The effects of vitamin D pretreatment on structural and biochemical changes in the brain of gerbils exposed to transient global cerebral ischemia

Cerebralna ishemija nastupa kada protok krvi opadne ispod 20% normalnog protoka, dovodeći do smanjenog dotoka kiseonika i glukoze u mozak, i posledično poremećaja jonske homeostaze, smanjenje sinteze ATP-a, povećano oslobađanje glutamata i ekscitotoksičnost. U patogenezi moždane ishemije važno mesto ima povećano oslobađanje slobodnih radikala (ROS) odnosno nastanak oksidativnog stresa. Važno je što ranije ponovo uspostaviti cirkulaciju, međutim reperfuzija uzrokuje još veću produkciju slobodnih radikala i iscrpljivanje antioksidativnih kapaciteta ćelije. Potencijalni izvor ROS u ishemiji i reperfuziji mozga predstavljaju enzimi NADPH oksidaze (nikotinamid adenin dinukleotid fosfat oksidaze), čija je fiziološka funkcija stvaranje superoksidnog anjona. U ćelijama CNS-a (neuronima, astrocitima, mikrogliji), detektovana je ekspresija NOX2 (gp91phox) proteina, koji u asocijaciji sa p22phox, GTP-Rac, p47phox, p67phox i p40phox produkuje superoksidni anjon, dok je NOX4 je najzastupljenija izoforma na nivou vaskularne mreže. Kako NOX2 i NOX4 mogu predstavljati značajan izvor oksidativnog stresa nakon ishemije mozga ove izoforme predstavljaju potencijalne terapijske mete. Ishemijsko/reperfuziono (I/R) oštećenje pokreće i proces apoptoze i izaziva poremećaj procesa autofagije pri čemu uloga koju autofagija ima u ishemiji mozga još uvek nije razjašnjena. Sve se više proučava uloga vitamina D (vitD) u prevenciji kardiovaskularnih i cerebrovaskularnih bolesti. Dosadašnje studije su pokazale da je snižena koncentracija vitamina D u serumu povezana sa povećanim rizikom od ishemijskog moždanog udara, kao i sa pogoršanjem ishemijskog oštećenja, težim funkcionalnim oporavkom i kognitivnim disbalansom. Uloga i mehanizmi delovanja vitamina D u cerebralnoj ishemiji još uvek nisu u potpunosti razjašnjeni. Cilj: Ispitati efekte pretretmana vitaminom D na parametre oksidativnog stresa, apoptoze, autofagije i zastupljenost pojedinih ćelija centralnog nervnog sitstema upotrebom odgovarajućih markera u prefrontalnom korteksu i hipokampusu mongolskih džerbila izloženih desetominutnoj prolaznoj globalnoj ishemiji mozga i reperfziji u trajanju od jednog, tri ili sedam dana...Cerebral ischemia occurs when blood flow drops below 20% of normal flow, leading to a reduced supply of oxygen and glucose to the brain, which further affects the disorder of ionic homeostasis, ATP synthesis, glutamate release, and excitotoxicity, which ultimately results in ischemic neuronal damage. Another mechanism thats plays an important role in the pathogenesis of cerebral ischemia is the disturbance of oxidative balance, which manifests itself through increased release of free radicals (FR) and oxidative stress. In ischemic tissue, it is of utmost importance to establish circulation, but reperfusion leads to even greater free radical production, exhaustion of antioxidative capacity and further oxidative damage. Potential FR source in ischemia and brain reperfusion is NADPH oxidase family (nicotinamide adenine dinucleotide phosphate oxidase), who’s main physiological function is superoxide anion production. Expression of NOX2 (gp91phox) protein was detected in CNS cells (neurons, astrocytes, microglia), which in association with p22phox, GTP-Rac, p47phox, p67phox and p40phox, produces a superoxide anion. NOX4 is the most common isoform at the level of the vascular network. As NOX2 and NOX4 could be a significant source of FR after brain ischemia, these isoforms represent potential therapeutic targets. In addition to oxidative stress, ischemic/reperfusion (I/R) injury also triggers the apoptosis and distorts the autophagy. The role of autophagy in brain ischemia has not yet been clarified. Recent studies focused on the prevention of cardiovascular and cerebrovascular diseases have been researching the impact of vitamin D. It has been shown that the reduced serum concentration of vitamin D is associated with an increased risk of ischemic stroke, as well as with exacerbation of ischemic damage, more severe functional recovery, and cognitive impairment. Calcitriol exhibits effects in the body through the vitamin D (VDR) nuclear receptor, which is present in the brain in both neurons and glial cells. The role and mechanism of vitamin D in cerebral ischemia have not yet been fully clarified..

