Estradiol and Estrogen-like Alternative Therapies in Use: The Importance of the Selective and Non-Classical Actions.

Estrogen is one of the most important female sex hormones, and is indispensable for reproduction. However, its role is much wider. Among others, due to its neuroprotective effects, estrogen protects the brain against dementia and complications of traumatic injury. Previously, it was used mainly as a therapeutic option for influencing the menstrual cycle and treating menopausal symptoms. Unfortunately, hormone replacement therapy might be associated with detrimental side effects, such as increased risk of stroke and breast cancer, raising concerns about its safety. Thus, tissue-selective and non-classical estrogen analogues have become the focus of interest. Here, we review the current knowledge about estrogen effects in a broader sense, and the possibility of using selective estrogen-receptor modulators (SERMs), selective estrogen-receptor downregulators (SERDs), phytoestrogens, and activators of non-genomic estrogen-like signaling (ANGELS) molecules as treatment.

Identification of a newly isolated lytic bacteriophage against K24 capsular type, carbapenem resistant Klebsiella pneumoniae isolates.

The increasing incidence of carbapenemase-producing K. pneumoniae strains (CP-Kps) in the last decade has become a serious global healthcare problem. Therapeutic options for the treatment of emerging hospital clones have drastically narrowed and therefore novel approaches must be considered. Here we have isolated and characterized a lytic bacteriophage, named vB_KpnS_Kp13, that was effective against all Verona integron-encoded metallo-ß-lactamase (VIM) producing K. pneumoniae isolates originating from hospital samples (urine, blood, sputum and faeces), belonging to the ST15 clonal lineage and expressing the K24 capsule. Morphological characterization of vB_KpnS_Kp13 showed that the newly identified phage belonged to the Siphoviridae family, and phylogenetic analysis showed that it is part of a distinct clade of the Tunavirinae subfamily. Functional analysis revealed that vB_KpnS_Kp13 had relatively short latent period times (18 minutes) compared to other K. pneumoniae bacteriophages and could degrade biofilm by more than 50% and 70% in 24 and 48 hours respectively. Complete in vivo rescue potential of the new phage was revealed in an intraperitoneal mouse model where phages were administered intraperitoneally 10 minutes after bacterial challenge. Our findings could potentially be used to develop specific anti-CP-Kps bacteriophage-based therapeutic strategies against major clonal lineages and serotypes.

Characterization of the Rhodococcus sp. MK1 strain and its pilot application for bioremediation of diesel oil-contaminated soil.

Petroleum hydrocarbons and derivatives are widespread contaminants in both aquifers and soil, their elimination is in the primary focus of environmental studies. Microorganisms are key components in biological removal of pollutants. Strains capable to utilize hydrocarbons usually appear at the contaminated sites, but their metabolic activities are often restricted by the lack of nutrients and/or they can only utilize one or two components of a mixture. We isolated a novel Rhodococcus sp. MK1 strain capable to degrade the components of diesel oil simultaneously. The draft genome of the strain was determined and besides the chromosome, the presence of one plasmid could be revealed. Numerous routes for oxidation of aliphatic and aromatic compounds were identified. The strain was tested in ex situ applications aiming to compare alternative solutions for microbial degradation of hydrocarbons. The results of bioaugmentation and biostimulation experiments clearly demonstrated that - in certain cases - the indigenous microbial community could be exploited for bioremediation of oil-contaminated soils. Biostimulation seems to be efficient for removal of aged contaminations at lower concentration range, whereas bioaugmentation is necessary for the treatment of freshly and highly polluted sites.

Bacteriophage therapy against staphylococci.

The emergence of the multi-drug-resistant Staphylococcus aureus strains has prompted interest in alternatives to conventional drugs. Among the possible options one of the most promising is the therapeutic use of bacteriophages. Over the recent decades, increasing amount of literature has validated the use of bacteriophages for therapy and prophylaxis against drug-resistant staphylococci. This work attempts to review the current knowledge on bacteriophages and their usages for treatment of staphylococcal diseases.

Dietary phosphatidylcholine supplementation attenuates inflammatory mucosal damage in a rat model of experimental colitis.

This study was designed to follow the time course of inflammatory activation in a rodent model of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis. We hypothesized that oral phosphatidylcholine (PC) pretreatment regimens may influence leukocyte-mediated microcirculatory reactions in this condition. In series I, Wistar rats were monitored 1 day after colitis induction (n = 24), and in series II (n = 24) on day 6 following a TNBS enema. The PC-pretreated animals received a 2% PC-enriched diet for 6 days before the TNBS enema (series I), or for 3 days before and 3 days after TNBS treatment (series II). The macrohemodynamics, serosal microcirculation (visualized by intravital videomicroscopy), colonic xanthine oxidoreductase, myeloperoxidase and nitric oxide end products, and changes in proinflammatory cytokine levels in plasma were measured. The mucosal structural injury was monitored in vivo by means of confocal laser scanning endomicroscopy. The TNBS enema induced a systemic hyperdynamic circulatory reaction with increased serosal capillary blood flow and significantly elevated colonic inflammatory enzyme activities, levels of nitric oxide production, and cytokine concentrations. Acute colitis caused disruption of the capillary network, whereas the morphologic damage was less severe in series II. The PC pretreatment protocols led to significant decreases in the serosal hyperemic reaction, the cytokine levels, and the inflammatory enzyme activities. The objective signs of tissue damage were reduced in both series, and the number of mucus-producing goblet cells in the resolving phase of colitis was increased. Dietary PC efficiently decreases the cytokine-mediated progression of inflammatory events and preserves the microvascular structure in the large intestine.