Endocrine disruption in Crohn's disease: Bisphenol A enhances systemic inflammatory response in patients with gut barrier translocation of dysbiotic microbiota products.

The relevance of environmental triggers in Crohn's disease remains poorly explored, despite the well-known association between industrialization and disease onset/progression. We have aimed at evaluating the influence of endocrine disrupting chemicals in CD patients. We performed a prospective observational study on consecutive patients diagnosed of CD. Serum levels of endocrine disruptors, short-chain fatty acids, tryptophan and cytokines were measured. Bacterial-DNA and serum endotoxin levels were also evaluated. Gene expression of ER-α, ER-ß and GPER was measured in PBMCs. All patients were genotyped for NOD2 and ATG16L1 polymorphisms. A series of 200 CD patients (140 in remission, 60 with active disease) was included in the study. Bisphenol A was significantly higher in patients with active disease versus remission and in colonic versus ileal disease. GPER was significantly increased in active patients and correlated with BPA levels. BPA was significantly increased in patients with bacterial-DNA and correlated with serum endotoxin levels, (r = 0.417; P = .003). Serum butyrate and tryptophan levels were significantly lower in patients with bacterial-DNA and an inverse relationship was present between them and BPA levels (r = -0.491; P = .001) (r = -0.611; P = .001). Serum BPA levels correlated with IL-23 (r = 0.807; P = .001) and IL-17A (r = 0.743; P = .001). The multivariate analysis revealed an independent significant contribution of BPA and bacterial-DNA to serum levels of IL-23 and IL-17A. In conclusion, bisphenol A significantly affects systemic inflammatory response in CD patients with gut barrier disruption and dysbiotic microbiota secretory products in blood. These results provide evidence of an endocrine disruptor playing an actual pathogenic role on CD.

In Vitro Interaction of 5-Aminoorotic Acid and Its Gallium(III) Complex with Superoxide Radical, Generated by Two Model Systems.

Increased levels of the superoxide radical are associated with oxidative damage to healthy tissues and with elimination of malignant cells in a living body. It is desirable that a chemotherapeutic combines pro-oxidant behavior around and inside tumors with antioxidant action near healthy cells. A complex consisting of a pro-oxidant cation and antioxidant ligands could be a potential anticancer agent. Ga(III) salts are known anticancer substances, and 5-aminoorotic acid (HAOA) is a ligand with antioxidant properties. The in vitro effects of HAOA and its complex with Ga(III) (gallium(III) 5-aminoorotate (GaAOA)) on the in vitro accumulation of superoxide and other free radicals were estimated. Model systems such as potassium superoxide (KO2), xanthine/xanthine oxidase (X/XO), and rat blood serum were utilized. Data suggested better antioxidant effect of GaAOA compared to HAOA. Evidently, all three ligands of GaAOA participated in the scavenging of superoxide. The effects in rat blood serum were more nuanced, considering the chemical and biochemical complexity of this model system. It was observed that the free-radical-scavenging action of both compounds investigated may be manifested via both hydrogen donation and electron transfer pathways. It was proposed that the radical-scavenging activities (RSAs) of HAOA and its complex with Ga(III) may be due to a complex process, depending on the concentration, and on the environment, nature, and size of the free radical. The electron transfer pathway was considered as more probable in comparison to hydrogen donation in the scavenging of superoxide by 5-aminoorotic acid and its gallium(III) complex.

Icariin promotes early and late stages of fracture healing in rats.

