A study of chemiluminescence via flash photolysis

We are interested in understanding the mechanistic details of photo-initiated chemiluminescent reactions. Currently, we are examining reactions which lead to luminescent from electronically excited nitric oxide. Stedman has reported observing NO gamma-band emission in the thermal reaction of hydrazoic acid, HN3 with O(3P). The rate constant for the production of NO* is low and, consequently, the emission intensity is weak. We are endeavoring to generate excited NO from HN3 and O(1D), the later produced in the flash photolysis of ozone. It is hoped that a greater population of NO* will be produced yielding a greater chemiluminescent intensity. By observing the temporal behavior of the NO emission, it is hoped that the mechanistic details of the reaction can de elucidated. This paper contains a comprehensive summary of the pertinent literature as well as an experimental foundation for what will be an extended investigation into the chemistry of 1D oxygen

Urinary extracellular vesicle protein profiling and endogenous lithium clearance support excessive renal sodium wasting and water reabsorption in thiazide induced hyponatremia

IntroductionThiazide diuretics are amongst the most widely used anti-hypertensive medicines worldwide. Thiazide-Induced Hyponatremia (TIH) is one of their most clinically significant adverse effects. A priori TIH must result from excessive saliuresis and/or water reabsorption. We hypothesised that pathways regulating the thiazide-sensitive NCC and the water channel AQP2 may be involved. Our aim was to assess whether patients with TIH show evidence of altered NCC and AQP2 expression in urinary extracellular vesicles (UEVs), and also whether abnormalities of renal sodium reabsorption were evident using Endogenous Lithium Clearance (ELC).MethodsBlood and urine samples were donated by patients admitted to hospital with acute symptomatic TIH, after recovery to normonatremia, and also from normonatremic controls on and off thiazides. UEVs were isolated and target proteins evaluated by Western blotting and by Nanoparticle Tracking Analysis (NTA). ELC was assessed by Inductively Coupled Plasma Mass Spectrometry.ResultsUEVs analysis by Western blotting showed that patients with acute TIH display reduced total NCC and increased phospho-NCC and AQP2 relative to appropriate control groups; smaller differences in NCC and AQP2 expression persisted after recovery from TIH. These findings were confirmed by NTA. Renal ELC was lower in acute TIH compared to controls and convalescent cases.ConclusionReduced NCC expression and increased AQP2 expression would be expected to result in saliuresis and water reabsorption in TIH patients. This study raises the possibility that UEV analysis may be of diagnostic utility in less clear cut cases of thiazide associated hyponatremia and may help identify those at risk of TIH before thiazide initiation

High dose interleukin-2 (Aldesleukin) - expert consensus on best management practices-2014

Interleukin-2 (IL-2) was historically one of the few treatments for adults with stage IV solid tumors that could produce complete responses (CRs) that were often durable for decades without further therapy. The majority of complete responders with metastatic renal cell carcinoma (mRCC) and metastatic melanoma (mM) could probably be classified as "cures". Recent publications have suggested improved efficacy, perhaps due to improved patient Selection based on a better understanding of clinical features predicting outcomes. Guidelines for clinical management were established from experience at the National Cancer Institute (NCI) and an affiliation of institutions known as the Cytokine Working Group (CWG), who were among the first to utilize HD IL-2 treatment outside of the NCI. As new centers have opened, further management variations have emerged based upon center-specific experience, to optimize administration of IL-2 and provide high quality care for patients at each individual site. Twenty years of evolution in differing environments has led to a plethora of clinical experience and effective management approaches. The goal of this review is to summarize the spectrum of HD IL-2 treatment approaches, describing various effective strategies that incorporate newer adjunctive treatments for managing the side effects of IL-2 in patients with mRCC and mM. The goal for IL-2 therapy is typically to administer the maximum number of doses of IL-2 without putting the patient at unacceptable risk for severe, irreversible toxicity. This review is based upon a consensus meeting and includes guidelines on pre-treatment screening, criteria for administration and withholding doses, and defines consensus criteria for safe administration and toxicity management. The somewhat heterogeneous best practices of 2014 will be compared and contrasted with the guidelines provided in 2001 and the package inserts from 1992 and 1998