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Evaluation of pharmacokinetic properties is a significant step at the early stages of drug development. In this study, an in vitro evaluation of the pharmacokinetic properties of five newly synthesized compounds was performed. These compounds belong to N-hydroxyurea and hydroxamic acid derivatives and analogs of NSAIDs indomethacin, flurbiprofen, diclofenac, ibuprofen, and naproxen (compounds 1, 2, 3, 11, and 12, respectively) with dual COX-2 and 5-LOX inhibitory activity. Two in vitro methods (biopartitioning micellar chromatography (BMC) and PAMPA) were used to evaluate passive gastrointestinal absorption, while high-performance affinity chromatography (HPAC) and differential pulse voltammetry (DPV) were used to evaluate binding to human serum albumin (HSA). The introduction of N-hydroxyurea and hydroxamic acid groups into the structure of NSAIDs decreases both expected passive gastrointestinal absorption (BMC k values were from 3.02 to 9.50, while for NSAIDs were from 5.29 to 13.36; PAMPA –logPe values were between 3.81 and 4.76, while for NSAIDs were ≤3.46) and HSA binding (HPAC logk values were from 2.03 to 9.54, while for NSAIDs were ≥11.03; DPV peak potential shifts were between 7 and 34, while for NSAIDs were ≥54). Structural modifications of all tested compounds that increase lipophilicity could be considered to enhance their passive gastrointestinal absorption. Considering lower expected HSA binding and higher lipophilicity of tested compounds compared to corresponding NSAIDs, it can be expected that the volume of distribution of compounds 1, 2, 3, 11, and 12 will be higher. Reduced HSA binding may also decrease interactions with other drugs in comparison to corresponding NSAIDs. All tested compounds showed significant microsomal instability (25.07–58.44% decrease in concentration) in comparison to indomethacin (14.47%) and diclofenac (20.99%).

Apart from cytotoxicity, inhibitors of the COX-2 enzyme have demonstrated additional effects important for cancer treatment (such as radiosensitization of tumor cells and cell antimigratory effects); however, the relationship between the inhibition of other inflammation-related enzyme 5-LOX inhibitors and anticancer activity is still not well understood. In our study, the cytotoxicity of thirteen COX-2 and 5-LOX inhibitors previously presented by our group (1–13) was tested on three cancer cell lines (HCT 116, HT-29 and BxPC-3) and one healthy cell line (MRC-5). Compounds 3, 5, 6 and 7 showed moderate cytotoxicity, but good selectivity towards cancer cell lines. IC50 values were in the range of 22.99–51.66 µM (HCT 116 cell line), 8.63–41.20 µM (BxPC-3 cell line) and 24.78–81.60 µM (HT-29 cell line; compound 7 > 100 µM). In comparison to tested, commercially available COX-2 and 5-LOX inhibitors, both cytotoxicity and selectivity were increased. The addition of compounds 6 and 7 to irradiation treatment showed the most significant decrease in cell proliferation of the HT-29 cell line (p < 0.001). The antimigratory potential of the best dual COX-2 and 5-LOX inhibitors (compounds 1, 2, 3 and 5) was tested by a wound-healing assay using the SW620 cell line. Compounds 1 and 3 were singled out as compounds with the most potent effect (relative wound closure was 3.20% (24 h), 5,08% (48 h) for compound 1 and 3.86% (24 h), 7.68% (48 h) for compound 3). Considering all these results, compound 3 stood out as the compound with the most optimal biological activity, with the best dual COX-2 and 5-LOX inhibitory activity, good selectivity towards tested cancer cell lines, significant cell antimigratory potential and a lack of toxic effects at therapeutic doses.

