Search

Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations.

Considering the urgency of finding a cure for vicious diseases such as tumors, we have synthesized and characterized a small series of new copper(ii) complexes with biologically important ligands such as acylpyruvate. In addition to this, we used another four copper(ii) complexes, with ligands of the same type to examine the antitumor potential. The antitumor potential of the copper(ii) complexes was examined on three tumor cell lines and one normal human cell line using the MTT assay. All seven tested complexes showed very good cytotoxic effects. Two copper complexes that showed the best antitumor potential were selected for further testing that showed the best potential for potential application in the future. The mechanism of activity of these complexes was examined in detail using tests such as cell cycle, ROS level, oxidative DNA damage, and proteins related to hypoxia analysis. In addition, we examined the binding abilities of these complexes with biomolecules (Guo, Ino, 5′-GMP, BSA, and DNA). The results showed that the tested compounds bind strongly to DNA molecules through intercalation. Also, it has been shown that the tested compounds adequately bind to the BSA molecule, which indicates an even greater potential for some future application of these compounds in clinical practice. © 2022 The Royal Society of Chemistry.

Background/Aim. Exposure of living organisms to γ-radiation results in the overproduction of free radicals. The aim of the study was to test if the subacute administration of micronized zeolite (MZC) accomplishes radioprotective role based on the evaluation of the status of oxidative stress (OS) in the brain and 8-hydroxyguanosine (8-OH-dG) in the plasma of the rats exposed to the single γ-ray irradiation of 2 and/or 10 Gray (Gy). Methods. Wistar rats were on a four-week normal or 5% MZC supplemented diet and afterward exposed to the single γ-ray irradiation of 2 and 10 Gy. Groups of rats were: a) on a normal diet (the control group, and 2Gy and 10Gy groups); b) on 5% MZC supplemented diet (the control group – MZC, MZC + 2Gy, and MZC + 10Gy groups). We measured malondialdehyde (MDA), glutathione (GSH) total, and activity of total super-oxide dismutase (tSOD) and manganese superoxide dismutase (MnSOD) in vulnerable brain regions (cerebellum, hippocampus, and cerebral cortex) and 8-OH-dG in plasma. Results. Lower MDA was found in the MZC+2Gy and MZC+10Gy groups compared to the 2Gy and 10Gy groups. Activity od total SOD was higher in the MZC+10Gy group than in the 10Gy one. GSH was the highest in the 10Gy group. Compared to the control group, 8-OH-dG was extremely higher in groups radiated with 10 Gy regardless of a diet, but slightly lower in the MZC+2Gy and 2Gy groups. Conclusion. Subacute MZC pretreatment accomplished partial radioprotective effect in irradiated rats compared to non-irradiated rats, based on suppressed SOD activity at 2 Gy, and reduced brain MDA when exposed to 2 Gy and 10 Gy., Background/Aim. Exposure of living organisms to γradiation results in the overproduction of free radicals. The aim of the study was to test if the subacute administration of micronized zeolite (MZC) accomplishes radioprotective role based on the evaluation of the status of oxidative stress (OS) in the brain and 8-hydroxyguanosine (8-OH-dG) in the plasma of the rats exposed to the single γ-ray irradiation of 2 and/or 10 Gray (Gy). Methods. Wistar rats were on a four-week normal or 5% MZC supplemented diet and afterward exposed to the single γ-ray irradiation of 2 and 10 Gy. Groups of rats were: a) on a normal diet (the control group, and 2Gy and 10Gy groups); b) on 5% MZC supplemented diet (the control group – MZC, MZC + 2Gy, and MZC + 10Gy groups). We measured malondialdehyde (MDA), glutathione (GSH) total, and activity of total superoxide dismutase (tSOD) and manganese superoxide dismutase (MnSOD) in vulnerable brain regions (cerebellum, hippocampus, and cerebral cortex) and 8-OH-dG in plasma. Results. Lower MDA was found in the MZC+2Gy and MZC+10Gy groups compared to the 2Gy and 10Gy groups. Activity od total SOD was higher in the MZC+10Gy group than in the 10Gy one. GSH was the highest in the 10Gy group. Compared to the control group, 8-OH-dG was extremely higher in groups radiated with 10 Gy regardless of a diet, but slightly lower in the MZC+2Gy and 2Gy groups. Conclusion. Subacute MZC pretreatment accomplished partial radioprotective effect in irradiated rats compared to non-irradiated rats, based on suppressed SOD activity at 2 Gy, and reduced brain MDA when exposed to 2 Gy and 10 Gy.