8-Iso-prostaglandin F2α as a potential biomarker in patients with unipolar and bipolar depression

Objective: Previous studies have shown that the disturbance of redox homeostasis plays a role in the pathogenesis of mood disorders. It is currently unclear whether oxidative stress parameters can be used as biomarkers (state vs. trait). The aim of the present study was to investigate oxidative stress markers in patients with major depressive disorder (MDD) and bipolar disorder (BP) in acute depressive episodes and remission, and healthy individuals. Patients and methods: Thirty-two patients with a diagnosis of MDD, 32 patients with a diagnosis of BP and 32 matched healthy controls were included in the study. We measured the serum levels of markers of oxidative damage, including 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-Iso-prostaglandin F2α (8-iso-PGF2α; 8-isoprostane), and malondialdehyde (MDA), and also serum activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR) in both acute and remission phase, and in control group. Results: After controlling for the effects of age, sex, body mass index, and smoking status, serum 8-iso-PGF2α levels were significantly higher in both patient groups compared to controls, regardless of disease phase. The activities of GPX and GR were significantly lower in the acute phase in MDD patients compared to controls. Serum GR activity was lower in both acute and remission phase in MDD compared to BP. Conclusions: Our results suggest that both MDD and BP are associated with a disturbed redox balance with a particularly pronounced increase in serum 8-iso-PGF2α levels in both groups and the presence of glutathione metabolism disorders in MDD patients. Further research is needed to confirm the importance of oxidative stress parameters as potential biomarkers of MDD and BP

Potential impact of engineered nanomaterials release into environment

Engineered nanomaterials (ENMs) are defined as a materials with at least one dimension between 1 nm to 100 nm. They have large surface area and specific electronic, optoelectronic, thermal and catalytic properties in comparison to their bulk counterparts, which make them particularly useful. ENMs that are found in different products (paints, cosmetics, medicines, food, sun tan lotions, remediation treatments, etc.) are usually designed to achieve desired properties. Those materials can be released into the environment throughout their entire life cycle and their extensive usage nowdays could led to their accumulation into environment. Over the last twenty years, ENMs have significantly increased in quantity produced, thus their presence in environment could have significant impact. However, understanding the effects that engineered nanomaterials (ENMs) have on environment through these applications is still limited. The aim of this paper is to point out issues releated to release of ENMs into the environment

The immobilization of copper from waste printing developer sludge

The electrocoagulation (EC) treatment of the waste printing developer in laboratory conditions was produced the sludge with a high amount of copper. The solidification/stabilization (S/S) treatment of electrocoagulation sludge (ECS) has been conducted with four immobilization agents: Portland cement, calx, bentonite, and local clay. The efficiency of the S/S treatment was monitored by applying standard German (DIN 38414-4) leaching test. The characterization of ECS in terms of its toxicity was evaluated by comparing the copper concentration levels in the leaching solution with maximum allowed concentrations according to current regulations

Maternal deprivation causes CaMKII downregulation and modulates glutamate, norepinephrine and serotonin in limbic brain areas in a rat model of single prolonged stress

