Possible explanation of the hemoglobin glycation index by the biokinetic model of glycation / A glikációs index lehetséges magyarázata a hemoglobinglikáció biokinetikus modellje alapján.

Összefoglaló. Bevezetés: A HbA1c integrált retrospektív mutatója az elmúlt idoszak vércukrának, rendszeres vizsgálata a cukorbetegek anyagcserekontrolljának megítélésében elengedhetetlen. Helyes értékelése azonban nem egyszeru, mert a HbA1c és a vércukor közötti összefüggés nem lineáris. A mérést közvetlenül megelozo hyperglykaemiás epizódok hatása a HbA1c szintjére nagyobb, mint azoké, amelyek régebben történtek. A jelenségre a glikáció biokinetikus modellje ad magyarázatot. Célkituzés: A mért és a biokinetikus modell alapján számított HbA1c közötti egyezés, illetve diszkordancia vizsgálata. Módszer: A vizsgálatokat 157, 1-es és 2-es típusú cukorbeteg 1793, laboratóriumban mért éhomi vércukor- és 511 HbA1c-adatából végeztük. A különbséget a glikációs index segítségével számítottuk, amely a mért és a számított HbA1c-érték aránya. Eredmények: Egyezést mindössze a vizsgált betegek kevesebb mint egyötödödében találtunk, 60%-ban az index értéke alacsony (<0,95) és 21%-ban magas (>1,05) volt. Az adatok részletes analízise szerint jó anyagcserekontroll esetében gyakoribb a vártnál magasabb, mért HbA1c-érték, mint a biokinetikus egyenlet által számítotté, és rosszabb kontroll (magasabb átlagos vércukor) esetében ez fordítva van. Egyezés esetén a regressziós egyenlet együtthatói gyakorlatilag azonosak a modell alapján számított értékekkel. Következtetés: Vizsgálataink felvetik azt a lehetoséget, hogy a biokinetikus modell magyarázatot adhat a vércukor és a HbA1c közötti diszkordanciára. Orv Hetil. 2021; 162(41): 1652-1657. INTRODUCTION: HbA1c is an integrated retrospective marker of previous blood glucose concentrations and its regular measurement is indispensable in the assessment of glycaemic compensation of diabetic patients. However, its proper interpretation is not simple becasuse the relationship between HbA1c and average glycemia is not a linear one. Hyperglycemic episodes occuring immediately before the measurement have greater impact on the HbA1c level as compared with those taking place earlier. OBJECTIVE: Assessment of concordance and discordance between measured and according to the biokinetic model calculated values of HbA1c. METHOD: The calculations were made from averages of 1793 fasting blood glucose and 511 HbA1c of 157, type 1 and 2 diabetic patients. The glycation index is the quotient between measured and calculated HbA1c. RESULTS: Agreement was found in less than one fifth of the 157 patients; in 60% the value of glycation was low (<0.95) and in 21% high (>1.05). Analysis of the glycation index according to the level of glycemic compensation revealed that in patients with good compensation, the measured HbA1c value was more often higher than the expected and in patients with unsatisfactory compensation the opposite was true. CONCLUSION: These results raise the possibility that the discordance between average glycemia and measured HbA1c can be explained by the biokinetic model. Orv Hetil. 2021; 162(41): 1652-1657.

Improvement of mortality prediction accuracy in critically ill patients through combination of SOFA and APACHE II score with markers of stress haematopoiesis.

INTRODUCTION: In critically ill patients nucleated red blood cells (NRBC) and immature granulocytes (IG) appear in the peripheral blood as the consequence of stress haematopoesis. The aim of this retrospective study was to evaluate the diagnostic value of NRBC and IG and to propose a model of improved mortality prediction including these parameters in the assessment of critically ill patients. METHODS: The study included 338 critically ill adult patients hospitalized at Department of Anaesthesiology and Intensive Medicine, Louis Pasteur University Hospital in Kosice. As NRBC positive patients were considered patients with peripheral NRBC > 0.01 × 109 /L and IG positivity as >0.03 × 109 /L. Apache II index was calculated 24 hours after admission and Systemic Organ Failure Assessment (SOFA) on the day with the worst clinical condition. RESULTS: NRBC positivity was found in 27.6% of patients. The mortality of NRBC positive patients was 48.38%, significantly higher than 23.7% of NRBC negative patients. IG positivity was 79.0% and their mortality was also higher as compared with that of IG negative patients (69.3% vs 33.8%). Three regression models predicting mortality including stress haematopoiesis markers, APACHE II, SOFA scores and age had sufficient level of sensitivity and specificity. CONCLUSION: The presence of NRBC in the peripheral blood and the IG increase are available early risk predictors of mortality in critically ill patients. Regression models designed by combination of SOFA, APACHE II, and the new haematological parameters increase the accuracy and effectivity of diagnostic process in predicting prognosis and risk of mortality with high sensitivity and specificity.

