Binding, Antioxidant and Anti-proliferative Properties of Bioactive Compounds of Sweet Paprika (Capsicum annuum L.).

The scope of this research was to determine the bioactive composition, antioxidant, binding, and anti-proliferative properties of red sweet paprika growing under artificial light. The amounts of carotenoids, chlorophyll, polyphenols, tannins, and flavonoids in red paprika (RP), cultivated in Korea, before and after light treatments under high pressure sodium (HPS) and lighting emitting plasma (LEP) lamps (RPControl, RPHPS, RPLEP), were analyzed in water (W) and ethanolic extracts (Et). Spectroscopic, radical scavenging assays, fluorescence and cytotoxicity measurements were applied. The results of this study showed that total chlorophyll and carotenes were the highest in RPHPS (10.50 ± 1.02 and 33.90 ± 3.26 µg/g dry weight (DW)). The strongest antioxidant capacity (µM TE/g DW) in a 2, 2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) diammonium salt (ABTS(•+)) assay was in RPControlEt (24.34 ± 2.36), in a ferric-reducing/antioxidant power (FRAP) assay in RPHPSW (27.08 ± 2.4) and in a cupric reducing antioxidant (CUPRAC) in RPLEPW (70.99 ± 7.11). The paprika ethanolic extracts showed lower values in their bioactivity than the water ones. The binding and cytotoxicity abilities of extracted polyphenols correlated with their amounts. LEP treatment is better for plant growth characteristics than other conventional treatments. The investigated paprika samples can be used as a source of antioxidants.

The influence of raw and processed garlic and onions on plasma classical and non-classical atherosclerosis indices: investigations in vitro and in vivo.

Garlic and white and red varieties of onion were subjected to processing by a variety of culinary methods, and bioactive compounds then determined. For in vivo studies, 84 male Wistar rats were randomly divided into 14 diet groups, each of six rats, including two control groups (one with no supplementation and one with cholesterol supplementation only). During the 30-day trial, the basal diets of the other 12 groups were supplemented with 1% cholesterol and raw or processed vegetables. Both raw red onion and red onion subjected to blanching for 90 s hindered the rise in plasma lipids more than the other vegetables studied in the supplemented diets. The decrease in antioxidant activity compared to the cholesterol-supplemented control group was significantly less for the group fed with red onion subjected to blanching for 90 s. No histological changes were detected in the studied organs of rats that had been fed cholesterol. In conclusion, blanching for 90 s most fully preserved the bioactive compounds and antioxidant potentials, and hindered the rise in plasma lipid levels and the decrease in plasma antioxidant activity of rats fed cholesterol. Alkaline phosphatase levels correlated with classical atherosclerosis indices, and determination of alkaline phosphatase is suggested as an additional index in atherosclerosis testing.

Influence of Porous Dressings Based on Butyric-Acetic Chitin Co-Polymer on Biological Processes In Vitro and In Vivo.

In spite of intensively conducted research allowing for the development of more and more advanced wound dressing materials, there is still a need for dressings that stimulate not only reparative and regenerative processes, but also have a positive effect on infected and/or difficult-to-heal wounds. Porous dressing materials based on butyric-acetic chitin co-polyester containing 90% of butyryl and 10% of acetyl groups (BAC 90/10) can also be included in the group mentioned above. Two types of dressings were obtained by the salt leaching method, i.e. a porous sponge Medisorb R and Medisorb Ag with an antibacterial additive. The aim of the study was to evaluate biological effects of porous Medisorb R and Medisorb Ag dressings under in vitro and in vivo conditions. In an in vitro biodegradation test, no mass loss of Medisorb R dressing was observed within 14 days of incubation in physiological fluids at 37 °C. However, on the basis of the FTIR (Fourier Transform Infrared Spectroscopy) tests, surface degradation of Medisorb R dressing was observed. Additionally, the antibacterial activity of the porous Medisorb Ag dressing containing microsilver as an antibacterial additive was confirmed. The in vivo studies included inflammatory activity, skin irritation and sensitisation tests, as well an assessment of local effect after contact with subcutaneous tissue up to 6 months and skin wounds up to 21 days. In the in vivo tests, the dressings exhibited neither effects of skin irritation nor sensitisation. Under macroscopic examination, in full thickness defects of subcutaneous tissue and skin, the dressings caused wound healing with no inflammation, undergoing the most gradual biodegradation between weeks 4 and 8, and the observed differences were statistically significant. In the histological assessment, a weakened, limited inflammatory process associated with degradation of the material has been observed. The process of skin wound healing under Medisorb R dressing in the early period was accelerated compared to that observed in the control group with a gauze dressing.

