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.

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.

[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.

[New findings on the clinical significance of magnesium]. / Nekteré novejsí poznatky o klinickém významu magnézia.

Recent findings are concerned with the diagnosis, incidence, and therapy of hypomagnesaemia. The authors discuss the importance of Mg in stress, cardiac diseases, bone metabolism, neoplasms, blood clotting, in physical exertion and the Mg content of the diet.

Conjugations of acrylonitrile and glycidonitrile with glutathione--a contribution to problems of metabolism of acrylonitrile.

The study of the conjugation of acrylonitrile and glycidonitrile with glutathione has demonstrated the capacity of glutathione of eliminating both acrylonitrile (manifesting mostly cyanide effects) and the primary product of its oxidative turnover, glycidonitrile (mutagenic effect), from acting toxicly. It appears, at the same time, however, that massive doses of acrylonitrile may endanger the biological system by depletion of large quantities of glutathione a schematic chart of the metabolic exchanges of acrylonitrile was suggested demonstrating that a part of the total amount of the excreted thiocyanate in the urine might also be accounted for by the cyanide having been produced by the enzymatically catalyzed conjugation of glycidonitrile with glutathione, with the ensuing secondary breakdown of the intermediary product cyanohydrin.

Acrylonitrile metabolism in the rat.

Acrylonitrile (AN) is metabolized by an oxidative pathway via glycidonitrile and glycolaldehyde cyanohydrin to cyanide (CN-), which is transformed to thiocyanate. The major route of AN metabolism (more than 2/3), however, proceeds via cyanoethylation of glutathione, to N-acetyl-S-(2-cyanoethyl)cysteine (AN-mercapturic acid) as a final product.

Two routes of acrylonitrile metabolism.

Acrylonitrile (AN) is metabolized in two different routes. The minor route of AN metabolism is its conversion to cyanide. In vitro experiments confirmed that this biotransformation proceeds via glycidonitrile (catalyzed by hepatic monooxygenases) and glycolaldehyde cyanohydrin (catalyzed by epoxide hydrase). Cyanohydrin is spontaneously decomposed to cyanide, which is then metabolized in vivo to thiocyanate by rhodanese. A major route of AN-metabolism (more than 2/3), however, proceeds via its conjugation with glutathione catalyzed by glutathione S-alkenetransferases, to N-acetyl-S-(2-cyanoethyl)cysteine as a final product.

Acrylonitrile biotransformation in rats, mice, and chinese hamsters as influenced by the route of administration and by phenobarbital, SKF 525-A, cysteine, dimercaprol, or thiosulfate.

Female wistar rats, conventional albino mice, and Chinese hamsters were given a single dose of acrylonitrile, 0.5 or 0.75 mM/kg body weight. The elimination in the urine of thiocyanate, which is the main metabolite of acrylonitrile, indicated a decreasing proportion of biotransformation after oral (over 20%), intraperitoneal, or subcutaneous (2 to 5%), and intravenous (1%) administration in rats. Oral administration of acrylonitrile in hamsters and mice was also followed by higher biotransformation than intraperitoneal administration. Pretreatment of rats with phenobarbital, SKF 525 A, cysteine, or dimercaprol did not significantly influence elimination of thiocyanate in the urine after the administration of acrylonitrile, but simultaneous administration of thiosulfate significantly increased the metabolized portion of acrylonitrile given intraperitoneally in rats (almost twice) and mice (more than three times). Acrylonitrile was found to be strongly bound in blood. The study confirmed the marked effect of distribution (first-pass metabolic phenomenon) on the metabolic fate of foreign compounds. The strong acrylonitrile binding and cyanoethylation are apparently responsible for the unusually high influence of the different routes of administration on the metabolic fate of acrylonitrile. Acrylonitrile was more effectively metabolized to thiocyanate in mice than in rats after oral, intraperitoneal, and intravenous administration. A greater response of acrylonitrile to thiocyanate metabolism and a larger decrease in its acute toxicity after thiosulfate in mice than in rats indicate possible differences in the mechanism of acrylonitrile toxicity in these animals. Cyanide apparently plays a minor role in the acrylonitrile toxicity in rats, but may play quite an important one in mice.