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Purpose: To evaluate the effect of denatonium benzoate (DB) in histamine-induced model of inflammation and the effect of the selective H1 receptor agonist (2-(2-Pyridyl) ethylamine) on rat gastric smooth muscle strips pretreated with DB.Methods: The anti-inflammatory effect of DB was evaluated in vivo on histamine-induced rat paw edema. In vitro studies on spontaneous muscle contraction were performed on smooth muscle strips isolated from rat gastric corpus.Results: The results showed a well-defined anti-inflammatory effect of DB (15 mg/kg) during the early stage of rat paw edema at the 15th (p < 0.001), 30th (p < 0.01) and 60th min (p < 0.001) compared to control. In vitro experiments indicated reduced spontaneous contractile activity of smooth muscle strips to H1 receptor agonist in the presence of DB (0.5 μM). The vascular effects of histamine are mediated by H1 receptors. Substances, which reduce the effect of histamine on the H1 receptors could influence the early stage of histamine-induced inflammation.Conclusion: The results show that the anti-inflammatory activity of DB probably is related to its antagonistic activity on histamine H1 receptors. The results would contribute to the search for new antiinflammatory drugs. Keywords: Denatonium benzoate, Inflammation, Histamine, Muscle contraction

Introduction: Obesity is linked to the development of low-grade, chronic inflammation. Obesity-related inflammation appears to be a different type of inflammation, mainly due to excessive food intake and unusual homeostasis. It can be evaluated by measuring the concentration of pro- and anti-inflammatory marker molecules – C-reactive protein (CRP), serum amyloid-A (SAA) and interleukin-4. Aim: The aim of the present study is to evaluate the rate of the inflammatory process in heart, provoked by the consumption of a high-fat diet. Materials and methods: Sixty 8-week-old male Wistar rats were used in this experiment. The laboratory animals were fed orally with two different types of rodent food for 14 or 18 weeks – a high-fat diet (experimental groups) and standard rodent food (control groups). They all were kept under standard housing conditions. The levels of the pro- and anti-inflammatory markers in tissue homogenates from heart were analyzed using ELISA. Their expression in tissue samples was detected immunohistochemically by the biotin-streptavidin-peroxidase method. The total protein concentration was determined by the Lawry method. Results: CRP levels showed no significant differences when the control group was compared with the groups fed with a high-fat diet (p>0.05). The SAA levels detected were also insignificantly changed. Only the IL-4 tissue levels showed tendency to increase (p Conclusions: Our experiment indicates that there is a specific reaction of the heart to a high-fat diet. It also refers to the existence of adaptive mechanisms allowing the heart to counteract the development of dietary induced inflammation.

Lichen planus is a chronic mucocutaneous inflammatory disease aff ecting 1-2% of the general population with maximum prevalence of the disease in women above the age of 40. Its aetiology remains unclear and the pathogenesis is still the object of much speculation. It is considered to be an autoimmune disorder mediated mainly by the T-lymphocytes. The present paper presents the most well-known external agents (viruses in particular), internal agents like stress, and the heat shock protein thought to be trigger factors and describes the action of diff erent cells and proteins associated with the development of that disease. Diagnosis is based on clinical and histopathologic evidence; direct and indirect immunofluorescence techniques can also be of use. Despite the wide variety of therapeutic modalities, treatment outcomes are often insufficient. Currently, topical corticosteroids are widely accepted as a standard therapy, but also retinoids, calcineurin inhibitors and other immunosuppressants can be administered. Because of the aspect relevant to these drugs, priority is given to alternative harmless methods such as LLLT and PDLT. There is an ongoing controversy in the literature about the possible premalignant character of oral lichen planus, however, periodic followup is recommended.

Clinically, there is an urgent need to identify new therapeutic strategies for selectively treating cancer cells. One of the directions in this research is the development of biocompatible therapeutics that selectively target cancer cells. Here, we show that novel aminated graphene oxide (haGO-NH2) nanoparticles demonstrate increased toxicity towards human hepatocellular cancer cells compared to pristine graphene oxide(GO). The applied novel strategy for amination leads to a decrease in the size of haGO-NH2 and their zeta potential, thus, assuring easier penetration through the cell membrane. After characterization of the biological activities of pristine and aminated GO, we have demonstrated strong cytotoxicity of haGO-NH2 toward hepatic cancer cells—HepG2 cell line, in a dose-dependent manner. We have presented evidence that the cytotoxic effects of haGO-NH2 on hepatic cancer cells were due to cell membrane damage, mitochondrial dysfunction and increased reactive oxygen species (ROS) production. Intrinsically, our current study provides new rationale for exploiting aminated graphene oxide as an anticancer therapeutic.

