Metformin and Its Sulfenamide Prodrugs Inhibit Human Cholinesterase Activity

The results of epidemiological and pathophysiological studies suggest that type 2 diabetes mellitus (T2DM) may predispose to Alzheimer’s disease (AD). The two conditions present similar glucose levels, insulin resistance, and biochemical etiologies such as inflammation and oxidative stress. The diabetic state also contributes to increased acetylcholinesterase (AChE) activity, which is one of the factors leading to neurodegeneration in AD. The aim of this study was to assess in vitro the effects of metformin, phenformin, and metformin sulfenamide prodrugs on the activity of human AChE and butyrylcholinesterase (BuChE) and establish the type of inhibition. Metformin inhibited 50% of the AChE activity at micromolar concentrations (2.35 μmol/mL, mixed type of inhibition) and seemed to be selective towards AChE since it presented low anti-BuChE activity. The tested metformin prodrugs inhibited cholinesterases (ChE) at nanomolar range and thus were more active than metformin or phenformin. The cyclohexyl sulfenamide prodrug demonstrated the highest activity towards both AChE (IC50 = 890 nmol/mL, noncompetitive inhibition) and BuChE (IC50 = 28 nmol/mL, mixed type inhibition), while the octyl sulfenamide prodrug did not present anti-AChE activity, but exhibited mixed inhibition towards BuChE (IC50 = 184 nmol/mL). Therefore, these two bulkier prodrugs were concluded to be the most selective compounds for BuChE over AChE. In conclusion, it was demonstrated that biguanides present a novel class of inhibitors for AChE and BuChE and encourages further studies of these compounds for developing both selective and nonselective inhibitors of ChEs in the future

A cultivation unit for forest nursery seedbeds

Hodowla sadzonek drzew leśnych w korytach (inspektach Dunemanna) daje możliwość intensyfikacji produkcji leśnego materiału rozmnożeniowego, jednak konstrukcja samych obiektów nie sprzyja mechanizacji poszczególnych zabiegów agrotechnicznych. Przygotowanie podłoża odbywa się zwykle poprzez ręczny wysiew nawozu i mieszanie go z substratem za pomocą ręcznie prowadzonej glebogryzarki napędzanej silnikiem spalinowym, następnie zagrabienie i uwałowanie powierzchni. W niniejszym opracowaniu zaprezentowano urządzenie, które nie ma odpowiednika w technice szkółkarskiej, umożliwiające precyzyjne dozowanie nawozu, mieszanie z podłożem do zadanej głębokości, formowanie powierzchni siewnej oraz wałowanie gleby. Czasochłonność przygotowania podłoża przy wykorzystaniu agregatu nowej konstrukcji w porównaniu do tradycyjnej ręcznej technologii jest ponad 8-krotnie mniejsza.Forest tree seedling cultivation in Dunemann seedbeds facilitates the intensification of production of forest reproductive material. However, the construction of seedbeds themselves is not conducive to mechanisation of individual agrotechno-logical operations. Substrate preparation is usually performed by manual spreading of a fertiliser and by mixing it with the substrate by means of a manually operated rotary tiller powered by an internal combustion engine, which is followed by surface raking and compaction. This study presents a device that has no equivalent in nursery technology. The unit en-ables precise measurement of a fertiliser amount, mixing it with the soil to a given depth, forming a sowing surface, and soil compaction. Thanks to the use of the novel cultivation unit, the time-consuming substrate preparation becomes over 8 times lower as compared to the traditional manual technology

Nursery squeezer of seedlings from polystyrene containers

Autorzy współpracując z polskimi producentami maszyn i urządzeń dla gospodarki leśnej, opracowali szereg nowych rozwiązań zwłaszcza z obszaru nasiennictwa i szkółkarstwa leśnego. Wprowadzenie na szeroką skalę hodowli sadzonek drzew leśnych na bazie tzw. modelu francuskiego - w kontenerach styropianowych - niesie wiele korzyści, natomiast problemem technologicznym są trudności w wydobyciu sadzonek celem wysadzania lub przechowywania w chłodni. W ramach prac badawczo-rozwojowych dokonano pomiaru sił jednostkowych potrzebnych do odspojenia bryłek korzeniowych oraz opracowano konstrukcję kompaktowej wyciskarki sadzonek.In cooperation with Polish producers of forest management machinery and equipment, the present authors have developed a number of novel solutions, especially in the field of seed production and forest nursery. The large-scale introduction of forest tree seedling cultivation based on the so-called French model, i.e. in foamed polystyrene containers, has many benefits, while the technological problem lies in the difficulty of extracting seedlings in order to plant them or store in a cold store. The present research and development project included measurement of the unit forces needed for root ball detachment as well as construction of a compact seedling squeezer