Dosadašnja istraživanja mehanizama toksičnosti alkohola i kadmijuma (Cd) pri pojedinačnoj i udruženoj izloženosti eksprimantalnih životinja potvrđuju da oba agensa dovode do reproduktivne toksičnosti. Brojne epidemiološke studije su takođe ukazale da su pušenje i alkoholizam uzročnici poremećaja u spermatogenezi i neplodnosti kod muškaraca. S obzirom na činjenicu da je duvanski dim značajan izvor izloženosti Cd, kao i da su alkoholičari uglavnom i pušači, potrebno je utvrditi kako disulfiram (DSF), lek koji se koristi u averzivnoj terapiji alkoholizma, utiče na reproduktivnu toksičnost izazvanu pomenutim toksikantima. Cilj ove studije je bio da se ispita efekat DSF na narušenu homeostazu bioelemenata, redoks i androgeni status u testisima pacova prethodno izloženih alkoholu i/ili Cd kao i tokom koekspozicije sa Cd. Slobodna sulfhidrilna grupa (–SH) u hemijskoj strukturi metabolita DSF, dietilditiokarbamata (DDTC), ukazuje na redukcioni i helirajući potencijal DSF koji umnogome može da promeni metabolizam kako ispitivanih toksičnih agenasa (alkohola i Cd), tako i esencijalnih bioelemenata, kao i endogenih jedinjenja koja poseduju –SH grupe zbog mogućih reakcija tiolnog ukrštanja.Studija na životinjama (mužjaci pacova Wistar soja, n = 288) je dizajnirana sa ciljem da se imitiraju navike alkoholičara-pušača pre i nakon uvođenja DSF. Životinje su bile izložene ispitivanim supstancama subakutno (alkoholu i DSF), odnosno subhronično (Cd). Alkohol, DSF i maslinovo ulje (MU) kao rastvarač za DSF, su davani putem oralne sonde (per os), a Cd intraperitonelano (i.p.), svakodnevno u jednoj dozi. Životinje su slučajnim odabirom podeljene na kontrolne grupe i 7 eksperimentalnih grupa, od kojih je svaka grupa podeljena u 4 ili 6 podgrupa (n = 6) u odnosu na dužinu izloženosti svakoj od ispitivanih supstanci pojedinačno ili njihovoj kombinovanoj primeni. Podela eksperimentalnih životinja na grupe u odnosu na trajanje ekspozicije (1, 3, 10, 21 i 42 dana) je sledeća: tri kontrolne gr, Previous animal studies on the mechanisms of toxicity after exposure or co-exposure to alcohol and cadmium (Cd) confirmed that both agents induce reproductive toxicity. Numerous epidemiological studies have also suggested that smoking and alcoholism cause disturbances in spermatogenesis and infertility in men. Due to the fact that tobacco smoke is an important source of Cd exposure, as well as alcoholics are usually smokers too, it is necessary to determine if disulfiram (DSF), a drug used in aversive therapy of alcoholism, affects the reproductive toxicity induced by the abovementioned toxicants. The aim of this study was to examine the effect of DSF on disturbed bioelements’ homeostasis, redox and androgen status in the testes of rats previously exposed to alcohol and / or Cd and during co-exposure with Cd. Free sulfhydryl group (-SH) in the chemical structure of the DSF’s metabolite, diethyldithiocarbamate (DDTC), indicates the reducing and chelating potential of DSF, which in many ways can change the metabolism of tested toxic agents (A and Cd), as well as essential bioelements, and endogenous compounds containing -SH groups due to possible reactions of thiol linking.The animal study (male Wistar rats, n = 288) was designed in order to imitate the conditions of alcoholics-smokers before and after the introduction of DSF. The animals were exposed to the tested substances subacute (alcohol and DSF) and subchronic (Cd). Alcohol, DSF, and olive oil (OL), as a solvent for DSF, were administered via oral gavage (per os), and Cd intraperitoneally, in a single daily dose. Animals were randomly divided into control groups and 7 experimental groups, each group was divided into 4 or 6 subgroups (n = 6) according to the duration of exposure to the tested substances alone or in combination. The division of the groups of the experimental animals with respect to the exposure time (1, 3, 10, 21 and 42 days) was as follows: three control groups (C1-42, OL1-21 and C1-21 / OL22-42