[Barriers of the initiation of insulin treatment in type 2 diabetic patients - conquering the "psychological insulin resistance"]. / Az inzulinkezelés elkezdésének gyakorlati akadályai 2-es típusú cukorbetegekben ­ a "pszichológiai inzulinrezisztencia" leküzdése.

Type 2 diabetes is a progressive disease and its consequence is the gradual decrease of endogenous insulin secretion to a very low level. Beyond this point, without insulin it is not possible to achieve proper metabolic compensation. The authors are trying to explain why the insulin therapy is often delayed in type 2 diabetic patients despite existing guidelines about its initiation and continuation. The causes of delay can be divided into two groups. One is the fear and disagreement of the patients (psychological insulin resistance - PIR) arising from different cognitive, emotional and other reasons. The second is the "clinical inertia", when the physicians are not able to explain in an effective and persuasive way the rationale and necessity of insulin treatment to their patients. The common background of both causes is the lack of sufficient knowledge about the pathogenesis of type 2 diabetes and the rationale of insulin treatment together with an insufficient level of communication between doctor and patient. The authors see the solution in the improvement of pre- and postgradual education of doctors and other health care providers (nurses, educators, psychologists), in their mutual cooperation and the translation of their knowledge towards a system of successful patient education. Orv Hetil. 2019; 160(3): 93-97.

Toluene abuse markers in marginalized populations.

Toluene abuse is one of the most common addictions among marginalized Roma. The aim of the study was the comparison of urinary toluene metabolite levels in marginalized population of Eastern Slovakia as compared to the majority population, and to verify the validity of the answers, given in the questionnaires, regarding toluene abuse. The study was carried out as part of the HEPA-META project aiming to map the prevalence of health problems in marginalized Roma. The majority of people living outside the area of the segregated Roma communities comprised the control group. The total number of study participants was 770. Statistically significant differences in the levels of hippuric acid and o-cresol were found between Roma and the majority population. Variations in urinary hippuric acid levels in addition to toluene abuse can be caused also by dietary factors, medical treatment as well as alcohol consumption, which is frequent (not only) in marginalized communities.

Can imprinting play a role in the response of Tetrahymena pyriformis to toxic substance exposure?

Among protozoa, Tetrahymena pyriformis is the most commonly ciliated model used for laboratory research. All living organisms need to adapt to ever changing adverse conditions in order to survive. This article focuses on the phenomenon that exposure to toxic doses of the toxicants protects against a normally harmful dose of the same stressor. This first encounter by toxicant provokes the phenomenon of epigenetical imprinting, by which the reaction of the cell is quantitatively modified. This modification is transmitted to the progeny generations. The experiments demonstrate the possibility of epigenetic effects at a unicellular level and call attention to the possibility that the character of unicellular organisms has changed through to the present day due to an enormous amount of non-physiological imprinter substances in their environment. The results point to the validity of epigenetic imprinting effects throughout the animal world. Imprinting in Tetrahymena was likely the first epigenetic phenomenon which was justified at cellular level. It is very useful for the unicellular organisms, as it helps to avoid dangerous molecules more easily or to find useful ones and by this contributes to the permanence of the population's life.

Lifetime exposure to low doses of lead in rats: effect on selected parameters of carbohydrate metabolism.

