Ketamine - A New Antidepressant Drug with Anti-Inflammatory Properties.

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.

Gut Microbiota Metabolites Differentially Release Gliotransmitters from the Cultured Human Astrocytes: A Preliminary Report.

Butyrate and indole-3-propionic acid represent the CNS-available gut microbiota metabolites exhibiting potentially beneficial effects on human brain function and being tested as antidepressants. Astrocytes represent one of the putative targets for the gut metabolites; however, the mechanism of action of butyrate and indole-3-propionic acid is not well understood. In order to test this mechanism, a human astrocyte cell-line culture was treated with the compounds or without them, and the supernatants were collected for the analysis of ATP and glutamate gliotransmitter release with the use of luminescent and fluorescent methods, respectively. A 10-min incubation of astrocytes with 1-5 mM butyrate increased the ATP gliotransmitter release by 78% (95%CI: 45-119%), p < 0.001. The effect was found to be mediated by the cytosolic Ca2+ mobilization. Both 10-min and 24-h treatments with indole-3-propionic acid produced no significant effects on the release of gliotransmitters. The results for glutamate release were inconclusive due to a specific glutamate release pattern discovered in the tested model. This preliminary report of butyrate-induced ATP gliotransmitter release appears to provide a novel mechanistic explanation for the beneficial effect of this gut microbiota metabolite on brain function; however, the results require further evaluation in more composed models.

Diosmin and Bromelain Stimulate Glutathione and Total Thiols Production in Red Blood Cells.

Diosmin and bromelain are bioactive compounds of plant origin with proven beneficial effects on the human cardiovascular system. We found that diosmin and bromelain slightly reduced total carbonyls levels and had no effect on TBARS levels, as well as slightly increased the total non-enzymatic antioxidant capacity in the RBCs at concentrations of 30 and 60 µg/mL. Diosmin and bromelain induced a significant increase in total thiols and glutathione in the RBCs. Examining the rheological properties of RBCs, we found that both compounds slightly reduce the internal viscosity of the RBCs. Using the MSL (maleimide spin label), we revealed that higher concentrations of bromelain led to a significant decrease in the mobility of this spin label attached to cytosolic thiols in the RBCs, as well as attached to hemoglobin at a higher concentration of diosmin, and for both concentrations of bromelain. Both compounds tended to decrease the cell membrane fluidity in the subsurface area, but not in the deeper regions. An increase in the glutathione concentration and the total level of thiol compounds promotes the protection of the RBCs against oxidative stress, suggesting that both compounds have a stabilizing effect on the cell membrane and improve the rheological properties of the RBCs.

Association of Polymorphic Variants in Argonaute Genes with Depression Risk in a Polish Population.

Argonaute (AGO) proteins, through their key role in the regulation of gene expression, participate in many biological processes, including cell differentiation, proliferation, death and DNA repair. Accurate regulation of gene expression appears to be important for the proper development of complex neural circuits. Loss of AGO proteins is known to lead to early embryonic mortality in mice with various malformations, including anomalies of the central nervous system. Single-nucleotide polymorphisms (SNPs) of AGO genes can lead to deregulation of the processes in which AGO proteins are involved. The contribution of different SNPs in depression has been extensively studied. However, there are hardly any studies on the contribution of AGO genes. The aim of our research was to assess the relationship between the occurrence of depression and the presence of SNPs in genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) in a Polish population. One hundred and one subjects in the study group were diagnosed with recurrent depressive disorder by a psychiatrist. The control group comprised 117 healthy subjects. Study participants performed the HDRS (Hamilton Depression Scale) test to confirm or exclude depression and assess severity. The frequency of polymorphic variants of genes AGO1 (rs636882) and AGO2 (rs4961280; rs2292779; rs2977490) was determined using TaqMan SNP genotyping assays and the TaqMan universal PCR master mix, no AmpErase UNG. The rs4961280/AGO2 polymorphism was associated with a decrease in depression occurrence in the codominant (OR = 0.51, p = 0.034), dominant (OR = 0.49, p = 0.01), and overdominant (OR = 0.58, p = 0.049) models. Based on the obtained results, we found that the studied patients demonstrated a lower risk of depression with the presence of the polymorphic variant of the rs4961280/AGO2 gene-genotype C/A and C/A-A/A.

Diclofenac Diminished the Unfolded Protein Response (UPR) Induced by Tunicamycin in Human Endothelial Cells.