The aim of the study was to investigate if alcohol and disulfiram (DSF) individually and in combination affect bioelements' and red-ox homeostasis in testes of the exposed rats. The animals were divided into groups according to the duration of treatments (21 and/or 42 days): C-21/C-42 groups (controls); OL21 and OL22-42 groups (0.5 mL olive oil intake); A(1-21) groups (3 mL 20% ethanol intake); DSF1-21 groups (178.5 mg DSF/kg/day intake); and A(21)+DSF22-42 groups (the DSF ingestion followed previous 21 days' treatment with alcohol). The measured parameters in testes included metals: zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg) and selenium (Se); as well as oxidative stress (OS) parameters: superoxide anion radical (O-2(center dot-)), glutathione reduced (GSH) and oxidized (GSSG), malondialdehyde (MDA), hydrogen peroxide (H2O2) decomposition and activities of total superoxide dismutase (tSOD), glutathione-Stransferase (GST) and glutathione reductase (GR). Metal status was changed in all experimental groups (Fe rose, Zn fell, while Cu increased in A(21)+DSF24-32 groups). Development of OS was demonstrated in A(1-21) groups, but not in DSF1-21 groups. In A(21)+DSF22-42 groups, OS was partially reduced compared to A groups (A(1-21)>MDA>C; A(1-21) lt GSH lt C). High metal-binding affinity of DSF/DDTC changes red-ox homeostasis in rat testes.

The objective of our study was to examine testicular toxicity of cadmium (Cd), focusing on oxidative stress (OS), essential metals and androgenic status and morphological changes. Male Wistar rats [controls and four Cd-subgroups (n = 6) organized according to the exposure (1, 3, 10 and 21 days)] were intraperitoneally (i.p.) treated with 1 mg CdCl2/kg/day. Testicular Cd deposition was noticed from the 1st day. After 10 and 21 days, copper (Cu) and iron (Fe) increased by 60-109% and 43-67%, respectively, while zinc (Zn) decreased by 24-33%. During 121 days of the exposure, decrease in testicular total superoxide dismutase (SOD) and total glutathione-s-transferase (GST) activities occurred gradually by 30-78% and 15-84%, respectively, while superoxide anion radical (O-2(center dot-)) increased gradually by 114-271%. After 10-21 days, decrease in testicular catalase (CAT) activity appeared by 13-31%. After 21 days, malondialdehyde (MDA) decreased by 44% and the ratio of oxidized glutathione/reduced glutathione (GSSG/GSH) increased by 130% in testes of the rats exposed to Cd. Additionally, decreased testicular testosterone level and the relative testes mass, along with induced microscopic and macroscopic changes were occured, what can be explained as the consequence of instantly developed OS, impaired essential metals status and Cd testicular deposition.

The aim of our study was to test the effect of subacutely applied micronized zeolite [micronized clinoptilolite (MZC)] on brain status of iron (Fe), reactive oxygen and nitrogen species (ROS, RNS), and radioprotective role against brain oxidative/nitrosative stress (OS/NS) initiated by single ionizing radiation of 2 or 10Gray (Gy). Wistar rats on normal (n=18) and 5% MZC supplemented diet (n=18), during 4 weeks, were internally subdivided into 3 subgroups (6 rats in each subgroup), with one of subgroup remaining as a control, and the other two subjected to single ionizing radiation of 2Gy or 10Gy. Thus, we had groups on normal diet: C – controls, 2Gy and 10Gy; and on 5% MZC supplemented diet: MZC, MZC+2Gy and MZC+10Gy. Concentrations of nitrates (a final RNS metabolite) and superoxide anion radical (O2 •-) (an initial ROS) were measured in homogenates of selective vulnerable brain regions (cerebellum, hippocampus and forebrain cortex), while Fe was determined in whole brain of rats. Results documented a significant drop of Fe in MZC and MZC+2Gy/10Gy groups; decrease of O2 •- and nitrate in MZC group; almost equal drop of O2 •- , in 2Gy and MZC+2Gy groups; and nitrate increase in 10Gy and MZC+10Gy groups. We confirmed that subacute MZC pretreatment contributes to partially accomplished brain radioprotective effect in rats exposed to single radiation dose of 2Gy and 10Gy, probably due to reduced OS/NS and Fe.

