9 research outputs found
Parkinsonās disease ā state of the art
Parkinsonova bolest (PB) je kompleksno progresivno neurodegenerativno oboljenje sa nerazjaŔnjenom
etiopatogenezom. Odlikuje je, izmeÄu ostalog, naruÅ”ena struktura i funkcija komponenti dopaminskog sistema
u delu mozga u kome se nalaze centri za izvoÄenje voljnih pokreta, kogniciju i pamÄenje, dok su na
Äelijskom nivo karakteristiÄne neuroinflamacija, naruÅ”avanje strukture i funkcija mnogih organela ukljuÄujuÄi
mitohondrije, lizozome ili transportne vezikule, poremeÄen redoks status, nepravilno savijanje proteina
koje uslovljava njihovo neadekvatno funkcionisanje, stvaranje unutarÄelijskih depozita razliÄitih
supstanci (molekula/jona). ObiÄno se manifestuje kombinacijom niza motornih i nemotornih simptoma,
ukljuÄujuÄi tremor pri mirovanju, usporenost i osiromaÅ”enost pokreta (bradikinezija), ukoÄenost miÅ”iÄa
(rigidnost) ruku, nogu i vrata, gubitak posturalnih refleksa, fleksibilan položaj tela, kao i konstipacija, urinarna
disfunkcija, impotencija, poremeÄaji faza sna, prekomerna dnevna pospanost, nemoguÄnost gutanja
pljuvaÄke, znojenje, muÄnina, anksioznost, apatija, depresija, demencija. Dijagnostikovanje PB se vrÅ”i
posredno na osnovu prisustva minimum dva motorna simptoma i adekvatan odgovor na antiparkinson
terapiju, a sa sigurnoÅ”Äu se potvrÄuje tek post-mortem analizama utvrÄivanjem postojanja karakteristiÄnih
patohistoloÅ”kih promena u razliÄitim regionima mozga. Kao potencijalni uzroÄnici njenog nastanka i
progresije izdvajaju se genski faktori, faktori spoljaÅ”nje sredine, kao i njihovo meÄusobno delovanje. Izazovi
PB su ne samo nemoguÄnost ranog uspostavljanja dijagnoze, poteÅ”koÄe u procenjivanju toka bolesti,
identifikacija potencijalnih biomarkera i signalnih puteva koji su ukljuÄeni u patogenezu, njihova uloga
u kliniÄkoj prezentaciji bolesti, veÄ i terapija. Iako se ovo hroniÄno oboljenje leÄi razliÄitim lekovima (farmakoterapija),
hirurŔkim zahvatima, i potpornim, komplementarnim i alternativnim terapijama, ni jedan
od navedenih vidova terapije ne omoguÄava potpuno ozdravljenje veÄ kontrolu simptoma radi Å”to dužeg
nezavisnog funkcionisanja obolelih.Parkinsonās disease (PD) is a complex progressive neurodegenerative disease with uncertain etiopathogenesis.
Among others, it is characterized by impaired structure and function of components of the dopamine
system in regions of the brain responsible for performing voluntary movements, cognition and
memory; neuroinflammation; disruption of structure and function of various organelles including mitochondria,
lysosomes or transport vesicles, disturbed redox status, misfolding of proteins, intracellular deposition
of various substances (molecules/ions). Usually PD is manifested by a combination of several
motor and non-motor symptoms, including resting tremor, slowness of movement and speed (bradykinesia),
stiffness of arms, legs and neck muscles (rigidity), loss of postural reflexes, flexible body position,
along with constipation, urinary dysfunction, impotence, sleep disorders, excessive daytime sleepiness,
inability to swallow saliva, sweating, nausea, anxiety, apathy, depression, dementia. Diagnosing is performed
indirectly based on the presence of at least two motor symptoms and an adequate response to antiparkinsonian
therapy, while it can be confirmed with certainty only by post-mortem analysis according
to the existence of characteristic pathohistological changes in different regions of the brain. In PD pathogenesis
the relative contribution of genes, environmental/lifestyle factors, as well as their specific interactions
has been recognized. The challenges of PD are not only the impossibility of early diagnosis,
difficulties in assessing the course of the disease, the identification of potential biomarkers and signaling
pathways involved in pathogenesis, their role in the clinical presentation of the disease, but also the therapy.
