The glycation products before and after therapy for acute and chronic pain.

Pain increased the number of free radicals in the body. Previously, we studied changes mainly in oxygen and nitroxide free radicals and described these changes relative to the lipids and saccharides. In this article we focus on changes relative to proteins. Assessment of AGE products (advanced glycation end-products) was carried out by measuring fluorescence. Patients were divided into two groups: 15 patients with acute pain and 17 patients with chronic pain. Acute pain was associated with a variety of surgical procedures and patients were examined before and after surgical procedures. The group of patients with chronic pain suffered from various types of chronic pain, but mainly back pain. In patients with acute pain, total protein (TP) decreased after surgery, as did the level of AGE and the AGE/TP ratio. Nonetheless, post-operative pain increased. In patients with chronic pain, neither total protein, AGE, or AGE/TP changed, despite significant pain relief being reported after treatment. Changes in proteins, as biochemical markers, before and after pain treatment did not show any significant changes. In patients with acute pain, the recorded changes only lasted for 3-5 days after the operation. While in chronic pain, there were no significant changes at all. The assumption that changes in proteins, as biomarkers, would have the same importance as changes in lipids and saccharides was not proven.

[Chronic fatifue syndrome.] / Chronický Únavový syndrome.

Chronic fatigue syndrome - CFS is a disease that lasts about 6 months in adults and in children three months. Other names are myalgia encephalomyelitis, postviral immune syndrome, chronic fatigue immune dysfunction syndrome. The reasons are biological, genetical, infectious or psychological. The paper discusses the history of chronic fatigue syndrome, epidemiology and its prevalence, clinical course, pathophysiology, diagnosis, therapy and prognosis, and also economics.

[Antioxidants and their gastrointestinal absorption and interferences of their effects]. / Antioxidanty a jejich gastrointestinálni absorpce a interference jejich ucinku.

Antioxidants and trace elements are using by hundreds millions of people. Effective are especially mixtures of antioxidants. Usually is declared only the composition of the tablets, but nowadays it is not satisfactory. Substantial is how much of the antioxidants is absorbed and where, how it increases the antioxidant capacity in the blood, which effect it has, the stability of them and who, how much, which and when they are to be used. It is also very important which antioxidants during the detoxication of free radicals react first and therefore they are soon exhausted and whether at all or how quickly can they be reduced back to an active component. In aging the antioxidant capacity decreases, it is influenced by the season, all of factors are to be taken in account. The absorption and the effect are influenced by the state of gastrointestinal tract, including the microbiological flora, pH, the size of the molecules, sometimes by partial oxygen tension in the blood. Free radicals are generated mostly after a load and therefore it is suitable to have the antioxidants capacity on a high level, it is possible to increase it during the load and it is recommended the administration of them after the load. Some authors recommend low doses of antioxidants five times a day. In some diseases the antioxidants are effluenced from the tissues to the blood and then there is a defficit in tissues of them. Important are the interferences during the absorption, their metabolism in organism; it may decrease their level or increase their effectivness, the metabolism can infuence to which tissues are the antioxidants deposited, and how long will stay the increased level of antioxidant capacity. The speed of elimination by urine and stool is also important. It is useful to know from which and how much of isomers the antioxidant is composed, because the single isomer may have a different effect. The origin of antioxidants is important, as natural antioxidants are usually more effective than the sythetic ones. The toxicity of the substances should not to be neglected. Storing of antioxidants sometimes deteriorate them, or sometimes they are contaminated by anabolic steroids. Some substances like phytates can bind them and so decrease their bioavavilability. Lipid soluble substances need lipids in the diet, some antioxidants are differently absorbed from different sources of nutrition. Genetic equipment is important as well. It is apparent that the administration of antioxidants and trace elements is not simple and that the informations of commercial preparates is usually not sufficient, probably in the future at least may be mentioned total antioxidant capacity.

[Free radicals and antioxidants in otorhinolaryngology]. / Volné radikály a antioxidanty v otorhinolaryngologii.

Free radicals in otorhinolaryngology participate in the pathogenesis of many diseases. Antioxidants can act or preventively or ameliorate the diseases. Oxidative stress, in which is the predominance of free radicals to antioxidants, is present in many states like inflammation, atherosclerosis or tumors. Antioxidant capacity is increased not only by the application of antioxidants, but also due to positive emotions. In nasal and paranasal diseases is the role of the nitroxide radical very important. Vasocontrictive drugs decrease its level, pathologically increased levels are observed in asthma, allergic rhinitis and in sinusitis. Nitroxide protects organism against microorganisms and viruses. Oxidative stress supports the origin of nasal polyposis, takes part in disturbances of the hearing. Increased reactive oxygen species are engaged in tinnitus. In otitis media the level of lipoperoxides may be the marker of the severity of the disease. In Ménicre's syndrome the total antioxidant capacity is decreased. It is possible to conclude, that free radicals and antioxidants play an important role in otorhinolaryngological diseases.