OBJECTIVES: This study aims to evaluate the effects of locally applied icariin on bone fracture healing in femur fractured rat model. MATERIALS AND METHODS: The study included 64 male Sprague-Dawley rats (mean age 6 months; weighing, 280-490 g) in eight main study groups. Fracture healing process and level were evaluated with radiography, histopathology and dual energy X-ray absorptiometry to investigate the effects of local administration of icariin at varying doses, which is an exogenous osteo-inductive substance. Activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured in the peripheral blood in addition to glutathione (GSH) and myeloperoxidase (MPO) levels to investigate the effects of icariin on the oxidant-antioxidant systems. RESULTS: Radiological bone mineral density measurements and histopathological findings revealed that icariin improved all these parameters in the two healing periods tested. Superoxide dismutase activity decreased in association with local icariin application to the fractured side whereas GPx and GSH increased and MPO remained unchanged. Icariin increased the GPx and GSH levels which are responsible from scavenging hydroxyl radical and hydrogen peroxide. CONCLUSION: Locally administered icariin to the fracture accelerated bone healing by reducing the oxidative stress.

Molecular Adsorbent Recirculating System Treatment Can Reduce Blood Levels of N-Acetylcysteine in Patients With Acetaminophen Overdose: Case Reports.

BACKGROUND: Acetaminophen poisoning continues to be a major cause of liver failure that can lead to liver transplantation. N-acetylcysteine (NAC) is the cornerstone of treatment. Some authors use a Molecular Adsorbent Recirculating System (MARS) system in acetaminophen poisoning. It is reported that the MARS system eliminates acetaminophen more efficiently than conventional dialysis. It is theoretically possible that treatment with MARS administered after NAC will increase the effectiveness of treatment. CASE REPORTS: The first patient, a woman of 14 years old, presented blood levels of 112 mg/dL 12 hours after ingestion of 15 g of acetaminophen. Treatment with NAC was initiated. At 17 and 23 hours after ingestion, blood levels were 23.5 µg/mL and 5.9 µg/mL, respectively. The second patient, a woman of 28 years old, presented blood levels of 115 mg/dL 4 hours after ingestion of 40 g of acetaminophen. Treatment with NAC was initiated. At 14 and 23 hours after ingestion, blood levels were 15.8 µg/mL and <2 µg/mL, respectively. In both patients, we performed MARS after completing treatment with NAC, and after the first session, blood levels were below the lower limit of detection (≤2 µg/mL). DISCUSSION: The correct timing of MARS to avoid interactions with the administered dose of NAC in acetaminophen overdose is essential so as to not impair the effectiveness of this treatment. These considerations in the management of this entity help in the resolution of liver failure, thus avoiding the need for a liver transplant.

Detection and scavenging of hydroxyl radical via D-phenylalanine hydroxylation in human fluids.

Hydroxyl radical (.OH) is highly reactive, and therefore very short-lived. Finding new means to accurately detect .OH, and testing the ability of known .OH scavengers to neutralize them in human biological fluids would leverage our ability to more effectively counter oxidative (.OH) stress-mediated damage in human diseases. To achieve this, we pursued the evaluation of secondary products resulting from .OH attack, using a detection system based on Fenton reaction-mediated D-phenylalanine (D-Phe) hydroxylation. This reaction in turn generates o-tyrosine (o-tyr), m-tyrosine (m-tyr) and p-tyrosine (p-tyr). Here, these isomers were separated by HPLC, equipped with fluorescence detectors due to the natural fluorescence of these hydrotyrosines. By extension, we found that, adding radical scavengers competed with D-Phe on .OH attack, thus allowing to determine the .OH quenching capacity of a given compound expressed as inhibition ratio percent (IR%). Using a kinetic approach, we then tested the .OH scavenging capacity (OHSC) of well-known antioxidant molecules. In a test tube, N,N'-dimethylthiourea (DMTU) was the most efficient scavenger as compared to Trolox and N-Acethyl-L-cysteine, with NAC being the less effective. OHSC assay was then applied to biological fluid samples as seminal plasma, human serum from normal subjects and patients undergoing hemodialysis (HD), colostrum and human breast milk from mothers that received daily doses of 30g of chocolate (70% cocoa) during pregnancy. We found that a daily administration of dark chocolate during pregnancy almost doubled OHSC levels in breast milk (1.88 ± 0.12 times, p < 0.01). Furthermore, HD treatment determined a significant reduction of serum OHSC concentration (54.63 ± 2.82%, p < 0.001). Our results provide evidence that Fenton reaction-mediated D-Phe hydroxylation is a suitable method for routine and non-invasive evaluation of .OH detection and its scavenging in human biological fluids.