Durian (Durio zibethinus Murr.) cultivars as nutritional supplementation to rat's diets.

The properties of Mon Thong, Chani and Kan Yao durian (Durio zibethinus Murr.) cultivars were compared in vitro and in vivo studies in order to find the best one as a supplement to antiatherosclerotic diet. Total polyphenols (361.4+/-35.3 mgGAE/100g FW), flavonoids (93.9+/-8.9 mgCE/100g FW) and total antioxidant capacity determined by DPPH and beta-carotene-linoleic acid assays (261.3+/-25.3 microMTE/100g FW and 77.8+/-7.8% of inhibition) were maximal in Mon Thong in comparison with Chani and Kan Yao and showed a good correlation between these three variables (R(2)=0.9859). Five groups of rats were fed diets supplemented with cholesterol and different durian cultivars. Diets supplemented with Mon Thong and to a lesser degree with Chani and Kan Yao significantly hindered the rise in the plasma lipids (TC - 8.7%, 16.1% and 10.3% and (b) LDL-C - 20.1%, 31.3% and 23.5% for the Chol/Kan Yao, Chol/Mon Thong and Chol/Chani, respectively) and the decrease in plasma antioxidant activity (P<0.05). Nitrogen retention remained significantly higher in Chol/Mon Thong than in other diet groups. Diet supplemented with Mon Thong affected the composition of plasma fibrinogen in rats and showed more intensity in protein bands around 47 kDa. No lesions were found in the examined tissue of heart and brains. Mon Thong cultivar is preferable for the supplementation of the diet as positively influenced the lipid, antioxidant, protein and metabolic status. The durian fruit till now was not investigated extensively, therefore based on the results of this study durian cultivars can be used as a relatively new source of antioxidants.

Influence of mussels (Mytilus galloprovincialis) from polluted and non-polluted areas on some atherosclerosis indices in rats fed cholesterol.

The influence of diets supplemented with mussels, from polluted (MPoll) and non-polluted (MNPoll) areas, on some atherosclerosis indices in rats fed cholesterol (Chol) were studied. According to the results of our investigation in vitro, mussels from polluted areas had higher contents of proteins, metals and antioxidant compounds, mostly phenolics and higher antioxidant capacities. 28 male Wistar rats were divided into 4 groups of 7 and named Control, Chol, Chol/MPoll and Chol/MNPoll. The rats of the Control group received basal diet (BD) only, and the diets of the other 3 groups were supplemented with 1% of non-oxidized cholesterol (NOC), 1% of NOC and 5.6% of mussel dry matter (DM) from polluted and 1% of NOC and 5.6% of mussel DM from non-polluted areas for Chol, Chol/MPoll and Chol/MNPoll, respectively. The histology of the aorta and brain in rats fed cholesterol did not show any signs of atherosclerosis. Some differences were registered in the electrophoretic protein patterns of plasma in rats, with mussel-supplemented diets. In full plasma electrophoretic patterns of the Chol/MPoll diet group more proteins were detected than in both Chol and Control groups, and the differences were significant. In conclusion, in groups of rats fed cholesterol with mussels supplementation, a significant hindering in the rise of plasma lipid levels and also hindering in the decrease of plasma antioxidant activity were registered.