Diclofenac belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs), which are amongst the most frequently prescribed drugs to treat fever, pain and inflammation. Despite the presence of NSAIDs on the pharmaceutical market for several decades, epidemiological studies have shown new clinical applications of NSAIDs, and new mechanisms of their action were discovered. The unfolded protein response (UPR) activated under endoplasmic reticulum (ER) stress is involved in the pathophysiology of many diseases and may become a drug target, therefore, the study evaluated the effects of diclofenac on the tunicamycin-induced UPR pathways in endothelial cells. RT PCR analysis showed that diclofenac significantly inhibited activation of ER stress-responsive genes, i.e., CHOP/DITT3, GRP78/HSPA5 and DNAJB9. Additionally, the drug diminished the significant upregulation and release of the GRP78 protein, as evaluated using the ELISA assay, which was likely to be involved in the mechanism of the UPR activation resulting in apoptosis induction in endothelial cells. These results suggest the value of diclofenac as a factor capable of restoring the ER homeostasis in endothelial cells by diminishing the UPR.

Determinants of Knowledge About Dietary Supplements Among Polish Internet Users: Nationwide Cross-sectional Study.

BACKGROUND: An accurate understanding of dietary supplements (DS) is a prerequisite for informed decisions regarding their intake. However, there is a need for studies on this understanding among the public based on validated research tools. OBJECTIVE: This study aims to assess the knowledge about DS among Polish internet users with no medical education and to identify its determinants and design an appropriate predictive model. METHODS: The study protocol was prospectively registered with a statistical analysis plan. Polish users of a web-based health service and a social networking service were administered a survey consisting of the recently developed questionnaire on knowledge about DS, the questionnaire on trust in advertising DS, the beliefs about medicines questionnaire, and several other health-related single-item measures and sociodemographic questions. The results were subjected to general linear modeling. RESULTS: A total of 6273 participants were included. Of the 17 yes or no questions in the questionnaire of knowledge about DS, the mean number of correct responses was 9.0 (95% CI 8.9-9.1). Health service users performed worse than social networking users by 2.3 points (95% CI 2.1-2.5) in an analysis adjusted for potential confounders. Internet users had fewer true beliefs about DS if they presented higher trust in their advertising (adjusted ß=-.37; 95% CI -.39 to -.34), used DS (adjusted ß=-.14; 95% CI -.17 to -.12), experienced their positive effect (adjusted ß=-.16; 95% CI -.18 to -.13), were older or younger than 35 years (adjusted ß=-.14; 95% CI -.17 to -.12), expressed interest in the topic of DS (adjusted ß=-.10; 95% CI -.13 to -.08), reported getting information about the products from friends (adjusted ß=-.13; 95% CI -.15 to -.11), and believed that medicines are harmful (adjusted ß=-.12; 95% CI -.15 to -.10). The proposed 5-predictor model could explain 31.2% of the variance in knowledge about DS. The model appeared resistant to overfitting and was able to forecast most of the observed associations. CONCLUSIONS: Polish internet users with no medical education exhibit some false beliefs regarding DS. Trusting the advertising of DS appears to conflict with knowledge about them. There is an urgent need for effective web-based educational campaigns on DS and the promotion of advertising literacy. After the proposed predictive model is externally validated, it may help identify the least informed target audience.

Innate Immune Response against Staphylococcus aureus Preincubated with Subinhibitory Concentration of trans-Anethole.

The study aimed to analyze morphological and functional changes of Staphylococcus aureus cells due to trans-anethole (a terpenoid and the major constituent of fennel, anise, or star anise essential oils) exposition, and their consequences for human neutrophils phagocytic activity as well as IL-8 production (recognized as the major chemoattractant). The investigation included the evaluation of changes occurring in S. aureus cultures, i.e., staphyloxanthin production, antioxidant activities, cell size distribution, and cells composition as a result of incubation with trans-anethole. It was found that the presence of trans-anethole in the culture medium reduced the level of staphyloxanthin production, as well as decreased antioxidant activities. Furthermore, trans-anethole-treated cells were characterized by larger size and a tendency to diffuse in comparison to the non-treated cells. Several cell components, such as phospholipids and peptidoglycan, were found remarkably elevated in the cultures treated with trans-anethole. As a result of the aforementioned cellular changes, the bacteria were phagocytized by neutrophils more efficiently (ingestion and parameters associated with killing activity were at a higher level as compared to the control system). Additionally, IL-8 production was at a higher level for trans-anethole modified bacteria. Our results suggest that trans-anethole represents a promising measure in combating severe staphylococcal infections, which has an important translational potential for clinical applications.

Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors.

Several lines of evidence suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide playing an important role as a neuromodulator. It has been indicated that PACAP is associated with mental diseases, and that regulation of the PACAPergic signals could be a potential target for the treatment of such psychiatric states as schizophrenia. Recent studies have suggested that action of neuroleptic drugs is mediated not only by dopaminergic and serotonergic neurotransmission, but also via neuropeptides which may act both as neurotransmitters and as neuromodulators. The present study examines whether currently-used neuroleptics influence the action of PACAP receptors, whose expression is altered in a schizophrenic patient. Real-time polymerase chain reaction (PCR) was used to examine the effects of haloperidol, olanzapine and amisulpride on the expression of genes coding PAC1/VPAC type receptors in the T98G glioblastoma cell line, as an example of an in vitro model of glial cells. PAC1 mRNA expression fell after 24-h incubation with haloperidol or olanzapine; however the effect was not maintained after 72 h, and haloperidol even up-regulated PAC1 mRNA expression in a dose-dependent manner. All the examined drugs decreased VPAC2 mRNA expression, especially after 72-h incubation. Haloperidol (typical neuroleptic) was distinctly more potent than atypical neuroleptic drugs (olanzapine and amisulpride). In addition, PACAP increased PAC1 and VPAC2 mRNA expression. In conclusion, our findings suggest PACAP receptors may be involved in the mechanism of typical and atypical neuroleptic drugs.

[Evaluation of selected vascular active factors in patients after myocardial infarction subjected to cardiac rehabilitation]. / Ocena stezenia wybranych czynników naczyniowo aktywnych u chorych po ostrym zespole wiencowym poddanych rehabilitacji kardiologicznej.

Atherosclerosis is an inflammatory process that develops in the coronary arteries. Clinically active agents such as proinflammatory interleukins, TNF-α, tissue inhibitors of metalloproteinases (including TIMP-1), and vascular endothelial growth factor (VEGF), are important factors in the development of acute coronary syndromes. AIM: The aim of the study was to evaluate the effect of cardiac rehabilitation (stage II) on the concentration of selected vascular active factors (IL- 1, IL-6, TIMP-1, VEGF). MATERIALS AND METHODS: The study involved 24 patients after ACS who underwent complex cardiac rehabilitation (stage II) in the Department of Internal Medicine and Cardiac Rehabilitation at the Medical University of Lodz. The study involved 20 men and 4 women aged 42-78 years (average age 58.75 ± 8.45 years). The ELISA method was used in the vascular endothelial cell assay using readymade sets for determining individual molecules: Human Quantum ELISA Kit (DTM100; R & D Systems, BIOKOM, Poland), Human VEGF Quantikine ELISA Kit (DVE00; R & D Systems, BIOKOM, Poland) Human IL-1 beta / IL-1F2 Quantikine ELISA Kit (DLB50; R & D Systems, BIOKOM, Poland), Human IL-6 Quantikine ELISA Kit (D6050, R & D Systems, BIOKOM, Poland). TIMP-1 concentration is expressed in ng / ml, VEGF in pg / ml, IL-1 in pg / ml, IL-6 pg / ml. The results of the study were analyzed statistically at significance level p <0,05. RESULTS: There was no significant effect of cardiac rehabilitation on vascular endothelial factors: TIMP-1, VEGF, IL-6. Significant effect of cardiac rehabilitation was observed on the increase of IL-1 concentration (p=0.016). CONCLUSIONS: The absence of post-cardiac rehabilitation in patients after ACS, significant changes in vascular endothelial activity, confirm the hypothesis that adequate physical effort does not involve changes in blood concentrations and justifies perception of rehabilitation as a safe and risk-free intervention.

[The usefulness of the scale before exercise and exercise to identify coronary artery disease by physiotherapists]. / Przydatnosc skali przedwysilkowej i wysilkowej do rozpoznawania choroby wiencowej przez fizjoterapeutów.