Biodistribution and Pharmacokinetic Study of 3,3' Diseleno Dipropionic Acid (DSePA), A Synthetic Radioprotector, in Mice.

BACKGROUND AND OBJECTIVES: 3,3' Diseleno dipropionic acid (DSePA), a synthetic compound has been shown to have radioprotective activity, especially as a lung radioprotector. In this study, the pharmacokinetics and biodistribution of DSePA in MX-1 tumour bearing SCID mice were evaluated. METHODS: Twenty SCID mice were administered DSePA (50 mg/kg bodyweight) by oral gavage following which four animals each were sacrificed at 15, 30 min, 1, 2 and 4 h. Blood and tissue samples were collected for determination of DSePA concentration by graphite furnace atomic absorption spectrometry (GFAAS) method. The control group (n = 4) was administered sterile water and sacrificed at 4 h. RESULTS: Peak plasma concentration (C max) of 2.7 µg/ml was observed at 15 min which returned to near baseline (baseline = 0.6 µg/ml) at 1 h following drug administration. Biphasic pharmacokinetics characterized by rapid distribution phase and a slower elimination phase were observed. Highest maximal concentration (C max) of the drug was observed in lung (19.2 µg/g at 30 min) followed by intestine (14.64 µg/g at 15 min) and kidney (12.96 µg/g at 15 min). There was negligible uptake in tumor tissue and no uptake in brain. CONCLUSIONS: DSePA has a favorable pharmacokinetic profile which makes it a potentially good candidate for further development as a radioprotective agent.

Comparative evaluation of serum superoxide dismutase and glutathione levels in periodontally diseased patients: an interventional study.

BACKGROUND: Periodontal disease is an immune-inflammatory disease characterized by connective tissue breakdown, loss of attachment, and alveolar bone resorption. Under normal physiological conditions, a dynamic equilibrium is maintained between the reactive oxygen species (ROS) and antioxidant defense capacity. Oxidative stress occurs when this equilibrium shifts in favor of ROS. Oxidative stress is thought to play a causative role in the pathogenesis of periodontal diseases. AIM: The present study was designed to estimate and compare the superoxide dismutase (SOD) and glutathione (GSH) levels in the serum of periodontitis, gingivitis, and healthy individuals before and after nonsurgical periodontal therapy. MATERIALS AND METHODS: The present study was conducted in the Department of Periodontics, A. B. Shetty Memorial Institute of Dental Sciences, Deralakatte, Mangalore. The study was designed as a single blinded interventional study comprising 75 subjects, inclusive of both sexes and divided into three groups of 25 patients each. Patients were categorized into chronic periodontitis, gingivitis, and healthy. The severity of inflammation was assessed using gingival index and pocket probing depth. Biochemical analysis was done to estimate the SOD and GSH levels before and after nonsurgical periodontal therapy. RESULTS obtained were then statistically analyzed using ANOVA test and paired t-test. RESULTS: The results showed a higher level of serum SOD and GSH in the healthy group compared to the other groups. The difference was found to be statistically significant (P < 0.0001). The post-treatment levels of SOD were statistically higher than the pre-treatment levels in periodontitis and gingivitis group.

Effect of uvulopalatopharyngoplasty on leptin and endothelial function in sleep apnea.

