Physicochemical Properties of Biochar Produced from Goldenrod Plants

Torrefaction is one of the methods of thermal treatment of biomass, which allows obtaining a product of better quality in the form of biochar. The aim of the paper was to analyze the possibility of using goldenrod (Solidago canadensis, Solidago gigantea) for the production of biochar. The torrefaction process involved the vegetative and generative parts as well as the whole plant at temperatures of 250 °C and 275 °C, for 3 h. Next, the physicochemical properties of the raw material and biochar were determined, namely moisture content, ash content, volatile matter content, calorific value, and heat of combustion. The bulk density of raw biomass and biochar was also determined. It was found that after biomass torrefaction, the ash content, calorific value, and heat of combustion increased, while volatile matter content decreased. It has been observed that in both the case of raw biomass and biochar, the plant species and the sampled parts have a significant impact on the ash content, volatile matter content, calorific value, and heat of combustion.     

Anionic block polymerization initiated by potassium solutions, 2. Synthesis of poly(2-oxetanone)-block-polystyrene-block-poly(2-oxetanone)

The block polymerization of styrene with 2-oxetanone (β-propiolactone) proceeds fast with a yield of more than 90%, in the presence of potassium solutions in THF containing 18-crown-6. Poly(2-oxetanone)-block-polystyrene-block-poly(2-oxetanone) ABA triblock polymers having the expected molecular mass and composition are formed. Their glass transition and melting temperatures as well as their melting enthalpies determined by DSC show a strict correlation with block polymer composition. The mechanism of this block polymerization involving acyloxygen and alkyl-oxygen bond scission in 2-oxetanone is in good agreement with previous results of the homopolymerization of β-lactones by alkali metal solutions abounding in potassium anions.     

In vitro and in vivo anticancer activity of mitozolomide and sparsomycin in human tumor xenografts,murine tumors and human bone marrow

Summary The colony formation in agar of human tumor xenografts, of murine tumors and of human bone marrow was used as a test system to determine the in vitro activity of the two novel cytostatic agents, mitozolomide and sparsomycin. Mitozolomide was additionally studied in vivo in nine human tumor xenografts. The comparison of in vitro/in vivo activity allows an assessment of the relevant in vitro dose based on in vivo pharmacological behavior of a compound. Both compounds showed clear dose/response effects in vitro. A dose of 3 g/ml mitozolomide, given by continuous exposure, was active (colony number of test <30% of the control group) in 12/42 (29%) human tumor xenografts as well as in the four murine tumors, P388, L1210, B16 melanoma and colon carcinoma 38, whereas the two human bone marrows showed no significant suppression of the ability to form colonies in culture. The comparison of in vitro with in vivo activity suggests that the in vitro dose of 3 g/ml corresponds best to the activity observed in animal experiments. The highest activity was observed in small-cell cancer of the lung (4/5), followed by melanomas (2/7) and non-small-cell cancer of the lung (2/9). Furthermore, activity was found in a cancer of the large bowel, stomach, breast and in one sarcoma. In the treatment of nine human tumor xenografts growing subcutaneously in nude mice, mitozolomide effected a complete or partial remission in 6 out of 9 tumors. In comparison to standard drugs mitozolomide is one of the most effective compounds in these tumors. These data indicate that mitozolomide possesses potent broad-spectrum activity in human tumor xenografts. Sparsomycin (0.1 g/ml, continuous exposure) was active in 11/46 (24%) human tumor xenografts and in 4/5 of the murine tumors, whereas the colony-forming capacity of four human bone-marrows showed no inhibition, suggesting that this dose level may be the relevant in vitro dose. However, the high in vitro activity in murine tumors is incompatible with the in vivo activity. In mice the only responsive tumor was leukemia P388, whereas the L1210, B16 melanoma and colon carcinoma 38 were resistant. At the dose level of 0.03 g/ml only 3/30 (10%) of the human tumor xenografts were sensitive. In an earlier clinical phase I study the dose-limiting adverse effect was eye toxicity and not bone-marrow suppression. This example illustrates that comparing in vitro with in vivo activity in the same tumor results in a more reliable estimation of the relevant in vitro dose than does comparing in vitro activity with in vitro effects on human bone marrow.Abbreviations Mitozolomide 8-carbamoyl-3-(2-chloroethyl)imidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one - NSC 353451 formerly known as azolastone - sparsomycin NSC 59 729 - DTIC 5-(3,3-dimethyltriazen-1-yl)-imidazole-4-carboxamide - MTIC 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide - DMSO dimethylsulfoxide Dedicated to Professor Dr. D. Schmähl, Heidelberg, on the occasion of his 65th birthday     