[The significance of free radicals and antioxidants due to the load induced by sport activity]. / Význam volných radikálu a antioxidantu sportovní záteze.

Sport performance is followed by a high production of free radicals. The main reasons are reperfusion after the previous imbalance between the increased need of the organism and the ability of blood supply by oxygen, increased production of ATP, decomposition of the cells particularly white blood cells, oxidation of the purin basis from DNA, stress, output of epinephrine release of free iron, increased temperature in the muscle and its inflammation, and the reception of free radicals from external environment. Peroxidation of lipids, proteins, DNA and other compounds follows the previous biochemical steps. Antioxidants are consumed by free radicals, antioxidative enzymes are released into blood plasma, intracellular calcium is increased, the production of nitric oxide rises, the levels of hydrogen peroxide and hypochlorous acid increase. These penetrate through the membranes and oxidatively damage the tissues. Training improves the ability of the organism to balance the increased load of free radicals. The damage can be lowered by the application of a mixture of antioxidants, the most important are vitamin C, A, E, glutathione, selenium, carnosine, eventually bioflavonoids and ginkgo biloba. The lack of antioxidants can significantly diminish the sport performance and therefore the supplementation with antioxidants is for top sportsmen but also for aged people advisable.

[Free radicals and antioxidants in cerebrospinal fluid in central nervous system diseases]. / Vysetrování mozkomísního moku z hlediska volných radikálu a antioxidantu u nekterých onemocnení CNS.

Free radicals and antioxidants may play a role in the etiology and pathogenesis of some central nervous diseases. The brain tissue is relatively insufficiently protected by antioxidants against the free radical induced damage. The brain situation may be reflected by the cerebrospinal fluid examination, which has not enough attention. It seems, that from this point of view subarachnoical hemorrhagy, meningitis, hydrocephalus, Alzheimer's, Parkinson's and Huntington's diseases, multiple sclerosis and probably schizophrenia should receive a special attention.

What is the source of free radicals causing hemolysis in stored blood?

The quality of stored blood can be deteriorated by hemolysis caused by free radicals. The purpose of this study was to elucidate whether neutrophile leukocytes are the source of free radicals in stored blood as in hemodialyzed patients. Resuspensions with low (LL) or high (HL) leukocyte concentrations were prepared from samples of twenty healthy volunteers. The samples were incubated for 10 days at 4 degrees C and then for one day at 37 degrees C. Markers of hemolysis and free radical metabolism were examined before and after incubation in LL and HL samples. In spite of the difference of leukocytes counts in LL and HL resuspensions (p<0.0001), the pre-incubation values of all laboratory parameters were practically identical. In post-storage samples, superoxide dismutase and glutathione peroxidase activities did not differ in either group. Reduced glutathione in erythrocytes and extracellular antioxidant capacity were insignificantly lower in HL resuspensions, but the increase of malondialdehyde was much more pronounced in the HL samples (p<0.0001). The degree of hemolysis, expressed as the extracellular increase of potassium (p<0.001), hemoglobin (p<0.05) and lactate dehydrogenase (p<0.05), was higher in the HL samples. Our results support the hypothesis that leukocytes participate in free radical production in stored blood.

[Antioxidant effects of melatonin]. / Antioxidacní úcinek melatoninu.

Increase in knowledge about reactive oxygen species action mechanisms and oxidative stress effects in living organisms led to intensive seeking for new, more effective substances, which prevent extreme development of oxidative stress or are able to decrease its negative influence, damaging cell structures and many cell functions. These substances are called antioxidants, scavengers, trappers or quenchers. In nineties, melatonin became the centre of the interest in the filed of investigation of antioxidative properties of different chemical substances. This is in living organisms ubiquitous substance with relatively simple chemical structure, good physical properties and wide physiological effects. The main role of endogenous melatonin comprises receptor-mediated biological rhythms synchronisation. Among other functions mentioned later belong anti-gonadotropic, immunotropic and non-receptor-mediated antioxidative effects. Melatonin is said to have also antineoplastic properties. Its anti-aging effect is discutable.

[Free radicals in immunology and infectious diseases]. / Volné radikály v imunologii a u infekcních chorob.

Free radicals contribute significantly in modification of immune processes and inflammatory reactions. They are produced by activated phagocytes which use them for killing microorganisms. Free radicals facilitate production of cytokines, which are important as modifiers of inflammatory reactions. Formation of free radicals is influenced by antioxidants which can thus modify the intensity of inflammatory reaction and immune response. The authors describe in detail the contribution of free radicals in etiology and pathogenesis of autoimmune diseases including rheumatoid arthritis, multiple sclerosis or amyotrophic lateral sclerosis. The role of free radicals and modifying influence of antioxidants in viral, bacterial, parasitic and mycotic diseases is described in the second part of the review. Finally, influence of free radicals and antioxidants on immunity changes in patients with malignant tumours, during aging and physical exercise is discussed.