In Vitro Screening of Bioactive Compounds in some Gluten-Free Plants.

Electrophoretic, antioxidant, and FTIR profiles of some varieties of amaranth, quinoa, and buckwheat seeds and their by products were compared. Water extracts of these products were evaluated by the Folin-Ciocalteau method in order to determine total phenolic content. The antioxidant activities were determined by 2,2'-azobis-2-methyl-propanimidamide, ferric-reducing/antioxidant power, and cupric reducing antioxidant capacity radical scavenging assays. FTIR spectra showed the secondary structure of pseudocereals in the ranges of amides I, II, and III shifts. Results of evaluated methods could be used to control several products (seeds, flours, extracts, flakes, roasting) with high phenolic content and antioxidant activity suitable for supplementation in food applications. Graphical Abstract ᅟ.

The atherosclerotic heart disease and protecting properties of garlic: contemporary data.

This article reviews the contemporary data concerning atherosclerosis and protecting properties of garlic. Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis. These new findings provide important links between risk factors and the mechanisms of atherogenesis and garlic properties. Numerous in vitro studies have confirmed the ability of garlic to reduce the parameters of the risk of atherosclerosis: total cholesterol, LDL, triglycerides, oxidized LDL. Bioactive compounds and antioxidant potentials in fresh, cooked, boiled and commercial garlic from different regions are presented, using beta-carotene, 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) with K2S2O8 or MnO2, ferric-reducing/antioxidant power (FRAP), cupric reducing antioxidant capacity (CUPRAC) and others assays for antioxidant status. In vivo studies were reviewed on with garlic and cholesterol supplemented diets. The positive influences of garlic on plasma lipids, proteins, antioxidant activity, and some indices of blood coagulation are dose dependent. Garlic could be a valuable component of atherosclerosis-preventing diets only in optimal doses. Many recently published reports show that garlic possesses plasma lipid-lowering and plasma anticoagulant and antioxidant properties and improves impaired endothelial function.

The effect of short-term lyophilized beer consumption on established hypertension in rats.

Effects of short-term lyophilized beer (LB) consumption on normotensive (WKY) and hypertensive (SHR) rats are reported. It was found that LB contains high quantities of bioactive compounds and has a high antioxidant potential. The WKY and SHR rats were divided into four groups of 8, two experimental and two controls, which were named LBWKY and LBSHR and ControlWKY and ControlSHR, respectively. LB was given to the rats of the LBWKY and LBSHR groups intragastrically at a dose of 2.72 g/kg in a volume of 10 ml/kg for 10 days. The rats of the control groups received saline solution. The following indices were determined: body weight gain, heart rate, systolic blood pressure, using a tail cuff method and GABA accumulation in the hypothalamus and the pons-medulla as measured by GABA-T inhibition. It was found that the treatment of rats with LB had no effect on the blood pressure and heart rate values. In both rat strains, LB decreased GABA accumulation in the hypothalamus and the pons-medulla. A significant reduction of body weight gain was observed in both LB-treated groups when compared with the corresponding controls. In conclusion, LB contains high quantities of bioactive compounds and possesses a high antioxidant potential. Diet supplemented with LB causes significant reduction of the central GABAergic activity in WKY and SHR rats without any effect on cardiovascular function. In addition, in both animal strains there was an apparent inverse association between LB intake and body weight gains.

The bioactivity of processed garlic (Allium sativum L.) as shown in vitro and in vivo studies on rats.

