Ambenonium Chloride

Sets of 346 herbicides in use and 163 no longer in use were collected from open access online sources and compared in silico with cholinesterases inhibitors (ChI) and drugs in terms of physicochemical profile and estimated toxic effects on human health. The screening revealed at least one potential adverse consequence for each herbicide class assigned according to their mode of action on weeds. The classes with most toxic warnings were K1, K3/N, F1 and E. The selection of 11 commercial herbicides for in vitro biological tests on human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), the enzymes involved in neurotoxicity and detoxification of various xenobiotics, respectively, was based mainly on the structural similarity with inhibitors of cholinesterases. Organophosphate anilofos and oxyacetanilide flufenacet were the most potent inhibitors of AChE (25 μM) and BChE (6.4 μM), respectively. Glyphosate, oxadiazon, tembotrione and terbuthylazine were poor inhibitors with an estimated IC₅₀ above 100 μM, while for glyphosate the IC₅₀ was above 1 mM. Generally, all of the selected herbicides inhibited with a slight preference towards BChE. Cytotoxicity assays showed that anilofos, bensulide, butamifos, piperophos and oxadiazon were cytotoxic for hepatocytes (HepG2) and neuroblastoma cell line (SH-SY5Y). Time-independent cytotoxicity accompanied with induction of reactive oxygen species indicated rapid cell death in few hours. Our results based on in silico and in vitro analyses give insight into the potential toxic outcome of herbicides in use and can be applied in the design of new molecules with a less impact on humans and the environment.

Myasthenia gravis (MG) is a rare autoimmune disorder of neuromuscular junction. MG healthcare burden has not been studied in Poland before.

Data were drawn from the National Health Fund database; MG patient was defined as a person who received at least once medical service with ICD-10 code MG (G70) and at least two reimbursed prescriptions for pyridostigmine bromide or ambenonium chloride in two consecutive years. We have analyzed treatment: immunosuppression, intravenous immunoglobulins (IVIg), plasma exchange (PE), the number and length of hospitalizations (LOS), intensive care unit (ICU) care, and deaths between 2013 and 2018.

In 2018, there were 9012 MG patients (F:M 1.62:1), and 30.6% had early -onset MG (<50 years). 66.3% received symptomatic treatment only, 33.7%-glucocorticoids (CS) and/or other immunosuppressants (IS), 64.6%-CS only, 17.5%-azathioprine plus CS, 11%-azathioprine only, 4.6%-CS plus other IS (methotrexate, mycophenolate mofetil, cyclosporine, or tacrolimus), and 2%-other IS only. In 2018, 42.3% of patients were hospitalized at least once (mean 2.05/year), 13.7% due to MG (1.47/year). In 2018, 1.63% patients received PE, 2.33% IVIg. In 2013-2018, 2.7%-3.2% of MG patients required hospitalization in ICU. ICU mean LOS 2013-2018 was 11.5-15.0 days/per patient/year. 2.1% of all MG patients had myasthenic crisis. Mean age at death was 75.7 years for MG and 73.9 for general population (p = .006). All-cause mortality was higher for men (4.1%-5.1%) than for women (2.5%-3.1%), p < .01.

Our findings confirm significant healthcare burden of MG, comprising a tool to plan resources needed for MG patients.