Myocardial ischemia can be assessed by ECG at rest or doing the stress test, which also serves to evaluate the results of cardiac rehabilitation. AIM: The aim of this study was to determine the usefulness of the scale before exercise and exercise to assess the risk of coronary heart disease and recognition by physiotherapists. MATERIALS AND METHODS: The study included three groups of people: 1. 65 patients with stable coronary heart disease (IHD), including 45 men and 20 women, ranging in age from 33 to 79 years, an average of 60.18 ± 9.43 years who exercise test was positive; 2. 24 patients after myocardial infarction undergoing subsequent rehabilitation, including 20 men and 4 women, aged from 42 to 78 years, an average of 58.75 ± 8.45 years; 3. 70 healthy subjects without ischemic heart disease, including 34 men and 36 women, ranging in age from 24 to 70 years, an average of 56.24 ± 12.33 years. All healthy people and patients were hospitalized in the Department of Internal Medicine and Cardiac Rehabilitation, University Hospital im. WAM in Lodz. The study groups were assessed risk of coronary heart disease based on the result obtained in the scale before exercise and exercise. The results were statistically analyzed using Statistica version 12 (StatSoft, Poland). For the statistically significant level of p<0.05. RESULTS: Compared to healthy individuals in both the ischemic heart disease (p=0.04) and in the group treated with rehabilitation (p=0.03) results in a scale before stress was significant higher. Compared to healthy individuals, both in the group of ischemic heart disease (p <0.001) and in the group treated with rehabilitation (p<0.001) The results on a scale of exercise were significantly higher. CONCLUSIONS: The use of scale before exercise to assess the risk of coronary heart disease is useful for physical therapists in their professional practice. There legitimacy of the use of scale exercise for the initial diagnosis of coronary artery disease without knowing the interpretation of the ECG stress test.

[Evaluation of oxidative-reduction markers of blood in patients with acute coronary syndromes (ACS) subjected to cardiac rehabilitation]. / Evaluation of oxidative-reduction markers of blood in patients with acute coronary syndromes (ACS) subjected to cardiac rehabilitation.

Role in the pathogenesis of atherosclerosis play a reactive oxygen species. In the case of disturbance of dynamic balance between their production and antioxidant defense mechanisms comes to undesirable consequences - oxidative stress. Excessive exercise can, among others, disrupting the balance. AIM: The aim of the study was to evaluate the exponents of the processes of oxidation - reduction of blood in patients with ACS undergoing rehabilitation in a hospital setting. MATERIALS AND METHODS: The study included 25 patients after ACS STEMI, including 19 men and 6 women, aged 51.5±6.5 years, underwent rehabilitation in the Department of Internal Medicine and Cardiac Rehabilitation, University Hospital im. WAM in Lodz. Blood samples were taken after an initial exercise test (I) and after the final exercise test (IV). Marked: SOD-1, CAT, GPX- in red blood cells, plasma antioxidant activity (TAS) and the concentration of MDA in the red blood cells. Cardiac rehabilitation program included 15 interval training, each lasting 40-45 minutes. RESULTS: The results were statistically analyzed. For the statistically significant level of p<0.05. No significant effect of cardiac rehabilitation on the activity of GPX, SOD-1, MDA and antioxidant activity of plasma. There was only a significant impact on the rehabilitation of CAT activity (p=0.002). CONCLUSIONS: Properly conducted cardiac rehabilitation does not disturb the balance of oxidation - reduction of blood in patients with ACS. Exercise should be selected in such a way that this balance is maintained.

[Metabolic safety of antidepressant medicines]. / Metabolic safety of antidepressant medicines.

Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents. AIM: The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component). RESULTS: In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

Antipsychotic Drugs Differentially Affect mRNA Expression of Genes Encoding the Neuregulin 1-Downstream ErbB4-PI3K Pathway.

BACKGROUND/AIMS: The PIK3CD gene encodes the delta catalytic subunit of phosphoinositide 3-kinase (PI3K), an element of the neuregulin 1-downstream ErbB4-PI3K signaling pathway, which was recently identified as a molecular target for the treatment of schizophrenia. The aim of the study was to examine the effect of haloperidol (HALO), clozapine (CLO), olanzapine (OLA), quetiapine (QUE) and amisulpride (AMI) on the mRNA and protein expression of genes encoding the elements of ErbB4-PI3K pathway, in a human central nervous system cell line. METHODS: The U-87MG human glioblastoma cell line was used as an experimental model. Quantitative polymerase chain reaction was used to examine the expression of mRNA and enzyme-linked immunosorbent assay for protein expression. RESULTS: At concentrations reached in clinical settings in the brain, CLO, as well as OLA and QUE to a lesser extent, but not AMI and probably not HALO, decreased the mRNA expression of PIK3CD. Protein expression of the gene did not confirm the mRNA expression profile. CONCLUSIONS: The tested antipsychotic drugs (APDs) in the U-87MG glioblastoma cell line differentially regulates the mRNA expression of PIK3CD; however, the protein expression does not confirm these findings. The results of the study may help deepen the understanding of the mechanism of action of APDs.

