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Background: Alzheimer's Disease (A.D.) is a multifactorial process. Advanced glycation end products (AGEs) have been correlated with disease development1. Additionally, high concentrations of antibodies against the food derived antigens egg‐albumin and bovine casein, have been detected in patients with Alzheimer's disease in preliminary research presented by our team, previously (AAIC 2018). In the present study, antibodies against egg‐albumin and bovine casein as well as AGEs were detected in the cerebrospinal fluid of 36 patients with mild and 35 patients with severe Alzheimer's Disease and 13 healthy individuals and a correlation between the measured parameters and sample properties was attempted. Method: ELISA plates pre‐treated with highly hydrophilic microlon resin were used for the purpose of this study2. Egg‐albumin or bovine casein antigens were attached at the ELISA plates for the measurement of antibodies. Additionally, polyclonal antibodies against multiple AGE products were used to detect attached sample CSF AGEs. Result: According to the results, 48,6% of of the samples of patients with severe AD had anti‐egg albumin concentration higher than mean concentration of healthy idividuals+2SD (characterized as positive) compared to 8.3% of positive samples in patients with mild disease. An overall 265% increase in mean concentration was observed in severe compared to mild patients, indicating association with severity. The observed difference was significant at p = 0.01 according to mann witney U test. Lower anti‐egg albumin concentrations were observed in female samples of either mild or severe disease (Figure 1). Much lower incidence of anti‐casein antibody positive samples was found in in severe AD (5.7% positive in severe versus 0% in mild AD). A slight, not statisticaly significant, increase in mean anti‐casein antibodies concentration (23.7%) and AGEs (16.2%) was observed in severe compared to mild disease with the higher concentrations also detected in the most positive to anti‐egg albumin samples. Conclusion: The results indicated a potential correlation of antibodies against egg‐albumin with the severity of Alzheimer's disease with increased incidence in male patients. A lower correlation was observed in case of anti‐casein antibodies and AGEs. References: 1. Takeuchi et al., Current Pharmaceutical Design, 14(10), 2008, 973‐978. 2. P. Eleftheriou, etal. Biomed. Res. Int., 2014. [ABSTRACT FROM AUTHOR]

Reverse transcriptase (RT) inhibitors play a major role in the therapy of human immunodeficiency virus type 1 (HIV-1) infection. Although, many compounds are already used as anti-HIV drugs, research on development of novel inhibitors continues, since drug resistant strains appear because of prolonged therapy. In this paper, we present the synthesis and evaluation of HIV-1 RT inhibitory action of eighteen novel (4/6-halogen/MeO/EtO-substituted benzo[d]thiazol-2-yl)thiazolidin-4-ones. The two more active compounds (IC50 : 0.04 µM and 0.25 µM) exhibited better inhibitory action than the reference compound, nevirapine. Docking analysis supports a stable binding of the most active derivative to the allosteric centre of RT. Kinetic analysis of two of the most active compounds indicate an uncompetitive inhibition mode. This is a desired characteristic, since mutations that affect activity of traditional non-competitive NNRTIs may not affect activity of compounds of this series. Interestingly, the less active derivatives (IC50 > 40 µM) exhibit a competitive mode of action. [ABSTRACT FROM AUTHOR]

Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects. Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock. Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis. Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms. [ABSTRACT FROM AUTHOR]

Background: HIV is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), an infectious disease with increasing incidence worldwide. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) play an important role in the treatment of AIDS. Although, many compounds are already being used as anti-HIV drugs, research for the development of new inhibitors continues as the virus develops resistant strains. Methods: The best features of available NNRTIs were taken into account for the design of novel inhibitors. PASS (Prediction of activity spectra for substances) prediction program and molecular docking studies for the selection of designed compounds were used for the synthesis. Compounds were synthesized using conventional and microwave irradiation methods and HIV RT inhibitory action was evaluated by colorimetric photometric immunoassay. Results: The evaluation of HIV-1 RT inhibitory activity revealed that seven compounds have significantly lower ΙC50 values than nevirapine (0.3 μΜ). It was observed that the activity of compounds depends not only on the nature of substituent and it position in benzothiazole ring but also on the nature and position of substituents in benzene ring. Conclusion: Twenty four of the tested compounds exhibited inhibitory action lower than 4 μΜ. Seven of them showed better activity than nevirapine, while three of the compounds exhibited IC50 values lower than 5 nM. Two compounds 9 and 10 exhibited very good inhibitory activity with IC50 1 nM. [ABSTRACT FROM AUTHOR]

