Preconditioning of isolated rat heart with ischemia and proton pump inhibitors: Effects on cardiodinamic and coronary flow

Cilj ove studije je bio da ispita efekate prekondicioniranja ishemijom i efekte akutne administracije različitih lekova iz grupe inhibitora protonske pumpe kao farmakoloških agenasa u modelu prekondicioniranja na funkcionisanje miokarda i koronarnu cirkulaciju izolovanog srca pacova kao i moguću ulogu oksidacionog stresa. Metode. U studiji je analizirano 60 pacova (Vistar albino soj, muški pol, starosti 8 nedelja, telesne mase 250±50g) kojima se izolovalo srce i perfundovalo metodom retrogradne perfuzije po Langendorfu (Langendorff apparatus, Experimetria Ltd, 1062 Budapest, Hungary) pri konstantnom koronarnom perfuzionom pritisku od 70 sm H2O. Istraživanje je bilo podeljeno u pet (5) eksperimentalnih grupa. Vrednost koronarnog protoka su određivane floumetrijski. U levoj komori su kontinuirano praćeni parametri funkcije leve komore: a) dp/dt max - maksimalna stopa promene pritiska u levoj komori, b) dp/dt min - minimalna stopa promene pritiska u levoj komori, v) SLVP - sistolni pritisak leve komore, g) DLVP - dijastolni pritisak leve komore i đ) HR - srčana frekvenca. U uzorcima koronarnog venskog efluenta spektrofotometrijskim metodama su određivani sledeći markeri oksidacionog stresa: indeks lipidne peroksidacije – meren kao TBARS, azot monoksid u formi nitrita (NO2), superoksid anjon radikal (O2 -), i vodonik peroksid (H2O2). Rezultati. Rezultati istraživanja su prikazani na 10 tabela i 50 grafikona. Sumarno posmatrano, ishemijsko prekondicioniranje je najpozitivniji efekat ostvarilo u očuvanju perfuzije miokarda i srčane frekvence, dok je prekondicioniranje farmakološkim agensima (lekovima iz grupe inhibitora protonske pumpe) pokazalo bolje rezultate u očuvanju oba parametra kontraktilnosti. Kardiodinamski efekti svih ispitivanih lekova iz grupe IPP nisu bili posredovani oksidacionim stresom. Zaključak. Obe vrste prekondicioniranja su pokazale pozitivan efekat na funkcionalni oporavak miokarda, s tim što je taj uticaj u slučaju farmakološkog prekondicioniranja bio dominanatan na očuvanje kontraktilne sile, dok je u slučaju ishemijskog prekondicioniranja efekat bio fokusiran na očuvanje koronarne reaktivnosti srca. Prilikom međusobnog poređenja ostvarenih efekata ispitivanih IPP, možemo zaključiti da se najznačajniji pozitivni efekat na oporavak miokarda sreće u slučaju omeprazola i pantoprazola.The aim of this study was to investigate the effect of applying preconditioning ischemia and effects of acute administration of different drugs from the group of proton pump inhibitors as pharmacological agents in the model of preconditioning on myocardial function and coronary circulation in isolated rat heart as well as the possible role of oxidative stress. Methods. Sixty rats (Wistar, albino, males, aged 8 weeks, body weight 250±50 g) had the hearts isolated and perfused by using retrograde perfusion method according to Lagendorff (Langendorff apparatus, Experimetria Ltd, 1062 Budapest, Hungary) at constant coronary perfusion pressure of 70 cm H2О. The research included five (5) experimental groups. The values of coronary flow were determined fluorometrically. The next parameters of left ventricle function were continuously followed: a) dp/dt max – maximum rate of pressure change in the left ventricle, b) dp/dt min - minimum rate of pressure change in the left ventricle c) SLVP – systole left ventricle pressure, d) DLVP - diastole left ventricle pressure and e) HR – heart rate. In the samples of coronary venous effluent the following parameters were determined using spectrophotometric methods: lipid peroxidation index – measured as TBARS, nitrogen monoxide in the form of nitrite (NO2), superoxide anion radical (O2 -), and hydrogen peroxide (H2О2). Results. The research results are presented in 10 tables and 50 graphs. In summary, ischemic preconditioning is the most positive effect achieved in the preservation of myocardial perfusion and heart rate, while the preconditioning pharmacological agents (drugs from the group of proton pump inhibitors) showed better results in terms of both parameters contractility. Effects on cardiodynamic of all the tested drugs from the group of PPIs were not mediated by oxidative stress. Conclusion. Both types of preconditioning showed positive effect on functional recovery of the myocardium, with the impact in the event of pharmacological preconditioning that was most dominant on the preservation of contractile force, while in the case of ischemic preconditioning effect was focused on preservation of coronary heart reactivity. When mutual comparison of actual effects of tested IPP, we can conclude that the most important positive effect on the recovery of myocardial we noted in the case of omeprazole and pantoprazole

