46 research outputs found
The examination of inflammatory, oxidative stress and lipid status parameters in sarcoidosis patients
Sarkoidoza je inflamatorno oboljenje ismatra se da genetska predispozicija organizma i specifiÄni agensi iz spoljaÅ”nje sredine igraju znaÄajnu ulogu u prekomernoj aktivaciji imunskog sistema koji se nalazi u osnovi oboljenja. MeÄu agensima iz spoljaÅ”nje sredine, mikobakterijski antigeni imaju najveÄi znaÄaj. Novije publikacije govore o postojanju mikobakterijskog antigena - katalaza-peroksidaza (mKatG) u sarkoidnim granulomima. Smatra se da ovaj antigen dovodi do stimulacije imunskog odgovora i tako doprinosi inicijaciji oboljenja.
ImunoloÅ”ki odgovor zapoÄinje akumulacijom aktiviranih T pomoÄniÄkih (āhelperā) limfocitai makrofaga na mestima inflamacije. Usled kompleksnih interakcija T limfocita i makrofaga, formira se sarkoidni granulom. Granulomi su sastavljeni od visoko-diferentovanih mononuklearnih fagocita i limfocita. Aktivirane Äelije imunskog sistema produkuju razliÄite proinflamatorne medijatore meÄu kojima su znaÄajni interleukin (IL) -2, IL-12, IL-15, faktor nekroze tumora Ī± (TNF Ī±), angiotenzin konvertujuÄi enzim (ACE). C-reaktivni protein (CRP) kao inflamatorni marker se takoÄe poveÄano sintetiÅ”e u jetri kao odgovor na poveÄanu produkciju proinflamatornih citokina, ali nije dokazano da on moÅ£e da posluÅ£i kao koristan marker za procenu aktivnosti bolesti. U kliniÄkoj dijagnozi granulomatoznih oboljenja izdvojio se ACE, ali su utvrÄeni nedostaci i ovog parametra. Noviji radovi naglaÅ”avaju znaÄaj serumskog amiloida A (SAA) kao vaÅ£nog markera granulomatozne inflamacije jer, osim Å”to predstavlja deo granuloma, on reguliÅ”e njegovo formiranje, ali utiÄe i na produkciju citokina. Sinteza SAA se poveÄava u jetri i oslobaÄa se zajedno sa CRP-om pod uticajem IL-1 i IL-6.
Sarkoidoza se prema toku moÅ£e podeliti na akutnu ili hroniÄnu, a manifestacije mogu da budu pluÄne i/ili vanpluÄne. Akutna bolest je ograniÄenog toka, sa Äestim spontanim remisijama dok hroniÄna perzistira i praÄena je progresijom oboljenja. Pored pluÄa, mogu biti zahvaÄeni srce, oÄi, nervni system, miÅ”iÄi, kostii drugi organi. VanpluÄna manifestacija koja uglavnom ukljuÄuje i pluÄno tkivo predstavlja teÅ£i oblik od iskljuÄivo pluÄne manifestacije.
Poznato je da se u inflamatornim stanjima poveÄava nivo oksidativnog stresa i smanjuje nivo antioksidativne zaÅ”tite. Inflamatorne Äelije pojaÄano stvaraju superoksid anjon radikal (O2.-) koji se konvertuje do vodonik-peroksida (H2O2). Dejstvom oksidanasa na lipidne molekule najpre se generiÅ”u lipidni hidroperoksidi, dok u krajnjem stadijumu lipidne peroksidacije nastaje
malondialdehid (MDA)...Sarcoidosis is an inflammatory disease and it has been considered that genetic predisposition and specific environmental agents play significant role in the excessive activation of the immune system that is major characteristic of the disease. Among environmental agents, mycobacterial antigens are thought to be most important. Recent publications reported the presence of mycobacterial antigen catalase-peroxidase (mKatG) in sarcoid granulomas. This antigen leads to immune response stimulation contributing to disease onset.
Immune response begins with accumulation of T helper lymphocytes and macrophages at the sites of inflammation. Complex interactions between lymphocytes and macrophages contribute to granuloma formation. Granulomas consist of highly-differentiated mononuclear phagocytes and lymphocytes. Activated cells of immune system produce different proinflammatory mediators such as interleukin (IL) -2, IL-12, IL-15, tumor necrosis factor Ī± (TNFĪ±), angiotensin converting enzyme (ACE). C-reactive protein (CRP) is synthesized in the liver and its production is increased as a response to proinflammatory cytokines, but the significance of CRP as a useful marker of disease activity has not been proved. ACE became important in clinical diagnosis of granulomatous diseases, but this marker also has its disadvantages. Recent reports pointed out the significance of serum amyloid A (SAA), suggesting it as an important marker of granulomatous inflammation, because it regulates granuloma formation and influences the cytokines production. IL-1 and IL-6 stimulate the increased production of SAA in the liver and its release into the bloodstream together with CRP.
