"Novichok" refers to a new group of nerve agents called the A-series agents. Their existence came to light in 2018 after incidents in the UK and again in 2020 in Russia. They are unique organophosphorus-based compounds developed during the Cold War in a program called Foliant in the USSR. This review is based on original chemical entities from Mirzayanov's memoirs published in 2008. Due to classified research, a considerable debate arose about their structures, and hence, various structural moieties were speculated. For this reason, the scientific literature is highly incomplete and, in some cases, contradictory. This review critically assesses the information published to date on this class of compounds. The scope of this work is to summarize all the available and relevant information, including the physicochemical properties, chemical synthesis, mechanism of action, toxicity, pharmacokinetics, and medical countermeasures used to date. The environmental stability of A-series agents, the lack of environmentally safe decontamination, their high toxicity, and the scarcity of information on post-contamination treatment pose a challenge for managing possible incidents.
- MeSH
- kontaminace léku * MeSH
- nervová bojová látka * toxicita MeSH
- organofosforové sloučeniny MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Cucurbit[n]urils are macrocyclic compounds capable of forming host-guest complexes with different molecules. In this study, we focused on cucurbit[7]uril (CB[7]) safety and pharmacokinetics. We investigated CB[7] cytotocixity in human renal cells ACHN using the xCELLigence system. We also determined maximum tolerated doses (MTD) and no observed adverse effect levels (NOAEL) after intramuscular (i.m.), intraperitoneal (i.p.), and intragastric (i.g.) administration in mice using clinical observation, blood biochemistry, and histopathology. At NOAELs, we studied its pharmacokinetics in plasma and kidneys. Finally, we performed a 7 day repeated-dose toxicity study at 50% of NOAEL after i.p. administration, assaying CB[7] concentration in plasma, brain, kidney, and liver; we also assessed the liver and kidney histopathology. In vitro, CB[7] did not show toxicity up to 0.94 mg/mL. MTDs in vivo were set at 300, 350, and 600 mg/kg, and NOAEL were established at 150, 100, and 300 mg/kg after i.m., i.p., and i.g. administration, respectively. Parenteral administration produced tissue damage mainly to the kidney, while i.g. administration caused only minor liver damage. Parenteral CB[7] administration led to fast elimination from blood, accompanied with kidney accumulation; absorption from the gastrointestinal tract was minimal. Short repeated i.p. administration was well tolerated. After initial CB[7] accumulation in blood and kidney, the concentrations stabilised and decreased during the experiment. Approximately 3.6% of animals showed signs of nephrotoxicity. Although CB[7] appears to be a promising molecule, nephrotoxicity may be the most critical drawback of its parenteral use, because the kidney represents the main organ of its elimination.
AIM: The comparison of neuroprotective and central reactivating effects of the oxime K870 in combination with atropine with the efficacy of standard antidotal treatment in tabun-poisoned rats. METHODS: The neuroprotective effects of antidotal treatment were determined in rats poisoned with tabun at a sublethal dose using a functional observational battery 2 h and 24 h after tabun administration, the tabun-induced brain damage was investigated by the histopathological evaluation and central reactivating effects of oximes was evaluated by the determination of acetylcholinesterase activity in the brain using a standard spectrophotometric method. RESULTS: The central reactivating efficacy of a newly developed oxime K870 roughly corresponds to the central reactivating efficacy of pralidoxime while the ability of the oxime HI-6 to reactivate tabun-inhibited acetylcholinesterase in the brain was negligible. The ability of the oxime K870 to decrease tabun-induced acute neurotoxicity was slightly higher than that of pralidoxime and similar to the oxime HI-6. These results roughly correspond to the histopathological evaluation of tabun-induced brain damage. CONCLUSION: The newly synthesized oxime K870 is not a suitable replacement for commonly used oximes in the antidotal treatment of acute tabun poisonings because its neuroprotective efficacy is only slightly higher or similar compared to studied currently used oximes.
