Correlations between variations of electrical field at the body surface and contractions of the stomach in guinea pig.

1. The slow potentiel changes of the base line of the electrocardiogram recorded by cutaneous electrodes, here called EGEG (electrogastroenterogram) have been recorded simultaneously with the electromyogram and pressure variations of the stomach antrum. 2. Periodic fluctuations of EGEG, 400 microV amplitude, were correlated with activities of the antrum EMG consisting of 3 to 6 mV spikes superimposed on slow wave of depolarization, and with gastric intraluminal pressure of 5 to 7 cm of water. 3. An anticholinergic drug abolished all those activities. A gastric contracture flattened the EGEG. 4. Rhythmic distensions of the antrum induced a synchronous modulation of EGEG, the magnitude of which was correlated with the amplitude of distension. These result suggest that the origin of EGEG is essentially the movements of stomach.     

CHARACTERIZATION AND PROTEIN ANALYSIS OF MYELIN SUBFRACTIONS IN RAT BRAIN: DEVELOPMENTAL AND REGIONAL COMPARISONS

—Myelin preparations from the whole brains of 16-day-old rats and from cortical regions and brainstem, respectively, of 40-day-old rats were separated into light, medium and heavy subfractions on a discontinuous sucrose gradient by a procedure previously used for whole adult rat brain (Matthieu, et al., 1973). The total dry weight of myelin recovered from the 16-day-old rats was only 2·4mg/g fresh brain in comparison to 20 mg from adult brains. In 16-day-old rat brains, the percentage of the total myelin protein in the light fraction was higher than that found in adult brains; the percentage in the medium fraction was only one-third that in adults; while the percentage in the heavy fraction was about the same at both ages. The heavy fraction from the 16-day-old rats contained less basic protein and proteolipid than the light fraction, and the levels of the 2′3′-cyclic nucleotide 3′-phosphohydrolase (CNP) and glycoprotein were less than half those in the light and medium fractions. Double labelling experiments with radioactive fucose indicated that the major labelled glycoprotein in the heavy and medium fractions had a slightly higher apparent mol. wt than that in the light fraction. Electron microscopy showed much readily identifiable, compact myelin in the light and medium fractions from the 16-day-old rats, whereas the heavy fraction contained more single membranous structures and much less multilamellar myelin. The yield of myelin/g fresh wt from brainstem of 40-day-old rats was 4-fold higher than from cortical regions, and the percentage recovered in the light fraction was greater in the brainstem. In both regions basic proteins decreased from the light to the heavy fraction, whereas high mol. wt proteins, the glycoprotein and CNP increased. The biochemical and morphological results suggest that in both 16-day-old and young adult rats the light fraction is enriched multilamellar, compact myelin. In contrast, the heavy fraction at both ages is enriched in loose, uncompacted myelin and myelin-related membranes, although the heavy fraction from 16-day-old rats also may be substantially contaminated with membranes which are unrelated to myelin.     

Association-dependent active folding of alpha and beta subunits of lutropin (luteinizing hormone).

The kinetics of the structural transition of ovine lutropin (luteinizing hormone) from a dissociated and partially unfolded state to a biologically active, folded and associated state were studied from pH 1.8 to 6.5 by difference spectroscopy, circular dichroism, light scattering and ultracentrifugation under various conditions of temperature and ionic strength. Between pH 2.8 and 5.3 there is a thermodynamically reversible equilibrium between the two states of the hormone with a half-transition pH of 4.3 ± 0.1 at 26 °C. The interconversion of native folding to dissociated state is strictly first-order, and most of the kinetic results can be described in terms of two exponential decays with lifetimes of 20 and 100 seconds at pH 2 and 26 °C with one intermediate. A second intermediate with a short lifetime (1.5 s) is detected with stopped-flow experiments; its spectroscopic contribution is small. Refolding from the dissociated state is always second-order in the concentration range studied (12 to 110 μm lutropin), with rates at 26 °C, 1.4 m⁻¹ s⁻¹ at pH 4.3 and 2.2 m⁻¹ s⁻¹ at pH 5.3. The temperature dependence of the rate constant of active folding at pH 5.3 corresponds to activation parameters $\text{ΔH}{}^1\text{= +23.5}\text{kcal mol}{}^{\mathrm{-1}}\text{and}\text{ΔS}{}^1\text{= +21.6}\text{cal deg}{}^{\mathrm{-1}}$ mol⁻¹.From these data and computer-simulation studies, a simplest possible mechanism is proposed that involves the formation of a loose complex between the α and β subunits of the hormone, followed by a slow step of formation of the active, folded state. In the pituitary gland this would be a necessary pathway towards the active form. The storage of the hormone in the gland would offer enough time for this activation step to proceed.     