Background: Overproduction of free radicals accompanied with their insufficient removal/neutralization by antioxidative defense system impairs redox hemostasis in living organisms. Oxidative stress has been shown to be involved in all the stages of carcinogenesis and malignant melanocyte transformation. The aim of this study was to examine association between oxidative stress development and different stages of melanoma. Methods: The measured oxidative stress parameters included: superoxide anion radical, total and manganese superoxide dismutase, catalase and malondialdehyde. Oxidative stress parameters were measured spectrophotometrically in serum samples from melanoma patients (n=72) and healthy control subjects (n=30). Patients were classified according to AJCC clinical stage. Results: Average superoxide anion and malondialdehyde concentrations were significantly higher in melanoma patients than in control group, with the highest value of superoxide anion in stage III, while malondialdehyde highest value was in stage IV. The activity of total and manganese superoxide dismutase was insignificantly higher in melanoma patients than in control group, while catalase activity was significantly higher. The highest activity of total superoxide dismutase was in stage III, while the highest activity of manganese superoxide dismutase was in stage IV. Catalase activity was increasing with the disease progression achieving the maximum in stage III. Conclusions: Results of our study suggest that melanoma is oxidative stress associated disease, as well as deteriorated cell functioning at mitochondrial level.

The initial steps in preclinical drug developing research concern the synthesis of new compounds for specific therapeutic use which needs to be confirmed by in vitro and then in vivo testing. Nine thiazolidinone derivatives (numerically labeled 1-9) classified as follows: 1,3-thiazole-based compounds (1 and 2); 1,3,4-thiadiazole based compounds (3 and 4); substituted 5-benzylideno-2-adamantylthiazol[3,2-b] [1,2,4] triazol-6(5H) ones (5-8); and an ethylaminothiazole-based chalcone (9), were tested for antioxidant activity (AOA) by using three in vitro assays: DPPH (1,1-diphenyl-2-picrylhydrazyl scavenging capacity test); FRAP (ferric reducing antioxidant power test); and TBARS (thiobarbituric acid reactive substances test). Compounds 1-4 and 9 in particular are newly synthesized compounds. Also, traditional antioxidants Vitamins E and C and alpha-lipoic acid (alpha-LA) were tested. The results of DPPH testing: Vitamin C 94.35%, Vitamin E 2.99% and alpha-LA 1.57%; compounds: 4 33.98%; 2 18.73%; 1 15.62%; 5 6.59%; 3 4.99%; 6-9 demonstrated almost no AOA. The results of TBARS testing (% of LPO inhibition): Vitamin C 62.32%; Vitamin E 36.29%; alpha-LA 51.36%; compounds: 1 62.11%; 5 66.71%; 9 60.93%; 4, 6 and 7 demonstrated similar to 50%; 3 and 8 displayed similar to 38%; 2 23.51%. By FRAP method, Vitamins E and C showed equal AOA, similar to 100%, unlike alpha-LA (no AOA), and AOA of the tested compounds (expressed as a fraction of the AOA of Vitamin C) were: 2 and 4-75%; 8, 3 and 1-45%; 5-7 and 9-27%. Different red-ox reaction principles between these assays dictate different AOA outcomes for a single compound. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Vitamin C appeared to be the superior antioxidant out of the traditional antioxidants; and compound 4 was superior to other tested thiazolidinone derivatives. Phenyl-functionalized benzylidene, amino-carbo