According to disease course, sarcoidosis can be acute or chronic, with disease manifestations on lungs and/or other tissues. Acute disease has limited course and spontaneous remissions often occur, while chronic disease persists and isusually progressive. Besides lungs, other tissues/organs that can be affected are: heart, eyes, nervous system, muscles, bones and others. Combined pulmonary and extrapulmonary manifestations are more severe forms than isolated pulmonary form.
It is well established that, in inflammatory conditions, the levels of oxidative stress increase and the levels antioxidative defence decrease. Inflammatory cells produce superoxide anion radical (O2.-) that is dismutated into hydrogen peroxide (H2O2). Oxidants lead to damage of
lipids generating lipid hydroperoxides and further oxidative modification leads to malondialdehyde (MDA) formation..
Redox homeostasis, oxidative stress and antioxidant system in health and disease: The possibility of modulation by antioxidants
Redox imbalance occurs when the factors of oxidative stress, known as prooxidants, outweigh the mechanisms of antioxidant protection. In a healthy state, homeostatic mechanisms ensure the balanced production of free radicals and a complete series of antioxidants responsible for their safe removal. The generation of free radicals is a part of physiological processes in a healthy organism, some of which act as specific signaling molecules, and their presence and activity are necessary in these processes. In various diseases such as cancer, cardiovascular disease, diabetes, autoimmune diseases, rheumatic diseases, systemic lupus, and skin diseases, the generation of free radicals overwhelms the protective mechanisms, leading to the development of "oxidative stress" that damages cells and tissues. To prevent the harmful effects of free radicals within cells, there exists a system of enzymatic antioxidant protection composed of superoxide dismutase (SOD), glutathione peroxidase (GSHPx), glutathione reductase (GR), glutaredoxin, reduced/oxidized glutathione (GSH/GSSG), and thioredoxin (TRX). The examples of non-enzymatic antioxidants are: antioxidant vitamins such as A, C and E, dihydrolypoic acid, metallothioneins, ceruloplasmin, coenzyme Q 10, urea, creatinine, etc. Redox balance is influenced by the circadian rhythm and external factors that constitute the "exposome", including dietary habits and lifestyle. Antioxidant supplementation has become increasingly popular for maintaining optimal body function. However, it is important to note that some antioxidants can exhibit prooxidant activity, emphasizing the need for controlled use. The relationship between the redox status of the body and the action of antioxidants enables the development of multidisciplinary research that connects biochemistry, molecular biology, nutritional science, natural product chemistry, and clinical practice
Oxidative status parameters in children with urinary tract infection
Introduction: Urinary tract infection (UTI) is one of the most common bacterial infectious diseases in children. The aim of this study was to determine the total prooxidant and antioxidant capacity of children with UTI, as well as changes of oxidative status parameters according to acute inflammation persistence and acute kidney injury (AKI) development. Materials and methods: The patients enrolled in the study comprised 50 Caucasian children (median age was 6 months) with UTI. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), inflammation marker C-reactive protein (CRP) and renal function parameters urea and creatinine were analyzed in patient's serums. Results: According to duration of inflammation during UTI, TAS values were significantly higher (0.99 vs. 0.58 mmol/L, P = 0.017) and OSI values were significantly lower (0.032 vs. 0.041 AU, P = 0.037) in the subjects with longer duration of inflammation than in the subjects with shorter duration of inflammation. We did not find significant difference in basal values of oxidative status parameters according to AKI development. Conclusions: OSI values could detect the simultaneous change of TAS and TOS due to change in the oxidative-antioxidant balance during the recovery of children with UTI. TAS and OSI as markers of oxidative stress during UTI are sensitive to accompanying inflammatory condition. Further investigations are needed to evaluate whether TAS, TOS and OSI could be used to monitor disease severity in children with UTI
Izmenjena struktura i antioksidativni kapacitet lipoproteinskih Äestica visoke gustine u preeklampsiji
Background/Aim. One of the complications that can oc-
cur during pregnancy is the development of preeclampsia
(PE). The main characteristics of this condition are high
blood pressure and very often signs of kidney damage or
other organ damage. The condition affects 5ā7% of all
pregnant women and is one of the main factors of maternal
and perinatal morbidity and mortality worldwide. The aim
of this study was to investigate the structural and functional
modifications of high-density lipoprotein (HDL) particles
during high-risk pregnancies (HRP) for PE development.