Garlic (Allium sativum L.) is widely used as an obligatory part in many cooked dishes loosing during this process a certain part of its bioactivity. Antioxidant capacity measured by the ferric-reducing/antioxidant power (FRAP) method and by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical assay was the highest in raw and in a short time processed garlic samples by cooking. 70 Wistar rats were randomly divided into 10 diet groups, each of seven. They were named Control, NPG, PG1, PG2, PG3, Chol, Chol/NPG, Chol/PG1, Chol/PG2 and Chol/PG3. The rats of the Control group were fed basal diet (BD), which included wheat starch, casein, soybean oil, cellulose, mineral and vitamin mixtures. To the BD of the nine other groups were added 25mg of lyophilized non processed garlic equivalent of 500 mg non processed garlic/kg body weight (NPG), the same quantity of processed garlic for 20, 40 and 60 min for PG1, PG2 and PG3, respectively, 1% of cholesterol (Chol), 1% of cholesterol and 25mg/kg body weight of lyophilized non processed garlic (Chol/NPG), 1% of cholesterol and the same quantity of processed garlic for 20, 40 and 60 min for Chol/PG1, Chol/PG2 and Chol/PG3, respectively. The dose of 500 mg (25mg of lyophilized garlic/kg body weight) was chosen as the most effective (Banerjee, S.K., Maulik, M., Mancahanda, S.C., Dinda, A.K., Gupta, S.K., Maulik, S.K., 2002. Dose-dependent induction of endogenous antioxidants in rat heart by chronic administration of garlic. Life Sciences 70, pp. 1509-1518). Plasma lipid profile and the total antioxidant capacity in rats significantly differed in diet groups with addition of garlic samples cooked for a long time. In summary, garlic cooked for a short time preserves a high bioactivity of non processed garlic. The diet supplemented with these samples and cholesterol improved lipid indices, decreased fibrinogen and increased antioxidant activity in plasma of rats. Therefore, for preservation of garlic bioactivity optimal regime has to be used.

The nutritional and metabolic indices in rats fed cholesterol-containing diets supplemented with durian at different stages of ripening.

The aim of this investigation was to assess the nutritional and health properties of Mon Thong durian cultivar at different stages of ripening. The assessment was carried out in vitro and in vivo. The contents of dietary fibers, minerals and trace metals at different stages of ripening were comparable. Total polyphenols (mgGAE/100 g FW) and flavonoids (mg CE/100 gFW) in ripe durian (358.8 +/- 31.4 and 95.4 +/- 9.3) were significantly higher (p < 0.05) than in mature (216.1 +/- 1 and 39.9 +/- 3.8) and overripe (283.3 +/- 26.2 and 53.5 +/- 4.9). Antioxidant capacity (muMTE/100 g FW) in total polyphenol extracts of ripe durian measured by 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) and [2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid)] (ABTS) assays (259.4 +/- 23.6 and 2341.8 +/- 93.2) were significantly higher (p < 0.05) than that of mature (151.6 +/- 15.2 and 1394.6 +/- 41.5) and overripe (201.7 +/- 19.4 and 1812.2 +/- 61.4) samples. The correlation coefficients between the bioactive compounds in different stages of ripening and their antioxidant capacities were high (R;{2} = 0.99). Then 35 male Wistar rats were divided into 5 dietary groups each of 7 and named Control, Chol, Chol/Mature, Chol/Ripe and Chol/Overripe. During 30 days of the experiment the rats of all 5 groups were fed basal diet (BD), which included wheat starch, casein, soybean oil, vitamin and mineral mixtures. The rats of the Control group were fed a BD only. To the BD of the Chol group was added 1% of cholesterol. The BD of the Chol/Mature, Chol/Ripe and Chol/Overripe groups was supplemented with 1% of cholesterol and 5% of the mature, ripe and overripe durian as freeze-dried powder, respectively. Diets containing ripe and to a lesser degree mature and overripe durian significantly hindered the rise in plasma lipids and also hindered a decrease in plasma antioxidant activity. The nitrogen retention in rats of the Chol/Ripe group was significantly higher (63.6%, P < 0.05) than in other diet groups and the level of the plasma glucose remained normal. A decrease in fibrinogen fraction with ripe durian included in rat's diets was shown by electrophoretic separation. These changes were detected mostly in the low molecular weight proteins of rat's serum. Histological examination of aorta showed only slight differences in the tissue. In conclusion, ripe durian contains higher quantity of bioactive compounds, has higher antioxidant capacity and nutritional value. It positively affects the plasma lipid profile, the plasma glucose and the antioxidant activity in rats fed cholesterol enriched diets. Therefore, the ripe durian supplemented diet could be beneficial for patient suffering from hypercholesterolemia and diabetes mellitus. <

[The histopathological evaluation of the local tolerance of alendronate containing medicines]. / Ocena histopathologiczna tolerancji miejscowej preparatów zawierajacych alendronian.

