Udział reaktywnych form tlenu (RFT) w nieswoistych zapaleniach jelit. Użyteczność diagnostyczna wybranych markerów. Część 1

Malfunctioning of environmental, immunologic or genetic mechanisms brings about a disorder of system homeostasis, which results in the development of diseases of arduous course. Inflammatory bowel diseases are a group of disorders which house a pathological inflammation of the wall of the gastrointestinal tract. It is postulated that one reason for the resulting changes may be free radical reactions. As a result of the ongoing inflammation under the course of the disease an influx of neutrophils into the lumen begins. Although endoscopic examination constitutes an irreplaceable method in the evaluation of the resulting changes, laboratory tests are an essential tool in the diagnostic process. In recent years it has been proven that the role of faecal calprotectin as a non-invasive test can be used to differentiate organic and functional gastrointestinal diseases, and evaluate remission or exacerbation of inflammatory bowel disease [6,28]. It has also been noted that there is a need to seek other new markers that would facilitate the diagnosis.W wyniku nieprawidłowego działania mechanizmów środowiskowych, immunologicznych czy genetycznych dochodzi do zaburzenia homeostazy ustrojowej, co skutkuje rozwojem chorób o uciążliwym przebiegu. Nieswoiste zapalenia jelit stanowią grupę schorzeń, w których dochodzi do patologicznego zapalenia ściany przewodu pokarmowego. Postuluje się, iż jedną z przyczyn powstałych zmian mogą być reakcje wolnorodnikowe. W wyniku toczącego się procesu zapalnego w przebiegu tych chorób rozpoczyna się napływ neutrofilów do światła jelita. Mimo, iż niezastąpioną metodą w ocenie powstałych zmian jest badanie endoskopowe, badania laboratoryjne stanowią niezbędne narzędzie w procesie diagnostycznym. W ostatnich latach udowodniona jest rola kalprotektyny kałowej, jako nieinwazyjnego badania służącego do różnicowania organicznych i czynnościowych chorób przewodu pokarmowego, oceny remisji bądź zaostrzenia nieswoistego zapalenia jelit [6,28]. Wskazuje się także na potrzebę poszukiwania innych nowych markerów, które przyczyniłyby się do ułatwienia diagnostyki

Share of reactive oxygen species (ROS) in inflammatory bowel disease. The diagnostic usefulness of selected markers. Part 1

Malfunctioning of environmental, immunologic or genetic mechanisms brings about a disorder of system homeostasis, which results in the development of diseases of arduous course. Inflammatory bowel diseases are a group of disorders which house a pathological inflammation of the wall of the gastrointestinal tract. It is postulated that one reason for the resulting changes may be free radical reactions. As a result of the ongoing inflammation under the course of the disease an influx of neutrophils into the lumen begins. Although endoscopic examination constitutes an irreplaceable method in the evaluation of the resulting changes, laboratory tests are an essential tool in the diagnostic process. In recent years it has been proven that the role of faecal calprotectin as a non-invasive test can be used to differentiate organic and functional gastrointestinal diseases, and evaluate remission or exacerbation of inflammatory bowel disease [6,28]. It has also been noted that there is a need to seek other new markers that would facilitate the diagnosis.W wyniku nieprawidłowego działania mechanizmów środowiskowych, immunologicznych czy genetycznych dochodzi do zaburzenia homeostazy ustrojowej, co skutkuje rozwojem chorób o uciążliwym przebiegu. Nieswoiste zapalenia jelit stanowią grupę schorzeń, w których dochodzi do patologicznego zapalenia ściany przewodu pokarmowego. Postuluje się, iż jedną z przyczyn powstałych zmian mogą być reakcje wolnorodnikowe. W wyniku toczącego się procesu zapalnego w przebiegu tych chorób rozpoczyna się napływ neutrofilów do światła jelita. Mimo, iż niezastąpioną metodą w ocenie powstałych zmian jest badanie endoskopowe, badania laboratoryjne stanowią niezbędne narzędzie w procesie diagnostycznym. W ostatnich latach udowodniona jest rola kalprotektyny kałowej, jako nieinwazyjnego badania służącego do różnicowania organicznych i czynnościowych chorób przewodu pokarmowego, oceny remisji bądź zaostrzenia nieswoistego zapalenia jelit [6,28]. Wskazuje się także na potrzebę poszukiwania innych nowych markerów, które przyczyniłyby się do ułatwienia diagnostyki