Dosadašnja istraživanja mehanizama toksičnosti alkohola i kadmijuma (Cd) pri pojedinačnoj i udruženoj izloženosti eksprimantalnih životinja potvrđuju da oba agensa dovode do reproduktivne toksičnosti. Brojne epidemiološke studije su takođe ukazale da su pušenje i alkoholizam uzročnici poremećaja u spermatogenezi i neplodnosti kod muškaraca. S obzirom na činjenicu da je duvanski dim značajan izvor izloženosti Cd, kao i da su alkoholičari uglavnom i pušači, potrebno je utvrditi kako disulfiram (DSF), lek koji se koristi u averzivnoj terapiji alkoholizma, utiče na reproduktivnu toksičnost izazvanu pomenutim toksikantima. Cilj ove studije je bio da se ispita efekat DSF na narušenu homeostazu bioelemenata, redoks i androgeni status u testisima pacova prethodno izloženih alkoholu i/ili Cd kao i tokom koekspozicije sa Cd. Slobodna sulfhidrilna grupa (–SH) u hemijskoj strukturi metabolita DSF, dietilditiokarbamata (DDTC), ukazuje na redukcioni i helirajući potencijal DSF koji umnogome može da promeni metabolizam kako ispitivanih toksičnih agenasa (alkohola i Cd), tako i esencijalnih bioelemenata, kao i endogenih jedinjenja koja poseduju –SH grupe zbog mogućih reakcija tiolnog ukrštanja. Studija na životinjama (mužjaci pacova Wistar soja, n = 288) je dizajnirana sa ciljem da se imitiraju navike alkoholičara-pušača pre i nakon uvođenja DSF. Životinje su bile izložene ispitivanim supstancama subakutno (alkoholu i DSF), odnosno subhronično (Cd). Alkohol, DSF i maslinovo ulje (MU) kao rastvarač za DSF, su davani putem oralne sonde (per os), a Cd intraperitonelano (i.p.), svakodnevno u jednoj dozi. Životinje su slučajnim odabirom podeljene na kontrolne grupe i 7 eksperimentalnih grupa, od kojih je svaka grupa podeljena u 4 ili 6 podgrupa (n = 6) u odnosu na dužinu izloženosti svakoj od ispitivanih supstanci pojedinačno ili njihovoj kombinovanoj primeni. Podela eksperimentalnih životinja na grupe u odnosu na trajanje ekspozicije (1, 3, 10, 21 i 42 dana) je sledeća: tri kontrolne g, Previous animal studies on the mechanisms of toxicity after exposure or co-exposure to alcohol and cadmium (Cd) confirmed that both agents induce reproductive toxicity. Numerous epidemiological studies have also suggested that smoking and alcoholism cause disturbances in spermatogenesis and infertility in men. Due to the fact that tobacco smoke is an important source of Cd exposure, as well as alcoholics are usually smokers too, it is necessary to determine if disulfiram (DSF), a drug used in aversive therapy of alcoholism, affects the reproductive toxicity induced by the abovementioned toxicants. The aim of this study was to examine the effect of DSF on disturbed bioelements’ homeostasis, redox and androgen status in the testes of rats previously exposed to alcohol and / or Cd and during co-exposure with Cd. Free sulfhydryl group (-SH) in the chemical structure of the DSF’s metabolite, diethyldithiocarbamate (DDTC), indicates the reducing and chelating potential of DSF, which in many ways can change the metabolism of tested toxic agents (A and Cd), as well as essential bioelements, and endogenous compounds containing -SH groups due to possible reactions of thiol linking. The animal study (male Wistar rats, n = 288) was designed in order to imitate the conditions of alcoholics-smokers before and after the introduction of DSF. The animals were exposed to the tested substances subacute (alcohol and DSF) and subchronic (Cd). Alcohol, DSF, and olive oil (OL), as a solvent for DSF, were administered via oral gavage (per os), and Cd intraperitoneally, in a single daily dose. Animals were randomly divided into control groups and 7 experimental groups, each group was divided into 4 or 6 subgroups (n = 6) according to the duration of exposure to the tested substances alone or in combination. The division of the groups of the experimental animals with respect to the exposure time (1, 3, 10, 21 and 42 days) was as follows: three control groups (C1-42, OL1-21 and C1-21 / OL22-4