OBJECTIVES: This study evaluated the effects of uvulopalatopharyngoplasty (UPPP) on serum leptin levels and endothelial function in patients with obstructive sleep apnea syndrome (OSAS). METHODS: Fifteen healthy subjects and 35 patients with moderate to severe OSAS who desired UPPP were prospectively enrolled. The serum levels of leptin and nitric oxide derivative (NOx) from their peripheral blood samples were measured by enzyme-linked immunosorbent assay. All subjects participated in sleep studies, which were repeated 3 months after UPPP in the patients with OSAS. RESULTS: Before UPPP, the patients with OSAS had a higher serum level of leptin and a lower NOx level than did the control subjects. The serum leptin levels in the 17 of the 35 patients with OSAS who were surgical responders decreased from 24.2 ± 6.1 ng/mL before operation to 15.9 ± 6.0 ng/mL after operation. The serum NOx levels in these 17 patients increased from 18.5 ± 7.5 µmol/L before operation to 27.3 ± 8.2 µmol/L after operation. In the 18 patients who were unresponsive to surgery, the serum leptin and NOx levels remained impaired after the UPPP. CONCLUSIONS: Successful treatment of OSAS with UPPP leads to the normalization of serum leptin and NOx levels.

The assessment of treatment efficacy in age related macular degeneration by evaluating the oxidative stress markers and OCT measurements.

UNLABELLED: Age related macular degeneration (AMD) is the most frequent cause of blindness in the elderly. AIM: To establish the role of oxidative stress in retinal structural lesions in AMD and to monitor the evolution of oxidative stress markers and OCT measurements before and after treatment. MATERIAL AND METHODS: This is a case-control study that included 19 patients diagnosed with AMD and 40 matched healthy controls. According to the AREDS classification, patients were divided into mild, moderate and severe AMD and received treatment with antioxidants, neurotrophic drugs, intravitreal corticosteroids and/or anti-VEGF. We followed the patients by assessment of visual acuity, optical coherence tomography (OCT) and oxidative stress markers, such as superoxide-dismutase (SOD), thiobarbituric acid reactive substances (TBARS), and C-reactive protein (CRP) from blood samples before and after treatment. RESULTS: The OCT showed that the macular edema in patients with severe disease was significantly reduced after treatment, while the cases with normal retinal thickness increased significantly (p = 0.005). Comparing the mean values of SOD, TBARS and CRP in the two groups, we found that they were significantly higher in the study group compared to controls (p < 0.01), being higher in patients with severe disease. These values decreased post treatment, but they were still higher than in controls. CONCLUSIONS: The present research supports the role of oxidative stress and inflammation in AMD and highlights the role of therapy directed against these risk factors. By monitoring the oxidative stress markers in the evolution of the disease, we showed that high values persist after treatment, thus supporting the idea that treatment should be followed for a long time.

Antidote removal during haemodialysis for massive acetaminophen overdose.

CONTEXT: Haemodialysis is sometimes used for patients with massive acetaminophen overdose when signs of "mitochondrial paralysis" (lactic acidosis, altered mental status, hypothermia and hyperglycaemia) are present. The role of haemodialysis is debated, in part because the evidence base is weak and the endogenous clearance of acetaminophen is high. There is also concern because the antidote acetylcysteine is also dialyzable. We prospectively measured serum acetylcysteine concentrations during haemodialysis in three such cases. CASE DETAILS: Three adults each presented comatose and acidemic 10 to ~18 h after ingesting > 1000mg/kg of acetaminophen. Two were hypothermic and hyperglycaemic. Serum lactate concentrations ranged from 7 mM to 12.5 mM. All three were intubated, and initial acetaminophen concentrations were as high as 5980 µM (900 µg/mL). An intravenous loading dose of 150 mg/kg acetylcysteine was initiated between 10.8 and ~18 h post ingestion, and additional doses were empirically administered during haemodialysis to compensate for possible antidote removal. A single run of 3-4 h of haemodialysis removed 10-20 g of acetaminophen (48-80% of remaining body burden), reduced serum acetaminophen concentrations by 56-84% (total clearance 3.4-7.8 mL/kg/min), accelerated native acetaminophen clearance (mean elimination half-life 580 min pre-dialysis, 120 min during and 340 min post-dialysis) and corrected acidemia. Extraction ratios of acetylcysteine across the dialysis circuit ranged from 73% to 87% (dialysance 3.0 to 5.3 mL/kg/min). All three patients recovered fully, and none developed coagulopathy or other signs of liver failure. DISCUSSION: When massive acetaminophen ingestion is accompanied by coma and lactic acidosis, emergency haemodialysis can result in rapid biochemical improvement. As expected, haemodialysis more than doubles the clearance of both acetaminophen and acetylcysteine. Because acetylcysteine dosing is largely empirical, we recommend doubling the dose during haemodialysis, with an additional half-load when dialysis exceeds 6 h.

