Spiroergometric evaluation of the effectiveness of treatment of cardiac insufficiency with cardiac glycosides

There were 29 patients with rheumatic heart disease and early stages of cardiac insufficiency under observation. Spiroergometry with the "Ergotest" device was conducted in dynamics to check whether the proper dose of the cardiac glycoside had been chosen. The results attest to the considerable improvement in the spiroergometric indices in patients with early stages of cardiac insufficiency who had been treated with digitalis. Spiroergometry yielded important additional criteria of the effectiveness of digitalization, particularly in individuals with normal or diminished rate of cardiac contractions.     

Mechanisms of dimer and trimer formation from ultraviolet-irradiated α-tocopherol

α-Tocopherol (α-TH) undergoes ultraviolet (UV)-induced photooxidation on the surface of mouse skin to produce a dihydroxydimer, a spirodimer, and trimers as the major products. To study the photochemistry involved, we UV-irradiated α-TH in a thin film on a glass petri dish. Photooxidation yielded a mixture of dihydroxydimer, spirodimer, and trimers. In the time-course studies, the dihydroxydimer accumulated and then was further oxidized, whereas the spirodimer and trimers accumulated more gradually. Reaction of two tocopheroxyl radicals forms the dihydroxydimer, whereas the spirodimer may be formed either by photooxidation of α-TH to an orthoquinone methide (o-QM) followed by a Diels-Alder reaction or by photooxidation of α-TH to the dihydroxydimer, followed by two-electron oxidation. Irradiation of a mixture of d ₁₀-labeled and unlabeled (d ₀) dihydroxydimer produced a mixture of labeled and unlabeled spirodimers as detected by positive atmospheric pressure chemical ionization-mass spectrometry. The absence of mixed label spirodimers among products indicated that direct oxidation of the dihydroxydimer is a facile route to the spirodimer and is probably the major spirodimer-forming reaction in α-TH photooxidations. Trimer formation from the dihydroxydimer and the spirodimer was observed, however, and requires an o-QM intermediate. Photooxidation of d ₁₀-labeled and unlabeled (d ₀) dihydroxydimers yielded mixed isotopomers of the trimer products, thus demonstrating that the dihydroxydimer and spirodimers underwent conversion to o-QM intermediates. Photochemical conversion of α-TH to UV-absorbing dimer and trimer products may contribute to photoprotection by topically applied α-TH.     

The Antipsychotic D2AAK1 as a Memory Enhancer for Treatment of Mental and Neurodegenerative Diseases

The treatment of memory impairments associated with the central nervous system diseases remains an unmet medical need with social and economic implications. Here we show, that a multi-target ligand of aminergic G protein-coupled receptors with antipsychotic activity in vivo (D2AAK1) stimulates neuron growth and survival and promotes neuron integrity. We focused on the multilevel evaluation of the D2AAK1-related effects on neurons in terms of behavioral, cellular, molecular, and biochemical features in vivo and in vitro, such as memory-related responses, locomotor activity, tissue sections analysis, metabolic activity, proliferation level, neurons morphology, and proteins level involved in intracellular signaling pathways. In silico studies indicate that activation of calcium/calmodulin-dependent protein kinase I (CaMKI) may underline some of the observed activities of the compound. Furthermore, the compound increases hippocampal neuron proliferation via the activation of neurotrophic factors and cooperating signals responsible for cell growth and proliferation. D2AAK1 improves memory and learning processes in mice after both acute and chronic administration. D2AAK1 also causes an increase in the number of hippocampal pyramidal neurons after chronic administration. Because of its neuroprotective properties and pro-cognitive activity in behavioral studies D2AAK1 has the potential for the treatment of memory disturbances in neurodegenerative and mental diseases.     

Sustainability of Small Reservoirs and Large Scale Water Availability Under Current Conditions and Climate Change

Semi-arid river basins often rely on reservoirs for water supply. Small reservoirs may impact on large-scale water availability both by enhancing availability in a distributed sense and by subtracting water for large downstream user communities, e.g. served by large reservoirs. Both of these impacts of small reservoirs are subject to climate change. Using a case-study on North-East Brazil, this paper shows that climate change impacts on water availability may be severe, and impacts on distributed water availability from small reservoirs may exceed impacts on centralised water availability from large reservoirs. Next, the paper shows that the effect of small reservoirs on water availability from large reservoirs may be significant, and increase both in relative and absolute sense under unfavourable climate change.     

Laboratory and Field Investigations of Polymer and Crumb Rubber Modified Bitumen

In this paper, properties of new kind of modified bitumen are presented. Bituminous binder was modified with mix modification using polymer and additive of crumb rubber. Terminal blend process at the refinery was applied to produce the mixed modified binder. Laboratory tests were focused on the characterization of the properties of 45/80-55 CR binder with comparison to reference 50/70 and conventional polymer modified 45/80-55 bitumen. Based on conventional binder tests such as penetration, softening point and Fraass breaking point as well as BBR （bending beam rheometer） and DSR （dynamic shear rheometer） tests, rheological properties were investigated. For determination of stability of the polymer and crumb rubber, modified bitumen tube testing method was used. Based on the results analysis, improvement of the viscoelastic properties of polymer and crumb rubber modified bitumen was observed. Conventional properties and stability tests showed that it is possible to pass standard requirements for polymer modified bitumen. Mixed modification and terminal blend allow to use crumb rubber as a modifier with elimination of the separation of crumb rubber during transportation and storage at high temperature. In this paper, experience from filed sections with use of the asphalt mixture with new kind of modified bitumen is presented.     

Factors controlling the leaching of major and minor constituents from processed rundle oil shale

The chemical characteristics of leachates from columns of processed oil shale from the Rundle resource, Queensland, were determined and the factors controlling the rate of release of the major and minor constitutents were delineated. The studies were carried out in two types of laboratory columns and a weathering column (lysimeter) exposed to prevailing weather conditions. The flow in the laboratory columns was maintained in an unsaturated mode in order to simulate the flow conditions found in the field.The major constitutents leached from Rundle spent shale are the sulphates and chlorides of Ca, Mg, K and Na. Most of these salts are eluted in the first few pore volumes of leachate. The only major constituents significantly constrained by solubility factors are Ca and SO₄, this being due to solution saturation with respect to gypsum (CaSO₄ · 2H₂O). Chemical equilibria with respect to the ion pairs CaSO₄^o and MgSO₄^o are important in determining the rate of release of Ca, Mg and SO₄.Ion exchange and sorption phenomena are significant in controlling the leaching rate of both the major cationic metal species and the minor (or trace) elements. Many of these minor elements are probably in the anionic form (e.g. As, Se and V), yet are still absorbed by the shale which exhibits no significant anion exchange capacity. Weathering reactions appear to play a significant role in the continued slow leaching of the major and minor species which is observed even after many pore volumes of liquid have eluted.     

Prevention of recurrent atrial fibrillation with chronic dual-site right atrial pacing

OBJECTIVES: We investigated 1) the feasibility, safety and efficacy of multisite right atrial pacing for prevention of atrial fibrillation (AF); and 2) the ability of atrial pacing in single- and dual-site modes to increase arrhythmia-free intervals in patients with drug-refractory AF. BACKGROUND: We recently developed and applied a novel technique of dual-site right atrial pacing in an unselected group of consecutive patients with AF requiring demand pacing. A prospective crossover study design was used to evaluate single- and dual-site right atrial pacing modes. METHODS: The frequency of AF during the 3 months before pacemaker implantation was analyzed. Consecutive consenting patients underwent insertion of two atrial leads and one ventricular lead with a DDDR pulse generator. Patients were placed in a dual-site pacing mode for the first 3 months and subsequently mode switched to single site pacing for 3 months. Mode switching was repeated at 6-month intervals thereafter. RESULTS: Atrial pacing resulted in a marked decline in AF recurrences (p < 0.001). During dual-site pacing with an optimal drug regimen, there was no AF recurrence in any patient compared with five recurrences in 12 patients during single-site pacing (p = 0.03). The mean (+/-SD) arrhythmia-free interval before pacing (14 +/- 14 days) was prolonged with dual- (89 +/- 7 days, p < 0.0001) and single-site pacing (76 +/- 27 days, p < 0.0001). Symptomatic AF episodes showed a declining trend during dual- and single-site pacing compared with those during the preimplantation period (p = 0.10). Mean antiarrhythmic drug use for all classes declined from 4 +/- 1.9 drugs before implantation to 1.5 +/- 0.5 (p < 0.01) drugs after implantation. Twelve (80%) of 15 patients remained in atrial paced rhythm at 13 +/- 3 months. CONCLUSIONS: We conclude that multisite right atrial pacing is feasible, effective and safe for long-term application. Atrial pacing significantly prolongs arrhythmia-free intervals in patients with drug-refractory paroxysmal AF. Dual-site right atrial pacing may offer additional benefits and should be considered either as the primary mode or in patients unresponsive to single-site pacing.     

Ciprofloxacin pharmacokinetics in burn patients

Cyproterone acetate (CPA), a synthetic progestin recently found to induce genotoxic effects in hepatocytes from female rats and from humans of both genders, and two structural analogues, chlormadinone acetate (CMA) and megestrol acetate (MGA), have been compared for their capacity to induce DNA repair synthesis as measured by quantitative autoradiography. Exposure of primary human hepatocytes for 20 h to concentrations of CPA, CMA and MGA ranging from 2 to 50 microM induced positive responses in cultures from donors of both genders and the amounts of DNA repair elicited by the three progestins were similar. Under the same experimental conditions substantial differences were observed in the amounts of DNA repair elicited by the three progestins in primary hepatocytes from female rats, their potency decreasing in the following order CPA > CMA > MGA, and the three compounds failed to induce DNA repair in hepatocytes from male rats. These results, which agree with previous findings, suggest that for these sex steroids extrapolation to humans of results obtained in rats might be questionable.