Consequences of an incomplete differential diagnosis
James W. Albers, Stanley Berent in Neurobehavioral Toxicology: Neurological and Neuropsychological Perspectives, 2005
A 62 year-old retired chemist experienced the insidious onset of gait difficulty, characterized by an unsteady and stiff gait. He also described numbness and tingling of his legs, perineum, and lower abdomen. He could not describe a precise time of onset, but the problem seemed to have developed over about 20 years. He also described urinary urgency and impotence of about 5 years’ duration. He sought neurological evaluation on numerous occasions. The evaluations included a lumbar puncture, imaging of his entire spine, myelography, and numerous evaluations of blood and urine, all of which were unremarkable. He denied pain. One of his physicians told him that his problem could have been caused by ‘chemicals,’ as he had been employed as a chemist for over 40 years. He described himself as an inorganic chemist. He was aware of numerous chemical exposures at work, but unaware of any particular incidents producing symptoms. He and his company practiced good industrial hygiene. No co-worker had experienced a similar problem. The past medical history was unremarkable, as was the family history for neuromuscular disease. He sought additional evaluation looking for the ‘cause’ of his difficulty.
Organotin Chemistry
Nate F. Cardarelli in Tin as a Vital Nutrient:, 2019
The chemist first must find if the proposed new composition of matter has been reported before. Here Chemical Abstracts is the indispensible source. For specific formulations the formula indices afford an easy first approach. For classes of compounds the search is more difficult since the exact designation utilized in the system of controlled vocabulary must be identified. Computerized bibliographic searching of the Chemical Abstracts files is also available world-wide and can proceed quickly by the registry number for individual compounds. All chemists are data retrievers some of the time; some chemists are data retrievers all the time (pace Lincoln). Popular organotin compounds are listed in the Handbook of Chemistry and Physics,62 or in the Merck Index,63 or in Comprehensive Organometallic Chemistry.64 All organotins of each class are described in the Gmelin Handbook of Inorganic Chemistry to the closing date for each volume.20–29
Introduction
Frank A. Barile in Barile’s Clinical Toxicology, 2019
Fast-forward to the latter half of the twentieth century—once again, the field of toxicology derived impetus from analytical chemists, who sought to understand the action of xenobiotics by isolating and identifying the components. Until these developments crystallized, most traditional toxicologists were trained in classical quantitative chemical analysis as well as organic and inorganic chemistry. Eventually, the field would flourish into a variety of specialties, which today are well accepted as part of the biomedical sciences. Currently, clinical toxicology (also known as pharmacotoxicology) enjoys its own particular designation, the subject of which is advanced in the subsequent chapters.
Metallo therapeutics for COVID-19. Exploiting metal-based compounds for the discovery of new antiviral drugs
Published in Expert Opinion on Drug Discovery, 2021
Damiano Cirri, Alessandro Pratesi, Tiziano Marzo, Luigi Messori
When a new severe disease appears for which there are no effective medical treatments as it is the case of COVID-19 disease, all the possible therapeutic opportunities must be explored. We believe that inclusion of a large array of metal-based agents in the screening libraries and programs may significantly expand the chemical space and increase the chance of finding effective drugs. In doing this, some favorable properties intrinsic to the metal centers such as the Lewis acidity and the soft character may provide an ‘added value’ that is not found in standard organic compounds. Thus, we may expect that medicinal inorganic chemistry may offer a significant contribution to the fight against COVID-19. It may be hypothesized that so many unusual and unique metal centers may hopefully produce some important and favorable effects on this new pathogen that are difficult to predict a priori and may lead to the rapid identification of clinically useful substances. Indeed, a first analysis of the main druggable targets of SARS-CoV-2 highlights the presence of a few enzymes, in particular two crucial cysteine proteases and the helicase, that might be optimal targets for compounds bearing soft metal centers. Notably, a few preliminary results suggest that selected gold and bismuth compounds are able to produce a strong inhibition of those catalytic activities thus contrasting very effectively virus replication.
Novel Re(I) tricarbonyl coordination compounds based on 2-pyridyl-1,2,3-triazole derivatives bearing a 4-amino-substituted benzenesulfonamide arm: synthesis, crystal structure, computational studies and inhibitory activity against carbonic anhydrase I, II, and IX isoforms†
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2019
Yassine Aimene, Romain Eychenne, Sonia Mallet-Ladeira, Nathalie Saffon, Jean-Yves Winum, Alessio Nocentini, Claudiu T. Supuran, Eric Benoist, Achour Seridi
Over recent decades, rhenium(I) tricarbonyl complexes have been intensively studied by the inorganic chemist community, due to their significant photophysical and photochemical properties. These features make them interesting tools for numerous potential practical applications, such as photo sensitisers in solar cells1, CO2 reduction catalysts2, organic light-emitting devices (OLEDs)3, luminescence sensors4, and CO-releasing moieties (CORMs)5. Additionally, radioactive fac-[188Re(CO)3]+ complexes have recently drawn the attention of several research groups for their use as therapeutic radiopharmaceuticals6.
Radiation protection biology then and now
Published in International Journal of Radiation Biology, 2019
Andrzej Wojcik, Mats Harms-Ringdahl
The discovery of radiation by Röntgen in 1895 and following discovery of radioactivity by Henrie Becquerel and Marie and Pierre Curie (Macklis 1996) coincided with advances in inorganic chemistry and in biochemistry (Hunter 2000). The identification of enzymes as catalysts made it possible to understand how biological reactions are catalyzed but left the question open regarding the vital energy which was responsible for building order in biological systems. The natural aspect of radioactivity coming from the earth element radium sparked the belief that radiation may be the vital force driving biochemical reactions. This belief was reinforced by the discovery that waters in many spas were radioactive which, in turn, initiated the use of radiation as a cure for any disease (Macklis 1996) (Figure 1). Harmful effects of radiation were believed to be restricted to high doses and beneficial action of low radiation doses was confirmed by results of often poorly designed biological experiments on a variety of species and endpoints demonstrating stimulatory effects (Luckey 1980; Luckey and Lawrence 2006). A change in the perception of risk associated with radiation exposure occurred during early 1930ties, but not due to more careful biological experiments. Rather, it resulted from the widely reported death of Eben Byers in 1932 (Macklis 1993) and of numerous radium dial painters caused by radium ingestion (Clark 1997). Especially the latter events demonstrated that internal exposure to fairly low activities of radium was dangerous and should be prevented. However, what level of radium exposure cold be tolerated by an organism was not known. In order to find this out, researchers from the Massachusetts Institute of Technology were requested in 1936 by the Food and Drug Administration of U.S.A. to carry out experiments with rats to determine how much radium should be allowed in such consumer products as creams, toothpaste or contraceptive vaginal jellies (Caufield 1989). However, rats were soon found to be several hundred times more resistant to radium than humans. Therefore, further studies focused on humans who were occupationally or medically exposed to radium. Based on analyzing 27 human cases it was concluded that ingestion of <0.5 mCi (∼18 MBq) caused no harmful effects in the body. Indeed injuries were observed in those people who ingested more than 1.2 mCi (∼44 MBq). It was then recommended by the National Bureau of Standards that occupational exposure to radium be stopped when the radium activity in a worker’s body exceeded 0.1 mCi (ca 4 MBq) (Caufield 1989). Similarly as with the tolerance dose of external exposure, the internal exposure limit to radium was not based on any sound biological or epidemiological analyses but rather on out of the gut feeling.