Background: The erosive-atrophic form of oral lichen planus (OLP) is associated with severe pain and burning sensation and is often unresponsive to treatment. Topical corticosteroids are considered as a medication of first choice but they can produce adverse effects. Therefore, new therapeutic approaches are required. Aim: The aim of this study was to investigate the effectiveness of biomodulation with diode laser in patients presenting with long-standing erosive-atrophic OLP. Materials and methods: Twelve patients, clinically and histologically diagnosed with OLP, participated in this study. The level of pain and the clinical scores of total 59 lesions were recorded before treatment using visual analog scale and Thongprasom sign scoring system respectively. All patients received low level laser therapy (LLLT) with diode laser (810 nm) with parameters (0.5 W, 30 s, 1.2 J/cm2) three times weekly for a month. The response rate was assessed according to the decrease in pain and sign scores. Treatment efficacy index was calculated. Results: There was a significant reduction in pain after LLLT (p Conclusion: The present results indicate that LLLT is an effective and harmless modality for management of erosive-atrophic OLP.

The aim of this study is to evaluate the antihyperalgesic and antinociceptive effects of two formulations containing peat water extracts using a model of carrageenan-induced hyperalgesia, combined with a test with a mechanical stimulus, and a hot plate test. Rats were divided into seven groups (n = 6) and received local treatment with two peat formulations and two diclofenac formulations dissolved in carbopol gel and Wolff® basis creme, respectively. Carbopol gel, Wolff® basis creme and 0.9 % NaCl without tested substances were used as controls. Both peat formulations exerted an unambiguous antihyperalgesic effect 60 minutes after the treatment. In the hot plate test, the rats treated with the Wolff® basis creme peat formulation showed a tendency to prolonged latency on the first hour. The results could be explained by partial activation of peripheral α2-adrenoceptors and the possible COX-2 suppressive activity.

Betahistine dihydrochloride, which is widely prescribed for the treatment of symptoms associated with Meniere’s syndrome, is generally administered orally in solid or liquid formulations. There is a strong need of profound investigation of alternative routes of administration of betahistine to overcome difficulties related to oral administration. The aim of this study was to evaluate betahistine cytotoxicity and permeability in vitro and to assess the drug’s relevance for incorporation in drug delivery systems for nasal administration. RPMI epithelial model was used to evaluate drug permeability in vitro. The cytotoxicity of betahistine was assessed by MTT test. Chitosan microspheres were used as a betahistine delivery system. RPMI 2650 formed a thick, impermeable cell layer on the apical side of the filter inserts and developed enough TEER values to confirm confluence. According to the obtained results, BET showed high permeability coefficients (Papp values in the range 2.3 × 10 −5 to 19 × 10 −5 ) and could, therefore, be successfully used in nasal drug delivery formulations. Also, BET exhibited a good safety profile regarding nasal epithelium toxicity. A dose-dependent reduction in cell viability was observed. The microspheres as drug delivery systems affected BET permeation profiles due to the presence of chitosan as an absorption enhancer.

Nanotechnology-based drug delivery systems for cancer therapy are the topic of interest for many researchers and scientists. Graphene oxide (GO) and its derivates are among the most extensively studied delivery systems of this type. The increased surface area, elevated loading capacity, and aptitude for surface functionalization together with the ability to induce reactive oxygen species make GO a promising tool for the development of novel anticancer therapies. Moreover, GO nanoparticles not only function as effective drug carriers but also have the potential to exert their own inhibitory effects on tumour cells. Recent results show that the functionalization of GO with different functional groups, namely, with amine groups, leads to increased reactivity of the nanoparticles. The last steers different hypotheses for the mechanisms through which this functionalization of GO could potentially lead to improved anticancer capacity. In this research, we have evaluated the potential of amine-functionalized graphene oxide nanoparticles (GO-NH2) as new molecules for colorectal cancer therapy. For the purpose, we have assessed the impact of aminated graphene oxide (GO) sheets on the viability of colon cancer cells, their potential to generate ROS, and their potential to influence cellular proliferation and survival. In order to elucidate their mechanism of action on the cellular systems, we have probed their genotoxic and cytostatic properties and compared them to pristine GO. Our results revealed that both GO samples (pristine and aminated) were composed of few-layer sheets with different particle sizes, zeta potential, and surface characteristics. Furthermore, we have detected increased cyto- and genotoxicity of the aminated GO nanoparticles following 24-hour exposure on Colon 26 cells. The last leads us to conclude that exposure of cancer cells to GO, namely, aminated GO, can significantly contribute to cancer cell killing by enhancing the cytotoxicity effect exerted through the induction of ROS, subsequent DNA damage, and apoptosis.