Background: Early life stress is a major risk factor for later development of psychiatric disorders, including post-traumatic stress disorder (PTSD). An intricate relationship exists between various neurotransmitters (such as glutamate, norepinephrine or serotonin), calcium/calmodulin-dependent protein kinase II (CaMKII), as an important regulator of glutamatergic synaptic function, and PTSD. Here, we developed a double-hit model to investigate the interaction of maternal deprivation (MD) as an early life stress model and single prolonged stress (SPS) as a PTSD model at the behavioral and molecular levels. Methods: Male Wistar rats exposed to these stress paradigms were subjected to a comprehensive behavioral analysis. In hippocampal synaptosomes we investigated neurotransmitter release and glutamate concentration. The expression of CaMKII and the content of monoamines were determined in selected brain regions. Brain-derived neurotrophic factor (BDNF) mRNA was quantified by radioactive in situ hybridization. Results: We report a distinct behavioral phenotype in the double-hit group. Double-hit and SPS groups had decreased hippocampal presynaptic glutamatergic function. In hippocampus, double-hit stress caused a decrease in autophosphorylation of CaMKII. In prefrontal cortex, both SPS and double-hit stress had a similar effect on CaMKII autophosphorylation. Double-hit stress, rather than SPS, affected the norepinephrine and serotonin levels in prefrontal cortex, and suppressed BDNF gene expression in prefrontal cortex and hippocampus. Limitations: The study was conducted in male rats only. The affected brain regions cannot be restricted to hippocampus, prefrontal cortex and amygdala. Conclusion: Double-hit stress caused more pronounced and distinct behavioral, molecular and functional changes, compared to MD or SPS alone

Effects of Vitamin D3 on the NADPH Oxidase and Matrix Metalloproteinase 9 in an Animal Model of Global Cerebral Ischemia.

Decreased blood flow in the brain leads to a rapid increase in reactive oxygen species (ROS). NADPH oxidase (NOX) is an enzyme family that has the physiological function to produce ROS. NOX2 and NOX4 overexpression is associated with aggravated ischemic injury, while NOX2/4-deficient mice had reduced stroke size. Dysregulation of matrix metalloproteinases (MMPs) contributes to tissue damage. The active form of vitamin D3 expresses neuroprotective, immunomodulatory, and anti-inflammatory effects in the CNS. The present study examines the effects of the vitamin D3 pretreatment on the oxidative stress parameters and the expression of NOX subunits, MMP9, microglial marker Iba1, and vitamin D receptor (VDR), in the cortex and hippocampus of Mongolian gerbils subjected to ten minutes of global cerebral ischemia, followed by 24 hours of reperfusion. The ischemia/reperfusion procedure has induced oxidative stress, changes in the expression of NOX2 subunits and MMP9 in the brain, and increased MMP9 activity in the serum of experimental animals. Pretreatment with vitamin D3 was especially effective on NOX2 subunits, MMP9, and the level of malondialdehyde and superoxide anion. These results outline the significance of the NOX and MMP9 investigation in brain ischemia and the importance of adequate vitamin D supplementation in ameliorating the injury caused by I/R

The effects of vitamin D pretreatment on structural and biochemical changes in the brain of gerbils exposed to transient global cerebral ischemia