The aim of the study was to assess the effects of exposure to low doses of lead dissolved in drinking water (average daily dose of 2.2 mg kg(-1) day(-1)) on selected carbohydrate metabolism parameters in 20 wistar rats. Animals were divided into two groups - control (C) (group drinking clear water) and experimental group (Pb; group exposed to low doses of lead acetate in a concentration of 100 µmol l(-1) of drinking water). In this study, we studied the biochemical parameters (glucose, haemoglobin (Hb), glycated haemoglobin (HbA1c), lactate dehydrogenase (LDH) and amylase (AMS)) in rat blood. Glucose and Hb concentration and AMS activity decreased, LDH activity increased but HbA1c concentration levels did not change in rats exposed to lead. Our results well documented that lifetime exposure to lead affected carbohydrate metabolism of rats. Some parameters like concentration of Hb as well as activities of AMS and LDH are useful markers of intoxication of rats with lead. For the evaluation of results (e.g. AMS), not only the data at the end of the experiment should be taken into account but also the entire duration of trials (i.e. more time steps) that makes results more objective should be considered.

Changes of procalcitonin level in multiple trauma patients.

BACKGROUND: Some aspects of the pathophysiology of complications in multiple-trauma patients still remain unclear. Mediators of inflammation have been postulated as playing a key role in being responsible for life threatening complications of multiple trauma patients. The objective of this study was to evaluate the prognostic value of procalcitonin (PCT) level in multiple trauma patients. METHODS: A prospective study took place including patients with multiple trauma hospitalised in several hospital units. PCT level was measured in blood from 45 patients, aged 18-70 years using enzyme-linked immunoassay. The patients were divided into three groups: group I - individuals with multiple trauma with central nervous system injury; group II - those with multiple trauma without CNS injury; and group III - patients with isolated central nervous system injury. RESULTS: Initial PCT levels were below 0.5 ng mL(-1) regardless of the cause of trauma. In the 24th hour of observation, a statistically significant increase of PCT concentration vs. initial levels was recorded in all groups of patients. Then PCT levels decreased significantly at the 3rd measurement point in all groups, and they remained unchanged until the last measurement. The highest levels of PCT were observed in multiple trauma patients without CNS injury (group II). In this group of patients, a significantly longer duration of surgery in the post-trauma period affected PCT levels. PCT concentrations in patients who died were significantly greater than in survivors. CONCLUSIONS: A long lasting elevated concentration of procalcitonin in the post-traumatic period, or its repeated increase, is a good marker of developing complications observed earlier than clinical manifestations.

Flow cytometric analysis of the basophil cell activating impact of potential drug delivery nanoparticle-candidate.

INTRODUCTION: Carbon nanotubes ­ as artificial nano-size ranged materials ­have increasing role in the modern biomedical, diagnostic and therapeutic applications.There is a promising option for their use as more potential drug carriers. Despite the favourable properties, their impact (accumulation, elimination, etc.) on biological systems is largely unknown. The main limiting factor of medical use of nanomaterials in most cases is the potential hypersensitive side effect. It can develop in different route, but the activation of basophil granulocytes may play a central role in this process. OBJECTIVE: Our aim was to test the direct activation ability of different, surface modified nanotubes on basophil granulocytes in vitro. In parallel we tested the effectiveness of BasoTest planned to use for this study. MATERIALS AND METHODS: Using the blood samples of allergic and healthy volunteers we examined the basophil degranulation in the presence of nanotubes and the expression level changes of cell-surface CD63 on FACS Calibur instrument. Our results were compared to positive(fMLP, Mite, Grass) and negative control samples. RESULTS: The test we have chosen proved to be sufficiently sensitive and specific for further study. Significant basophil activation was observed in the presence of carbon nanotubes in healthy persons and allergic patients, as well. The activating effect of nanotubes was more prevailed in allergic population. CONCLUSION: Our experiments have proven the fact that nanotubes may play a role in the development of hypersensitive allergic reactions through their basophil granulocyte activator effect.

Effects of chronic low-dose cadmium exposure on selected biochemical and antioxidant parameters in rats.