Glutathione concentration, glutathione peroxidase and glutathione reductase activity in elderly patients with type II diabetes compared to hypertensives

Age-related oxidative stress is generated by a combination of increased production of free radicals, decreased antioxidants levels, diminished activity of antioxidant enzymes and impaired repair of oxidative damages. Oxidative stress is associated with many diseases commonly present in elderly such as hypertension and diabetes. In our study we have observed significantly (p<0,01) increased level of reduced glutathione in treated hypertensive compared to treated diabetic patients (3,1± 0,29 mmol/L and 2,72 ± 0,4 mmol/L, respectively) and significantly (p<0,01) increased activity of glutathione reductase (83,43± 15,25 U/g Hb and 65,74 ± 14,27 U/g Hb, respectively)

Glucocorticosteroids – a new target in the treatment of metabolic syndrome

Glucocorticoids are hormones belonging to the group of steroid hormones produced by the adrenal cortex and are necessary for the proper maintenance of metabolic (including lipid and carbohydrate metabolism) and homeostatic functions of the human body. Glucocorticoid secretion is regulated peripherally by the hypothalamic-pituitary-adrenal (HPA) axis in a double feedback fashion, but also at the tissue level by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and type 2 (11β-HSD2). 11β- hydroxysteroid dehydrogenase type 1 is an enzyme that catalyzes the intracellular conversion of biologically inactive cortisone into biologically active cortisol, while 11β- hydroxysteroid dehydrogenase type 2 catalyzes the reverse reaction. Excess glucocorticoids disrupt the body's metabolic management, which leads to the development of metabolic disorders such as abdominal obesity, insulin resistance, or dyslipidemia. In recent years, it has been proven that impaired regulation of the activity of 11β-hydroxysteroid dehydrogenase type 1, especially that located in visceral adipose tissue, is the pathogenetic basis of diseases such as obesity or type 2 diabetes, which are related and constitute important components of the metabolic syndrome. Therefore, inhibition of 11β-HSD1 is a promising concept for the therapy of diseases associated with the metabolic syndrome. Therefore, over the last three decades, there has been significant activity in the academic and pharmaceutical communities towards exploring the role of this enzyme in the pathogenesis of the metabolic syndrome and discovering new chemical compounds as specific 11β-HSD1 inhibitors. The aim of the following study was to present the role of glucocorticosteroids and 11β-hydroxysteroid dehydrogenase type 1 in the pathogenesis of the metabolic syndrome and the importance of using 11β-HSD1 inhibitors in the therapy of this disease. In addition, the work reviews the most important 11β-HSD1 inhibitors and compounds currently being tested for the inhibition of this enzyme

Biochemical markers of oxidative stress in patients with inflammatory bowel diseases

Introduction: Inflammatory bowel disease (IBD) is a group of diseases of unexplained aetiology, characterized by periods of remissions and exacerbations. Reactive oxygen species (ROS) as far as disorders of balance between levels of prooxidants and antioxidants may also participate in the occurrence of IBD. The aim of the present study was an assessment of the antioxidative barrier of the organism in patients with inflammatory bowel disease. Material and methods: The study group consisted of 99 patients (80 with IBD as a study group and 19 healthy as a control group) from Jan Biziel University Hospital in Bydgoszcz, Poland. Venous blood was the material for biochemical analysis: HT, GSH, GPXp, GPXRBC, GST, GR, SOD-1, MDA, NO2-/NO3- and CP. Results: There were statistically significant differences in oxidative stress parameters observed between the study group and the control group, especially concerning HT, GSH, GPXRBC, GST, SOD-1, MDA and NO2-/NO3-. Discussion: The assumption that increased activity of antioxidative compounds may constitute a defence against the influence of oxidative stress may be true. Their decreased activity may participate in lowering an organism’s abilities to defend against oxidative stress and cause the development of free radical diseases. Further studies into targeted preventive strategies are needed. Conclusions: Prooxidative factors play an essential role in the pathogenesis of IBD. Due to the still unknown etiopathology of IBD, research on imbalances between pro-oxidants and antioxidants should be continued in larger groups of patients