Carbamoylation abrogates the antioxidant potential of hydrogen sulfide.

Hydrogen sulfide (H2S) has been identified as the third gasotransmitter. Beside its role as signaling molecule in the cardiovascular and nervous system the antioxidant and cyto-protective properties of H2S have gained much attention. In the present study we show that cyanate, an uremic toxin which is found in abundant concentration in sera of patients suffering from chronic kidney disease (CKD), can abrogate the antioxidant and cytoprotective activity of H2S via S-carbamoylation reaction, a reaction that previously has only been shown to have a physiological effect on cysteine groups, but not on H2S. Carbamoylation strongly inhibited the free radical scavenging (ABTS(+·) and alkylperoxyl ROO(·)) properties of H2S. The extent of intracellular ROS formation induced by ROO(·) was diminished by H2S whereas carbamoylation counteracted the protective effect. Reagent HOCl was rapidly inactivated by H2S in contrast to the carbamoylated compound. Protein modification by HOCl was inhibited by H2S but carbamoylation significantly reduced the effect. Thus, S-carbamoylation of low molecular weight thiols by abrogating their antioxidant potential may contribute to the higher oxidative stress observed in CKD.

Iron-induced fibrin in cardiovascular disease.

Accumulating evidence within the last two decades indicates the association between cardiovascular disease (CVD) and chronic inflammatory state. Under normal conditions fibrin clots are gradually degraded by the fibrinolytic enzyme system, so no permanent insoluble deposits remain in the circulation. However, fibrinolytic therapy in coronary and cerebral thrombosis is ineffective unless it is installed within 3-5 hours of the onset. We have shown that trivalent iron (FeIII) initiates a hydroxyl radical-catalyzed conversion of fibrinogen into a fibrin-like polymer (parafibrin) that is remarkably resistant to the proteolytic dissolution and thus promotes its intravascular deposition. Here we suggest that the persistent presence of proteolysis-resistant fibrin clots causes chronic inflammation. We study the effects of certain amphiphilic substances on the iron- and thrombin-induced fibrinogen polymerization visualized using scanning electron microscopy. We argue that the culprit is an excessive accumulation of free iron in blood, known to be associated with CVD. The only way to prevent iron overload is by supplementation with iron chelating agents. However, administration of free radical scavengers as effective protection against persistent presence of fibrin-like deposits should also be investigated to contribute to the prevention of cardiovascular and other degenerative diseases.

Citrulline: pharmacological perspectives and its role as an emerging biomarker in future.

