Analysis of total urinary catecholamines by liquid chromatography: methodology, routine experience and clinical interpretations of results

A simple routine method is described for simultaneous assay of total urinary adrenaline, noradrenaline and dopamine. The catecholamines are pre-purified on a small ion-exchange column, separated by reversed phase ion-pair liquid chromatography, and are quantitated by electrochemical detection. The method was routinely applied to 422 urines. Elevated values were found in four urine specimens obtained from patients with histologically proven phaeochromocytomas. Virtually no interference by endogenous or exogenous compounds was found. Values for urinary catecholamines determined by fluorimetric analysis agreed with those obtained by high pressure liquid chromatography with electrochemical detection. Within-day CVs for the compounds ranged from 5.2-11.9%, between-day CVs from 3.3-6.6%. The normal range (95% confidence level) was 20-230 micrograms/24 h for noradrenaline and 1-35 micrograms/24 h for adrenaline

Analysis of cold worked holes for structural life extension

Cold working holes for improved fatigue life of fastener holes are widely used on aircraft. This paper presents methods used by the authors to determine the percent of cold working to be applied and to analyze fatigue crack growth of cold worked fastener holes. An elastic, perfectly-plastic analysis of a thick-walled tube is used to determine the stress field during the cold working process and the residual stress field after the process is completed. The results of the elastic/plastic analysis are used to determine the amount of cold working to apply to a hole. The residual stress field is then used to perform damage tolerance analysis of a crack growing out of a cold worked fastener hole. This analysis method is easily implemented in existing crack growth computer codes so that the cold worked holes can be used to extend the structural life of aircraft. Analytical results are compared to test data where appropriate

Structural evolution in the neutron-rich nuclei 106Zr and 108Zr

The low-lying states in 106Zr and 108Zr have been investigated by means of {\beta}-{\gamma} and isomer spectroscopy at the RI beam factory, respectively. A new isomer with a half-life of 620\pm150 ns has been identified in 108Zr. For the sequence of even-even Zr isotopes, the excitation energies of the first 2+ states reach a minimum at N = 64 and gradually increase as the neutron number increases up to N = 68, suggesting a deformed sub-shell closure at N = 64. The deformed ground state of 108Zr indicates that a spherical sub-shell gap predicted at N = 70 is not large enough to change the ground state of 108Zr to the spherical shape. The possibility of a tetrahedral shape isomer in 108Zr is also discussed.Comment: 10 pages, 3 figures, Accepted for publication in Phys. Rev. Let

Tuning a Polar Molecule for Selective Cytoplasmic Delivery by a pH (Low) Insertion Peptide

Drug molecules are typically hydrophobic and small in order to traverse membranes to reach cytoplasmic targets, but we have discovered that more polar molecules can be delivered across membranes using water-soluble, moderately hydrophobic membrane peptides of the pHLIP (pH low insertion peptide) family. Delivery of polar cargo molecules could expand the chemical landscape for pharmacological agents that have useful activity but are too polar by normal drug criteria. The spontaneous insertion and folding of the pHLIP peptide across a lipid bilayer seeks a free energy minimum, and insertion is accompanied by a release of energy that can be used to translocate cell-impermeable cargo molecules. In this study, we report our first attempt to tune the hydrophobicity of a polar cargo, phallacidin, in a systematic manner. We present the design, synthesis, and characterization of three phallacidin cargoes, where the hydrophobicity of the cargo was tuned by the attachment of diamines of various lengths of hydrophobic chains. The phallacidin cargoes were conjugated to pHLIP and shown to selectively inhibit the proliferation of cancer cells in a concentration-dependent manner at low pH

Early Imaging Prediction of Malignant Cerebellar Edema Development in Acute Ischemic Stroke

Background and Purpose-Malignant cerebellar edema (MCE) is a life-threatening complication of acute ischemic stroke that requires timely diagnosis and management. Aim of this study was to identify imaging predictors in initial multiparametric computed tomography (CT), including whole-brain CT perfusion (WB-CTP). Methods-We consecutively selected all subjects with cerebellar ischemic WB-CTP deficits and follow-up-confirmed cerebellar infarction from an initial cohort of 2635 patients who had undergone multiparametric CT because of suspected stroke. Follow-up imaging was assessed for the presence of MCE, measured using an established 10-point scale, of which scores >= 4 are considered malignant. Posterior circulation-Acute Stroke Prognosis Early CT Score (pc-ASPECTS) was determined to assess ischemic changes on noncontrast CT, CT angiography (CTA), and parametric WB-CTP maps (cerebellar blood flow [CBF];cerebellar blood volume;mean transit time;time to drain). Fisher's exact tests, Mann-Whitney U tests, and receiver operating characteristics analyses were performed for statistical analyses. Results-Out of a total of 51 patients who matched the inclusion criteria, 42 patients (82.4%) were categorized as MCE-and 9 (17.6%) as MCE+. MCE+ patients had larger CBF, cerebellar blood volume, mean transit time, and time to drain deficit volumes (all with P0.05). Receiver operating characteristics analyses yielded the largest area under the curve values for the prediction of MCE development for CBF (0.979) and cerebellar blood volume deficit volumes (0.956) and pc-ASPECTS on CBF (0.935), whereas pc-ASPECTS on noncontrast CT (0.648) and CTA (0.684) had less diagnostic value. The optimal cutoff value for CBF deficit volume was 22 mL, yielding 100% sensitivity and 90% specificity for MCE classification. Conclusions-WB-CTP provides added diagnostic value for the early identification of patients at risk for MCE development in acute cerebellar stroke

Inhibition of Y1 receptor signaling improves islet transplant outcome

Failure to secrete sufficient quantities of insulin is a pathological feature of type-1 and type-2 diabetes, and also reduces the success of islet cell transplantation. Here we demonstrate that Y1 receptor signaling inhibits insulin release in β-cells, and show that this can be pharmacologically exploited to boost insulin secretion. Transplanting islets with Y1 receptor deficiency accelerates the normalization of hyperglycemia in chemically induced diabetic recipient mice, which can also be achieved by short-term pharmacological blockade of Y1 receptors in transplanted mouse and human islets. Furthermore, treatment of non-obese diabetic mice with a Y1 receptor antagonist delays the onset of diabetes. Mechanistically, Y1 receptor signaling inhibits the production of cAMP in islets, which via CREB mediated pathways results in the down-regulation of several key enzymes in glycolysis and ATP production. Thus, manipulating Y1 receptor signaling in β-cells offers a unique therapeutic opportunity for correcting insulin deficiency as it occurs in the pathological state of type-1 diabetes as well as during islet transplantation.Islet transplantation is considered one of the potential treatments for T1DM but limited islet survival and their impaired function pose limitations to this approach. Here Loh et al. show that the Y1 receptor is expressed in β- cells and inhibition of its signalling, both genetic and pharmacological, improves mouse and human islet function.info:eu-repo/semantics/publishe