Value of D-dimer and HDL cholesterol concentrations in predicting the occurrence of acute pulmonary embolism.

UNLABELLED: Pulmonary embolism (PE) usually is a clinical manifestation of venous thromboembolism. The lack of simple and safe laboratory test to confirm or exclude PE is a problem that slows down the diagnosis. AIM: The aim of the study was the assessment the usefulness of D-dimer and HDL cholesterol concentration in predicting the occurrence of acute pulmonary embolism. MATERIALS AND METHODS: The study group comprised 86 patients. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels were measured by catalase HDL-C and LDLC assay. The D-dimer level was assessed using immunoenzymatic method with high sensitivity test (VIDAS D-Dimer Exclusion). Pulmonary embolism was diagnosed using contrast-enhanced multidetector computer tomography (16-row GE Light Speed Pro and 64-row Toshiba Aquilion Systems). RESULTS: In all patients with PE, higher D-dimer concentration was found. Odds ratio (OR) calculated for the D-dimer indicates that the concentration of D-dimer ≥859,5 ng/ml increases the risk of PE 612 times, compared with those with levels below 859,5 ng/ml. HDL cholesterol level in patients with PE was significantly lower compared with the control group (p < 0,05). Odds ratio (OR) calculated for the HDL cholesterol indicates that the risk of PE in subjects with the concentration of HDL-C ≤44 mg/dl is 26,89 times higher, compared with individuals with HDL-C >44 mg/dl. CONCLUSIONS: According the studies, increase D-dimer and decrease HDL levels are an independent risk factors for occurrence of acute pulmonary embolism.

The effect of clary sage oil on staphylococci responsible for wound infections.

INTRODUCTION: The spreading of bacterial antibiotic resistance among clinical strains of pathogenic bacteria has made investigators to search for other active antibacterial agents which could provide a valuable complement to the existing therapies. AIM: To determine the antibacterial activity of clary sage oil (Salvia sclarea L.) against Staphylococcus clinical strains which were isolated from patients with wound infections. MATERIAL AND METHODS: A comprehensive evaluation of Staphylococcus clinical strain resistance to antibiotics was performed. The constituents of clary sage oil were assayed by GC-FID-MS analysis. The minimal inhibitory concentration (MIC) of the tested essential oil against staphylococci by the micro-dilution broth method was determined. RESULTS: The clary sage oil was active against Staphylococcus aureus, S. epidermidis and S. xylosus with MIC values ranging from 3.75 to 7.00 µl/ml. CONCLUSIONS: The results of the in vitro tests encourage to use formulations containing sage oil as the active natural antimicrobial agent. Because of its antimicrobial properties clary sage oil may be applied to treat wounds and skin infections.

The biological activities of cinnamon, geranium and lavender essential oils.

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.

[The antibacterial activity of cinnamon oil on the selected gram-positive and gram-negative bacteria]. / Przeciwbakteryjne dzialanie olejku cynamonowego na wybrane bakterie gram-dodatnie i gram-ujemne.

INTRODUCTION: The aim of our study was to determine the antibacterial activity of cinnamon bark oil against Gram-positive and Gram-negative isolates belonging to Staphylococcus, Enterococcus, Enterobacter and Acinetobacter genera come from different clinical specimens. METHODS: The microdilution method was used to determine the minimum inhibitory concentration--MIC for cinnamon bark oil. Susceptibility testing to antibiotics was carried out using disc-diffusion method. RESULTS: Our investigations showed that the tested cinnamon bark oil was inhibiting activity against all isolates. The MIC for Gram-positive bacteria were between 01.25 and 1.5 µl/ml and for Gram-negative between 1.0 and 1.75 µl/ml. The tested bacteria come from Staphylococcus, Enterococcus, Enterobacter and Acinetobacter genera were susceptible to essential oil obtained from Cinnamomum zeylanicum Ness in low concentrations, despite the fact that the bacteria characterized the high resistance to recommended antibiotics. No correlation was found between the antibiotic resistance of the bacterial strains and their sensitivity to essential oil. CONCLUSIONS: The cinnamon bark oil due to the strong activity can be used as alternative antibacterial agents in cosmetics, toiletries and disinfectants applied in hospital environment.

