The effect of bariatric-metabolic surgery on selected components of metabolic syndrome and visceral adipose tissue - the pilot study.

The aim of this study was to monitor changes in the components of the metabolic syndrome defined by Adult Treatment Panel III and the risk of adipose tissue. The study population consisted of 45 patients (30 women, 15 men) who underwent one bariatric procedure - partial jejuno-ileal derivation (n=17), sleeve resection (n=14) or laparoscopic gastric - plication (n=14). Components of metabolic syndrome such as waist circumference, morning glycemia/antihypertension, TAG, HDL cholesterol and blood pressure (BP)/antihypertension were monitored in probands. In addition, Dual Energy X-Ray Absorciometry measurements were performed. Parameters were monitored over the course of one year. The study shows that it is an effective method of weight reduction for the study population with metabolic effects in the risk components of metabolic syndrome - fasting glycemia, increase in HDL cholesterol and reduction in triacylglycerols in the blood, reduction in waist circumference and BP or direct disappearance of metabolic syndrome. Significantly, of the entire cohort, 68.9 % of the probands studied showed signs of metabolic syndrome when measured before the intervention. At the end of follow-up, only 22.2 % of probands showed metabolic syndrome. It was also found that if the amount of visceral fat was reduced, the overall risk of metabolic syndrome was also reduced. The study demonstrates a significant positive effect of bariatric surgery on parameters of metabolic syndrome. The study also showed a positive effect of reduced visceral fat volume on the components of metabolic syndrome.

Partial magnetic jejunal diversion (PMJD) in severely obese patients.

Most patients with type 2 diabetes mellitus suffer from obesity. Studies show that surgical intervention is a suitable method for the improvement or remission of type 2 diabetes mellitus. However, a very small percentage of the total number of obese patients (diabetics in addition) undergo surgery. For this reason, less invasive endoscopic methods appear to be an appropriate alternative. The primary aim of a pilot study of partial jejunal diversion using the SFM (Self-Forming Magnetic) device for the creation of jejuno-ileal anastomosis was to verify the technical feasibility and safety of the new procedure. Secondary goals included achieving weight reduction and improving metabolic parameters in patients with type II diabetes. Key words.

One-year measurements of chloroethenes in tree cores and groundwater at the SAP Mimon Site, Northern Bohemia.

Chlorinated ethenes (CE) are among the most frequent contaminants of soil and groundwater in the Czech Republic. Because conventional methods of subsurface contamination investigation are costly and technically complicated, attention is directed on alternative and innovative field sampling methods. One promising method is sampling of tree cores (plugs of woody tissue extracted from a host tree). Volatile organic compounds can enter into the trunks and other tissues of trees through their root systems. An analysis of the tree core can thus serve as an indicator of the subsurface contamination. Four areas of interest were chosen at the experimental site with CE groundwater contamination and observed fluctuations in groundwater concentrations. CE concentrations in groundwater and tree cores were observed for a 1-year period. The aim was to determine how the CE concentrations in obtained tree core samples correlate with the level of contamination of groundwater. Other factors which can affect the transfer of contaminants from groundwater to wood were also monitored and evaluated (e.g., tree species and age, level of groundwater table, river flow in the nearby Ploucnice River, seasonal effects, and the effect of the remediation technology operation). Factors that may affect the concentration of CE in wood were identified. The groundwater table level, tree species, and the intensity of transpiration appeared to be the main factors within the framework of the experiment. Obtained values documented that the results of tree core analyses can be used to indicate the presence of CE in the subsurface. The results may also be helpful to identify the best sampling period for tree coring and to learn about the time it takes until tree core concentrations react to changes in groundwater conditions. Interval sampling of tree cores revealed possible preservation of the contaminant in the wood of trees.

Cardiac troponin T following repeated administration of pyridoxal isonicotinoyl hydrazone in rabbits.

Pyridoxal isonicotinoyl hydrazone (PIH) is a new tridentate Fe-chelating agent that should be very promising in many pathological states resulting from both an iron-overload and formation of free radicals. The aim of our study was to investigate the effect of PIH on the cardiovascular system focusing to the regulatory protein -- cardiac troponin T (cTnT). The study was carried out in two groups of Chinchilla male rabbits: 1) PIH (50 mg/kg dissolved in 10 % Cremophor i.p., once a week, 10 administrations, n=8) and 2) Cremophor (2 ml/kg i.p. in the same schedule, n=7). Plasma concentrations of cTnT (as a marker of myocardial damage) were measured using a commercial kit (Roche). cTnT was within the physiological range (i.e. < 0.1 microg/l) during the whole experiment in the Cremophor group. In the PIH group, the cTnT levels were not significantly increased when compared with the control group or with the initial values (except with those before the 5th administration). Furthermore, we analyzed the cytosolic and myofibrillar fraction of cTnT in the left ventricular myocardium. Using SDS-PAGE and Western blot we resolved three isoforms. The profiling of TnT did not differ significantly between the PIH-treated group and the Cremophor-treated group. Our data concerning cTnT support the opinion that the possible cardiotoxicity of PIH is very low.

