Mednarodno gibanje za renesanso širšega zdravstvenega varstva Zdrava mesta je projekt dveh sektorjev Svetovne zdravstvene organizacije, in sicer sektorja za pospeševanje zdravja in sektorja za ...varstvo okolja. Nastalo je kot posledica že pred desetletjem začete strategije SZO pod geslom Zdravje za vse do leta 2000. Prva mednarodna konferenca tega gibanja je bila leta 1986 v Ottawi.
Oxidative Stress in Schizophrenia Grabnar, Iztok; Vovk, Tomas; Kores Plesnicar, Blanka ...
Current neuropharmacology,
2011-June, 2011-Jun, 2011-06-01, 20110601, Letnik:
9, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Increasing evidence indicates that oxidative damage exists in schizophrenia. Available literature about possible mechanisms of oxidative stress induction was reviewed. Furthermore, possibilities of ...measuring biomarkers of schizophrenia outside the central nervous system compartment, their specificity for different types of schizophrenia and potential therapeutic strategies to prevent oxidative injuries in schizophrenia were discussed. Data were extracted from published literature found in Medline, Embase, Biosis, Cochrane and Web of Science, together with hand search of references. Search terms were: schizophrenia, oxidative stress, antipsychotics, antioxidants and fatty acids. Finding a sensitive, specific and non invasive biomarker of schizophrenia, which could be measured in peripheral tissue, still stays an important task. Antioxidant enzymes, markers of lipid peroxidation, oxidatively modified proteins and DNA are most commonly used. As it considers the supplemental therapy, according to our meta-analysis vitamin E could potentially improve tardive dyskinesia, while for the effect of therapy with polyunsaturated fatty acids there is no clear evidence. Oxidative stress is a part of the pathology in schizophrenia and appears as a promising field to develop new therapeutic strategies. There is a need for well designed, placebo controlled trials with supplementation therapy in schizophrenia.
Nine shikonin pigments: shikonin (S), acetylshikonin (AS), propionylshikonin (PS), isobutyrylshikonin (IBS), tiglylshikonin (TS), 3,3-dimethylacrylshikonin (DAS), angelylshikonin (ANS), 2-methyl-
...n-butyrylshikonin (MBS) and isovalerylshikonin (IVS) were identified in the root epidermis of
Echium italicum L. for the first time. A new thin-layer chromatographic (TLC) method for the separation of enantiomers alkannin and shikonin proved only shikonin after saponification of the root extract, and was afterwards esterified with the corresponding acyl chloride to acquire seven standard compounds (all except ANS). The developed isocratic high-peformance liquid chromatographic (HPLC) methods with VIS and mass spectrometry (MS) detection, allowed for the first time simultaneous separation of all nine compounds with similar structures including positional and geometric isomers in a short time. Structures of the main five compounds (AS, IBS, ANS, MBS, IVS) isolated from the extract by a new semi-preparative HPLC on C18 have additionally been confirmed by
1H and
13C nuclear magnetic resonance spectra, which were reported for AS and MBS for the first time.
Objectives: Previously, oxidative damage has been associated with severity of clinical symptoms and supplementation with antioxidants and essential polyunsaturated fatty acids (EPUFAs) was proposed ...to have beneficial effects in schizophrenia. We evaluated the effects of supplementation with EPUFAs and vitamin E in patients treated with haloperidol depot injection.
Design: This was a double-blind randomized placebo-controlled study with four arms (Placebo, vitamin E, EPUFAs, and vitamin E + EPUFAs). Biomarkers of oxidative stress, neurochemistry, psychopathology, and extrapyramidal symptoms were assessed at baseline and after 4 months.
Results: In EPUFAs group of patients, reduced glutathione concentration was increased compared to placebo. Concentration of oxidized glutathione was decreased in patients receiving vitamin E. In addition, compared to placebo a non-significant trend of increased activity of catalase and superoxide dismutase was observed in all three treatment groups. Patients receiving vitamin E experienced less motor retardation. No difference in extrapyramidal symptoms was found.
Discussion: Our study indicates that supplementation with vitamin E and EPUFAs may improve the antioxidative defense, especially glutathione system, while there is no major effect on symptoms severity. Supplemental treatment with EPUFAs and vitamin E in schizophrenia patients treated with haloperidol is potentially beneficial and a larger independent study appears warranted.
