Proregenerative Activity of IL-33 in Gastric Tissue Cells Undergoing Helicobacter Pylori-Induced Apoptosis

: Interleukin (IL)-33 is a proinflammatory mediator that alerts the host immune system to disorders in tissue homeostasis. Aim. To understand the role of IL-33 in modulating gastric tissue cell growth affected by Helicobacter pylori (H. pylori). Methods. IL-33 production in guinea pigs (Caviae porcellus) experimentally infected with H. pylori was evaluated by ELISA or immunohistochemical staining. The proregenerative activity of IL-33 was evaluated using gastric epithelial cells and fibroblasts that were naive or transfected with IL-33 siRNA exposed to H. pylori glycine acid extract antigenic complex (GE), as well as by measuring cell migration, proliferation, metabolic activity and apoptosis. Animals infected by H. pylori responded with increased production of IL-33. Also, cells treated in vitro with GE released more IL-33 than cells that were unstimulated. Silencing IL-33 in cells resulted in downregulation of metabolic activity, adhesion, migration and proliferation, especially after treatment with H. pylori GE, as well as upregulation of cells apoptosis associated with caspase 3 increase and Bcl-xL decrease, suggesting proregenerative activity of IL-33. Interestingly, upregulation of cell proliferation by IL-33 was Erk independent. Our results indicate that IL-33 may protect gastric tissue from loss of homeostasis caused by deleterious effects of H. pylori components and the inflammatory response developed during infection

Validation of LC/MS/MS method for assessment of the "in vitro" activity of selected rat cytochrome P450 isoenzymes : application to early drug metabolism screening

A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for simultaneous determination of seven metabolites of CYP450 model substrates (acetaminophen, 4-hydroxytolbutamide, 4'-hydroxymephenytoin, 1-hydroxybufuralol, 6-hydroxychlorzoxazone. 1'-and 4-hydroxymidazolam) in rat liver microsomes was developed. The assay used Kinetex analytical column and a gradient mobile phase consistent of acetonitrile and water with addition of 0.1\% formic acid. The analysis was performed in selected reaction monitoring (SRM) mode both in positive and negative (for 6-hydroxychlorzoxazone) mode. The method was validated over the concentration ranges of 10-2000 ng/mL for 4-hydroxymephenytoin and 4-hydroxytolbutamide, 50-2000 ng/mL for 1-hydroxybufuralol and 25-2000 ng/mL for the rest of the analytes. The intra- and inter-day precision (2-12%) and accuracy (93-119%) were within the limits set by the FDA and EMA guidelines. The developed method was successfully applied to assess the activity of selected CYP450 isoenzymes in rat liver microsomes after addition of ketoconazole

Validation of LC/MS/MS method for assessment of the "in vitro" activity of the selected rat cytochrome P450 isoenzymes : application to early drug metabolism screening

A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for simultaneous determination of seven metabolites of CYP450 model substrates (acetaminophen, 4-hydroxytolbutamide, 4í-hydroxymephenytoin, 1-hydroxybufuralol, 6-hydroxychlorzoxazone, 1í- and 4í-hydroxymidazolam) in rat liver microsomes was developed. The assay used Kinetex analytical column and a gradient mobile phase consistent of acetonitrile and water with addition of 0.1% formic acid. The analysis was performed in selected reaction monitoring (SRM) mode both in positive and negative (for 6-hydroxychlorzoxazone) mode. The method was validated over the concentration ranges of 10-2000 ng/mL for 4í-hydroxymephenytoin and 4-hydroxytolbutamide, 50-2000 ng/mL for 1-hydroxybufuralol and 25-2000 ng/mL for the rest of the analytes. The intra- and inter-day precision (2-12%) and accuracy (93-119%) were within the limits set by the FDA and EMA guidelines. The developed method was successfully applied to assess the activity of selected CYP450 isoenzymes in rat liver microsomes after addition of ketoconazole

Beyond the Aesthetics: Understanding Risks in Nonsurgical Rhinoplasty

Nonsurgical rhinoplasty (NSR), colloquially referred to as a "liquid nose job," is a procedure that employs injectable fillers to modify the shape and contour of the nose. This procedure is particularly suited to patients presenting with minor imperfections and nasal defects. The procedure typically entails the injection of hyaluronic acid-based fillers, which are preferred due to their reversibility and safety profile. Although rare, dangerous complications are possible, therefore it is important to be aware of the risks associated with performing NSR and how to recognise and manage them. This article examines a number of potential complications associated with the procedure, including minor side effects such as bruising and swelling, as well as more serious risks such as vascular obstruction, skin necrosis and blindness. It is evident that the practitioner's experience and anatomical knowledge are of paramount importance in order to minimise the aforementioned risks. The aim of this review is to delineate the potential hazards associated with NSR. It is imperative that both clinicians and patients are cognizant that NSR is not a risk-free procedure. Dissemination of information may facilitate the implementation of safer practices and superior outcomes in facial aesthetic procedures

Z zagadnień bezpieczeństwa biznesu

Praca recenzowana / peer-reviewed pape

Hepatoselective Nitric Oxide (NO) Donors, V-PYRRO/NO and V-PROLI/NO, in Nonalcoholic Fatty Liver Disease: A Comparison of Antisteatotic Effects with the Biotransformation and Pharmacokinetics