Evaluation of cardiac effects of the new antineoplastic drug --dimethoxybenfluron--in the rabbit.

Cardiotoxicity ranks among the most serious adverse effects of some cytostatics. The cardiac effects of repeated i.v. administration of a new antineoplastic agent, dimethoxybenfluron (once a week, 10 administrations), were investigated in rabbits with respect to cardiac function and the release of cardiac troponin T (cTnT). Different doses of dimethoxybenfluron were administered to two groups of animals (12 mg/kg; n = 7 and 24 mg/kg; n = 6) and compared with either a control group (saline 1 ml/kg; n = 6) or a group with experimentally induced cardiomyopathy (daunorubicin 50 mg/m2; n = 13). In daunorubicin-induced cardiomyopathy, cTnT levels in animals with premature deaths were significantly higher (0.31 +/-0.11 microg/l) in comparison with the surviving animals (0.04 +/- 0.03 microg/l). However, cardiac TnT levels after the administration of dimethoxybenfluron in both doses were within the physiological range (lower than 0.1 microg/l) during the whole experiment as it was in the control group. The lack of cardiotoxicity of this new antineoplastic drug was supported by the absence of alterations in PEP:LVET ratio, left ventricle dP/dtmax or histological heart examination as well as by the fact that no premature death of animals occurred following repeated administration of dimethoxybenfluron. It is possible to conclude that no signs of cardiotoxicity were observed following repeated i.v. administration of dimethoxybenfluron.

[Plasma levels of troponin T in rabbits after administration of new antineoplastic agents (Oracin and Dimefluron) and daunorubicin]. / Plazmatické hladiny troponinu T u králíku po podání nových antineoplastických látek (Oracinu a Dimefluronu) s daunorubicinem.

Recently, cardiac troponin T (cTnT) has been shown to be a sensitive marker of anthracycline-induced cardiomyopathy. In our study, the cardiotoxicity of repeated i.v. administration (once a week, 10 administrations) of daunorubicin combined with new antineoplastic drugs (with mild side-effects) were followed in two groups of rabbits: 1) Dimefluron (3,9-dimethoxybenfluron hydrochloride-12 mg/kg) + daunorubicin (3 mg/kg), 2) Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride--10 mg/kg) + daunorubicin (3 mg/kg) and compared with the control group (saline--1 ml/kg) and the group with experimentally induced cardiomyopathy (daunorubicin--3 mg/kg). The concentration of cTnT in heparinized plasma samples was measured using commercial kit (Roche). In the control group, plasma levels of cTnT were always within the physiological range (i.e. lower than 0.1 microgram/l) during the experiment. During the development of daunorubicin-induced cardiomyopathy, after the eighth administration of drug, cTnT was significantly higher (0.31 +/- 0.11 microgram/l) in animals with premature deaths compared with the rest of the group (0.04 +/- 0.03 microgram/l). The animals with pathological values of cTnT were at higher risk of premature deaths (P = 0.0006). The combination of daunorubicin either with Oracin or with Dimefluron caused neither significant changes of cTnT levels nor significant deterioration of other followed-up parameters (especially, functional and toxicological parameters). Similarly to the daunorubicin group, the animals with pathological levels of cTnT after the eighth administration of antineoplastic drugs were at higher risk of premature death (P = 0.025). Our results show that the plasma concentration of cardiac troponin T could be a suitable predictive marker of cardiotoxicity of antineoplastic drugs.

Anthracycline-induced cardiotoxicity.

