Historical ferrous slag induces modern environmental problems in the Moravian Karst (Czech Republic).

Ferrous slag produced by a historic smelter is washed from a slagheap and transported by a creek through a cave system. Slag filling cave spaces, abrasion of cave walls / calcite speleothems, and contamination of the aquatic environment with heavy metals and other toxic components are concerns. We characterize the slag in its deposition site, map its transport through the cave system, characterize the effect of slag transport, and evaluate the risks to both cave and aqueous environments. The study was based on chemical and phase analysis supported laboratory experiments and geochemical modeling. The slag in the slagheap was dominated by amorphous glass phase (66 to 99 wt%) with mean composition of 49.8 ± 2.8 wt% SiO2, 29.9 ± 1.6 wt% CaO, 13.4 ± 1.2 wt% Al2O3, 2.7 ± 0.3 wt% K2O, and 1.2 ± 0.1 wt% MgO. Minerals such as melilite, plagioclase, anorthite, and wollastonite / pseudowollastonite with lower amounts of quartz, cristobalite, and calcite were detected. Slag enriches the cave environment with Se, As, W, Y, U, Be, Cs, Sc, Cd, Hf, Ba, Th, Cr, Zr, Zn, and V. However, only Zr, V, Co, and As exceed the specified limits for soils (US EPA and EU limits). The dissolution lifetime of a 1 mm3 volume of slag was estimated to be 27,000 years, whereas the mean residence time of the slag in the cave is much shorter, defined by a flood frequency of ca. 47 years. Consequently, the extent of slag weathering and contamination of cave environment by slag weathering products is small under given conditions. However, slag enriched in U and Th can increase radon production as a result of alpha decay. The slag has an abrasive effect on surrounding rocks and disintegrated slag can contaminate calcite speleothems.

Movement disorders, cerebral palsy and vaccination.

This review focused on vaccination in children with movement disorders, including cerebral palsy and the movement disorders triggered by vaccination in children with and without neurological disabilities. The following clinical questions were addressed: 1) Can children with movement disorders be vaccinated? 2) Can vaccination trigger movement disorders in children without neurological disabilities? 3) Can vaccination trigger movement disorders in children with neurological disabilities? and 4) Is there any consensus of care concerning vaccination in children with movement disorders? Following the PRISMA reporting guidelines, 1096 records were identified and 34 relevant papers were included. No evidence that vaccinations are contraindicated for children with movement disorders was noticed. Several reports of neurological adverse events, including movement disorders in children without neurological disabilities after various types of vaccination, were found. The reporting rates were low, the causality was controversial, and patient outcomes were mostly favourable. There was limited (if any) evidence in our search that any vaccination leads to any movement disorder exacerbation. Finally, no generally accepted consensus or standards of care concerning vaccination in patients with movement disorders were found. In summary, we found few precautions for vaccination in this group of patients and concluded that general best practice guidelines for immunization should be followed. In addition, influenza and pneumococcal vaccines are recommended because they can reduce morbidity and mortality in individuals severely affected by movement restrictions.

Cardioprotective effect of 2,3-dehydrosilybin preconditioning in isolated rat heart.

2,3-dehydrosilybin (DHS) is a minor component of silymarin, Silybum marianum seed extract, used in some dietary supplements. One of the most promising activities of this compound is its anticancer and cardioprotective activity that results, at least partially, from its cytoprotective, antioxidant, and chemopreventive properties. The present study investigated the cardioprotective effects of DHS in myocardial ischemia and reperfusion injury in rats. Isolated hearts were perfused by the Langendorff technique with low dose DHS (100 nM) prior to 30 min of ischemia induced by coronary artery occlusion. After 60 min of coronary reperfusion infarct size was determined by triphenyltetrazolium staining, while lactatedehydrogenase activity was evaluated in perfusate samples collected at several timepoints during the entire perfusion procedure. Signalosomes were isolated from a heart tissue after reperfusion and involved signalling proteins were detected. DHS reduced the extent of infarction compared with untreated control hearts at low concentration; infarct size as proportion of ischemic risk zone was 7.47 ±â€¯3.1% for DHS versus 75.3 ±â€¯4.8% for ischemia. This protective effect was comparable to infarct limitation induced by ischemic preconditioning (22.3 ±â€¯4.5%). Selective inhibition of Src-family kinases with PP2 (4-Amino-3-(4-chlorophenyl)-1-(t-butyl)-1H-pyrazolo[3,4-d]pyrimidine) abrogated the protection afforded by DHS. This study provides experimental evidence that DHS can mediate Src-kinase-dependent cardioprotection against myocardial damage produced by ischemia/reperfusion injury.