INTRODUCTION: In order to be effective, treatment for osteoporosis must be long-term. Unfortunately, according to clinical trials and clinical practice the most frequent cause of patient resignation from the treatment is adverse reactions to the medications. In the case of bisphosphonates they are most frequently connected with irritant impact of the drug on gastrointestinal mucosa. The aim of our study was to answer the question whether alendronate tablets coated with a thin neutral layer may protect gastrointestinal mucosa from the irritant effects of the active substance. MATERIAL AND METHODS: Three types of tablets were administered into the cheek pouches of 18 Syrian hamsters (divided into 3 experimental groups: I, II, III) i.e. regular alendronate tablets, coated alendronate tablets and placebo. The tablets were applied for 4 minutes a day on 4 consecutive days. 24 hours after the last application, the animals were sacrificed and segments of buccal tissue were taken for histopathological examination. Oral tissue reaction was assessed using the microscopic examination grading system developed by ISO. The following adverse changes of the tissue were recorded: epithelial lesions, leucocyte infiltration, vascular congestion and oedema. Later the irritation index was calculated. RESULTS: The irritation index was 11.0 (moderately irritant), 0.0 and 0.0 (none-irritant), in each group respectively. CONCLUSION: It appears that the administration of the coated alendronate tablets reduces the frequency and intensity of the local adverse events from the gastrointestinal tract.

Dose-dependent influence of commercial garlic (Allium sativum) on rats fed cholesterol-containing diet.

The aim of this investigation was to evaluate the dose-dependent influence of commercial garlic on rats fed cholesterol-containing diets. It was found that commercial garlic contains high concentrations of dietary fibers, microelements, and total polyphenols, and its total antioxidant capacity as determined by two independent assays [1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS)] was similar to that of the original garlic samples. Wistar rats (35) were randomly divided into five diet groups, named control, Chol, Garlic500, Garlic750, and Garlic1000. Control rats were fed basal diet (BD), which included wheat starch, casein, soybean oil, and vitamin and mineral mixtures. To the BD of the Chol group was added 1% of cholesterol. To the BD of the other three groups (Garlic500, Garlic750, and Garlic1000) were added 1% of cholesterol and commercial garlic equal to 500, 750, and 1000 mg of raw garlic per kilogram of animal weight. After 4 weeks of the experiment only in rats from the Garlic500 group were a significant hindering in the rise in plasma lipids and also a significant hindering in a decrease of plasma antioxidant activity registered. A significant decrease in plasma circulating fibrinogen and an increase in the clotting time were found in the same group of rats (P < 0.05 in both cases). The fibrinogenolytic effect of garlic diets was visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the fibrinogen fraction of Garlic500 the 66, 24, and 14 kDa protein bands were detected with weaker protein intensity than in the corresponding ones in the Garlic750 and Garlic1000 diet groups. In conclusion, the positive influences of commercial garlic on plasma lipids, proteins, antioxidant activity, and some indices of blood coagulation are dose-dependent. Therefore, commercial garlic (Elena, Zelazków, Poland) could be a valuable component of atherosclerosis-preventing diets only in optimal doses.

Red Star Ruby (Sunrise) and blond qualities of Jaffa grapefruits and their influence on plasma lipid levels and plasma antioxidant activity in rats fed with cholesterol-containing and cholesterol-free diets.

