Pituitary body in its relation to the skeleton

The pituitary body in its relation to the skeleton: a review of the literature, with a preliminary report on personal experiments, and notes on experimental surgery.This research is not presented as a completed scientific investigation. It may be worth while, however, to give an account of the objects in view and the methods employed, together with a preliminary communication of the results obtained up to the present time.The object of this research is primarily to further the elucidation of the problems which concern diseases of bones. It is recognized that a thorough knowledge of the physiological conditions which influence bone growth, bone maintenance and bone repair is essential before pathological states are fully comprehensible and their rational treatment possible. The subject of normal bone growth and maintenance has therefore been taken up first; and the investigation resolves itself into an inquiry into the factors which exercise an important influenc on this.Before proceeding to apply the scheme of investigation ... it is necessary to review any previous investigations bearing on the subject. This must include the effects of pituitary disturbances on the other endocrine organs, and the influence of any such disturbance of another organ on bone. The importance of this general review is obvious when we consider the interdependence of the members of the endocrine group, the complex derangements which may thus follow a lesion of any one of them, and the consequent difficulty in interpreting the results of such a lesion. This subject is dealt with in Section I.The available methods of investigation then fall to be considered. In Section II the more general points are set forth; and in Section III the operative methods used are given in detail. The general results of operations and pituitary feeding are dealt with in Section IV. Section V contains summaries of individual experiments; and Section VI gives my own results in relation to bone growth

Provenance and geochemistry of exotic clasts in conglomerates of the Oligocene Torehina Formation, Coromandel Peninsula, New Zealand

Non-marine pebble to cobble conglomerates of the lower Torehina Formation (Oligocene) crop out along western Coromandel Peninsula and overlie, with strong angular discordance, continental-margin metasedimentary rocks (Manaia Hill Group) of Mesozoic (Late Jurassic to ?Early Cretaceous) age. The conglomerates contain provenance information that identifies a pre-Oligocene depositional history obscured by the unconformable juxtaposition of these Tertiary and Mesozoic strata. Most clasts in the lower Torehina Formation are visually similar to local bedrock lithologies, including metamorphosed sandstones and argillites, but are kaolinitic and contain more detrital and authigenic chert, quartz, and potash feldspar. Local derivation of these clasts seems unlikely. By comparing geochemical ratios with those defined for continental margin sandstones, and well characterised New Zealand tectonic terranes, we interpret the majority of clasts in the lower Torehina Formation to have been derived from a dissected orogen, with mixtures of felsic and volcanogenic-derived sediment. The most likely sources are the Waipapa and Torlesse Terranes. The remaining 20–30% of the clasts in the lower Torehina Formation were originally friable, are coarse grained, and appear to be lithologically exotic relative to known metamorphosed sandstones in basement terrane sources on North Island. Some clasts contain coal laminae and particles, and all contain detrital kaolinite as lithic fragments and matrix. Such characteristics imply a non-marine to marginal-marine source containing sediment derived from strongly weathered granite or granodiorite. Mechanical fragility implies a likely proximal, easily erodible source. We propose that this group of clasts was derived from an Upper Cretaceous sedimentary cover, either part of a locally developed basin fill or part of a once regionally extensive cover on North Island. Either case defines a more widely distributed Cretaceous source than found today

Intravenous sildenafil citrate and post-cardiac surgery acute kidney injury: a double-blind, randomised, placebo-controlled trial

Clinical trial registration ISRCTN18386427. open access articleBackground This study assessed whether i.v. sildenafil citrate prevented acute kidney injury in at-risk patients undergoing cardiac surgery with cardiopulmonary bypass. Methods In a double-blind RCT, adults at increased risk of acute kidney injury undergoing cardiac surgery in a single UK tertiary centre were randomised to receive sildenafil citrate 12.5 mg kg−1 i.v. over 150 min or dextrose 5% at the commencement of surgery. The primary outcome was serum creatinine measured at six post-randomisation time points. The primary analysis used a linear mixed-effects model adjusted for the stratification variables, baseline estimated glomerular filtration rate, and surgical procedure. Secondary outcomes considered clinical events and potential disease mechanisms. Effect estimates were expressed as mean differences (MDs) or odds ratios with 95% confidence intervals. Results The analysis population comprised eligible randomised patients that underwent valve surgery or combined coronary artery bypass graft and valve surgery, with cardiopulmonary bypass, between May 2015 and June 2018. There were 60 subjects in the sildenafil group and 69 in the placebo control group. The difference between groups in creatinine concentration was not statistically significant (MD: 0.88 μmol L−1 [–5.82, 7.59]). There was a statistically significant increase in multiple organ dysfunction scores in the sildenafil group (MD: 0.54 [0.02, 1.07]; P=0.044). Secondary outcomes, and biomarkers of kidney injury, endothelial function, and inflammatory cell activation, were not significantly different between the groups. Conclusions These results do not support the use of i.v. sildenafil citrate for kidney protection in adult cardiac surgery