Anthracycline antibiotics are among the most effective and widely used antineoplastic drugs. Their usefulness is limited by a cumulative dose-related cardiotoxicity, whose precise mechanisms are not clear as yet. The principal role is possibly exerted by free oxygen radicals generated by "redox-cycling" of anthracycline molecule and/or by the formation of anthracycline-ferric ion complexes. The iron catalyzes the hydroxyl radical production via Haber-Weiss reaction. The selective toxicity of ANT against cardiomyocytes results from high accumulation of ANT in cardiac tissue, appreciable production of oxygen radicals by mitochondria and relatively poor antioxidant defense systems. Other additional mechanisms of the anthracycline cardiotoxicity have been proposed--calcium overload, histamine release and impairment in autonomic regulation of heart function. The currently used methods for an early identification of anthracycline cardiotoxicity comprise ECG measurement, biochemical markers, functional measurement and morphologic examination. Among a plenty of studied cardioprotective agents only dexrazoxane (ICRF-187) has been approved for clinical use. Its protective effect likely consists in intracellular chelating of iron. However, in high doses dexrazoxane itself may cause myelotoxicity. This fact encourages investigation of new cardioprotectants with lower toxicity. Orally active iron chelators and flavonoids attract more attention. Modification of dosage schedule and synthesis of new anthracycline analogues may represent alternative approaches to mitigate anthracycline cardiotoxicity while preserving antitumour activity.

[Effects of new antineoplastic agents (dimethoxybenflurone and Oracin) on the cardiovascular system and other parameters in the rabbit in vivo]. / Ucinky nových antineoplastických látek (dimethoxybenfluronu a Oracinu) na kardiovaskulární systém a dalsí parametry u králíku in vivo.

Anthracycline derivatives belong among the most effective antineoplastic drugs but their therapeutic use is limited by their side effects--a dose-related cardiotoxicity. The influence of repeated i.v. administration (once weekly, max. 10 weeks) of new antineoplastic agents--dimethoxybenfluron (DMB) (3,9-dimethoxybenfluron hydrochloride, C23H24O4NCl, M.w. 413.9, Institute of Experimental Biopharmaceutics, Czech Academy of Sciences, Hradec Králové, Czech Republic; 12 or 24 mg base/kg) and Oracin (6-[2-(2-hydroxyethyl)aminoethyl]-5,11-dioxo-5,6-dihydro-11H- indeno[1,2c]isoquinoline hydrochloride), C20H19N2O3Cl, M.w. 370.84, Research Institute for Pharmacy and Biochemistry, Prague, Czech Republic; 5 or 10 mg/kg) on cardiovascular, biochemical, haematological and histological parameters were studied in rabbits in vivo. Data obtained in these groups were compared with the group with experimentally induced cardiomyopathy (daunorubicin 50 mg/m2 i.v.) and with the control group (saline 1 ml/kg). Only mild and mostly no significant changes of the cardiovascular parameters (DMB 12 group: PEP:LVET ratio--0.408-0.502, LV dP/dtmax.--1337.0 kPa/s; DMB 24 group: PEP:LVET ratio--0.407-0.433, LV dP/dtmax.--1438.2 kPa/s), biochemical parameters (decrease in natrium, ALP and increase in glucose, GPX and GSH levels) and haematological parameters (increase in erythrocytes and decrease in leukocytes after the larger dose of the drug) were found in the dimethoxybenfluron groups. Repeated administration of the lower dose of Oracin induced only mild and mostly no significant changes of parameters (PEP:LVET ratio--0.393-0.475, LV dP/dtmax.--1092.4 kPa/s) in comparison with the control group. Though significant in some intervals, only a mild oscillation of the PEP:LVET ratio (0.368-0.446), decrease in LV dP/dtmax. (991.2 kPa/s) and--in comparison with control group--significantly higher blood pressure and lower heart rate were found after the higher dose of Oracin. In the most of haematological and biochemical parameters (with the exception of chlorides, protein and albumin levels) no significant changes were present. Histological examination of the heart revealed normal structure of the myocardium including minute changes of myocardium following administration of antineoplastic agents in all groups. Administration of new antineoplastic agents induced mostly mild changes of the followed-up parameters (PEP:LVET ratio, LV dP/dtmax., heart rate, levels of cardiac troponin T, survival of animals, haematological and biochemical parameters); the values of parameters were mostly significantly different from those in rabbits with daunorubicin-induced cardiomyopathy. On the basis of our results it is possible to conclude that the administration of dimethoxybenflurone and Oracin did not induce signs of cardiotoxicity in rabbits in vivo. This observation is considered to be important from the viewpoint of possible further clinical use of these new antineoplastic agents.

IGF-I in experimental daunorubicin-induced cardiomyopathy in rabbits.