Methods. The longitudinal prospective study included a to-
tal of 91 pregnant women with a HRP for developing PE.
Out of this total number, 71 women did not develop PE
until delivery, and this group was designated as the group
without PE (WPE). The rest of the 20 HRP women devel-
oped PE before delivery and were designated as the PE
group. The blood was sampled toward the end of each tri-
mester and before the delivery. The distribution of HDL
particles was determined by the vertical 3ā31% polyacryla-
mide gradient gel electrophoresis method. The antioxidative capacity of HDL particles was measured by the activity of
the HDL-associated enzyme ā paraoxonase 1 (PON1).
PON1 activity was determined by the method of kinetic
spectrophotometry from serum samples. Results. The re-
sults have shown that the proportions of HDL 2b particles
significantly increased in the 2nd trimester (p Ė 0.05) and
remained increased until the end of pregnancy in the WPE
group. PON1 activity was significantly higher in the 3 rd tri-
mester (p < 0.05) of the WPE group. In the PE group, we
found that the proportions of HDL 3a particles significantly
decreased in the 2 nd trimester (p < 0.05) and remained de-
creased until the end of pregnancy. PON1 activity has not
changed in the PE group during pregnancy. Conclusion.
Dyslipidemia in pregnancy could be associated with differ-
ent modifications of HDL particles. The adaptive pregnancy
mechanisms expressed as a functional modification of HDL
particles in pregnant women who develop PE seem inade-
quate and, therefore, lose their atheroprotective role.Uvod/Cilj. Jedna od komplikacija koja se može javiti
tokom trudnoÄe je razvoj preeklampsije (PE). Glavne
karakteristike ovog stanja su visok krvni pritisak i vrlo Äesto
znaci oÅ”teÄenja bubrega ili drugih organa. Ovo stanje
pogaÄa 5ā7% svih trudnica i jedan je od glavnih faktora
morbiditeta i mortaliteta trudnica i fetusa ili novoroÄenÄadi.
Cilj ovog rada bio je ispitivanje strukturnih i funkcionalnih
modifikacija lipoproteinskih Äestica visoke gustine (high-
density lipoprotein ā HDL) u trudnoÄama sa visokim rizikom
(TVR) za razvoj PE. Metode. U longitudinalnoj
prospektivnoj studiji uÄestvovala je ukupno 91 trudnica sa
TVR od razvoja PE. Od ukupnog broja trudnica, kod njih 71, PE se nije razvila do kraja trudnoÄe i ova grupa je
oznaÄena kao grupa bez PE (BPE). Kod preostalih 20 žena
sa TVR se razvila PE do poroÄaja, i one su svrstane u grupu
PE. Krv je uzimana za analizu na kraju svakog trimestra i
pred poroÄaj. Raspodela HDL Äestica je odreÄivana
metodom vertikalne elektroforeze u 3ā31% gradijentu
poliakrilamidnog gela. Antioksidativni kapacitet HDL
Äestica je odreÄivan na osnovu aktivnosti enzima
paraoksonaze 1 (PON1) vezanog za HDL. Aktivnost
PON1 u serumu je odreÄivana metodom kinetiÄke
spektrofotometrije. Rezultati. Rezultati su pokazali da se
udeo HDL 2b Äestica znaÄajno poveÄao u drugom trimestru
(p < 0,05) i ostao je poveÄan do kraja trudnoÄe u grupi BPE.
Aktivnost PON1 bila je znaÄajno veÄa u treÄem trimestru (p < 0,05) kod ove grupe trudnica. Udeo HDL 3a
Äestica se znaÄajno smanjio u drugom trimestru u PE grupi
trudnica (p < 0,05) i ostao je snižen do kraja trudno Äe.