Neuroinflammation in Autism and Supplementation Based on Omega-3 Polyunsaturated Fatty Acids: A Narrative Review

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by persistent deficits in social communication and social interaction across multiple contexts and restricted, repetitive patterns of behavior, interests and activities. The maternal status of polyunsaturated fatty acids (PUFA) regulates microglial activity and neuroinflammatory pathways during a child’s brain development. In children with ASD, the metabolism of PUFA is thought to be deficient or abnormal, leading to increased production of proinflammatory cytokines, increased oxidative stress and an imbalance in the formation and action of neurotransmitters. In addition, nutritional deficits in omega-3 PUFA may affect gut microbiota and contribute to ASD by the gut–brain axis. The aim of this study was to review the possible role of neuroinflammation in ASD development and the effect of omega-3 PUFA supplementation in children with ASD. Due to a wide heterogeneity across RCTs, no definitive conclusion about omega-3 PUFA effects in ASD can be drawn. Supplementation with PUFA could be considered as one of the aspects in regulating the biological status of the organism and could provide added value to standard medical and psychological interventions for reducing behavioral deficits

Urban regeneration : Smederevo riverfront through the application of information communication technologies

Smederevo has great potential for development - cultural, historical, industrial and natural heritage. In this sense, as a generator for the maximal utilization of all potentials, information and communication technologies (ICT) have been applied in certain places - "points" in the urban structure of the city. On the points. ICT equipment can be used to view the elements of virtual and augmented reality - wildlife and history of the Danube, the Smederevo Fortress in the Middle Ages. Smederevo in the future with new elements of infrastructure and robotics (cyberpunk). etc. The application of ICT has also been achieved in urban design - elevated footpaths for a new view of the city and fortress with digital equipment redevelopment of railway wagons and new materialization of thermochromic pigment paving stones and furniture that changes color under the influence of many WIFl users or their moods. At the end, ICT tools are a base for the comprehensive urban regeneration of the central part of Smederevo Riverfront

Standardized Aronia melanocarpa Extract as Novel Supplement against Metabolic Syndrome: A Rat Model

The aim of our study was to examine the effects of different dietary strategies, high-fat (HFd) or standard diet (Sd) alone or in combination with standardized oral supplementation (0.45 mL/kg/day) of Aronia melanocarpa extract (SAE) in rats with metabolic syndrome (MetS). SAE is an official product of pharmaceutical company Pharmanova (Belgrade, Serbia); however, the procedure for extraction was done by EU-Chem company (Belgrade, Serbia). Rats were divided randomly into six groups: control with Sd, control with Sd and SAE, MetS with HFd, MetS with HFd and SAE, MetS with Sd and MetS with Sd and SAE during 4 weeks. At the end of the 4-week protocol, cardiac function and liver morphology were assessed, while in the blood samples glucose, insulin, iron levels and systemic redox state were determined. Our results demonstrated that SAE had the ability to lower blood pressure and exert benefits on in vivo and ex vivo heart function. Moreover, SAE improved glucose tolerance, attenuated pathological liver alterations and oxidative stress present in MetS. Obtained beneficial effects of SAE were more prominent in combination with changing dietary habits. Promising potential of SAE supplementation alone or in combination with different dietary protocols in triggering cardioprotection should be further examined in future

