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Frontiers in Neuroscience 2023The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former... (Review)
Review
The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.
PubMed: 36860617
DOI: 10.3389/fnins.2023.1005096 -
Experimental Neurology Aug 1978The toxic derivative of hydrazine, monomethylhydrazine, at a dosage of 10 mg/kg is a potent convulsant, producing tonic-clonic seizures in the cat. In this study the...
The toxic derivative of hydrazine, monomethylhydrazine, at a dosage of 10 mg/kg is a potent convulsant, producing tonic-clonic seizures in the cat. In this study the effects of enforced restraint on susceptibility to MMH-induced seizures was examined in naive animals and in cats prepared neurosurgically with indwelling polygraphic recording electrodes. Using a counterbalanced design, latency to seizure following the intraperitoneal administration of the drug (10 mg/kg) was measured twice in all animals, under restraint and in freely moving conditions. Susceptibility to seizures was significantly decreased under the condition of restraint. Additionally, polygraphic recordings showed that restraint was accompanied by an increased incidence of “synchronous” EEG patterns. These results were not explained by metabolic variables, duration of intertrial interval, or changes in weight. The relationship between observed polygraphic patterns and seizure response is discussed in terms of the physiological alterations attendant upon restraint.
Topics: Animals; Cats; Electroencephalography; Female; Male; Methylhydrazines; Monomethylhydrazine; Restraint, Physical; Seizures
PubMed: 680066
DOI: 10.1016/0014-4886(78)90187-5 -
British Journal of Cancer Nov 1974Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes...
Single toxic doses of 1,2-dimethylhydrazine induced mild centrilobular necrosis of the liver in rats and mice. Ultrastructural studies showed hepatic nuclear changes including nucleolar microsegregation and changes in the endoplasmic reticulum and mitochondria. 1-Methylhydrazine caused little morphological change in the liver. Tumours of the colon and kidney and also massive cystic hyperplasia of the liver were found in some of the rats and tumours of the anal margin and kidney in some of the mice, following single doses of 1,2-dimethylhydrazine. Incorporation of amino acids into rat liver proteins was inhibited by 1,2-dimethylhydrazine, which also caused disaggregation of hepatic polysomes. No effects on hepatic protein synthesis by 1,1-dimethylhydrazine or 1-methylhydrazine were observed. Similarities between the effects of 1,2-dimethylhydrazine, cycasin and dimethylnitrosamine are discussed.
Topics: Animals; Colonic Neoplasms; Dimethylhydrazines; Endoplasmic Reticulum; Hydrazines; Kidney Neoplasms; Lethal Dose 50; Leucine; Liver; Male; Mice; Mitochondria; Monomethylhydrazine; Neoplasms; Neoplasms, Experimental; Rats; Ribosomes
PubMed: 4469195
DOI: 10.1038/bjc.1974.217 -
Molecules (Basel, Switzerland) May 2012Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key...
Sixteen novel pyrazole acyl thiourea derivatives 6 were synthesized from monomethylhydrazine (phenylhydrazine) and ethyl acetoacetate. The key 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl chloride intermediates 4 were first generated in four steps through cyclization, formylation, oxidation and acylation. Thess were then reacted with ammonium thiocyanate in the presence of PEG-400 to afford 5-chloro-3-methyl-1-substituted-1H-pyrazole-4-carbonyl isothiocyanates 5. Subsequent reaction with fluorinated aromatic amines resulted in the formation of the title compounds. The synthesized compound were unequivocally characterized by IR, ¹H-NMR, ¹³C-NMR and elemental analysis and some of the synthesized compounds displayed good antifungal activities against Gibberella zeae, Fusarium oxysporum, Cytospora mandshurica and anti-TMV activity in preliminary antifungal activity tests.
Topics: Acetoacetates; Acylation; Antifungal Agents; Antiviral Agents; Cyclization; Fusarium; Gibberella; Hydrocarbons, Fluorinated; Microbial Sensitivity Tests; Oxidation-Reduction; Phenylhydrazines; Polyethylene Glycols; Pyrazoles; Structure-Activity Relationship; Thiocyanates; Thiourea; Tobacco Mosaic Virus
PubMed: 22555301
DOI: 10.3390/molecules17055139 -
Blood Jul 1994Oxidative damage induced by free globin chains has been implicated in the pathogenesis of the membrane abnormalities observed in alpha and beta thalassemia. We have...
Oxidative damage induced by free globin chains has been implicated in the pathogenesis of the membrane abnormalities observed in alpha and beta thalassemia. We have evaluated transport of Na+ and K+ in erythrocytes of patients with thalassemias as well as in two experimental models that use normal human red blood cells, one for alpha thalassemia (methylhydrazine treatment, alpha thalassemia like) and one for beta thalassemia (phenylhydrazine treatment, beta thalassemia like). With the exception of the Na-K pump, similar alterations in membrane transport were observed in thalassemia and thalassemia-like erythrocytes. These were: increased K-Cl cotransport, Na-Li countertransport and reduced Na-K-Cl cotransport. The Na-K pump was reduced in thalassemia-like cells, whereas it was increased in severe alpha thalassemia and in beta thalassemia cells. The increased K-Cl cotransport activity could be observed in light and dense fractions of beta-thalassemic cells. K-Cl cotransport in thalassemic and thalassemia-like erythrocytes was partially inhibited by [(dihydro-indenyl) oxy] alkanoic acid and completely abolished by dithiothreitol. Thus, oxidative damage represents an important factor in the increased activity of the K-Cl cotransport observed in thalassemias, and of the K+ loss observed in beta-thalassemia erythrocytes.