Bioactive compounds of peels and peeled red Star Ruby (Sunrise) and blond qualities of Jaffa grapefruits were analyzed and their antioxidant potential was assessed. The dietary fibers were determined according to Prosky et al., the total polyphenol content by Folin-Ciocalteu method and measured at 765 nm, minerals and trace elements by atomic absorption spectrometer, phenolic and ascorbic acids by HPLC and the antioxidant potential by two different antioxidant assays (DPPH and beta-carotene linoleate model system). It was found that the contents of most studied bioactive compounds in both qualities are comparable. Only the contents of total polyphenols and flavonoids were higher in red grapefruits, but not significant. The antioxidant potentials of red peeled grapefruits and their peels were significantly higher than of blond peeled grapefruits and their peels (P<0.05 in both cases). Diets supplemented with peeled red and blond qualities of Jaffa grapefruits and their peels have increased the plasma antioxidant capacity and improved plasma lipid levels, especially in rats fed with cholesterol added diet. In conclusion, both qualities of Jaffa grapefruits contain high quantities of bioactive compounds, but the antioxidant potential of red grapefruits is significantly higher. Diets supplemented with both qualities of Jaffa grapefruits improve the plasma lipid levels and increase the plasma antioxidant activity, especially in rats fed with cholesterol added diets. Jaffa grapefruits, especially their red Star Ruby quality, could be a valuable supplementation for diseases-preventing diets.

Comparison of the bioactive compounds and antioxidant potentials of fresh and cooked Polish, Ukrainian, and Israeli garlic.

Garlic (Allium sativum L.) is an essential part of Polish, Ukrainian, and Israeli cuisine. The aim of this investigation was to compare the changes in bioactive compounds, proteins, and antioxidant potentials in fresh Polish, Ukrainian, and Israeli garlic samples after subjection to cooking temperature. Dietary fiber and essential trace elements were comparable. The antioxidant potentials were determined by four scavenging methods using beta-carotene, 1,1-diphenyl-2-picrylhydrazyl (DPPH), nitric oxide (NO), and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS(*)(+)) radical cation with K(2)S(2)O(8) or MnO(2) assays. Polyphenols, tocopherols, proteins, and antioxidant potentials were higher in Polish garlic, but not significantly (P > 0.05). The SDS- and native-PAGE electrophoretic patterns of all three fresh garlic samples were without significant differences. Most of the proteins were in the molecular mass range of 24-97 kDa, and the more intensive major bands were concentrated at 50 and 12 kDa. The 50 kDa protein nearly disappears and the intensity of the 12 kDa lectin bands slightly decreases during cooking. It was observed that the bioactive compounds, antioxidant potential, and proteins in garlic decrease significantly after 20 min of cooking at 100 degrees C (P < 0.05). In conclusion, (a) the bioactive compounds, electrophoretic patterns, and antioxidant potential of fresh Polish, Ukrainian, and Israeli garlic samples are comparable; (b) garlic samples subjected to 100 degrees C during 20 min preserve their bioactive compounds, antioxidant potential, and protein profile and are comparable with fresh garlic; and (c) fresh garlic should be added to dishes cooked at 100 degrees C in the last 20 min of the cooking process.

In vitro antioxidative and binding properties of phenolics in traditional, citrus and exotic fruits.

Many polyphenols bind proteins, therefore our research was focused on the potential of protein binding to polyphenols of investigated fruits and their health-related effects. The contents of polyphenols and related antioxidant activities of traditional, citrus and exotic fruits were compared. The presence of polyphenols (flavonoids and phenolic acids) in the investigated samples and their interaction with human serum albumin (HSA) was studied by HPLC, Fourier Transform Infrared (FT-IR) and three dimensional fluorescence spectroscopy (3D-FL). The highest levels of polyphenols, antioxidant and binding capacities were found in red and blond grapefruits (citrus group), followed by strawberries and apples (traditional group) and mangosteen and kiwi fruit (exotic fruit), which also contained the highest levels of protocatechuic, p-coumaric, ferulic acids and quercetin. In conclusion, for the first time, the interaction of the polyphenols with human serum albumin was evaluated by fluorometry/FTIR. The obtained binding profiles allowed the comparison of three different groups of fruits. A mixture of these fruits can be recommended for consumption.