Aktivnost PON1 enzima u PE gripi se nije menjala u toku
trudnoÄe. ZakljuÄak. Dislipidemija u trudnoÄi može biti
posledica razliÄitih modifikacija HDL Äestica. Strukturne i
funkcionalne modifikacije HDL Äestica, kao jedan od adaptivnih mehanizama, kod trudnica kod kojih se razvila
PE, nisu adekvatne i kao takve gube svoju ateroprotektivnu
ulogu
Cholesterol Metabolic Profiling of HDL in Women with Late-Onset Preeclampsia
A specific feature of dyslipidemia in pregnancy is increased high-density lipoprotein (HDL) cholesterol concentration, which is probably associated with maternal endothelium protection. However, preeclampsia is most often associated with low HDL cholesterol, and the mechanisms behind this change are scarcely explored. We aimed to investigate changes in HDL metabolism in risky pregnancies and those complicated by late-onset preeclampsia. We analyze cholesterol synthesis (cholesterol precursors: desmosterol, 7-dehydrocholesterol, and lathosterol) and absorption markers (phytosterols: campesterol and Ī²-sitosterol) within HDL particles (NCSHDL), the activities of principal modulators of HDL cholesterolās content, and major HDL functional proteins levels in mid and late pregnancy. On the basis of the pregnancy outcome, participants were classified into the risk group (RG) (70 women) and the preeclampsia group (PG) (20 women). HDL cholesterol was lower in PG in the second trimester compared to RG (p < 0.05) and followed by lower levels of cholesterol absorption markers (p < 0.001 for campesterolHDL and p < 0.05 for Ī²-sitosterolHDL). Lowering of HDL cholesterol between trimesters in RG (p < 0.05) was accompanied by a decrease in HDL phytosterol content (p < 0.001), apolipoprotein A-I (apoA-I) concentration (p < 0.05), and paraoxonase 1 (PON1) (p < 0.001), lecithinācholesterol acyltransferase (LCAT) (p < 0.05), and cholesterol ester transfer protein (CETP) activities (p < 0.05). These longitudinal changes were absent in PG. Development of late-onset preeclampsia is preceded by the appearance of lower HDL cholesterol and NCSHDL in the second trimester. We propose that reduced capacity for intestinal HDL synthesis, decreased LCAT activity, and impaired capacity for HDL-mediated cholesterol efflux could be the contributing mechanisms resulting in lower HDL cholesterol
Pulmonary function, oxidative stress and inflammatory markers in severe COPD exacerbation
Background: Oxidative stress and inflammation play an important role in the pathogenesis of chronic: obstructive pulmonary disease (COPD). Objective: Pulmonary function, oxidative stress parameters and inflammatory markers were measured in 74 patients with severe COPD exacerbation and 41 healthy subjects. In patients all parameters were assessed at two time points: Firstly, one day after admission and secondly, after 7-10 days when they were clinically stable enough to be discharged. Patients were divided in two groups according the presence of ischemic heart disease (IHD): IHD positive (IHD+) patients and IHD negative (IHD-) patients. Methods and Results: During hospitalisation O(2)(center dot-), malondialdehyde (MDA), advanced oxidation protein products (AOPP) and total oxidant status (TOS) increased and were higher at discharge compared with admission and the control group. Superoxide dismutase (SOD) activity was significantly lower in COPD patients at both time points compared with the control group. Total antioxidant status (TAS) was significantly lower and the prooxidant-antioxidant balance (PAB) was higher at both time points in COPD patients compared with the control group. High sensitive C-reactive protein (hsCRP) and also the neutrophil count were significantly higher at admission compared with discharge. Paraoxonase 1 (PON1) enzymatic activities in COPD patients did not differ compared with the control group. IHD+ COPD patients had significantly lower PON1 activity but higher PAB levels and hsCRP concentrations, compared with IHD- COPD patients. Conclusion: The oxidant/antioxidant imbalance was significantly pronounced in patients with COPD exacerbation for at least 24 hours following their admission and when they were clinically stable enough to be discharged. Increased oxidative stress, elevated systemic inflammation and decreased antioxidant defence were common in end-stage disease and particularly COPD patients with ischemic heart disease
Biochemical and hematological parameters in the 1st trimester of pregnancy
The 1st trimester of pregnancy is accompanied with changes in different biochemical and hematological parameters. Analyses scheduled to be performed in the 1st trimester are complete blood count, blood group, Rh factor and the double test. Many experts also suggest the determination of lipid status parameters as a routine analysis in the early pregnancy. Reliable data about maternal and fetal health can be obtained by the assessment of the above-mentioned parameters. They may be helpful in assessing the risk for pregnancy complication development and/or perinatal adverse outcomes