L-Citrulline is a naturally occurring non-essential amino acid, an intermediate in urea cycle and conditionally essential in intestinal pathology. It is a potent hydroxyl radical scavenger and much more effective precursor of arginine and nitric oxide (NO) than arginine itself so exploited in therapeutics. Plasma citrulline concentration is used by clinicians to assess functional enterocyte mass in various chronic and acute small bowel pathologies like short bowel syndrome that has become an indication in clinical practice. Its supplementation is likely to be used in conditions like erectile dysfunction, sickle cell anemia, short bowel syndrome (to restore nitrogen balance), hyperlipidemia, cancer chemotherapy, hypercholestremia, in hyperoxic lung damage, urea cycle disorders, Alzheimers disease, multi-infarct dementia and as an immunomodulator. Its emerging role as a biomarker in intestinal pathology and early diagnosis of Rheumatoid arthritis has spread considerable interest. Antibody detection to Anti-cyclic citrullinated peptide (ACCP) antibodies can be recommended for early detection of RA decreasing joint damage and deformity, because these are detected well before the onset of disease manifestations of RA. The test is highly specific than RF (Rheumatoid factor), with moderate sensitivity, but much useful in differentiating RA from other disorders. Further studies and exploration is required in these areas.

[Integrated pharmacokinetic study of multiple effective components of tea polyphenols and its correlation with anti-free radical pharmacodynamics in rats].

LC-MS/MS method was used to simultaneously determine anti-oxidative active catechins EGCG, ECG, EGC and EC in plasma of rats treated with tea polyphenols (TP). The integrated plasma concentration (C') of TP was calculated by means of self-defined weighing coefficient based on percent AUC of individual components, thereby assessing integrated pharmacokinetic (PK) parameters of TP via log C'-T curve. The anti-free radical effects of TP were estimated using inhibitory rate of drug-containing serum collected at different times from rats against in vitro lipid peroxidation of mouse liver homogenate. The obtained E-T curves were used to calculate anti-free radical pharmacodynamic (PD) parameters of TP. E-logC and E-log C' plots and linear regression were carried out in order to obtain the correlation coefficient (R2). The results indicated that the log C'-T curves of TP, which could be best described by three-compartment model, corresponded to elimination rule of iv administration of drugs. The integrated PK parameters showed that TP was distributed in body rapidly and widely, and eliminated from deep compartment slowly. From comparison of R2 values and consistence of C'-T course and E-T course, it was evident that TP integrated PK behaviors correlated much better with its PD behaviors than individual active components, and thus demonstrated that integrated PK parameters could characterize to maximal extent holistic disposition of Chinese herbal drugs and reflect residence properties of holistic effective substances in biological body.

N-Acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to determine whether oral dosing with N-acetylcysteine (NAC) increases intraplatelet levels of the antioxidant, glutathione (GSH), and reduces platelet-monocyte conjugation in blood from patients with type 2 diabetes. METHODS: In this placebo-controlled randomised crossover study, the effect of oral NAC dosing on platelet-monocyte conjugation and intraplatelet GSH was investigated in patients with type 2 diabetes (eligibility criteria: men or post-menopausal women with well-controlled diabetes (HbA(1c) < 10%), not on aspirin or statins). Patients (n = 14; age range 43-79 years, HbA(1c) = 6.9 ± 0.9% [52.3 ± 10.3 mmol/mol]) visited the Highland Clinical Research Facility, Inverness, UK on day 0 and day 7 for each arm of the study. Blood was sampled before and 2 h after oral administration of placebo or NAC (1,200 mg) on day 0 and day 7. Patients received placebo or NAC capsules for once-daily dosing on the intervening days. The order of administration of NAC and placebo was allocated by a central office and all patients and research staff involved in the study were blinded to the allocation until after the study was complete and the data fully analysed. The primary outcome for the study was platelet-monocyte conjugation. RESULTS: Oral NAC reduced platelet-monocyte conjugation (from 53.1 ± 4.5% to 42.5 ± 3.9%) at 2 h after administration and the effect was maintained after 7 days of dosing. Intraplatelet GSH was raised in individuals with depleted GSH and there was a negative correlation between baseline intraplatelet GSH and platelet-monocyte conjugation. There were no adverse events. CONCLUSIONS/INTERPRETATION: The NAC-induced normalisation of intraplatelet GSH, coupled with a reduction in platelet-monocyte conjugation, suggests that NAC might help to reduce atherothrombotic risk in type 2 diabetes. FUNDING: Chief Scientist Office (CZB/4/622), Scottish Funding Council, Highlands & Islands Enterprise and European Regional Development Fund. TRIAL REGISTRATION: isrctn.org ISRCTN89304265.