Selenitetriglycerides-Redox-active agents.

BACKGROUND: Human prostate cancer (hPCa) is the most commonly diagnosed cancer in elderly men and is the second leading cause of male cancer death. Data from epidemiological, eco-environmental, nutritional prevention and clinical trials suggest that selenium Se(IV) can prevent prostate cancer. Selol, a new organic semisynthetic derivative of Se(IV), is a mixture of selenitetriglycerides. This mixture is non-toxic and non-mutagenic, and after po treatment - 56-times less toxic (in mice) than sodium selenite. It exhibits strong anti-cancer activity in vitro in many cancer cell lines and can overcome the cell resistance to doxorubicin. Selol seems a promising compound for prostate cancer therapy. MATERIALS AND METHODS: The aim of the present study is the evaluation of Selol's influence on intracellular redox state (Eh) of prostatic tumors and the liver in androgen-dependent hPCa-bearing mice, and extracellular redox state in serum of these mice. RESULTS AND CONCLUSIONS: The anticancer activity of Selol involves perturbation of the redox regulation in the androgen dependent hPCa (LNCaP) cells, but not in healthy cells. After Selol treatment, intracellular Eh has increased in tumors from -223 mV to -175 mV, while in serum it has decreased (-82 mV vs -113 mV). It shows significant changes Eh in the extra- and intracellular environment. The difference decreases from 141 mV to 62 mV. The changes suggest that a tumor cell was probably directed toward apoptosis. This is exemplified in a significant decrease in cancer tumor mass by approx. 17% after the three weeks of Selol administration.

Olive oils improve lipid metabolism and increase antioxidant potential in rats fed diets containing cholesterol.

The effect of olive oils on lipid metabolism and antioxidant activity was investigated on 60 male Wistar rats adapted to cholesterol-free or 1% cholesterol diets. The rats were divided into six diet groups of 10. The control group (control) consumed the basal diet (BD) only, which contained wheat starch, casein, cellulose, and mineral and vitamin mixtures. To the BD were added 10 g/100 g virgin (virg group) or Lampante (Lamp group) oils, 1 g/100 g cholesterol (chol group), or both (chol/virg group) and (chol/Lamp group). The experiment lasted 4 weeks. Plasma total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides (TG), total phospholipids (TPH), HDL-phospholipids (HDL-PH), total radical-trapping antioxidative potential (TRAP), malondialdehyde lipid peroxidation (MDA), and liver TC were measured. Groups did not differ before the experiment. In the chol/virg and chol/Lamp vs chol group, the oil-supplemented diets significantly (P < 0.05) lessened the increase in plasma lipids due to dietary cholesterol as follows: TC (25.1 and 23.6%), LDL-C (39.3 and 34.7%), TG (19.3 and 17.0%), and TC in liver (36.0 and 35.1%) for the chol/virg and chol/Lamp group, respectively. The chol/virg and chol/Lamp diets significantly decreased the levels of TPH (24.7 and 21.2%; p < 0.05 in both cases) and HDL-PH (22.9 and 18.0%; p < 0.05 in both cases) for the chol/virg and chol/Lamp group, respectively. Virgin and Lampante oils in rats fed basal diet without cholesterol did not affect the lipid variables measured. Virgin, and to a lesser degree Lampante, oils have increased the plasma antioxidant activity in rats fed BD without cholesterol (an increase in TRAP, 20.6 and 18.5%; and a decrease in MDA, 23.2 and 11.3%, respectively). In the rats of chol/virg and chol/Lamp vs Chol diet groups the added oils significantly hindered the decrease in the plasma antioxidant activity (TRAP, 21.2 and 16.7%; and MDA, 27.0 and 22.3%, respectively). These results demonstrate that virgin, and to less degree Lampante, oils possess hypolipidemic and antioxidant properties. It is more evident when these oils are added to the diets of rats fed cholesterol. These positive properties are attributed mostly to the phenolic compounds of the studied oils.