Cerebralna ishemija nastupa kada protok krvi opadne ispod 20% normalnog protoka, dovodeći do smanjenog dotoka kiseonika i glukoze u mozak, i posledično poremećaja jonske homeostaze, smanjenje sinteze ATP-a, povećano oslobađanje glutamata i ekscitotoksičnost. U patogenezi moždane ishemije važno mesto ima povećano oslobađanje slobodnih radikala (ROS) odnosno nastanak oksidativnog stresa. Važno je što ranije ponovo uspostaviti cirkulaciju, međutim reperfuzija uzrokuje još veću produkciju slobodnih radikala i iscrpljivanje antioksidativnih kapaciteta ćelije. Potencijalni izvor ROS u ishemiji i reperfuziji mozga predstavljaju enzimi NADPH oksidaze (nikotinamid adenin dinukleotid fosfat oksidaze), čija je fiziološka funkcija stvaranje superoksidnog anjona. U ćelijama CNS-a (neuronima, astrocitima, mikrogliji), detektovana je ekspresija NOX2 (gp91phox) proteina, koji u asocijaciji sa p22phox, GTP-Rac, p47phox, p67phox i p40phox produkuje superoksidni anjon, dok je NOX4 je najzastupljenija izoforma na nivou vaskularne mreže. Kako NOX2 i NOX4 mogu predstavljati značajan izvor oksidativnog stresa nakon ishemije mozga ove izoforme predstavljaju potencijalne terapijske mete. Ishemijsko/reperfuziono (I/R) oštećenje pokreće i proces apoptoze i izaziva poremećaj procesa autofagije pri čemu uloga koju autofagija ima u ishemiji mozga još uvek nije razjašnjena. Sve se više proučava uloga vitamina D (vitD) u prevenciji kardiovaskularnih i cerebrovaskularnih bolesti. Dosadašnje studije su pokazale da je snižena koncentracija vitamina D u serumu povezana sa povećanim rizikom od ishemijskog moždanog udara, kao i sa pogoršanjem ishemijskog oštećenja, težim funkcionalnim oporavkom i kognitivnim disbalansom. Uloga i mehanizmi delovanja vitamina D u cerebralnoj ishemiji još uvek nisu u potpunosti razjašnjeni. Cilj: Ispitati efekte pretretmana vitaminom D na parametre oksidativnog stresa, apoptoze, autofagije i zastupljenost pojedinih ćelija centralnog nervnog sitstema upotrebom odgovarajućih markera u prefrontalnom korteksu i hipokampusu mongolskih džerbila izloženih desetominutnoj prolaznoj globalnoj ishemiji mozga i reperfziji u trajanju od jednog, tri ili sedam dana...Cerebral ischemia occurs when blood flow drops below 20% of normal flow, leading to a reduced supply of oxygen and glucose to the brain, which further affects the disorder of ionic homeostasis, ATP synthesis, glutamate release, and excitotoxicity, which ultimately results in ischemic neuronal damage. Another mechanism thats plays an important role in the pathogenesis of cerebral ischemia is the disturbance of oxidative balance, which manifests itself through increased release of free radicals (FR) and oxidative stress. In ischemic tissue, it is of utmost importance to establish circulation, but reperfusion leads to even greater free radical production, exhaustion of antioxidative capacity and further oxidative damage. Potential FR source in ischemia and brain reperfusion is NADPH oxidase family (nicotinamide adenine dinucleotide phosphate oxidase), who’s main physiological function is superoxide anion production. Expression of NOX2 (gp91phox) protein was detected in CNS cells (neurons, astrocytes, microglia), which in association with p22phox, GTP-Rac, p47phox, p67phox and p40phox, produces a superoxide anion. NOX4 is the most common isoform at the level of the vascular network. As NOX2 and NOX4 could be a significant source of FR after brain ischemia, these isoforms represent potential therapeutic targets. In addition to oxidative stress, ischemic/reperfusion (I/R) injury also triggers the apoptosis and distorts the autophagy. The role of autophagy in brain ischemia has not yet been clarified. Recent studies focused on the prevention of cardiovascular and cerebrovascular diseases have been researching the impact of vitamin D. It has been shown that the reduced serum concentration of vitamin D is associated with an increased risk of ischemic stroke, as well as with exacerbation of ischemic damage, more severe functional recovery, and cognitive impairment. Calcitriol exhibits effects in the body through the vitamin D (VDR) nuclear receptor, which is present in the brain in both neurons and glial cells. The role and mechanism of vitamin D in cerebral ischemia have not yet been fully clarified..

A Fuzzy Set-Based Approach to Range-Free Localization in Wireless Sensor Networks

Abstract Localization in Wireless Senso

Analysis of kinds of conoid at small deformations

In this paper we consider general conoid surfaces. We consider mathematical and constructional aspects of these surfaces. In the constructional meaning conoids are thin shells which are used for spatial roof structures either in complete form or in parts. In mathematical sense it is a geometrical surface on which it is possible to determine rotational and translational fields and check the rigidity