The effects of long-term (1 yr) exposure to low doses of cadmium (Cd) dissolved in drinking water on selected biochemical and antioxidant parameters were studied in Wistar rats. Rats were divided into four groups: male control group (C-m), female control group (C-f), male Cd-exposed group (Cd-m), and female Cd-exposed group (Cd-f). Cd groups were exposed to Cd dissolved in drinking water (cadmium dichloride 4.8 mg CdCl2/L, i.e., 2.5 mg Cd/L, 500-fold of maximal allowable concentration for potable water). The experiment was terminated on d 370. In all groups, biochemical parameters (total protein [TP], albumin, alanine aminotransferase, aspartate aminotransferase, glucose, cholesterol, triacylglycerols, urea, and creatinine) and antioxidant parameters (glutathione peroxidase, superoxide dismutase, and total antioxidant capacity) were measured in the blood. Total protein and albumin concentrations were decreased significantly in the Cd-m group. Other biochemical parameters did not change in Cd groups compared to control groups. Superoxide dismutase fell significantly in both male and female Cd-exposed groups. Activity of glutathione peroxidase was markedly lower in Cd-exposed groups. Total antioxidant capacity increased significantly in Cd-f group. These results suggest that chronic low-dose oral Cd exposure induces oxidative stress.

Red cell antioxidant enzymes and prognostic indexes in patients with burns.

Red cell superoxide dismutase (SOD), glutathione peroxidase (GPX) and catalase (CAT) were measured in 66 burned patients (57 men, 9 women, age 16-78 years). BSAB varied from 15 to 93% and ABSI from 3 to 14 points. In the first week after injury the activity of SOD was significantly decreased as compared with the activity of the enzymes in the control group and was also below the reference values. Later the activity of SOD increased up to the normal range. The activity of CAT followed a similar pattern but the differences were not significant. No significant changes in red cell GPX were found during the monitored period. We did not find any significant association between the antioxidant enzyme activities and the markers of burns severity. On the other side there was a significant indirect association between the change of SOD activity (calculated as a difference between the first week values after the injury and the activities measured later) and BSAB.

Professor Frantisek Pór, MD--an outstanding internist in the former Czechoslovakia.

Professor Frantisek Pór, MD, (1899-1980) graduated at the German Medical Faculty of Charles University (GMF-CHU) in Prague in 1926. In January 26, 1945 he was captured, together with his wife, by the Gestapo and they were deported to the concentration camp to Sered' and later to Terezín (Czechoslovakia) from where they were liberated by the Soviet Army on May 8, 1945. He was a founder and the head of the Internal Clinic of the new Medical Faculty in Kosice, from October 1, 1948 until 1971. Professor Pór, MD created a school of internal medicine specialists in Eastern Slovakia and many of his co-workers achieved considerable success in internal medicine in Slovakia. He was the founder of Eastern Slovakian Medical Meetings in Nový Smokovec, in the High Tatras, in 1961, the 50th Meeting was held in 2011. Since 1994 the Medical Society in Kosice has organized an annual Meeting in his memory.

Determination of immunological stress and oxygen free radical formation in white blood cells during allergen immunotherapy.

BACKGROUND: Airway inflammation represents the basis of respiratory allergic disease and is generally associated with increased oxidative stress. As a consequence of successful treatment leading to hyposenzibilization and remission of symptoms, decrease of reactive oxygen formation is expected. MATERIAL/METHODS: This preliminary study evaluates the production of oxygen free radicals in white blood cells and changes in basic immunological parameters in a cohort of 50 patients (27 females and 23 males, age 14-48 years) with upper airway allergic inflammation caused by pollens, before and during specific immunotherapy. RESULTS: We found an unexpected significant increase in the free radical concentration during and after treatment in comparison to values before the treatment and to the control group. Statistical analysis also found significant increase of IgG3 after initial treatment and also 1 year after allergen immunotherapy. Although there were similar trends in the elevated ROS and elevated IgG3, these were not statistically significant. CONCLUSIONS: We observed changes in oxidative mechanisms in white blood cells of patients treated with AIT. Allergen immunotherapy works at a multilayer level and influences airway inflammation as well as the protective antimicrobial defense in treated patients. Further studies for understanding the mechanisms involved in oxidative stress as well as for laboratory monitoring of therapeutic approaches in allergic diseases are needed.

Age dependency on some physiological and biochemical parameters of male Wistar rats in controlled environment.