This study aimed to determine the variability properties of four major types of Amaranthus species in protein and amino acids content in leaves and flowers. Obtained results by ion exchange chromatography in our study have shown high values for the content of essential amino acids lysine and methionine. In the leaf, the lysine content ranged from 3.9 (A. caudatus) to 7.0 (A. cruentus; A. moleros), and in the flowers from 4.2 (A. caudatus) to 6.7 (A. molleros). The methionine content ranged from 3.1 (A. caudatus) to 7.4 (A. mantegazzianus) in the leaf and in the flower from 2.9 (A. caudatus) to 6.7 (A. mantegazzianus). Besides lysine and methionine, significant values of other essential amino acids were recorded, respectively. Significant concentrations of total proteins were recorded in all examined genotypes. The heritability of the studied characters as protein and mineral content of seeds and leaves, and oil contents of seed were significantly high. The maximum values of the protein content of seeds were 16.55% (A. cruentus), in leaves 20.10% (A. caudatus), and the minerals in seeds 2.73% (A. moleros), and leaves 18.76% (A. mantegazzianus). The oil content of seeds was 6.16% (A. moleros). The oil content of the seed’s proportion of genetic variance to total phenotypic variance was 72%, and it has a significant impact on ecological factors. Tested divergent Amaranthus genotypes may serve as parents for further crossing. Amaranth seeds is gluten-free and is important in the diet of celiac patients and contains amino acids, especially lysine, which acts against the herpes virus. Amaranth from amaranth leaves biologically active substance that prevents heart muscle damage during ischemic processes. Amaranth seed oil has hypolipemic, anti-atherosclerotic, hypotensive and antioxidant activity.

The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8–14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1–7 and 8–14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 µM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.

Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds 7a, 7d, and 7f were promising. Among these, 7f (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds 7a, 7d and 7f were also tested for their cytotoxic effects on healthy cell line but only compound 7d showed selectivity. Compounds 7a, 7d, and 7f showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC50 value was observed for 7c (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds 7a (3.78 µM), 7c (2.60 µM), 7e (3.3 µM), and 7f (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds 7c, 7e, and 7f to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, 7a and 7f were identified as the most promising compounds.

The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1–5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 μM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agent.

Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1–13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and “type B hydroxamic acids” (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests. The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties.

This research investigates current preferences in wine purchase patterns and factors that affect the online purchase of wine by Generation Y and older cohorts in the Republic of Serbia. Our research utilizes descriptive statistics, chi-squared tests, the Mann–Whitney nonparametric test, and binary logistic regression. The results indicate that wine purchasing is conducted on an occasional basis—mostly monthly and weekly—with a tendency to buy wine throughout the whole year. The older cohort has a more pronounced rank, compared to Generation Y, regarding WTP for wines with a specific geographical origin and local wines. Although Generation Y and the older cohort have no habit of buying wine online, the information on geographical origin represents the most important online information related to online purchase intention. The strongest influence on online wine purchasing among members of the older cohort is a link that connects producers with consumers to allow the latter to obtain additional information and send remarks, suggestions, and/or praise, as well as a link to the winemakers’ association website, and the very significant influence of female gender. The strongest influence on online wine purchasing in Generation Y is the information on geographical origin. Female gender and income are also very significant. As wine consumption in the Republic of Serbia is gradually increasing, a growing interest in online wine purchases is expected. Our findings can provide useful information for building profiles of online wine consumers, depending on age cohort.

Increased content of pesticides in food chain resulted in using microorganisms asagents of biological control. The potato cyst nematodes (PCN) - Globodera pallida and G.rostochiensis belong to the group of the most important parasites - the quarantine organisms.The external and internal area of a cyst harbor numerous fungal and bacterial species.The aim of this study was to identify antagonistic fungi associated with some PCN populationsfrom Serbia. Fungal antagonists of potato cyst nematodes have not been previouslyinvestigated in our country. The diversity of PCN fungal antagonists is not reflected only atthe species level but also at the level of higher taxonomic categories.

For the last several decades, ecologists have been warning the public about the issues of overuse and damage of natural resources, resulting in loss of biodiversity, and the need for environmental conservation. Vojvodina is a flat and deforested territory, characterised by strong winds causing wind erosion. Since planting forests on soils belonging to the first three categories was forbidden by the law, planting shelterbelts can provide a solution. They can provide relatively cheap and long-term solution. When properly planned, shelterbelts provide numerous economic, social and environmental benefits. They reduce wind impact, control snow spreading trapping it, protect livestock, buildings and gardens. Shelterbelts also provide habitat for wildlife and decorate the environment.