Examination of cadmium (Cd) toxicity and disulfiram (DSF) effect on liver was focused on oxidative stress (OS), bioelements status, morphological and functional changes. Male Wistar rats were intraperitoneally treated with 1mg CdCl2/kg BW/day; orally with 178.5 mg DSF/kg BW/day for 1, 3, 10 and 21 days; and co-exposed from 22nd to 42nd day. The co-exposure nearly restored previously suppressed total superoxide dismutase (SOD), catalase (CAT) and increased glutathione peroxidase (GPx) activities; increased previously reduced glutathione reductase (GR) and total glutathione-S-transferase (GST) activities; reduced previously increased superoxide anion radical (O-2(center dot-)) and malondialdehyde (MDA) levels; increased zinc (Zn) and iron (Fe), and decreased copper (Cu) (yet above control value), while magnesium (Mg) was not affected; and decreased serum alanine aminotransferases (ALT) levels. Histopathological examination showed signs of inflammation process as previously demonstrated by exposure to Cd. Overall, we ascertained partial liver redox status improvement, compared with the formerly Cd-induced impact.

The aim of our work was to optimize and apply simple high-performance liquid chromatography method with ultraviolet detection (HPLC-UV) for simultaneous determination of reduced (GSH) and oxidized (GSSG) glutathione in biological matrix (specifically, the rat liver tissue was used herein), since the ratio between oxidized and reduced glutathione forms (GSSG-GSH) has been recognized as an important biological marker of oxidatively depleted GSH in oxidative stress (OS)-associated diseases and poisonings. An isocratic chromatographic separation of GSH and GSSG (2.8 min and 6.3 min, respectively) was performed with the mobile phase consisted of sodium perchlorate solution (pH adjusted to 2.8) at flow rate of 1 mL min(-1), detection set at 215 nm, and column temperature of 40 degrees C. The method offers short run time, linearity in the range of 0.01-200 mu M concentration for both compounds (R-2 = 1), low limits of detection and quantification (GSH: 0.18 mu M and 0.56 mu M, GSSG: 0.52 mu M and 1.58 mu M, respectively), precision, accuracy (bias lt 2%), and high reproducibility. Through suitable sample handling, an overestimation of GSSG was prevented. High recovery (>99%) was achieved. The method was successfully applied for the analysis of GSH and GSSG in liver homogenates of Wistar rats intraperitoneally exposed to cadmium (Cd) (1 mg kg(-1) CdCl2/21 days). Regardless of other Cd-mediated hepatotoxicity mechanisms, herein, we have exclusively interpreted/emphasized oxidative GSH depletion. The presented method is acceptable for a routine analysis of GSH and GSSG in biological matrix, while the calculated ratio GSSG-GSH is considered as a valuable OS marker.

Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins engaged in activity of excitatory and inhibitory systems as well as redox homeostasis. Our aim was to investigate the effect of single (SS) and repeated session (RS) of intermittentand continuous theta-burst stimulation (iTBS; cTBS) on the expression of vesicular and plasmatic glutamate transporters 1 (vGluT1 and GLT-1), glial fibrillary acidic protein (GFAP) and influence on oxidative status in rats cerebellar tissue and plasma. Redox state parameters in cerebellar tissue and plasma were assessed 24 h after single and 48 h after the last TBS session. Molecular changes were examined by immunofluorescence. Stimulation significantly increased thiol groups (SH) in tissue of SS iTBS group, and decreased in iTBS RS. Activity of glucose-6-phosphate-dehydrogenase (G6PD) was increased markedly in cTBS RS. Immunoreactivity of vGluT1 in cTBS RS decreased, while GLT-1 increased in cTBS SS and cTBS RS, compared to control. Present study gives insight in molecular and biochemical mechanisms by which iTBS and cTBS exerts its effects on rats cerebellar cortex.