Does exogenous melatonin influence the free radicals metabolism and pain sensation in rat?

Melatonin has been shown to play a role in antioxidative defence. We therefore studied its effect on oxidative damage to the rat cerebral cortex evoked by painful stimulation and immobilization-induced stress. Moreover, the effect of melatonin on chronic pain perception was examined. Rats were injected with either a high dose of melatonin (100 mg/kg i.p.) or a vehicle for five days and were subjected to painful stimulation or immobilization stress 30 min after the treatment. To determine the degree of oxidative stress, the levels of free radicals, thiobarbituric acid reactive substances (TBARS) as indicators of lipid peroxidation and glutathione peroxidase (GSHPx) were estimated in somatosensory cortex. Pain perception was measured by the tail-flick and plantar test. Melatonin reduced the level of TBARS previously increased by painful stimulation. Melatonin also exhibited a slight analgesic effect in those animals exposed to painful stimulation but its role in free radical scavenging did not contribute to this effect.

Anticipation of acute stress in isoprenaline-sensitive and - resistant rats: strain and gender differences.

The effect of stress anticipation was studied in two inbred Wistar rat strains with high and low sensitivity to isoprenaline. The animals were exposed to tail-flick and 4-hr water immersion restraint stress on two consecutive days. On the first day stress was applied to one group and the next day to the anticipation group. The changes in adrenal, heart and spleen weights, tail-flick latency, incidence of gastric ulcers, and the antioxidant defense system in the sensorimotor cortex were compared with two non-stressed control groups. Anticipatory stress decreased adrenal weights. The content of thiobarbituric acid reactive substances (TBARS) was increased both in acute and anticipatory stress; superoxide dismutase, glutathione peroxidase, and antioxidative capacity were increased in anticipatory stress only. Stress anticipation decreased the pain threshold in the isoprenaline-sensitive and increased in the isoprenaline-resistant rats and led to more frequent gastric ulcers in the isoprenaline-resistant group. Significant sex differences were observed both in adrenal weights and TBARS content. The relative adrenal weights were negatively correlated with the TBARS content. We suggest that the outcome of anticipatory stress may depend upon the relation between the hormonal and antioxidant functions of the adrenals and that anticipation-induced activation of antioxidant enzymes may ameliorate the acute stress response. Anticipation itself was found to be a stronger stressor than physical acute stress.

[Antioxidants and protection of the skin against the effect of ultraviolet rays]. / Antioxidanty a ochrana kuze pred pusobením UV zárení.

Ultraviolet radiation causes increase of production of the reactive oxygen species in the human skin, which are responsible for oxidative stress and damage of many important cellular components in the target tissue. The complex of antioxidants represents the major protective system against the oxidative damage of the skin. Many antioxidants, namely vitamin E, can be successfully used in photoprotection.

[Antioxidative properties of ascorbic acid]. / Antioxidacní vlastnosti kyseliny askorbové.

Vitamin C (ascorbic acid) is an important hydrophilic compound with antioxidative effect. In the introduction the authors describe possible consequences of loss of vitamin C synthetic ability in an evolutionary ancestor of Anthropoidea. Metabolism of this vitamin is described briefly along with possibilities of its supplementation and determination in biological fluids. Highest attention is paid to metabolic effects of vitamin C, respectively to changes which can be observed after its deprivation, or after the supplementation with this vitamin. Protective effect of vitamin C against lipoperoxidation, its role in modulation of immunity and tumorigenesis are described. Many effects of vitamin C can be explained by its antioxidative activity. The authors show that under concrete conditions, administration of vitamin C can be accompanied by a prooxidative effect. Since vitamin C works in cooperation with other antioxidants, its administration in diseases which are followed by oxidative stress is move effective when used in combined preparations.

Suppression of adjuvant arthritis in rats with chronic bromocriptine treatment does not prevent associated oxidative stress.