Nitrogen is one of the most important nutrient elements used all over the world with the aim of increasing and sustainability of the production of the agricultural crops. During the 'Green Revolution', nitrogen fertilisers contributed to the increase and maintenance of crop yields under different agroecosystems. Nitrogen was a key of economic variability of the agricultural production worldwide, and in this way, it was globally a key of food. On the other hand, anthropogenic influences (fossil fuel combustion) contributed to a greater release of gases, such as carbon dioxide and nitrogen oxides, resulting in global warming of our planet. The application of organic and mineral nitrogen fertilisers can cause losses of nitrogen in gaseous states, as well as, nitrite leaching. Therefore, nitrite contamination of drinking water is already a serious problem in many parts of the world. New technologies in the application of nitrogen fertilisers and crop growing, such as: a precise technique of the plant production, quick tests (in situ) for analysing concentrations of nitrite nitrogen in the plant tissues, rapid tests for chlorophyll determination, the use of computer models of simulation for the improvement of production planning and organising - can affect the increase of the average efficiency in the nitrogen utilisation under different agroecosystems by more than 50%. This paper presents the modes and possibilities of the rational application of nitrogen fertilisers in the seed maize production, which is specific in many of its parameters, as a necessary procedure to maintain a safe agroecosystem.

Authors of this paper research necessaries of orientation and improvement of education of staff for purpose of sustainable development of agriculture and environment protection. According with global questions of education improvement, this paper especially realizes basis and aims of high education in function of orientation sustainable development agriculture and environment protection. In addition, it point was on role of highly professional staff in function of abetment of development organic agriculture and healthy safe food production on familys husbandry and farm economies. Improvement of education highly professional agricultural staff in our country is connected with Bologna declaration demands and developing of Bologna process in Europe. From this point education of agricultural staff, we must have in mind facts that European market will become unique market for students and professors.

This paper realizes and defines comparative programs of agriculture production. For this, purpose previous pointed on diversity and comparatively available natural resources (climate, soil, water biodiversity of flora and fauna). Also realizes technical-technological accomplishments and possibilities to adjust sustainable development of agriculture and agrarian sector. In according with available structure and quality of agro ecological conditions, market demands, in this paper was define comparative and developing programs of agriculture production and agrarian manufactured products. Comparative programs of these products, defined according to agriculture organic production and possibilities of production biological quality organic products for advance realizes segment of market. In frame of quality developing of agrarian products, pointed on politics and modalities of apply international standards in function of process managing and quality of products, manufacture and market exchange of agrarian products. For these purpose, pointed on specificity of creating, certificating and marking of agrarian products.

This paper researches and demonstrates the profitability of organic food production. The paper examines the following factors of consumer behavior in countries with different levels of development: - the extent of information given the consumer regarding the impact of food on the human - body, - the standards of living, and current consumer tastes, and - habits. The authors are suggesting possibilities for increasing capital for production of organic food by macro and micro redistribution of expanded reproduction costs. In conclusion, this paper will demonstrate the profitability of organic food production. Until the present time, due to a lack of scientific research, the profitable production of organic food has not been developed. However, the latest medical research will alter this situation. The realization of this change will initially begin in developed countries.

The World Commission on Environment and Development called attention to the basic changes in human population growth, need for strategies for attaining security in food production and need for conversation of natural resources. Sustainable agriculture goals may be shortly abridged to stable market supply by biologically quality food, on employment of rural population and suppressing of poverty, as well as the management of natural resources and environment protection on local and global level. For the system of such sustainable and organic agriculture, ecology provides basic conditions through the development of diversified agro ecological systems. Integration of plant and animal biodiversity, which improves complex of interaction and synergy, is the advantage. This enables biological regulation of harmful organisms, nutrition circling, biomass production and accumulation. The result of the agro ecological planning is improvement of economical and ecological agro ecology system maintenance. Strategy of sustainable agriculture development is basically based on improvement of conservation and increase of local agricultural resources. Within this, the greatest efforts are necessary for harmonization of environment laws with needs of macro economic policy on national and international levels. In accomplishing of these aims are included new initiatives in education, application of economical stimulations and development of relevant new technologies.

There is a multitude of concerns about the impact of genetically modified crops (GMCs) on the environment. The main important enviromental assessment of GM crops are putative invasiveness, vertical and/or horizontal gene flow, other ecological mechanisms, effects on biodiversity and the impact of presence of GM material in other products. These invetigations are all highly interdisciplinary and complex issues. Deposite the potential benefits of this new technology to improve the reliability and quality of the world food supply, public and scientific concerns have been raised about the environmental and food safety of Gm crops. In these paper same of most important problems related to the GM crops into the environment are inspect such as; plant protection, ecological effects of HRCs, gene flow, biodiversity, stress, effects on the soil ecosystem etc. Not enough scientific research has been done to evaluate the environmental and health risks of GMCs, an unfortunate trend. Most scientists feel that such knowledge is crucial to have before biotechnological innovations are implemented. There is a clear need to further assess the severity, magnitude and scope of risks associated with the massive field deployment of transgenic crops. The putative impacts identified for GMCs are very similar to the impacts of new cultivars derived from traditional breeding. When assessing GMCs relative to existing cultivars, the increased knowledge base underpinning the development of GMCs will provide greater confidence in the assurances plants science can give on the risks of releasing such crops.