Audiometry and biochemical analysis in patients with tinnitus — prelimiary findings

Introduction: Tinnitus is a sound experience despite the lack of acoustic stimuli in the environment. The aim of this study was to report the audiometry and biochemical analysis of those patients with tinnitus compared with reference group. Material and methods: The study included a total of 26 patients aged from 20 to 72 years with diagnosed idiopathic tinnitus and 19 healthy subjects as a control group. All patients underwent audiometric tone test, speech audiometry, distortion otoacoustic emissions product testing, study of evoked auditory potentials of short latency, and biochemical analysis of venous blood concerning values of activity or concentration of the selected parameters of oxidative stress. Results: Mean values of activity or concentration of the selected parameters of oxidative stress in the study and control groups showed reduced effectiveness of the body's natural antioxidant barrier and intensification of treatment of lipid peroxidation. Discussion: There are a lot of factors suspected to generate tinnitus. A lot of them seem to be connected with biochemical disturbances inside cochlea and in central nervous system. It will be helpful to set such battery of tests that contains the predictive indicators of tinnitus. It will be the best if it is the battery of standard, not expensive tests of blood. Conclusions: Proper level of antioxidants may protect hearing. Glutathione and antioxodative enzymes may protect hearing organ against damages caused by free radicals. Lower level of the antioxidants and associated intensificaation of lipids peroxidation processes may increase free radicals-associated damages and lead to hearing organ dysfunction

Change of the State of the Natural Antioxidant Barrier of a Body and Psychological Parameters in Patients Aged above 60

Background. The goal of this study is to assess the natural antioxidant barrier of the organism and selected psychological aspects of the aging process in patients above 60 years old. Methods. The study included a total of 52 patients aged above 60 (mean age 67 ± 3.4) and 32 healthy subjects (mean age 22 ± 3.4) as a control group. All patients underwent psychological assessment using Test of Attentional Performance version 2.3 (TAP 2.3, four subtests: alertness, cross-modal integration, neglect with central task, and working memory) and biochemical analysis of venous blood concerning values of the selected parameters of oxidative stress (HT, GSH, GPXOS, GPXRBC, GRRBC1, SODRBC1, MDARBC1, NO2−/NO3−, and CP). Results. Disorders of attention were observed mainly in elderly people, but an assumption that elderly people have developed more efficient ways of working memory use than younger people may be true. Results showed the reduced effectiveness of the body’s natural antioxidant barrier in elderly people. Moderate positive and negative correlations among parameters of oxidative stress and psychological parameters were observed in the control group. Discussion. Intensification of the attention deficits and oxidative stress may be observed as one of the pathogenic factors of age-dependent diseases

Application of ELISA Technique and Human Microsomes in the Search for 11β-Hydroxysteroid Dehydrogenase Inhibitors