ABSTRACT V-PYRRO/NO [O(2)-vinyl-1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate] and V-PROLI/NO (O2-vinyl-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate), two structurally similar diazeniumdiolate derivatives, were designed as liver-selective prodrugs that are metabolized by cytochrome P450 isoenzymes, with subsequent release of nitric oxide (NO). Yet, their efficacy in the treatment of nonalcoholic fatty liver disease (NAFLD) and their comparative pharmacokinetic and metabolic profiles have not been characterized. The aim of the present work was to compare the effects of V-PYRRO/NO and V-PROLI/NO on liver steatosis, glucose tolerance, and liver fatty acid composition in C57BL/6J mice fed a high-fat diet, as well as to comprehensively characterize the ADME (absorption, distribution, metabolism and excretion) profiles of both NO donors. Despite their similar structure, V-PYRRO/NO and V-PROLI/NO showed differences in pharmacological efficacy in the murine model of NAFLD. V-PYRRO/NO, but not V-PROLI/NO, attenuated liver steatosis, improved glucose tolerance, and favorably modified fatty acid composition in the liver. Both compounds were characterized by rapid absorption following i.p. administration, rapid elimination from the body, and incomplete bioavailability. However, V-PYRRO/NO was eliminated mainly by the liver, whereas V-PROLI/NO was excreted mostly in unchanged form by the kidney. V-PYRRO/NO was metabolized by CYP2E1, CYP2C9, CYP1A2, and CYP3A4, whereas V-PROLI/NO was metabolized mainly by CYP1A2. Importantly, V-PYRRO/NO was a better NO releaser in vivo and in the isolated, perfused liver than V-PROLI/NO, an effect compatible with the superior antisteatotic activity of V-PYRRO/NO. In conclusion, V-PYRRO/NO displayed a pronounced antisteatotic effect associated with liver-targeted NO release, whereas V-PROLI/NO showed low effectiveness, was not taken up by the liver, and was eliminated mostly in unchanged form by the kidney

Quantification and pharmacokinetics of 1-methylpyridinium and 1,4-dimethylpyridinium in rats by liquid chromatography tandem mass spectrometry : tissue distribution of 1,4-dimethylpyridinium in rats

A sensitive and specific liquid chromatography tandem mass spectrometry method for quantification of 1-methylpyridinium (1-MP) and 1,4-dimethylpyridinium (1,4-DMP) in rat plasma and tissues homogenates was developed. Chromatographic separation was performed on an Aquasil C18 analytical column with an isocratic elution of acetonitrile and water, both with an addition of formic acid (0.1%, v/v). Detection was achieved by triple quadrupole mass spectrometer TSQ Quantum Ultra equipped with a heated electrospray ionization source (HESI). The limit of quantification for both compounds was 0.05 μg/mL in plasma and 0.25 μg/g in studied tissues. The method was applied to pharmacokinetics and bioavailability of both 1-MP and 1,4-DMP with tissue distribution of 1,4-DMP in rats. Pharmacokinetic studies of 1-MP and 1,4-DMP were carried out following their intravenous or intragastric administration to male Wistar rats at the dose of 100 mg/kg. The terminal half-lives of 1-MP and 1,4-DMP after their intravenous administration were 55.3 and 70.8 min, respectively. The absolute bioavailability was 51 and 31% for 1-MP and 1,4-DMP, respectively

Genetic characteristics of three Baltic <i>Zostera marina</i>

We performed genetic analyses of three Baltic eelgrass (Zostera marina) populations in Puck Bay (PB), Cudema Bay (CB) and Greifswalder Bodden (GB). The aim of this study was to identify the eelgrass population genetically closest to that from the PB, which could potentially serve as a reservoir for the restoration of the underwater meadows in this bay, seriously degraded in the past. We applied a 12-microsatellite assay to test the genetic distance between the target eelgrass populations. We found that the allelic richness values of the GB, PB and CB populations were 2.25, 3.77 and 3.50 respectively. The genetic diversity found in GB was low and could be explained by the population's history, whereas the diversity of CB was higher than expected in a population located at the edge of the species' range. Analyses of genetic differentiation and structure showed that of the three populations studied, PB and CB were closer to each other than to the GB population. The reasons for this differentiation in eelgrass populations and the implications of the results of their genetic analysis on the planned restoration of the PB populations are discussed

Genetic characteristics of three Baltic Zostera marina populations* This work was financially supported by the project: ‘ZOSTERA: Restoration of ecosystem key elements in the inner Puck Bay’.

We performed genetic analyses of three Baltic eelgrass (Zostera marina) populations in Puck Bay (PB), Cudema Bay (CB) and Greifswalder Bodden (GB). The aim of this study was to identify the eelgrass population genetically closest to that from the PB, which could potentially serve as a reservoir for the restoration of the underwater meadows in this bay, seriously degraded in the past. We applied a 12-microsatellite assay to test the genetic distance between the target eelgrass populations. We found that the allelic richness values of the GB, PB and CB populations were 2.25, 3.77 and 3.50 respectively. The genetic diversity found in GB was low and could be explained by the population’s history, whereas the diversity of CB was higher than expected in a population located at the edge of the species’ range. Analyses of genetic differentiation and structure showed that of the three populations studied, PB and CB were closer to each other than to the GB population. The reasons for this differentiation in eelgrass populations and the implications of the results of their genetic analysis on the planned restoration of the PB populations are discussed