1. The occurrence of IGF-I was investigated in rabbits with experimentally daunorubicin-induced cardiomyopathy. IGF-I was measured in the heart, serum, liver and skeletal muscle. 2. A significant increase in the IGF-I was found in the left heart ventricle in daunorubicin cardiomyopathy (152.9 +/- 10.0 ng/g vs 95.1 +/- 4.2 ng/g in the control group). This site of increased IGF-I activity corresponded well with the maximum of morphological changes (dispersed cytolysis of cardiomyocytes mostly without developed subsequent interstitial myofibrosis). 3. The highest levels of IGF-I were present in right and left cardiac atrium (but without significant differences between the groups). Furthermore, in skeletal muscle, the levels of IGF-I in the daunorubicin group (839.0 +/- 142.1 ng/g) were significantly higher in comparison with the control group (482.5 +/- 83.1 ng/g). 4. The level of IGF-I in the left ventricle in the daunorubicin group (but not in the control group) was significantly higher than that in the liver. There were no correlations observed between the levels of IGF-I in the heart and in the serum. 5. The increase in IGF-I concentrations in the left heart ventricle after the administration of daunorubicin may thus reflect possible autocrine/paracrine role of IGF-I in cardiomyopathy.

Cholinesterases in dexrazoxane-treated daunorubicin cardiomyopathy in rabbits.

Changes in cholinesterases activities in daunorubicin cardiomyopathy and in dexrazoxane (DRZX)-treated daunorubicin cardiomyopathy were investigated in rabbits. Acetyl- and butyrylcholinesterase (AChE and BuChE) were determined using Ellman's method. In the serum, a significant decrease of BuChE was observed in the daunorubicin group (9.05 at the beginning and 7.15 microcat/l at the end of the experiment). After DRZX, no significant changes were found and a significant increase in BuChE was observed in the control group (10.26-12.38 microcat/l). AChE activity in the left and right cardiac ventricles was not significantly different between the groups while in the septum there was a significantly lower AChE activity found in the daunorubicin group only. BuChE activity was significantly decreased in the left (15.64 ncat/g) and right (19.27 ncat/g) heart ventricles, in the septum and in the liver in the daunorubicin group. A significant decrease in serum total protein and albumin was demonstrated only in the daunorubicin group. Our results support the hypothesis about the influence of daunorubicin on protein (and enzyme) synthesis in the liver and heart. A protective effect of DRZX on cholinesterases activity was observed. The changes in cholinesterase activities may thus reflect their possible role in cardiomyopathy.

The influence of dimethoxybenfluron on biochemical and haematological parameters in rabbits.

The influence of repeated i.v. administration of dimethoxybenfluron (NO-1-B) (12 or 24 mg base/kg once weekly, 10 weeks) on biochemical and haematological parameters were studied in rabbits in vivo. No significant changes were mostly found in the serum ion levels between the dimethoxybenfluron and the control groups, as well as in most of other biochemical parameters (including total protein and albumin levels). Nevertheless, the lower dose of dimethoxybenfluron caused an increase in the glucose level. Furthermore, no significant changes were mostly present also in haematological parameters in the dimethoxybenfluron groups of rabbits (a mild decrease in thrombocytes and leucocytes). The results of our study support an assumption of good tolerance of dimethoxybenfluron from the viewpoint of its influence on biochemical and haematological parameters in rabbits and may be considered of importance for a possible therapeutic use of the derivatives.

Lichen ruber and bullous pemphigoid.

The authors describe the case of a male patient, 20 years old, with a rapidly developing picture of disseminated lichen ruber planus together with the formation of vesicles and blisters. Immunofluorescent examination demonstrated lichen ruber associated with bullous pemphigoid. A good therapeutic effect was obtained with a combination of Triamcinolon and Tigason.

The incidence of allergy to propolis in 605 consecutive patients patch tested in Prague.

605 consecutive patients were patch tested with the standard CDRG test series and with a 10% alcoholic solution of propolis. Positive allergic reactions to propolis were observed in 25 patients (4.2%); thirteen of them exhibited a simultaneous positive patch test to balsam of Peru. In view of the relatively high incidence of allergic reactions and the appearance of pseudo-cross-sensitivity to another common allergen, balsam of Peru, propolis should not be used in topical medicaments or as a component of cosmetic preparations.

Sacroiliac joints in chronic dermatoses.

In 34 patients with different chronic skin diseases (including eczemas, lichen ruber, erythrodermia, pyodermia, pemphigus erythematosus, vasculitis, parapsoriasis varioliformis, scleroderma adultorum Buschke, prophyria cutanea tarda, rosacea, dermatomyositis, erythematodes chronicus discoides and indurative tuberculosis), X-ray studies revealed sacroiliac-changes consistent with a low-grade inflammation. This oteoarthritis slightly differs from the patterns disclosed earlier by the same authors in psoriatic patients, lacking any clinical bone or joint symptoms. So far, it has not been possible to explain their nature, cause or development.