The metabolic syndrome is defined by impaired carbohydrate metabolism and lipid disorders and often accompanied by hypertension, all of which will lead to obesity and insulin resistance. Glucocorticoids play a regulatory role in the metabolism of proteins, lipids, and carbohydrates. There is growing evidence for a role of glucocorticoids in the development of the metabolic syndrome. The most important factor that regulates the access of endogenous glucocorticoids to receptors after release of glucocorticoids and their diffusion into the cytoplasm of target cells is the steroid metabolism involving a microsomal enzyme, 11β-hydroxysteroid dehydrogenase (11β-HSD). The changes in intracellular glucocorticoid metabolism in the pathogenesis of obesity indicate the participation of modulation by 11β-HSD1, which may represent a new therapeutic target for the treatment of diseases such as type 2 diabetes, visceral obesity, or atherosclerosis. The aim of our study was to determine the fast and effective method to assess inhibition activity of compounds in relation with 11β-hydroxysteroid dehydrogenase. The material for this study was human liver and kidney microsomes. In this study we used ELISA technique using 96-well microplates coated with antibodies which were specific for analyzed enzymes. The method can quickly and efficiently measure the inhibition of both 11β-HSD1 and 11β-HSD2. This method can be used to search for and determine inhibitors of this enzyme. Cortisone and cortisol were used as the substrates for corresponding enzyme assays. Furthermore, 3-N-allyl-2-thiouracil derivatives were used by us for comparison purposes in developing the method, although, due to their structure, those derivatives have not previously been considered as potential inhibitors of 11β-HSD1. 3-N-Allyl-2-thiouracil derivatives are a group worth considering, because by modifying their structure (e.g., by introducing other substituents into the pyrimidine ring) it will be possible to obtain an increase in the activity of compounds in this regard. In conclusion, this study shows an efficient and fast method of determining inhibition activity of compounds in relation with 11β-hydroxysteroid dehydrogenase

11&beta;-Hydroxysteroid Dehydrogenase Type 1 as a Potential Treatment Target in Cardiovascular Diseases

Glucocorticoids (GCs) belong to the group of steroid hormones. Their representative in humans is cortisol. GCs are involved in most physiological processes of the body and play a significant role in important biological processes, including reproduction, growth, immune responses, metabolism, maintenance of water and electrolyte balance, functioning of the central nervous system and the cardiovascular system. The availability of cortisol to the glucocorticoid receptor is locally controlled by the enzyme 11&beta;-hydroxysteroid dehydrogenase type 1 (11&beta;-HSD1). Evidence of changes in intracellular GC metabolism in the pathogenesis of obesity, metabolic syndrome (MetS) and cardiovascular complications highlights the role of selective 11&beta;-HSD1 inhibition in the pharmacotherapy of these diseases. This paper discusses the role of 11&beta;-HSD1 in MetS and its cardiovascular complications and the importance of selective inhibition of 11&beta;-HSD1

The Oxime Ethers with Heterocyclic, Alicyclic and Aromatic Moiety as Potential Anti-Cancer Agents

Chemotherapy is one of the most commonly used methods of cancer disease treatment. Due to the acquisition of drug resistance and the possibility of cancer recurrence, there is an urgent need to search for new molecules that would be more effective in destroying cancer cells. In this study, 1-(benzofuran-2-yl)ethan-1-one oxime and 26 oxime ethers containing heterocyclic, alicyclic or aromatic moiety were screened for their cytotoxicity against HeLa cancer cell line. The most promising derivatives with potential antitumor activity were 2-(cyclohexylideneaminoxy)acetic acid (18) and (E)-acetophenone O-2-morpholinoethyl oxime (22), which reduced the viability of HeLa cells below 20% of control at concentrations of 100–250 μg/mL. Some oxime ethers, namely thiazole and benzothiophene derivatives (24–27), also reduced HeLa cell viability at similar concentrations but with lower efficiency. Further cytotoxicity evaluation confirmed the specific toxicity of (E)-acetophenone O-2-morpholinoethyl oxime (22) against A-549, Caco-2, and HeLa cancer cells, with an EC50 around 7 μg/mL (30 μM). The most potent and specific compound was (E)-1-(benzothiophene-2-yl)ethanone O-4-methoxybenzyl oxime (27), which was selective for Caco-2 (with EC50 116 μg/mL) and HeLa (with EC50 28 μg/mL) cells. Considering the bioavailability parameters, the tested derivatives meet the criteria for good absorption and permeation. The presented results allow us to conclude that oxime ethers deserve more scientific attention and further research on their chemotherapeutic activity