Silymarin Constituent 2,3-Dehydrosilybin Triggers Reserpine-Sensitive Positive Inotropic Effect in Perfused Rat Heart.

2,3-dehydrosilybin (DHS) is a minor flavonolignan component of Silybum marianum seed extract known for its hepatoprotective activity. Recently we identified DHS as a potentially cardioprotective substance during hypoxia/reoxygenation in isolated neonatal rat cardiomyocytes. This is the first report of positive inotropic effect of DHS on perfused adult rat heart. When applied to perfused adult rat heart, DHS caused a dose-dependent inotropic effect resembling that of catecholamines. The effect was apparent with DHS concentration as low as 10 nM. Suspecting direct interaction with ß-adrenergic receptors, we tested whether DHS can trigger ß agonist-dependent gene transcription in a model cell line. While DHS alone was unable to trigger ß agonist-dependent gene transcription, it enhanced the effect of isoproterenol, a known unspecific ß agonist. Further tests confirmed that DHS could not induce cAMP accumulation in isolated neonatal rat cardiomyocytes even though high concentrations (≥ 10 µM) of DHS were capable of decreasing phosphodiesterase activity. Pre-treatment of rats with reserpine, an indole alkaloid which depletes catecholamines from peripheral sympathetic nerve endings, abolished the DHS inotropic effect in perfused hearts. Our data suggest that DHS causes the inotropic effect without acting as a ß agonist. Hence we identify DHS as a novel inotropic agent.

Effect of pomiferin administration on kidney ischaemia-reperfusion injury in rats.

The aim of the study was to analyse protective effects of different doses of pomiferin in therapy of reperfusion injury. Rats were randomly divided into five groups (n=10). One group was intact. Three medicated groups and one placebo group were subjected to ischaemia and reperfusion of the left kidney. Pomiferin was administrated by single gastric gavage in 2 ml of 0.5% Avicel solution in doses of 5, 10 and 20 mg/kg. The placebo group was given only Avicel solution. On day 15, all the animals were exsanguinated and the reperfused kidneys were recovered. Selected biochemical markers were assessed in blood: antioxidative enzymes, total antioxidative capacity, malondialdehyde, creatinine, urea and uric acid. Creatinine, urea and total proteins were analysed in urine and 24-hour diuresis was recorded. The kidney tissue samples were used for histopathological examination.The results confirmed the expected protective effects of pomiferin. Pomiferin supported defensive reactions of the body against free radicals (increased levels of superoxide dismutase, total antioxidative capacity), decreased lipid peroxidation (decreased malondialdehyde) and contributed to the recovery of kidney functions (creatinine and urea in blood). The best biochemical and histopathological results were achieved after pomiferin administration in the dose of 5 mg/kg.

Changes in biomechanical parameters during heart perfusion and after midazolam pre-medication--experimental pilot study.

BACKGROUND: Midazolam is a frequently used benzodiazepine in anaesthesiology and intensive care. AIM: The aim of pilot study was to monitor its effect during heart perfusion in the laboratory rat. METHODS: The same groups of animals (n = 10). The 1(st) group was treated with midazolam in a dose of 0.5mg/kg i.p. The 2(nd) group was a placebo. After i.p. administration of heparine injection of 500 IU dose, the hearts were excised and perfused (modified Langendorf's method). Working schedule: stabilization/ischaemia/reperfusion proceed at intervals of 20/30/60 min. Monitored parameters in isolated heart: left ventricle pressure (LVP), end-diastolic pressure (LVEDP), contractility (+dP/dt(max)). RESULTS: The treated hearts showed improved postischemic recovery, reaching LVP values of 92 +/- 6 % at the end of the reperfusion, placebo only 61 +/- 7 %. In placebo hearts LVEDP rose from 10.0 +/- 0.5 mmHg to 43 +/- 4 mmHg after, in treated animals only about 25 mmHg. The treated hearts improved +dP/dt(max) recovery during reperfusion to 91 +/- 8 %. These values were significantly greater than those obtained from the placebo hearts. CONCLUSIONS: Positive changes in monitored parameters were found in this experimental pilot study. We conclude that the administration of midazolam in laboratory rats has a cardioprotective potential against ischemia-reperfusion induced injury.

Effects of prenylated isoflavones osajin and pomiferin in premedication on heart ischemia-reperfusion.