The aim of the study was to assess the age dependence on some physiological and serum chemistry parameters of male Wistar rats for the estimation of reference values in controlled environment. We are presenting values obtained from a large number of animals such as survival, average life span, body mass, food and water intake, serum chemistry parameters as total protein, albumin, transferrin and ferritin in serum. One part of this work compares the relationship between rat and human age. The maximal life span of our rats was determined to be about 4.4 years. The average life span was 3.75 years. The body weight quickly rose to the 85th week of life and then remained in the range of about 640-660 g up to the 163rd week when it began to decline. Food intake rose from the beginning to the maximum of about 39 g in the 33rd week and then decreased to about 20 g in the 163rd week. The water intake had a similar dynamics (about 43 mL in the 33rd week and 33 mL in the 163rd week). Levels of total protein in serum increased with age, in contrast, albumin levels decreased. Transferrin and ferritin decreased to approximately the 160th week of life and then increased.

Effect of lifetime low dose exposure to heavy metals on selected serum proteins of Wistar rats during three subsequent generations.

The aim of the study was to assess the effects of exposure to low doses of lead, cadmium and mercury dissolved in drinking water (at a concentration 200-fold of maximum allowable concentration) on selected serum proteins of 120 Wistar rats during three subsequent generations. Animals were divided into four groups in all observed generation-control (C) and three experimental groups exposed to low doses of heavy metals (lead acetate in concentration 100 µM; mercuric chloride in 1 µM; cadmium chloride in 20 µM of drinking water). We studied the biochemical parameters as well as total protein, albumin, transferrin and ferritin in the serum. Exposure to lead and mercury shortened life span, decreased body weight of the animals in each generation whereas cadmium had no such effect. Total protein increased after exposure to lead and mercury (P<0.001), albumin increased after exposure to lead and mercury in 1st filial and 2nd filial generation (P<0.05) and insignificantly decreased after exposure to cadmium in parental and 1st filial generation. Transferrin and ferritin increased in all exposed groups and generations (P<0.05). Transferrin and ferritin are good markers for intoxication of rats with heavy metals. For the results evaluation, not only data at the end of experiment should be taken into account, but entire duration of trials (i.e., more time steps), which makes results more objective.

Vitamin E-coated dialyzer and antioxidant defense parameters: three-month study.

Atherosclerotic cardiovascular disease is the most frequent cause of death in patients with end-stage renal disease who have undergone dialysis treatment. Oxidative stress, increased lipid peroxidation, and impaired function of antioxidant systems may contribute to the accelerated development of atherosclerosis in chronic renal failure patients during renal replacement therapy. The aim of this study was to investigate the influence of a vitamin E-coated dialyzer on antioxidant defense parameters in hemodialysis (HD) patients. In 14 HD patients, hemodialysis was performed using a vitamin E-coated dialyzer (Terumo CL-E15NL; Terumo Corporation, Tokyo, Japan) during a 3-month study. In these patients, erythrocyte (ER) antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX), glutathione reductase (GR) and catalase (CAT), plasma total antioxidant capacity (TAC), RBC glutathione (GSH), plasma malondialdehyde (MDA), plasma, and RBC vitamin E were investigated. Each parameter was measured at the beginning of the study, after the 1st, 2nd, and 3rd month of the study, and 10 weeks after the interruption of the use of vitamin E-coated dialyzer. All HD patients were treated by erythropoietin (EPO) and received vitamin C 50 mg/d, pyridoxine 20 mg/d, and folic acid 5 mg/wk during the entire study. The 3-month treatment with the vitamin E-coated dialyzer led to a significant decrease of plasma MDA level (from 2.85 +/- 0.44 to 2.25 +/- 0.37 micromol/L) and to an increase of plasma TAC, RBC, GSH, and the vitamin E levels both in plasma (from 25.9 +/- 2.8 to 33.6 +/- 3.8 micromol/L) and in the RBCs (from 6.7 +/- 0.8 to 7.4 +/- 0.7 micromol/L) by 30% and 10.5%, respectively. Ten-week interruption of the use of the vitamin E-coated dialyzer led to near initial values of MDA (2.90 +/- 0.28 micromol/L), plasma (28.6 +/- 3.5 micromol/L), and RBC (6.9 +/- 0.7 micromol/L) vitamin E and of other investigated parameters. Statistical analysis of results was performed by conventional methods and analysis of variance. The findings of the current study confirm the beneficial effect of the vitamin E-coated dialyzer against oxidative stress in HD patients.