The ability of hyaluronan fragments to reverse the resistance of C6 rat glioma cell line to temozolomide and carmustine.

AIM OF THE STUDY: Hyaluronan (HA) is an extracellular matrix (ECM) polymer that may contribute to the emergence of anti-cancer drug resistance. Attempts to reverse drug resistance using small hyaluronan oligomers (oHA) are being made. The initial reports suggest that the oHA fraction may effectively reverse anti-cancer drug resistance in glioma models. However, the reversal effects of oHA of defined molecular length on glioma cells have not been investigated yet. In this study, we examined HA fragments containing 2 disaccharide units (oHA-2), 5 disaccharide units (oHA-5), and 68 kDa hyaluronan polymer (HA-68k) as agents possibly reversing the resistance of a C6 rat glioma cell line to temozolomide (TMZ) and carmustine (BCNU). MATERIAL AND METHODS: A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay was used to assess the cytotoxicity of TMZ and BCNU in the presence or absence of the hyaluronan fragments. By comparing viability of the cells, the reversal effects of HA fragments on TMZ and BCNU resistance in C6 glioma cells were assessed. RESULTS: We found statistically significant decreases in the viability of cells in the presence of TMZ+oHA-5 as compared to TMZ alone (51.2 ±4.5 vs. 74.2 ±5.8, p = 0.0031), BCNU+o-HA5 as compared to BCNU alone (49.3 ±4.4 vs. 65.6 ±5.7, p = 0.0119), and BCNU+HA-68k as compared to BCNU alone (55.2 ±2.3 vs. 65.6 ±5.7, p = 0.0496). CONCLUSIONS: Hyaluronan oligomers of 5 disaccharide units (oHA-5) significantly reversed the resistance of C6 cells to TMZ and BCNU. The results are only preliminary and a more thorough follow-up investigation is required to assess their actual role.

Contribution of staphylococcal virulence factors in the pathogenesis of thrombosis.

Staphylococci are responsible for many infections in humans, starting with skin and soft tissue infections and finishing with invasive diseases such as endocarditis, sepsis and pneumonia, which lead to high mortality. Patients with sepsis often demonstrate activated clotting pathways, decreased levels of anticoagulants, decreased fibrinolysis, activated endothelial surfaces and activated platelets. This results in disseminated intravascular coagulation and formation of a microthrombus, which can lead to a multiorgan failure. This review describes various staphylococcal virulence factors that contribute to vascular thrombosis, including deep vein thrombosis in infected patients. The article presents mechanisms of action of different factors released by bacteria in various host defense lines, which in turn can lead to formation of blood clots in the vessels.

Thiol protein groups correlate with cognitive impairment in patients with recurrent depressive disorder.

BACKGROUND: Depressive disorders are multifactorial diseases in which cognitive impairments are one of typical features. Thiol protein groups (TPGs) are elements of chemical structure of compounds having antioxidative properties (glutathione peroxidase, metallothioneins) and their oxidation reflects the lost of compensatory capacity of antioxidative mechanisms. The purpose of this study was to determine the level of TPGs in patients with recurrent depressive disorder (rDD) and to define relationship between plasma levels of TPGs and the cognitive performance. MATERIAL AND METHODS: The study comprised 76 subjects: patients with rDD (n=43) and healthy subjects (comparison group, CG - n=33). Cognitive function assessment was based on the following 4 tests: the Trail Making Test (TMT), the Stroop Test, Verbal Fluency Test (VFT) and Auditory Verbal Learning Test (AVLT). RESULTS: The level of TPGs was higher in patients with rDD. In rDD group, the elevated concentration of TPGs in plasma was associated with a decrease in efficiency of declarative-memory, working memory and verbal fluency. The higher was the concentration of plasma TPGs, the greater was the severity of depressive symptoms measured by 21-item Hamilton Depression Rating Scale (HDRS), before and after pharmacotherapy. In CG group, the elevated TPGs levels were associated with worse cognitive test performance (AVLT and VFT tests). CONCLUSIONS: 1) Our study confirms previous results showing increased TPGs level in depression. 2) Our data suggest relation between increased plasma TPGs level in depression and cognitive impairment. 3) The elevated levels of plasma TPGs are related to impairment of the short-term and delayed declarative memory, verbal fluency and working memory.