The present 15 days study was undertaken to evaluate the cardioprotective potential of the prenylated isoflavones osajin and pomiferin isolated from the infructences of Maclura pomifera, Moraceae, against ischemia-reperfusion induced injury in rat hearts as a model of antioxidant-based composite therapy. The study was performed on isolated, modified Langendorff-perfused rat hearts and the ischemia of heart was induced by stopping coronary flow for 30 min followed by 60 min of reperfusion (14 ml min(-1)). The Wistar rats were divided into four groups. The first treatment group received osajin (5 mg/kg/day in 0.5% Avicel); the second treatment group received pomiferin (5 mg/kg/day in 0.5% Avicel); the placebo group received only 0.5 Avicel; the last was an untreated control group. Biochemical indicator of oxidative damage-lipid peroxidation product malondialdehyde, antioxidant enzymes - superoxide dismutase, glutathione peroxidase, total antioxidant activity in serum and myocardium were evaluated. The effect of osajin and pomiferin on cardiac function, left ventricular end-diastolic pressure, left ventricular pressure and peak positive +dP/dt ischemia and reperfusion, also was examined. The results demonstrate that osajin and pomiferin attenuates the myocardial dysfunction provoked by ischemiareperfusion. This was confirmed by an increase in both antioxidant enzyme values and total antioxidant activity. The cardioprotection provided by osajin and pomiferin treatment results from the suppression of oxidative stress and this correlates with improved ventricular function.

Effect of a new ultrashort betalytic agent on aconitine-induced arrhythmia.

The anti-arrhythmic effect was tested on the model of aconitine-induced arrhythmia. The experiment was performed in vivo with 31 male Wistar laboratory rats. Group A was first administered aconitine and, after the onset of the first sinus rhythm disorders, the 44Bu compound was administered. Group B was first administered the 44Bu compound and only after that the aconitine. The control group was administered aconitine and saline as a replacement of the tested compound. In group A, there was a decrease in the ventricular fibrillation occurrence from 100 % to 8 % (p < 0.001) after the administration of the 44Bu compound. In the B group, the onsets of all monitored arrhythmia types were delayed by an average of 15.6 min. Ventricular rhythm occurrence was decreased from 100 to 20 %, as well as ventricular fibrillations, from 100 to 0 % (p < 0.001).

Influence of antioxidant effect of stobadine derivative in condition of kidney ischemia-reperfusion in a pre-clinical experiment (effect in therapy).

The goal of the study was to monitor the antioxidative effect of stobadine derivative under conditions of ischemia-reperfusion of laboratory rat kidney tissue. 40 animals were subjected to kidney tissue ischemia (60 min) followed by reperfusion (10 min). After that, the animals were divided by random selection into 4 groups (n = 10). The treated groups were given stobadine derivative in peroral doses of 5, 10 and 20 mg/kg in 0.5% solution of Avicel once a day, the placebo group was given only the solution of Avicel. One group (n = 10) was an intact group (without ischemia-reperfusion and without treatment), for comparison. Once a week, selected laboratory parameters were determined in all animals. On the 15th day the animals were exsanquined and organs were recovered for histopathological examination. We discovered a statistically significant changes of the superoxiddismutase and glutathione peroxidase catalytic activity; changes of total antioxidative capacity and malondialdehyde in the treated groups compared to the groups of placebo and intact. Other examined laboratory parameters (creatinine, urea and uric acid in blood; creatinine, urea, total protein in urine; diuresis) exhibited significant changes too. The results of biochemical examination show a protective antioxidative effect of the compound studied. The results of histopathological examination support this assumption.

Influence of antioxidant effect of stobadine derivative in condition of kidney ischemia-reperfusion in a pre-clinical experiment (effect in prophylaxis).

The goal of the study was to monitor the antioxidative effect of stobadine derivative in the conditions of ischemia-reperfusion of laboratory rat kidney tissue. The animals were divided by random selection into 5 groups (n = 10). The treated groups were given stobadine derivate in peroral doses of 5, 10 and 20 mg/kg in 0.5 % solution of Avicel once a day; the placebo group was given only the solution of Avicel. The last group was an intact group (without ischemia-reperfusion and without treatment). After conclusion of medication on the 15th day all animals were subjected to kidney tissue ischemia (60 min.) followed by reperfusion (10 min.). All animals were subsequently exsanquined and single identification of superoxiddismutase, glutathion peroxidase, total antioxidative capacity, and malondialdehyde level in the blood were determined. Kidneys were recovered for histopathological examination. A statistically significant decrease of the superoxiddismutase and statistically significant increase of the glutathione peroxidase catalytic activity in the treated groups compared to the groups of placebo and intact was discovered. There was also a statistically highly significant increase of total antioxidative capacity in the treated groups compared to the groups of placebo and intact. A statistically significant decrease of malondialdehyde level was identified in the treated groups compared to the groups of placebo and intact. The results of biochemical examination show a protective antioxidative effect of stobadine derivative. The results of histopathological examination support this assumption.