We studied the effect of prolactin (PRL) inhibition by bromocriptine (BRC) in the first phase of adjuvant induced arthritis (AA), up to day 11(BRCl-AA), and in the whole time course of AA, up to day 23 (BRC-AA), on the development of the disease in male Lewis rats. On day 24, arthritic rats showed inhibition of PRL secretion, but not PRL mRNA expression in adenopituitaries. BRC treatment suppressed PRL serum levels and PRL mRNA expression in adenopituitaries. In BRC/-AA group PRL levels and PRLmRNA were at the level of rats with AA. Serum corticosterone (CORT) was stimulated by AA from 16.9+/-5.8 to 59.1+/-8.7 ngml(-1), p<0.05, to the same level in BRC-control (BRC-C) and BRC-AA group and further potentiated in BRCI-AA group (148.2+/-33.1 ngml(-1), p<0.05 vs. group with AA). Hind paw swelling was reduced but not completely inhibited in BRC1-AA group and totally prevented in BRC-AA rats as was the core temperature (36.5+/-0.1 degrees C vs. 37.4+/-.0.1 degrees C in AA rats on day 23, p<0.01). Serum concentration of NO-ZNO-3 rose in rats with AA to 28.7+/-2.5 &mgr;mo1L-1 against. 13.9+/-1.9 &mgr;molL(-1) in controls (p<0.01), remained elevated in BRC-AA group and was potentiated in BRC1-AA group (48.2+/-3.5 &mgr;mol(-1), p<0.01 vs. AA or BRC1-AA group) Thiobarbituric acid reactive substances (TBARS) and antioxidant capacity in the spleen were enhanced in rats with AA and to the same extent in BRC-AA or BRC1-AA groups. These results show a discrepancy between the suppression of clinical symptoms and persisting oxidative stress in AA rats after the BRC induced PRL inhibition. The potentiation of nintric oxide (NO-) production after the sudden cessation of PRL inhibition during the disease may promote further joint damage.

[Indicators of oxidative stress in cardiovascular diseases. I. Lipoperoxidation]. / Indikátory oxidacního stresu z hlediska kardiovaskulárních chorob. I. Problematika lipoperoxidace.

The level od malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS) respectively, in blood is changing very quickly and therefore isoprostanes scam to be better markers of atherogenesis. Oxidized LDL belong to the most important reasons of the origin of foam cells and therefore of atherogenesis. That is why the inhibition of the oxidation of LDL particles should belong to the standard therapy of cardiovascular diseases. The value of antibodies against oxidized LDL is difficult to interpret, because they are multifactor dependent, especially under genetic control. Antibodies against LDL modified by malondialdehyde (MDA-LDL) are increased in smokers and individuals with a rapid atherosclerotic progression. HDL-cholesterol protects LDL through the oxidized lipid exchange. Oxidized HDL formed during this process has then an increased clearance from circulation.

[Indicators of oxidative stress in cardiovascular diseases. II. Nitrogenous substances, AGE-substances and antioxidants]. / Indikátory oxidacního stresu z hlediska kardiovaskulárních chorob. II. Dusíkaté látky, AGE-látky a antioxidanty.

By oxidation of nitrogen oxide nitrites and nitrates are formed which can be considered markers of inflammation. AGE-substances (products of advanced glycation) are formed not only from proteins (e.g. Hb-AGE) but also from lipids (AGE-LDL) and DNA (AGE-DNA) and lead to an increased number of mutations. They are toxic and are deposited in the vascular wall. They cause coagulopathy, stimulate cytokines and inactivate nitrogen oxide and thus prevent relaxation of the vascular wall. Extracellular superoxide dismutase (EC-SOD) has a variant (mutation Arg213Gly with a 4% incidence) which causes deterioration of the cardiac prognosis. Selenium deficiency leads also to an increased frequency of cardiovascular diseases.

[Indicators of effects of free radicals in workers at risk of lead exposure]. / Ukazatelé pusobení volných radikálu u pracovníku v riziku olova.

The authors examined indicators of the action of free radicals in 40 workers exposed to the risk of lead (work with lead containing glazing and prints). The lead concentration in the atmosphere did not exceed the highest permissible concentrations and the biological exposure tests as regards lead exposure did not exceed the highest permissible limits. In the examined subjects the authors found a significantly elevated level of superoxide dismutase activity (p < 0.05) which suggests long-term increased peroxide formation. The correlation of the selenium concentration in blood and the period of lead exposure was at the borderline of statistical significance (p = 0.1159). Further investigations will be focused on subjects with symptoms of increased exposure to lead and lead intoxication where the probability of pathological findings is greater.

[Significance of free radicals in the pathogenesis of rheumatic diseases and possibilities of decreasing their pathogenic effects]. / Význam volných radikálu v patogenezi revmatických chorob a moznosti snízení jejich patogenního pusobení.

The authors present the result of their work where they provide evidence that in inflammatory and degenerative diseases the break-down on superoxide in inadequate. This oxygen radicals and its metabolites play a significant role in the pathogenesis of these diseases. The authors revealed a severe defect in superoxide degeneration in particular in articular exudates of patients with active synovitis. Administration of the preparation Selzink-Plus of PRO.MED.CS Co. Prague which contains selenium, zinc, beta-cyrotene, vitamin C and E along with antirheumatic treatment improves according to the authors the breakdown of superoxide and its metabolites and improves thus the patient's prognosis. Long-term administration of the preparation seems to produce even better results.