Although the PD patients are treated with various drugs (pharmacotherapy), surgical interventions,
and supportive, complementary and alternative therapies, none of the mentioned types of therapy provide
the healing but they enable the control of the symptoms for the longest possible independent functioning
of the patients
Mass Spectrometry in Clinical Laboratories
The analyses performed in clinical laboratories require a high level of precision, selectivity, and sensitivity. The rising number of therapeutic agents from both the field of small and large molecules and the increasing use of modern screening approaches have brought mass spectrometry into almost every clinical laboratory. The need to screen the patients and to follow the therapyās success can often be fulfilled only by the highly selective and sensitive targeted approach with mass spectrometry. With improving instrument design and miniaturization of the separation technologies, mass spectrometry is no longer an exotic analytical approach. The use of mass spectrometry is now not restricted to the use in a clinical laboratory, but it is used in operating rooms for instant and on-site helping the surgeons with defining the margin of the tissue to be extracted. In this manuscript, we describe the use of mass spectrometry for selected clinical applications and show the possible way of future applications
Investigation of Ion Release and Antibacterial Properties of TiN-Cu-Nanocoated Nitinol Archwires
Background: The use of nitinol (NiTi) archwires in orthodontic treatment has increased significantly due to unique mechanical properties. The greatest obstacle for safe orthodontic treatment is chemically or microbiologically induced corrosion, resulting in nickel (Ni) release. The aim of this investigation was to enhance corrosion resistance and introduce antibacterial properties to NiTi archwires by coating them with copper (Cu) doper titanium nitride (TiN-Cu). Methods: NiTi archwires were coated with TiN-Cu using cathodic arc evaporation (CAE) and direct current magnetron sputtering (DC-MS). The morphology of the sample was analyzed via field emission scanning electron microscopy (FESEM) and chemical composition was assessed using energy-dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD) and Fourier transformed infrared spectroscopy (FTIR). Inductively coupled plasma optical emission spectrometry (ICP-OES) was used to estimate the ion release. The biocompatibility of samples was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay. Antibacterial activity was tested against Streptococcus mutans and Streptococcus mitis. Results: Physicochemical characterization revealed well-designed coatings with the presence of TiN phase with incorporated Cu. TiN-Cu-nanocoated archwires showed a statistically lower Ni release (p < 0.05). Relative cell viability was the highest in 28-day eluates of TiN-Cu-nanocoated archwires (p < 0.05). The most remarkable decrease in Streptococcus mitis concentrations was observed in the case of TiN-Cu-coated archwires (p < 0.05). Conclusion: Taking into account biocompatibility and antibacterial tests, TiN-Cu-nanocoated archwires may be considered as a good candidate for further clinical investigation
Biological properties of nitinol archwires coated with titanium nitride- copper films
Objectives: The main purpose of orthodontic treatment (OT) is to accomplish an optimal occlusal relationship in order to obtain adequate oral function and aesthetic appearance. Under optimal economic conditions, demand for OT reaches at least 35%, but in higher socioeconomic areas in US more than 50% of children are receiving orthodontic care. Acceptance of OT in Europe, like in western population and Scandinavian countries, is at similar levels. Very desirable mechanical characteristics, such as shape memory effect and superelasticity, expanded the use of nitinol (NiTi) archwires in orthodontics significantly. The complex conditions present in the oral cavity, including biofilm formation on the exposed surfaces, substantially alter the surface and structural properties of the NiTi archwires compromising the safety of OT. The necessity for developing novel material coating that would decrease Ni release and improve biological properties is of a great importance. Materials-Methods: Copper doped titanium nitride films (TiN-Cu) on the surface of NiTi archwires were obtained by combination of the cathodic arc evaporation and DC magnetron sputtering. The physicochemical characterization was performed using energy-dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). Ion release was assessed using inductively coupled plasma optical emission spectrometry (ICP-OES). The cytotoxicity of NiTi