Amorphous formulations of indomethacin and griseofulvin prepared by electrospinning

Following an array of optimization experiments, two series of electrospun polyvinylpyrrolidone (PVP) fibers were prepared. One set of fibers contained various loadings of indomethacin, known to form stable glasses, and the other griseofulvin (a poor glass former). Drug loadings of up to 33% w/w were achieved. Electron microscopy data showed the fibers largely to comprise smooth and uniform cylinders, with evidence for solvent droplets in some samples. In all cases, the drug was found to exist in the amorphous physical state in the fibers on the basis of X-ray diffraction and differential scanning calorimetry (DSC) measurements. Modulated temperature DSC showed that the relationship between a formulation’s glass transition temperature (<i>T</i>_g) and the drug loading follows the Gordon–Taylor equation, but not the Fox equation. The results of Gordon–Taylor analysis indicated that the drug/polymer interactions were stronger with indomethacin. The interactions between drug and polymer were explored in more detail using molecular modeling simulations and again found to be stronger with indomethacin; the presence of significant intermolecular forces was further confirmed using IR spectroscopy. The amorphous form of both drugs was found to be stable after storage of the fibers for 8 months in a desiccator (relative humidity <25%). Finally, the functional performance of the fibers was studied; in all cases, the drug-loaded fibers released their drug cargo very rapidly, offering accelerated dissolution over the pure drug

GRaNIE and GRaNPA: inference and evaluation of enhancer-mediated gene regulatory networks

Enhancers play a vital role in gene regulation and are critical in mediating the impact of noncoding genetic variants associated with complex traits. Enhancer activity is a cell-type-specific process regulated by transcription factors (TFs), epigenetic mechanisms and genetic variants. Despite the strong mechanistic link between TFs and enhancers, we currently lack a framework for jointly analysing them in cell-type-specific gene regulatory networks (GRN). Equally important, we lack an unbiased way of assessing the biological significance of inferred GRNs since no complete ground truth exists. To address these gaps, we present GRaNIE (Gene Regulatory Network Inference including Enhancers) and GRaNPA (Gene Regulatory Network Performance Analysis). GRaNIE (https://git.embl.de/grp-zaugg/GR aNIE) builds enhancer-mediated GRNs based on covariation of chromatin accessibility and RNA-seq across samples (e.g. individuals), while GRaNPA (https://git.embl.de/grp-zaugg/GRaNPA) assesses the performance of GRNs for predicting cell-type-specific differential expression. We demonstrate their power by investigating gene regulatory mechanisms underlying the response of macrophages to infection, cancer and common genetic traits including autoimmune diseases. Finally, our methods identify the TF PURA as a putative regulator of pro-inflammatory macrophage polarisation

Spatial and temporal facies evolution of a Lower Jurassic carbonate platform, NW Tethyan margin (Mallorca, Spain)

The variety of depositional facies of a Lower Jurassic carbonate platform has been investigated on the island of Mallorca along a transect comprising six stratigraphic profiles. Twenty-nine facies and sub-facies have been recognized, grouped into seven facies associations, ranging in depositional environment from supratidal/terrestrial and peritidal to outer platform. Spatial and temporal (2D) facies distribution along the transect reflects the evolution of the carbonate platform with time showing different facies associations, from a broad peritidal platform (stage 1) to a muddy open platform (stage 2), and finally to a peritidal to outer carbonate platform (stage 3). Stage 1 (early Sinemurian to earliest late Sinemurian) corresponds to a nearly-flat peritidal-shallow subtidal epicontinental platform with facies belts that shifted far and fast over the whole study area. The evolution from stage 1 to stage 2 (late Sinemurian) represents a rapid flooding of the epicontinental shallow platform, with more open-marine conditions, and the onset of differential subsidence. During stage 3 (latest Sinemurian), peritidal and shallow-platform environments preferentially developed to the northeast (Llevant Mountains domain) with a rapid transition to middle-outer platform environments toward the northwest (Tramuntana Range domain). Stages 1 and 3 present facies associations typical of Bahamian-type carbonates, whereas stage 2 represents the demise of the Bahamian-type carbonate factory and proliferation of muddy substrates with suspension-feeders. The described platform evolution responded to the interplay between the initial extensional tectonic phases related to Early Jurassic Tethyan rifting, contemporaneous environmental perturbations, and progressive platform flooding related to the Late Triassic–Early Jurassic worldwide marine transgression and associated accommodation changes