Flow-mediated dilation and gender in patients with coronary artery disease: arterial size influences gender differences in flow-mediated dilation

BACKGROUND: The risk of atherosclerosis and its complications differs between male and female subjects. This is probably associated with gender differences in endothelial function as reflected by endothelium-dependent vasodilation. The aim of the study was to compare flow-mediated dilatation (FMD) in males and females with coronary artery disease (CAD), and to determine factors that might potentially influence FMD. METHODS: Ninety-six patients with stable CAD (CCS II-III): 76 males (mean age: 57.7 +/- 10 years) and 20 postmenopausal females (mean age: 60.1 +/- 10 years) were included into the study. Clinical data, pharmacotherapy, concomitant diseases, and FMD were all assessed. FMD was measured with high-resolution ultrasound as the percent change of brachial artery diameter (BAd) after a 3-minute occlusion (%FMD), and following the administration of 0.4 mg sublingual nitroglycerin (%NTG-MD). RESULTS: The percentage of FMD was significantly decreased (P < 0.05), and BAd was significantly larger (P < 0.001) in males as compared to females. Clinical data, pharmacotherapy, and concomitant diseases were comparable in the study groups.In all subjects examined, %FMD was related to BAd (r =-0.415, P < 0.001) and the percentage of ejection fraction (EF%) (r = 0.325, P < 0.01) in the univariate analysis, and to BAd only (r =-0.343, P < 0.01) in the multivariate analysis. The percentage of nitroglycerine-mediated vasodilatation (NTG-MD) correlated negatively with BAd (r =-0.430, P < 0.001), and positively with EF% (r = 0.334, P < 0.01) in the univariate analysis, and with BAd (r =-0.288, P < 0.05) in the multivariate analysis. Index %FMD x BAd was comparable for male and female subjects. CONCLUSIONS: Males and postmenopausal females with CAD show differences in endothelium-dependent vasodilatation that seem to secondarily result from differences in the BAd. Objective comparison of %FMD is only possible between patients with the same brachial artery size.     

Neuroprotective effect of L-carnitine in the 3-nitropropionic acid (3-NPA)-evoked neurotoxicity in rats

A plant and fungal toxin, 3-NPA, acts as an inhibitor of mitochondrial function via irreversible inactivation of the mitochondrial inner membrane enzyme, succinate dehydrogenase (SDH). Inhibition of SDH disturbs electron transport and leads to cellular energy deficits and neuronal injury. We have shown that pretreatment with l-carnitine, while not significantly attenuating SDH inhibition, prevented hypothermia and oxidative stress-associated increased activity of free radical-scavenging enzymes. Here, a neurohistological method was applied to examine the effect of carnitine pretreatment against 3-NPA-induced neurotoxicity. Twenty adult male Sprague-Dawley rats were randomly divided into two groups (n = 10/group). Rats in the first group were injected twice with 3-NPA at 30 mg/kg s.c., 2 days apart, and the second group of animals received l-carnitine pretreatment at 100 mg/kg 30-40 min before 3-NPA administration. Rats in both groups were perfused 7 days later and their brains harvested. Degenerating neurons were identified and localized via the fluorescent marker Fluoro-Jade B. In the three animals that survived 3-NPA dosing, one exhibited no pathology, one exhibited moderate unilateral damage to the striatum, and the third exhibited extensive bilateral neuronal degeneration in multiple forebrain regions. In the seven surviving animals that received l-carnitine prior to 3-NPA insult, six exhibited no lesions, while one exhibited a modest unilateral lesion in the striatum. It appears that l-carnitine is protective against 3-NPA-induced toxicity, as reflected by both reduced mortality and significantly reduced neuronal degeneration.     

Acute metabolic responses to a 24-h ultra-marathon race in male amateur runners

The study was conducted to evaluate the metabolic responses to a 24 h ultra-endurance race in male runners. Paired venous and capillary blood samples from 14 athletes (mean age 43.0 ± 10.8 years, body weight 64.3 ± 7.2 kg, VO_2max 57.8 ± 6.1 ml kg⁻¹ min⁻¹), taken 3 h before the run, after completing the marathon distance (42.195 km), after 12 h, and at the finish of the race, were analyzed for blood morphology, acid–base balance and electrolytes, lipid profile, interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and serum enzyme activities. Mean distance covered during the race was 168.5 ± 23.1 km (range 125.2–218.5 km). Prolonged ultra-endurance exercise triggered immune and inflammatory responses, as evidenced by a twofold increase in total leukocyte count with neutrophils and monocytes as main contributors, nearly 30-fold increase in serum IL-6 and over 20-fold rise in hsCRP. A progressive exponential increase in mean creatine kinase activity up to the level 70-fold higher than the respective pre-race value, a several fold rise in serum activities of aspartate aminotransferase and alanine aminotransferase, and a fairly stable serum γ-glutamyl transferase level, were indicative of muscle, but not of liver damage. With duration of exercise, there was a progressive development of hyperventilation-induced hypocapnic alkalosis, and a marked alteration in substrate utilization towards fat oxidation to maintain blood glucose homeostasis. The results of this study may imply that progressive decline in partial CO₂ pressure (hypocapnia) that develops during prolonged exercise may contribute to increased interleukin-6 production.     

Hemodialysis Affects Phenotype and Proliferation of CD4-Positive T Lymphocytes

CD4⁺ T lymphocytes of patients with chronic kidney disease (CKD) are characterized by reduced levels of crucial surface antigens and changes in the cell cycle parameters. Recombinant human erythropoietin (rhEPO) normalizes their altered phenotype and proliferative capacity. Mechanisms leading to the deficient responses of T lymphocytes are still not clear but it is postulated that immunological changes are deepened by hemodialysis (HD). Study of activation parameters of CD4⁺ T lymphocytes in hemodialyzed and predialysis CKD patients could bring insight into this problem. Two groups of patients, treated conservatively (predialysis, PD) and hemodialyzed (HD), as well as healthy controls, were included into the study; neither had received rhEPO. Proportions of main CD4⁺CD28⁺, CD4⁺CD25⁺, CD4⁺CD69⁺, CD4⁺CD95⁺, and CD4⁺HLA-DR⁺ lymphocyte subpopulations and proliferation kinetic parameters were measured with flow cytometry, both ex vivo and in vitro. No differences were seen in the proportions of main CD4⁺ lymphocyte subpopulations (CD4⁺CD28⁺, CD4⁺CD25⁺, CD4⁺HLA-DR⁺, CD4⁺CD69⁺, CD4⁺CD95⁺) between all examined groups ex vivo. CD4⁺ T lymphocytes of HD patients exhibited significantly decreased expression of co-stimulatory molecule CD28 and activation markers CD25 and CD69 after stimulation in vitro when compared with PD patients and healthy controls. HD patients showed also decreased percentage of CD4⁺CD28⁺ lymphocytes proliferating in vitro; these cells presented decreased numbers of finished divisions after 72 h of stimulation in vitro and had longer G0→G1 time when compared to healthy controls. CD4⁺ T lymphocytes of PD patients and healthy controls were characterized by similar cell cycle parameters. Our study shows that repeated hemodialysis procedure influences phenotype and proliferation parameters of CD4⁺ T lymphocytes.     

Severe dilated cardiomyopathy as a consequence of Ecstasy intake

Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure with a prevalence of 1:2500. There are several primary and secondary etiologic factors, including gene mutations, infection agents, particularly viruses, toxins, autoimmune, and systemic disorders, and pheochromocytoma, neuromuscular, metabolic, mitochondrial, and nutritional disorders. However, a precise diagnosis can be reached only in no more than 50% of all cases. Herein, we report a rare case of hepatic damage and severe DCM as a consequence of relatively popular socially used narcotic-Ecstasy (3,4-methylenedioxy-N-methylamphetamine [MDMA]).     

Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease

Parkinson's disease (PD) is a common neurodegenerative disorder caused by genetic and environmental factors that results in degeneration of the nigrostriatal dopaminergic pathway in the brain. We analyzed neural cells generated from induced pluripotent stem cells (iPSCs) derived from PD patients and presymptomatic individuals carrying mutations in the PINK1 (PTEN-induced putative kinase 1) and LRRK2 (leucine-rich repeat kinase 2) genes, and compared them to those of healthy control subjects. We measured several aspects of mitochondrial responses in the iPSC-derived neural cells including production of reactive oxygen species, mitochondrial respiration, proton leakage, and intraneuronal movement of mitochondria. Cellular vulnerability associated with mitochondrial dysfunction in iPSC-derived neural cells from familial PD patients and at-risk individuals could be rescued with coenzyme Q(10), rapamycin, or the LRRK2 kinase inhibitor GW5074. Analysis of mitochondrial responses in iPSC-derived neural cells from PD patients carrying different mutations provides insight into convergence of cellular disease mechanisms between different familial forms of PD and highlights the importance of oxidative stress and mitochondrial dysfunction in this neurodegenerative disease.