Unprecedented Therapeutic Potential with a Combination of A2A/NR2B Receptor Antagonists as Observed in the 6-OHDA Lesioned Rat Model of Parkinson's Disease

In Parkinson''s disease, the long-term use of dopamine replacing agents is associated with the development of motor complications; therefore, there is a need for non-dopaminergic drugs. This study evaluated the potential therapeutic impact of six different NR2B and A_2A receptor antagonists given either alone or in combination in unilateral 6-OHDA-lesioned rats without (monotherapy) or with (add-on therapy) the co-administration of L-Dopa: Sch-58261+ Merck 22; Sch-58261+Co-101244; Preladenant + Merck 22; Preladenant + Radiprodil; Tozadenant + Radiprodil; Istradefylline + Co-101244. Animals given monotherapy were assessed on distance traveled and rearing, whereas those given add-on therapy were assessed on contralateral rotations. Three-way mixed ANOVA were conducted to assess the main effect of each drug separately and to determine whether any interaction between two drugs was additive or synergistic. Additional post hoc analyses were conducted to compare the effect of the combination with the effect of the drugs alone. Motor activity improved significantly and was sustained for longer when the drugs were given in combination than when administered separately at the same dose. Similarly, when tested as add-on treatment to L-Dopa, the combinations resulted in higher levels of contralateral rotation in comparison to the single drugs. Of special interest, the activity observed with some combinations could not be described by a simplistic additive effect and involved more subtle synergistic pharmacological interactions. The combined administration of A_2A/NR2B-receptor antagonists improved motor behaviour in 6-OHDA rats. Given the proven translatability of this model such a combination may be expected to be effective in improving motor symptoms in patients.     

Enzyme and protein composition of myelin isolated in the presence of EGTA

The efficiency of ethyleneglycol-bis (β-amino-ethyl ether) N,N′-tetra-acetic acid (EGTA) in removing possible contamination from myelin was tested. Myelin fractions were isolated in the presence or absence of EGTA. An axolemma-enriched fraction was also prepared. Gel electrophoresis showed no important alteration of the protein pattern of myelin treated with EGTA. Only a minor band of about 41,000 daltons was selectively removed when EGTA was used during the two density gradient and differential centrifugation steps. EGTA, when used in the final washes, did not remove this band. It was absent from axolemma-enriched fractions. Different hypotheses are considered to explain these findings.     

[3 5S]Sulfate incorporation into myelin glycoproteins II. Peripheral nervous tissue

The in vivo incorporation of [^{3 5}S]sulfate, [³H]fucose and [³H]leucine into sciatic nerve myelin was investigated. Polyacrylamide gel electrophoresis of the proteins indicated that the ^{3 5}S-labeling of proteins occurred almost exclusively in the major myelin protein. A smaller myelin glycoprotein migrating just ahead of the major one was labeled with [³H]fucose but did not incorporate ^{3 5}S to a detectable extent. There was little or no ^{3 5}S associated with basic proteins on polyacrylamide gels when the proteins were extracted with chloroform/methanol. Fucose-labeled myelin glycoproteins were converted to glycopeptides by pronase digestion. The glycopeptides gave a single peak on Sephadex G-50 in which the ³H and ^{3 5}S coincided. The association of ^{3 5}S with glycopeptides was not caused by binding of sulfatide or free inorganic sulfate. This study shows that the major myelin protein in the sciatic nerve of the rat is glycosylated and sulfated.     

Microwave-assisted Synthesis of Novel Thiazolocarbazoles and Evaluation as Potential Anticancer Agents. Part III

Novel 6-substituted thiazolocarbazole derivatives have been synthesized under microwave irradiation via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor potential of these polyheterocyclic compounds was evaluated. Among all the tested thiazolocarbazoles, compound 10 is the most effective in inhibiting cell growth.     

Fluorescent (Au@SiO2)SiC Nanohybrids: Influence of Gold Nanoparticle Diameter and SiC Nanoparticle Surface Density

Gold@silica core–shell nanoparticles were prepared with various gold core diameters (ranging from 20 to 150 nm) and silica thicknesses (ranging from 10 to 30 nm). When the gold diameter is increased, the size dispersion became larger, leading to a broader plasmon band. Then, silicon carbide (SiC) nanoparticles were covalently immobilized onto silica to obtain hybrid (Au@SiO₂) SiC nanoparticles. The absorption properties of these hybrid nanoparticles showed that an excess of SiC nanoparticles in the dispersion can be identified by a strong absorption in the UV region. Compared to SiC reference samples, a blue shift of the fluorescence emission, from 582 to 523 nm, was observed, which was previously attributed to the strong surface modification of SiC when immobilized onto silica. Finally, the influence of several elaboration parameters (gold diameter, silica thickness, SiC concentration) on fluorescence enhancement was investigated. It showed that the highest enhancements were obtained with 10 nm silica thickness, low concentration of SiC nanoparticles, and surprisingly, with a 20-nm gold core diameter. This last result could be attributed to the broad plasmon band of big gold colloids. In this case, SiC emission strongly overlapped gold absorption, leading to possible quenching of SiC fluorescence by energy transfer.