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Ion Beam Analysis: Analytical Applications
Published in Vlado Valković, Low Energy Particle Accelerator-Based Technologies and Their Applications, 2022
Blewer (1974) has performed analysis of near-surface helium and hydrogen isotope depth profiles by a proton backscattering technique. The method used has been demonstrated as a means to characterize the concentration, initial position, and subsequent migration behaviour of all atom species. The projected range of helium implanted at 50 keV in Nb, V, Ti and Cu has been measured and, for the latter two metals, has been found to agree with theoretical calculations within 10 nm. Deuterium has also been detected and profiled (in Ti) using this technique. Detection sensitivity has been demonstrated at the 7 at % level for D in Ti and at the 0.5 at % level for 4He in Cu. In addition, surface and bulk distributions of carbon, oxygen and 3He have been profiled and, in principle, the depth distributions of tritium, 6Li, 7Li, Be, B, N and F are also simultaneously resolvable if contained within the foil samples. The technique has been used to investigate the effect of radiation damage and in situ annealing on implanted helium profiles in copper.
The Poisoned Chalice
Published in Alan Perkins, Life and Death Rays, 2021
In February 1990 routine health monitoring of staff working at the Point Lepreau Nuclear Generating Station in New Brunswick on the east coast of Canada showed elevated levels of radioactivity in urine samples. A disgruntled 33-year-old assistant plant operator Daniel George Maston, who worked at the power plant, took a sample of heavy water from the boron reactor moderator system and poured it into the chilled 5 gallon water dispenser in the staff dining area. Heavy water which is also known as deuterium oxide is not radioactive itself, but it is used to cool the reactor and becomes radioactive as it circulates through the reactor core. Eight employees drank the contaminated water. One individual who was working in a high-temperature area was carrying out stress work, requiring alternating periods of work, rest and rehydration. He consumed significantly more water than the other employees. The incident was discovered when the urine samples from the staff showed elevated urinary levels of tritium, a radioactive form of hydrogen (hydrogen-3). Maston was arrested and during a short court hearing witnesses described him as a ‘quiet guy’. A number of workers at the plant thought that this was intended as a bad practical joke rather than a malicious act. The long-term health consequences on the affected staff were considered to be negligible.
Images from Radioactivity: Radionuclide Scans, SPECT, and PET
Published in Suzanne Amador Kane, Boris A. Gelman, Introduction to Physics in Modern Medicine, 2020
Suzanne Amador Kane, Boris A. Gelman
The nuclei of many chemical elements can be found in several different forms in nature determined by their mixture of nucleon species. For example, the element hydrogen can be found in three forms, all of which have one proton but different numbers of neutrons. These alternate versions of a single element are called isotopes; each isotope has the same atomic number Z, but different total numbers of nucleons. Since changing the number of neutrons in a nucleus leaves its charge unaltered and only modifies its mass, different isotopes have virtually identical chemical properties. The different isotopes of a particular chemical element are indicated either by noting the number of nucleons or by adding a superscript to the letter symbol for the element. The superscript refers to the total number of nucleons (called the mass number) in the isotope's nucleus. For example, the three forms of hydrogen are: normal hydrogen, hydrogen-1 or 1H (1 proton); deuterium, hydrogen-2 or 2H (1 proton + 1 neutron); and tritium, hydrogen-3 or 3H (1 proton + 2 neutrons). Any one of these isotopes can play a chemical role similar to that of normal hydrogen. For example, normal water consists of one oxygen and two hydrogens, while “heavy water” is made of one oxygen and two deuterium atoms. The various isotopes occur in nature in varying abundances; for example, seawater contains a small fraction of heavy water.
Treatment of tardive dyskinesia: a review and update for dermatologists managing delusions of parasitosis
Published in Journal of Dermatological Treatment, 2022
Christian Cheng, Nicholas Brownstone, John Koo
Using the same criteria for treatment success as defined above, 34% of deutetrabenazine patients were noted to have at least 50% decrease in the dyskinesia score as opposed to only 12% achieving this among the placebo group (2). Unlike valbenazine, the dosage of deuterobenzene needs to be individualized. The dosing is typically started with 6 mg PO BID and increased every week by 6 mg PO per day until the maximum dose of 48 mg PO per day (32). The medication is absorbed better when taken with food. Deutetrabenazine was very well tolerated by the patient so that no side effects evaluated reached an occurrence rate of ≥5%. Discontinuation because of adverse events was seldom encountered. Deutetrabenazine may also prolong the QT interval and therefore should be avoided in any patients with congenitally long QT syndrome or any patients with arrhythmias involving an increased QT interval. For patients who are poor CYP2D6 metabolizers, the maximum dose is 36 mg PO per day (33). Of note, this medication was the first drug approved by the US FDA that contains the heavy hydrogen isotope deuterium (34). The addition of deuterium reduces the metabolism of the drug which allows for lower and less frequent dosing that may result in a more favorable safety profile (35).
Deutetrabenazine for treatment of involuntary movements in patients with tardive dyskinesia
Published in Expert Review of Neurotherapeutics, 2021
Benjamin J. Dorfman, Joohi Jimenez-Shahed
In order to address the pharmacokinetic challenges seen with tetrabenazine, a deuterated form called deutetrabenazine (Austedo®, Teva Pharmaceuticals) was developed. Deuterium is an isotope of hydrogen containing one neutron, in contrast with the most common isotope of hydrogen, protium, which has no neutrons. Deuterium-carbon bonds are stronger than carbon-hydrogen bonds, and thus, substituting deuterium for hydrogen at sites that are targets for enzymatic degradation may delay the rate of metabolism [39–43]. This has the effect of both prolonging a drug’s half-life and providing a more stable plasma concentration [42,43]. As a result, deuterated drugs can be given at lower doses and reach an effective plasma concentration and therapeutic benefit while reaching a lower Cmax, which may lower risks of peak-dose AEs [44].
Ab-Ligity: identifying sequence-dissimilar antibodies that bind to the same epitope
Published in mAbs, 2021
Wing Ki Wong, Sarah A. Robinson, Alexander Bujotzek, Guy Georges, Alan P. Lewis, Jiye Shi, James Snowden, Bruck Taddese, Charlotte M. Deane
The highest resolution method for studying antibody-antigen binding configurations is co-crystal complex structures. These give atomic level information but are expensive and difficult to obtain.2 Experimental mapping is often used as a surrogate because it is able to identify the binding regions of the antigen (“epitopes”) and antibody (“paratopes”; ref. 3). Competition assays exploit the cross-blocking effect of antibodies that displace one another if they bind to similar or neighboring epitopes.3,4 This method gives a coarse representation of which binders may share similar target sites, as minimal epitope overlap can be sufficient for a pair of antibodies to compete with each other.4 A more refined approach is hydrogen deuterium exchange (HDX). HDX assesses the solvent accessibility of the bound and unbound forms of the partner proteins, and highlights regions with the maximum changes upon binding (e.g., ref.5,6). The resolution is typically up to the range of peptides in the immediate proximity of the binding site. To achieve residue-level resolution, point mutations of the interacting proteins can be used to indicate key binding residues. Mutagenesis studies measure the binding kinetics upon mutation of specific residues, but structural integrity may be compromised by the mutations, leading to spurious results.7 All three of these experimental techniques provide an approximation of the binding regions, but are usually unable to provide a fine mapping of exact epitopes and paratopes.