Topics: Chlorides; Erythrocyte Membrane; Humans; Ion Transport; Monomethylhydrazine; Phenylhydrazines; Potassium; Sodium-Potassium-Exchanging ATPase; Thalassemia
PubMed: 8018927
DOI: No ID Found -
The Journal of Biological Chemistry Mar 1990The dissimilatory nitrite reductase, cytochrome cd1, from Pseudomonas aeruginosa (ATCC 19429) was irreversibly inactivated by methyl- or phenylhydrazine but was only...
The dissimilatory nitrite reductase, cytochrome cd1, from Pseudomonas aeruginosa (ATCC 19429) was irreversibly inactivated by methyl- or phenylhydrazine but was only reduced by hydrazine itself. The reaction required oxygen and several turnovers, approximately four, of the cytochrome acting to transfer reducing equivalents from phenylhydrazine to oxygen. The reaction with methyl- or phenylhydrazine altered the visible spectrum of the cytochrome. Bands characteristic of reduced heme c appeared plus new features that were not characteristic of either oxidized or reduced heme d1. Extraction of the heme from phenylhydrazine-treated cytochrome yielded a covalently modified form of the original heme d1. Visible, 1H NMR, and mass spectra were obtained on the purified modified heme and on the metal-free esterified derivative. The spectroscopic data indicate that the modification was the regiospecific substitution of the 5 meso-proton by a phenyl group.
Topics: Chromatography, Gel; Chromatography, High Pressure Liquid; Cytochromes; Electron Transport Complex IV; Hydrazines; Hydroquinones; Kinetics; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Monomethylhydrazine; Nitrite Reductases; Oxygen Consumption; Phenylhydrazines; Pseudomonas; Spectrophotometry
PubMed: 2155216
DOI: No ID Found -
Heliyon Mar 2023N- Nitrosodimethyl amine, the simplest member of the N-Nitrosamine family, is a carcinogenic and mutagenic agent that has gained considerable research interest owing to...
N- Nitrosodimethyl amine, the simplest member of the N-Nitrosamine family, is a carcinogenic and mutagenic agent that has gained considerable research interest owing to its toxic nature. Ozonation of industrially important hydrazines, such as unsymmetrical dimethylhydrazine (UDMH) or monomethylhydrazine (MMH), has been associated with NDMA formation and accumulation in the environment. UDMH/MMH - ozonation also leads to several other transformation products such as acetaldehyde dimethyl hydrazine (ADMH), tetramethyl tetra azene (TMT), diazomethane, methyl diazene, etc, which can be either precursors or competitors for NDMA formation. However, the relevant chemistry detailing the formation of these transformation products from UDMH/MMH -ozone reaction and their subsequent conversion to NDMA is not well understood. In this work, we explored the formation mechanism of ADMH and TMT from UDMH-ozonation and their further oxidation to NDMA using the second-order Moller Plesset perturbation theory employing the 6-311G(d) basis set. We have also investigated how MMH selectively forms methyl diazene and diazomethane under normal conditions and NDMA in the presence of excess ozone. Our calculations indicate that the reactions proceed via an initial H abstraction from the hydrazine -NH group, followed by the oxidation of the generated N-radical species. The formation of ADMH from the UDMH-ozone reaction involves an acetaldehyde intermediate, which then reacts with a second UDMH molecule to generate ADMH. The preferable attack of ozone molecule on N=C bond of ADMH generates DMAN intermediate, which subsequently undergoes oxidation to form NDMA. Unlike other transformation products, TMT formation occurs via the dimerization of DMAN. Though there exists an N=N bond in the TMT, which are preferable attacking sites for ozone, experimental studies show the lower yields of NDMA formation, which corroborates with the high activation barrier required for the process (42 kcal/mol). Overall, our calculated results agree well with the experimental observations and rate constants. Computational calculations bring new insights into the electronic nature and kinetics of the elementary reactions of this pathway, enabled by computed energies of structures that are not possible to access experimentally.
PubMed: 36967895
DOI: 10.1016/j.heliyon.2023.e14511 -
Molecules (Basel, Switzerland) Nov 2020Recently discovered hybrid perovskites based on hypophosphite ligands are a promising class of compounds exhibiting unusual structural properties and providing...
Recently discovered hybrid perovskites based on hypophosphite ligands are a promising class of compounds exhibiting unusual structural properties and providing opportunities for construction of novel functional materials. Here, we report for the first time the detailed studies of phonon properties of manganese hypophosphite templated with methylhydrazinium cations ([CHNHNH][Mn(HPO)]). Its room temperature vibrational spectra were recorded for both polycrystalline sample and a single crystal. The proposed assignment based on Density Functional Theory (DFT) calculations of the observed vibrational modes is also presented. It is worth noting this is first report on polarized Raman measurements in this class of hybrid perovskites.
Topics: Calcium Compounds; Cations; Density Functional Theory; Ions; Manganese; Materials Testing; Microscopy, Confocal; Models, Molecular; Monomethylhydrazine; Oxides; Phosphites; Quantum Theory; Software; Spectrophotometry, Infrared; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman; Temperature; Titanium; Vibration
PubMed: 33182446
DOI: 10.3390/molecules25215215