Linker histones are major players in chromatin organization and per se are essential players in genome homeostasis. As the fifth class of histone proteins the linker histones not only interact with DNA and core histones but also with other chromatin proteins. These interactions prove to be essential for the higher levels of chromatin organization like chromatin loops, transcription factories and chromosome territories. Our recent results have proved that Saccharomyces cerevisiae linker histone – Hho1p, physically interacts with the actin-related protein 4 (Arp4) and that the abrogation of this interaction through the deletion of the gene for the linker histone in arp4 mutant cells leads to global changes in chromatin compaction. Here, we show that the healthy interaction between the yeast linker histone and Arp4p is critical for maintaining genome stability and for controlling cellular sensitivity to different types of stress. The abolished interaction between the linker histone and Arp4p leads the mutant yeast cells to premature ageing phenotypes. Cells die young and are more sensitive to stress. These results unambiguously prove the role of linker histones and chromatin remodelling in ageing by their cooperation in pertaining higher-order chromatin compaction and thus maintaining genome stability.

Multiple sclerosis (MS) is associated with cytokine imbalance and high rate (40-70%) of cognitive impairment. The objective of this study is to investigate the relationship between serum concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-17A, IL-18, IL-10, and cognitive performance in patients with relapsing-remitting MS (RRMS). Methods The study comprised 159 patients with RRMS (mean age 40.08 ± 8.48 years) in remission phase and 86 age-, gender-, and education-matched healthy controls. Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities test (SDMT), and Isaacs test were used for assessment of working memory, attention, visuo-perceptual abilities, information processing speed, and executive functions. Serum cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA). Results Patients had significantly increased serum concentrations of TNF-alpha and IL-17A and decreased levels of IL-10 compared to the controls (p

Purpose: The anti-inflammatory effects of 1,8‑cineole (eucalyptol) in the treatment of acute bronchitis and treatment of chronic airway diseases like asthma as well as hay fever have been observed in clinical practice for some time. The anti-inflammatory effect has been proven in numerous studies. Material and methods: The effect of 1,8-cineole on the activity of cyclooxygenase and its two isoforms (COX‑1 and COX‑2) were analysed and compared with the effects of indomethacin and celecoxib. Results: The ratio between the concentrations required to achieve 50% inhibition of COX‑1 and COX‑2 isoform activity was found to be 73.5. Discussion: For indomethacin, the ratio is 9.71 and for celecoxib 79.5. For indomethacin, it is about 10 times less than that of 1,8‑cineole. Conclusion: The present study provides useful data suggesting that 1,8‑cineole is a specific COX‑2 blocker.

Propolis is a natural product with different biological activities. Current research is focused on its ability to suppress tumor growth by induction of apoptosis. However, its selective influence on normal and transformed cells is not fully studied yet.Our previous investigations determined the McCoy-Plovdiv cell line as a model system for in vitro examination of propolis. In the present study we analysed ethanol extracts of propolis from the region of East Rodopi mountains in final concentrations 0,001; 0,1; 1,0; 10 μg/ml.The proliferative activity was examined with MTT and NR cell vitality tests. The type of cell dead was proven via TUNEL test and by fluorescent detection of phosphatidylserine (PS) externalization. Cytotoxicity tests showed decreased cell vitality from 100 to 0% increasing with propolis concentration. The TUNEL test proved the presence of apoptotic cells. Propolis in concentrations 0,001-1,0 μg/ml induced apoptosis in a large number of cells. The results from PS externalization ...

The mechanisms of action of propolis can be studied in detail by comparing the effects of propolis and the effects of its constituent components.To clarify and compare the effects of Bulgarian propolis and caffeic acid phenethyl ester (CAPE, a chemically synthesized component of propolis)--by using a set of cellular, molecular-biological and immunological techniques.The McCoy-Plovdiv cell line was treated with propolis and CAPE in increasing concentrations (0.01, 0.1, 1.0, 10 mg/L, and 2.5, 4, 8, 16 mg/L, respectively). The expression of the proliferating cell nuclear antigen (PCNA) and the tumour-suppressor protein p53 was studied immunocytochemically. Apoptosis was measured using a highly sensitive microgel electrophoresis technique (comet assay).The results of the study showed corresponding changes in the expression of the examined proliferative antigens. PCNA was detected in all examined concentrations of the tested substances the expression being dose-dependent. Molecule localization changed from the nucleus to the cytoplasm. Treatment with CAPE brought about gradual attenuation of PCNA expression. High propolis concentrations induced increased synthesis of p53. No p53 expression was found when cells were treated with CAPE. The studied substances in their highest concentrations (10 mg/L propolis and 16 mg/L CAPE) had a cytotoxic effect. The comet assay showed DNA degradation kinetics characteristic for apoptosis.The present study demonstrates that high concentrations of propolis and CAPE cause apoptosis-induced cell death in McCoy-Plovdiv cells.