ETA mediates the vasoconstrictor effect of ET on vascular smooth muscle, whereas ETB is expressed primarily on vascular endothelial cells where it induces nitric oxide synthesis and acts to clear ET from the circulation. Ambrisentan is the first ETA selective ERA approved for use in the US. Recently published clinical trials in patients with PAH demonstrate improvement in functional capacity and pulmonary hemodynamics similar to other ETA selective and non-selective ERAs. Its once daily dosing and lower incidence of serum aminotransferase elevation offer potential advantages over other ERAs, but further experience with this agent is needed to fully understand its long-term efficacy and safety. This review discusses the endothelin family of proteins and receptors and their role in the pathophysiology of pulmonary hypertensive diseases. It also examines the development process, safety profile and clinical trials that have resulted in ambrisentan being approved for treatment of PAH

The ammonite genus Diaziceras Spath, 1921, from the Campanian of KwaZulu-Natal, South Africa, and Madagascar

The ammonite genus Diaziceras Spath, 1921, and the type species, D. tissotiaeforme are revised and referred to the subfamily Lenticeratinae Hyatt, 1900, of the family Sphenodiscidae Hyatt, 1900. Skoumalia Summesberger, 1979, is interpreted as a junior synonym of Diaziceras. Diaziceras guillantoni Hourcq, 1949, and D. spathi Hourcq, 1949, are regarded as synonyms of D. tissotiaeforme, and all are referred to the Lower Campanian on the basis of records from Madagascar

Cretaceous faunas from Zululand and Natal, South Africa. The ammonite genus Codazziceras Etayo-Serna, 1979

A new species of the Coniacian ammonite genus Codazziceras Etayo-Serna, 1979, previously known with certainty only from Colombia, is described from the St Lucia Formation of northern KwaZulu-Natal

Cretaceous faunas from Zululand and Natal, South Africa. A new species of the ammonite genus Salaziceras Breistroffer, 1936, from the Lower Cenomanian Mzinene Formation

A diminutive ammonite collected by E.C.N. Van Hoepen from the Cenomanian part of the Mzinene Formation of the Skoenberg in northern KwaZulu-Natal, is described as Salaziceras simplex sp. nov., and interpreted as one of the last survivors of the genus

Diagnosis and Management of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension is a rare disease, which requires a high index of suspicion to diagnose when patients initially present. Initial symptoms can be nonspecific and include complaints such as fatigue and mild dyspnea. Once the disease is suspected, echocardiography is used to estimate the pulmonary arterial (PA) pressure and to exclude secondary causes of elevated PA pressures such as left heart disease. Right heart catheterization with vasodilator challenge is critical to the proper assessment of pulmonary hemodynamics and to determine whether patients are likely to benefit from vasodilator therapy. Pathologically, the disease is characterized by deleterious remodeling of the distal pulmonary arterial and arteriolar circulation, which results in increased pulmonary vascular resistance. In the last fifteen years, medications from three different classes have been approved for the treatment of pulmonary arterial hypertension. These include the prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors

Cretaceous faunas from Zululand and Natal, South Africa. Systematic palaeontolgy and stratigraphical potential of the Upper Campanian-Maastrichtian Inoceramidae (Bivalvia)

Thirty three species of Inoceramidae, of which two are new, are described from KwaZulu. They fall into four zonal assemblages that can be correlated with sequences recognized elsewhere: the Cataceramus flexus Zone and the 'Inoceramus' tenuilineatus Zone are referred to the lower Upper Campanian. The Trochoceramus radiosus Zone is referred to the upper Lower Maastrichtian. The 'Inoceramus' ianjonaensis Zone is referred to the lower Upper Maastrichtian, and represents the youngest known assemblage of true inoceramids. There is no evidence for upper Upper Campanian or lower Lower Maastrichtian inoceramids, and this, together with the geological context of the faunas, indicates the presence of a regional unconformity at this level. This is confirmed by the associated ammonite assemblages. The inoceramid faunas include many taxa that have a wide distribution in the northern hemisphere, and provide a basis for correlation with the ammonite and inoceramid zonations recognized in the U.S. Western Interior, and the European ammonite and belemnite succession