archwires, stainless steel (SS) archwires and TiN-Cu coated archwires was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) test. In order to evaluate bacterial adhesion and biofilm formation, the following strains were used: Streptococcus mutans and Streptococcus mitis. Results: Physicochemical characterization revealed well-designed coatings with the presence of TiN phase with incorporated Cu. The release of Ni was the lowest regarding TiN-Cunanocoated archwires (p < 0.05) and increased in acidic conditions, while the release of Ti was constant. Contrary, the release of Cu was higher in neutral conditions and decreased during the observation time (p < 0.05). The cytotoxicity was the lowest in 28-day eluates of TiN-Cu-nanocoated archwires (p < 0.05). The coating inhibited the adhesion and growth of bacteria such as Streptococcus mitis and Streptococcus mutans (p < 0.05). Conclusion: Taking into account the results of cytotoxicity test and biofilm formation, TiN-Cunanocoated archwires may be considered as a good candidate for further clinical investigations.27th BaSS : November 9-11, Istanbul, Turkey, 2023
Titanium(IV) oxide nanoparticles surface-modified with salicylic and 5-aminosalicylic acid affect lipid and protein oxidation in the brain of Wistar rats
13th Neuronus 2024 Neuroscience Forum Krakow, 25-27 April 2024
UÄinak ekstrakta korijena žute lincure na mononuklearne stanice periferne krvi ovisi o njegovoj koncentraciji i vremenu izlaganja
Yellow gentian (Gentiana lutea L.), a medicinal plant widely used in traditional medicine, displays multiple biological effects, ranging from beneficial to toxic. Since many promising applications have been reported so far, our aim was to evaluate its potential concentration- and time- dependent cytotoxic and genotoxic effects in vitro. To that end we exposed human peripheral blood mononuclear cells to 0.5, 1, and 2 mg/mL of yellow gentian root extract (YGRE) to determine its effects on oxidative stress parameters [pro/antioxidant balance (PAB) and lipid peroxidation], DNA damage (alkaline comet assay and chromosome aberrations), and cell viability (trypan blue exclusion test). Cell viability decreased with increasing concentrations and treatment duration. Only the lowest YGRE concentration (0.5 mg/mL) increased oxidative stress but produced minor DNA damage and cytotoxicity. At higher concentrations, redox parameters returned to near control values. The percentage of chromosome aberrations and percentage of DNA in the comet tail increased with increased YGRE concentration after 48 h and declined after 72 h of treatment. This points to the activation of DNA repair mechanism (homologous recombination), evidenced by the formation of chromosomal radial figures after 72 h of treatment with the highest YGRE concentration of 2 mg/mL. Our results suggest that YGRE, despite induction of cytotoxic and genotoxic effects, activates cell repair mechanisms that counter oxidative and DNA lesions and induce cell death in highly damaged cells. Therefore, observed protective effects of yellow gentian after longer exposure could be a result of activated repair and removal of cells with irreparable damage.Žuta lincura (Gentiana lutea L.), ljekovita biljka koja se Äesto koristi u tradicionalnoj medicini, pokazuje viÅ”estruke bioloÅ”ke uÄinke, od korisnih do toksiÄnih. BuducĢi da je do sada zabilježeno mnogo moguÄih primjena, cilj nam je bio procijeniti potencijalne citotoksiÄne i genotoksiÄne uÄinke ekstrakta korijena te biljke, koji ovise o njegovoj koncentraciji i vremenu izlaganja in vitro. Mononuklearne stanice ljudske periferne krvi izložili smo ekstraktu korijena žute lincure (YGRE), koncentracije 0,5 mg/mL, 1 mg/mL i 2 mg/mL, da bismo utvrdili njegove uÄinke na parametre oksidacijskoga stresa [pro/antioksidacijski balans (PAB) i peroksidacija lipida], oÅ”tecĢenja DNA (alkalni komet test i kromosomske aberacije) i preživljavanje stanica (tripan plavo bojenje). Preživljavanje stanica smanjivalo se s poveÄanjem koncentracije i trajanja izlaganja. Samo najniža koncentracija YGRE-a (0,5 mg/mL) dovela je do poveÄanja oksidacijskoga stresa, ali je proizvela manja oÅ”tecĢenja DNA i citotoksiÄnost. Pri viÅ”im koncentracijama, redoks parametri vratili su se blizu razine kontrolnih vrijednosti. Postotak kromosomskih aberacija i postotak DNA u repu kometa povecĢavao se s povecĢanom koncentracijom YGRE-a nakon 48 sati i smanjivao nakon 72 sata tretmana. To upuÄuje na aktiviranje mehanizma popravka DNA (homologna rekombinacija), Å”to dokazuje prisutnost kromosomskih radijalnih struktura nakon 72 sata tretmana najviÅ”om koncentracijom YGRE-a od 2 mg/mL. NaÅ”i rezultati pokazuju da YGRE, unatoÄ induciranju citotoksiÄnih i genotoksiÄnih uÄinaka, aktivira mehanizme popravka stanica koji suzbijaju oksidacijske i DNA lezije i induciraju smrt visoko oÅ”tecĢenih stanica. ZakljuÄak je da uoÄeni zaÅ”titni uÄinci dužeg izlaganja ekstraktu korijena žute lincure mogu biti rezultat aktivnoga popravka i uklanjanja stanica s nepopravljivim oÅ”tecĢenjima