Oxidative stress modulates the organization of erythrocyte membrane cytoskeleton.

BACKGROUND: Apart from their main role in transporting oxygen and carbon dioxide, erythrocytes play also an important role in organism antioxidative defence. Direct exposure to reactive oxygen species (ROS) results in shortening of their half-life, even by 50%. The presence of glucose, being the substrate in pentose phosphate pathway (PPP) cycle, is one of the factors that can have influence on the level of oxidative stress. The activity of PPP increases during oxidative stress. Glucose guarantees normal PPP functioning with the production of reductive equivalents in the amounts necessary to reproduction of glutathione--nonenzymatic free radical scavenger. In available literature there are no reports regarding the changes in protein contents of erythrocyte cytoskeleton exposed to t-butyl hydroperoxide in relation to glucose presence in incubation medium. MATERIAL/METHODS: Erythrocytes taken from 10 healthy subjects were used to assess the influence of generated free radicals on erythrocyte proteins and chosen parameters of oxidative stress. Erythrocytes were incubated in the solutions containing deferent concentrations of t-butyl hydroperoxide and glucose. Electrophoresis was performed on polyacrylamide gel in denaturating conditions. The contents of tryptophan in membranes was evaluated spectrofluorometrically. RESULTS/CONCLUSIONS: In vitro conditions oxidative stress leads to protein damage in erythrocyte cytoskeleton, both in proteins inside the cell as well as having contact with extracellular environment. In consequence, the amount of low-molecular proteins--mainly globin, which bind to cytoskeleton, increases. This process takes place independently of glucose presence in incubation medium. One of the element of protein cytoskeleton, tryptophan, also undergoes degradation. The decrease of its contents is higher during erythrocyte exposure to t-BOOH in environment containing glucose, what can suggest prooxidative influence of glucose in conditions in vitro.

Effects of high molecular weight alcohols from sugar cane fed alone or in combination with plant sterols on lipid profile and antioxidant status of Wistar rats.

The effect of feeding a mixture of high molecular weight alcohols derived from sugarcane (SCA), both alone and in combination with phytosterols (PS), on changes in plasma lipids, organ cholesterol accumulation, and antioxidant status of Wistar rats was undertaken. Three separate experiments were conducted and each experiment had 3 subsets. In experiment 1, rats were fed on an AIN-76, semi-synthetic diet supplemented with 0%, 0.5%, and 5% SCA w/w. The second experiment consisted of feeding rats an atherogenic diet (AIN-76+0.5% cholesterol) containing 0%, 0.5%, and 5% SCA w/w. The third experiment consisted of feeding rats an atherogenic diet that contained 2% PS in combination with 0%, 0.5%, and 5% SCA. Rats fed the atherogenic diet exhibited significant elevations in total and low-density lipoprotein cholesterol, and significant reductions in the high-density lipoprotein/total cholesterol ratio, regardless of the presence of 0.5% or 5% SCA mixture. Serum cholesterol increased 29% to 35% in these animals compared with animals fed the nonatherogenic diets. In contrast, animals fed atherogenic diets that contained 2% PS exhibited no difference in serum lipids compared with counterparts fed nonatherogenic diets. The combined presence of SCA with PS had no effect on further lowering plasma cholesterol. No changes in C-reactive protein were observed, but plasma oxygen radical scavenging capacity values significantly (p < 0.05) decreased when rats were fed the atherogenic diets that contained the combination of PS and SCA. This result corresponded to an apparent greater (p < 0.05) susceptibility of red blood cells to oxidative stress.

Use of blood markers in early diagnosis of oxidative stress in age related macular degeneration.