In vivo study of angiogenic plasmid preparations--the bicistronic plasmid as a new type of drug for vascular diseases.

Angiogenic gene therapy is thought to be a new method for the treatment for vascular diseases. Plasmid preparations encoding angiogenic factors like a vascular endothelial growth factor (VEGF) or a fibroblast growth factor (FGF) effectively stimulate the formation of new vessels. The first clinical trials with novel angiogenic drugs--genetic preparations have already been reported. Nevertheless, gene transfer and expression efficiency still require a lot of experimental work. Here, three different angiogenic preparations were studied. We used monocistronic vectors encoding VEGF165 or FGF-2 and bicistronic construct expressing both of them. The angiogenic potency of the plasmids was evaluated by in vivo angiogenesis tests. We also tested the plasmid DNA maintenance in mouse tissue as well as the transcriptional activity of the angiogenic preparations. We saw that all plasmids effectively stimulate the formation of new vessels in in vivo conditions up to 20 days. The most powerfull angiogenic potency was demonstrated by the bicistronic vector. It was shown that after 3, 13, 21, 31 and 41 days post-transfection the plasmid DNA still persisted in tissue, more or less on the same level but the mRNA transcripts after 13 days slowly decreased. This work confirmed effectiveness of gene therapy, and gave new information about angiogenic plasmid preparations useful for practical applications.

Bone regeneration potential of the new chitosan-based alloplastic biomaterial.

Over the last few years, alloplastic bone substitute materials are raising much interest as an alternative to autologic transplants and xenogenic materials especially in oral surgery. These non-immunogenic and completely resorbable biomaterials are becoming the basis for complete and predictable guided bone regeneration in many cases. The objective of our research was to evaluate the dynamics of bone formation in rats' skulls after implantation of the new chitosan/tricalcium phosphate/alginate biomaterial in comparison to the commercially available alloplastic bone graft. A total of 45 adult male rats weighing 300-400 g were used for the study. The 85-mm-diameter defects in calvaria bone were prepared with a trephine bur, and then filled with the bone substitute materials: chitosan/tricalcium phosphate/alginate or easy-graft Classic (Degradable Solutions AG) (EA) or left just with the blood clot. Animals were sacrificed at 1 and 3 months for histological, histomorphometrical and micro-tomographic evaluations. Histological evaluation at 1 month showed early new bone formation, observed around the experimental biomaterial (CH/TCP/Alg). There were no features of purulent inflammation and necrosis or granulomatous inflammation. Microscopic examination after 3 months following the surgery revealed trabecular bone formation around chitosan-based bone graft with no significant inflammatory response. Less satisfactory and differing results were observed for the commercially available EA and control blood clot. The tested material (chitosan) showed a high degree of biocompatibility and osteoconductivity in comparison with the control groups. Additionally, it seemed to be a "user-friendly" material for oral surgeons.

DNA methyltransferase inhibitors and their emerging role in epigenetic therapy of cancer.

The DNA methyltransferase (DNMT) inhibitors azacytidine and decitabine are the most successful epigenetic drugs to date and are still the most widely used as epigenetic modulators, even though their application for oncological diseases is restricted by their relative toxicity and poor chemical stability. Zebularine (1-(ß-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one), a more stable and less toxic cytidine analog, is another inhibitor of DNMT with concomitant inhibitory activity towards cytidine deaminase. Unfortunately, there is no new information related to the possible clinical applications of zebularine. Although many new inhibitors of DNMT have been identified, none of them can so far replace azacytidine, decitabine and, to a lesser degree, zebularine. This review summarizes the current data and knowledge about azacytidine, decitabine and zebularine, and their role in present and possible future epigenetic cancer therapy. We also discuss the molecular modes of action of these agents with consideration of their different toxicities and demethylation profiles, reflecting their complex and partially overlapping biological effects.