Antioksidativni status i kliniÄko-patoloÅ”ki parametri kod obolelih od Parkinsonove bolesti
Backgroun / Aim. Constant production of free radicals and antioxidants (AO) in the cell is a part of normal cellular function. Their imbalance might take a part in pathophysiology of many diseases, including Parkinsonās disease (PD). Evaluation of the disease status, prooxidant-antioxidant balance (PAB) and antioxidants are being widely estimated. The aim of this study was to examine potential interaction between several AO variables (GSH, SOD, CAT and PAB) and clinicopathological features of patients with PD, particularly Hoehn and Yahr (H&Y) stage. Methods. A multivariate analysis of variance (MANOVA) was conducted to test the hypothesis of the mean differences between clinicopathological characteristics (gender, age at examination, duration of the disease, and H&Y stage) and AO variables, compared with age/sex matched healthy controls. The study included 91 patients with idiopatic PD patients and 20 healthy controls. Results. The multivariate effect size was estimated at 0.269, p <0.001, implying that 27.0% of the variance of the dependent variables was accounted for H&Y stage. Univariate tests showed that there were significant differences (p <0.001) across the H&Y stage on all AO variables. The H&Y stage remained significant predictor after controlling for the second variable, the disease duration (p <0.001, Ī·2 = 0.249), and there were still significant differences across the H&Y stage on all variables, with effect size ( Ī·2) ranging from 0.132, p =0.011 (lnGSH) to the still high values of 0.535 (lnPAB), 0.627 (lnSOD) and 0.964 (lnCAT). Conclusion. The results indicate that higher level of oxidative stress in blood of PD patients is possibly related to PD stage. Along with reduction of SOD and GSH level, CAT activity was elevated in comparison to healthy subjects. Furthermore, Pwas shifted toward oxidative stress
Serum High-Mobility Group Box 1 and Heme Oxygenase-1 as Biomarkers in COVID-19 Patients at Hospital Admission
The careful monitoring of patients with mild/moderate COVID-19 is of particular importance because of the rapid progression of complications associated with COVID-19. For prognostic reasons and for the economic management of health care resources, additional biomarkers need to be identified, and their monitoring can conceivably be performed in the early stages of the disease. In this retrospective cross-sectional study, we found that serum concentrations of high-mobility group box 1 (HMGB1) and heme oxygenase-1 (HO-1), at the time of hospital admission, could be useful biomarkers for COVID-19 management. The study included 160 randomly selected recovered patients with mild to moderate COVID-19 on admission. Compared with healthy controls, serum HMGB1 and HO-1 levels increased by 487.6 pg/mL versus 43.1 pg/mL and 1497.7 pg/mL versus 756.1 pg/mL, respectively. Serum HO-1 correlated significantly with serum HMGB1, oxidative stress parameters (malondialdehyde (MDA), the phosphatidylcholine/lysophosphatidylcholine ratio (PC/LPC), the ratio of reduced and oxidative glutathione (GSH/GSSG)), and anti-inflammatory acute phase proteins (ferritin, haptoglobin). Increased heme catabolism/hemolysis were not detected. We hypothesize that the increase in HO-1 in the early phase of COVID-19 disease is likely to have a survival benefit by providing protection against oxidative stress and inflammation, whereas the level of HMGB1 increase reflects the activity of the innate immune system and represents levels within which the disease can be kept under control
Analysis of plasma lipid composition and lipid peroxidation parameters according to stage and duration of ParkinsonŹ¼s disease and applied therapy disease and applied therapy
Parkinsonova bolest (PB) je hroniÄna neurodegenerativna bolest koja nastaje usled poremeÄaja multiplih neurotransmitera, izmeÄu kojih prednjaÄi nedostatak dopamina u delu mozga u kome se nalaze centri za izvoÄenje voljnih pokreta. Iako je PB predmet mnogobrojnih dugogodiÅ”njih istraživanja, taÄna etiopatologija je nepoznata. Pretpostavlja se da je pored razliÄitih faktora, jedan od kljuÄnih uzroÄnika njenog nastanka i progresije prekomerna produkcija reaktivnih kiseoniÄnih i azotnih vrsta i naruÅ”en kapacitet njihovog uklanjanja koje mogu pokrenuti kaskadu promena i izazivati oÅ”teÄenja biomolekula, poput proteina i lipida.