Immunohistochemical Analysis of 4-HNE, NGAL, and HO-1 Tissue Expression after Apocynin Treatment and HBO Preconditioning in Postischemic Acute Kidney Injury Induced in Spontaneously Hypertensive Rats

Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). The aim of this study was to perform the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression after apocynin (APO) treatment and hyperbaric oxygenation (HBO) preconditioning, applied as single or combined protocol, in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026 bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. Apocynin was applied in a dose of 40 mg/kg body weight, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham-operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning, with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, apocynin treatment and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition

Hyperbaric oxygen preconditioning and the role of NADPH oxidase inhibition in postischemic acute kidney injury induced in spontaneously hypertensive rats

Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI) and hypertension might contribute to the increased incidence of AKI. The purpose of this study was to investigate the effects of single and combined hyperbaric oxygen (HBO) preconditioning and NADPH oxidase inhibition on oxidative stress, kidney function and structure in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. HBO preconditioning was performed by exposing to pure oxygen (2.026 bar) twice a day for two consecutive days for 60 minutes, and 24h before AKI induction. For AKI induction, the right kidney was removed and ischemia was performed by clamping the left renal artery for 45 minutes. NADPH oxidase inhibition was induced by apocynin (40 mg/kg b.m., intravenously) 5 minutes before reperfusion. AKI significantly increased renal vascular resistance and reduced renal blood flow, which were significantly improved after apocynin treatment. Also, HBO preconditioning, with or without apocynin treatment showed improvement on renal hemodynamics. AKI significantly increased plasma creatinine, urea, phosphate levels and lipid peroxidation in plasma. Remarkable improvement, with decrease in creatinine, urea and phosphate levels was observed in all treated groups. HBO preconditioning, solitary or with apocynin treatment decreased lipid peroxidation in plasma caused by AKI induction. Also, combined with apocynin, it increased catalase activity and solitary, glutathione reductase enzyme activity in erythrocytes. While AKI induction significantly increased plasma KIM- 1 levels, HBO preconditioning, solitary or with apocynin decreased its levels. Considering renal morphology, significant morphological alterations present after AKI induction were significantly improved in all treated groups with reduced tubular dilatation, tubular necrosis in the cortico-medullary zone and PAS positive cast formation. Our results reveal that NADPH oxidase inhibition and hyperbaric oxygen preconditioning, with or without NADPH oxidase inhibition may have beneficial effects, but their protective role should be evaluated in further studies

Hyperbaric Oxygen Preconditioning Upregulates Heme OxyGenase-1 and Anti-Apoptotic Bcl-2 Protein Expression in Spontaneously Hypertensive Rats with Induced Postischemic Acute Kidney Injury

Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI

Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin

The quest for sustainable biomaterials with excellent biocompatibility and tailorable properties has put polyhydroxyalkanoates (PHAs) into the research spotlight. However, high production costs and the lack of bioactivity limit their market penetration. To address this, poly(3- hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was combined with a bacterial pigment with strong anticancer activity, prodigiosin (PG), to obtain functionally enhanced PHBV-based biomaterials. The samples were produced in the form of films 115.6–118.8 m in thickness using the solvent casting method. The effects of PG incorporation on the physical properties (morphology, biopolymer crystallinity and thermal stability) and functionality of the obtained biomaterials were investigated. PG has acted as a nucleating agent, in turn affecting the degree of crystallinity, thermal stability and morphology of the films. All samples with PG had a more organized internal structure and higher melting and degradation temperatures. The calculated degree of crystallinity of the PHBV copolymer was 53%, while the PG1, PG3 and PG3 films had values of 64.0%, 63.9% and 69.2%, respectively. Cytotoxicity studies have shown the excellent anticancer activity of films against HCT116 (colon cancer) cells, thus advancing PHBV biomedical application potential

Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen

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 agen