Background: Synthesized aminocoumarins are heterocyclic compounds possessing potential for the treatment of insulin-dependent diabetes mellitus with unexplored anti-glycative action. Results: In this study 4-aminocoumarin derivatives (4-ACDs) were evaluated in vitro for antiglycation (AG) activities by using the human serum albumin (HSA)/glucose system, for 8 weeks of incubation. The glycation and conformational alteration of HSA in the presence of the tested compounds were evaluated by Congo red assay, fluorescence and circular dichroism spectroscopy. The antioxidant (AO) capacity were also tested by four different assays including: DPPH (2,2'-diphenyl-1-picrylhydrazyl radical), ABTS (2,2-azinobis (3-ethylbenzothiazoline-6-sulphonate) diammonium salt), FRAP (ferric reducing antioxidant power) and beta-carotene-linoleic acid assay. The tested compounds showed AG and AO effects. The intensity of the accomplished AO potential is related to the type of the used assay. Significant alterations in the secondary (monitored by CD spectropolarimetry) and tertiary structure (assessed by spectrofluorimetry) of HSA upon glycation were mitigated by the 4-ACDs, suggesting their suppressive role in the late stage (post-Amadori) of the HSA glycation. Conclusions: By the analogues, in vitro ascertained AO and AG properties of 4-ACDmay be recognized as rationale for their protective role against oxidative changes of proteins, thereby precluding diabetic complications in humans.

Vibracioni dodavači sa elektromagnetnom pobudom, odnosno elektromagnetni vibracioni dodavači (EMVD) su najčešće korišćeni u procesnoj industriji za obezbeđenje gravimetrijskog protoka sitnozrnih i rasutih materijala. Ovi pogoni obezbeđuju laku i jednostavnu kontrolu masenog protoka transportujućih materijala. U poređenju sa ostalim pogonima (pneumatskim, inercionim, centrifugalnim, itd.), oni su jednostavnije i kompaktnije konstrukcije, robusni i pouzdani u radu. Odsustvo habajući mehaničkih delova kao što su reduktori, kišnici, ekscentri i sl., čine EMVD veoma ekonomičnom opremom. Standardni pretvarački izlazni stepeni namenjeni za kontrolu EMVD su bazirani na SCR elementima (tiristorima i trijacima). Njihovo korišćenje podrazumeva korišćenje kontrole faznog ugla (KFU) i stoga konstantnu učestanost vibracija. Na ovaj način kontrolno kolo mora biti sinhronizovano sa mrežnom učestanošću 50(60)Hz. Uz pomoć KFU je jedino moguće ostvariti podešavanje amplitude vibracija, ali ne i njihove učestanosti. Primena prekidačkih tranzistorskih (IGBT ili MOSFET) energetskih pretvarača, omogućava amplitudsku i (ili) frekventnu kontrolu EMVD. Njihovo korišćenje podrazumeva pobudu EMVD nezavisno od mrežne učestanosti. Dodatno, frekventna kontrola dozvoljava rad u oblasti mehaničke rezonance. Rad u ovoj oblasti je veoma efikasan, pošto je moguće obezbediti značajne izlazne pomeraje, veoma malom ulaznom snagom. Optimalan i efikasan rad zahteva praćenje rezonantne učestanosti. U ovom radu su predstavljeni jedno moguće rešenje vibracione kontrole EMVD, kao i odgovarajući simulacioni i eksperimentalni rezultati., The vibratory feeders with electromagnetic excitation called electromagnetic vibratory feeders (EMVF) are commonly used for performing gravimetric flow of granular and particulate materials in processing industry. This drives offer easy and simple control the mass flow of conveying materials. In comparison with other drives (pneumatics, inertial, centrifugal, etc...), these have a more simple construction and they are compact, robust and reliable in operation. The absence of wearing mechanical part, such as gears, cams belts, bearings, eccentrics, etc., makes EMVF, most economical equipment. Standard power electronic output stages intended for control of the EMVF using SCR devices (thyristors and triacs). This implies phase angle control (PAC) and constant frequency of vibration. In this way control circuit must be synchronized to the mains supply frequency 50(60) Hz. PAC can only accomplish tuning amplitude of vibration, but not vibratory frequency. Application of transistor (IGBT or MOSFET) switch mode power converters enables accomplishing the amplitude and (or) frequency control of EMVF. Their use implies the excitation of an EMVF independent of the mains supply frequency. In addition, the frequency control ensures operation in the region of mechanical resonance. This operation is highly efficient, because large output displacement is provided by small input power. An optimal and efficient operation requires tracking of resonant frequency. This paper presents possible solution of the amplitude frequency control of EMVF and corresponding simulation and experimental results.