Cilj ovog istraživanja bio je da se identifikuju potencijalni biomarkeri za evaluaciju stanja pacijenata obolelih od PB praÄenjem promena parametara oksidativnog stresa (OS) (prooksidativni-antioksidativni balans (PAB), produkti oksidovane modifikacije proteina (AOPP), 4-hidroksinonenal (HNE), malondialdehid (MDA)), odnosa intenziteta pikova fosfatidilholina (PC) i lizofosfatidilholina (LPC), kao i parametara antioksidativne (AO) zaÅ”tite (superoksid dizmutaza (SOD), katalaze (CAT) i glutationa (GSH)) u zavisnosti od kliniÄko-patoloÅ”kih karakteristika (pola, starosti, Hoehn i Yahr (H&Y) stadijuma i dužine trajanja bolesti). TakoÄe, prouÄavan je i efekat terapije na ispitivane parametre. Studija je obuhvatila ispitanike, kontrole i pacijente sa PB utvrÄenom prema dijagnostiÄkom kriterijumu UK PB Society Brain Bank Research criteria. Promene parametara OS i AO zaÅ”tite kod 111 ispitanika (20 kontrola i 91 pacijenta) su praÄenje pomoÄu spektrofotometrijskih metoda i imunoblot tehnikom, dok je lipidni profil kod 35 ispitanika (10 kontrola i 25 pacijenata) odreÄivan MALDI TOF (eng. Matrix Assisted Laser Desorption and Ionization Time Of Flight) masenom spektrometrijom Å”to ujedno predstavlja prvo ispitivanje PC/LPC inteziteta kod pacijenata sa PB.
Analiza ispitivanih parametara ukazuje na poveÄan nivo svih OS parametara, kao i poremeÄenu AO zaÅ”titu i naruÅ”en lipidni profil pacijenata sa PB, ali i na njihovu vezu sa kliniÄko-patoloÅ”kim karakteristikama. Sa druge strane, uticaj doze i tipa terapije nije uoÄen ni na jednom od ispitivanih parametara...Parkinson's disease (PD) is a chronic neurodegenerative disease assosiated with alteration of multiple neurotransmitters, including dopamine deficiency, in the brain region responsible for voluntary movement. Although PD has been subject of many studies over the years, the underlying etiopathology still remains unknown. PD onset and progression might be a consequence of the overproduction of reactive oxygen and nitrogen species and impaired capacity for their removal that could initiate a cascade of events and induce damage of biomolecules, including proteins and lipids.
The aim of current study was to identify potential biomarkers for the evaluation of patients with PD by monitoring changes of oxidative stress (OS) parameters (pro-oxidant-antioxidant balance (PAB), advanced oxidized protein products (AOPP), 4-hydroxynonenal (HNE), malondialdehyde (MDA)), phosphatidylcholine (PC) and lysophosphatidylcholine (LPC) peak intensity ratios, along with antioxidant (AO) defence parameters (superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH)) and their relation to clinical and pathological characteristics (such as gender, age at examination, duration of the disease, and Hoehn and Yahr (H&Y) score). Furthermore, the effect of therapy (dose and type) on the examined parameters was also studied. The study included controls and patients with PD determined by the diagnostic criteria of the UK PB Society Brain Bank Research criteria. Changes in parameters of OS and AO defence in 111 subjects (20 controls and 91 patients) were monitored using spectrophotometric methods and immunoblot technique, while the lipid profile in 35 subjects (10 controls and 25 patients) was determined by MALDI TOF (Matrix Assisted Laser Desorption and Ionization Time Of Flight) mass spectrometry which represents the first attempt to investigate PC/LPC intensity ratio in plasma of PD patients.
The obtained results revealed the increased levels of investigated OS parameters along with an altered AO defence response and imparied lipid profile of PD patients and their relationship with clinic-pathological characteristics. Moreover, dose and type of therapy had no influence on any investigated parameter..