- MeSH
- acetylcholinesterasa MeSH
- antidota farmakologie MeSH
- chemické bojové látky * toxicita MeSH
- cholinesterasové inhibitory farmakologie MeSH
- jedy * MeSH
- krysa rodu rattus MeSH
- organofosfáty * MeSH
- oximy * farmakologie MeSH
- potkani Wistar MeSH
- pralidoximové sloučeniny MeSH
- pyridinové sloučeniny * farmakologie MeSH
- reaktivátory cholinesterázy * farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Gastrointestinal injury caused by dextran sodium sulphate (DSS) is a reliable porcine experimental model of inflammatory bowel disease (IBD). The purpose of this study was to evaluate the effect of probiotic Lactobacillus casei DN 114001 (LC) on DSS-induced experimental IBD. RESULTS: Eighteen female pigs (Sus scrofa f. domestica, weight 33-36 kg, age 4-5 months) were divided into 3 groups (6 animals per group): controls with no treatment, DSS, and DSS + LC. LC was administered to overnight fasting animals in a dietary bolus in the morning on days 1-7 (4.5 × 1010 live bacteria/day). DSS was applied simultaneously on days 3-7 (0.25 g/kg/day). On day 8, the pigs were sacrificed. Histopathological score and length of crypts/glands (stomach, jejunum, ileum, transverse colon), length and width of villi (jejunum, ileum), and mitotic and apoptotic indices (jejunum, ileum, transverse colon) were assessed. DSS increased the length of glands in the stomach, length of crypts and villi in the jejunum and ileum, and the histopathological score of gastrointestinal damage, length of crypts and mitotic activity in the transverse colon. Other changes did not achieve any statistical significance. Administration of LC reduced the length of villi in the jejunum and ileum to control levels and decreased the length of crypts in the jejunum. CONCLUSIONS: Treatment with a probiotic strain of LC significantly accelerated regeneration of the small intestine in a DSS-induced experimental porcine model of IBD.
Background: The goal of our research is to show the effects and impacts of hyperbaric oxygen therapy (HBOT) on acute model wounds in animal subjects. Methods: Three experimental groups were created using injured rabbits (N=36)-randomly divided into three groups (N=12 per group). One group was treated only with standard wound care management. Two groups were additionally treated with HBOT either once or twice a day. The wounds were surgical, uninfected, and in healthy animal test subjects. We compared the immunohistochemical and histological parameters in 4-, 7- and 10-day intervals.Results: The detection of epidermal leaf parameters, the number of microabscesses, the Histopathological Superficial Epithelium Healing Score, Connective Tissue Healing Score, Histopathological Acute Inflammation Score and Total Histopathological Wound Healing Score all showed significant changes between time intervals within the individual groups.Conclusion: The results did not show that HBOT had a significant effect on the healing process of uncomplicated acute wounds.
- Klíčová slova
- Hyperbaric oxygen, Wound healing, Animal models, Adjunctive treatment,
- MeSH
- biopsie MeSH
- hojení ran MeSH
- hyperbarická oxygenace * metody veterinární MeSH
- králíci zranění MeSH
- Check Tag
- králíci zranění MeSH
- Publikační typ
- abstrakt z konference MeSH
Early changes after radiation exposure may serve as predictors as well as targets for alleviation of radiation-induced injury in the lung. The aim of our study was to examine alterations on the cell and tissue levels in the lung and blood changes of immunological and cytokines profiles induced by ionizing radiation (IR) during the first month after irradiation in the mice experimental model. Female C57BL/6 mice were total body irradiated (TBI) by 8 Gy. Lung tissue samples and blood and were collected 4, 8 and 24 h, 7, 21 and 30 d after TBI. We measured absolute cell counts, cell populations and cytokines profile in the blood and evaluated histopathological analysis in the lung, immunophenotypization of the main lung cell populations and cytokine profiles. In blood, the acute radiation syndrome developed with recovery being observed at 21-30 d, observed by hematological markers. In the lung tissue, a biphasic response occurred. At first, a significant decreased of lymphocytes, resident tissues macrophages and air/tissue ratio associated with increased neutrophils was observed at 8 - 24 h. Subsequently, increase in infiltrating CD4+ T-lymphocytes, neutrophils and resident tissues macrophages and decreased airiness were measured 21 and 30 d after TBI. In summary, our study describes the mechanisms that lung tissue enables to cope with non-lethal injury.