Targeting to the synthesis of potent dual acting COX/LOX inhibitors as future anti-inflammatory drugs, we attempted a modification of the compounds based on docking analysis results. A substitution of the oxygen of the oxo-group of the oxazin-2-one ring by sulphur resulted in a four to over ten fold improvement of COX and LOX inhibitory action. N-phenyl derivatives exhibited the best biological properties with the 4-methoxy-phenyl derivative showing the best COX-1 and LOX inhibitory action and the 4-Br-phenyl derivative exhibiting the best COX-2 inhibitory action combined with good COX-1 and LOX inhibitory capacity. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency is recognised as a pandemic in the developed world. However, the importance of prudent sun exposure tends to be overlooked, which is responsible for this pandemic., Methods: We investigated the vitamin D status in 326 adults, 165 females and 161 males: 99 Osteoporosis patients, 53 Type 1 Diabetes patients, 51 Type 2 Diabetes patients, and 123 Athletic Healthy individuals, from Northern Greece, through the measurement of total calcidiol in winter and summer by immunoenzymatic assay., Results: In the Whole Sample 23.31% had severe deficiency, 13.50% mild deficiency, 17.48% insufficiency, and 45.71% adequacy at the end of winter. Mean concentrations differed significantly (p <0.001) between males and females. The prevalence of deficiency in the young was significantly lower than in the middle-aged (p = 0.004) and in the elderly (p <0.001), while it was significantly lower (p = 0.014) in the middle-aged than in the elderly. The best vitamin D status was found in the Athletic Healthy individuals, followed by the Type 1 and Type 2 Diabetic patients, while Osteoporotic patients had the poorest status. The difference in mean concentrations between winter and summer was significant (p <0.001)., Conclusions: Vitamin D status deteriorated with increasing age and it was better in males than in females. Our findings suggest that outdoor physical activity in a Mediterranean country can cover the vitamin D needs of the young and the middle-aged, but not of the elderly, without the need for dietary supplements., Competing Interests: No potential conflict of interest was reported by the authors

Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects., Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock., Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis., Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.

Apart from their anti-inflammatory action, COX inhibitors have gathered the interest of many scientists due to their potential use for the treatment and prevention of cancer. It has been shown that cyclooxygenase inhibitors restrict cancer cell growth and are able to interact with known antitumor drugs, enhancing their in vitro and in vivo cytotoxicity. The permutation of hydrophilic and hydrophobic aryl groups in COX inhibitors leads to cardinal changes in the biological activity of the compounds. In the present study, thirteen heterocyclic coxib-like 4,5-diarylfuran-3( 2H )-ones and their annelated derivatives-phenanthro[9,10-b]furan-3-ones-were synthesized and studied for anti-inflammatory and COX-1/2 inhibitory action and for their cytotoxic activity on the breast cancer (MCF-7) and squamous cell carcinoma (HSC-3) cell lines. The F-derivative of the -SOMe substituted furan-3( 2H )-ones exhibited the best activity (COX-1 IC 50 = 2.8 μM, anti-inflammatory activity (by carrageenan paw edema model) of 54% (dose 0.01 mmol/kg), and MCF-7 and HSC-3 cytotoxicity with IC 50 values of 10 μM and 7.5 μM, respectively). A cytotoxic effect related to the COX-1 inhibitory action was observed and a synergistic effect with the anti-neoplastic drugs gefitinib and 5-fluorouracil was found. A phenanthrene derivative exhibited the best synergistic effect with gefitinib.