Background/Aim. Multidetector computed tomography pulmonary angiography (MCTPA) has emerged as the most suitable method for diagnosing acute pulmonary embolism (APE) in hemodynamically stable patients. In addition to its diagnostic role, MCTPA facilitates the measurement and calculation of certain parameters that can be used as prognostic markers for outcomes in APE. Since the introduction of the method, there have been a lot of studies that pointed out there may be a significant difference in the prognostic value of MCTPA for APE concerning sex. Methods. The study population consisted of consecutive patients with a diagnosis of APE confirmed by MCTPA. Positive MCTPA findings and a diagnosis of APE were established if the patient had at least one segmental artery thrombus. APE severity was estimated using the simplified Pulmonary Embolism Severity Index (sPESI). Allcause and APE-related intrahospital deaths were the coprimary outcomes of this study. Results. In total, 1,612 patients were enrolled in the study (750 men and 862 women). Women with a centrally positioned pulmonary thrombus detected on MCTPA were more likely to die from PE-related death than those without one (10.4% vs. 4.2%, respectively; p = 0.016). Women with a right ventricle (RV) and left ventricle (LV) diameter ratio (RV/LV) > 1 died almost twice as often as those with a ratio ≤ 1 (15.5% vs. 8.6%, respectively; p = 0.017). Women with an RV/LV > 1 detected with MCTPA were significantly more likely to die from PE than those with a ratio ≤ 1 (11% vs. 5.2%, respectively; p = 0.017). Women who died from PE-related causes had a significantly higher value of the embolic burden score system (EBSS) than did the surviving women (18.00 vs. 11.00, respectively; p = 0.025). Independently of age, sPESI, and renal function, the presence of a central thrombus [odds ratio (OR) 2.278, 95% confidence interval (CI): 1.050–4.944, p = 0.037] and the RV/LV ratio > 1 (OR 2.015, 95% CI: 1.042–3.893, p = 0.037) were associated with intrahospital PE-related death in women. Conclusion. In women, MCTPA parameters, a centrally placed thrombus, the RV/LV ratio, and the EBSS had prognostic significance for PE-related mortality. The RV/LV ratio had prognostic significance for all-cause intrahospital mortality. In men, the MCTPA parameters had no prognostic significance for both overall and PErelated mortality. [ABSTRACT FROM AUTHOR]

Introduction. Portal vein (PV) thrombosis (PVT) is a partial or complete obstruction of blood flow as a result of a thrombus mass in the lumen of PV. In the acute phase, the symptoms such as right upper quadrant pain, nausea, and fever are unspecific. A diversity of subacute and chronic symptoms is associated with complications related to PVT and portal hypertension. Case report. A 50-year-old female was admitted to the hospital due to acute abdominal cramping pain. The pain lasted for 15 to 20 min and was followed by defecation of normal stool and hematochezia on three occasions. The abdominal pain recurred after several hours, again followed by hematochezia and tenesmus every 10 min. After admission, a colonoscopy was performed, and it revealed vulnerable, erythematous mucosa of the colon with contact bleeding from the lienal flexure to the rectosigmoid junction. During the colonoscopy, a biopsy was performed. A computed tomography (CT) scan revealed partial PVT of intrahepatic branches of PV, and thrombosis of the inferior mesenteric vein. After conservative treatment with low molecular weight heparin (LMWH) and other supportive measures, the digestive bleeding ceased, and defecation became normal. During the one-month follow-up, the patient had no complications, and the control CT scan revealed normal PV flow without thrombosis. Conclusion. Although rare, a non-malignant and non-cirrhotic PVT should not be neglected in the differential diagnosis because timely and vigilant therapy with LMWH can lead to complete resolution without serious complications. [ABSTRACT FROM AUTHOR]