UNLABELLED: Age related macular degeneration (AMD) is the most frequent cause of irreversible blindness in the elderly population, affecting approximately 30-50 million people around the world. AIM: to establish the role of oxidative stress in retinal structural lesions. MATERIALS AND METHODS: It is a case-control study that included 19 patients diagnosed with AMD. Depending on the severity of the diagnosis, patients were divided into 3 groups: group 1 - mild AMD, group 2 - moderate, atrophic AMD, group 3 - severe, neovascular AMD. They were followed by assessment of visual acuity, optical coherence tomography (OCT) and oxidative stress markers like superoxide-dismutase (SOD), thiobarbituric acid reactive substances (TBARS) and inflammatory marker - C-reactive protein (CRP). RESULTS: Risk factors involved in patients with AMD are arterial hypertension, smoking, hyperlipidemia and diet poor in antioxidants, as revealed in the questionnaire. Retinal thickness assessed by optical coherence tomography showed that values in patients with severity level 2 is within normal limits, while in patients with severity level 3, these values are significantly increased due to macular edema. The mean values of SOD, TBARS and CRP in the studied group were significantly higher compared to controls, being higher in group severity level 3. CONCLUSIONS: This study shows the role of oxidative stress and inflammation in retinal structural lesions in AMD and the importance of blood markers in early detection of oxidative stress and thus of retinal lesions in this disease.

Importance of the cytoplasmic super-oxide dismutase in the normal tissue of the endometrium and the endometrium carcinoma.

OBJECTIVES: The objective of the study is comparing pathohistological picture and test results of the activity of the enzymes of the anti-oxidative protection -cytoplasmic super-oxide dismutase (CuZnSOD) from the blood and endometrium in the promotion of the progression or regression of the hyperplasia and endometrium carcinoma. MATERIALS AND METHODS: The study has been carried out on 70 patients. We have analysed:The age patients, the supersonic test - transvaginal probe, pathohistological diagnosis (PHD) analysis of the curet of the patient-we have gathered the tissue of the normal and the pathologicaly changed endometrium from the exploratory curretage, determining the CuZnSOD in the blood and in the tissue of the normal and pathological endometrium of the uterus. The Group A has been made out of 30 of them who did not have the irregular bleeding from the uterus, and 40 of them represented the Group B with the irregular bleeding, who also had PHD confirmed hyperplasia or malign changes of the endometrium. We have tested if there has been the pathalogical changes in the small pelvis (the ovary tumor, myoma etc.) in both groups. RESULTS: Dominant age in the Group B is 41 - 50 (55%), in Group A, age difference is not that apparent (p > 0.05). The results of the arithmetic mean of the CuZnSOD in the blood (19.90%) and (29.05%) in the endometrium which is lower than the Group A (blood-29.95%, endometrium-32.56%). Lower values CuZnSOD in the blood (18.9%) and endometrium (30.09%) we have in the experimental group patients who have had bleeding as well as those beside bleeding had some other gynecological - patological proces (myoma, cyst on the ovary etc.) CONCLUSIONS: According to the facts we can see the significance of the activity of the enzymes of the anti-oxidative system in the diagnostic of the hyperplasia and endometrium carcinoma as well as the possibility of their application in the clinical practice.

Plasmalogens the neglected regulatory and scavenging lipid species.

Plasmalogens are a class of phospholipids carrying a vinyl ether bond in sn-1 and an ester bond in sn-2 position of the glycerol backbone. Although they are widespread in all tissues and represent up to 18% of the total phospholipid mass in humans, their physiological function is still poorly understood. The aim of this review is to give an overview over the current knowledge in plasmalogen biology and pathology with an emphasis on neglected aspects of their involvement in neurological and metabolic diseases. Furthermore a better understanding of plasmalogen biology in health and disease could also lead to the development of better diagnostic and prognostic biomarkers for vascular and metabolic diseases such as obesity and diabetes mellitus, inflammation, neuro-degeneration and cancer.