Celotno besedilo
Dostopno za:
DOBA, FSPLJ, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract In this study the role of oxidative stress in schizophrenia was investigated by evaluating the relationship of oxidative stress markers with neurochemistry, psychopathology, and ...extrapyramidal symptoms. Antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and concentrations of malondialdehyde, protein carbonyls, nitrite, nitrate, glutathione, dopamine, noradrenaline, adrenaline, and serotonin were measured in 52 outpatients with DSM-IV diagnosis of schizophrenia treated with haloperidol decanoate. Psychopathology and extrapyramidal symptoms were assessed by positive and negative syndrome scale, global assessment of functioning, abnormal involuntary movement scale, Simpson Angus scale, and Barnes akathisia rating scale. Haloperidol dose was positively correlated with plasma protein carbonyls. Longer duration of illness was associated with decreased levels of glutathione peroxidase. Increased activity of superoxide dismutase was associated with increased levels of catalase, glutathione peroxidase, glutathione reductase and reduced glutathione, and decreased concentration of malondialdehyde, indicating joint action of various antioxidative systems. Increased levels of nitrite and noradrenaline were associated with decreased level of malondialdehyde. Akathisia was greater in patients with decreased catalase activity, indicating involvement of impaired antioxidant defense in developing extrapyramidal symptoms. These results confirm the hypothesis that oxidative stress is involved in pathophysiology of schizophrenia and severity of extrapyramidal symptoms.
The application of artificial neural networks in the pharmaceutical sciences is broad, ranging from drug discovery to clinical pharmacy. In this study, we explored the applicability of ...counter-propagation artificial neural networks (CPANNs), combined with genetic algorithm (GA) for prediction of topiramate (TPM) serum levels based on identified factors important for its prediction.
The study was performed on 118 TPM measurements obtained from 78 adult epileptic patients. Patients were on stable TPM dosing regimen for at least 7 days; therefore, steady-state was assumed. TPM serum concentration was determined by high performance liquid chromatography with fluorescence detection. The influence of demographic, biochemical parameters and therapy characteristics of the patients on TPM levels were tested. Data analysis was performed by CPANNs. GA was used for optimal CPANN parameters, variable selection and adjustment of relative importance.
Data for training included 88 measured TPM concentrations, while remaining were used for validation. Among all factors tested, TPM dose, renal function (eGFR) and carbamazepine dose significantly influenced TPM level and their relative importance were 0.7500, 0.2813, 0.0625, respectively. Relative error and root mean squared relative error (%) and their corresponding 95% confidence intervals for training set were 2.14 (-2.41) - 6.70 and 21.5 18.5 - 24.1; and for test set were -6.21 (-21.2) - 8.77 and 39.9 31.7 - 46.7, respectively.
Statistical parameters showed acceptable predictive performance. Results indicate the feasibility of CPANNs combined with GA to predict TPM concentrations and to adjust relative importance of identified variability factors in population of adult epileptic patients.
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The objective of the study was to develop population pharmacokinetic model of topiramate (TPM) using nonlinear mixed effects modelling approach. Data were collected from 78 adult ...epileptic patients on mono- or co-therapy of TPM and other antiepileptic drugs, such as carbamazepine (CBZ), valproic acid, lamotrigine, levetiracetam, phenobarbital and pregabalin. Steady-state TPM concentrations were determined in blood samples by high performance liquid chromatography with fluorescence detection. A one-compartment model with first order absorption and elimination was used to fit the concentration-time TPM data. Volume of distribution of TPM was estimated at 0.575l/kg. The influence of demographic, biochemical parameters and therapy characteristics of the patients on oral clearance (CL/F) was evaluated. Daily carbamazepine dose (DCBZ) and renal function estimated by Modification of diet in renal disease (MDRD) formula significantly (p<0.001) influenced CL/F and were included in the final model:
CL/F·(l/h)=1.53(l/h)·1+0.476·DCBZ(mg/day)/1000(mg/day)·EXP0.00476·MDRD(ml/min)-95.72(ml/min)..
Increase of CL/F with DCBZ and MDRD was best described by linear and exponential models. Mean TPM CL/F during CBZ co-therapy was 2.46l/h, which is higher for 60.8% than in patients not co-treated with CBZ. Evaluation by bootstrapping showed that the final model was stable. The predictive performance was evaluated by adequate plots and indicated satisfactory precision. This model allows individualisation of TPM dosing in routine patient care, especially useful for patients on different CBZ dosing regimen.
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