Acinetobacter sp. represent an important cause of nosocomial infections. Their resistance to some antibiotics, their ability to survive on inanimate surfaces in the hospital environment and their ability to produce biofilms contributes to their virulence. The aim of the study was to determine the antibacterial properties of cinnamon, lavender and geranium essential oils against bacteria of the genus Acinetobacter isolated from several clinical materials and from the hospital environment. A comprehensive evaluation of the susceptibility of Acinetobacter sp. clinical strains to recommended antibiotics was performed. The constituents of cinnamon, lavender and geranium essential oils were identified by GC-FID-MS analysis, and their Minimal Inhibitory Concentrations (MICs) against tested clinical strains were determined by the micro-dilution broth method. In addition, the effects of essential oils on the viability of human microvascular endothelial cells (HMEC-1) and glioblastoma cell line (T98G) were evaluated. Cinnamon bark oil was the most active against clinical and environmental strains of Acinetobacter baumannii with MIC values ranging from 0.5 to 2.5 µL/mL. The MIC values for geranium oil were between 7.5 and 9.5 µL/mL, and between 10.5 and 13.0 µL/mL for lavender oil. These essential oils can be best employed in the fight against infections caused by bacteria from Acinetobacter genus as components of formulations for hygiene and disinfection of hospital environment.

Ketamine is a new, potent and rapid-acting antidepressant approved for therapy of treatment-resistant depression, which has a different mechanism of action than currently-available antidepressant therapies. It owes its uniquely potent antidepressant properties to a complex mechanism of action, which currently remains unclear. However, it is thought that it acts by modulating the functioning of the glutamatergic system, which plays an important role in the process of neuroplasticity associated with depression. However, preclinical and clinical studies have also found ketamine to reduce inflammation, either directly or indirectly (by activating neuroprotective branches of the kynurenine pathway), among patients exhibiting higher levels of inflammation. Inflammation and immune system activation are believed to play key roles in the development and course of depression. Therefore, the present work examines the role of the antidepressant effect of ketamine and its anti-inflammatory properties in the treatment of depression. Significance Statement The present work examines the relationship between the antidepressant effect of ketamine and its anti-inflammatory properties, and the resulting benefits in treatment-resistant depression (TRD). The antidepressant mechanism of ketamine remains unclear, and there is an urgent need to develop new therapeutic strategies for treatment of depression, particularly TRD.

The clinical symptoms of Parkinson’s disease (PD) appear when dopamine (DA) concentrations in the striatum drops to around 20%. Simultaneous inhibitory effects on histamine H₃ receptor (H₃R) and MAO B can increase DA levels in the brain. A series of compounds was designed and tested in vitro for human H₃R (hH₃R) affinity and inhibitory activity to human MAO B (hMAO B). Results showed different activity of the compounds towards the two biological targets. Most compounds had poor affinity for hH₃R (K_i > 500 nM), but very good inhibitory potency for hMAO B (IC₅₀ < 50 nM). After further in vitro testing (modality of MAO B inhibition, permeability in PAMPA assay, cytotoxicity on human astrocyte cell lines), the most promising dual-acting ligand, 1-(3-(4-(tert-butyl)phenoxy)propyl)-2-methylpyrrolidine (13: hH₃R: K_i = 25 nM; hMAO B IC₅₀ = 4 nM) was selected for in vivo evaluation. Studies in rats of compound 13, in a dose of 3 mg/kg of body mass, confirmed its antagonistic effects for H₃R (decline in food and a water consumption), decline in MAO B activity (>90%) in rat cerebral cortex (CTX), and an increase in DA content in CTX and striatum. Moreover, compound 13 caused a slight increase in noradrenaline, but a reduction in serotonin concentration in CTX. Thus, compound 13 is a promising dual-active ligand for the potential treatment of PD although further studies are needed to confirm this.

Many central nervous system (CNS) diseases, including major depressive disorder (MDD), are underpinned by the unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress. New, more efficient, therapeutic options for MDD are needed to avoid adverse effects and drug resistance. Therefore, the aim of the work was to determine whether UPR signalling pathway activation in astrocytes may serve as a novel target for antidepressant drugs. Among the tested antidepressants (escitalopram, amitriptyline, S-ketamine and R-ketamine), only S-ketamine, and to a lesser extent R-ketamine, induced the expression of most ER stress-responsive genes in astrocytes. Furthermore, cell viability and apoptosis measuring assays showed that (R-)S-ketamine did not affect cell survival under ER stress. Under normal conditions, S-ketamine played the key role in increasing the release of brain-derived neurotrophic factor (BDNF), indicating that the drug has a complex mechanism of action in astrocytes, which may contribute to its therapeutic effects. Our findings are the first to shed light on the relationship between old astrocyte specifically induced substance (OASIS) stabilized by ER stress and (R-)S-ketamine; however, the possible involvement of OASIS in the mechanism of therapeutic ketamine action requires further study.