The effect of photobleaching on bee (Hymenoptera: Apoidea) setae color and its implications for studying aging and behavior

Historically, bee age has been estimated using measurements of wing wear and integument color change.  These measurements have been useful in studies of foraging ecology and plant-pollinator interactions.  Wing wear is speculated to be affected by the behaviors associated with foraging, nesting, and mating activities.  Setal color change may be an additional parameter used to measure bee age if it is affected by sun exposure during these same activities.  The objectives of this study were to experimentally assess the effect of direct sun exposure on setal color, unicellular hair-like processes of the integument, and determine whether wing wear and integument photobleaching are correlated.  To quantify photobleaching of setae, we measured changes in hue of lab-reared Bombus huntii Greene (Apidae) exposed to natural sunlight.  We found that sun exposure was a significant variable in determining setal bleaching.  To assess the relationship between wing wear and setal photobleaching, we scored wing wear and measured setal hue of B. huntii, Melecta pacifica fulvida Cresson (Apidae), and Osmia integra Cresson (Megachilidae) from museum specimens.  Wing wear and setal hue values were positively correlated for all three species; however, the strength of the relationship varies across bee species as indicated by correlation coefficient estimates.  Our results suggest that setal color change is affected by sun exposure, and is likely an accurate estimate of bee age.  We suggest that future investigations of bee aging consider a suite of morphometric characteristics due to differences in natural history and sociobiology that may be confounded by the use of a single characteristic

Fabricating High-Resolution X-Ray Collimators

A process and method for fabricating multi-grid, high-resolution rotating modulation collimators for arcsecond and sub-arcsecond x-ray and gamma-ray imaging involves photochemical machining and precision stack lamination. The special fixturing and etching techniques that have been developed are used for the fabrication of multiple high-resolution grids on a single array substrate. This technology has application in solar and astrophysics and in a number of medical imaging applications including mammography, computed tomography (CT), single photon emission computed tomography (SPECT), and gamma cameras used in nuclear medicine. This collimator improvement can also be used in non-destructive testing, hydrodynamic weapons testing, and microbeam radiation therapy

Off-fault Damage Patterns Due to Supershear Ruptures with Application to the 2001 Mw 8.1 Kokoxili (Kunlun) Tibet Earthquake

We extend a model of a two-dimensional self-healing slip pulse, propagating dynamically in steady state with slip-weakening failure criterion, to the supershear regime in order to study the off-fault stressing induced by such a slip pulse and investigate features unique to the supershear range. Specifically, we show that there exists a nonattenuating stress field behind the Mach front that radiates high stresses arbitrarily far from the fault (practically this would be limited to distances comparable to the depth of the seismogenic zone), thus being capable of creating fresh damage or inducing Coulomb failure in known structures at large distances away from the main fault. We allow for both strike-slip and dip-slip failure induced by such a slip pulse. We show that off-fault damage is controlled by the speed of the slip-pulse, scaled stress drop, and principal stress orientation of the prestress field. We apply this model to study damage features induced during the 2001 Kokoxili (Kunlun) event in Tibet, for which it has been suggested that much of the rupture was supershear. We argue that an interval of simultaneous induced normal faulting is more likely due to a slip partitioning mechanism suggested previously than to the special features of supershear rupture. However, those features do provide an explanation for otherwise anomalous ground cracking at several kilometers from the main fault. We also make some estimates of fracture energy which, for a given net slip and dynamic stress drop, is lower than for a sub-Rayleigh slip pulse because part of the energy fed by the far-field stress is radiated back along the Mach fronts.Earth and Planetary SciencesEngineering and Applied Science