Biohemijski i hematoloÅ”ki parametri u prvom trimestru trudnoÄe
The 1st trimester of pregnancy is accompanied with changes in different biochemical and
hematological parameters. Analyses scheduled to be performed in the 1st trimester are complete
blood count, blood group, Rh factor and the double test. Many experts also suggest the
determination of lipid status parameters as a routine analysis in the early pregnancy. Reliable data
about maternal and fetal health can be obtained by the assessment of the above-mentioned
parameters. They may be helpful in assessing the risk for pregnancy complication development
and/or perinatal adverse outcomes.Prvi trimestar trudnoÄe praÄen je promenama razliÄitih biohemijskih i hematoloÅ”kih
parametara. Analize koje se rade u 1. trimestru su kompletna krvna slika, krvna grupa, Rh faktor
i tzv. ādoubleā test. Mnogi struÄnjaci predlažu odreÄivanje parametara lipidnog statusa kao
rutinsku analizu u ranoj trudnoÄi. Procenom gore navedenih parametara mogu se dobiti pouzdani
podaci o zdravlju majke i fetusa, a mogu da posluže i za procenu rizika za razvoj komplikacija u
trudnoÄi i/ili perinatalnih neželjenih ishoda
Matriks metaloproteinaze-9 i tkivni inhibitori matriks metaloproteinaza-1 kod pacijenata sa sarkoidozom
Matrix metaloproteinases (MMPs) and their specific inhibitors - tissue inhibitors of matrix metalloproteinases (TIMPs) play an important role in pulmonary extracellular matrix destruction. Sarcoidosis is an inflammatory disease affecting multiple organs. It has been reported that MMP-9 and TIMP-1 levels were increased in bronchoalveolar lavage fluid and induced sputum of sarcoidosis patients. The aim of our study was to evaluate MMP-9, TIMP-1 and MMP-9/TIMP-1 complex concentrations and MMP-9/TIMP-1 ratio in sarcoidosis patients, their relationship with inflammatory markers and their ability do predict the existence of disease. We included 101 sarcoidosis patients and 50 healthy subjects. Serum samples were analyzed. Besides routine biochemical parameters, high-sensitive C-reactive protein (hsCRP), serum amyloid A (SAA), MMP-9, TIMP-1 and MMP-9/TIMP-1 complex concentrations were measured. MMP-9 (P lt 0.05), hsCRP, SAA and TIMP-1 (P lt 0.001) concentrations were significantly increased in patients whereas MMP-9/TIMP-1 complex was higher in patients, but with marginal significance. In sarcoidosis, TIMP-1 correlated significantly positively with inflammatory parameters (P lt 0.05). Uni-variate analysis showed that MMP-9, TIMP-1, hsCRP and SAA had the ability to predict the existence of sarcoidosis. In the model consisted of MMP- 9, TIMP-1, hsCRP and SAA, only SAA remained significant predictor of disease (P lt 0.01). Results showed the significance of MMP-9 and TIMP-1 in sarcoidosis.Matriks metaloproteinaze (MMP) i tkivni inhibitori matriks metaloproteinaza (TIMP) imaju znaÄajnu ulogu u destrukciji pluÄnog ekstracelularnog matriksa. Sarkoidoza je inflamatorno oboljenje koje zahvata razliÄite organe. UtvrÄeno je da su koncentracije MMP-9 i TIMP-1 poveÄane u bronhoalveolarnom lavatu i sputumu pacijenata sa sarkoidozom. Cilj naÅ”e studije je bio da se odrede koncentracije MMP-9, TIMP-1 i MMP-9/TIMP-1 kompleksa, MMP- 9/TIMP-1 odnosa u sarkoidozi, njihova povezanost sa parametrima inflamacije, kao i njihov potencijal za predviÄanje postojanja bolesti. Ispitivanjem su obuhvaÄeni 101 pacijent sa sarkoidozom i 50 zdravih ispitanika. Analizirani su uzorci seruma. Pored rutinskih biohemijskih parametara, merene su koncentracije visoko-osetljivog C-reaktivnog proteina (hsCRP), serumskog amiloida A (SAA), MMP-9, TIMP-1 i MMP-9/TIMP-1 kompleksa. MMP-9 (P lt 0,05), hsCRP, SAA i TIMP-1 (P lt 0,001) su bili znaÄajno veÄi kod pacijenata dok je koncentracija MMP-9/TIMP-1 kompleksa bila veÄa, ali sa graniÄnom znaÄajnoÅ”Äu. U sarkoidozi, TIMP-1 je znaÄajno pozitivno korelirao sa inflamatornim parametrima (P lt 0,05). Uni-varijantna analiza je pokazala da su MMP-9, TIMP-1, hsCRP i SAA imali znaÄajan potencijal za predviÄanje postojanja bolesti. U modelu koji je sadržao MMP-9, TIMP-1, hsCRP i SAA, samo SAA je ostao znaÄajan u ovom predviÄanju (P lt 0,01). Rezultati pokazuju znaÄaj MMP-9 i TIMP-1 u sarkoidozi
Effects of Gestational Diabetes Mellitus on Cholesterol Metabolism in Women with High-Risk Pregnancies: Possible Implications for Neonatal Outcome
Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1āT3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, Ī²-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of Ī²-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum Ī²-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newbornās size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM