Angle-Resolved Electron Scattering from H_{2}O near 0°.

An electron beam, characterized by a high-angular discrimination (≃0.7°), has been used to measure the total (elastic plus inelastic) cross section of H_{2}O in the energy range 3-100 eV. Broad coincidence is found with recent experiments, including a pronounced shoulder in the 6-12 eV region. However, at energies ≲6 eV, the present cross sections are ≃30% higher. Furthermore, forward scattering has been probed in the angular range 0°-3.5° and measures of the average (rotationally and vibrationally summed) differential elastic cross sections for incident energies ≤12 eV are obtained at a scattering angle ≃1^{∘}. The measurements, which provide the first test of theoretical predictions in an angular region experimentally unexplored until now, are found to be within 1 standard deviation of corresponding ab initio R-matrix calculations.

High-Resolution Measurements of e

Using a purely electrostatic positron beam, the total cross section of positrons scattering from H_{2}O has been measured for the first time with a high angular discrimination (≃1°) against forward scattered projectiles. Results are presented in the energy range (10-300) eV. Significant deviations from previous measurements are found which are, if ascribed entirely to the angular acceptances of various experimental systems, in quantitative accord with ab initio theoretical predictions of the differential elastic scattering cross section.

Energy-sharing asymmetries in ionization by positron impact.

The triply differential cross section of molecular hydrogen for ionization by 50 eV positrons has been determined, for the first time, for both the ejected electron in coincidence with the remnant ion and for the scattered projectile. Asymmetries in the energy sharing between the two light particles in the final state are observed, with the electron spectrum being shifted to significantly lower (and the scattered positron to correspondingly higher) energies than expected. A similar shape is observed in the case of the ejected electron spectrum from a helium target at the same excess energy.

(-)-Spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha 7 nicotinic acetylcholine receptor.

Neuronal nicotinic acetylcholine receptors are members of the ligand-gated ion channel receptor superfamily and may play important roles in modulating neurotransmission, cognition, sensory gating, and anxiety. Because of its distribution and abundance in the CNS, the alpha 7 nicotinic receptor is a strong candidate to be involved in some of these functions. In this paper we describe the synthesis and in vitro profile of AR-R17779, (-)-spiro[1-azabicyclo[2.2. 2]octane-3,5'-oxazolidin-2'-one] (4a), a potent full agonist at the rat alpha 7 nicotinic receptor, which is highly selective for the rat alpha 7 nicotinic receptor over the alpha 4 beta 2 subtype. Preliminary SAR of AR-R17779 presented here indicate that there is little scope for modification of this rigid molecule as even minor changes result in significant loss of the alpha 7 nicotinic receptor affinity.

The importance of bioimpedance (BIA) analysis and Cardio Tens (24-h ABPM and ECG) monitoring in the dialysis programme.

The authors performed bioimpedance analysis and Cardio Tens (24-h ABPM and ECG) monitoring in 66 patients (28 males, 38 females) treated in the chronic haemodialysis programme. They investigated the correlations between the body weights before, during and after dialysis, the changes of the water compartments and fat body weight, and the recorded values of blood pressure and ECG alterations. On the basis of the measurements by this non-invasive method it is concluded that, as a result of dialysis and ultrafiltration, the total body weight and total body water are decreasing in a greater extent in men than in women. By gradually decreasing the body weight, the optimal dry weight could be attained, which resulted in the reduction of blood pressure or even normotension. In the course of dialysis the values of bioimpedance and bioreactance increase. The intradialytic hypotensive indispositions were accompanied by a significant reduction of bioreactance (n = 16). The BMI, total body weight and total body water hyperlipidaemic, hypalbuminic patients with treatment-resistant hypertension are considerably larger than those of the patients with normal blood pressure (p<0.01). During Cardio Tens monitoring 53% of the patients proved to be dippers, 47% of whom had ST depression, while in 73% of the non-dippers ischaemic alterations were encountered together with high hyperbaric impact values. The total body weights and total water compartments of patients returning to dialysis with an excess body weight of more than 3.5 kg were significantly larger than of patients who were cooperative and had no oedemas. In the last hour of dialysis and during the following few hours, arrhythmias and ST depressions of the cardiovascularly instable patients appeared more frequently. The total water compartments of these patients are significantly larger than normotensive, normolipaemic patients with appropriate serum albumin concentrations. The importance of the BIA and Cardio Tens monitoring in determining the optimal dry body weight and improving the cardiovascular condition of the patients is emphasized.

In vitro muscarinic activity of spiromuscarones and related analogs.

The cholinergic hypothesis of Alzheimer's disease suggests that cholinergic agonists may have therapeutic potential for treating the attendant memory deficits of the disease. As part of a program aimed at preparing metabolically stable, nonquaternary analogs of muscarone, 1-oxa-2,8-dimethyl-8-azaspiro[4.5]decan-3-one, 2a, and related analogs have been synthesized and their in vitro muscarinic activity evaluated. The synthetic strategy in the formation of the 1-spiro[4.5]decan-3-one ring system of 2a involved cyclization of the diol 4 in the presence of Nafion-Hg. The spiromuscarone 2a was found to displace [3H]Oxo-M binding with a Ki value of 7 nM. Affinities of the oxime and hydrazone analogs of 2a were lower than 2a. The compounds in these series were partial muscarinic agonists as demonstrated by stimulation of phosphatidyl inositol hydrolysis assay, with 2a showing the highest intrinsic intrinsic activity (60% as compared with carbachol). The results from this study indicate that an exo double bond at the C-3 position is essential for the receptor binding.

Characteristics of stretch-release induced tension development in arterial smooth muscle.

Stretching helical strips of porcine a. carotis comm. to 1.7 times the resting length increases myosin light chain phosphorylation from 0.22 to 0.67 mol phosphate/mol light chain. While stretch is maintained, the stretch induced light chain phosphorylation decreases and reaches the resting level over a period of 60 minutes. The fully stretched arterial strips containing maximally phosphorylated myosin light chain cannot generate active tension which indicates, according to the sliding filament theory, the lack of overlap between actin and myosin filaments. When stretch is released from these muscle strips active tension develops. The amplitude of this stretch-release induced tension depends on the level of myosin light chain phosphorylation related to the time interval between stretch and release as well as on the extent of the overlap zone related to the length of the released strip. Three-dimensional graphic representation of both measured and interpolated data points in an active tension-light chain phosphorylation-muscle length space reveals a contractility surface which demonstrates that active tension appears as a sigmoidal function of light chain phosphorylation, on the one hand and shows maximum as a function of muscle length, on the other hand.

Effects of pH, Ca2+ and lanthanides on conformation of the sarcoplasmic reticulum Ca(2+)-ATPase catalytic site.

The conformational changes at the ATP-catalytic site of the sarcoplasmic reticulum (SR) Ca(2+)-ATPase have been studied by the fluorescence of the fluorescein 5-isothiocyanate (FITC) bound to the adenine subsite. The FITC-SR fluorescence parameters have been examined in the pH range 5.7-8.0 in the presence of EGTA, Ca2+ or Ln3+ (La3+, Pr3+, Nd3+, Tb3+, etc.). A quantitative method to calculate the equilibrium between the protein conformers is proposed on the basis of the fluorometric titration curve analysis. The distance Nd(3+)-FITC was estimated to be about 1 nm at pH 6-7 and 1.7 nm at pH 8 which can be interpreted as an increase of the distance between the nucleotide and phosphorylation domains of Ca(2+)-ATPase in alkaline media. These studies suggest that the ligand-stabilized E1-form of Ca(2+)-ATPase can exist in two conformational states with the closed and opened interdomain cleft in the pH range 5.7-8.0. The pH-dependence of the ratio of these states correlates with that of the E1----E2 equilibrium without ligands. These dependences were approximated by simple Henderson-Hasselbach equations with pK 7.0 +/- 0.1, i.e. the transition between two protein conformations is probably governed by one proton dissociation.

New approach of three-dimensional crystallization of the Ca(2+)-ATPase of sarcoplasmic reticulum.

Selective extraction procedure was applied for obtaining different proteins from sarcoplasmic reticulum vesicles following the main steps of previous observations. High concentration of a nonionic detergent, such as polyoxyethylene-10-lauryl ether (C12E10) prevented the formation of Ca(2+)-ATPase crystals. It has been observed that only the 300 kDa protein could induce crystallization from among proteins being undissolved from of membrane. A modification of MacLennan's procedure--applied for ATPase precipitation from deoxycholate solubilized sarcoplasmic reticulum--has been described and an ammonium acetate precipitated Ca(2+)-ATPase was used in the experiments for increase of Ca(2+)-ATPase concentration in the crystallization process. The repeated supplementation of purified and C12E10 solubilized Ca(2+)-ATPase with ammonium acetate precipitated Ca(2+)-ATPase made possible a formation of larger and larger crystals with different periodicity.

Effect of sodium-ascorbate and vanadate on the Rb+-uptake of human red blood cells.

To follow the Rb+-uptake of human red blood cells (rbc-s) under different circumstances, a micro-method was developed. According to our experiments the Rb+-uptake of rbc-s in a healthy person was about 3.5-4.0 mumoles Rb/mg Fe at 37 degrees C during 120 minutes. When red cells were incubated with solutions containing different concentrations, between 15 and 120 mmole/l, of Na-ascorbate [Na-ascorbate was applied at the expense of Na-isethionate (sodium salt of 2-hydroxyethan-1-sulfonic acid)] the Rb+-uptake of red cells increased at 37 degrees C with 37 to 70% respectively. In other experiments it was established that the ouabain-sensitive Rb+-uptake of rbc-s decreased with 50% in the presence of 0.1 mmole/l vanadate, while if Na-ascorbate was applied simultaneously with different concentrations of vanadate, or after a preincubation with 1 mmole/l vanadate, the Rb+-uptake of red cells, which had been reduced by vanadate, returned close to that of control. This effect can be explained by the reductive property of Na-ascorbate, i.e. by the transformation of vanadate to vanadil.

Changes of calcium compartmentalization of skeletal muscle under ionic and drug influence.

Compartmentalization of calcium was studied in frog semitendinosus using 45Ca radioisotope under exchange diffusion condition. Computer based deconvolution was employed to determine the "volume" and the apparent binding constant of the resolved six components. Assuming kinetically parallel and independent compartments nickel treatment slows down the calcium movement through the sarcoplasmic reticulum membrane and for the calcium ions causes competition of the membrane of transverse tubuli and of the sarcoplasmic reticulum. Veratrine treatment caused different effect in the presence and in the absence of sodium ions, demonstrating the essential role of Na+ in equilibrium with Ca2+ exchange processes/ATPases in the Ca2+ uptake and release by sarcoplasmic reticulum. Effect of caffeine and Dantrolene basically opposite on the compartment corresponds to the sarcoplasmic reticulum and similar on the transverse tubuli in term of speed of exchange diffusion.